Medical Articles. Evidence-Based Summaries.

Journal of pharmacokinetics and pharmacodynamics

Exposure-safety analyses of talazoparib in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial.

The TALAPRO-2 trial (NCT03395197) showed that the addition of talazoparib, a potent PARP inhibitor, to enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC. Due to adverse events (AEs), approximately 62% of patients experienced dose interruption and 53% of patients experienced dose reduction of talazoparib in TALAPRO-2 trial. Hematologic AEs such as anemia, thrombocytopenia, and neutropenia were the most common AEs leading to dose interruptions or reductions. We investigated the relationship between talazoparib exposure as well as baseline patients/disease characteristics and Grade ≥ 3 anemia, thrombocytopenia, and neutropenia using graphical examination and Cox proportional hazard models. The results indicated that higher talazoparib exposure, Cavg, t, was associated with a higher risk of Grade ≥ 3 anemia, thrombocytopenia, and neutropenia. Additionally, among the other baseline factors, we observed that higher risk of all tested safety endpoints was associated with lower baseline hemoglobin. In addition, higher risk of anemia was associated with lower baseline body weight and higher baseline lactate dehydrogenase. Higher risk of neutropenia was associated with lower baseline absolute neutrophil count and lower baseline body weight. These findings support the proposed dose modification algorithm as an effective approach for management of AEs.

1 min5 Jun 2026

Worldviews on evidence-based nursing

The Efficacy of Self-Management Interventions Based on E-Health in Quality of Life in Patients With Cancer: A Meta-Analysis of Randomized Controlled Trials.

The diagnosis of cancer results in psychophysiological distress in patients, significantly reducing quality of life (QoL). Currently, self-management interventions based on e-health have been used to improve QoL among cancer patients, but the overall effects remain inconsistent. To assess the impact of self-management interventions based on e-health on the QoL of cancer patients. Studies were retrieved from six databases up to November 6, 2024. The methodological quality assessment was performed via ROB 2. Data synthesis and subgroup analyses were performed in Review Manager 5.3. Meta-regression was conducted using Stata 15.0. Thirty RCTs were included. The results of meta-analysis revealed self-management interventions based on e-health significantly improved QoL (SMD = 0.18, 95% CI: 0.08 to 0.28, p < 0.01). Subgroup analyses showed that long-term, mixed-mode, theory-supported, or facilitator-supervised interventions were more effective, with greater improvements in QoL observed among patients with breast cancer than among other types. Self-management interventions based on e-health were valuable supplements for enhancing the QoL of cancer patients. Intervention duration, delivery modes, cancer types, theoretical frameworks, and facilitators' involvement should be considered in the design of future interventions. However, additional high-quality studies are needed to confirm these findings. The protocol was registered on PROSPERO (Registration number: CRD420251017709).

1 min5 Jun 2026

Impact of continuous glucose monitoring on patient-reported outcomes in adults with type 2 diabetes: a Systematic Review and meta-analysis.

This research intended to systematically evaluate the impact of continuous glucose monitoring (CGM) on the emotional well-being of individuals with type 2 diabetes. It focused on the effects of CGM in four distinct patient-reported outcome domains: diabetes distress (measured by the diabetes distress scale [DDS]), treatment satisfaction (diabetes treatment satisfaction questionnaire [DTSQ]), psychological well-being (world health organization-5 well-being index [WHO-5]), and health-related quality of life (EuroQol five-dimensional questionnaire [EQ-5D]). PubMed, Web of Science, Embase, and Cochrane Library were retrieved from inception until April 2026 to collect randomized controlled trials (RCTs) comparing CGM with self-monitoring of blood glucose (SMBG). After two researchers independently performed literature screening, data extraction, and quality assessment, meta-analysis was conducted using Stata 16.0. A total of 9 RCTs comprising 1,453 individuals were included. All five studies reporting treatment satisfaction (DTSQ) showed a direction of effect favoring CGM over SMBG, although the magnitude of improvement varied widely and heterogeneity was extremely high (I²=98.9%), precluding a meaningful single summary estimate. However, no statistically significant differences were observed between the two groups in terms of diabetes distress (DDS) [standardized mean difference (SMD)=-0.25, 95% confidence interval (CI) (-0.98, 0.17)], psychological well-being (WHO-5) [SMD = 0.08, 95% CI (-0.09, 0.25)], or health-related quality of life (EQ-5D) [SMD = 0.22, 95% CI (-0.20, 0.64)]. Current evidence indicates that CGM may improve treatment satisfaction in individuals with type 2 diabetes, although this finding is limited by very high heterogeneity. Its effects on alleviating diabetes distress, improving psychological well-being, and enhancing health-related quality of life remain unclear and should be further investigated. https://www.crd.york.ac.uk/prospero/, identifier CRD42025634725.

2 min5 Jun 2026

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

Pre-treatment quality of life and survival outcomes in lung cancer patients: a systematic review and meta-analysis.

Lung cancer is a leading cause of cancer-related mortality, with baseline (pre-treatment) quality of life (QOL) increasingly recognized as a potential prognostic factor for survival. This systematic review and meta-analysis evaluates the association between baseline (pre-treatment) QOL and mortality in lung cancer patients. Following PRISMA guidelines and PROSPERO registration (CRD42023398206), we searched PubMed/MEDLINE, Web of Science, and Scopus up to July 2025 for observational studies examining baseline (pre-treatment) QOL and survival in lung cancer patients. Eligible studies used validated QOL tools and reported hazard ratios (HRs) for mortality. Data were extracted independently by two reviewers, and study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analyses quantified associations between global and domain-specific QOL (physical, emotional, cognitive, social) and mortality, with heterogeneity assessed via I2 statistics. Thirty-nine studies (n = 20,235 patients) across 18 countries were included. Lower baseline (pre-treatment) global QoL was associated with increased mortality risk (pooled HR = 1.07; 95% CI: 1.02-1.12), with similar associations observed for physical, emotional, and social QoL domains. Cognitive QoL (HR = 0.99; 95% CI: 0.97-1.00) and FACT-G/FACT-L scores (HR = 0.94; 95% CI: 0.80-1.09) showed no significant association. Substantial heterogeneity (I2 = 72-92%) was observed, likely due to variations in study design, QOL tools, and patient characteristics. Lower baseline QoL is associated with increased mortality risk, indicating that higher QoL is protective and associated with improved survival. Standardized methodologies are needed to address heterogeneity and enhance evidence quality. Findings may vary by disease stage; stage-stratified estimates were rarely reported.

2 min4 Jun 2026

The Indian journal of medical research

Inflammation-driven carcinogenesis in oral cancer: A systematic review of cellular mechanisms and clinical perspectives.

Background and objectives Oral squamous cell carcinoma (OSCC) represents the predominant form of oral cancer and remains a major cause of morbidity and mortality worldwide. Beyond traditional risk factors such as tobacco, alcohol, and betel quid consumption, mounting evidence implicates chronic inflammation as a driving force in oral carcinogenesis. This review synthesises current literature exploring how inflammatory mediators contribute to tumour initiation, progression, and clinical outcomes in OSCC. Methods A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases was conducted according to PRISMA 2020 guidelines. Studies from 2020-2025 examining molecular and clinical interactions between inflammation and OSCC were analysed. Extracted data included inflammatory biomarkers, activated signalling pathways, and prognostic or therapeutic implications. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane RoB-2 tool. The review protocol was registered with PROSPERO (CRD420251141942). Results Forty-three eligible studies revealed that inflammatory cytokines such as TNF-α, IL-6, and IL-1β, together with chemokines like CXCL8, trigger oncogenic cascades involving NF-κB and STAT3, leading to enhanced proliferation, angiogenesis, and epithelial-mesenchymal transition. Oxidative DNA damage and immune suppression mediated by M2 macrophages and PD-1/PD-L1 signalling further facilitate tumour aggressiveness. Elevated COX-2, STAT3, and systemic inflammatory ratios were strongly associated with poor prognosis. Interpretation and conclusions Persistent inflammation acts as a critical determinant in OSCC pathogenesis. Integrating inflammation-related biomarkers and anti-inflammatory therapeutic strategies may improve early detection, prognostication, and patient survival outcomes.

2 min4 Jun 2026

Journal of the American College of Cardiology

Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses.

Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial. Participants with type 2 diabetes and CKD were randomized to once-weekly subcutaneous semaglutide 1.0 mg vs placebo. Baseline subgroups included atherosclerotic cardiovascular disease (ASCVD), heart failure, and high total cardiovascular disease risk without established cardiovascular disease (10-year PREVENT [Predicting Risk of cardiovascular disease EVENTs] score ≥20%). The primary outcome was ≥50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m2, dialysis, transplantation, and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome. At baseline, 1,198 (33.9%) of 3,533, 678 (19.2%) of 3,532, and 1,329 (66.5%) of 2,000 participants had ASCVD, heart failure, or high total cardiovascular disease risk in those without established cardiovascular disease, respectively. Semaglutide reduced the primary outcome risk in subgroups with (119 of 593 vs 146 of 605) or without (212 of 1,174 vs 264 of 1,161) ASCVD (HR: 0.80; 95% CI: 0.63-1.02; and HR: 0.74; 95% CI: 0.62-0.89, respectively; P for interaction = 0.62), with (67 of 342 vs 88 of 336) or without (264 of 1,424 vs 322 of 1,430) heart failure (HR: 0.67; 95% CI: 0.49-0.93; and HR: 0.79; 95% CI: 0.67-0.93, respectively; P for interaction = 0.40), and with (134 of 675 vs 168 of 654) or without (44 of 331 vs 58 of 340) high total cardiovascular disease risk (HR: 0.73; 95% CI: 0.58-0.91; and HR: 0.73; 95% CI: 0.49-1.08, respectively; P for interaction = 0.99). Numbers needed to treat to prevent 1 primary kidney outcome at 3 years were 22, 13, and 17 in the ASCVD, heart failure, and PREVENT score ≥20% subgroups, respectively. Semaglutide also reduced risks of all-cause death with (99 of 593 vs 121 of 605) or without (128 of 1,174 vs 158 of 1,161) ASCVD (HR: 0.82; 95% CI: 0.63-1.07; and HR: 0.78; 95% CI: 0.62-0.99, respectively; P for interaction = 0.79), with (64 of 342 vs 79 of 336) or without (163 of 1,424 vs 200 of 1,430) heart failure (HR: 0.75; 95% CI: 0.54-1.05; and HR: 0.81; 95% CI: 0.66-0.99, respectively; P for interaction = 0.74), and with (73 of 675 vs 98 of 654) or without (23 of 331 vs 28 of 340) high total cardiovascular disease risk (HR: 0.71; 95% CI: 0.52-0.95; and HR: 0.82; 95% CI: 0.47-1.43, respectively; P for interaction = 0.63). Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk. (Evaluate Renal Function with Semaglutide Once Weekly [FLOW]; NCT03819153).

3 min3 Jun 2026

Is it time to focus on expiratory muscle training in children with asthma? A randomized controlled trial.

Respiratory muscle dysfunction contributes to reduced pulmonary and extrapulmonary outcomes in children with asthma. Although inspiratory muscle training has been widely studied, the effects of expiratory muscle training (EMT) in pediatric asthma remain unclear. This study investigated the effects of EMT on pulmonary function, respiratory and peripheral muscle strength, peak cough flow (PCF), functional capacity, and asthma control in children with asthma. This prospective, single-blinded randomized controlled trial included 30 clinically stable children with asthma aged 8-18 years. Participants were randomly assigned to an experimental group (EG) receiving EMT in addition to a home-based chest physiotherapy program or a sham group (SG) performing the same program with minimal resistance. EMT was performed once daily for 8 weeks at 30% of maximal expiratory pressure (MEP) with weekly load adjustments. Pulmonary function, respiratory and peripheral muscle strength, PCF, functional capacity, and asthma control test (ACT) scores were assessed at baseline and after 8 weeks. FVC and FEV₁ improved significantly only in the EG, whereas PEF increased in both groups with greater improvement in the EG. MIP increased in both groups, while MEP and MEP (% predicted) improved only in the EG. PCF, quadriceps strength, and 6MWT distance improved in both groups, with greater gains in the EG. ACT scores increased significantly in both groups but improved more in the EG. Adding 8 weeks of EMT to chest physiotherapy improved pulmonary function, respiratory and peripheral muscle strength, cough effectiveness, functional capacity, and asthma control in children with asthma. EMT appears to be a safe and effective adjunct to pediatric asthma management. The study was prospectively registered on the ClinicalTrials.gov website (registration number: NCT07169071; Date: 09/05/2025). • Respiratory muscle dysfunction is common in children with asthma and may contribute to reduced pulmonary function, ineffective cough, and decreased exercise capacity. • Most respiratory muscle training studies in asthma have focused primarily on inspiratory muscle training, while the role of expiratory muscle training remains largely unexplored. • This randomized controlled trial investigates the effects of expiratory muscle training (EMT) in children with asthma when combined with a home-based chest physiotherapy program. • The addition of 8 weeks of EMT resulted in greater improvements in pulmonary function, respiratory muscle strength, cough effectiveness, functional capacity, and asthma control compared with sham training.

HRS-7535 for Type 2 Diabetes Inadequately Controlled With Metformin: A Randomized Clinical Trial.

Oral small-molecule glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may address limitations of injectable and peptide-based agents for type 2 diabetes. To evaluate the efficacy and safety of HRS-7535, an oral nonpeptide GLP-1 RA, as add-on therapy among adults with type 2 diabetes inadequately controlled with metformin. This 16-week, phase 2, double-blind, placebo-controlled randomized clinical trial was conducted at 44 centers in China. Adults aged 18 to 75 years with type 2 diabetes, hemoglobin A1c (HbA1c) levels ranging from 7.5% to 11.0%, and receiving stable metformin therapy were enrolled between May 10 and December 18, 2023. Data were analyzed from May 8 to 22, 2024. Participants were randomized (1:1:1:1:1) to once-daily oral HRS-7535 (15, 30, 60, or 90 mg) or matching placebo. The 60- and 90-mg treatment groups used dose-escalation regimens. The primary outcome was change in HbA1c level from baseline to week 16. Secondary outcomes included changes in fasting plasma glucose level, 2-hour postprandial glucose level, body weight, and the proportion of patients achieving HbA1c levels less than 7.0%. Safety outcomes included adverse events (AEs), hypoglycemia, and AEs of special interest. Of 194 randomized patients (mean [SD] age, 52.3 [11.0] years; 115 [59.3%] men; mean [SD] HbA1c level, 8.5% [0.7]), 177 (91.2%) completed treatment. The mean changes in HbA1c level at week 16 were -1.19% (95% CI, -1.54% to -0.84%) with the 15-mg dose, -1.59% (95% CI, -1.94% to -1.24%) with the 30-mg dose, -1.82% (95% CI, -2.16% to -1.48%) with the 60-mg dose, and -1.64% (95% CI, -1.97% to -1.30%) with the 90-mg dose compared with -0.25% (95% CI, -0.60% to 0.09%) with placebo; placebo-adjusted differences ranged from -0.94% (95% CI, -1.43% to -0.45%) to -1.57% (95% CI, -2.05% to -1.08%) (all P < .001). HbA1c level less than 7.0% was achieved in proportions ranging from 48.7% (95% CI, 32.4%-65.2%) to 63.2% (95% CI, 46.0%-78.2%) of HRS-7535-treated patients vs 15.4% (95% CI, 5.9%-30.5%) with placebo. The 90-mg group had greater body weight reduction than placebo (-2.63% [95% CI, -3.72% to -1.54%] vs -1.30% [95% CI, -2.46% to -0.15%]). AEs occurred in 28 of 39 (71.8%) to 33 of 39 (84.6%) HRS-7535-treated patients and 28 of 39 (71.8%) placebo-treated patients and were predominantly mild to moderate gastrointestinal events. Level 1 hypoglycemia occurred in 9 HRS-7535-treated patients; no level 2 or 3 hypoglycemia, pancreatitis, or elevations of alanine aminotransferase or aspartate aminotransferase levels greater than 3 times the upper limit of normal occurred. In this randomized clinical trial of adults with type 2 diabetes inadequately controlled with metformin, oral HRS-7535 improved glycemic control and was associated with modest weight reduction, with a safety profile consistent with that of GLP-1 RAs. Because HRS-7535 is a nonpeptide oral GLP-1 RA that does not require fasting administration or injection, it may be a viable treatment option, pending confirmation in phase 3 trials. ClinicalTrials.gov Identifier: NCT05759897.

3 min3 Jun 2026

CNS neuroscience & therapeutics

Association of Circulating Tumor DNA With Brain Metastases: A Systematic Review and Meta-Analysis.

Brain metastases are a major contributor to morbidity and mortality in patients with advanced solid tumors; however, early detection and accurate prognostic assessment remain significant clinical challenges. ctDNA is a minimally invasive biomarker that allows real-time monitoring of tumor behavior and provides information on systemic tumor burden and molecular diversity. This study aimed to systematically evaluate the diagnostic and prognostic value of ctDNA in brain metastases, with particular emphasis on the complementary roles of plasma and CSF ctDNA. PubMed, Embase, Cochrane Library, Web of Science, and ScienceDirect were systematically searched up to January 2025. Pooled ORs, SMDs, and HRs with 95% CIs were calculated using fixed-effects or random-effects models according to heterogeneity. Fifteen studies (N = 1763) were included. ctDNA positivity was significantly associated with increased risk of brain metastases (OR = 1.67, 95% CI: 1.24-2.26, p = 0.001). Subgroup analysis showed that NGS had notably higher predictive performance (OR = 5.50, 95% CI: 1.92-15.76, p = 0.002). Plasma ctDNA levels were significantly higher in patients with brain metastases (SMD = 0.51, 95% CI: 0.18-0.84, p = 0.002). Notably, CSF ctDNA positivity was strongly associated with worse overall survival (HR = 2.75, 95% CI: 1.75-4.32, p < 0.001). Plasma ctDNA serves as a non-invasive biomarker for systemic metastatic risk, whereas CSF ctDNA provides superior prognostic value for intracranial disease. Using these biomarkers together in a clinical workflow could enhance risk assessment and guide treatment decisions in patients with brain metastases.

The journal of sexual medicine

Effects of exercise on sexual activity and sexual dysfunction in patients with prostate cancer: a systematic review and meta-analysis.

At present, there is a lack of systematic evidence clarifying the overall effects of exercise interventions on sexual activity and sexual dysfunction in patients with prostate cancer, as well as the relative contributions of different exercise prescription parameters. To systematically evaluate the effects of exercise interventions on sexual activity and sexual dysfunction in patients with prostate cancer. Randomized controlled trials investigating the effects of exercise interventions on sexual activity and sexual dysfunction in patients with prostate cancer were systematically identified through searches of PubMed, Web of Science, The Cochrane Library, and Embase from inception to June 20, 2025. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and the Physiotherapy Evidence Database (PEDro) scale was used as a supplementary measure of methodological quality. Meta-analysis, sensitivity analysis, subgroup analysis, and publication bias assessment were conducted using Stata software, and the certainty of evidence was evaluated using the GRADE approach. Ten randomized controlled trials involving 558 patients were included. The mean PEDro score was 7, indicating generally acceptable methodological quality, while RoB 2 suggested that most studies had some risk of bias. According to GRADE, the certainty of evidence was high for sexual activity and moderate for sexual function. Meta-analysis showed that exercise significantly improved sexual activity (SMD = 0.38, 95% CI 0.19-0.57, P < .001) and sexual function (SMD = 0.32, 95% CI 0.07-0.56, P = .01). Subgroup analyses showed that these effects may vary according to treatment modality and exercise prescription. Exercise interventions improve sexual activity and sexual function in patients with prostate cancer, with a dose-response relationship observed for sexual activity and intensity- and duration-related effects for sexual function. This systematic review was registered with PROSPERO (CRD420251089117).

Clinical effectiveness of efgartigimod in a broad population of patients with generalized myasthenia gravis: subgroup analyses from a randomized, double‑blind, placebo‑controlled, phase 3 trial (ADAPT).

The ADAPT phase 3 trial (NCT03669588) showed efgartigimod was well tolerated and efficacious in acetylcholine receptor antibody-positive (AChR-Ab +) patients with generalized myasthenia gravis (gMG). This analysis utilized data from the ADAPT trial to investigate the efficacy and safety of efgartigimod in different patient subgroups. ADAPT included a broad population of AChR-Ab + participants who received a stable dose of ≥ 1 (any) treatment for gMG and were randomized 1:1 to efgartigimod (10 mg/kg) or placebo (administered as four once-weekly infusions per cycle) for 26 weeks. Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) responder rates in cycles 1 and 2, and rates of treatment-emergent adverse events (TEAEs) were analyzed in the following patient subgroups: history of nonsteroidal immunosuppressive treatment (NSIST), concomitant use of gMG treatments throughout the study, and baseline patient and disease characteristics, including time since diagnosis, age, baseline MG-ADL score, body mass index (BMI), sex, and prior thymectomy. In total, 129 AChR-Ab + participants were included (efgartigimod, n = 65; placebo, n = 64). Across all subgroups, higher MG-ADL and QMG responder rates were observed in participants treated with efgartigimod versus placebo during cycles 1 and 2. Rates of TEAEs were similar between participants treated with efgartigimod and placebo, regardless of concomitant gMG treatment type. Similar to outcomes observed in the ADAPT overall population, efgartigimod was well tolerated and efficacious across a broad range of patients, regardless of NSIST treatment history, concomitant use of gMG treatments, or baseline patient and disease characteristics. ClinicalTrials.gov: NCT03669588 (registered September 13, 2018).

Journal of neurology

Research landscape, thematic evolution, and translational insights of immune checkpoint inhibitor-induced colitis: a bibliometric analysis (2006-2025).

In recent years, immune checkpoint inhibitors have been widely adopted in cancer therapy. However, their use is frequently associated with the development of colitis. This study employs bibliometric methods to analyze the knowledge structure and current research trends in immune checkpoint inhibitors induced colitis. A systematic literature search was conducted within the Web of Science Core Collection database. Data analysis and visualization were performed using CiteSpace, VOSViewer, and the Bibliometrix package in R software. The present study collated 1,010 papers on ICI-induced colitis from Web of Science Core Collection, encompassing literature from 62 countries/regions, 1,873 institutions, 7,385 authors, and 373 journals. The United States demonstrated leadership in two key metrics: publication volume, with a total of 470 publications, and total citations, with a total of 41,125 citations. The University of Texas MD Anderson Cancer Center produced the highest number of publications (n=83). Wang Yinghong (n=48) emerged as the most prolific author. The Journal for Immunotherapy of Cancer was the most widely disseminated publication in this field (n=60). An analysis of keywords identified research trends beyond ICI, colitis, and irAE, including Ipilimumab, immunotherapy, Nivolumab, melanoma, cancer, and Pembrolizumab. This study performed a visual analysis of the fundamental knowledge structure underlying immune checkpoint inhibitors mediated colitis. The results indicate that future research should prioritize the exploration of combination therapies, clinical case management strategies, underlying pathogenic mechanisms, fecal microbiota transplantation, and the identification of predictive and diagnostic biomarkers for adverse events.

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

What is the best surgical approach for Pineal Region Tumors? A systematic literature review and anatomical comparative study.

Pineal region tumors pose significant surgical challenges due to their deep location and proximity to critical neurovascular structures. Despite multiple described techniques, no consensus exists on the optimal surgical approach, with the supracerebellar infratentorial (SCIT) and occipital interhemispheric transtentorial (OITA) approaches representing the most adopted corridors. A systematic literature review was conducted to evaluate surgical approaches for pineal region tumors and their associated complication profiles. In addition, anatomical dissections combined with a tumor simulation technique were used as illustrative tools to compare exposure patterns obtained through SCIT, SCIT with tentorial incision (SCIT + T), and OITA approaches. The systematic review, comprising 27 studies and 1774 patients, identified OITA (42.21%) and SCIT (38.27%) as the most frequently employed approaches. SCIT was more commonly associated with cerebellar complications, cerebrospinal fluid leaks, meningitis, and Parinaud's syndrome (p < 0.005), whereas OITA was associated with a higher incidence of homonymous hemianopia (p = 0.0011). From an anatomical perspective, infratentorial approaches provided broader exposure of the inferior quadrants (Q1, Q2), while OITA offered greater visualization of the superior ipsilateral quadrant (Q3). The addition of a tentorial incision to SCIT facilitated visualization of supratentorial quadrants (Q3, Q4), which are otherwise less accessible through the standard infratentorial corridor. Tumor simulations further illustrated that approach selection is influenced by the tumor's relationship to the deep venous system, with supratentorial routes favoring lesions anterior to the veins and infratentorial corridors favoring posterior extension. Selection between SCIT and OITA should be individualized based on tumor characteristics, venous relationships, and tentorial anatomy. Tentorial incision may expand the versatility of SCIT in selected cases.

Journal of neuro-oncology

A comparative study of Ommaya reservoir versus lumbar puncture for intrathecal chemotherapy in patients with leptomeningeal metastasis: a systematic review and meta-analysis.

Leptomeningeal metastasis (LM) is a lethal complication of advanced malignancy with limited therapeutic options and poor survival. Intrathecal chemotherapy represents a standard treatment for LM and can be administered via repeated lumbar puncture (LP) or an intraventricular Ommaya reservoir. However, the comparative efficacy and safety of these two administration routes remain unclear. This study aims to compare the clinical outcomes of intrathecal chemotherapy delivered by Ommaya reservoir versus LP in patients with LM, and to provide further evidence for clarifying the advantages of the Ommaya reservoir in clinical practice. We systematically searched PubMed, Embase and Web of Science for relevant studies published between 1986 and 2026. Studies directly comparing intrathecal chemotherapy delivered via Ommaya reservoir and LP were included in the meta-analysis. Disease control rate (DCR) was pooled as odds ratios (OR) using a random-effects Mantel-Haenszel model to account for between-study heterogeneity, and overall survival (OS) was pooled as hazard ratios (HR) using the inverse-variance method. Because adverse events (AEs) were incompletely reported in comparative studies, an additional safety analysis including single-arm cohorts was conducted using a binomial generalized linear mixed model (GLMM) with a logit link. Risk of bias was assessed using the ROBINS-I tool. A total of four comparative studies with a moderate overall risk of bias were included in our meta-analysis. Three studies contributed data on DCR, and three studies contributed data on OS. The pooled analysis showed no significant difference in DCR between the Ommaya and LP groups (OR 2.03; 95% CI 0.53-7.78, p = 0.30), with moderate heterogeneity (I² = 66%). In contrast, Ommaya-based intraventricular delivery was associated with significantly improved OS compared with LP (HR 0.39; 95% CI, 0.25-0.61, p < 0.0001), with no significant heterogeneity (I² = 0%). In the exploratory safety analysis of six single-arm cohorts, the estimated probability of overall AEs was numerically lower in the Ommaya group (OR 0.43; 95% CI, 0.21-0.87, p = 0.0191). While this finding is derived from non-comparative data and should be treated cautiously, it offers valuable insight into safety profile. Ommaya reservoir-based intraventricular administration of intrathecal chemotherapy may provide a survival advantage over LP in patients with LM, while demonstrating a generally acceptable and manageable safety profile. Further comparative studies with standardized response criteria and rigorous safety reporting are warranted.

Comparative Effectiveness of Resilience-Focused Psychological Interventions on Resilience, Anxiety, and Depression in Patients With Cancer: A Network Meta-Analysis of Randomized Controlled Trials.

Patients with cancer often experience psychological distress, which can reduce resilience, increase anxiety, and depression. Resilience-focused psychological interventions have been increasingly implemented; however, their comparative effectiveness remains unclear, as existing evidence is largely limited to pairwise comparisons. This study aimed to compare and rank the effectiveness of resilience-focused psychological interventions on resilience, anxiety, and depression among adults with cancer using a network meta analysis of randomized controlled trials. A systematic search of seven databases (CINAHL, Embase, MEDLINE Ovid, PubMed, Scopus, Web of Science, and Cochrane) was conducted from inception to December 2025. A frequentist random-effects network meta-analysis was performed using the netmeta package in R. Effectiveness was evaluated using standardized mean differences (SMDs) with 95% confidence intervals (CIs), prediction intervals, P-scores, and certainty of evidence. Twenty-six randomized controlled trials involving 2159 adults with cancer were included. Cognitive behavioral therapy (CBT) demonstrated the largest improvement in resilience (SMD = 1.14; 95% CI: 0.80, 1.48), followed by positive psychology interventions (SMD = 0.79; 95% CI: 0.56, 1.03) and Acceptance and Commitment Therapy (ACT) (SMD = 0.70; 95% CI: 0.04, 1.35). For anxiety, ACT (SMD = -0.97; 95% CI: -1.85, -0.10) and CBT (SMD = -0.73; 95% CI: -1.19, -0.27) showed the largest average reductions. For depression, CBT (SMD = -0.61; 95% CI: -0.97, -0.25) and positive psychology (SMD = -0.55; 95% CI: -0.89 to -0.20) were significant symptom reductions. Resilience-focused psychological interventions were effective, with CBT showing the most consistent benefits, followed by positive psychology interventions and ACT. These findings support integrating resilience-based interventions into oncology care to improve psychological well-being.

Psycho-oncology

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

Diagnostic predictive models for cancer-related fatigue: current evidence and future directions.

To evaluate the performance and methodological quality of published diagnostic prediction models for cancer-related fatigue (CRF), and to provide evidence for clinical practice and future research. A systematic review and meta-analysis were conducted. PubMed, Web of Science, the Cochrane Library, Embase, and Scopus were searched from inception to October 18, 2024, for studies developing or validating diagnostic prediction models for CRF. The pooled area under the receiver operating characteristic curve (AUC) and 95% confidence interval (CI) were calculated using R. Heterogeneity was assessed using the I2 statistic and Cochran's Q test, publication bias was explored using funnel plots and Egger's test, and risk of bias was evaluated with the Prediction Model Risk of Bias Assessment Tool (PROBAST). A total of 8418 records were identified, of which 13 studies met the inclusion criteria. These studies included 23 cohorts, 444,447 cancer patients, and 11 diagnostic prediction models. The pooled AUC was 0.83 (95% CI = 0.78-0.87), indicating moderate-to-good discrimination. However, substantial heterogeneity was observed (I2 > 94%), suggesting that the pooled estimate should be interpreted with caution. PROBAST assessment indicated a high risk of bias in most studies, mainly related to statistical analysis and reporting. Egger's test suggested possible funnel plot asymmetry, but this finding should be considered exploratory because of the small number of studies and high heterogeneity. Existing CRF diagnostic prediction models show moderate-to-good discrimination in research settings, but their performance varies across populations, outcome definitions, and modeling approaches. Future studies should prioritize large-scale, multi-center, multiethnic, and externally validated models to improve early identification and precise management of CRF.

The American journal of clinical nutrition

Exploring associations between maternal vitamin D-binding protein, vitamin D, and offspring asthma/recurrent wheeze.

Vitamin D-binding protein (DBP) transports vitamin D metabolites and regulates vitamin D levels in circulation. Additionally, maternal vitamin D levels during pregnancy play an important role in lung development and childhood asthma occurrence. In this post hoc analysis of a randomized controlled trial, the joint associations of maternal 25-hydroxyvitamin-D (25OHD) and DBP with offspring asthma/recurrent wheeze, for both the full cohort and stratified by maternal asthma status, are analyzed. Additionally, associations between estimated maternal free 25OHD and offspring asthma/recurrent wheeze are investigated. A total of 518 participants from the Vitamin D Antenatal Asthma Reduction Trial were included in this analysis. The primary outcome was offspring asthma/recurrent wheeze by age 3 y. Maternal plasma DBP levels were measured for 517 and 516 participants at 10-18 and 32-38 wk of gestation, respectively. Total 25OHD and DBP levels were compared across haplotypes of the group-specific component (GC) gene, which codes for DBP. Logistic regression models estimated the relationships between maternal DBP, total 25OHD, and offspring asthma/recurrent wheeze. In addition, offspring asthma/recurrent wheeze was modeled as a function of estimated maternal free 25OHD. Maternal DBP levels generally increased as pregnancy progressed. Maternal DBP and total 25OHD levels varied significantly across GC haplotypes. A significant positive interaction effect between maternal DBP and total 25OHD on offspring asthma/recurrent wheeze risk was observed for the subset of mothers without asthma. For the subset of mothers with asthma, we observed a significant negative association between estimated maternal free 25OHD and offspring asthma/recurrent wheeze, surpassing the effects of DBP or total 25OHD individually. Our study gives insight into the interplay between vitamin D metabolites during pregnancy and their associations with offspring asthma/recurrent wheeze. These results also suggest that maternal free vitamin D during pregnancy may be more biologically relevant than total vitamin D for offspring's respiratory health. This trial was registered at clinicaltrials.gov for VDAART as NCT00920621.

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

Percutaneous left atrial appendage closure following catheter ablation therapy of atrial fibrillation: outcomes stratified by bleeding risk - a sub-analysis of the OPTION study.

Concerns have been raised over the safety and necessity of continuing oral anticoagulation (OAC) in patients following catheter ablation for atrial fibrillation (AF). OPTION demonstrated the safety and efficacy of left atrial appendage closure (LAAC) in a post-ablation population. We sought to analyse the impact of baseline bleeding risk, per HAS-BLED scores, on the outcomes for patients in a pre-specified sub-analysis. Patients with AF and high stroke risk undergoing catheter ablation were randomly assigned to LAAC vs. OAC in OPTION and were stratified by HAS-BLED score: 0, 1, 2, ≥3. OPTION enrolled 1600 patients (CHA2DS2-VASc score: 3.5 ± 1.3; HAS-BLED score: 1.2 ± 0.8); randomized 1:1 to ablation/LAAC or ablation/OAC. Primary effectiveness (all-cause death/stroke/systemic embolism) and safety (bleeding composite) endpoints were directionally similar in HAS-BLED subgroups; both thromboembolic and bleeding event rates were higher in patients with increasing HAS-BLED score. A significant reduction in primary safety bleeding events was noted in favour of LAAC across HAS-BLED subgroups, with more striking reductions noted for lower HAS-BLED scores of 0 (n = 265; hazard ratio: 0.25; 95% confidence interval: 0.20, 0.50) and 1 (n = 890; hazard ratio: 0.41, 95% confidence interval: 0.27-0.61). Regardless of bleeding risk, LAAC is comparable to OAC in stroke protection while demonstrating greater freedom from bleeding in a post-ablation AF population, even in patients with low HAS-BLED scores. The OPTION study highlights an opportunity to mitigate future bleeding risk with a strategy of LAAC after ablation in patients deemed at high risk of stroke according to clinical guidelines. NCT03795298.

Multi-ancestry, trans-generational GWAS meta-analysis of gestational diabetes and glycaemic traits during pregnancy reveals limited evidence of pregnancy-specific genetic effects.

Gestational diabetes mellitus (GDM) affects ~14% of pregnancies and increases maternal type 2 diabetes mellitus (T2DM) risk. The GenDiP Consortium presents trans-generational, multi-ancestry genome-wide association study meta-analyses of GDM and pregnancy glycemic traits in up to 38,305 GDM cases and 776,145 controls. We identify 37 GDM-associated loci (7 novel) and five novel loci for pregnancy glycemic traits, all operating through the maternal genome. We classify 12 GDM variants with stronger effects in GDM than T2DM into five biologically informed categories, revealing pleiotropy patterns, pregnancy-dependent effect modification, and diagnostic heterogeneity. While all these loci overlap with T2DM and/or non-pregnant glycaemic traits, four (G6PC2, CAST-PCSK1, HKDC1, FOXA2) lack genome-wide-significant T2DM associations; GCK shows distinct causal variants for GDM, and MTNR1B exhibits pregnancy-amplified effects. Our findings provide new genetic insights into GDM and highlight the need for larger, ancestrally diverse studies of GDM and glycaemic traits during pregnancy to understand potential pregnancy-specific effects.

Nature communications

1 min2 Jun 2026

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne

Engaging with the All My Relations Advisory Board in a healthy food incentive randomized controlled trial: a qualitative process evaluation.

The FoodRx randomized controlled trial (RCT) studied the impact of a healthy food incentive program among adults with type 2 diabetes and food insecurity (including an Indigenous subset), and engaged an advisory board (All My Relations [AMR]) to advise on aspects relevant to Indigenous Peoples. We sought to explore the evolution of the board's role and its contribution and influence on the RCT. We conducted a qualitative process evaluation within community-based participatory research. We conducted semistructured interviews with AMR board members and FoodRx academic members, and sourced AMR board meeting notes. We analyzed these data iteratively using directed content analysis and continuous engagement with the AMR board. Seven AMR board members, 3 FoodRx academic members, and 4 AMR board members and FoodRx academics participated in interviews. Our analysis showed 4 key interconnected themes: Culture and ceremony (celebrating the importance of Indigenous languages, naming ceremonies, and spiritual practices fostering inclusivity and connection); Transformative environment (emphasizing a sacred gathering space where voices are equal, trust thrives, and personal growth is cultivated); Indigenous Ways of Knowing (embracing the application of Indigenous wise practices, challenging Western research ideals, and advocating for RCT design equity); and Equitable partnership (affirming the centrality of relationship building, acknowledging Indigenous knowledge, redistributing decision-making power, and increasing transparency). Our findings emphasized the importance of authentic involvement of Indigenous community representatives in the conduct of research. Research involving Indigenous participants requires a commitment to respect for Indigenous values and incorporating Indigenous Ways of Knowing, as well as involving Indigenous partners early in the planning of the project.

Asian Pacific journal of cancer prevention : APJCP

Epstein-Barr Virus and Helicobacter pylori Co-Infection in Gastric Cancer: A Systematic Review and Meta-Analysis of Case-Control and Cross-Sectional Studies.

Gastric cancer (GC) is a multifactorial malignancy in which both Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV) have been implicated. Given the high prevalence of both pathogens, we performed a systematic review and meta-analysis to estimate the prevalence of H. pylori-EBV co-infection (HECo) in GC and to evaluate its association with GC. A systematic literature search was performed using a search strategy consisting of appropriate keywords in online databases including MEDLINE, Embase, and Web of Science from inception to July 2024. Eligible case-control and cross-sectional studies in English reported H. pylori and EBV status assessed using validated assays (e.g., PCR, serology, immunohistochemistry/in situ hybridization, rapid urease test), enabling ascertainment of HECo within the same participant. Study quality was assessed using the "Newcastle-Ottawa Quality Assessment Scale" (NOS) and the Appraisal Tool for Cross-Sectional Studies (AXIS tool). Random-effects meta-analyses were used to pool prevalence estimates and odds ratios (ORs) with 95% confidence intervals (CIs), and heterogeneity was quantified using I². Eighteen studies (n = 4364; 1999-2023) were included. HECo prevalence among GC patients was 21.44% (95% CI: 9.46-33.42). HECo was associated with increased odds of GC (pooled OR = 3.09, 95% CI: 1.66-5.73; I² = 69.1%). Subgroup estimates by age (high vs low) were based on two studies per stratum and showed wide CIs (high age: OR = 9.61, 95% CI: 1.90-48.64; low age: OR = 9.52, 95% CI: 1.83-49.54) and should be interpreted cautiously. There was a significant association between the presence of metastasis, the high stage of GC, and HECo. Our results showed no significant association between moderately or poorly differentiated GC, diffuse-type GC, the presence of vessel invasion, and HECo. HECo is associated with a higher risk of GC. Future primary studies should report mutually exclusive infection categories (HP only, EBV only, both, neither) and clarify the temporal relationship between infection and GC, to better disentangle independent versus joint effects and to inform prevention strategies.

Signal transduction and targeted therapy

Dual epitope anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR)-T-cell therapy for relapsed/refractory acute myeloid leukemia.

Acute myeloid leukemia (AML) is a rapidly progressive malignancy with poor prognosis. To date, chimeric antigen receptor (CAR) T-cell therapy in AML has been limited by the lack of antigens with high specificity for AML cells. Here, we developed a synthetic T-cell receptor and antigen receptor-T (STAR-T) cell therapy targeting LILRB4, an immunosuppressive receptor highly expressed on monocytic AML blasts but not on hematopoietic stem cells. Two nanobodies with the highest affinity for LILRB4 were identified through phage display library screening and used to construct nanobody-based dual epitope anti-LILRB4 STAR-T cells, which exhibit more potent tumor inhibition in vitro and in vivo than single epitope anti-LILRB4 STAR-T cells or dual epitope anti-LILRB4 CAR-T cells do. We subsequently conducted the first human clinical trial (NCT05548088) involving 9 patients with LILRB4-positive relapsed and refractory (R/R) AML. Six patients completed the safety and efficacy evaluation (median follow-up, 10.7 months). No immune effector cell-associated neurotoxicity (ICANS) or grade ≥3 cytokine release syndrome (CRS) was observed. Three patients died due to laboratory-confirmed infections. The best overall response rate (ORR) was 50.0% (3/6) in the efficacy assessable set and 33.3% in the full analysis set. The number of LILRB4-positive STAR-T cells significantly increased, and the number of LILRB4-positive target cells decreased. Single-cell RNA sequencing revealed that monocyte-mediated suppression of autologous T-cell function may be a primary mechanism underlying the failure of STAR-T therapy in nonresponders. In conclusion, this first-in-human trial demonstrates the therapeutic potential of targeting LILRB4 with STAR-T-cell therapy in AML and warrants further investigation.

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

Preserving the right gastric artery reduces early anastomotic stenosis after McKeown minimally invasive esophagectomy: a randomized controlled trial.

Cervical anastomotic stenosis remains a common complication following totally minimally invasive McKeown esophagectomy. The role of the right gastric artery in gastric conduit perfusion is debated, especially with narrow-tube reconstructions. This study aimed to evaluate the impact of RGA preservation versus ligation on anastomotic outcomes. In a single-center randomized controlled trial, 120 patients undergoing totally laparoscopic and thoracoscopic McKeown esophagectomy for esophageal squamous cell carcinoma were assigned to RGA preservation (n = 60) or ligation (n = 60). All procedures utilized a standardized 3-cm-wide gastric conduit. The RGA was preserved laparoscopically by skeletonizing its trunk along the lesser curvature. Sample size was calculated based on the primary endpoint of anastomotic stenosis incidence. The primary endpoint was the anastomotic stenosis rate at 2 and 4 months, while the secondary endpoint was the anastomotic leakage rate. At 2 months postoperatively, stenosis was significantly lower in the preservation group (30.0% vs. 60.0%, P < 0.05). The mean number of endoscopic dilation sessions was significantly lower in the preservation group (1.5 ± 0.6) compared to the ligation group (2.8 ± 1.1) (P < 0.05). By 4 months, stenosis rates decreased to 10.0% and 18.3%, respectively (P = 0.152). As a secondary endpoint, anastomotic leakage occurred in 10.0% of the preservation group versus 16.7% in the ligation group (P = 0.283). Lymph node harvest was comparable between groups, and no conversion to open surgery occurred. Laparoscopic preservation of the right gastric artery during totally minimally invasive McKeown esophagectomy significantly reduces early anastomotic stenosis without compromising lymphadenectomy. This technique represents a safe and feasible modification in narrow-conduit reconstruction, with potential benefits for functional recovery and postoperative quality of life in the early postoperative period.

Korean journal of radiology

Assessing Treatment Response in Soft Tissue Sarcoma Using Dynamic Contrast-Enhanced MRI: A Systematic Review.

Conventional size-based criteria have limitations in accurately assessing neoadjuvant therapy (NAT) response in soft tissue sarcomas (STS). This systematic review evaluated the association between dynamic contrast-enhanced MRI (DCE-MRI) parameters and histopathology-based response to NAT in STS and summarized which DCE-MRI parameters show the most consistent associations across diverse clinical contexts. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted to identify studies evaluating treatment response to NAT in STS using DCE-MRI. Thirteen studies comprising 234 patients were included. Quantitative DCE-MRI parameters, particularly Ktrans, showed a strong predictive performance for treatment response and demonstrated high discriminatory ability in several cohorts during both early and late post-treatment phases. Related measures such as ΔKtrans, Kep, and Ve also correlated significantly with histopathologic necrosis. Semi-quantitative markers, including the integrated area under the curve in the first 60 seconds after injection (iAUC60), wash-in rate, and time-to-peak, showed consistent associations with tumor perfusion and hypoxia. Qualitative features, including time-intensity curve patterns, effectively differentiated responders from non-responders, with type II curves most strongly associated with favorable outcomes. In conclusion, DCE-MRI, particularly quantitative pharmacokinetic parameters such as Ktrans, shows promise for assessing treatment response in STS and demonstrates generally concordant associations with histopathology-based response. However, protocol and endpoint heterogeneity and small cohort sizes limit the ability to establish definitive cutoffs and reduce generalizability, highlighting the need for standardized prospective validation.

[177Lu]Lu-dota-tate versus sunitinib in patients with metastatic progressive neuroendocrine tumours of the pancreas (OCLURANDOM): a randomised, controlled, phase 2 trial.

To our knowledge, no randomised trial with peptide receptor radionuclide therapy has been done in patients with metastatic pancreatic neuroendocrine tumours. We aimed to evaluate the antitumour activity and safety of [177Lu]Lu-dota-tate in this setting. OCLURANDOM is a randomised, open-label, non-comparative, phase 2 trial conducted in ten academic centres in France. Patients aged 18 years and older with pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1) using web-based software to receive intravenous [177Lu]Lu-dota-tate (7·4 GBq every 8 weeks up to four cycles) with concomitant amino acid infusion or oral sunitinib (37·5 mg once daily). Amino acid infusion was for at least 4 h starting 30 min before [177Lu]Lu-dota-tate infusion and included 16·8 g of arginine and 22 g of lysine in 2 L until May, 2018, and, from that date, a solution of 25 g of arginine and 25 g of lysine in 2 L. Randomisation was stratified according to Ki-67, liver involvement, and previous therapies. The primary endpoint was progression-free survival at 12 months assessed by real-time central review using Response Evaluation Criteria in Solid Tumours version 1.1 in the intention-to-treat population. Cross-over was allowed. Adverse events in the as-treated population were assessed continuously during the active phase of treatment and then every 3 months. Patients and the public were not involved in the design, conduct, reporting, or dissemination plans of this research. This trial was registered with ClinicalTrials.gov, NCT02230176, and is closed to enrolment. Between Feb 13, 2015, and July 16, 2020, 84 patients were enrolled and randomly assigned to the [177Lu]Lu-dota-tate group (n=41) or the sunitinib group (n=43). 44 (52%) patients were women and 40 (48%) were men. Median follow-up was 72·5 months (IQR 61·4-88·4). Progression-free survival rate at 12 months was 33 (80·5% [90% CI 67·5-89·9]) of 41 patients in the [177Lu]Lu-dota-tate group versus 18 (41·9% [29·1-55·5]) of 43 patients in the sunitinib group. Grade 3-4 adverse events occurred in 18 (44%) of 41 patients in the [177Lu]Lu-dota-tate group and 31 (72%) of 43 patients in the sunitinib group. The most common grade 3-4 adverse events for all treatment groups were neutropenia (two [5%] of 41 in the [177Lu]Lu-dota-tate group vs 13 [30%] of 43 in the sunitinib group) and hypertension (four [10%] in the [177Lu]Lu-dota-tate group vs eight [19%] in the sunitinib group). Drug-related serious adverse events occurred in six (15%) patients in the [177Lu]Lu-dota-tate group (transaminase increase, neutropenia, thrombosis, and fever) and ten (23%) in the sunitinib group (gastrointestinal, general disorders, and sepsis). There was a 10·3-point (95% CI 2·4-18·2) difference in the Global Health Status score between the two groups in favour of [177Lu]Lu-dota-tate. Late adverse events (grade 2 or worse) were reported in 24 (60%) patients in the [177Lu]Lu-dota-tate group and in three (43%) of seven patients in the sunitinib group. One treatment-related death (acute leukaemia) occurred in the [177Lu]Lu-dota-tate group. Using sunitinib as an internal control, our results show clinically significant antitumour efficacy of [177Lu]Lu-dota-tate in pretreated, progressive, somatostatin receptor-positive, metastatic pancreatic neuroendocrine tumours, and a better quality of life during the treatment phase. Late adverse events were reported in the [177Lu]Lu-dota-tate group that might affect the tolerance of subsequent lines of treatment. French Ministry of Health, through the National Institute for Cancer.

The Lancet. Oncology

3 min2 Jun 2026

Signal transduction and targeted therapy

Sintilimab plus concurrent chemoradiotherapy for treatment of locally advanced small cell lung cancer (SINCE-01): a phase II clinical trial.

Patients diagnosed with limited-stage small cell lung cancer (LS-SCLC) face dismal long-term outcomes, as relapse occurs frequently even after standard concurrent chemoradiotherapy. Integrating immune checkpoint blockade into chemoradiotherapy regimens may enhance sustained disease control, yet prospective evidence for this strategy in LS-SCLC remains sparse. In this single-arm phase II study, we investigated sintilimab in combination with concurrent chemoradiotherapy (CCRT) among LS-SCLC patients who had favorable functional status. Twenty-two histologically verified LS-SCLC patients were treated with four 3-weekly cycles of chemotherapy alongside sintilimab, with concurrent thoracic radiation (45 Gy delivered in 30 fractions). The primary endpoint was progression-free survival (PFS). After a median follow-up of 44.7 months, the median PFS reached 29.6 months, with 12- and 24-month PFS rates of 72.7% and 54.5%, respectively. Median overall survival (OS) stood at 40.6 months, and the corresponding 12- and 24-month OS rates were 95.5% and 72.7%, respectively. An objective response rate (ORR) of 95.5% was observed. Most grade 3-4 adverse events were hematologic in nature, particularly neutropenia and thrombocytopenia. Three patients developed pneumonitis, one of whom had grade 2 or higher. No deaths attributable to treatment occurred. Elevated human leukocyte antigen class I (HLA-I+) tumor cell expression correlated with longer PFS, suggesting potential value as a predictive biomarker. These findings suggest that concurrent administration of sintilimab with CCRT demonstrates encouraging antitumor efficacy and a manageable safety profile in LS-SCLC. (Trial registration number: ChiCTR2100043184).

Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.

About 30% of men with localised prostate cancer undergoing radiotherapy with curative intent have disease recurrence associated with progression-related symptoms and substantial toxicity of salvage therapies. Previous studies with aglatimagene besadenovec (CAN-2409, hereafter referred to as aglatimagene) showed synergy with radiation and immune-mediated cytotoxicity in patients with prostate cancer. We aimed to assess whether addition of aglatimagene plus prodrug (valacyclovir) to standard-of-care external beam radiation therapy (EBRT) could improve disease-free survival in this population. We conducted a phase 3, randomised, double-blind, placebo-controlled trial at 51 medical centres (26 community and 25 institutional or military) across the USA and Puerto Rico in patients with intermediate or high-risk prostate cancer. Patients aged at least 18 years who were planning to undergo EBRT and with an Eastern Cooperative Oncology Group score of 0-2 were eligible. Patients were randomly assigned (2:1) via central block-randomisation to receive either three courses of intraprostatic aglatimagene (5 × 1011 viral particles) plus valacyclovir or placebo plus valacyclovir, with randomisation stratified by risk category and androgen deprivation therapy (ADT) use. Patients received standard-of-care EBRT (78 Gy in 2 Gy fractions) or hypofractionated EBRT (60 Gy in 3 Gy fractions or 70 Gy in 2·5 Gy fractions) with optional ADT. The primary endpoint was disease-free survival, defined as time-from-randomisation to prostate cancer recurrence or death in the intent-to-treat population (all randomly assigned patients). Safety was assessed in all individuals who received at least one injection. The trial is registered at ClinicalTrials.gov, NCT01436968, and long-term follow-up is ongoing. Between Feb 21, 2012, and Sept 9, 2021, 745 men (591 [79%] White, 121 [16%] Black) were randomly assigned to receive aglatimagene plus valacyclovir (n=496) or placebo plus valacyclovir (n=249). After a median follow-up of 50·3 months (IQR 35·2-63·3), median disease-free survival was not reached (95% CI 121·78 to not reached) in the aglatimagene plus valacyclovir group versus 86·1 (IQR 29·7-143·0) months in the placebo plus valacyclovir group (hazard ratio 0·70, 95% CI 0·52-0·94; p=0·016). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 40 (8%) of 479 patients in the aglatimagene group and 17 (7%)of 232 patients in the placebo group. The most common TEAE of grade 3 or worse was acute kidney injury in both the aglatimagene group (nine [2%] of 479 patients) and the placebo group (four [2%] of 232 patients). Serious adverse events occurred in 28 (6%) of 479 patients in the aglatimagene group and 17 (7%) of 232 in the placebo group. Treatment-related serious adverse events occurred in eight (2%) patients in the aglatimagene group (four acute kidney injury, two pyrexia, and one each influenza-like symptoms and urinary retention) and five (2%) in the placebo group (four acute kidney injury, and one each increased creatinine levels and skin rash; one patient reported two serious adverse events). No treatment-related deaths were reported. Aglatimagene plus valacyclovir was associated with longer disease-free survival than placebo plus valacyclovir when added to standard of radiotherapy for the treatment of localised prostate cancer, offering a meaningful benefit without increasing clinically significant toxicity. Candel Therapeutics and US National Institutes of Health.

The Lancet. Oncology

3 min2 Jun 2026

Holter-ECG findings after acute ischemic stroke and TIA: A systematic analysis of the MonDAFIS randomized trial.

Holter-ECG monitoring is a critical component of post-stroke diagnostics, guiding cardiac work-up and secondary stroke prevention. Abnormal ECG findings beyond atrial fibrillation (AF) in stroke patients remain understudied. The prospective multicenter MonDAFIS trial randomized patients with acute ischemic stroke or transient ischemic attack (TIA) without known AF to Holter-ECG recording up to 7 days or usual care. Holter-ECG findings from the first 72 h of the intervention arm were analyzed to provide a reference guide in clinical practice. Furthermore, 24-hour and 72-hour Holter-ECG monitoring were compared to analyze the value of prolonged monitoring. 24-hour Holter-ECGs from 1,665 patients (median age 67; 40.4% women) identified supraventricular tachycardia (SVT) in 4.1% and newly-diagnosed AF in 2.2% of patients. Premature ventricular complexes were common (85.8%), ventricular couplets (28.0%) or bigeminy (14.0%) less common. Non-sustained ventricular tachycardia (nsVT) was detected in 1.7% of patients. Extended 72-hour-monitoring in 1,283 patients led to higher detection rates across all abnormalities, doubling nsVT (4.4%) and SVT (8.8%) detection rates. Generally, we observed higher detection rates with older age. Detection rates of supraventricular arrhythmias were higher in women, whereas men exhibited higher rates of ventricular abnormalities. Post-stroke ECG monitoring detects various arrhythmias beyond AF in a substantial proportion of individuals. Longer monitoring and older age are associated with increased detection rates, with notable sex-specific differences.

The Journal of international medical research

Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular outcomes in chronic obstructive pulmonary disease: A systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials.

ObjectiveSodium-glucose cotransporter 2 inhibitors are widely used in the management of diabetes mellitus and have demonstrated substantial cardiovascular and renal protective effects, particularly in patients with heart failure. However, their impact on cardiovascular outcomes in patients with chronic obstructive pulmonary disease remains insufficiently characterized.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients with chronic obstructive pulmonary disease. The primary outcome was the composite cardiovascular outcome (defined as cardiovascular mortality and total hospitalization for heart failure). Secondary outcomes included all-cause mortality, cardiovascular death, hospitalization for heart failure, and adverse events.ResultsThree randomized controlled trials involving 1986 patients with chronic obstructive pulmonary disease were included; in total, 1113 patients received sodium-glucose cotransporter 2 inhibitors treatment and 873 received placebo. Compared with the placebo, sodium-glucose cotransporter 2 inhibitors significantly reduced the risk of the composite cardiovascular outcome (risk ratio, 0.76; 95% confidence interval: 0.65-0.87; p < 0.001) and hospitalization for heart failure (risk ratio, 0.69; 95% confidence interval: 0.58-0.83; p < 0.001). Although not statistically significant, trends toward reduced all-cause mortality (risk ratio, 0.89; 95% confidence interval: 0.73-1.08; p = 0.23) and cardiovascular death (risk ratio, 0.96; 95% confidence interval: 0.74-1.24; p = 0.73) were observed. The incidence of adverse events was comparable between the two groups.ConclusionsThe use of sodium-glucose cotransporter 2 inhibitors is associated with a reduced risk of composite cardiovascular outcomes and hospitalization for heart failure in patients with chronic obstructive pulmonary disease, without an increased risk of adverse events. However, given the limited number of available trials, these findings should be interpreted with caution, and further large-scale studies are warranted.PROSPERO registration number: CRD42024545310.

Does resistance training alone or in combination with aerobic training improve vascular function indices in adults with type 2 diabetes? A systematic review and meta-analysis of randomized controlled trials.

To systematically evaluate and meta-analytically quantify the effects of RT-based interventions-defined as resistance training alone or resistance training combined with aerobic training-on vascular function in adults with T2DM. Following PRISMA guidelines, we systematically searched PubMed, Embase, Web of Science, the Cochrane Library, Ovid, CNKI, Wanfang Data, VIP, and CBM from inception to August 2025 for randomised controlled trials evaluating resistance training alone or combined with aerobic training on vascular function in adults with T2DM. Random-effects meta-analyses were conducted using Hedge' s g and 95% confidence intervals (CIs). Heterogeneity was assessed with I², and prespecified subgroup analyses and meta-regression were performed to explore potential moderators. Compared with non-exercise controls, RT-based interventions significantly reduced arterial stiffness (Hedge' s g = -0.24, 95% CI -0.39 to -0.09; p = 0.0015) and improved endothelial function, as reflected by flow-mediated dilation (Hedge' s g = 0.61, 95% CI 0.32 to 0.89; p < 0.0001), in adults with T2DM. Subgroup analyses suggested that combined RT+AT generally produced more consistent benefits than RT alone, particularly in higher-intensity and longer-duration interventions, although meta-regression did not identify significant linear associations (p > 0.05). No significant effects were observed for wave reflection indices (Hedge' s g = -0.10, 95% CI -0.45 to 0.25; p = 0.58), and effects on peripheral haemodynamics remained inconclusive (Hedge' s g = 0.44, 95% CI -0.00 to 0.88; p = 0.05). These pooled findings should therefore be interpreted as reflecting RT-based interventions overall, rather than isolated RT per se. RT-based interventions, particularly when delivered as combined RT+AT, may improve vascular function in adults with T2DM, especially arterial stiffness and endothelial function, with moderate-certainty evidence supporting these benefits. However, because the pooled estimates reflect RT-based programmes overall and the evidence for RT alone was more limited for several outcomes, conclusions regarding isolated RT should remain cautious. Evidence for wave reflection indices remains inconclusive (moderate certainty), and evidence for peripheral haemodynamics remains inconclusive (low certainty). Further well-designed, adequately powered RCTs with standardised vascular assessments are needed to define optimal exercise prescriptions in adults with T2DM. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420261323648.

Development and application of an evidence-based three-dimensional, four-phase discharge preparation plan for type 2 diabetes patients.

To develop an evidence-based "three-dimensional integrated" four-stage discharge preparation plan for patients with type 2 diabetes mellitus (T2DM), and to investigate its effects on discharge readiness, glycemic control, self-management ability, prognosis, and to evaluate its health economic value. An evidence-based nursing approach was adopted to retrieve, appraise, and synthesize relevant evidence, forming an intervention program integrating three dimensions (evidence, process, and tools) across four stages: admission assessment, inpatient intervention, discharge reinforcement, and post-discharge follow-up. A total of 120 hospitalized patients with T2DM admitted to the endocrinology department of our hospital from April 2025 to October 2025 were randomly assigned to an intervention group and a control group, with 60 patients in each group. The control group received routine discharge guidance, while the intervention group was treated with the discharge preparation plan. Discharge readiness (RHDS scores), glycemic control indicators, self-management ability (SDSCA scores), readmission rates, and medical costs were compared between the two groups at baseline and at 1 and 3 months post-discharge, and a cost-effectiveness analysis was conducted. After the intervention, the intervention group demonstrated significantly higher RHDS total scores at discharge (75.4 ± 7.1 vs. 62.6 ± 6.8, p < 0.001) and at 3 months (87.4 ± 8.0 vs. 67.2 ± 7.6, p < 0.001). SDSCA total scores were also significantly higher in the intervention group at 3 months (78.0 ± 9.0 vs. 60.7 ± 8.5, p < 0.001). Levels of fasting blood glucose, 2-h postprandial blood glucose, and glycated haemoglobin were significantly lower in the intervention group compared with the control group (p < 0.05). Glycemic control rate at 3 months was 80.0% in the intervention group versus 46.7% in the control group (p < 0.001). The 3-month all-cause readmission rate was significantly lower in the intervention group (5.00% vs. 16.67%, p = 0.040). The average direct medical cost per patient was reduced by 633.9 yuan compared with the control group, and the cost-effectiveness ratio was more favorable (53.23 vs. 104.83 CNY/unit effect). The evidence-based three-dimensional integrated four-stage discharge preparation plan for patients with T2DM can effectively improve discharge readiness and self-management ability, optimize glycemic control, reduce readmission rates, and demonstrate clear health economic advantages, indicating that it is worthy of clinical promotion.

Prenatal exposure to asthma medications and risk of neurodevelopmental disorders and educational difficulties: A systematic review and meta-analysis.

Since asthma exacerbations during pregnancy risk maternal and fetal health, continued medication is important. However, some studies have reported adverse neurodevelopmental outcomes following prenatal exposure to asthma medication. Therefore, this systematic review aimed to collate the existing evidence on the associations between prenatal exposure to asthma medication and neurodevelopmental and educational outcomes. A systematic review was conducted in accordance with PRISMA guidelines and the PECO framework. PubMed, Medline and Embase databases were searched for studies investigating prenatal exposure to one or more asthma medication and neurodevelopmental or educational outcomes published, in English, between January 2003 and September 2024, and updated in November 2025. Studies of asthma medication used for other indications were excluded. Study quality was assessed using the Newcastle-Ottawa scale. Random-effects meta-analyses were conducted where appropriate and heterogeneity was evaluated using Cochran's Q and I2 tests. Of 16,824 studies identified by the initial search, seven were eligible for inclusion. All investigated beta-2-adrenergic agonists (B2AA), with one including B2AA as mono- and polytherapy-and one study also investigated inhaled corticosteroids (ICS) exposure. Two reported associations with autism spectrum disorder (ASD) and one with attention-deficit hyperactivity disorder (ADHD). An updated search identified one additional eligible study, which examined both ADHD and ASD, as well as other neurodevelopmental disorders. The included eight studies (n = 3,867,170 participants) comprised cohort (n = 5) and case-control (n = 3) designs and reported inconsistent results. Meta-analysis of three studies (n = 1,380,871) indicated significant associations with ASD for exposure to B2AA both preconception (aOR 1.34, 95% CI [1.19,1.52]) and during pregnancy (aOR 1.29, 95% CI [1.16,1.42]). Heterogeneity was low, with no evidence of significant publication bias. Limitations of the included studies comprised residual confounding and exposure misclassification. Additionally, studies included in the meta-analysis were few in number and did not adequately distinguish between medication effects and underlying maternal asthma. Meta-analysis suggested an association between prenatal exposure to B2AA and ASD. An association with ADHD, reported in a single study, requires corroboration. To date, based on our search strategy, no association has been reported with communication skills, motor skills, problem-solving and personal-social skills, or cerebral palsy.

PLoS medicine

Journal of palliative medicine

Narrative Medicine to Enhance the Well-Being of Caregivers in the Care of Pediatric Patients with Complex or Serious Illnesses: A Systematic Review.

Being the caregiver of a pediatric patient with a complex or serious illness can be emotionally intense and stressful. Caregiver burden significantly affects the biopsychosocial well-being of both the child and the caregiver. Interventions such as Narrative Medicine (NM) may help alleviate this burden by enhancing emotional resilience and strengthening support networks. This review aimed to explore which NM interventions can reduce the emotional burden of caregivers of pediatric patients under the age of 18. A systematic literature review was conducted to examine the benefits of NM interventions on caregiver well-being. Primary studies were included if they described NM interventions involving active written narration by caregivers (e.g., diaries, digital writing). Studies relying solely on oral storytelling or third-party facilitation (e.g., interviews, dignity therapy) were excluded. Only studies in English or Italian were considered; studies focusing on adult patients or targeting the patient rather than the caregiver were excluded. The review followed PRISMA guidelines. A comprehensive search was conducted in MEDLINE, Embase, CINAHL, Cochrane Library, and APA PsycInfo in July 2024 with no time limits. Study quality was assessed using JBI and NIH tools, and data were synthesized narratively and in tables. The search identified 1078 unique references. After screening, four studies met the inclusion criteria. Interventions ranged from narrative diaries in pediatric intensive care units to online journaling. All studies showed feasibility and acceptability, with reported benefits including emotional expression, perceived support, improved coping, and greater self-reflection. Most participants were women (85%), although the review included all caregivers regardless of gender. In conclusion, NM appears to be a promising tool to support caregivers of pediatric patients with complex or serious conditions. While preliminary findings are encouraging, further research is needed to assess long-term outcomes. Structured workshops and the involvement of NM facilitators may further support caregiver well-being and reduce psychological burden.

Digital Self-Management of Symptoms and Quality of Life for Patients With Advanced Cancer: A Randomized Clinical Trial.

Patients with advanced cancer experience substantial symptom burden that impairs health-related quality of life (HRQOL) and contributes to emergency department (ED) visits and hospitalizations. Evidence for application (app)-facilitated palliative care interventions remains limited. To evaluate whether an app-facilitated palliative care intervention integrating digital symptom monitoring with nurse-led clinical follow-up can improve outcomes among patients with advanced cancer. This multicenter randomized clinical trial was conducted at 6 palliative care clinics in Hong Kong from January 25, 2023, to February 5, 2025. Community-dwelling adults with advanced solid cancer who were no longer receiving systemic anticancer treatment were randomized 1:1 to digital symptom monitoring plus usual care or usual care alone and followed up for 18 weeks. Digital symptom monitoring combined weekly symptom reporting using the Integrated Palliative Care Outcome Scale, automated self-management guidance, and nurse-led follow-up for severe symptom alerts. The primary outcome was change in HRQOL as measured by EuroQol 5-dimension 5-level (EQ-5D-5L) assessment. Secondary outcomes included self-efficacy (6-item Self-Efficacy for Managing Chronic Disease Scale), Eastern Cooperative Oncology Group performance status (ECOG PS), ED visits, and hospitalizations. Among 1214 randomized participants (590 to digital symptom monitoring and 624 to usual care; median age, 78 [range, 31-103] years; 617 [50.8%] male), including 821 caregivers (67.6%) as application users, HRQOL was better maintained with digital symptom monitoring at week 18. Mean changes from baseline favored the intervention compared with usual care for EQ-5D-5L utility (0.49 to 0.52 vs 0.50 to 0.38; mean difference in change, -0.15 [95% CI, -0.21 to -0.10]; P < .001) and EQ-5D visual analogue scale (63.16 to 65.72 vs 63.87 to 59.69; mean difference, -6.09 [95% CI, -8.67 to -3.51] points; P < .001). Self-efficacy was better maintained with the digital symptom monitoring intervention (5.29 to 5.34 vs 5.43 to 4.87; mean difference, -0.53 [95% CI, -0.78 to -0.27]; P < .001). Deterioration in ECOG PS (44 of 367 [12.0%] vs 66 of 379 [17.4%]; odds ratio [OR], 1.22 [95% CI, 0.83-1.79]; P = .31) and ED utilization (74 of 367 [20.2%] vs 97 of 379 [25.6%]; OR, 1.27 [95% CI, 0.97-1.67]; P = .09) were similar between groups. Hospitalization outcomes favored digital symptom monitoring, including fewer participants with worsening unplanned hospitalization episodes (63 of 367 [17.2%] vs 108 of 379 [28.5%]; OR, 1.59 [95% CI, 1.21-2.10]; P = .001) and fewer inpatient days during follow-up (mean [SD], 3.4 [8.9] vs 7.3 [15.5]). In this randomized clinical trial of patients with advanced cancer, an app-facilitated palliative care intervention helped maintain HRQOL and self-efficacy and reduced acute care use compared with usual care. ClinicalTrials.gov Identifier: NCT07475312.

3 min1 Jun 2026

Japanese Encephalitis Vaccine Decision Aid for Travelers: A Randomized Clinical Trial.

Japanese encephalitis (JE) is a mosquito-borne disease with low infection risk but high consequences. Low uptake of JE vaccines among travelers persists despite effective vaccines. Tools that improve decision quality may help address this gap. To evaluate whether a web-based JE vaccine decision aid (JEVaDA) improves decision-making and vaccine uptake among Australian travelers compared with an online government JE resource. This parallel-group, single-blind randomized clinical trial was conducted online across Australia from November 6, 2024, to July 14, 2025. Adults (aged ≥18 years) planning travel to a JE-endemic country within 6 months were recruited via a research panel. Participants were randomized 1:1 to the JEVaDA intervention, developed to International Patient Decision Aid Standards, or an online government JE resource (the active comparator). The primary outcome was postintervention decisional conflict, measured using the Decisional Conflict Scale (DCS) (scores range from 0 to 100, with higher scores indicating greater conflict). Secondary outcomes included change in JE knowledge, intention to vaccinate, and self-reported vaccine uptake. Analyses used regression models adjusted for baseline values, age, and gender. Of the 1879 individuals screened, 814 were randomized and 769 completed preintervention and postintervention assessments (modified intention-to-treat population: 373 in the intervention group and 396 in the comparator group). Their mean (SD) age was 44.7 (15.2) years; 394 (51.2%) identified as women. The intervention and comparator groups showed significant reductions in decisional conflict (mean DCS score change, -10.94 [95% CI, -12.81 to -9.07] vs -11.58 [-13.24 to -9.91] points, respectively; both P < .001), with no between-group difference (β, -0.87 [95% CI, -2.93 to 1.19]; P = .41). JE knowledge improved in both groups (intervention vs comparator: 2.27 [95% CI, 2.00-2.54] vs 2.63 [95% CI, 2.36-2.91] correct responses; P < .001), with no between-group difference (incidence rate ratio [IRR], 0.95 [95% CI, 0.90-1.00]; P = .07). Positive change in intention to vaccinate occurred in 72 participants (19.3% [95% CI, 1.53%-2.33%]) in the intervention group vs 66 (16.7% [95% CI, 1.30%-2.04%]) in the comparator group (adjusted odds ratio [AOR], 1.19 [95% CI, 0.80-1.76]; P = .40). Among the 348 travelers completing follow-up after travel to JE risk areas, vaccine uptake was 35.1% overall (n = 122) and was significantly higher in the intervention group than in the comparator group (69 of 161 [42.9%] vs 53 of 187 [28.3%]; AOR, 2.22 [95% CI, 1.36-3.61]; P = .001). In this randomized clinical trial, the web-based JEVaDA was not associated with a further reduction in decisional conflict compared with an active comparator but was associated with higher vaccine uptake. These findings suggest that decision aids can support informed, values-congruent choices in complex, preference-sensitive health decisions such as travel vaccination and beyond. anzctr.org.au Identifier: ACTRN12624001176550.

3 min1 Jun 2026

Feasibility and Preliminary Effectiveness of the ChulaCancer Mobile Chatbot for Supportive Care of Patients With Breast or Colorectal Cancer Receiving Chemotherapy: Pilot Randomized Controlled Trial.

Chemotherapy-related toxicities often lead to unscheduled health care use and diminished quality of life. Digital health interventions, such as chatbots, offer a scalable solution for supportive care; however, evidence regarding their effectiveness in resource-limited, low- and middle-income settings remains limited. This study aimed to evaluate the feasibility, use, and preliminary effectiveness of a closed-loop chatbot (ChulaCancer Chatbot) in reducing unscheduled hospital visits and stabilizing quality of life among patients receiving chemotherapy for breast or colorectal cancer. This pilot randomized controlled trial enrolled 40 patients at a single academic center in Thailand, randomized 1:1 to either ChulaCancer chatbot plus usual care or usual care alone. The primary end point was the proportion of unscheduled hospital visits due to chemotherapy-related toxicities within 12 weeks of treatment initiation. Secondary end points included longitudinal quality of life changes (30-item EORTC Quality of Life Questionnaire) measured at baseline, following chemotherapy cycle 2, and following cycle 4. Use metrics were extracted from the chatbot platform. Data were analyzed using the Fisher exact test and linear mixed-effects models. The platform recorded 2393 total messages with a 70.5% (503/713) successful response rate for user-initiated queries. Unscheduled hospital visits occurred in 15% (3/20) of the chatbot group compared to 35% (7/20) of the usual care group (P=.24). While infection-related visits were similar between groups, the usual care group recorded multiple visits for low-acuity symptoms (eg, anxiety, headache, and edema) that were absent in the chatbot group. Regarding quality of life, the chatbot group demonstrated a significant mitigation of cancer-related fatigue following cycle 4 compared with the usual care group (P=.02 between groups). Additionally, the chatbot group significantly improved in global health status (P=.04) and avoided the decline in physical functioning observed in the control arm (P=.04). The integration of a closed-loop chatbot into oncology care is feasible and provides a potential secure triage mechanism that may reduce acute care use for low-acuity concerns. Future large-scale trials incorporating agentic artificial intelligence are warranted to further validate clinical and economic benefits. Thai Clinical Trials Registry TCTR20251220014; https://tinyurl.com/5b6k3e63.

JMIR formative research

Journal of robotic surgery

Percutaneous thermal ablation versus robot-assisted partial nephrectomy for localized renal cell carcinoma: a systematic review and meta-analysis stratified by tumor complexity.

Robot-assisted partial nephrectomy (RAPN) and percutaneous thermal ablation (PTA) are established treatment options for localized renal tumors. While RAPN remains the standard-of-care, PTA is increasingly adopted, particularly in patients unfit for surgery. Evidence on how tumor complexity influences comparative outcomes between these two approaches remains limited. We conducted a systematic review of major database up to December 2025 and meta-analysis. Studies directly comparing PTA and RAPN in patients with localized Renal Cell Carcinoma (RCC) were included. Outcomes of interest included local recurrence (LR), recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), estimated glomerular filtration rate (eGFR) variation, and complication rates (overall and Clavien-Dindo ≥ III). When feasible, subgroup analyses were performed according to tumor complexity (RENAL ≥ 7 or PADUA ≥ 8). Seventeen studies encompassing 2516 patients met the inclusion criteria. Patients undergoing PTA were older with higher comorbidity burden than those treated with RAPN. Primary technical failure of the first PTA session occurred in approximately 10.9% of cases. Compared with RAPN, PTA was associated with a significantly higher rate of local recurrence (pooled logRR 0.97, 95%CI 0.65, 1.28) and this finding persisted in intermediate-high complexity tumors (logRR 1.09, 95%CI 0.74, 1.44). RAPN was associated with a significantly lower hazard of recurrence (pooled logHR - 0.92; 95%CI -1.29 to -0.56), whereas the difference did not reach significance in the intermediate-high complexity subgroup (pooled logHR - 0.75; 95%CI -1.6 to 0.1). No significant differences were observed in major complications or short- and long-term eGFR variation between techniques. No significant between-group differences were found for metastatic progression, CSS, or OS. RAPN offers superior local tumor control compared to PTA, including in anatomically complex renal lesions, without an associated increase in major complications or deterioration of renal function. Long-term survival outcomes appear comparable. PTA remains an appropriate therapeutic option for carefully selected high-risk patients. However, the higher local recurrence rate and the requirement for rigorous post-treatment surveillance should be carefully considered within the context of shared decision-making.

Journal of robotic surgery

Resection quality and oncologic outcomes after robotic versus laparoscopic total mesorectal excision for mid and low rectal cancer: a systematic review and meta-analysis of randomised trials.

Total mesorectal excision (TME) for mid and low rectal cancer is technically demanding, and resection quality strongly influences local control and survival. Robotic platforms may offer technical advantages over conventional laparoscopy, but oncologic benefits remain uncertain. This meta-analysis evaluates resection quality and early oncologic outcomes using evidence exclusively from randomised trials. A PRISMA aligned systematic review of MEDLINE, Embase, CENTRAL and Google Scholar was performed to 22 September 2025. Eligible studies were parallel-group randomised controlled trials comparing robotic with laparoscopic TME for mid or low rectal adenocarcinoma, defined as tumour height of 10 cm or less from the anal verge. Co-primary outcomes were circumferential resection margin (CRM) positivity and completeness of the mesorectum. Secondary outcomes included conversion to open surgery, intraoperative complications, and three-year locoregional recurrence, disease-free survival, and overall survival. Odds ratios and hazard ratios were pooled using random effects models. Four randomised trials met inclusion, enrolling 1,952 patients. Robotic TME reduced CRM positivity (OR 0.58, 95% CI 0.38 to 0.87) and increased complete TME rates (OR 1.55, 95% CI 1.14 to 2.12). Conversion to open surgery was less frequent with robotics (OR 0.41, 95% CI 0.21 to 0.79). Intraoperative and early postoperative complications did not differ. Two trials reported three-year oncologic outcomes. Robotic TME was associated with lower three-year locoregional recurrence (OR 0.43, 95% CI 0.23-0.81) and a modest improvement in disease-free survival (HR 0.78, 95% CI 0.61-0.99), although event rates were low and estimates should be interpreted cautiously. Overall survival did not differ (HR 0.79, 95% CI 0.57-1.11). In mid and low rectal cancer, robotic TME was associated with improved pathological resection quality and lower conversion rates compared with laparoscopic TME, without clear differences in early perioperative morbidity There is emerging evidence of improved three-year locoregional recurrence and disease-free survival.

Antibody-Drug Conjugates for Locally Advanced and Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

Antibody-drug conjugates (ADCs), including enfortumab vedotin, disitamab vedotin, and sacituzumab govitecan, are altering the therapeutic landscape for locally advanced or metastatic urothelial carcinoma (la/mUC). Comprehensive comparative evidence evaluating their translation in the clinical setting and modifying clinical covariates is required. To synthesize multidimensional evidence from interventional and observational settings to evaluate clinical outcomes, define the evolving therapeutic positioning of enfortumab vedotin, disitamab vedotin, and sacituzumab govitecan, and identify drivers of heterogeneity through meta-regression. PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from database inception to October 23, 2025. Interventional and observational studies of adults with la/mUC treated with enfortumab vedotin, disitamab vedotin, or sacituzumab govitecan. Independent reviewers extracted data following PRISMA guidelines. A rigorous metadata deduplication algorithm prevented patient double-counting. Random-effects models pooled data. Bayesian network meta-analysis (NMA) used reconstructed individual patient data. Inverse-variance weighted meta-regression assessed clinical covariates. Primary outcomes were disease control rate, objective response rate (ORR), and clinical complete response. Forty independent studies involving 6085 patients were included. For enfortumab vedotin monotherapy, the pooled ORR was 43.9% (95% CI, 40.4%-47.5%) in interventional studies and 44.6% (95% CI, 41.0%-48.2%) in observational cohorts. For enfortumab vedotin plus pembrolizumab, interventional cohorts were associated with a pooled ORR of 67.5% (95% CI, 63.5%-71.3%) overall and 65.4% (95% CI, 60.0%-70.5%) in cisplatin-ineligible patients. Furthermore, disitamab vedotin plus programmed cell death protein 1 (PD-1) inhibitors was associated with an ORR of 74.7% (95% CI, 69.4%-79.4%) in interventional trials and 61.7% (95% CI, 52.6%-70.1%) observationally. Meta-regression identified prior PD-1/L1 exposure (β = -0.071; P = .003) and treatment regimen (β = -0.890; P < .001) as factors associated with primary response. Notably, the pure randomized clinical trial network meta-analysis of first-line treatments for cisplatin-ineligible patients revealed that enfortumab vedotin monotherapy was associated with a statistically significant overall survival advantage over chemotherapy (HR, 0.50; 95% CI, 0.29-0.86; posterior probability >99%). In this meta-analysis of ADCs for la/mUC, enfortumab vedotin-based regimens were associated with robust outcomes across clinical settings, and disitamab vedotin combined with immunotherapy was associated with potent clinical activity. Meta-regression indicated that prior immunotherapy exposure and hepatic tumor burden were associated with attenuated treatment responses.

Journal of the International Society of Sports Nutrition

12‑weeks fisetin supplementation and interval resistance with aerobic training: changes in Maresin‑1 and inflammatory markers in men with obesity: a randomized controlled trial.

Obesity is characterized by low‑grade chronic inflammation and impaired insulin sensitivity. Maresin‑1 (MaR1), a specialized pro‑resolving mediator, plays a critical role in terminating inflammation and supporting metabolic homeostasis; however, interventional data in humans remain scarce. This study examined whether fisetin supplementation augments the effects of concurrent interval resistance-aerobic training on Maresin‑1, pro‑inflammatory markers, and insulin resistance in obese men. In a 12‑week parallel‑group randomized controlled trial, 44 obese adult males (BMI > 30 kg/m²) completed one of four interventions: control-placebo (CP), fisetin (F) (200 mg/day), training-placebo (TP), or training-fisetin (TF). Training comprised eight resistance exercises at 60% 1RM with active rest followed by progressive aerobic bouts (50%-70% HRmax). Anthropometric and biochemical parameters, including plasma Maresin‑1, interleukin-6 (IL‑6), tumor necrosis factor-alpha (TNF‑α), fasting blood glucose (FBS), insulin, and HOMA‑IR, were assessed pre‑ and post‑intervention. Significant group × time interactions were observed for Maresin‑1 (p = 0.034), IL‑6 (p = 0.001), TNF‑α (p = 0.001), FBS (p = 0.001), insulin (p = 0.001), and HOMA‑IR (p = 0.001). Maresin‑1 increased in the TP (p = 0.001) and TF (p = 0.001) groups. IL‑6 decreased in T (p = 0.006), TF (p = 0.001), and F (p = 0.013) groups. TNF‑α decreased in all intervention groups (F, TP, and TF) (p = 0.002). FBS, insulin, and HOMA‑IR decreased significantly in all active arms (p = 0.003), with the greatest reductions in the TF group. Twelve weeks of concurrent interval resistance-aerobic training, especially when combined with fisetin, improved inflammatory resolution (↑Maresin‑1, ↓IL‑6, and ↓TNF‑α) and metabolic control (↓FBS, ↓insulin, and ↓HOMA‑IR) in obese men. The synergy between exercise‑induced adaptations and fisetin's anti‑inflammatory properties offers a promising non‑pharmacological strategy for mitigating obesity‑related metabolic risk.

2 min31 May 2026

The clinical efficacy of Astragalus-containing Chinese patent medicines in the effective treatment of heart failure: A systematic review and network meta-analysis.

The incidence of cardiovascular diseases, particularly heart failure, has been rising year by year. Traditional Chinese medicines containing Astragalus have been widely used in clinical research. However, there is no definitive research on the efficacy of proprietary Chinese medicines containing Astragalus. A network meta-analysis was conducted to investigate the efficacy and safety of oral traditional Chinese medicines containing Astragalus for the treatment of heart failure. This study searched 6 databases for clinical randomized controlled trials involving the use of traditional Chinese herbal medicines containing Astragalus alone or in combination with other drugs, with a search period from the establishment of the databases to May 27, 2025. Using the Cochrane Quality Assessment Manual, we conducted a bias analysis of the included studies, and the extracted data were analyzed using network meta-analysis in Stata 18. A total of 18 studies were included, involving 1584 patients with heart failure, with 16 types of traditional Chinese medicines containing Astragalus. The network meta-analysis via Surface Under the Cumulative Ranking Curve analysis indicated that: Compared to using Western medicine (WM) alone, Astragalus Granule + WM ranked best for improving overall clinical efficacy rate; Qiangxin Capsule + WM was optimal for improving six-minute walk test; Astragalus Granule + WM showed the best efficacy for reducing B-type natriuretic peptide levels; Yanxing Decoction + WM ranked first for lowering N-terminal pro-B-type natriuretic peptide levels; Xinlishen Compound + WM was the optimal combination for improving left ventricular ejection fraction; Qili Qiangxin Capsule + WM performed best for reducing left ventricular end-diastolic diameter; Yangxin Tongmai II Prescription + WM exhibited the highest efficacy for decreasing Minnesota Heart Failure Quality of Life Questionnaire scores. Adding oral traditional Chinese medicine containing Astragalus to WM treatment can further improve the clinical efficacy of heart failure. However, due to the limited number and quality of the included studies in this research, the above conclusions still require further validation through well-designed randomized double-blind controlled trials.

2 min30 May 2026

Triple oral therapy combining metformin, SGLT-2 and DPP-4 inhibitors versus dual therapy in type 2 diabetes mellitus: A systematic review and meta-analysis.

Triple oral therapy combining metformin, sodium-glucose cotransporter 2 inhibitor, and a dipeptidyl peptidase-4 inhibitor has been proposed as a synergistic approach to intensify glycemic control in patients with type 2 diabetes mellitus. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of triple therapy compared to dual therapy (metformin plus either sodium-glucose cotransporter 2 or dipeptidyl peptidase-4 inhibitor). Following preferred reporting items for systematic review and meta-analysis guidelines, we searched PubMed, Embase, Scopus, and Web of Science through January 2026. Studies included randomized controlled trials comparing triple versus dual therapy in adults with type 2 diabetes mellitus. Outcomes included hemoglobin A1c (HbA1c), fasting plasma glucose, body weight, achievement of HbA1c < 7%, and adverse events (AEs). Pooled standardized mean differences (SMDs) and risk ratios (RRs) were calculated using random-effects models. Eight studies encompassing 2606 participants were included. Findings indicate triple therapy significantly reduced HbA1c levels compared to dual therapy, with a SMD of - 0.54 (95% confidence interval [CI]: -0.92 to -0.16; P = .005). Triple therapy resulted in greater reduction in fasting plasma glucose, with an SMD of -0.30 (95% CI: -0.62 to 0.01; P = .06). Patients on triple therapy were more likely to achieve HbA1c levels below 7% (RR: 2.02; 95% CI: 1.55-2.63; P < .0001). Weight reduction was modest, with an SMD: -0.14 (95% CI: -0.22 to -0.07; P = .0002). No significant differences were found in total AEs (RR = 0.97; P = .69) or hypoglycemia (RR = 1.32; P = .32), although there was higher discontinuation due to AEs (RR = 2.62; P = .03). Triple therapy offers superior glycemic control over dual therapy without major safety trade-offs, though tolerability may affect long-term adherence.

2 min30 May 2026

Glucose cotransporter-2 inhibitors on mortality and hospitalization in heart failure patients: a comprehensive meta-analysis.

Heart failure (HF) remains a major global health challenge, with high rates of hospitalization and mortality despite advances in therapy. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed as antidiabetic agents, have demonstrated significant cardiovascular and renal benefits across a wide range of patients. This study aims to evaluate the impact of SGLT2 inhibitors on all-cause mortality, heart failure hospitalization, and secondary outcomes, including NT-proBNP levels, left ventricular (LV) systolic function, and diuretic efficiency in patients with heart failure, irrespective of ejection fraction or diabetes status. A systematic review and a meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases (PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science) were searched for randomized controlled trials (RCTs) published between January 2017 and November 2025. A total of 15 eligible RCTs encompassing 28,484 participants were included. Data were extracted on clinical and functional outcomes, and pooled estimates were calculated using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated using Egger's and Begg's tests. SGLT2 inhibitor therapy was associated with a 14% reduction in all-cause mortality (HR = 0.86, 95% CI: 0.79-0.92; p < 0.001) and a 26% reduction in heart failure hospitalization (HR = 0.74, 95% CI: 0.68-0.81; p < 0.001). Heterogeneity was low for mortality (I² = 18%) and moderate for hospitalization (I² = 39%). SGLT2 inhibitors also significantly decreased the NT-proBNP levels (mean difference -168.4 pg/mL, 95% CI: -245.6 to -91.2; p < 0.001) and improved the LV systolic function (LVEF + 3.8%, 95% CI: +2.4 to +5.2; p < 0.001). Diuretic efficiency improved by an average of 480 mL/day (95% CI: +290 to +640; p = 0.002). The benefits were consistent across subgroups, including patients with HFrEF and HFpEF, with or without diabetes, and across individual SGLT2 inhibitors (empagliflozin, dapagliflozin, and sotagliflozin). No significant publication bias was detected. SGLT2 inhibitors significantly reduce the mortality and heart failure hospitalizations while improving the biomarker and cardiac function parameters, independent of diabetes status or heart failure phenotype. The consistency and magnitude of benefit confirm a class effect and support SGLT2 inhibitors as foundational therapy for heart failure across all ejection fraction categories.

Pediatric transplantation

The Impact of Pre-Transplant Ventricular Assist Device Support on Survival After Heart Transplantation in Pediatric Patients: A Systematic Review and Meta-Analysis of Reconstructed Time-To-Event Data.

Heart transplantation is the gold standard therapy for pediatric end-stage heart failure. Ventricular assist devices (VADs) have improved waitlist survival, but their effect on post-transplant outcomes remains uncertain. This study aimed to evaluate the impact of pre-transplant VAD support on outcomes in pediatric heart transplant recipients. We performed a systematic review and a meta-analysis using three different databases to compare outcomes in pediatric heart transplant recipients with and without pre-transplant VAD support. The primary outcome was long-term survival. Secondary outcomes were postoperative stroke, hospital length of stay (LOS), and post-transplantation rejection. A total of 3247 studies were identified, of which five were included in the analysis. There was no significant difference in long-term survival among patients who survived to transplantation between the groups (HR 0.963; 95% CI 0.84 to 1.10; p = 0.582). However, the postoperative stroke rate was significantly higher in the VAD group (OR 2.17; 95% CI 1.63 to 2.89; p < 0.0001), while no significant differences were observed in hospital LOS (SMD -0.09; 95% CI -0.33 to 0.14; p = 0.4375) or post-transplant rejection (OR 1.18; 95% CI 1.00 to 1.39; p = 0.0505). Pre-transplant VAD support was associated with non-inferior survival despite greater baseline severity among patients who survived to transplantation, enabling access to transplantation, but at the cost of higher VAD-related complications, particularly stroke, with no differences in hospital LOS or rejection.

Probiotics, synbiotics and berberine in Type 2 diabetes mellitus: A systematic review, meta-analysis, and molecular dynamics simulation study.

Type 2 diabetes mellitus is characterized by impaired regulation of blood glucose. Probiotics, synbiotics, and berberine (BBR) have been proposed as adjunctive interventions, but their overall effectiveness remains uncertain. To evaluate the effects of these interventions on glycemic control and to explore a potential molecular interaction of BBR with a key carbohydrate-digesting enzyme. A systematic review and meta-analysis of randomized controlled trials was conducted. Pooled effects were estimated for fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) using random-effects models. A subgroup analysis compared probiotics with placebo. An exploratory computational analysis examined the interaction of BBR with α-glucosidase. More than 30 trials involving over 2,000 participants were included. The pooled analysis showed significant but modest reductions in FPG (-0.71 mmol·L ⁻ ¹) and HbA1c (-0.19%), with substantial between-study variability. Probiotics alone also reduced FPG (approximately -0.80 mmol·L ⁻ ¹) and HbA1c (approximately -0.21%) compared with placebo. Computational analysis indicated weaker enzyme binding for BBR than for the reference inhibitor acarbose. Probiotics, synbiotics, and BBR provide statistically significant but clinically modest improvements in glycemic control. These findings support their use as adjunctive, rather than primary, therapeutic options and highlight the need for larger and longer trials with standardized interventions. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251116387, identifier CRD420251116387.

PloS one

1 min29 May 2026

Comparison of effectiveness and safety of bexagliflozin and other sodium-glucose cotransporter 2 inhibitors for type 2 diabetes mellitus in adults: systematic review and network meta-analysis of randomized controlled trials.

Bexagliflozin exerts definite efficacy in the treatment of type 2 diabetes mellitus (T2DM). However, whether this novel sodium-glucose cotransporter 2 (SGLT2) inhibitor is superior to other SGLT2 inhibitors remains to be elucidated. We therefore performed this network meta-analysis (NMA) to compare bexagliflozin with other SGLT2 inhibitors and establish an efficacy hierarchy in T2DM management. We systematically searched PubMed, Embase, Web of Science and the ClinicalTrials.gov registry for eligible randomized controlled trials (RCTs) published up to January 2026. Statistical analysis was conducted using Stata 14.0. Risk of bias was assessed by the Cochrane tool, evidence certainty was evaluated using the Confidence in Network Meta-Analysis (CINeMA) approach, and intervention ranking was performed using surface under the cumulative ranking curve (SUCRA) values. This NMA included 48 studies with 26,838 patients. Bexagliflozin significantly reduced HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with placebo. For HbA1c reduction, canagliflozin (300 mg, 100 mg) and empagliflozin 25 mg were more effective than bexagliflozin, while bexagliflozin was comparable to other SGLT2 inhibitors. For FPG reduction, canagliflozin 300 mg and empagliflozin 25 mg showed slightly greater effects than bexagliflozin, with no significant differences between bexagliflozin and other comparators. Bexagliflozin was superior to dapagliflozin 5 mg but slightly inferior to canagliflozin 300 mg for weight loss, while showing comparable efficacy to other SGLT2 inhibitors. It achieved similar SBP and DBP reduction to other SGLT2 inhibitors, with a significantly greater DBP-lowering effect than empagliflozin 10 mg. Bexagliflozin had a lower incidence of urinary tract infection than dapagliflozin (5 mg, 10 mg), with comparable safety to other agents and placebo. Canagliflozin 300 mg showed the best efficacy for HbA1c, FPG and weight control. Bexagliflozin demonstrates comparable efficacy to most SGLT2 inhibitors in T2DM patients, with a relatively prominent benefit in body weight reduction and a similar safety profile. Canagliflozin 300 mg provides more effective glycemic and weight control.

Comparative effectiveness of high-intensity interval training versus moderate-intensity continuous training in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

To systematically evaluate and compare the effects of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) on key glycemic indicators and related metabolic parameters in patients with Type 2 Diabetes Mellitus (T2DM). Databases including PubMed, Web of Science, Cochrane Library, CNKI, and Wanfang were searched to collect randomized controlled trials (RCTs) published up to October 2025 on HIIT and MICT in T2DM. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. A meta-analysis was then performed using RevMan 5.4. A total of 21 RCTs involving 831 T2DM patients were included. The meta-analysis results showed that compared to a normal control group, both HIIT and MICT significantly reduced fasting blood glucose (FBG) and increased patients' VO2max levels. HIIT significantly reduced patients' glycated hemoglobin (HbA1c) levels, body mass index (BMI), and significantly increased high-density lipoprotein (HDL) levels. Compared to MICT, HIIT was more effective in reducing FBG and provided a greater increase in maximal oxygen uptake (VO2max). Both HIIT and MICT effectively reduced HbA1c in T2DM patients, although there was no significant difference in the effect between the two modalities. Regarding BMI, low-density lipoprotein (LDL), and HDL, the two exercise modalities did not show statistically significant differences. In the management of T2DM, HIIT offers greater advantages in improving FBG and enhancing VO2max, providing a basis for the scientific and effective management of T2DM. However, due to the limitations in the number and quality of the included studies, the above conclusions require verification through more high-quality research.

Journal of diabetes research

Achieving Diabetes Remission Through Dietary Intervention: A 12-Month Randomized Controlled Trial of Caloric-Carbohydrate Restriction in Overweight Patients With Early-Stage Type 2 Diabetes Mellitus.

We are aimed at evaluating the effects of a calorie-restricted low-carbohydrate diet (CR-LCD) on diabetes remission, weight control, and metabolic parameters in overweight patients with early-stage Type 2 diabetes mellitus (T2DM). This 6-month randomized intervention trial with a 12-month follow-up randomly assigned 68 adults with early-stage T2DM to receive either a CR-LCD or a control diet. Of the original cohort, data from 66 participants (two dropouts in the CR-LCD group) were analyzed. The primary outcome was diabetes remission, defined as achieving a glycated hemoglobin (HbA1c) level < 6.5% without glucose-lowering medications; secondary outcomes included anthropometric, glycemic, and lipid parameters. The CR-LCD group had a significantly higher 6-month diabetes remission rate than the control group (62.50% vs. 35.29%, χ2 = 4.885, p = 0.027). After multivariate adjustment, the intervention was associated with higher remission rates (odds ratio [OR] = 4.592, 95% confidence interval [CI]: 1.276-16.524; p = 0.020). At 12 months, between-group comparisons following false discovery rate (FDR) correction revealed significant differences in body mass index (FDR - adjusted p = 0.006, η2p = 0.150), waist circumference (FDR - adjusted p = 0.040, η2p = 0.085), fasting blood glucose (FDR - adjusted p < 0.001, r = 0.613), 2-h postprandial blood glucose (FDR - adjusted p = 0.040, η2p = 0.088), and high-density lipoprotein cholesterol (FDR - adjusted p = 0.040, η2p = 0.095). No severe adverse events were reported. A CR-LCD was effective in inducing diabetes remission in early-stage T2DM, suggesting that it may offer a viable nonpharmacological management strategy for this condition. Chinese Clinical Trial Registry: ChiCTR2600118189.

Effects of pneumatic tube systems on next-generation viscoelastic coagulation test devices in septic patients and healthy individuals: Results of the randomized controlled VETaPT trial.

Rapid coagulation assessment is essential in critical care to enable timely correction of coagulopathy. Viscoelastic testing (VET) supports this goal but may be affected by mechanical stress during transport by pneumatic tube systems (PTS). As PTS are widely used to expedite sample delivery, evaluating the robustness of next-generation VET and platelet function assays under these conditions is crucial for reliable, time-sensitive diagnostics in intensive care. This study investigated the impact of PTS transport on VET and platelet function testing in healthy individuals and septic patients, including quantitative analysis of acceleration forces. This randomized trial applied a non-systematic sample-level allocation of paired blood samples from 46 healthy volunteers and 45 septic patients to manual and PTS transport. Acceleration was quantified via three-axis accelerometry. Samples were analyzed using ClotPro, ROTEM, TEG PlateletMapping, and Multiplate. Primary objective was the difference in test results following both transport modes. Analyses were performed on paired datasets (manual vs. PTS) per participant and assay. As pre-specified in the protocol, logistic regression modeled the probability of a clinically relevant EX-test clotting time (CT) change (≥ 10 s) within each cohort. Given the absence of associations, secondary equivalence analyses (TOST [two one-sided tests] and bootstrap) assessed whether observed effects were within pre-specified bounds. Neither logistic regression nor correlation analysis indicated an effect of mechanical stress on variable changes (all ρ < 0.5; p > 0.01). Across platforms, most viscoelastic and platelet function variables remained within predefined equivalence margins after PTS transport. Exceptions were TEG PlateletMapping HKH-R and, by bootstrap, ADP/AA-inhibition. In healthy volunteers, equivalence was confirmed for all variables (TOST p < 0.001). In septic patients, minor shifts remained within clinically acceptable limits, with equivalence confirmed for ClotPro IN-test CT (± 16s, plower = 0.036; pupper < 0.001), EX-test MCF (± 2 mm, both p < 0.001), ROTEM INTEM CT (± 16s, both p < 0.001), Multiplate TRAP (± 10U, plower = 0.001; pupper < 0.001), and TEG PlateletMapping ADP/AA inhibition (± 5%, both p < 0.05). Most next-generation viscoelastic and platelet assays are robust to PTS-induced stress. Coagulation diagnostics can include PTS transport without compromising validity. Only selected TEG PlateletMapping variables exhibited variability, indicating limited robustness. Trial registration: The study is retrospectively registered with the German Clinical Trials Register (DRKS00036231; https://drks.de/search/de/trial/DRKS00036231/details on 20.02.2025).

African journal of reproductive health

A systematic review of pregnancy outcomes and management in polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) now known as Polyendocrine Metabolic Ovarian Syndrome (PMOS), affects 5-20% of women of reproductive age, it is the leading cause of anovulatory infertility accounting for 70-90% of cases and resulting in lower natural conception rates and a significant contributor to adverse pregnancy outcomes. Following PRISMA 2020 guidelines, this systematic review synthesized evidence from 2014–2025, evaluating the evolving landscape of PCOS pregnancy management. It explores the relationship between PCOS and reproductive outcomes, details specific maternal and perinatal complications, and discusses the latest evidence-based interventions and emerging therapies to improve pregnancy outcomes and the long-term health of both mother and child. The findings revealed that the syndrome's pathophysiology driven by hyperandrogenism, insulin resistance, and obesity significantly increases the risks of early pregnancy loss, gestational diabetes, and pre-eclampsia. There is a paradigm shift toward individualized, multidisciplinary care. Evidence-based strategies highlight the superiority of letrozole for ovulation induction, the metabolic benefits of metformin, and the necessity of nuanced lifestyle interventions over simple weight-loss models. Furthermore, emerging research into immune-metabolic pathways, such as Interleukin-22, suggests novel therapeutic directions. The review concludes that recognizing PCOS as a high-risk obstetric condition and integrating early metabolic screening into standard care are essential to improving maternal and neonatal outcomes. Le syndrome des ovaires polykystiques (SOPK), maintenant connu sous le nom de syndrome métabolique ovarien polyendocrinien (PMOS), qui touche 5 à 20 % des femmes en âge de procréer, est la principale cause d'infertilité anovulatoire (70 à 90 % des cas). Il entraîne une diminution des taux de conception naturelle et contribue significativement aux complications de la grossesse. Conformément aux recommandations PRISMA 2020, cette revue systématique a synthétisé les données probantes de 2014 à 2025, évaluant l'évolution de la prise en charge des grossesses chez les femmes atteintes de SOPK. Elle explore la relation entre le SOPK et les issues de la reproduction, détaille les complications maternelles et périnatales spécifiques et présente les interventions fondées sur des données probantes les plus récentes ainsi que les thérapies émergentes visant à améliorer les issues de grossesse et la santé à long terme de la mère et de l'enfant. Les résultats ont révélé que la physiopathologie du syndrome, caractérisée par un hyperandrogénisme, une résistance à l'insuline et une obésité, augmente significativement les risques de fausse couche précoce, de diabète gestationnel et de prééclampsie. On observe un changement de paradigme vers une prise en charge individualisée et multidisciplinaire. Les stratégies fondées sur des données probantes soulignent la supériorité du létrozole pour l'induction de l'ovulation, les bénéfices métaboliques de la metformine et la nécessité d'interventions nuancées sur le mode de vie plutôt que de simples programmes de perte de poids. De plus, les recherches émergentes sur les voies immunométaboliques, telles que l'interleukine-22, suggèrent de nouvelles pistes thérapeutiques. Cette revue conclut que la reconnaissance du SOPK comme une pathologie obstétricale à haut risque et l'intégration d'un dépistage métabolique précoce dans les soins courants sont essentielles pour améliorer les issues maternelles et néonatales.

3 min28 May 2026

European respiratory review : an official journal of the European Respiratory Society

Validating exacerbations of asthma in electronic health records: a systematic review.

Previous studies have shown that the algorithms and code lists used to define asthma exacerbations vary across different sources of data, if reported at all. Defining and validating asthma exacerbations in electronic health records (EHR) would help to improve future research on asthma using EHR by leading to more consistent and comparable evidence. We systematically reviewed the literature to evaluate studies that define exacerbations of asthma in EHR and report which algorithms have the highest validity. An adapted version of the QUADAS-2 designed for this review was used to assess risk of bias. Of the studies yielded by the search, only five met the inclusion criteria. Eligible studies used algorithms that contained codes from versions or modifications of either the 9th or 10th revisions of the International Statistical Classification of Diseases and Related Health (ICD-9 or ICD-10), and validity scores varied. Using the ICD-9 code 493 within algorithms to detect asthma exacerbations, sensitivity scores varied from 44.8% to 91.28% and specificity was >85%. Using the ICD-9 code 493.xx as the principal and secondary diagnosis in claims data, validity measures were all >85%. Using the ICD-10 code J45, scores for sensitivity, specificity and negative predictive value were also all >85%. Algorithms have been used to identify asthma exacerbations in EHR with varying degrees of validity. Algorithms including the ICD-9 code 493.xx or the ICD-10 code J45 to detect asthma exacerbations had high validity scores. However, there was a risk of bias in these studies and urgent work is needed using robust methods to validate definitions for future research using EHR.

2 min28 May 2026

Medicina (Kaunas, Lithuania)

Pharmacological Strategies for Preventing Postoperative Recurrence in Crohn's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background and Objectives: Despite surgical intervention for remission, recurrence is nearly inevitable in patients with Crohn's disease (CD). While several maintenance therapies are available, the optimal strategy for preventing postoperative recurrence remains uncertain. Materials and Methods: This systematic review and network meta-analysis included placebo-controlled or head-to-head randomized controlled trials (RCTs) from MEDLINE, Embase, and Cochrane Central up to 4 July 2024. Studies assessed maintenance therapies for CD after curative resection. Data were extracted from intention-to-treat (ITT) and per-protocol (PP) analyses separately. The primary outcomes were endoscopic and clinical relapse. A Bayesian network meta-analysis provided risk ratios (RRs) and 95% confidence intervals (CIs). This study is registered with PROSPERO (CRD42024629013). Results: From 1492 screened records, 45 randomized controlled trials met the inclusion criteria. Compared with placebo, clinically significant prevention of clinical recurrence was achieved with adalimumab (RR = 0.17; GRADE High), nitroimidazoles (RR = 0.35; High), infliximab (RR = 0.59; Moderate), thiopurine analogs (RR = 0.41; Moderate), and high-dose mesalamine (RR = 0.74; High), while azathioprine-metronidazole combination therapy demonstrated superior efficacy to azathioprine monotherapy. For endoscopic recurrence mitigation, therapeutic efficacy was confirmed for adalimumab (RR = 0.24; Low), infliximab (RR = 0.32; Moderate), vedolizumab (RR = 0.36; Low), and thiopurine analogs (RR = 0.64; Moderate). Conclusions: This network meta-analysis establishes pharmacological hierarchies for preventing postoperative Crohn's disease recurrence. Adalimumab is the most effective monotherapy for clinical recurrence prevention, while combination therapies of adalimumab/azathioprine plus nitroimidazole show superior efficacy. For endoscopic recurrence prevention, adalimumab also ranks as the most effective intervention. These findings guide therapy selection but require validation for newer agents through randomized trials.

The impact of comorbid type 2 diabetes on survival outcomes in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis focusing on lung cancer.

Tumor patients with type 2 diabetes mellitus (T2DM) have a more immunosuppressive tumor microenvironment and weaker T-cell immune response to tumors within the tumor compared to non-T2DM patients when treated with immune checkpoint inhibitors (ICIs).In addition, high blood glucose levels may promote tumor immune escape. These factors may lead to a poor response to ICIs treatment in tumor patients with T2DM, affecting treatment prognosis. Although some studies have explored the association between tumor patients with T2DM and the prognosis of ICIs treatment, there is still controversy. Therefore, this study systematically evaluated the impact of T2DM on the prognosis of ICIs treatment in tumor patients through a meta-analysis, aiming to provide more accurate guidance for clinical practice and optimize the treatment strategy for tumor patients with T2DM. We systematically searched PubMed, Embase, Web of Science, CNKI, and Wanfang Database to collect studies published from the database establishment to January 2026 that investigated the association between tumor patients with T2DM and the prognosis of ICIs treatment. The Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) was used to evaluate the risk of bias. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to assess the association between tumor patients with T2DM and the prognosis of ICIs treatment. The primary outcomes included overall survival (OS) and progression-free survival (PFS). Meta-analysis was conducted using RevMan 5.3 software. A total of six studies were included, involving 1,225 participants. The meta-analysis showed that patients with T2DM who received ICIs treatment had poorer OS (HR = 1.49, 95%CI:1.25-1.77, P < 0.00001) and PFS(HR = 1.38, 95%CI:1.04-1.83, P = 0.03).Subgroup analyses indicated that regardless of sample size (<200 vs >200) or type of survival analysis (univariate vs multivariate), patients with tumors and T2DM who received ICI treatment were consistently associated with poorer OS. Regarding PFS, a worse outcome was observed in T2DM patients when the sample size was less than 200 or when univariate analysis was applied. However, no significant statistical difference in PFS was found between non-T2DM and T2DM patients treated with ICIs when the sample size exceeded 200 or when multivariate analysis was performed. Based on the current limited evidence, this meta-analysis suggests that T2DM may be associated with poor OS in lung cancer patients treated with ICIs. However, due to the small number of included studies, limited sample size, inherent bias risks of the retrospective design, heterogeneity of tumor types, and the instability of PFS results. The conclusion of this study belongs to the 'put forward hypothesis' level and is not yet sufficient to support clinical practice recommendations. The current evidence cannot determine whether glycemic control can improve the efficacy of ICIs. Future studies need to verify this finding through large-sample, prospective cohort studies and clarify the independent impact of glycemic control levels on the efficacy of ICIs.

3 min27 May 2026

Medicina (Kaunas, Lithuania)

MASLD and Atherosclerosis in Patients with Type 2 Diabetes Mellitus: A Systematic Review.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among patients with type 2 diabetes (T2D) and has been increasingly recognized as a potential contributor to cardiovascular (CV) disease. However, the relationship between MASLD and subclinical/clinical atherosclerosis remains controversial, with inconsistent findings across imaging modalities and study populations. Methods: A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261347480). Literature searches were performed across the PubMed, Scopus, and Web of Science library databases from 1 January 2016 to 27 March 2026, using the terms: "MASLD AND (type 2 diabetes OR type 2 diabetes mellitus OR T2DM) AND atherosclerotic plaque" for each of the three databases. Inclusion criteria comprised original full-text English-language studies, published in the last 10 years and conducted in adults, reporting data regarding the evaluation of atherosclerosis in patients with T2D and MASLD/NAFLD. Exclusion criteria are letters to the editor, expert opinions, case reports, conference or meeting abstracts, reviews, and redundant publications; having unclear or incomplete data; and being performed in vitro (cell cultures) or in animal models. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Results: The included studies, predominantly cross-sectional and a single longitudinal study, as well as different modalities of evaluating atherosclerosis, showed heterogeneous findings. MASLD is associated with increased carotid plaque progression, including in lean individuals. Its relationship with carotid intima-media thickness (CIMT) is inconsistent across studies, with some reporting higher values and others finding no significant association after adjustment. Hepatic fibrosis appears more strongly linked to vascular aging than steatosis alone, with variability likely due to differences in study methods and populations. Conclusions: The presence of both MASLD and T2D may be associated with atherosclerosis across different stages, from subclinical changes to clinically manifest disease, particularly at more advanced stages such as plaque presence or progression, whereas its relationship with early markers like pulse wave velocity or CIMT remains inconsistent. Liver fibrosis may represent a stronger determinant of atherosclerosis than hepatic steatosis alone. Although the evidence base is limited and largely derived from a small number of predominantly cross-sectional studies, further standardized and prospective research is warranted to better define these relationships and evaluate CV risk stratification in patients with T2D.

Global research trends, reporting and handling of missing data in observational studies of type 2 diabetes mellitus with mild cognitive impairment from 2020 to 2025: a systematic review.

Missing data is common in observational studies, and even more so in type 2 diabetes mellitus with mild cognitive impairment(T2DM-MCI), which limits the completion of assessments. We evaluated the extent, current reporting, and handling of missing data, as well as the prevailing research trends in observational studies related to T2DM-MCI. A systematic search of PubMed, Embase, and Cochrane Library was conducted from January 2020 to April 2025 to identify observational studies related to T2DM-MCI. Bibliometrics was performed using VOSviewer and CiteSpace to evaluate publishing trends, authors, journals, and keywords. The reporting and handling of missing data were assessed according to the guidelines recommended by STROBE and Sterne et al., with a focus on the recording, causes, mechanisms, processing methods, and sensitivity analysis of missing data. Data analysis was conducted using SPSS 26, and visualization was performed using Origin Pro 2024. Among the 4,471 screened records, 88 studies (78 in English and 10 in Chinese) were included in this analysis. Among the 78 English articles, the annual publication volume exhibited fluctuations, peaking in 2024. Chinese institutions and authors led in research output. Diabetes, Metabolic Syndrome, and Obesity had the highest publication volume (7, 8.97%). Keyword identified five clusters: 1) resting-state functional magnetic resonance imaging, 2) metabolic disorders, 3) clinical assessment tools, 4) molecular mechanisms, and 5) emerging fields such as the gut microbiome. Only 22.7% (n = 20) of the studies quantified the missing data, with an average of 9.1%. Among studies with missing data (n = 23), 52.2% (n = 12) provided reasons for missing data, primarily citing poor quality of data collection (41.7%) and loss to follow-up (41.7%). Complete case analysis was the predominant method for addressing missing data (93.3%). No study articulated the hypothesized mechanisms underlying the missing data, and only 4.4% (n = 1) performed a sensitivity analysis. In the domain of T2DM-MCI, research outcomes post-COVID-19 pandemic indicate a rebound, with China maintaining a leading position in scientific research output. However, the reporting of missing data remains ambiguous, and the methods employed to handle such data are insufficient, which may potentially introduce bias. https://doi.org/10.17605/OSF.IO/EZDXM.

International journal of molecular sciences

Do We Have Enough Evidence That Metformin Is Superior to Other Antidiabetic Drugs in Pancreatic Cancer Risk Reduction?

The current literature indicates that type 2 diabetes (T2DM) significantly increases the risk of cancer, including pancreatic cancer (PC). While metformin's primary role is the management of T2DM, its utility extends to systemic anti-cancer effects against various cancers. Nevertheless, its impact appears limited to risk reduction, as its efficacy as a primary or adjuvant treatment for established cancer remains unproven in clinical settings. This meta-analysis aimed to evaluate the association between metformin use-both as monotherapy and in combination with other antidiabetic drugs (ADs)-and the risk of PC. We synthesized data from 16 observational studies identified through PubMed, Cochrane Library, and Clinical Trials using the Population, Intervention, Comparison, Outcomes, and Study Type (PICOT) framework. The data were analyzed using Cochrane Review Manager software 5.4, with results reported as the relative risk (RR) and 95% confidence interval (95% CI) for each comparative group; statistical significance was defined as p-value < 0.05. Our findings indicate that metformin demonstrated a significant reduction in overall PC risk when compared to the pooled group of alternative ADs. Furthermore, metformin significantly lowers PC risk compared to sulfonylureas (SUs), alpha-glucosidase inhibitors (AGIs), and insulin. Conversely, metformin use was associated with a markedly elevated PC risk relative to thiazolidinediones (TZDs) and DPP-4 inhibitors (DPP4i). Considering metformin monotherapy vs. its combination with other ADs, we found that metformin lowered the risk of PC compared to its combination with SUs and AGIs but elevated the PC risk relative to its combination with TZDs and DPP4i. To conclude, these results suggest that metformin may protect patients with T2DM from PC development. However, individual PC risk and diabetes compliance should be taken into account when deciding whether to add an additional AD(s) to metformin therapy.

Advances in respiratory medicine

Association Between Air Pollution and Childhood Asthma: A Systematic Review of Recent Evidence.

Air pollution is a major environmental determinant of respiratory health and a significant contributor to the global burden of childhood asthma. Although several recent narrative and systematic reviews have examined environmental triggers of asthma, highlighting air pollution as a consistent risk factor across diverse populations and study designs, recent epidemiological evidence-including multicenter cohort studies and region-specific analyses from Europe and Greece-has not been systematically synthesized. To systematically review recent epidemiological evidence (2000-2025) on the association between ambient air pollution and childhood asthma incidence and exacerbations, with emphasis on European and Greek populations. Following PRISMA guidelines, we systematically reviewed observational studies published between 2000 and 2025 in PubMed, Scopus, Web of Science, BMC, and Google Scholar. Studies evaluating quantitative exposure to PM2.5, PM10, NO2, O3, or SO2 and asthma incidence, prevalence, or exacerbations in children (≤18 years) were included. Evidence was synthesized by pollutant type, exposure window, geographic region, and study design. Twenty-four studies involving more than 3.5 million children were included. Consistent associations were observed across international and European cohorts between long-term exposure to PM2.5, PM10, and NO2 and increased asthma incidence. Risk estimates typically ranged from 15% to 30% increases in asthma incidence per 10 μg/m3 increase in long-term exposure to PM2.5 or NO2, as reported across multiple cohort analyses. Early-life exposure showed the strongest effects on asthma development and lung function decline. European and Greek studies demonstrated comparable trends, highlighting increased hospitalizations and symptom burden in urban populations despite pollutant concentrations often below current regulatory thresholds. Short-term pollution peaks were additionally associated with increased asthma exacerbations and hospital admissions, particularly during seasonal episodes of elevated particulate matter and ozone concentrations. This review provides an updated synthesis of 21st-century evidence demonstrating that ambient air pollution is a major and modifiable determinant of childhood asthma. The consistency of findings across regions, combined with limited longitudinal evidence from Greece, highlight the importance of improved air-quality management and continued public-health efforts to reduce exposure and the need for enhanced epidemiological monitoring.

Vitamin D Supplementation in Children with Asthma: An Umbrella Review.

Growing evidence suggests that vitamin D plays a role in the pathophysiology of childhood asthma. However, its effectiveness in reducing asthma exacerbations and improving asthma-related outcomes remains controversial. We systematically searched PubMed, Embase, and the Cochrane Library from inception to 25 February 2026. Meta-analyses of randomized controlled trials (RCTs) evaluating the effects of vitamin D supplementation on any health outcomes in children with asthma were included. Methodological quality was assessed using the AMSTAR 2 tool. The credibility of evidence was evaluated using pre-specified evidence classification criteria, and the certainty of evidence was graded using the GRADE approach. A total of 14 systematic reviews were included, of which one was rated as high quality, six as low quality, and seven as critically low quality according to AMSTAR 2. Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D levels in children with asthma (MD = 10.68 ng/mL; 95% CI, 6.30 to 15.05; n = 8 RCTs), although the evidence was of low credibility (class IV) and very low certainty. No significant improvements were observed in Childhood Asthma Control Test scores (MD = 0.15; 95% CI, -0.43 to 0.74; n = 3 RCTs; class V; moderate), overall asthma exacerbations (RR = 0.84; 95% CI, 0.65 to 1.08; n = 11 RCTs; class V; low), or lung function as measured by percent predicted forced expiratory volume in 1 second (SMD = 0.49; 95% CI, -0.05 to 1.04; n = 5 RCTs; class V; moderate). One meta-analysis suggested a possible reduction in asthma recurrence (RR = 0.53; 95% CI, 0.35 to 0.79; n = 6 RCTs; class IV; moderate). This umbrella review found no convincing evidence that vitamin D supplementation improves asthma control, reduces exacerbations, or enhances lung function in children with asthma, despite its effect on increasing serum 25-hydroxyvitamin D levels and a possible benefit for asthma recurrence. However, these findings should be interpreted with caution, considering that the available evidence was limited by generally low methodological quality, substantial overlap among meta-analyses, and incomplete reporting of clinically relevant modifiers.

Nutrients

Handgrip weakness is associated with motor cortex atrophy in rheumatoid arthritis: a cross-sectional study with a hand exercise intervention.

Handgrip strength (HGS) in rheumatoid arthritis (RA) is commonly attributed to joint pathology, but may also reflect extra-articular manifestations, including atrophy of motor-related brain regions. We investigated HGS as a marker of peripheral joint status, systemic immune regulation, and central motor integrity. Maximal HGS was assessed using a dynamometer. Joint pathology was evaluated using radiographic and clinical measures, and upper limb disability using questionnaire. Brain volumes were quantified using MRI and MAPER software. Transcriptome sequencing was performed on circulating CD4⁺ and CD14⁺ cells. In a six-month, single-arm pilot trial, a subgroup of patients performed daily hand exercises. Associations and longitudinal changes were analysed using linear mixed-effects models accounting for repeated measurements across hands and timepoints, with variable selection performed using LASSO regression. A total of 59 women with established RA were included in the cross-sectional analysis (median age 64 years [range 23-76], DAS28 2.46 [1.1-5.8], disease duration 11 years [0-45]). Lower HGS was associated with greater disability. HGS was also independently associated with premotor and supplementary motor cortex (PMA/SMA) volume after adjustment for age, hand dominance, and joint pathology. Among joint pathology measures, tender joint count showed a significant negative association with HGS. Transcriptome analyses of CD4⁺ and CD14⁺ cells indicated that lower HGS was associated with reduced immune responsiveness and altered cytokine signalling pathways. In a six-month pilot hand exercise trial (n = 12; median age 54 years [28-68], DAS28 2.87 [1.2-3.6], disease duration 14 years [1-40]), HGS increased at 3 months, with a non-significant trend at 6 months. Baseline PMA/SMA volume showed a non-significant trend towards predicting HGS improvement. Longitudinal analyses revealed region-specific brain changes, with a decrease in PMA/SMA volume and an increase in insular volume over time. Handgrip weakness in RA may reflect both joint pathology and motor cortex atrophy in the PMA/SMA. Hand exercise improved HGS and induced certain structural changes in the brain, though effects on motor regions remain uncertain and warrant further study. Clinical trial registration: ClinicalTrials.gov, NCT04378621. Registration date: May 5, 2020.

BMC medicine

Medicina (Kaunas, Lithuania)

Ear, Nose, and Throat Manifestations in Inflammatory Bowel Diseases: A Systematic Review of the Clinical Spectrum.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), represents a chronic immune-mediated disorder frequently associated with extraintestinal manifestations. While musculoskeletal, dermatologic, and ocular complications are well recognized, ear, nose, and throat (ENT) involvement remains underrecognized despite its potential morbidity. Objective: To systematically evaluate the spectrum of ENT manifestations in IBD, focusing on clinical presentation, diagnostic approaches, and outcomes. Methods: A systematic literature search was conducted in PubMed and Scopus in accordance with PRISMA 2020 guidelines. Eligible studies included English-language human studies (2015-2026) reporting ENT manifestations in UC or CD. Following screening, 23 studies were included in the qualitative synthesis. Extracted data comprised study design, IBD subtype, patient demographics, ENT manifestations, diagnostic methods, and clinical outcomes. Results: The majority of studies consisted of case reports and small observational series. Sensorineural hearing loss (SNHL) was the most frequently reported manifestation in both adult and pediatric populations, with evidence suggesting immune-mediated mechanisms and variable responsiveness to corticosteroids. Nasal involvement included pyoderma gangrenosum, pyoderma vegetans, and aseptic nasal septal abscess, occasionally resulting in severe structural complications such as saddle-nose deformity. Laryngeal and airway involvement included dysphonia, tracheitis, and rare but potentially life-threatening inflammatory airway disease. Additional findings included associations with chronic rhinosinusitis. Diagnosis relied on audiometry, imaging, endoscopy, and histopathology. Systemic corticosteroids were frequently effective; however, delayed recognition may lead to irreversible sequelae. Conclusions: ENT manifestations in IBD constitute a clinically heterogeneous but important group of extraintestinal complications. Increased awareness of ENT manifestations may support earlier diagnosis and multidisciplinary management of IBD, potentially reducing irreversible complications.

The New England journal of medicine

Stem-Cell-Derived Biologic Ventricular Assist Tissue in Heart Failure.

Biologic ventricular assist tissue (BioVAT) is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogeneic induced pluripotent stem cells for cardiac remuscularization in patients with heart failure and a reduced left ventricular ejection fraction. We conducted an open-label, phase 1-2 study of tissue-engineered heart repair by means of BioVAT transplantation. Patients with heart failure and a left ventricular ejection fraction of 35% or less and at least one hypokinetic or dyskinetic left ventricular segment were treated with BioVAT allografts, which consisted of 5, 10, or 20 engineered-heart-muscle units. All the patients received immunosuppression. Safety was assessed as adverse events related to the procedure. The primary efficacy end points were the change from baseline in the target heart-wall thickness, the left ventricular ejection fraction, and the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OSS). A total of 20 patients were treated in the study. Three patients died during the study (1 each from vasoplegia, coronavirus disease 2019, and aortic dissection). One patient underwent heart transplantation. Immunosuppression was discontinued in 4 patients because of implantation of a left ventricular assist device (in 2 patients), renal failure (in 1 patient), and urothelial carcinoma (in 1 patient). Of the 16 patients who were treated with the safe maximal dose (20 engineered-heart-muscle units), 12 patients completed the prespecified 3-month interim follow-up. The least-squares mean increase in the target-wall thickness was 4.5 mm (90% confidence interval [CI], 3.7 to 5.4; P<0.001), the increase in the left ventricular ejection fraction was 3.9 percentage points (90% CI, 0.9 to 6.8; P = 0.04), and the increase in the KCCQ-OSS was 6.7 points (90% CI, 1.0 to 12.5; P = 0.06). All the patients had at least one adverse event. In this interim analysis, cardiac remuscularization with BioVAT was associated with an increase in the target heart-wall thickness, left ventricular ejection fraction, and KCCQ-OSS at 3 months; all the patients had at least one adverse event. Longer-term follow-up and further clinical investigation are warranted. (Funded by the German Center for Cardiovascular Research and Repairon; BioVAT-HF ClinicalTrials.gov number, NCT04396899.).

European journal of nutrition

Differential associations of diet with hepatic and muscle insulin resistance: insights from an dietary pattern analysis in the PERSON study.

The relationship between dietary patterns (DPs) and type 2 diabetes is well established, but the potential role of tissue-specific insulin resistance (IR) in this association remains unclear. This study aimed to derive DPs using reduced rank regression (RRR), incorporating hepatic IR index (HIRI) and muscle insulin sensitivity index (MISI) as response variables. We also examined whether these patterns are associated with insulin sensitivity and pancreatic β-cell function. We conducted a cross-sectional analysis of 700 adults with overweight or obesity participating in the screening phase of the PERSON study. Dietary intakes were assessed using a food frequency questionnaire. RRR was used to derive DPs based on HIRI and MISI. Associations with HOMA-IR, HOMA-β, Matsuda index and Disposition index were tested using multiple regression models adjusted for socio-demographic and lifestyle factors. One DP was retained, explaining 13.7% of the variation in HIRI, 2.8% in MISI, and 8.2% of the combined variation. This DP was characterized by high intakes of unprocessed red meat, processed meat, fresh cream and whipped cream, and low intakes of fruits, vegetables, and tea. It was significantly associated with higher HOMA-IR (β-coefficient ± SE: 0.04 ± 0.02) and HOMA-β (0.05 ± 0.01), and lower Matsuda index (- 0.08 ± 0.02). The identified DP was more strongly associated with hepatic than muscle IR. This finding highlights differential associations between diet and tissue-specific IR, and supports the relevance of considering tissue-specific insulin resistance phenotypes when investigating the relationship between diet, insulin resistance and type 2 diabetes risk. Trial registration The trial was registered at https://clinicaltrials.gov/study/NCT03708419 (identifier NCT03708419).

Effects of Specific Carob (Ceratonia siliqua L.) Liquid Concentrate on Glucose Metabolism in Subjects with Prediabetes: A Randomized Double-Blind Controlled Clinical Trial.

Background/Objectives: A 90-day randomized double-blind and placebo-controlled study was conducted to assess the effect of carob (Ceratonia siliqua L.) on glucose metabolism in subjects with confirmed prediabetes. Methods: The carob liquid concentrate containing inositols of the carob fruit (D-pinitol, myo-inositol, D-chiro inositol) was administered at a daily dose of 6.66 g, divided into two doses of 3.33 g each. Study variables included glucose- and insulin-related parameters obtained at fasting conditions and during a standard 2 h oral glucose tolerance test (OGTT) at baseline and after 45 and 90 days of administration of the study products. Results: The study population included 52 subjects (25 in the experimental group, 27 in the placebo group), 27 men and 25 women, with a mean age of 45.6 ± 13.9 years. Subjects who consumed the active product showed improvements in glycated hemoglobin (HbA1c) and glucose levels as compared with placebo (p < 0.001 of the time × group interaction). Fasting serum insulin showed within-group significant decreases in the experimental group, with insulin indexes (HOMA-IR and QUICKI) improving significantly in the experimental group only. In the OGTT, there were significant improvements in the AUC of glucose and insulin, as well as glucose peak in the experimental group only. The product was well tolerated and no adverse effects were recorded. Conclusions: The use of a specific carob-based liquid concentrate decreased HbA1c and glucose levels in subjects with prediabetes, which may suggest its potential clinical relevance in the prevention of the transition from prediabetes to overt type 2 diabetes.

Nutrients

European journal of nutrition

Comparison of mediterranean and healthy eating guideline interventions on the dietary inflammatory index in rheumatoid arthritis: results from a dietary randomised controlled intervention trial.

Anti-inflammatory diets, such as the Mediterranean Diet (MedDiet) have shown positive effects on disease activity in Rheumatoid Arthritis (RA). The Dietary Inflammatory Index (DII) has been associated with RA risk. However, the effect of improving diet quality with a MedDiet and impact on the DII and patient-reported outcome measures (PROMs) has not been investigated. To assess the effects of a MedDiet and adherence to the Irish Healthy Eating Guidelines (HEG) on change in DII and to determine whether change in DII and energy-adjusted DII (e-DII) scores is associated with improvements in PROMs in adults with RA in Ireland. 40 Participants were randomised to a MedDiet (n = 20) or a HEG intervention (n = 20) for 12 weeks. DII was calculated based on food diaries collected. Between and within group data was analysed in SPSS. Baseline e-DII was 0.99 ± 2.37, 0.79 ± 2.60, 1.20 ± 2.16 for total cohort (n = 40), MedDiet, and HEG groups, respectively (p = 0.588). e-DII significantly improved for the cohort following the MedDiet (p = 0.022) and HEG (p = 0.004) groups. Differences in PROMs across tertiles of e-DII change were not statistically significant, irrespective of diet assignment. Participants in the most anti-inflammatory e-DII tertile group had significantly greater intakes of omega-3 fatty acids, dietary fibre, vitamin A, vitamin E, folic acid, and beta-carotene compared to those in the pro-inflammatory tertile group (p < 0.05). Improving dietary quality with either a MedDiet or the Irish HEG improved e-DII scores in a cohort of people living with RA, however, no statistically significant change in PROMs were observed.

Prognostic factors in malaria patients with acute kidney injury: a systematic review and meta analysis.

This systematic review and meta-analysis aims to evaluate the predictors of mortality in malaria patients with AKI. Studies were searched in PubMed, Scopus, Ebsco, and ScienceDirect. We included observational studies that showed the association between clinical or laboratory abnormalities and mortality, reported in odds ratio. The quality of each study was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using R. Sixteen studies with 1,104 patients were analyzed. Factors significantly associated with mortality were respiratory distress syndrome (OR: 18.50, p < 0.001), neurological involvement (OR: 12.83, p < 0.001), disseminated intravascular coagulation (OR: 12.00, p < 0.001), hypotension (OR: 18.23, p < 0.001), oliguria (OR: 3.41, p = 0.002), ventilator requirement (OR: 30.35, p < 0.001), leukocytosis (OR: 4.87, p = 0.003), hyponatremia (OR: 3.67, p = 0.048), acidosis (OR: 4.88, p < 0.001), hyperkalemia (OR: 3.99, p < 0.001), and jaundice (OR: 5.03, p = 0.001). ARDS, neurological involvement, DIC, hypotension, oliguria, ventilator requirement, leukocytosis, hyponatremia, acidosis, hyperkalemia, and jaundice were associated with mortality in malaria patients with AKI. The findings underscored the importance of heightened awareness and vigilance in managing patients with these conditions.

1 min26 May 2026

Complication rates of 16- and 18-gauge needles for native kidney biopsies: a systematic review and proportional meta-analysis.

This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16 G) or 18-gauge (18 G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16 G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18 G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16 G and 17.5 with 18 G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist. What was knownKidney biopsy is essential for diagnosing many medical kidney diseases and guiding treatment, requiring adequate tissue samples for subsequent analyses.Modern biopsy techniques use spring-loaded, ultrasound-guided devices with smaller gauge needles, but optimal needle size remains uncertain.While 14G needles are associated with higher complication risk, evidence on whether 16G or 18G needles differ in safety or diagnostic yield is conflicting.This study addsIn this systematic review and meta-analysis of 62 studies involving 22,208 adult native kidney biopsies, we found no statistically significant difference in major complication rates between studies using 16G and 18G needles.In study-level meta-regression analyses, studies with a higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, and lower mean hemoglobin reported higher pooled major complication rates.Potential impactStudies using both 16G and 18G needles reported similarly low major complication rates, although comparisons are based on indirect evidence with substantial heterogeneity.Findings support the ethical feasibility and clinical relevance of a large, randomized controlled trial to definitively guide needle size selection in native kidney biopsies.

The Impact of Physical Training on Circulating Retinol-Binding Protein 4: A Systematic Review.

Obesity and type 2 diabetes mellitus (T2DM) are strongly associated with insulin resistance and chronic inflammation. Retinol-Binding Protein 4 (RBP4), an adipokine secreted by the liver and adipose tissue, has been implicated in metabolic dysfunction, with elevated circulating levels linked to impaired glucose homeostasis. Exercise is known to improve insulin sensitivity; however, its effects on RBP4 remain unclear. This systematic review aimed to synthesize the available evidence on the impact of exercise interventions on circulating RBP4 concentrations and to evaluate differences by exercise modality and population characteristics. The review followed PRISMA guidelines. A systematic search of PubMed, Web of Science, and Google Scholar (2005-2025) was conducted. Inclusion criteria were human studies ?18 years evaluating structured aerobic, resistance, or combined training with pre- and post-intervention RBP4 measurement. Non-exercise interventions and animal studies were excluded. Data extraction and quality appraisal were independently performed using Joanna Briggs Institute checklists. Out of 1,422 records screened, 16 studies met the eligibility criteria, including randomized controlled trials, quasi-experimental studies, and pre-post designs. Participants included healthy individuals, obese subjects, and patients with T2DM or metabolic syndrome. The exercise interventions varied from a single session to structured aerobic or combined aerobic-resistance programs lasting up to 12 weeks. Results showed context-dependent effects with conflicting results between different studies. Aerobic and combined aerobic-resistance exercise were associated with significant reductions in circulating RBP4 levels among obese and T2DM groups, whereas results in healthy individuals remained inconsistent. In contrast, single-session and endurance training interventions did not produce significant effects. Exercise training demonstrates potential to lower circulating RBP4, particularly in metabolically compromised populations. However, inconsistent results highlight the need for larger, standardized trials to clarify exercise modality-specific effects.

Physiological research

Roxadustat for CKD-related anemia in patients undergoing peritoneal dialysis: a systematic review and meta-analysis.

CKD-related anemia remains a major complication in patients receiving peritoneal dialysis (PD), with limited treatment options beyond erythropoiesis-stimulating agents. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, has shown promise in correcting CKD-related anemia and modulating iron and metabolic parameters. However, its evidence in PD remains limited. We conducted a systematic search of PubMed, Scopus, and Web of Science from inception to July 20, 2025. We included studies reporting the efficacy and safety of roxadustat in PD. Statistical analysis was performed using Review Manager (RevMan 5.4 for Windows) and R Studio. Eight studies were included in the meta-analysis (n = 607). Roxadustat significantly increased hemoglobin at all time points (MD 0.35 g/dL, 95% CI 0.28-0.41; p < 0.00001), serum iron (MD 0.95 µmol/L, 95% CI 0.02-1.89; p = 0.05), and total iron-binding capacity (MD 6.25 µmol/L, 95% CI 3.95-8.55; p < 0.00001), and reduced hepcidin (MD - 12.28 ng/mL, 95% CI - 21.06 to - 3.50; p = 0.006). No significant effects were observed for ferritin (p = 0.49), transferrin saturation (p = 0.45), cholesterol (p = 0.07), LDL (p = 0.14), HDL (p = 0.27), triglycerides (p = 0.26), CRP (p = 0.75), systolic blood pressure (p = 0.10), or diastolic blood pressure (p = 0.08). Heterogeneity was low to moderate for most outcomes. Roxadustat is effective in improving hemoglobin and iron metabolism in patients with PD, while exerting neutral effects on lipids, inflammation, and blood pressure. These findings support its role as a promising therapy for CKD-related anemia in PD. Not applicable.

BMC nephrology

Depressive symptoms are a key determinant of health-related quality of life in ICU survivors with psychological distress.

Survivors of critical illness frequently experience persistent impairments in health-related quality of life (HRQoL), with psychological symptoms contributing substantially to this burden. The relative contribution of co-occurring depression, anxiety, and post traumatic stress symptoms remains insufficiently understood. To address this gap, we conducted a cross-sectional analysis of pre-randomization data from the PICTURE randomized controlled trial, a multicenter study of a brief primary care-based psychological intervention for post-traumatic stress disorder symptoms following critical illness, including 319 intensive care unit survivors. Clinical, demographic, and mental health assessments were obtained after ICU discharge. Latent profile analysis, random forest modeling, and quantile regression were applied to identify determinants of HRQoL measured by the EuroQol Five-Dimension Five-Level (EQ-5D-5L) index and visual analog scale (VAS). The mean EQ-5D-5L index was 0.71 (SD 0.27; median 0.81) and the mean EQ VAS score was 60.7 (SD 19.4; median 60.0), indicating considerable overall impairment. Depression, anxiety, and post-traumatic stress symptoms showed substantial overlap and formed four distinct symptom profiles associated with specific functional impairments. Screening positive for depression on the 2-item Patient Health Questionnaire (PHQ-2) with ≥ 3 points was associated with a median reduction of -0.13 (95% CI -0.19 to -0.07) on the EQ-5D-5L index and -12.45 points (95% CI -17.93 to -6.96) on the EQ VAS, exceeding clinical and demographic predictors. These findings indicate that depressive symptoms are a major determinant of impaired health related quality of life among intensive care survivors with psychological distress and support routine brief depression screening in post-intensive care follow up.Trial registration: ClinTrials.gov: NCT03315390 (Registration date: 2017-10-20); German Clinical Trials Register: DRKS-ID: DRKS00012589 (Registration date: 2017-10-17).

Safety and preliminary efficacy of allogeneic umbilical cord-derived mesenchymal stem cells administered via the hepatic artery in patients with liver cirrhosis: A phase I open-label trial.

Liver cirrhosis causes substantial morbidity, and options beyond transplantation are limited. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) may support liver repair, but their delivery via the hepatic artery has not been evaluated. This study assessed the safety and exploratory efficacy of allogeneic UC-MSCs infusion in cirrhosis. Twenty patients with liver cirrhosis entered a single-center open-label pilot trial in Hanoi, Vietnam, between 2020 and 2023; 17 completed follow-up and were included in exploratory analyses. All received a single hepatic artery infusion of UC-MSCs at 1 × 106 cells/kg and were assessed at baseline, 3, 6, and 12 months for liver function, Model for End-stage Liver Disease (MELD) and Child-Pugh scores, Chronic Liver Disease Questionnaire (CLDQ), and adverse events. No serious adverse events occurred; mild events were self-limited. Albumin increased at 3 and 6 months (P = 0.048; P = 0.027). Bilirubin, liver enzymes, coagulation, and MELD remained stable. Child-Pugh score decreased transiently at 3 months (P = 0.024). CLDQ increased across most domains, except systemic symptoms. Hepatic artery infusion of UC-MSCs was safe and well tolerated, with observed increases in albumin and in most CLDQ domains, while other parameters remained stable. Findings are exploratory because of the small sample size and lack of a control group and therefore require confirmation in larger, controlled studies.

Cell transplantation

Protocolized Weaning From Mechanical Ventilation in the PICU: A Systematic Review and Meta-Analysis.

The use of standardized weaning protocols for invasive mechanical ventilation (IMV) is well established in adult critical care, but evidence in pediatric populations remains limited and heterogeneous. To evaluate the impact of protocolized weaning compared to usual care on clinical outcomes in pediatric intensive care units (PICUs). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and non-randomized interventional studies comparing protocolized weaning with usual care in critically ill children. Databases searched included PubMed, Embase, Cochrane Library, and ClinicalTrials.gov, through July 2025, without language or date restrictions. Two reviewers independently extracted data and assessed risk of bias using RoB 2 and ROBINS-I tools. Seventeen studies were included (seven RCTs and ten non-randomized studies), involving 16,805 pediatric patients. Among RCTs, protocolized weaning showed a non-significant trend toward reduced IMV duration (mean difference [MD]: -9.68 h; 95% CI: -19.62 to 0.26; p = 0.06). Non-randomized studies showed a significant reduction (MD: -30.30 h; 95% CI: -59.42 to -1.18; p = 0.04). In the combined analysis, protocolized weaning was associated with a statistically significant reduction in IMV duration (MD: -20.86 h; 95% CI: -33.31 to -8.40; p = 0.001). PICU length of stay was also reduced in the overall analysis, though not in RCTs alone. No significant differences were observed for hospital length of stay, extubation failure, or mortality. Trial Sequential Analysis showed that current RCT evidence remains inconclusive. Protocolized weaning was associated with shorter mechanical ventilation duration in some analyses, although the certainty of this evidence is low due to high risk of bias and heterogeneity.

Pediatric pulmonology

CardiologyReview

Clinic Value of Blood Urea to Creatinine Ratio in Heart Failure Patients: A Systematic Review.

To synthesize the existing evidence on the association of BCR with clinical outcomes in patients with heart failure. A comprehensive and systematic search of observational studies was conducted across five major databases-PubMed, Embase, Scopus, Web of Science, and Google Scholar-covering all records up to February 2024. The primary outcomes of interest included mortality, rehospitalization, cardiovascular events, and renal complications. To evaluate the methodological quality, the Newcastle-Ottawa scale was applied, allowing for the structured assessment of bias across the selection, comparability, and outcome domains. Additionally, the certainty of the evidence was appraised using the GRADE framework. Twenty studies including 21 397 HF patients were analyzed. For ≥ 1-year mortality (11 661 participants, 11 studies), hazard ratios ranged from 1.30 to 2.19, with the strongest association in HF with preserved ejection fraction (HR: 3.28, 95% CI: 2.00-5.38) with very low certainty. It also correlated with worse NYHA class IV versus II (MD: 12.03, 95% CI: 10.54-13.52) and increased risk of 1-month major adverse cardiovascular events (OR: 2.47, 95% CI: 1.01-6.01), both with very low certainty. Most included cohort studies were rated as low risk of bias, with only two studies at moderate risk and one study at high risk. Elevated BCR is associated with adverse outcomes in patients with heart failure. However, its discriminative performance appears limited, and its incremental value over established biomarkers such as NT-proBNP remains unclear. Further prospective studies are required to determine its clinical utility.

Clinical cardiology

Lipid biomarkers for the prediction of type 2 diabetes risk, an umbrella review and updated meta-analyses of prospective observational studies.

Although multiple prospective studies have examined associations between lipid metabolism disorders and the risk of type 2 diabetes (T2D), a systematic review and data updates are still lacking. Nowadays, some noval lipid metabolism biomarkers have received increasing attention, but who is the most predictive biomarkers of T2D? this study aims to conduct the in-depth exploration. We conducted an umbrella review of meta-analyses of prospective cohort studies by searching PubMed, Web of Science, Cochrane Library, and Embase from inception to 14 February 2025. Methodological quality was assessed using the AMSTAR 2, and evidence strength was evaluated using predefined credibility criteria. The study protocol was registered in PROSPERO (CRD420250649341). A total of 13 meta-analyses, 133 original articles (including 39 newly included articles) and 1, 226, 322 participants were included. The results of meta-analysis showed significant positive correlation between several lipid metabolism parameters and the risk of T2D. The strongest associations were observed for the hypertriglyceridemic waist (HTW) phenotype [Relative risk (RR) = 3.54, 95% CI: 1.92, 6.53]. Significant positive correlations were also confirmed for the lipid accumulation product (LAP) (RR = 2.94, 95% CI: 2.31, 3.73), the triglyceride glucose (TyG) index (RR = 2.51, 95% CI: 2.13, 2.95), the atherogenic index of plasma (AIP) (RR = 1.97, 95% CI: 1.54, 2.52), the visceral adiposity index (VAI) (RR = 1.77, 95% CI: 1.61, 1.94), the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio (RR = 1.51, 95% CI: 1.36, 1.69), and non-high-density lipoprotein cholesterol (non-HDL-C) (RR = 1.27, 95% CI: 1.07, 1.52). In contrast, lipoprotein(a) [Lp(a)] showed an inverse association (RR = 0.73, 95% CI: 0.56, 0.96). Dose-response meta-analysis suggested that there was a significant linear relationship between the TG/HDL-C ratio and T2D risk (P for nonlinearity = 0.2502), whereas significant nonlinear associations were observed for the VAI, LAP, TyG index, and AIP (P for nonlinearity < 0.05). Furthermore, the analysis results of fatty acids revealed positive associations between palmitic acid (C16:0; RR = 1.19, 95% CI: 1.07, 1.33), palmitoleic acid (C16:1n-7; RR = 1.33, 95% CI: 1.19, 1.49), dihomo-γ-linolenic acid (DGLA, C20:3n-6; RR = 1.36, 95% CI: 1.21, 1.53) and the risk of T2D. In contrast, negative associations were found between pentadecanoic acid (C15:0; RR = 0.82, 95% CI: 0.73, 0.92), arachidic acid (C20:0; RR = 0.78, 95% CI: 0.68, 0.90), linoleic acid (LA, C18:2n-6; RR = 0.80, 95% CI: 0.74, 0.87) and the occurrence of T2D. This systematic review supportsed the predictive value of multiple lipid biomarkers for the risk of T2D, especially some composite indicators such as the HTW, LAP, TyG index, AIP, VAI and TG/HDL-C ratio, but larger-scale and longer-term prospective studies are warranted to validate these associations.

3 min25 May 2026

Prevalence and risk factors of herpes zoster in patients with rheumatoid arthritis: a systematic review and meta-analysis.

The co-occurrence of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) represents a significant public health concern, with notable implications for both physical and mental health. This meta-analysis aims to systematically evaluate the pooled proportion of HZ in RA patients and identify associated factors. A comprehensive literature search was conducted across eight databases: PubMed, Web of Science, Embase, Cochrane Library, CNKI, VIP, WANFANG Data, and CBM. The review was conducted in accordance with PRISMA guidelines, and the quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS). All statistical analyses were performed using Stata 17.0. A total of 17 observational studies (seven case-control and ten cohort) comprising 472,150 patients were included in this meta-analysis, indicating a descriptive pooled proportion of herpes zoster of 6% (95% CI: 4%-8%). However, the 95% prediction interval was 5% to 45%, reflecting substantial heterogeneity. This estimate represents an average across diverse settings rather than a universally generalizable figure. Eleven potential factors were evaluated, and the results indicated that the following were significantly associated with HZ in RA patients: female gender (OR = 1.47, 95% CI, 1.15-1.89, P = 0.002), age (OR = 1.12, 95% CI, 1.02-1.22, P = 0.012), corticosteroid dosage ≥7.5 mg/day (OR = 2.16, 95% CI, 1.85-2.53, P < 0.001), corticosteroid use (OR = 1.42, 95% CI, 1.19-1.69, P < 0.001), use of tumor necrosis associated factor inhibitors (OR = 1.94, 95% CI, 1.43-2.63, P < 0.001), methotrexate use (OR = 1.68, 95% CI, 1.39-2.02, P < 0.001), hydroxychloroquine use (OR = 2.67, 95% CI, 1.24-5.74, P = 0.012), history of pulmonary disease (OR = 1.42, 95% CI, 1.10-1.83, P = 0.007), history of hypertension (OR = 1.43, 95% CI, 1.15-1.77, P = 0.001), history of kidney disease (OR = 1.30, 95% CI, 1.04-1.62, P = 0.022), and history of heart disease (OR = 2.30, 95% CI, 1.17-4.52, P = 0.016). Our meta-analysis indicates that the observed 6% pooled proportion of HZ in patients with RA constitutes a significant burden compared to the general population, highlighting the necessity for timely prevention. Moreover, when assessing HZ risk, factors such as female gender, age, corticosteroid use and dosage ≥7.5 mg/day, use of tumor necrosis factor inhibitors, methotrexate, hydroxychloroquine, and a history of pulmonary disease, hypertension, kidney disease, or heart disease should be carefully considered. These findings highlight the need for further research into the associated factors and underlying biological mechanisms of HZ in RA patients and support the development of targeted prevention strategies that address modifiable risks. https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420251050627.

Efficacy of Low-Voltage Area Ablation Across Substrate Size in Persistent Atrial Fibrillation: A Post Hoc Analysis of the SUPPRESS-AF Randomized Trial.

Larger low-voltage areas (LVAs) in the left atrium are associated with increased arrhythmia recurrence after atrial fibrillation (AF) ablation. The benefit of adjunctive LVA ablation may therefore depend on substrate extent. This study examined the efficacy of LVA ablation across a spectrum of LVA sizes in persistent AF. The SUPPRESS-AF (Efficacy and Safety of Left Atrial Low-Voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial screened 1364 patients undergoing initial ablation for persistent AF, of whom 342 with left atrial LVAs (≥5 cm2) were randomized to pulmonary vein isolation with or without adjunctive LVA ablation. In the 341 analyzed patients, LVA size was categorized as small (<10 cm2, n=106), moderate (≥10 to <20 cm2, n=127), or extensive (≥20 cm2, n=108). The primary end point was recurrence of AF or atrial tachycardia within 1 year without antiarrhythmic drugs. Treatment effects across LVA sizes were evaluated using a Cox model with restricted cubic splines. AF/atrial tachycardia recurrence rates were similar between the pulmonary vein isolation+LVA ablation and pulmonary vein isolation-alone groups in patients with small (38.5% versus 29.6%; P=0.28) and moderate LVA sizes (40.6% versus 53.5%; P=0.15). However, adjunctive LVA ablation significantly reduced recurrence in patients with extensive LVAs (34.7% versus 57.6%; P=0.029; interaction P=0.054), driven mainly by lower AF recurrence (18.4% versus 42.4%, P=0.008). Spline analysis indicated a greater treatment benefit with increasing LVA size, reaching significance around 20 cm2. The efficacy of adjunctive LVA ablation increased with substrate size, with a significant benefit observed in patients with extensive LVAs. These findings support a substrate size-guided ablation strategy to optimize rhythm outcomes in persistent AF. URL: https://www.umin.ac.jp/ctr; Identifier: UMIN000035940.

Association of IL-6 and IL-17 with thyroid eye disease.

Thyroid Eye Disease (TED) is the most common extrathyroidal manifestation of Graves' disease. Interleukin-6 (IL-6) and interleukin-17 (IL-17) have been implicated in its pathogenesis, but individual study results remain inconsistent. However, existing findings on IL-6 and IL-17 levels in the serum or tears of TED patients remain inconsistent. This meta-analysis aimed to statistically evaluate the level of IL-6 and IL-17 in patients with TED. A systematic literature search was conducted across five electronic databases (PubMed, Web of Science, Elsevier Science Direct, Wiley Online Library, and CNKI). The search strategy targeted the terms "Thyroid Eye Disease" in conjunction with "Interleukin-6" or "Interleukin-17" in title and abstract fields. Results are presented as standardized mean differences (SMD) with 95% confidence intervals (CI). This meta-analysis demonstrated significantly elevated levels of both IL-6 and IL-17 in patients with TED compared to controls. Pooled estimates showed a substantial increase in IL-6 (SMD: 1.68; 95% CI: 0.83-2.53), with substantial heterogeneity. Similarly, IL-17 levels were markedly higher in TED patients overall (SMD: 1.78; 95% CI: 1.18-2.37). Furthermore, patients with active TED exhibited significantly higher IL-6 and IL-17 levels than those with inactive disease. To our knowledge, this meta-analysis is a large-scale systematic evaluation of IL-6 and IL-17 levels in patients with TED. These findings describe the circulating cytokine profile in the studied population and may inform future hypothesis-driven research. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261277844, identifier CRD420261277844.

Rheumatology international

Diffuse splenic calcifications in systemic lupus erythematosus: a case-based review.

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease with a wide spectrum of splenic manifestations. In recent literature, splenic calcifications have increasingly been recognized as a rare manifestation of SLE. We describe a patient presenting with fever in whom abdominal imaging revealed splenomegaly with diffuse splenic microcalcifications, prompting further diagnostic evaluation that ultimately led to the diagnosis of SLE. To contextualize this finding, we performed a systematic case-based literature review and identified 29 previously reported cases, resulting in a total of 30 cases including our own. Across reported cases, no distinct serological or clinical phenotype could be identified. However, a characteristic imaging pattern emerged, predominantly consisting of diffuse, small, round-to-rod-shaped splenic calcifications. When longitudinal data were available, calcifications were usually stable, although progression was reported in association with disease flares, sometimes evolving to functional autosplenectomy. This case illustrates that splenic calcifications may represent an early or presenting manifestation of SLE and that an incidental detection should prompt consideration of autoimmune disease in the broad differential diagnosis. By synthesizing previously scattered reports, this review provides an updated overview to support clinical interpretation and awareness.

1 min24 May 2026

The Medical journal of Australia

Evidence for Decreasing the Age of Atrial Fibrillation Screening for Indigenous People in Australia: A Systematic Review With Meta-Analysis.

To determine whether the screening age for atrial fibrillation (AF) should be lowered for Indigenous Australians with the goal of reducing risk of stroke and other health burdens. Systematic review of medical databases identified 24 studies reporting outcome measures: AF incidence/prevalence, age of AF occurrence/diagnosis, cardiovascular risk factors and stroke risk. Risk of bias was evaluated using the Joanna Briggs Institute quality appraisal tools. Meta-analysis of mean age of AF onset was performed. An expert panel reviewed the evidence and formed consensus recommendations regarding screening for AF for Indigenous Australians. MEDLINE, Embase, Scopus, Cochrane, CINAHL, Australian Indigenous HealthInfoNet and grey literature. The review yielded five key findings. Indigenous Australians when compared with non-Indigenous Australians have: (i) higher AF rates at every age group, and meta-analysis showed onset of AF for Indigenous people at 15.9 years (95% CI, 11.5-20.4), younger than for other Australians; (ii) higher prevalence of cardiovascular risk factors; (iii) higher stroke rates (38%-47% vs. 10%-15% of all strokes occur before age of 55 years), higher mortality and other adverse outcomes after stroke and the nationally age standardised risk ratio of death from AF was 1.8 for 1997-2022; (iv) less likelihood of receiving optimal treatment; and (v) greater cost of care for stroke rehabilitation. The evidence supports an amendment to the AF guideline to opportunistically screen Indigenous Australians from at least age 55 years, and when AF is found, follow guideline recommendations for management of rate, rhythm, stroke prevention and concomitant risk factors/comorbidities. Further, the logistics of care should be considered when deciding on the localised care pathway. National implementation of these recommendations should minimise missed diagnoses and ensure timely, accessible and appropriate care/treatment. Prospective registration with PROSPERO (CRD42024514586) on 13 May 2024.

2 min24 May 2026

A randomized controlled trial of adjunctive speleotherapy in asthma, COPD and long COVID.

Speleotherapy (underground climate therapy) is a non-pharmacological intervention for chronic respiratory diseases. This randomized controlled trial investigated whether a 3-week speleotherapy course (6 sessions, 2 h/week) improves respiratory outcomes in patients on standard background therapy with asthma, COPD, or Long COVID, and whether it affects blood CO2 levels. The control group did not receive speleotherapy but continued their standard therapy. A total of 208 patients (asthma: n = 107; COPD: n = 59; Long COVID: n = 42) were enrolled across nine centers in Germany, Austria, and Italy. Assessments were conducted pre-intervention (T1), post-intervention (T2), and at 3-month follow-up (T3). Outcome measures included airway inflammation (FeNO), pulmonary function parameters (FVC% predicted values, FEV₁% predicted values, FEV₁/FVC, PEF% predicted values), and respiratory muscle strength (MIP and MEP in absolute values). In addition the following validated questionnaires were administered: Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Nijmegen Questionnaire (NQ), and Fatigue Assessment Scale (FAS), along with the Long COVID questionnaire from the Median Clinic Group. CO2 levels were assessed via capillary blood (SpCO2) and end-tidal CO2 (PetCO2). Between-group comparisons used the Mann-Whitney U test; within-group changes were assessed with the Wilcoxon signed-rank test (Bonferroni-Holm corrected). In patients with asthma, the predefined primary endpoint (FeNO) showed no significant improvement. In contrast, patient-reported outcomes improved significantly, with clinically relevant gains in asthma control (ACT: p < 0.001) and asthma-related quality of life (total AQLQ: p = 0.005). Lung function parameters showed statistically significant but modest improvements at T2 (FVC: p = 0.011; PEF: p = 0.010; FEV₁ in participants < 70 years: p = 0.035). In patients with COPD, symptom burden improved according to CAT scores (p = 0.036), while no improvements in lung function were observed. Patients with Long COVID reported significant improvements in dysfunctional breathing (NQ: T2: p = 0.014), dyspnea (T2: p = 0.026; T3: p = 0.001), and "problems with stair climbing/muscle exertion" (T2: p = 0.042), as well as improvements in anxiety and sleep-related symptoms (T2: p = 0.021). No improvements in lung function were observed in this group. In the total cohort, the intervention group showed statistically significant improvements compared to controls in respiratory muscle strength (MIP: p = 0.002; MEP: p = 0.018) and dysfunctional breathing (NQ scores at T2: p = 0.007; T3: p = 0.017). In CO₂-rich speleotherapy centers, both SpCO₂ (p = 0.026) and PetCO₂ (p < 0.001) increased at T2. While speleotherapy did not improve FeNO, it was associated with clinically relevant improvements in patient-reported outcomes across disease groups. Changes in lung function and respiratory muscle strength were statistically significant but modest and should be interpreted with caution. Overall, speleotherapy may have direct effects on the airways and breathing regulation, with more consistent evidence for improvements in breathing patterns than for direct effects on the airways.Trial registration: DRKS00033365 (retrospectively registered).

3 min23 May 2026

Effects of fecal microbiota transplantation and probiotics on the gut microbiome in antibiotic-treated septic patients: A pilot randomized controlled trial.

Broad-spectrum antibiotics, essential for sepsis management in critically ill patients, cause significant gut dysbiosis. Restoring gut microbiota may improve outcomes, but the efficacy of interventions like fecal microbiota transplantation (FMT) and probiotics in this setting remains underexplored. This study aims to evaluate the feasibility and potential efficacy of FMT versus probiotics on gut microbiome restoration and inflammatory markers in critically ill, antibiotic-treated sepsis patients. In this single-center, prospective, exploratory pilot RCT, 40 sepsis patients were were randomized 2:1:1 to: Control (n = 20, antibiotics treatment), Probiotics (n = 10, antibiotics treatment combined one week of probiotics), and FMT (n = 10, antibiotics treatment combined one week of FMT) groups. Gut microbiota composition was analyzed using 16S rDNA sequencing, and clinical inflammatory markers were assessed at baseline, one week, and two weeks post-treatment. FMT significantly mitigated antibiotic-induced reductions in microbial diversity. At 2 weeks, the FMT group exhibited higher alpha-diversity (Chao1 index, p = 0.0125; Shannon/Simpson trends p = 0.06) compared to Control and Probiotics groups. FMT increased beneficial Bacteroides abundance and reduced Enterobacteriaceae. BugBase analysis revealed FMT significantly lowered pathogenic potential of gut microbiota (p = 0.021). Donor-recipient analysis showed FMT shifted recipient microbiomes toward donor enterotype. This study provides preliminary evidence that FMT, but not the probiotic regimen, effectively restores gut microbiome diversity and composition, reduces pathogenic potential, and may improve clinical outcomes in critically ill sepsis patients after broad-spectrum antibiotics. This study was registered on ClinicalTrials.gov (NCT05578196).

Virulence

2 min23 May 2026

Studies in health technology and informatics

Usability of a Telemonitoring System for People with Type 2 Diabetes on Insulin Therapy.

Telemonitoring may improve glycemic control in type 2 diabetes. Usability plays a critical role in successful implementation of telemonitoring interventions. This study aimed to explore the usability of a telemonitoring system for people with insulin-treated type 2 diabetes. The analysis was based on data from a randomized controlled trial comparing telemonitoring to usual care. The Telemedicine Usability Questionnaire was completed by 144 participants (88%) from the telemonitoring group. The overall mean usability was calculated across subscales and showed a median of 6.49 on a 7-point scale. The usability of the telemonitoring system was high, indicating wide acceptance among users.

1 min23 May 2026

The association between asthma and ADHD in children and adolescents: An observational study and a meta-analysis of Mendelian randomization studies.

Observational epidemiological analysis and a meta-analysis of Mendelian randomization (MR) were used to investigate the association between attention-deficit/hyperactivity disorder (ADHD) and asthma in children and adolescents. Based on data from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES), an analysis was conducted to evaluate the association between ADHD and asthma in children and adolescents aged between 4 and 19 years. ADHD and asthma were defined based on self- or parent/guardian proxy-reported physician/health-professional diagnoses from the NHANES Medical Conditions Questionnaire. After analyzing ADHD genome-wide association study data from the Psychiatric Genomics Consortium as instrumental variables, we performed two-sample MR analyses based on genome-wide association study data from 5 studies to examine the causal relationship between genetically predicted ADHD liabilities. In addition, we summarized the results of the inverse-variance weighted method using a random-effects meta-analysis. Asthma prevalence was higher among participants with ADHD than those without ADHD (10.2% vs 5.9%). ADHD was associated with higher odds of asthma (odds ratio = 1.64, 95% confidence interval = 1.36-1.98), and the pattern of results was broadly consistent across subgroups. In contrast, the MR meta-analysis did not support a causal effect of genetically predicted ADHD liability on childhood asthma (odds ratio = 0.94, 95% confidence interval = 0.84-1.05, P > .05). According to data from the NHANES, ADHD and asthma are significantly associated in children and adolescents. A meta-analysis of the MR data did not reveal a causal connection between genetically predicted ADHD liability and childhood asthma. This paradoxical finding illustrates the complex interplay of genetic and nongenetic mechanisms in the ADHD-asthma association.

2 min23 May 2026

Comparative effectiveness and safety of biologics and targeted small-molecule therapies plus stable background therapy in systemic lupus erythematosus: a systematic review and network meta-analysis.

To compare the efficacy and safety of biologics and targeted small molecule drugs plus stable background therapy for the systemic lupus erythematosus (SLE). A systematic search was conducted across PubMed, EMBASE and Cochrane Library for eligible randomized controlled trials (RCTs), and a network meta-analysis (NMA) was performed to investigate the efficacy and safety of biological agents and targeted small molecule drugs added to stable background therapy in SLE. The evaluation indicators included the rates of SLE Responder Index (SRI-4) response, BILAG-based Composite Lupus Assessment (BICLA) response, Cutaneous Lupus Erythematosus Disease Area and Severity Index-50 (CLASI-50), Lupus Low Disease Activity State (LLDAS), adverse events (AEs), serious adverse events (SAEs) and infection-related adverse events. A total of 32 studies were included, involving 17,121 patients. For SRI-4 response, Telitacicept was superior to Belimumab and Ustekinumab outperformed Epratuzumab. Upadacitinib demonstrated superior efficacy versus Baricitinib for both BICLA response and LLDAS attainment. Deucravacitinib and Anifrolumab were more effective for CLASI-50 achievement than Baricitinib. Anifrolumab, Iberdomide, and Telitacicept were associated with a higher incidence of AEs (e.g., upper respiratory tract infections, urinary tract infection, and herpes zoster) compared with other interventions, which may be related to their immunomodulatory mechanisms of action. Cenerimod was associated with the lowest risk of SAEs, and IL-2 showed the lowest risk of infection-related AEs. Telitacicept and Ustekinumab demonstrated superior efficacy for SRI-4 response; Upadacitinib superior for BICLA response and LLDAS achievement; Deucravacitinib and Anifrolumab showed advantages in CLASI-50 improvement, suggesting therapeutic potential for SLE with cutaneous manifestations. Although current findings indicate that these interventions have favorable efficacy and safety profiles, their long-term efficacy and safety still require further investigation and validation in the future. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024594766.

European journal of clinical pharmacology

The influence of hydroxychloroquine on the risk of pre-eclampsia, hypertension, and premature delivery in patients with systemic lupus erythematosus during pregnancy: a meta-analysis.

To evaluate the associations between hydroxychloroquine (HCQ) use and the risks of pre-eclampsia, hypertensive disorders of pregnancy (HDP), and preterm delivery in pregnant women with systemic lupus erythematosus (SLE). PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science were systematically searched from inception to May 30, 2024, for randomized controlled trials or observational studies investigating HCQ use in pregnant women with SLE. Study quality was assessed using the Newcastle-Ottawa Scale, and meta-analyses were performed using RevMan 5.1 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models as appropriate. Nine studies were included in the meta-analysis. Compared with no HCQ use, HCQ use was not associated with statistically significant differences in the incidence of pre-eclampsia (4 studies, 1145 patients, OR = 1.11, 95% CI 0.60-2.06, P > 0.05), miscarriage (3 studies, 395 patients, OR = 1.27, 95% CI 0.72-2.25, P > 0.05), HDP (4 studies, 4787 patients, OR = 0.70, 95% CI 0.09-5.65, P > 0.05), or preterm delivery (9 studies, 2503 patients, OR = 0.78, 95% CI 0.44-1.39, P > 0.05). However, HCQ use was associated with a significantly lower risk of fetal growth restriction (FGR) (3 studies, 278 patients, OR = 0.41, 95% CI 0.18-0.93, P < 0.05) and gestational diabetes mellitus (GDM) (2 studies, 563 patients, OR = 0.28, 95% CI 0.17-0.48, P < 0.05). This meta-analysis demonstrated that hydroxychloroquine administration during pregnancy could not reduce the incidence of gestational complications. The results are inconsistent with those of previous primary studies, which may be attributed to the absence of parity-based stratification in the original studies. Accordingly, close attention should be paid to the adverse reactions of hydroxychloroquine, which should be used carefully. Further high-quality studies with subgroup analysis based on parity are strongly recommended in the future.

Does inflammatory bowel disease play a role in cognitive decline? A systematic review.

Inflammatory bowel disease (IBD) has been increasingly linked to cognitive impairment (CI) and dementia, yet the underlying mechanisms driving this association remain poorly understood and population, clinical and experimental studies show controversial results. Among others, factors such as chronic inflammation, gut-brain axis dysfunction, and psychological comorbidities have been proposed as contributors to cognitive deficits in IBD patients. The objective of this systematic review was to evaluate the existing literature on the relationship between IBD and cognitive function, considering observational and preclinical studies, with the aim to identify key factors influencing CI and potential clinical implications. The main focus of this review is on the use of IBD treatments, which may have a potential impact on CI. We conducted a systematic review according to PRISMA guidelines. PubMed and Scopus were searched from database inception up to August 30, 2024, for studies assessing cognitive performance in individuals with IBD. Clinical and epidemiological studies, genetic investigations (Mendelian Randomization and Genome-wide Association studies), and preclinical models examining memory, attention, and executive functions were included. Two reviewers independently extracted data and assessed methodological quality and risk of bias. The research yielded 66 included studies, including 31 populations studies, 13 genetics studies, and 22 preclinical research studies. Our findings suggest that patients with IBD may exhibit impaired cognitive function, particularly in memory, attention, and executive processing. Disease activity, chronic inflammation and psychological stress appear to contribute to these deficits, while some treatment strategies seem to mitigate the risk of CI. IBD is associated with CI and increased dementia risk, with biologics potentially mitigating neuroinflammation-related decline. More longitudinal studies and randomized clinical trials, also on intermediate endpoints, are needed to clarify the neuroprotective role of some therapies and optimize treatment strategies.

Critical pathways in cardiology

Staged Versus Immediate Complete Revascularization in Patients With STEMI and Multivessel Disease: An Updated Meta-analysis of Randomized Controlled Trials With Trial Sequential Analysis.

Complete revascularization improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD); however, the optimal timing of noninfarct-related artery intervention during the index procedure, immediate revascularization (IR) versus a staged approach (SR), remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials comparing SR and IR in patients with STEMI and MVD. The primary outcome was major adverse cardiovascular events. Secondary outcomes included all-cause and cardiovascular mortality, recurrent myocardial infarction, unplanned ischemia-driven revascularization, stent thrombosis, stroke, major bleeding, acute kidney injury, and heart failure hospitalization. Random-effects models with Hartung-Knapp adjustment were used. Trial sequential analysis assessed evidence conclusiveness, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. Eight randomized trials, including 5077 patients (2556 SR; 2521 IR), were analyzed. No significant differences were observed between SR and IR for major adverse cardiovascular events [odds ratios (ORs), 1.07; 95% confidence intervals (CI), 0.76-1.49], recurrent myocardial infarction (OR, 1.30; 95% CI, 0.80-2.14), cardiovascular mortality (OR, 0.76; 95% CI, 0.51-1.13), or all-cause mortality (OR, 0.75; 95% CI, 0.54-1.06). Rates of stent thrombosis, stroke, unplanned ischemia-driven revascularization, major bleeding, acute kidney injury, and heart failure hospitalization were also comparable. Trial sequential analysis indicated insufficient information size to draw definitive conclusions, and the certainty of evidence ranged from very low to low. In patients with STEMI and MVD, staged and immediate complete revascularization provide comparable ischemic, safety, and mortality outcomes. Current evidence supports clinical equipoise, and revascularization timing should be individualized pending results from adequately powered trials.

CardiologyReview

Impact of the COVID-19 pandemic on diagnosis, and healthcare utilization, among patients with cancer (lung, breast, and pancreas) and cardiovascular diseases (HF, AF, hypertensive, and chronic ischemic heart disease) in Germany: two systematic reviews.

The COVID-19 pandemic and related non-pharmaceutical interventions (NPIs) (e.g., lockdowns and contact restrictions) disrupted routine healthcare delivery. In Germany, these measures affected diagnostic and treatment services for people with cancer and cardiovascular diseases, potentially delaying diagnosis and adversely influencing outcomes. We assessed whether and to what extent diagnosis, health utilization and health outcome among patients with selected cancer and cardiovascular conditions changed in Germany during the pandemic. We conducted two systematic reviews of studies from Germany on selected cancers (breast, lung and pancreatic) and cardiovascular conditions (atrial fibrillation/flutter, heart failure, hypertensive and chronic ischemic heart disease). Protocols were registered in PROSPERO and the reviews were reported in accordance with PRISMA. We searched PubMed, Web of Science, Cochrane Library, Scopus, and Embase and screened grey literature. Outcomes included changes in new diagnoses, healthcare utilization, treatment, and disease-specific mortality during the pandemic (2020-2023) compared with the pre-pandemic period (2018-2019). Two reviewers independently screened records, extracted data, and assessed risk of bias using an adapted ROBINS-E tool. Owing to heterogeneity, we synthesized findings narratively. We screened 1991 records for cancer and 4,981 records for cardiovascular diseases, and included 9 cancer studies and 10 cardiovascular studies. For cancer, several studies reported a relative reduction in new breast and lung cancer diagnoses of up to 25% during lockdown periods; hospital admissions decreased by up to 9%. For cardiovascular conditions, hospital admissions for atrial fibrillation/flutter and heart failure decreased by up to 20%, particularly during pandemic peaks. Evidence on treatment delays, changes in treatment, and mortality was limited, and outcomes for other included diagnoses were often not reported. The available evidence indicates substantial reductions in hospital admissions and new diagnoses among patients with cancer and cardiovascular disease in Germany during the pandemic, suggesting major disruptions to care delivery. However, heterogeneity and gaps in the evidence base limit a comprehensive assessment of downstream outcomes. More comprehensive, linked data and further research are needed to quantify the full pandemic's impact and to strengthen health-system resilience for future crises.

Systematic reviews

Phase II randomised, placebo-controlled study to evaluate the efficacy and safety of an MK2 inhibitor in ankylosing spondylitis.

CC-99677 (BMS-986371) is a novel, small-molecule covalent inhibitor of mitogen-activated protein kinase-activated protein kinase 2 (MK2). We aimed to evaluate the dose-dependent efficacy and safety of CC-99677 compared with placebo in subjects with ankylosing spondylitis (AS). This was a phase II, multicentre, randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of CC-99677 in subjects with AS. Subjects were randomised 1:1:1 to once-daily CC-99677 150 mg, CC-99677 60 mg or placebo. Main inclusion criteria were fulfilment of the modified New York criteria for AS, active symptoms (Bath Ankylosing Spondylitis Disease Activity Index ≥4 and total back pain ≥4) despite ≥2 non-steroidal anti-inflammatory drugs and naïve to biologic disease-modifying anti-inflammatory drugs. The primary end point was Assessment of SpondyloArthritis international Society 20% improvement criteria (ASAS20) response at 12 weeks. 147 subjects were enrolled and 123 (83.7%) subjects completed treatment in the double-blind, placebo-controlled period. The main reason for discontinuation was study termination based on futility at interim analysis. Baseline characteristics were typical of an AS trial population. Treatment with CC-99677 was generally well-tolerated. ASAS20 and ASAS40 at week 12 were 51.2% and 25.6% in the CC-99677 60 mg group, 56.1% and 34.1% in the 150 mg group and 48.8% and 22.0% in the placebo group. No significant treatment group differences were noted for secondary end points. There were trends in active treatment groups for improvement in MRI spine and sacroiliac joint inflammation scores but minimal inhibition of pro-inflammatory cytokines in serum. Inhibition of MK2 by CC-99677 was insufficient to lead to significant clinical benefits in AS. NCT04947579.

RMD open

Midodrine versus placebo in patients with acute-on-chronic liver failure with ascites-A randomized trial (MIDAS trial).

Ascites is common in patients with acute-on-chronic liver failure (ACLF) and can complicate the course of ACLF due to circulatory dysfunction and hemodynamic compromise. Oral midodrine has been variably reported to improve hemodynamics and reduce complications of ascites in patients with decompensated cirrhosis, but its role in patients with high MELD ACLF remains unknown, which we aimed to assess. In this single-center, double-blind, randomized trial, patients with ACLF were assigned 1:1 to receive midodrine (5-7.5 mg tid) or a placebo for 30 days, alongside standard care. Transplant-free survival (TFS) at 1 month was the primary outcome, while secondary outcomes included TFS at 3 months, the proportion of patients achieving ascites control, changes in mean arterial pressure (MAP) and plasma renin activity at 1 month, the incidence of cirrhosis complications, and diuretic-related complications. One hundred thirty patients with ACLF were enrolled. Midodrine use was not associated with improvement in TFS at 1 (HR, 0.99 [95% CI: 0.37-2.65]) and 3 months (HR, 0.93 [95% CI: 0.48-1.8]). Ascites control at day 30 (placebo: 9.2% [95% CI: 3.5-19] vs. midodrine: 20% [95% CI: 12.3-33.5]; p=0.08) and 90 (placebo: 44.6% [95% CI: 32.2-57.5] vs. midodrine: 53.8% [95% CI: 41-66.3]; p=0.29) was comparable. Midodrine increased the MAP (1.9 vs. 6.9 mm Hg; p=0.003) with an insignificant reduction in plasma renin activity levels (delta change: 0.22±1.6 vs. -1.6±2.2; p=0.09). Cirrhosis-related and diuretic-related complications were similar in both groups. Midodrine increases MAP in patients with ACLF and high MELD scores without TFS benefit and does not reduce the rate of ascites-related complications.

Can disease activity and treatment responses be captured by a core set of domains in SLE clinical trials? An analysis of phase III belimumab trial data.

Outcome measures used in SLE randomised controlled trials (RCTs) have impeded trial success and drug approval. In an ongoing global project to develop a novel outcome measure for SLE RCTs, a 'core set' of domains with which to determine treatment response was chosen via consensus. We investigated the impact of restricting disease activity assessment to this core set on responder classification in RCTs. Using pooled baseline and week 52 data from two phase III SLE RCTs (Belimumab in Subjects with Systemic Lupus Erythematosus (BLISS)-52, NCT00424476; BLISS-76, NCT00410384), we divided items from the British Isles Lupus Assessment Group (BILAG) disease activity index into core and non-core sets. The core set included 30 of 86 BILAG items across five domains: mucocutaneous (rash, alopecia, mucosal ulcers), haematological (thrombocytopenia, haemolytic anaemia), arthritis, serositis and nephritis. We analysed baseline disease activity and treatment response at week 52. We analysed 1526 patients. At baseline, the core set captured the majority of disease activity captured using the full BILAG (1426/1526 (93.5%) of patients). Cutaneous vasculitis, non-haemolytic anaemia, leucopenia, dyspnoea and fatigue were the most common non-core set manifestations present. At week 52, about 1278/1426 (89.5%) patients demonstrated concordant treatment responses measured with the core set only versus all BILAG items. Discordance was again driven by cutaneous vasculitis, non-haemolytic anaemia, leucopenia and fatigue. Limiting the classification of treatment response to a core set of domains has the potential to simplify SLE RCT endpoints without a significant negative impact on patient inclusion or responder classification.

Lupus science & medicine

Comparative efficacy of different mind-body exercises on functional capacity and quality of life in patients with chronic heart failure: a systematic review and network meta-analysis.

Mind-body exercise (MBE) has emerged as a vital adjunctive modality in the rehabilitation of chronic heart failure (CHF). However, the relative advantages of various MBE types in improving functional capacity and quality of life (QoL) remain elusively defined. This study aimed to compare the therapeutic efficacy of different MBEs on clinical outcomes in CHF patients using a network meta-analysis (NMA). A systematic search was conducted across databases including PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) investigating MBE interventions in CHF, spanning from database inception to January 12, 2026. Two researchers independently performed literature screening, data extraction, and risk of bias assessment (RoB 2.0). R software was utilized for network meta-analysis, SUCRA (Surface Under the Cumulative Ranking Curve) ranking, cluster analysis, and Egger's test for publication bias. The certainty of evidence was evaluated using the CINeMA (Confidence in Network Meta-Analysis) framework. Twenty-eight RCTs were ultimately included. The NMA results indicated that Yijinjing was significantly superior to conventional care in improving quality of life (MLHFQ), cardiopulmonary endurance (Peak VO2), and cardiac systolic function (LVEF), as well as in reducing cardiac load indicators (NT-proBNP). Furthermore, Yijinjing yielded the highest SUCRA values (0.858-1.000) across these outcomes, demonstrating a high potential intervention probability. Regarding the enhancement of exercise tolerance (6MWD), Meditation showed the highest potential probability (SUCRA = 0.675); however, pairwise comparisons revealed no statistically significant differences between any MBE and conventional care (p > 0.05). Cluster analysis further confirmed a synergistic trend of Yijinjing, Liuzijue, and Meditation in enhancing both QoL and exercise endurance. No significant publication bias was detected by Egger's test for any outcome (p > 0.05). The certainty of evidence based on CINeMA was rated as Moderate. Based on moderate-certainty evidence, Yijinjing shows the highest potential probability for promoting cardiac functional recovery and enhancing quality of life in CHF patients, while meditation particularly of the movement-integrated type shows potential advantages in strengthening functional exercise tolerance. Given the lack of statistical significance in certain indicators (e.g., 6MWD), future intervention designs should focus on the regulatory effects of mind-body integration on kinesiophobia to develop more precise and long-term validated rehabilitation strategies. www.crd.york.ac.uk/prospero, CRD420261308623.

Echocardiography (Mount Kisco, N.Y.)

Association of Left Atrial Echocardiographic Indices With Atrial Fibrillation in Cryptogenic Stroke: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is linked with cardioembolism and serves as an important underlying etiology of cryptogenic stroke (CS). Left atrial (LA) indices have been investigated as markers of asymptomatic AF among CS survivors. We aimed to evaluate the association between LA indices and newly detected AF following CS. A literature search through PubMed, Scopus, Cochrane Library, and Europe PMC identified observational studies enrolling CS patients without prior AF who were monitored for AF. Left atrial volume index (LAVI), left atrial reservoir strain (LASr), and left atrial contractile strain (LASct) were assessed using echocardiography at admission and compared between patients with or without new-onset AF. Subgroup analysis was conducted for patients with embolic stroke of undetermined source (ESUS). Pooled mean differences with 95% confidence intervals (CIs) were measured using the random-effects model. Twenty-three studies comprising 3475 participants (AF = 1050; non-AF = 2425) were included in the analysis, with 11 studies assessing exclusively ESUS patients. Meta-analysis demonstrated significantly higher LAVI (MD 7.76 mL/m2; 95% CI 6.04 to 9.49; I2 = 72%; p < 0.00001) and significantly lower LASr (MD -8.07%; 95% CI -10.13 to -6.01; I2 = 88%; p<0.00001) and LASct (MD -5.26%; 95% CI -6.69 to -3.83; I2 = 86%; p < 0.00001) in CS patients who developed AF compared with those who did not. Similarly, significantly higher LAVI and lower LASr and LASct were observed in ESUS patients with new-onset AF. In conclusion, AF occurrence is associated with higher LAVI and lower LASr and LASct among CS patients, suggesting an association between LA function and newly detected AF.

Ankylosing spondylitis and the gut microbiome: future research hotspots and trends.

Ankylosing spondylitis (AS) is an autoimmune disease. Its exact cause remains unclear. It is generally believed to result from a combination of genetic and environmental factors, as well as immune disorders. However, growing evidence suggests that the gut microbiota plays a key role in the pathogenesis of AS. Therefore, this study aims to systematically analyze the current state of research on AS and the gut microbiome. It also explores future research hotspots. We searched the Web of Science Core Collection (WoSCC) and PubMed databases, including relevant literature on AS and the gut microbiome published up to January 1, 2026. We then performed a visualized bibliometric analysis using CiteSpace, VOSviewer, and Bibliometrix software. The WoSCC dataset included 165 articles. Both the annual publication volume and citation counts showed an upward trend. Brown, Ma, and Liu B were the most productive authors. Regarding country output, China ranked first with 60 articles, followed by the USA with 36. Major contributing institutions were also primarily located in China and the USA. Current research hotspots focus on inflammation, Mendelian randomization, HLA-B27, probiotics, and short-chain fatty acids. A validation analysis using the PubMed database (115 articles) yielded results consistent with the WoSCC findings. Our study provides key insights into the relationship between the gut microbiota and AS. It clarifies current research hotspots and development trends. Future researchers should conduct prospective studies to confirm causality and combine multi-omics analysis to reveal underlying molecular mechanisms.

TL1A as a therapeutic renaissance in inflammatory bowel disease: a systematic review from molecular mechanisms to clinical translation.

Despite major therapeutic advances, many patients with inflammatory bowel disease (IBD) continue to experience inadequate treatment response, progressive disease, and irreversible complications requiring surgery. Current management is constrained by a biological efficacy ceiling and lack of agents directly targeting key drivers of fibrosis and barrier dysfunction. This systematic review synthesizes current knowledge on tumor necrosis factor-like cytokine 1A (TL1A) and death-domain receptor 3 (DR3) signaling pathways, critically evaluates the therapeutic potential of TL1A-targeted interventions, and explores future directions for precision medicine applications in IBD care. A comprehensive systematic search of PubMed, EMBASE, Cochrane library, Web of Science, and ClinicalTrials.gov was conducted according to PRISMA guidelines. Three independent reviewers screened preclinical and clinical studies using Rayyan software. Study selection, data extraction, and quality assessment were performed in duplicate. Eligible studies underwent narrative thematic synthesis. Of 250 studies identified, 63 met inclusion criteria. Preclinical data consistently demonstrate TL1A-DR3 signaling drives inflammation, fibrosis, and barrier dysfunction. Phase 2 clinical trials showed anti-TL1A monoclonal antibodies (Tulisokibart, Afimkibart, Duvakitug) achieved clinical remission/response rates between 26% and 66% in patients with moderate-to-severe IBD at 12-14 weeks, with favorable safety profiles. Emerging themes include extended dosing intervals, therapeutic benefit in treatment-refractory populations, potential anti-fibrotic effects, and opportunities for biomarker-guided patient stratification. TL1A inhibitors represent a promising novel therapeutic class with dual anti-inflammatory and anti-fibrotic properties, addressing critical unmet clinical needs in IBD. These agents hold the potential to become cornerstone therapies in the evolving landscape of precision medicine for IBD care.

Echocardiography (Mount Kisco, N.Y.)

Echocardiographic Parameters for Predicting Atrial Fibrillation Following Ischemic Stroke: The PER DIEM Echocardiography Substudy.

Atrial fibrillation (AF) detection following ischemic stroke is critical to guide management. Echocardiography (echo) is commonly performed poststroke and may help identify candidates for prolonged rhythm monitoring. The PER DIEM trial randomized poststroke patients without known AF to 12-months of implantable loop recorder (ILR) monitoring versus 30-days of external rhythm monitoring and demonstrated higher AF detection rates using ILR. This substudy of the PER DIEM trial investigated the association between baseline echo parameters and poststroke AF detection. PER DIEM trial participants with complete transthoracic echo performed at the time of ischemic stroke were included. Demographic, clinical, and echocardiographic parameters were compared between those with and without AF. Nineteen (12.4%) of the 153 patients included had poststroke AF. AF patients were significantly older and had higher CHA2DS2-VASc scores. Patients with AF had higher left atrial volume index (LAVI), lower absolute left ventricular global longitudinal strain (LV GLS) and lower contractile LA strain compared to those without AF. Univariate analysis showed that a higher LAVI (OR 1.30 per 5 mL/m2 increase, 95%CI 1.03-1.64, p = 0.025) and lower absolute LV GLS (OR 2.73 per 5% decrease, 95%CI 1.37-6.04, p = 0.007) were significantly associated with poststroke AF, with optimal cutoff values of 32.12 mL/m2 and 15.5%, respectively. In patients with ischemic stroke, LAVI and LV GLS were significantly associated with subsequent AF detection. These findings may help risk stratify AF monitoring strategies for postischemic stroke management.

Prognostic value of CT-derived fractional flow reserve for major adverse cardiovascular events in patients with suspected or known coronary artery disease: a systematic review and meta-analysis.

Fractional flow reserve derived from CT (FFR-CT) enables non-invasive functional assessment of coronary stenoses in patients with suspected or known coronary artery disease, but evidence regarding its prognostic value remains fragmented. We conducted a systematic review and meta-analysis to quantify the association between abnormal FFR-CT and major adverse cardiovascular events (MACE), updating the 2022 meta-analysis by Nørgaard et al METHODS: We searched PubMed, Embase and Scopus through December 2025 for studies comparing outcomes in patients with suspected or known coronary artery disease with FFR-CT ≤0.80 versus >0.80 (PROSPERO: CRD420261276897). Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was performed. Subgroup analyses examined FFR-CT technology, geography and follow-up duration. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. Twenty-two studies with 20 067 patients were included, representing a fourfold increase from the prior meta-analysis. Follow-up ranged from 12 to 120 months. Patients with FFR-CT ≤0.80 had significantly higher MACE risk (HR 3.94; 95% CI 2.92 to 5.31; p<0.0001) with substantial heterogeneity (I²=79.9%). However, restricting to hard endpoints (death/myocardial infarction; k=6) yielded HR 3.28 (95% CI 2.25 to 4.79) with zero heterogeneity (I²=0%). No significant differences emerged across FFR-CT technologies (p=0.812), including HeartFlow, machine learning and deep learning algorithms. Trim-and-fill analysis suggested possible publication bias, with adjusted HR 2.35. GRADE certainty was moderate. Abnormal FFR-CT is associated with nearly fourfold increased risk of MACE in patients with suspected or known coronary artery disease, with consistent prognostic value across technologies. The absence of heterogeneity for hard endpoints supports FFR-CT as a reliable prognostic marker. These findings address the evidence gap identified by current guidelines regarding FFR-CT prognostic utility. CRD420261276897. Not applicable (as this is a Systematic Review and Meta-Analysis and not a Clinical Trial).

Open heart

Advances in rheumatology (London, England)

Home-based transcranial direct current stimulation for persistent pain state in rheumatoid arthritis: a randomized trial.

Although effectively controlling inflammation, up to 50% of patients with rheumatoid arthritis (RA) experience persistent pain, associated with central sensitization and neuroinflammation. Home-based transcranial direct current stimulation (tDCS) has shown efficacy in chronic pain. To investigate whether anodal tDCS (a-tDCS) is more effective than sham stimulation in reducing pain. Randomized, double-blind, sham-controlled trial with 34 women (18-70 years) with RA and VAS > 40 mm. Participants were randomized to receive a-tDCS (n = 17) or sham tDCS (n = 17). Home-based tDCS (2 mA, 20 min/day) or sham (2 mA, 90 s) for four weeks, using anodal-left M1 montage. Primary outcomes was pain (Visual Analogue Scale, VAS), Secondary outcomes included pressure pain threshold (PPT), central sensitization (CSI), physical function (HAQ-DI), fatigue (FACIT-F), CNS biomarkers, adherence, and safety. Mean VAS reduction from baseline was greater in the a-tDCS group (-33.5 mm) versus s-tDCS (-14.1 mm), with a between-group difference of -19.4 mm (95% CI, -29.3 to -9.5; p = 0.003). Linear mixed-effects models showed that a-tDCS reduced VAS pain by 27.7% versus 6.0% with sham, a between-group difference of 21.7% (Cohen's d = 1.15). HAQ-DI improved by 38.0% versus 7.2% (ES = 1.10). a-tDCS reduced analgesic use by 62% (RR = 0.38; 95% CI, 0.18-0.79). Exploratory analyses suggested that neuroplasticity mechanisms might mediate these effects. Home-based a-tDCS effectively reduced pain, disability, and analgesic use in RA patients with persistent pain without objective inflammation.

The Cochrane database of systematic reviews

Perioperative use of disease-modifying anti-rheumatic drugs (DMARDs) in people with inflammatory arthritis.

Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of pharmacologic treatment for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis). DMARDs are immunomodulatory drugs which may increase the risk of infection, including surgical site infections; thus, some surgery guidelines recommend continuing some DMARDs and withholding others prior to surgery. On the other hand, discontinuation may result in worsening of the symptoms of the underlying inflammatory arthritis. Little is known about the optimal use of DMARDs during elective surgery. To assess the benefits and harms of perioperative interruption versus continuation of conventional synthetic (csDMARDs), biologic (bDMARDs) and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in people with inflammatory arthritis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and two trial registers up to 24 March 2025. We included randomised controlled trials (RCTs) comparing temporary discontinuation or a dose reduction of DMARDs with continued medication perioperatively in adults with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis) undergoing surgery (major orthopaedic surgery (including but not limited to joint arthroplasty and spinal fusion, or other)). When no RCTs were available for one or more types of DMARDs, we included observational studies, data from registries and insurance databases. The critical outcomes were flare of the underlying inflammatory disease, postoperative infections, prosthetic joint infections, mean disease activity score, function, total adverse events and serious adverse events. The prespecified primary time point was up to and including four weeks. As no trial reported outcomes before six weeks, we extracted the shortest time point reported for each outcome. We assessed risk of bias using the Cochrane risk of bias 1.0 tool. Two review authors independently used Cochrane methods for management of included studies. The main comparison was continuation of any DMARD versus discontinuation in the perioperative period. We synthesised effect estimates using a random-effects meta-analysis model. Three trials (306 participants) met inclusion. All compared perioperative discontinuation with perioperative continuation of csDMARDs in adults with rheumatoid arthritis undergoing elective orthopaedic surgery. Participants were 56.2 years old on average, and 83% of participants were women. In two trials, the discontinuation group stopped csDMARDs (methotrexate) two weeks prior to surgery and continued two weeks after the surgery, and in one trial, the discontinuation group stopped csDMARDs (leflunomide) one week prior to surgery and continued one month after the surgery. All trials were at risk of selection, performance, detection and selective outcome reporting biases. We did not find any trials assessing the perioperative use of (any) DMARDs in adults with rheumatoid arthritis undergoing non-orthopaedic surgery or adults with psoriatic arthritis or axial spondyloarthritis undergoing any surgery. We also did not find any trials assessing the perioperative use of bDMARDs, or tsDMARDs in adults with rheumatoid arthritis undergoing orthopaedic surgery. We identified nine observational studies with b/tsDMARDs in orthopaedic and non-orthopaedic surgery; six included participants with rheumatoid arthritis and the other three included mixed inflammatory arthritis populations. Results from the observational studies are presented narratively. As no trial reported outcomes at the designated primary time point of up to four weeks, we report the earliest time point for flare and postoperative infections (which varied across studies) and last follow-up for adverse events, serious adverse events and revision surgery. Low-certainty evidence indicates perioperative discontinuation of csDMARDs may increase the risk of flare, may have little or no effect on the number of people with postoperative infections, and may have little or no effect on the number of people reporting total or serious adverse events compared with perioperative continuation of csDMARDs. Only one trial measured prosthetic joint infections and reported no prosthetic joint infections in either group (very low-certainty evidence). None of the trials reported disease activity scores or function scores at follow-up. At eight months follow-up, 38/104 (36%) participants reported a flare in the discontinuation group compared to 0/120 (0%) in the continuation group (RR 32.99, 95% confidence interval (CI) 4.54 to 239.53, 2 studies, 224 participants, I2 = 0%). At 12 months follow-up, 5/145 (3%) participants in the discontinuation group had postoperative infections compared to 5/161 (3%) in the continuation group (RR 1.00, 95% CI 0.31 to 3.19, 3 studies, 306 participants). For total adverse events, 29/145 (20%) participants in the discontinuation group reported any adverse events compared to 17/161 (10%) in the continuation group (RR 1.89, 95% CI 0.20 to 18.00, 3 studies, 306 participants, I2 = 60%) after eight to 12 months follow-up. For serious adverse events, 9/113 (7%) participants reported events in the discontinuation group compared to 6/129 (5%) participants in the continuation group (RR 1.41, 95% CI 0.50 to 3.93, 2 studies, 242 participants, I2 = 4%) after 12 months follow-up. Evidence from observational cohort studies largely concurred with the findings from RCTs, indicating an increased risk of flare if DMARDs are discontinued, with no apparent reduction in the risk of postoperative infection. While we could not estimate the risk of prosthetic joint infections from trial data, observational data suggests that perioperative discontinuation of DMARDs does not reduce the likelihood of this outcome occurring. Perioperative discontinuation of DMARDs may increase the risk of flare, and may have little or no effect on the number of people with postoperative infections, the number reporting adverse events and serious adverse events. None of the studies reported on mean disease activity or function. The evidence is limited to rheumatoid arthritis and csDMARDs. Observational studies largely support the findings that there may be a risk of flare with discontinuation of csDMARDs in people with other inflammatory arthritis, but the risks associated with perioperative discontinuation of biologic or targeted synthetic DMARDs are less clear. Editorial note: This is a living systematic review. We search for new evidence approximately yearly and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. This Cochrane review had no dedicated funding. Protocol (2022). DOI: 10.1002/14651858.CD015096.

5 min20 May 2026

Association between pulse wave velocity and coronary artery calcification: a systematic review and meta-analysis.

Cardiovascular diseases are the leading cause of mortality and morbidity combined worldwide. Traditional risk factors may underestimate risk in individuals with subclinical atherosclerosis, prompting the development of novel markers. Coronary artery calcium assessment has been proposed as a promising marker of subclinical atherosclerosis, although it involves exposure to ionizing radiation. This systematic review and meta-analysis aimed to explore the association between a noninvasive marker, pulse wave velocity (PWV), and coronary calcification, as well as the factors influencing this association. A systematic review and meta-analysis were conducted via the PubMed, Scopus, and Web of Science databases in accordance with the MOOSE and PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were carried out on the basis of preestablished criteria. Twenty-six studies involving 103 222 individuals were included. Higher central PWV in the unadjusted and adjusted models [pooled odds ratio (p-OR) = 3.11, 95% confidence interval (CI): 2.07-4.67 and p-OR = 1.51, 95% CI: 1.26-1.81, respectively] and higher peripheral PWV in the unadjusted and adjusted models (p-OR = 2.49, 95% CI: 1.97-3.14 and p-OR = 1.68, 95% CI: 1.38-2.05, respectively) were associated with greater coronary calcification, with considerable heterogeneity. The percentage of women, total cholesterol, body mass index and diastolic blood pressure were related to the p-OR. The adjusted model for peripheral PWV showed publication bias. Our meta-analysis underscores a significant association between arterial stiffness and coronary calcification, highlighting PWV as a promising noninvasive biomarker. Its integration into clinical practice could enhance cardiovascular risk stratification, enabling earlier interventions. To maximize its clinical utility, standardization and further research are imperative.

Journal of hypertension

2 min20 May 2026

Prevalence of female sexual dysfunction among women with systemic lupus erythematosus: a systematic review and meta-analysis.

The prevalence of female sexual dysfunction (FSD) among women with systemic lupus erythematosus (SLE) is inconsistent, and whether SLE is a risk factor for FSD among women remains controversial. Therefore, this study aimed to conduct a systematic review and meta-analysis to estimate the prevalence of FSD among women with SLE and further explore the association between SLE and FSD. Literature on the prevalence of FSD among women with SLE was retrieved from PubMed, Web of Science, Cochrane Library, and Embase databases from inception to July 1, 2025. The pooled prevalence was calculated using a random-effects model for the meta-analysis. The Cochran Q and I 2 tests were employed to examine heterogeneity among the studies, while subgroup analyses and meta-regression were conducted to identify potential sources of heterogeneity. This meta-analysis included 13 studies involving 1,511 women with SLE and 2,246 healthy controls. The pooled prevalence of FSD among women with SLE was 58.8% (95% confidence interval [CI], 0.461-0.716). Compared with the healthy control group, women with SLE had a significantly increased risk of FSD (odds ratio, 2.64; 95% CI, 1.27-5.47). This systematic review and meta-analysis demonstrated a high prevalence of FSD among women with SLE and a significant association between SLE and an increased risk of FSD. https://inplasy.com/inplasy-2025-7-0092/,identifier 202570092.

2 min20 May 2026

The Cochrane database of systematic reviews

Dose reduction and discontinuation of non-tumor necrosis factor (TNF) biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for people with rheumatoid arthritis in remission or low disease activity.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the benefits and harms of dose reduction or discontinuation of non-TNF biologic or targeted synthetic DMARDs in people with rheumatoid arthritis who are in remission or have low disease activity.

1 min20 May 2026

Efficacy and safety of stem cell therapy for dry eye syndrome in Sjögren's syndrome: a systematic review and meta-analysis.

Stem cell therapy holds considerable potential for treating dry eye syndrome, though it has yet to receive clinical approval. This paper systematically quantifies the efficacy and safety of stem cell-based therapies in dry eye syndrome caused by Sjögren's syndrome, aiming to provide information for dry eye treatment efforts. This systematic review collected literature published prior to 16 January 2026 in PubMed, Embase, and the Cochrane Library concerning stem cell therapy for Sjögren's syndrome-induced dry eye disease. Efficacy outcomes comprised: OSDI scores, along with changes in NIKBUT first, Oxford score, and Schirmer test results. Safety outcomes comprised commonly reported adverse events. Continuous outcomes were expressed as mean difference (MD), while dichotomous outcomes used single-group rates, both presented with 95% CI. All data analyses were conducted using Review Manager 5.4 software, adhering to the PRISMA guidelines. This meta-analysis included five studies involving 114 patients with dry eye syndrome. Results demonstrated that stem cell therapy significantly altered the OSDI score compared to pre-treatment levels: -15.10 (95% CI: -18.65, -11.56; P < 0.00001). NIKBUT first scores increased significantly by 3.26 points post-treatment (95% CI: 2.17, 4.34; P < 0.00001). The Oxford score showed a change of -0.20 (95% CI: -0.85, 0.45; P = 0.55) post-treatment. The Schirmer test score exhibited an overall change of 3.87 (95% CI: 1.93, 5.81; P < 0.0001). Specifically, the MD at 2 weeks, 4 months, and 12 months was 8.76 (95% CI: 0.58, 16.94; P < 0.04), 3.52 (95% CI: 1.66, 5.38; P < 0.002), and 5.10 (95% CI: 0.24, 9.96; P < 0.04), respectively. The incidence of injection pain at 4 weeks was 14% (95% CI: -11%, 39%, P = 0.28). Ocular discomfort occurred in 16% of subjects at 4 weeks (95% CI: -4%, 35%, P = 0.11). Periorbital oedema occurred in 14% of subjects at 4 weeks (95% CI: -11%, 39%, P = 0.28). Blurred vision and periorbital paresthesia occurred at treatment with rates of 21% (95% CI: -7%, 50%, P = 0.14) and 15% (95% CI: -4%, 35%, P = 0.12), respectively. This meta-analysis indicates that stem cell therapy effectively reduces OSDI scores, increase Schirmer test scores, and enhances tear film stability in dry eye syndrome caused by Sjögren's syndrome. However, the increased incidence of adverse events in the short term suggests that benefits and risks must be carefully weighed prior to clinical application, with rigorous monitoring and close follow-up required throughout treatment. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261287054, identifier CRD420261287054.

2 min20 May 2026

Journal of Korean medical science

Standard-Dose Ursodeoxycholic Acid Improves Biochemical Liver Function and Fibrosis in Chronic Liver Disease: Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

This study evaluated the efficacy and safety of standard-dose ursodeoxycholic acid (UDCA; fixed daily dose of 300 mg/day) compared with placebo, in patients with chronic liver disease. A multicenter, randomized, double-blind, placebo-controlled phase IV clinical trial was conducted in academic hospitals in South Korea. Patients with chronic liver disease and abnormal serum alanine aminotransferase (ALT) levels in at least two consecutive results prior to screening, persisting for at least 6 months, were randomly assigned to receive 100 mg UDCA or placebo three times daily for 8 weeks. The primary endpoint was the mean relative change in ALT levels from baseline. The secondary endpoints included changes in fibrosis and drug-related adverse events. A total of 262 patients were analyzed (132 in the UDCA group and 130 in the placebo group). By week 8, there was a significantly greater reduction in serum ALT levels from baseline in the UDCA-treated patients than in the placebo group (-14.70 vs. -5.51 U/L; P = 0.010). The ALT normalization rates were higher in the UDCA group (26.52% vs. 13.08%; odds ratio, 2.60; P = 0.005). Fibrosis reduction, as assessed by the FibroTest score, was greater in the UDCA group (-0.03 vs. -0.00; P = 0.016). The frequency of adverse events in the two groups was similar, with no serious adverse events reported in the UDCA group. In patients with chronic liver disease, 100 mg UDCA three times daily for 8 weeks improved ALT levels and fibrosis, and had a favorable safety profile. ClinicalTrials.gov Identifier: NCT06272630.

Feasibility, acceptability and efficacy of a nurse-led palliative care health coaching intervention (Educate, Nurture, Advise before Life Ends) for patients with heart failure and their caregivers in Singapore: a randomised wait-list controlled pilot study of health coaching in Asian heart failure.

To evaluate the feasibility, acceptability and potential efficacy of the culturally adapted Educate, Nurture, Advise Before Life Ends (ENABLE) programme in Singapore for patients with heart failure (HF) and their family caregivers. Non-blinded randomised wait-list controlled pilot study, using Simon's randomised phase II trial design. Specialist outpatient clinics in a tertiary cardiac centre in Singapore. Patients had a diagnosis of American Heart Association Stage C or D HF, were symptomatic with New York Heart Association functional class 2 and above symptoms, had a prognosis of 6 months, a hospitalisation in prior 6 months and were on disease-directed HF management. Patients already known to palliative care (PC) were excluded. Recruited caregivers were family caregivers of patients. ENABLE integrates PC early into HF care. It starts with a comprehensive PC assessment with a PC physician and nurse. This is followed by a series of nurse coach-led health coaching sessions for both patients and caregivers. After the completion of health coaching, participants would receive follow-up phone calls to review their coping up to 6 months post-enrolment. Feasibility was defined by the proportion of approached patient-caregiver dyads who consented to participate and the proportion of participants who completed health coaching. Acceptability was defined by a score of at least 12 out of a maximum of 16 for the Client Satisfaction Questionnaire 4-Item Survey. Primary efficacy outcome measure was the change in patient quality of life (QOL) at 6 months as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) total score, with the target effect size (Cohen's d) being at least 0.25 SD in favour of ENABLE. Other secondary outcomes included patient/caregiver anxiety and depression scores on the Hospital Anxiety and Depression Scale, spirituality scores on the Functional Assessment of Chronic Illness Therapy-Spiritual Wellbeing Scale and caregiver QOL on the Singapore Caregiver Quality of Life Scale. Feasibility: recruitment was carried out from February 2022 to October 2023. We approached 164 patient-caregiver dyads and 60 patient-caregiver dyads (36.6%) consented. A total of 48 patients and 44 caregivers started on health coaching, of which 44 patients (91.7%) and 43 caregivers (97.7%) completed health coaching.Acceptability: patients' satisfaction was high, at 85.7% and 87.5% in the intervention and wait-list arm, respectively. Caregivers were similarly satisfied, at 100% and 87.5% in the two arms, respectively.Efficacy: intervention-arm patients had a higher mean total KCCQ score at 6 months than wait-list-arm patients (difference in means=12.4; 95% CI 0.9 to 24.0; Cohen's d=0.43). There was no difference in caregiver QOL changes between trial arms at 3 months and 6 months. Both patients and caregivers had improvements in anxiety at 3 months and sustained improvements in depression and spirituality at 6 months. Proportion of participants who completed health coaching was high, though proportion of approached participants who consented was lower than expected. Our acceptability and efficacy targets were met. Further phase III testing is planned. NCT05211882.

BMJ open

3 min19 May 2026

Causal relationship between systemic lupus erythematosus and coronary artery disease: Insights from a meta-analysis and Mendelian randomization.

Observational research has produced varied results concerning the association between systemic lupus erythematosus (SLE) and coronary artery disease (CAD). This study employed a meta-analysis of cohort studies alongside a 2-sample Mendelian randomization (MR) method to investigate the causal influence of SLE on CAD risk. A comprehensive literature search was executed across PubMed, Web of Science, Embase, and the Cochrane Library, covering all pertinent cohort studies from their inception to August 14, 2024. The data regarding the causal association between SLE and CAD were synthesized using relative risk (RR), with results presented within a 95% confidence interval (CI). For MR analysis, data were derived from genome-wide association studies (GWAS) focusing on SLE and CAD in European and East Asian populations, respectively. The primary MR analysis employed the inverse-variance weighted (IVW) method, with the weighted median method and MR-Egger regression serving as complementary approaches. This meta-analysis included 13 cohort studies with a total of 2517,781 participants. The combined findings indicated that compared to the general or healthy population, individuals with SLE had a higher risk of developing CAD in the total population (RR [95% CI] = 2.355 [1.924-2.883], 95% prediction interval [PI]: 1.199-4.628). This association was also observed among European (RR [95% CI] = 2.028 [1.310-3.138], 95% PI: 0.539-7.631), East Asian (RR [95% CI] = 2.628 [1.698-4.067], 95% PI: 0.014-487.335), and North American (RR [95% CI] = 2.711 [2.379-3.089], 95% PI: 2.193-3.352) groups. However, MR analysis utilizing the IVW method did not identify a genetically predicted causal relationship between SLE and CAD in either European or East Asian populations (all P > .05). Sensitivity analyses indicated an absence of heterogeneity or horizontal pleiotropy in the MR analysis. Findings from our meta-analysis indicated that SLE is associated with an elevated risk of CAD. Despite the lack of genetic evidence for a direct causal relationship between SLE and CAD, clinicians should remain vigilant and take proactive measures in monitoring CAD among SLE patients, considering the possible indirect effects of SLE on CAD risk.

Arquivos de gastroenterologia

ROLE OF STATINS IN CIRRHOTIC PORTAL HYPERTENSION: META-ANALYSIS OF RANDOMIZED STUDIES.

Physicians often use caution when prescribing statins to patients with chronic liver disease (CLD) due to potential hepatotoxicity. However, recent evidence indicates that hepatotoxicity is uncommon, and the risks of not using statins may often outweigh those associated with their use. Additionally, recent findings suggest that statins may have clinically beneficial effects on cirrhosis due to their pleiotropic properties. To evaluate the impact of statin use on the number of patients with chronic liver disease alive at the end of the trials and to assess its effects on portal hypertension, ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma. This meta-analysis analyzed 9 randomized clinical trials published in the MEDLINE, EMBASE, and SCOPUS databases that evaluated the use of statins in patients with cirrhosis. These studies included a total of 811 subjects with portal hypertension, of which 401 patients were in the intervention group. We assessed risk of bias using the Risk of Bias 2 (RoB 2) tool for randomized clinical trials, and we analyzed the quality of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) scale. We extracted data on the number of events and the total number of patients to perform a meta-analysis of proportions using the R software with the "meta" package (version 4.9-6). Our meta-analysis on patients alive at the end of the trials included 5 studies, involving a total of 718 patients (352 in the statin group and 366 in the control group). From these, 618 patients were alive at the end of the studies, with 301 from the intervention group and 287 from the control group. The overall odds ratio (OR) between the groups was 1.79 (95%CI -1.04 to 3.06; I²: 20.3%), favoring the use of statins. The results for variceal gastrointestinal bleeding showed an OR of 0.67 (95%CI, 0.41 to 1.09; I²: 0%); for hemodynamic response, the OR was 2.41 (95%CI, 0.65 to 8.92; I²: 66%); for hepatic encephalopathy, the OR was 0.41 (95%CI, 0.06 to 2.77; I²: 61%); for myalgia, an OR of 0.74 (95%CI, 0.22 to 2.46; I²: 1%); and for ascites, the OR was 0.84 (95%CI, 0.48 to 1.48; I²: 0%). The use of statins is associated with a greater number of patients with hepatic cirrhosis alive at the end of the trials. However, we were unable to determine the reason for this potential beneficial effect. Médicos frequentemente utilizam precaução ao prescrever estatinas para pacientes com doença hepática crônica (DHC) devido ao potencial de hepatotoxicidade. No entanto, evidências recentes indicam que a hepatotoxicidade é incomum, e os riscos de não utilizar estatinas frequentemente superam os riscos associados ao seu uso. Além disso, descobertas recentes sugerem que as estatinas podem ter efeitos clínicos benéficos na cirrose devido às suas propriedades pleiotrópicas. Avaliar o impacto do uso de estatinas na sobrevida de pacientes com doença hepática crônica e analisar seus efeitos sobre a hipertensão portal, ascite, encefalopatia hepática, hemorragia varicosa e carcinoma hepatocelular. Esta metanalise analisou nove ensaios clínicos randomizados publicados nas bases de dados MEDLINE, EMBASE e SCOPUS que avaliaram o uso de estatinas em pacientes com cirrose. Esses estudos incluíram um total de 811 indivíduos com hipertensão portal, dos quais 401 pacientes estavam no grupo de intervenção. O risco de viés foi avaliado utilizando a ferramenta Risk of Bias 2 (RoB 2) para ensaios clínicos randomizados, e a qualidade das evidências foi analisada com a escala GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Foram extraídos dados sobre o número de eventos e o total de pacientes avaliados para realizar meta-análises de proporções utilizando o software R com o pacote “meta” (versão 4.9-6). Nossa meta-análise sobre sobrevida incluiu cinco estudos com um total de 718 pacientes (352 no grupo que usou estatinas e 366 no grupo controle). Desses, 618 pacientes estavam vivos ao final dos estudos, sendo 301 do grupo de intervenção e 287 do grupo controle. A razão de chances (odds ratio, OR) geral entre os grupos foi de 1.79 (95%CI -1.04 to 3.06; I²: 20.3%), favorecendo o uso de estatinas. Os resultados para sangramento gastrointestinal varicoso mostraram uma OR de 0,67 (IC95%: -0,41 a 1,09; I²: 0%); para resposta hemodinâmica, a OR foi de 2,41 (IC95%: -0,65 a 8,92; I²: 66%); para encefalopatia hepática, a OR foi de 0,41 (IC95%: -0,06 a 2,77; I²: 61%); para mialgia, a OR foi de 0,74 (IC95%: -0,22 a 2,46; I²: 1%); e para ascite, a OR foi de 0,84 (IC95%: -0,48 a 1,48; I²: 0%). O uso de estatinas está associado à melhora da sobrevida em pacientes com cirrose hepática. No entanto, não conseguimos determinar a razão desse efeito benéfico.

4 min19 May 2026

The effect of virtual reality glasses used during inhaler treatment on anxiety, fear and vital signs in children: a randomized controlled trial.

This study aimed to determine the effect of virtual reality (VR) glasses used during inhaler treatment on anxiety, fear and vital signs in children. The study had an experimental, randomized controlled design. Participants were assigned to groups using a lottery method based on simple randomization. The random sequence was generated by physically mixing up 30 red (experimental) and 30 white (control) cards. All the data were collected and finalized by two trained researchers (Yasemin Özyer Güvener, a nurse researcher, and Şeyma Şimşirgil Kara, a pediatrician). Participants were recruited using a convenience sampling method from among individuals who met the inclusion criteria. In terms of baseline measurements, the experimental group had significantly higher mean pulse rate, fear scores, and anxiety scores (130.23 ± 14.64, 2.77 ± 1.25, and 4.60 ± 2.04, respectively) compared to the control group (118.83 ± 17.10, 2.07 ± 1.26, and 2.80 ± 2.07, respectively) (p = 0.007, p = 0.035, and p = 0.001, respectively). For post-intervention measurements, the experimental group had significantly lower mean fear and anxiety scores (0.443 ± 0.16 and 0.703 ± 0.22, respectively) compared to the control group (2.39 ± 0.16 and 3.197 ± 0.22, respectively) (p < 0.001 and p = 0.001, respectively). It was determined that VR glasses reduced anxiety and fear, increased oxygen saturation, and reduced respiratory and pulse rates. They can thus be used as an alternative method to reduce fear and anxiety levels and balance vital signs during inhalation therapy in children. • Virtual reality (VR) is an effective non-pharmacological method for reducing pain, anxiety, and fear in pediatric patients during various medical procedures. • VR applications create a sense of presence in a virtual world, limiting the impact of anxiety and fear in clinical settings. • Using VR glasses during the administration of inhaled medication significantly reduces anxiety and fear levels in children compared to traditional methods. • While evidence for VR use during inhalation therapy was previously limited, this study demonstrates its effectiveness as a promising alternative to improve treatment compliance and physiological responses in pediatric patients.

The Lancet. Respiratory medicine

Efficacy and safety of tezepelumab versus placebo in reducing oral corticosteroid use in adults with severe, oral corticosteroid-dependent asthma (SUNRISE): a multicentre, placebo-controlled, double-blind, phase 3 trial.

Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This study aimed to evaluate the oral corticosteroid-sparing effect of tezepelumab in adults with severe, oral corticosteroid-dependent asthma. SUNRISE was a phase 3, double-blind, placebo-controlled trial conducted across 63 sites in 12 countries. After oral corticosteroid optimisation, participants aged 18-80 years with physician-diagnosed asthma who were receiving medium-dose or high-dose inhaled corticosteroids for at least 12 months before screening were randomly assigned (2:1) to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 28 weeks. Participants were stratified by region and blood eosinophil count. Participants, investigators, and site staff were masked to treatment assignment. The primary outcome was the categorised percentage reduction from baseline in the daily maintenance oral corticosteroid dose at week 28 while maintaining asthma control. The primary outcome and safety outcomes were evaluated in all randomly assigned participants who received at least one dose of tezepelumab or placebo (ie, the full analysis set). This study is registered with ClinicalTrials.gov (NCT05398263). Between Aug 9, 2022, and March 24, 2025, when the study was terminated, 122 of 207 planned participants received tezepelumab (n=83) or placebo (n=39). 90 (74%) participants completed treatment. Of 122 participants, 25 (20%) did not complete the study owing to early study termination due to recruitment challenges. The odds of reaching a category of greater percentage oral corticosteroid reduction at week 28 were significantly higher with tezepelumab than placebo (odds ratio 2·93 [95% CI 1·43-6·03]; p=0·0034). Overall, 25 (30%) participants in the tezepelumab group and 23 (59%) participants in the placebo group had at least one asthma exacerbation over 28 weeks. Adverse events occurred in 47 (57%) participants in the tezepelumab group and 28 (72%) participants in the placebo group. Serious adverse events occurred in seven (8%) participants in the tezepelumab group and five (13%) participants in the placebo group. Three deaths occurred (two in the tezepelumab group during the post-treatment period and one in the placebo group during the treatment period); none were considered causally related to study treatment based on investigator assessment. In this study, tezepelumab treatment led to greater reductions from baseline in daily oral corticosteroid dose than placebo at week 28 despite early study termination. No safety concerns were identified for tezepelumab. These findings show that patients receiving tezepelumab can reduce maintenance oral corticosteroid use while maintaining asthma control and without compromising efficacy. AstraZeneca and Amgen.

Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi

[Effects of indoor environmental pollutants on allergic diseases in children: a Meta-analysis].

Objective: To evaluate the impact of indoor environmental pollution on childhood allergic diseases in recent years through Meta-analysis and explore the potential effects of pollution exposure on children's health. Methods: Literature published between January 2015 and March 2025 was retrieved from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Information Database, PubMed, and Web of Science. Additional studies were identified through reference tracing and manual supplementation. Studies meeting inclusion criteria were screened, and relevant data were extracted and analyzed. Results: A total of 36 studies from 9 countries were included, including 25 studies conducted in China. Most studies were cross-sectional ones (21), followed by cohort ones (8), case-control ones (4), and combined (cross-sectional and cohort) ones (3). Study participants were children aged 0-12 years. Indoor pollutants closely associated with allergic diseases included particulate matter, chemical pollutants, and biological pollutants. Meta-analysis results indicated that environmental tobacco exposure (OR=1.51, 95%CI:1.16-1.98, P=0.003) significantly increased the risk for childhood asthma; the exposure to new furniture (OR=1.44, 95%CI:1.13-1.83, P=0.003) was significantly associated with allergic rhinitis; the exposures to mold (OR=2.81, 95%CI:2.25-3.51, P<0.001), cockroach (OR=1.59, 95%CI:1.26-2.00, P<0.001), and damp or mouldy environmental surface (OR=1.42, 95%CI:1.26-1.62, P<0.001) significantly increased asthma risk. The exposure sensitivity varied across the development stages of children, with high sensitivity in infancy and early childhood. Conclusion: Children can expose to indoor environmental pollutants through multiple routes, including inhalation and skin contact, in daily life, which might increase the risk for allergic diseases by inducing abnormal immune responses and pose a significant threat to children's health. 目的： 通过Meta分析，评估近年来室内环境污染对儿童过敏性疾病的影响，并探讨污染暴露对儿童健康的潜在影响。 方法： 检索中国知网、万方数据知识服务平台、维普资讯数据库、PubMed和Web of Science 5个数据库中2015年1月至2025年3月发表的相关文献，结合参考文献回溯补充，筛选符合标准的文献并提取数据进行分析。 结果： 共纳入36篇文献，覆盖9个国家，其中研究地点为中国的文献25篇。研究类型以横断面研究为主（21篇），其余为队列研究（8篇）、病例对照研究（4篇）及横断面与队列结合研究（3篇）。研究对象年龄范围为0~12岁。与儿童过敏性疾病密切关联的室内污染物主要包括颗粒物、化学污染物及生物污染物。Meta分析结果显示，环境烟草烟雾暴露（OR=1.51，95%CI：1.16~1.98，P=0.003）显著增加儿童哮喘风险；新家具暴露（OR=1.44，95%CI：1.13~1.83，P=0.003）与过敏性鼻炎显著相关；霉菌（OR=2.81，95%CI：2.25~3.51，P<0.001）、蟑螂（OR=1.59，95%CI：1.26~2.00，P<0.001）及环境表面潮湿或发霉（OR=1.42，95%CI：1.26~1.62，P<0.001）显著增加哮喘风险。不同生长阶段的暴露敏感性存在差异，婴幼儿期为污染物影响的高敏感窗口。 结论： 儿童在日常生活中通过吸入或皮肤接触等多种途径暴露于室内环境污染物，这些污染物可能通过诱发免疫系统异常反应，增加过敏性疾病的发生风险，对儿童健康构成重要威胁。.

Rheumatology international

Targeting type I interferon in lupus panniculitis: a case-based systematic literature review.

Lupus panniculitis (LEP) is a rare form of cutaneous lupus (CLE) characterised by progressive, often disfiguring course and poor response to treatment. Type I interferon inhibition through anifrolumab (ANF) is effective in CLE but limited data are available for its use in LEP. To address this issue, we screened patients with CLE and/or systemic lupus erythematosus (SLE) for biopsy-proven diagnoses of LEP and treatment with ANF. Besides demographics, general clinical features, concomitant treatments before and after ANF and safety signals, we measured disease activity and damage with the SLE disease activity index 2000 (SLEDAI-2 K), the CLE Disease Area and Severity Index activity (CLASI-A) and damage scores and the SLE International collaborating clinics/American College of Rheumatology damage index. The same data were retrieved, when available, from existing cases extracted from systematic literature review. Sixteen cases were identified, including 3/421 newly described patients, with two receiving ANF as first-line immunosuppressant and one as an early treatment devoid of oral corticosteroids. All patients had a good response to treatment and most of them could taper or discontinue corticosteroids. CLASI-A scores were markedly reduced after ANF treatment [11.5 (7-29)] to 0 (0-2); p = 0.005]. The time to response was within five months in most cases. No significant adverse events were reported. Taken together, our data suggest that ANF might be effective in LEP and used as a first-line treatment to prevent LEP-related damage accrual.

Liver international : official journal of the International Association for the Study of the Liver

Prevalence and Impact of Steatotic Liver Disease in Autoimmune Liver Diseases: A Systematic Review and Meta-Analysis.

SLD is common in autoimmune liver diseases and may add a relevant metabolic burden. Screening for metabolic risk factors and steatosis may be particularly important in AIH, where SLD was linked to advanced fibrosis despite lower liver enzyme levels. These findings support multidisciplinary care and the need for further evidence to improve risk stratification. Autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), can coexist with steatotic liver disease (SLD); however, this overlap has not been systematically assessed. We aimed to determine the prevalence, clinical characteristics and outcomes of SLD in patients with AILDs. In this systematic review and meta‐analysis, we searched PubMed and Embase from inception to May 20, 2025 for observational studies reporting on hepatic steatosis in AILDs. Proportions were pooled using a generalized linear mixed model and pairwise meta‐analyses used random‐effects models to obtain pooled odds ratios (ORs) or standardized mean differences. PROSPERO ID: CRD420251057378. Forty‐seven studies (N = 10 734) were included. SLD prevalence was 29.7% (95% confidence interval [CI] 21.9–39.0, τ2 = 0.923, I2 = 94.2%) in AIH, 25.0% (95% CI 16.1–36.6, τ2 = 1.418, I2 = 94.7%) in PBC, and 17.1% (95% CI 10.8–26.0, τ2 = 0.500, I2 = 90.8%) in PSC. Patients with AILDs and SLD had a higher body mass index and a greater burden of metabolic comorbidities. In AIH, SLD was associated with lower liver enzymes, but increased odds of significant (OR 1.37, 95% CI 1.02–1.84, τ2 = 0, I2 = 0%) and advanced fibrosis (OR 1.84, 95% CI 1.37–2.47, τ2 = 0.024, I2 = 17.4%). Evidence on the prognostic impact of SLD in AILDs was limited and inconsistent, with no studies reporting on PSC. SLD is common across AILDs and may modify their clinical and prognostic profiles, especially in AIH. These data support potential systematic metabolic screening and multidisciplinary care in this population. Further research is needed to clarify the prognostic significance of SLD and inform risk stratification and management in AILDs.

Sedative Choice and Neurocognitive Outcomes After Critical Illness in Early Childhood.

Sedatives, commonly administered in the clinical treatment of young children with critical illness, may be harmful to early brain development. To investigate whether sedative choice during critical illness in early childhood is associated with long-term neurocognitive function. This prospective cohort study was conducted among a subset of cognitively appropriate children with acute respiratory failure who were aged 8 years or younger when enrolled in the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) cluster-randomized clinical trial conducted in 31 pediatric intensive care units (PICUs) comparing a nurse-implemented, goal-directed sedation protocol with usual care. Patients underwent neurocognitive testing 3 to 8 years after hospitalization at regional neuropsychology testing centers. Neurocognitive testing was conducted from February 16, 2015, to November 27, 2018. Assessors were blinded to the sedation provided. Data were analyzed from September 2022 to March 2026. Critical illness and sedation. The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Drug- and dose-dependent associations between sedatives and neurocognitive function were assessed, adjusting for baseline factors and severity and course of critical illness. Neurocognitive testing was performed among 256 children (median [IQR] age, 6.6 [5.4 to 9.0] years). Among 243 children with data, 228 children (93.8%) had age-appropriate global assessment of cognitive function (Pediatric Cognitive Performance Category = 1) at testing. Children were exposed to a median (IQR) of 8 (5 to 14) days of continuous sedation at a median (IQR) age of 1.0 (0.2 to 3.2) years. The mean (SD) estimated IQ was 100.3 (13.2), similar to the published test mean of 100. Mean (SD) estimated IQ at long-term follow-up was lowest in patients receiving an opioid- and benzodiazepine-only strategy (98.3 [11.8]), higher in patients receiving multiple sedative classes not including dexmedetomidine (100.6 [14.5]), and highest in patients receiving multiple sedative classes, including dexmedetomidine (101.9 [13.5]). Controlling for Hollingshead Socioeconomic Status score, severity of illness on PICU admission, and duration of mechanical ventilation, the adjusted mean difference in estimated IQ between the opioid- and benzodiazepine-only vs dexmedetomidine groups was -4.1 (95% CI, -7.3 to -0.9; P = .01). In this study of young children who received more than a week of PICU sedation, the estimated IQ was similar to that of the general population. Children who received an opioid- and benzodiazepine-only strategy scored lower than those who received a strategy that included dexmedetomidine when controlling for socioeconomic status, illness severity, and duration of mechanical ventilation. ClinicalTrials.gov Identifier: NCT02225041.

3 min19 May 2026

Effectiveness of Nursing Interventions for the Management of Critically Ill Patients With Severe Respiratory Conditions: A Systematic Review and Meta-Analysis.

Critically ill patients with severe respiratory conditions frequently require prolonged mechanical ventilation and intensive care, with high risks of complications and death. Nursing interventions may optimise ventilatory care, reduce ICU complications and improve patient outcomes. We synthesised the effectiveness of nursing interventions for managing severe respiratory conditions in ICU settings. We conducted a systematic review and meta-analysis following PRISMA 2020. Studies evaluating nursing interventions among critically ill adults with severe respiratory conditions in ICUs were included. Outcomes were duration of mechanical ventilation, length of ICU stay, mortality, adverse events and weaning success. Random effects inverse-variance meta-analyses were performed (standardised mean differences [SMD] for continuous outcomes; odds ratios [OR] for binary outcomes). Fourteen studies were included. Nursing interventions reduced duration of mechanical ventilation (11 studies; SMD = -1.63, 95% CI -2.29 to -0.96; substantial heterogeneity) and ICU length of stay (10 studies; SMD = -1.25, 95% CI -1.79 to -0.72). Mortality was lower with nursing interventions (5 studies; OR = 0.35, 95% CI 0.21-0.61; I2 = 0%). Adverse events were reduced (9 studies; OR = 0.31, 95% CI 0.22-0.43; low heterogeneity), and weaning success improved (6 studies; OR = 3.17, 95% CI 2.20-4.58; I2 = 0%). Egger's test suggested small-study effects for ventilation duration but not ICU length of stay. Nursing interventions in ICU respiratory care improve weaning success and reduce adverse events, mortality, ventilator duration and ICU stay, although effect sizes vary and publication bias is possible for ventilation duration. This review supports the adoption of structured, protocolised nursing interventions, particularly multi-component bundles and targeted nursing plans within respiratory-critical care pathways.

Nursing in critical care

Dental and medical problems

Association between periodontal disease and rheumatoid arthritis: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the association between periodontitis and rheumatoid arthritis (RA) in middle-aged populations.The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive search of major electronic databases was conducted for studies published between 2013 and 2023. In addition, a manual search was performed to identify relevant studies examining an association between these 2 conditions. The Newcastle-Ottawa scale was used to assess the risk of bias for the included cross-sectional and case-control studies. The certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis, and a meta-analysis of eligible studies was conducted.A total of 11 articles were included in the systematic review, with 9 incorporated into the meta-analysis. A statistically significant positive association was observed between periodontitis and RA for clinical attachment loss (CAL). The GRADE assessment indicated low to moderate level of certainty across studies, indicating strong evidence regarding clinical parameters. The meta-analysis showed a high overall odds ratio (OR) (OR = 11.37; 95% confidence interval (95% CI): 4.22-30.61; p < 0.01), suggesting that patients with RA have a significantly higher risk of developing periodontitis. In conclusion, this systematic review and meta-analysis identified a positive association between periodontitis and RA. However, the GRADE analysis highlights the need for clinical and longitudinal studies with extended follow-up periods to further clarify this relationship and account for potential confounding factors.

Development and testing of a smart empowerment education system for gout patients in suburban areas.

This study aimed to develop and evaluate an Intelligent Empowerment Education-based System (IEES), which integrates empowerment education, refined management protocols, and smart technologies, for application among gout patients in resource-limited suburban settings. The primary goal was to address key challenges including suboptimal self-management capacity, poor treatment adherence, and unfavorable long-term clinical outcomes. A smart gout management system was developed using a SpringBoot+Vue framework, incorporating deep learning algorithms for personalized recommendations. A total of 90 gout patients admitted to a community health service center from January 2023 to December 2023 were randomly divided into a control group (n = 45) and an observation group (n = 45) according to a random number table. The control group received routine outpatient health education, while the observation group received an additional intervention based on empowerment education combined with refined management. The system was successfully developed with key performance indicators including response time <200 ms and prediction accuracy of 89.7%. The self-management ability score of the observation group was (145.6 ± 4.5), significantly higher than that of the control group (p < 0.05). The fasting serum uric acid (SUA) value of the observation, and the liver and kidney function were significantly lower than those of the control group (p < 0.05). The intelligent empowerment education disease management system significantly improved SUA control, self-management ability, and renal function in suburban gout patients. This "Internet+" chronic disease management model demonstrates promise for scalable application.

2 min18 May 2026

Journal of nursing management

The Effect of a WhatsApp Chatbot-Based Training Program on Infection Control Knowledge and Practices Among Hemodialysis Nurses: A Cluster-Randomized Controlled Trial.

Patients undergoing hemodialysis are highly susceptible to infection; however, evidence suggests variability in nurses' infection control competencies. Although digital learning tools are increasingly used in nursing, there have been few randomized controlled trials assessing WhatsApp chatbot-based infection control training for hemodialysis nurses. Thus, the purpose of this study was to assess the effect of a WhatsApp chatbot-based training program on nurses' knowledge and practices related to infection control in hemodialysis units. A cluster-randomized controlled trial was conducted from July to September 2024, involving 50 hemodialysis nurses recruited via convenience sampling from five hospitals in Jordan. Ten clusters, defined by hospital site and work shift, were randomly assigned using a computer-generated sequence prepared by an independent researcher to either an intervention group, which received the WhatsApp chatbot-based training program, or a control group. Guided by constructivist learning theory, the intervention facilitated active knowledge construction through an interactive, automated chatbot dialogue delivered over 4 weeks. Outcome measures were collected using a self-reporting questionnaire at baseline and 4 weeks after completion of the 5-day intervention. Mixed-model repeated-measures ANOVA revealed that the intervention group showed statistically significant improvements in both knowledge (F (1, 48) = 19.34, p < 0.0001, η2 = 0.28) and practice (F (1, 48) = 14.52, p < 0.0001, η2 = 0.23), both indicating large effect sizes, compared with the control group. The study results indicate that the WhatsApp chatbot-based training program is an effective e-learning approach that helped hemodialysis nurses develop their infection control knowledge and practice. The results suggest that WhatsApp chatbot-based education provides nurse managers with a flexible and scalable method to enhance infection control competencies and improve patient safety in hemodialysis units.

2 min18 May 2026

Pharmacology research & perspectives

Meta Analysis of DHA and EPA Supplementation on Cardiovascular Outcomes and Atrial Fibrillation Risk.

Cardiovascular diseases (CVD) remain to impose a main global burden of morbidity and mortality despite advances in anticipation and treatment. Omega-3 fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been extensively studied for potential cardioprotective effects, yet their impact on cardiovascular outcomes remains debated due to heterogeneity in formulation, dose, and patient subgroups. This meta-analysis evaluated the effects of EPA and DHA supplementation on major adverse cardiovascular events (MACE) and atrial fibrillation (AF), including postoperative AF (POAF), in patients with established CVD. A systematic search of Embase, PubMed/MEDLINE, Scopus, and Web of Science (January 2010-December 2021) identified randomized controlled trials (RCTs) of combined EPA + DHA supplementation in secondary prevention or perioperative settings. Data were synthesized using RevMan v5.3 with a random-effects model, and study quality was assessed via the Cochrane RoB 2 tool. From 3682 records, 25 RCTs (n = 25 578 patients) were included. Pooled analysis showed no significant reduction in MACE (effect estimate 0.042 ± 0.0499, Z = 0.850, 95% CI [-0.055, 0.140], p = 0.396; low heterogeneity) or AF/POAF incidence (trend toward reduction: -0.198 ± 0.1498, Z = -1.319, 95% CI [-0.491, 0.096], p = 0.187; modest heterogeneity). Neutral findings likely reflect moderate-dose combined EPA + DHA use, limited subgroup reporting on metabolic comorbidities (e.g., diabetes, hypertriglyceridemia) or concomitant therapies (e.g., statins), and high background guideline-directed medical therapy reducing residual risk. Although omega-3 fatty acids exert anti-inflammatory, antithrombotic, and lipid-modulating effects, this analysis indicates no broad benefit in reducing MACE or AF risk with combined moderate-dose EPA + DHA in heterogeneous post-event populations. Recent evidence highlights more MACE reductions with high-dose purified EPA monotherapy in high-metabolic-risk subgroups, balanced against dose-dependent AF increases at high doses (> 1.5 g/day). Future large-scale RCTs should prioritize biomarker-verified compliance, metabolic/concomitant therapy stratification, and formulation-specific comparisons to define targeted therapeutic roles. Trial Registration: This study has been registered in PROSPERO, and the registration code is 642795.

2 min18 May 2026

Unraveling immunological heterogeneity in recalcitrant AIH-PBC/PSC overlap syndromes: from molecular crosstalk to precision therapeutics.

The clinical management of autoimmune liver diseases is frequently complicated by the concomitant presentation of hepatitic and cholestatic features, an entity clinically designated as Overlap Syndrome. While the majority of patients respond to conventional combinatorial therapy involving corticosteroids and ursodeoxycholic acid, a significant subset exhibits a recalcitrant phenotype characterized by biochemical non-response and rapid fibrotic progression. The pathogenesis driving this therapeutic resistance remains incompletely defined, though emerging evidence implicates a distinct immunological architecture rather than a simple superposition of two diseases. This review delineates the multidimensional immunopathogenesis of AIH-PBC and AIH-PSC overlap syndromes with a specific focus on the interface between adaptive immunity and biliary epithelial senescence. We critically examine recent single-cell transcriptomic data that reveal specific pro-inflammatory macrophage niches and exhausted T-cell signatures unique to the overlap phenotype. Furthermore, we discuss the molecular crosstalk involving bile acid signaling and inflammatory cascades that perpetuates liver injury despite standard immunosuppression. Finally, we propose a paradigm shift towards precision medicine by evaluating the rationale for emerging biologic agents, including JAK inhibitors and B-cell depleting therapies, in the management of difficult-to-treat overlap syndromes.

1 min18 May 2026

Predicting Salmonella Typhi incidence using prevalence metrics from sentinel studies of community-onset bloodstream infections: a secondary analysis of observational data.

Typhoid fever incidence estimates are central to policy decisions on vaccine introduction and investments in non-vaccine prevention and control but are often unavailable. We explored whether prevalence metrics from sentinel studies of community-onset bloodstream infections could accurately predict local Salmonella enterica serovar Typhi (Salmonella Typhi) incidence. Using a previous systematic review (January 2018-December 2024), we identified studies reporting both typhoid incidence and prevalence of community-onset bloodstream infections from sentinel sites. From authors, we requested data on blood culture isolates and analysed four metrics: (i) Salmonella Typhi prevalence among probable pathogens, (ii) Salmonella Typhi rank order, (iii) Salmonella Typhi to Escherichia coli ratio, and (iv) Salmonella Typhi to 'stably endemic' organisms ratio. Typhoid incidence was categorized as low (<10), medium (10-100) or high (>100) per 100,000 person-years. We used univariate ordinal regression to assess the association between each metric and typhoid incidence level. The model performance was evaluated by the c-statistic, sensitivity, and specificity. Analysis of 29 study sites (20 Africa, 9 Asia) yielded 4625 probable pathogens. The median (IQR) typhoid incidence was 140 (28-319) per 100,000 person-years. All metrics were associated with increased typhoid incidence level: for each 1% increase in Salmonella Typhi prevalence OR 1.07 (95%CI 1.02-1.15); for each unit increase in rank order OR 0.25 (95%CI 0.06-0.64); for each unit increase in the log Salmonella Typhi to E. coli ratio OR 2.88 (95%CI 1.48-7.39) for each unit increase in the log Salmonella Typhi to 'stably endemic' organisms ratio OR 3.74 (95%CI 1.80-10.7). A parsimonious model using Salmonella Typhi prevalence alone achieved c-statistics of 0.87 (0.58-0.97), 0.76 (0.51-0.91), and 0.88 (0.69-0.96) for low, medium, and high incidence, respectively. Sentinel prevalence metrics from bloodstream infections, particularly Salmonella Typhi prevalence among probable pathogens, could be useful for inferring local typhoid fever incidence where direct data are unavailable.

Vaccine

2 min17 May 2026

Effect of intra-dialytic pedaling exercise on dialysis adequacy: A randomized controlled trial.

In patients with chronic kidney disease undergoing hemodialysis, physical activity and rehabilitation are crucial for preventing declines in muscle strength and functional capacity. This study aimed to assess the impact of physical activity during hemodialysis on dialysis adequacy in patients undergoing hemodialysis. This randomized controlled trial (RCT) investigated the impact of pedaling exercise on dialysis effectiveness in 84 hemodialysis patients at hospitals in Bushehr. Participants were randomly assigned to either an experimental group (n = 42) that performed 30 minutes of pedaling exercise during their 4-hour dialysis sessions or a control group (n = 42) that received routine hemodialysis. Dialysis adequacy was assessed by comparing pre- and post-dialysis blood samples obtained from the arterial line. A conservative intradialytic exercise protocol, blood samples, and patient weight were measured using a calibrated digital scale. Data analysis was performed using SPSS version 24 software. The experimental and control groups were similar in demographic characteristics, except for age (X2 = -3.84, p = 0.001) and education levels (X2 = 10.100, p = 0.006). While there was no significant difference in weight between the groups before and after the intervention (t = 0.223, p = 0.82 before; t = 0.203, p = 0.84 after), both groups showed a substantial weight reduction overall (p < 0.0001). There were no statistically significant differences in weight change (t = 0.80, p = 0.25), BUN (t = 0.13, p = 1.52), or Kt/V (t = 1.62, p = 0.11) between the experimental and control groups. This study found that incorporating pedaling exercise during hemodialysis did not significantly improve dialysis effectiveness, as measured by weight change, BUN levels, or Kt/V. While both groups showed weight loss, there were no statistically significant differences between them. However, the study was limited by its small sample size and the specific exercise protocol employed. Further research with larger cohorts and a broader range of physical activities is needed to determine whether physical activity during hemodialysis can improve dialysis adequacy and overall patient outcomes. IRCT code number 20150529022466N15 and trial Code of Ethics IR.BPUMS.REC.1398.130E.

PloS one

Molecular nutrition & food research

Modulation of Microbiota-Derived Bile Acids Linked to Symptom Amelioration in Crohn's Disease: Insights From a Randomized Clinical Trial With Xanthohumol Supplementation.

Xanthohumol (XN), a dietary flavonoid from hops (Humulus lupulus), possesses anti-inflammatory and microbiome-modulatory properties with potential therapeutic benefits for Crohn's disease (CD). To investigate the effects of XN on the gut environment in CD, we conducted a randomized, placebo-controlled clinical trial-the XN Microbiome and Signature (XMaS) trial (NCT4590508). 19 participants with clinically active CD completed the study. They were randomized to receive 24 mg/day of XN or placebo for 8 weeks, with clinical assessments at baseline and every 2 weeks. We assessed changes to Crohn's disease activity index (CDAI) scores, systemic inflammation, gut barrier function, profiling of microbial metabolism of XN, and gut microbiota composition and metabolism. Integration analysis of gut microbiota abundance, fecal metabolites, and inflammatory markers with CDAI scores revealed a pattern in which reductions in secondary bile acids and increases in IL-10 were associated with improved CDAI score in XN-treated individuals. These findings suggest that XN beneficially modulates the gut environment in CD by influencing microbial bile acid metabolism and host inflammatory response, thereby improving symptoms in individuals with severe innate immune activation.

1 min15 May 2026

The clinical respiratory journal

Efficacy of Prone Positioning in Non-ARDS Patients With Hypoxemic Respiratory Failure: A Systematic Review and Meta-Analysis.

Prone positioning (PP) is established for the management of hypoxemic respiratory failure (HRF) due to acute respiratory distress syndrome (ARDS). However, its effectiveness in patients with HRF unrelated to ARDS remains unclear. This systematic review and meta-analysis aimed to evaluate the clinical outcomes of PP in patients with non-ARDS HRF. We systematically searched PubMed, Cochrane Library, Web of Science, and EMBASE (up to February 2025) for observational studies and randomized controlled trials (RCTs) evaluating PP in patients with HRF unrelated to ARDS. We included studies that enrolled either intubated or non-intubated patients. On the other hand, we excluded studies that combined PP with other positions and those that did not compare pre-and-post prone or did not have control groups. Two reviewers working independently screened the included studies and extracted the relevant data. Meta-analyses using a random-effects model were performed using the Review Manager software. Twenty-one studies comprising 3040 patients with HRF unrelated to ARDS were included. Thirteen were observational studies, one was a non-randomized clinical trial, and seven were RCTS. In non-intubated patients, PP improved PaO2/FiO2 compared with baseline (mean difference [MD]: -51.36 mmHg; 95% CI: -70.39 to -32.32; p < 0.00001), decreased the need for intubation compared with control/standard care (risk ratio [RR]: 0.74; 95% CI: 0.60-0.91; p = 0.004), and demonstrated a trend to improve mortality (RR: 0.81; 95% CI: 0.61-1.01; p = 0.07). In intubated non-ARDS HRF patients, the PaO2/FiO2 ratio was higher after PP, but not statistically significant (MD: -29.84; 95% CI: -77.51 to 17.83; p = 0.22). In non-intubated patients with HRF unrelated to ARDS, PP improved oxygenation and decreased the need for invasive ventilation without increasing mortality risk. Therefore, PP is likely an effective therapy for non-intubated patients with non-ARDS HRF. Furthermore, evidence suggests that PP can improve oxygenation in intubated patients with HRF unrelated to ARDS.

[Clinical characteristics of smoking asthma and efficacy of long-acting muscarinic antagonist in treating patients with smoking asthma].

Objective: To analyze the clinical characteristics of smoking asthmatic patients and to evaluate the efficacy of long-acting muscarinic antagonist (LAMA) in treating smoking asthmatic patients. Methods: The characteristic analysis study of smoking asthma was a case-control study, including 128 patients with bronchial asthma. According to whether the patients smoked, they were divided into the smoking asthma group and the non-smoking asthma group. The clinical data, blood indicators, lung function indicators [forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FEV1/FVC), maximum mid-expiratory flow (MMEF 75/25)], and fractional exhaled nitric oxide (FeNO) were compared between the two groups. The efficacy of LAMA in treating smoking asthma patients was a randomized controlled trial. A total of 60 male patients with moderate to severe asthma, who were smokers and in a non-acute attack phase, were screened. According to computer-generated random numbers, they were divided into the intervention group [administered inhaled corticosteroid (ICS)+long-acting beta agonist (LABA)+LAMA for 1 month] and the control group (administered ICS+LABA for 1 month) in a 1∶1 ratio. Clinical characteristics, blood indicators, lung function indicators, asthma control test (ACT) scores, and Asthma Quality of Life Questionnaire (AQLQ) scores were collected before and after 1 month of treatment, and efficacy indicators were compared within and between groups before and after treatment. Results: A total of 98 patients were included in the non-smoking asthma group, aged (61.9±14.3) years, and 30 were male. A total of 30 patients were included in the smoking asthma group, aged (60.4±15.2) years, all of whom were male. The proportion of males in the smoking asthma group [30.0 (100.0)% vs 30.0 (30.6)%], blood neutrophil count [(4.5±1.9)×109/L vs (3.3±2.0)×109/L], and blood neutrophil ratio [(64.0±16.5)% vs (51.2±23.2)%] were higher than those in the non-smoking asthma group (all P<0.05). The blood eosinophil count of the non-smoking asthma group [(0.2±0.2)×109/L vs (0.1±0.1)×109/L], blood eosinophil ratio [(2.2±1.8)% vs (1.5±1.1)%], IgE [(374.5±496.5)u/ml vs (161.2±187.6) U/ml], FEV1 [(1.9±0.6)L vs (1.4±0.5) L], FEV1/FVC [(74.9±11.4)% vs (65.8±11.7)%], MMEF 75/25 [(1.8±1.0)L/s vs (1.3±0.8) L/s], and FeNO [M(Q1, Q3)][34.5 (17.3, 57.3) ppb vs 25.0 (17.0, 35.0) ppb (1 ppb=1×10-9)] were all higher than those in the smoking asthma group (all P<0.05). In the study on the efficacy of LAMA treatment for smoking asthma, the intervention group included 30 cases, with an age of (49.6±10.5) years. There were 30 cases in the control group, aged (50.5±11.0) years. There was no significant difference between the two groups from baseline (all P>0.05). The number of cigarettes smoked in both groups decreased before and after treatment [intervention group: (20.3±8.0) cigarettes/d vs (8.7±6.2) cigarettes/d; control group: (20.5±7.6) cigarettes/d vs (8.3±5.3) cigarettes/d], but there was no significant difference between the two groups before and after treatment (all P>0.05). Intra-group comparison, FEV1, FVC, FEV1/FVC, MMEF 75/25, ACT score, and AQLQ score of intervention group after treatment were higher than those before treatment, and FeNO of intervention group after treatment was lower than before treatment (all P<0.05). After treatment, the ACT score and AQLQ score of control group were higher than those before treatment (all P<0.05). Between-group comparison showed that after treatment, the intervention group had higher FEV1 [(2.5±0.7) L vs (1.9±0.7) L], FVC [(3.2±0.9) L vs (2.7±0.9) L], FEV1/FVC [(78.6±6.7)% vs (72.8±11.7)%], ACT score [23.0 (23.0, 24.0) points vs 21.5 (20.3, 24.0) points], and AQLQ score [101.0 (98.0, 104.0) points vs 97.5 (93.0, 101.3) points], and lower FeNO [14.5 (10.0, 28.3) ppb vs 25.0 (19.3, 51.5) ppb] than the control group (all P<0.05). Conclusions: This study indicates that smoking asthmatic patients have worse pulmonary function but lower FeNO and peripheral blood eosinophil counts than non-smoking asthmatic patients. Compared to ICS+LABA alone, the addition of LAMA to ICS+LABA significantly improves pulmonary function, reduces FeNO, and enhances symptom control and quality of life in smoking asthmatic patients. 目的： 分析吸烟哮喘患者的临床特征，并探讨长效抗胆碱药物（LAMA）治疗吸烟哮喘患者的有效性。 方法： 吸烟哮喘的特征分析研究为病例对照研究，共纳入128例支气管哮喘患者，根据患者是否吸烟分为吸烟哮喘组和非吸烟哮喘组，比较两组间临床资料、血液指标、肺功能指标［第1秒用力呼气量（FEV1）、用力肺活量（forced vital capacity，FVC）、FEV1与用力肺活量比值（FEV1/FVC）、最大呼气中期流量（MMEF 75/25）］及呼出气一氧化氮（FeNO）。LAMA治疗吸烟哮喘患者的疗效为随机对照试验，共筛选出60例处于非急性发作期且吸烟的男性中重度哮喘患者，按照计算机软件生成随机数，以1∶1的比例分成干预组［给予吸入性糖皮质激素（ICS）+长效β2受体激动剂（LABA）+LAMA治疗1个月］和对照组（给予ICS+LABA治疗1个月）。收集患者治疗1个月前后临床特征、血液指标、肺功能指标及哮喘症状（ACT）评分及哮喘生命质量（AQLQ）评分，比较治疗前后组内和组间疗效指标。 结果： 非吸烟哮喘组共纳入98例患者，年龄为（61.9±14.3）岁，男30例。吸烟哮喘组共纳入30例患者，年龄为（60.4±15.2）岁，全部为男性。吸烟哮喘组男性比例［30.0（100.0）%比30.0（30.6）%］、血中性粒细胞计数［（4.5±1.9）×109/L比（3.3±2.0）×109/L］、血中性粒细胞比例［（64.0±16.5）%比（51.2±23.2）%］均高于非吸烟哮喘组（均P<0.05）。非吸烟哮喘组患者的血嗜酸性粒细胞计数［（0.2±0.2）×109/L比（0.1±0.1）×109/L］、血嗜酸性粒细胞比例［（2.2±1.8）%比（1.5±1.1）%］、IgE［（374.5±496.5）U/ml比（161.2±187.6）U/ml］、FEV1［（1.9±0.6）L比（1.4±0.5）L］、FEV1/FVC［（74.9±11.4）%比（65.8±11.7）%］、MMEF 75/25［（1.8±1.0）L/s比（1.3±0.8）L/s］以及FeNO［M（Q1，Q3）］［34.5（17.3，57.3）ppb比25.0（17.0，35.0）ppb（1 ppb=1×10-9）］均高于吸烟哮喘组患者（均P<0.05）。LAMA治疗吸烟哮喘的疗效研究干预组30例，年龄为（49.6±10.5）岁；对照组30例，年龄为（50.5±11.0）岁。两组间基线指标差异无统计学意义（均P>0.05）。两组患者治疗前后吸烟支数均减少［干预组：（20.3±8.0）支/d比（8.7±6.2）支/d；对照组：（20.5±7.6）支/d比（8.3±5.3）支/d］，但两组间治疗前后差异均无统计学意义（均P>0.05）。组内比较，干预组治疗后，FEV1、FVC、FEV1/FVC、MMEF 75/25、ACT评分、AQLQ评分均高于治疗前，治疗后FeNO低于治疗前（均P<0.05）；对照组治疗后，ACT评分、AQLQ评分均高于治疗前（均P<0.05）。组间比较，治疗后干预组FEV1［（2.5±0.7）L比（1.9±0.7）L］、FVC［（3.2±0.9）L比（2.7±0.9）L］、FEV1/FVC［（78.6±6.7）%比（72.8±11.7）%］、ACT评分［23.0（23.0，24.0）分比21.5（20.3，24.0）分］、AQLQ评分［101.0（98.0，104.0）分比97.5（93.0，101.3）分］均高于对照组，FeNO［14.5（10.0，28.3）ppb比25.0（19.3，51.5）ppb］低于对照组（均P<0.05）。 结论： 与非吸烟哮喘患者相比，吸烟哮喘患者的肺功能更差，FeNO和外周血嗜酸性粒细胞计数更低。在吸烟哮喘患者中，与ICS+LABA相比，LAMA+ICS+LABA能降低吸烟哮喘患者的FeNO，改善吸烟哮喘患者的肺功能、临床症状以及生活质量。.

Zhonghua yi xue za zhi

4 min15 May 2026

Hyperbaric oxygen therapy alters bowel perfusion and improves outcomes in patients with treatment-refractory ulcerative colitis: a prospective pilot trial.

Hyperbaric oxygen therapy (HBOT) delivers 100% oxygen in a pressurized chamber and enhances tissue oxygenation and neovascularization. While effective in radiation proctitis, acute severe ulcerative colitis, and perianal fistulizing Crohn's disease, its role in refractory ulcerative colitis (UC) remains underexplored. PARADOX was a prospective, open-label, phase 2a pilot trial in biologic-experienced patients with moderate-to-severe refractory UC (total Mayo > 5, Mayo endoscopic subscore (MES) ≥ 2, failure of ≥ 2 advanced therapies). Patients received 10 or 20 daily HBOT sessions (2.4 atmospheres absolute, 120 minutes/day) while continuing stable background therapy. The primary endpoint was composite clinical and endoscopic response at week 12 (≥ 3-point and 30% Mayo score reduction, rectal bleeding score = 0, and ≥ 1-point decrease in MES). Secondary outcomes included symptomatic, biochemical, and transmural response by intestinal ultrasound (IUS), including perfusion metrics via contrast-enhanced ultrasound (CEUS). In total, 16 patients (8 per group) were included in this pilot study. At week 12, composite response was achieved in 2/8 (10-session) and 4/8 (20-session) patients. Improvements in clinical, endoscopic, and IUS parameters were observed in both groups. Clinical responders showed increased CEUS perfusion at week 12 (peak enhancement Δ12.1 dB), while non-responders declined (Δ -5.4 dB). This pattern was consistent across wash-in/wash-out metrics, supporting a volume perfusion-based response. HBOT was well tolerated, with no serious adverse events or treatment discontinuations. HBOT is a well-tolerated adjunctive therapy in refractory UC, which improved clinical outcomes and perfusion kinetics. These findings support further evaluation in a randomized, dose-optimized trial.Euclinicaltrials.eu, EU CT number 2024-515278-28-00.

Extended Barrier Precautions vs Hand Hygiene Alone and Neonatal Sepsis in Intensive Care Patients: The BALTIC Cluster-Randomized Clinical Trial.

The effects of contact precautions (ie, gowns and gloves) for individual patients colonized with gram-negative (GN) drug-resistant bacteria on sepsis risk in neonates requiring intensive care remain to be clarified. To evaluate the noninferiority of standard hand hygiene disinfection vs standard hygiene disinfection plus extended barrier precautions for infants colonized with third-generation cephalosporins-resistant GN bacteria (3GCR-GNB). This cluster-randomized clinical trial was conducted from 2020 to 2023 in 12 German tertiary care neonatal intensive units caring for neonates with high risk for infections with GNB for 24 months, with crossover after 12 months. Follow-up and data curation were completed December 31, 2024, and statistical analysis was finalized on July 31, 2025. The intervention was standard hand hygiene disinfection compared with current recommendations, ie, hygiene disinfection plus extended barrier precautions with gowns and gloves for routine care of infants colonized with 3GCR-GNB. The primary outcome was the rate of health care-associated GNB bloodstream infections (BSI) at infant level in all neonates requiring intensive care in the cluster, assuming 5% as noninferiority margin delta; secondary outcomes included transmission rates of 3GCR-GNB and rates of any infection. The primary analysis was based on an overall sample size of 12 sites with crossover at 12 months, making 24 clusters with 9731 neonates. During the standard hand hygiene disinfection periods, 22 of 4699 infants (0.5%) developed GNB BSIs at infant level, compared with 25 of 5032 infants (0.5%) cared for during the extended barrier precaution periods (risk difference [RD], -0.03%; 95% CI, -0.43% to 0.38%; noninferiority P < .001). At least 1 nosocomial transmission with 3GCR-GNB was noted during 41 of 144 months in the intervention period and 54 of 144 months in the control period (RD, -9.03%; 95% CI, -27.79% to 9.74%), with involvement of 116 patients (2.5%) vs 149 patients (3.0%) (RD, -0.44%, 95% CI, -2.47% to 1.58%). The total rate of BSI was 2.1% in neonates during the intervention period vs 2.0% during the control period (RD, 0.12%; 95% CI, -1.39% to 1.64%). In this cluster-randomized clinical trial, standard hand hygiene disinfection for the care of infants colonized with 3GC-GNB was noninferior to standard hygiene disinfection plus extended barrier precautions. German Clinical Trials Register identifier: DRKS00019103.

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology

Optical coherence tomography versus angiographic guidance in true unprotected left main bifurcation disease: an OCTOBER substudy.

Dedicated randomised studies on intravascular imaging guidance in unprotected left main coronary artery (LMCA) disease are lacking. We aimed to investigate the clinical feasibility of optical coherence tomography (OCT) guidance in percutaneous coronary intervention (PCI) of true LMCA bifurcation lesions and to evaluate its prognostic impact compared with angiographic guidance. Patients with true LMCA bifurcation lesions who were randomised to either OCT or angiographic guidance in the OCTOBER Trial were included. The feasibility of OCT guidance was assessed as the proportion of patients with successful and analysable OCT pullbacks before, during, and after stenting. Clinical outcomes between the two groups were compared based on the incidence of a composite of major adverse cardiac events (MACE), comprising cardiac death, any myocardial infarction, or target lesion revascularisation. In total, 227 patients were included (OCT: 111, angiography: 116). OCT guidance was successful, with 98% of cases having a pre-stenting pullback performed and 96% a final pullback, as per protocol. The proximal LMCA stent edge was analysable in 43% of patients, and in the remaining 57%, only 5% were limited by insufficient image quality. No statistically significant difference in MACE was observed between the two groups (OCT: 14.4% vs angiography: 18.4%, hazard ratio 0.78, 95% confidence interval: 0.39-1.51). OCT-guided PCI in true LMCA bifurcation lesions was clinically feasible, but visibility of the LMCA ostium was limited by short pullbacks, insufficient clearance, or guide catheter shadowing. OCT guidance was associated with a non-significant reduction in MACE, consistent with the effect estimate in the main trial.

European journal of clinical pharmacology

The Effect of the combination therapy of statin and dapagliflozin, a selective inhibitor of sodium_glucose Co-transporter type 2, in the treatment of Ischemic heart disease with heart failure: A randomized controlled trial.

Gliflozins (SGLT2 inhibitors) and statins are key treatments commonly used in patients with ischemic heart failure. Although both are well known for diminishing cardiovascular risk and heart failure-related mortality, the possible synergistic benefits of using them together have not been thoroughly investigated. This study aimed to correlate serum levels of Statins and SGLT2i in addition to estimate the ejection fraction and selected laboratory parameters to indicate the synergistic effect of their combination in ischemic heart disease patients. In this prospective, randomized, controlled trial, 81participating patients with ischemic heart disease at department of cardiology, Fayoum University, were randomly enrolled into three groups: SGLT2i group (GPI) (n = 26) who took Dapagliflozin (10 mg) daily, Statin group (GPII) (n = 34) who administrated Atorvastatin (40 mg) or Rosuvastatin (40 mg) daily and Combination group (GPIII) (n = 21) who took both Statin and Dapagliflozin. They had been on treatment for three months before blood sampling. The trough plasma concentrations of the included patients were assessed by ultra-performance liquid chromatography (UPLC). Ejection fraction was assessed by echocardiography, laboratory tests were performed, and data were analyzed with SPSS v22 (p < 0.05). Group: III showed no adverse effects, maintained stable drug levels as the mean was 7.3 ng/ml and SD was 4.4 ng/ml (p-value 0.66), demonstrated improved ejection fraction, lipid profiles and additional metabolic benefits from SGLT2i. Dapagliflozin-statin combination therapy appears potentially beneficial for heart disease patients without affecting drug levels, though larger studies are needed to confirm.

Association of Edoxaban Pharmacokinetics With Bleeding in Older Patients With Atrial Fibrillation Treated With Low-Dose Edoxaban: A Post Hoc Analysis of a Randomized Controlled Trial.

Edoxaban is a direct oral anticoagulant used for stroke prevention in patients with atrial fibrillation (AF) and treatment of venous thromboembolism. We examined the relationship between trough edoxaban concentrations (E-trough) and prothrombin time (PT) and major bleeding in very old Japanese patients with atrial fibrillation and high bleeding risk. In this post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled ELDERCARE-AF (Study of DU-176b Aged 80 Years or Older) trial, patients were randomly assigned 1:1 to edoxaban 15 mg or placebo once daily. After 8 weeks of treatment, E-trough was determined and the incidence of major bleeding examined in each quartile. The incidence of major bleeding by PT was also examined. Data were obtained from 427 patients. E-trough (ng/mL) was ≤9.24 in the first quartile (107 patients), >9.24 to ≤13.6 in the second (111 patients), >13.6 to ≤21.6 in the third (103 patients), and >21.6 in the fourth (106 patients). Older age, lower body weight, lower creatinine clearance, and the presence of congestive heart failure were independent predictors of higher E-trough. Higher E-trough was associated with greater incidence of major bleeding (0.8%, 1.9%, 3.4%, and 4.7%/year, respectively, P=0.0408). There was a significant positive correlation between E-trough and PT (r=0.426, P<0.0001). Significantly more major bleeding events occurred in the longer (>13 seconds) versus shorter (≤13 seconds) PT subgroups (4.61% versus 0.98%/year, P=0.0060). Several factors were associated with higher E-trough and increased risk of major bleeding events. PT >13 seconds may be a useful predictor of the development of major bleeding. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02801669.

Regulatory B cell expansion and type 1 innate lymphoid cell suppression characterise immune modulation in paediatric lupus nephritis.

B-cell activating factor (BAFF) is essential for B-cell survival and innate immune activation, and its dysregulation contributes to the pathogenesis of lupus nephritis (LN). This study investigated whether BAFF-pathway inhibition alters the balance between regulatory B cells (Bregs) and type 1 innate lymphoid cells (ILC1s) in paediatric LN. In this prospective, open-label randomised study, 60 paediatric patients with biopsy-confirmed class III/IV LN were randomised to standard therapy (mycophenolate mofetil and corticosteroids; n=30) or standard therapy plus the belimumab (10 mg/kg intravenously every 4 weeks for 6 months; n=30). Ten healthy children and three patients with biopsy-confirmed minimal change disease served as controls. Flow cytometry quantified IL-10-producing Bregs and circulating ILC1s. Clinically indicated paired renal biopsies (n=3) underwent transcriptomic and immunofluorescence analyses. Belimumab was associated with greater increases in serum C3, reductions in antidouble-stranded DNA titres, decreased proteinuria, improved Systemic Lupus Erythematosus Disease Activity Index 2000 scores and reduced corticosteroid exposure. Belimumab expanded memory B cells and IL-10-producing CD19+CD5+ and CD19+CD24hi+CD38hi+ Bregs, with enhanced suppression of CD4+ T cell proliferation. Treatment reduced circulating and renal ILC1s, downregulated interferon (IFN)-stimulated genes and modulated inflammatory pathways. Serum cytokine profiling showed decreased IFN-γ, interleukin (IL)-17A, IL-10 and BAFF levels, alongside increased IL-35. Phosphorylation of the aryl hydrocarbon receptor and signal transducer and activator of transcription 3 (STAT3) in Bregs was partially restored. BAFF inhibition in paediatric LN is associated with rebalancing of innate and adaptive immunity through enhancement of Breg function and suppression of ILC1-driven inflammation.

RMD open

Comparative efficacy and safety of apixaban and rivaroxaban versus warfarin in atrial fibrillation patients with end-stage renal disease: a systematic review and meta-analysis.

This study aimed to evaluate the comparative efficacy and safety of apixaban and rivaroxaban versus vitamin K antagonists (VKAs) in anticoagulation management in a dialysis population. PubMed, Embase, and the Cochrane Library were searched for studies comparing apixaban or rivaroxaban with VKAs in patients with atrial fibrillation (AF) undergoing dialysis. The primary efficacy endpoints included stroke/systemic embolism (SSE) and all-cause mortality. Safety outcomes encompassed major bleeding, intracranial hemorrhage, and gastrointestinal bleeding. Risk ratios (RR) with 95% confidence intervals (CI) were synthesized using random-effects models. The meta-analysis included three randomized controlled trials (RCTs) and eight observational studies. Pooled analyses showed that apixaban and rivaroxaban were associated with lower risks of major bleeding (RR 0.57, 95% CI: 0.51-0.63), gastrointestinal bleeding (RR 0.66, 95% CI: 0.57-0.76), and intracranial hemorrhage (RR 0.54, 95% CI: 0.36-0.83) compared with VKAs. Additionally, apixaban and rivaroxaban were associated with reduced risk of SSE (RR 0.57, 95% CI: 0.46-0.72) and all-cause mortality (RR 0.73, 95% CI:0.63-0.83), although substantial heterogeneity was present. Exploratory dose-stratified analyses suggested both standard- and low-dose apixaban regimens were associated with favorable efficacy and hemostatic safety relative to warfarin. Consistent numerical trends were observed in the RCT-only analysis, though none reached statistical significance owing to limited sample size. In conclusion, apixaban and rivaroxaban are associated with lower risks of bleeding compared with VKAs in patients with AF and ESRD. However, evidence regarding their efficacy in preventing SSE, all-cause mortality and the optimal apixaban dosing regimen remains inconclusive and requires validation in large, dedicated RCTs.

European respiratory review : an official journal of the European Respiratory Society

Exploring the role of cold air in airway hyperresponsiveness and asthma diagnostic testing: a systematic review and meta-analysis.

Asthma is a heterogeneous disease, making uniform diagnosis challenging, resulting in both under- and overdiagnosis. We conducted a systematic review and meta-analysis to summarise the data on diagnostic accuracy of a cold air bronchial challenge test (CACh) in exercise-induced bronchoconstriction and asthma. Databases (PubMed, Embase, Web of Science core collection, Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature via EBSCO) were systematically screened for articles evaluating the use of CACh as a diagnostic tool in exercise-induced bronchoconstriction and asthma. A random-effects model was used to calculate the effect on the reduction in forced expiratory volume in 1 s (FEV1) by CACh in healthy controls compared to patients with asthma. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-Comparative. This study is registered with PROSPERO (www.crd.york.ac.uk/PROSPERO/ identifier number CRD42021290350). After screening and removal of duplicates, 39 studies were included. Aggregate sensitivity and specificity of a FEV1 decrease ≥10% after CACh were 0.808 and 0.959, respectively. The weighted mean difference in percentage FEV1 decrease after CACh for patients with asthma compared to healthy controls was -17.58. High heterogeneity (I2=99) was mainly explained by differences in reference tests to diagnose asthma. Application of the trim-and-fill method to account for publication bias imputed eight studies, resulting in a notable reduction in heterogeneity. The overall effect (a significant decrease in FEV1 in patients with asthma) remained statistically significant (-8.18, p<0.001). Our study shows the high sensitivity and specificity and possible clinical implications of a CACh in the diagnosis of asthma. Further research is needed to confirm this.

Mortality and hospitalization of heart failure patients between rural and urban areas: a systematic review and meta-analysis of 18 million patients.

Challenges in social determinants of health, fewer hospitals, further referral sites, and specialist scarcity in rural areas may hinder medical care, thus resulting in poorer outcomes for heart failure patients. This meta-analysis aims to assess the differences in mortality and other clinical outcomes of HF patients between rural and urban areas. A systematic search for eligible studies was conducted in PubMed, Embase, Medline, Science Direct, and Scopus databases. Primary outcomes were in-hospital, 30-day, and long-term mortality. Secondary outcomes were physician revisit and rehospitalization, ER readmission, and length of stay. Twenty studies with 18,893,519 participants were included. Odds ratios (ORs) or adjusted OR (aORs) and mean difference (MD) from each study were analyzed using Review Manager 5.4. HF patients in rural areas showed more significant long-term mortality (aOR = 1.09; 95% CI: 1.07-1.10; I2 = 0%; p < 0.001) and 30-day mortality (OR =1.14; 95% CI: 1.12-1.16; I2 = 33%; p < 0.001). Hospitalizations in rural areas resulted in shorter length of stay (MD = -0.95; 95% CI: -1.17-(-0.74); I2 = 32%; p < 0.001). Rural patients had more frequent 1-year ER readmission (OR =1.34; 95% CI: 1.03-1.76; I2 = 91%; p = 0.03). In conclusion, HF patients in rural areas demonstrated poorer outcomes, which may be related to shorter lengths of stay and suboptimal healthcare utilization.

Postgraduate medicine

1 min14 May 2026

Residual Angina Following Complete Revascularization in the ISCHEMIA Trial: Frequency, Clinical Characteristics, Health Status, and Cardiovascular Outcomes.

The frequency of residual angina and its impact on health status and death following anatomic complete revascularization in symptomatic patients with chronic coronary disease are unknown. Data were analyzed from ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial participants randomized to invasive management with baseline angina (Seattle Angina Questionnaire Angina Frequency score <100), no prior coronary artery bypass graft surgery, and anatomic complete revascularization within 90 days of randomization. The primary outcome was frequency of residual angina after revascularization, defined as a Seattle Angina Questionnaire Angina Frequency score <100 within 6 months of randomization. Secondary outcomes included 6-month health status and medication use and 5-year all-cause and cardiovascular death. Among 2588 participants randomized to invasive management, 1442 (56%) had baseline angina and no prior coronary artery bypass graft surgery; 1034 underwent revascularization within 90 days, and 436 achieved anatomic complete revascularization. Of these, 184 (42.2%) had residual angina within 6 months. Baseline characteristics were similar between those with and without residual angina. Percutaneous coronary intervention was more common than coronary artery bypass graft surgery in those with residual angina (88% versus 80%, P=0.03). At 6 months, residual angina participants reported lower quality of life (Seattle Angina Questionnaire Quality of Life: 70±20 versus 83±20, P<0.001), greater physical limitation (Seattle Angina Questionnaire Physical Limitation: 84±20 versus 95±11, P<0.001), more dyspnea (Rose Dyspnea Scale score: 1±1.3 versus 0.4±0.8, P<0.001), and more antianginal medication use (P=0.006). Five-year all-cause and cardiovascular death did not differ significantly between groups. Residual angina is common (>40%) following anatomic complete revascularization for chronic coronary disease and is associated with reduced quality of life and greater antianginal medication use but no increase in death. Unique Identifier: NCT01471522.

The Korean journal of internal medicine

LncRNA as a diagnostic marker for rheumatoid arthritis: a systematic review and meta-analysis.

Rheumatoid arthritis (RA) is categorized as an autoimmune disorder characterized by the absence of a definitive cure. In this investigation, we executed a systematic review and diagnostic meta-analysis to ascertain the diagnostic efficacy of long non-coding RNAs (lncRNAs) in the identification of RA. Our survey involved relevant studies published in PubMed, Web of Science, Embase, Cochrane library search engines. Specificity and sensitivity were calculated, as well as positive likelihood ratios (PLRs), negative likelihood ratios (NLRs), and diagnostic odds ratios (DORs). The operating characteristics of the overall receiver were plotted, and the area under the curve (AUC) was evaluated. This systematic review and meta-analysis incorporated 34 studies involving a total of 1,535 participants-comprising 853 individuals diagnosed with RA and 682 control subjects without the disease. The pooled specificity, sensitivity, NLR, PLR, and DOR were 0.88 (95% CI: 0.84-0.92), 0.86 (95% CI: 0.81-0.91), 0.15 (95% CI: 0.11-0.22), 7.51 (95% CI: 5.39-10.46), and 49.06 (95% CI: 30.31-79.41), respectively, and the AUC = 0.94 (95% CI: 0.91-0.96). Subgroup analysis was performed according to lncRNA expression in RA, sample size, sample type, RNA extraction, and control group type. This meta-analysis reveals that lncRNAs may serve as powerful biomarkers for RA. This systematic review and meta-analysis provides the first evidence showing the potential value of using lncRNAs as a diagnostic tool for RA.

European journal of pharmacology

Antifibrotic efficacy of adipose-derived mesenchymal stem cell-based therapeutic strategies in pre-clinical models of pulmonary fibrosis: A systematic review and meta-analysis.

Pulmonary fibrosis (PF) represents a heterogeneous group of chronic fibrotic lung diseases, characterized by excessive extracellular matrix (ECM) deposition and irreversible scarring, lacking curative therapies. This review highlights the antifibrotic efficacy of adipose-derived mesenchymal stem cells (AD-MSCs) in pre-clinical PF models. The review was prospectively registered in the PROSPERO database (registration number: CRD420251119193). Peer-reviewed experimental investigations/original articles were searched from Google Scholar, PubMed, and ScienceDirect up to April 2025. Risk of bias in in-vivo studies was assessed using SYRCLE's tool and for in-vitro studies, quality was evaluated with the QUIN tool. Results were synthesized narratively and quantitatively, using a random-effects model to pool mean differences (MD) with 95% confidence intervals for antifibrotic outcomes based on Ashcroft scores. Heterogeneity was assessed using Cochran's Q test and I2 statistic. A comprehensive literature search yielded 397 studies, out of which 19 studies selected after title-based, abstract-based, and full text-based screening. Forest plot showed overall mean difference as -1.35 [95% CI: -3.19, 0.49]. Ashcroft scores were lower in treated groups compared with control group, but overall mean difference was not statistically significant (z = 1.44, p = 0.15), likely due to small number of studies included and high heterogeneity. However, individual studies demonstrated reduced fibrosis in treated groups. AD-MSCs consistently reduced fibrosis in pre-clinical PF models while modulating pathways relevant to IPF pathogenesis i.e., Smad, NF-κB, ERK, and key miRNA networks. Collectively, current evidences position AD-MSCs and their derivatives as promising antifibrotic candidates with strong clinical translation potential.

The New England journal of medicine

Telitacicept for IgA Nephropathy - Interim Analysis of a Phase 3 Trial.

The pathogenesis of IgA nephropathy is mediated by B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Telitacicept is a fusion protein that targets and neutralizes both BAFF and APRIL and, as such, might be effective in IgA nephropathy. We now report a prespecified interim analysis of a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, which enrolled adults with biopsy-proven IgA nephropathy and persistent proteinuria (protein level, ≥1.0 g per day), despite appropriate supportive care. Patients were randomly assigned in a 1:1 ratio to receive subcutaneous once-weekly telitacicept (240 mg) or matching placebo. The primary end point was the geometric mean ratio of the 24-hour urinary protein-to-creatinine ratio at 39 weeks relative to baseline. Safety was also evaluated. A total of 318 patients were assigned to receive telitacicept or placebo (159 in each group). At week 39, the percentage change in the 24-hour urinary protein-to-creatinine ratio was -58.9% with telitacicept and -8.8% with placebo, which corresponded to a relative difference (based on the ratio of geometric mean reductions between the two groups) of -55.0% (95% confidence interval [CI], -61.3 to -47.6; P<0.001) in favor of active medication. The percentage change in the estimated glomerular filtration rate relative to baseline was -1.0% (95% CI, -3.2 to 1.2) with telitacicept and -7.7% (95% CI, -9.9 to -5.4) with placebo. Adverse events were more common with telitacicept than with placebo (in 89.3% vs. 78.6% of patients), although serious adverse events were less common (in 2.5% vs. 8.2%). No unexpected safety findings were reported with telitacicept. In patients with IgA nephropathy at high risk for progression, 39 weeks of treatment with telitacicept led to a greater reduction in the 24-hour urinary protein-to-creatinine ratio than placebo. (Funded by RemeGen; TELIGAN ClinicalTrials.gov number, NCT05799287.).

International journal of molecular sciences

Differential Acute Kidney Injury Profiles of GLP-1RAs and SGLT2is: A Network Meta-Analysis.

Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter 2 inhibitors (SGLT2is) have demonstrated protective effects against chronic kidney disease, their impact on acute kidney injury (AKI) remains unclear. AKI and chronic kidney disease share overlapping clinical features but differ in pathogenesis and risk profiles. Previous analyses often grouped diverse agents into single categories, potentially concealing medication-specific renal risks. Given the widespread assumption of renoprotection, particularly among newer agents, there is a need to evaluate the comparative AKI risk of GLP-1RAs and SGLT2is at the individual drug and dose level. We performed a Bayesian network meta-analysis (NMA) following Cochrane-recommended methodology for safety-focused assessments. A systematic literature search across eight databases identified 67 randomized controlled trials (RCTs), including 199,877 participants. Eligible trials reported AKI outcomes or sufficiently explicit acute renal injury-related events associated with GLP-1RA or SGLT2i interventions. The primary outcome was the incidence of AKI; all-cause dropout was analyzed as a general tolerability measure. Odds ratios (ORs) with 95% credible intervals (CrIs) were calculated, and surface under the cumulative ranking curves (SUCRA) were used to estimate relative safety rankings. Only high-dose tirzepatide (10-15 mg/week) was associated with a significantly increased risk of AKI compared to controls (absolute risk difference: 0.28%; number needed to harm: 357). In contrast, lixisenatide, high-dose canagliflozin (300 mg/day), empagliflozin, and dapagliflozin were associated with reduced AKI risk. Risk rankings consistently identified high-dose tirzepatide as the most likely to induce AKI. Subgroup analyses excluding patients with baseline renal impairment yielded consistent results. High-dose tirzepatide may elevate AKI risk despite its metabolic benefits. Clinicians should assess renal vulnerability when prescribing GLP-1RAs or SGLT2is, particularly in patients with preserved kidney function. Further prospective trials are needed to clarify causal mechanisms and inform clinical decision-making.

Exploring the psychological and physiological effects of a virtual reality-based bicycle exercise in hemodialysis patients: a randomized controlled trial.

This study aimed to evaluate the efficacy of a virtual reality (VR)-based bicycle exercise in psychological distress (depression and anxiety) and selected biochemical parameters among patients receiving maintenance hemodialysis (MHD). A total of 70 patients from the dialysis station at Changzhou Medical District of the No. 904th Hospital were randomly allocated into study group(VR-based bicycle exercise, n = 35) and control group(routine nursing care, n = 35). The depression and anxiety levels were assessed by Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS) respectively. Physiological indicators, including serum creatinine (Scr) and blood urea nitrogen (BUN) levels, were also analyzed. Following the intervention, the study group exhibited significant reductions in SDS and SAS scores (both P < 0.05). The levels of Scr and BUN in peripheral blood were also observed to be significantly decreased in study group (P < 0.05). Correlation analysis revealed a significant positive correlation between SAS/SDS scores with both Scr and BUN levels (P < 0.05 or P < 0.01). Furthermore, regression models identified SAS scores as significant predictors of Scr and BUN levels, accounting for 27.8% and 31.9% of their variance, respectively (P < 0.05 or P < 0.01). VR-based bicycle exercise can improve psychological well-being, and was associated with beneficial changes in pre-dialysis serum biomarkers (Scr and BUN) in MHD patients. This integrated intervention represents a promising non-pharmacological strategy to complement standard care in MHD patients.

The Assessment of Multidimensional Clinical, Biological and Patient-Reported Outcomes to Evaluate the Efficacy of Add-On Lactobacillus rhamnosus GG Supplementation in Mild Ulcerative Colitis: A Randomized Pilot Trial.

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca' Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4+ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management.

Nutrients

Addiction science & clinical practice

Twelve-month smoking cessation outcomes following immediate referral in people who smoke with chronic airway diseases: a randomized study.

Tobacco cessation support remains underutilized in routine care for patients with airway diseases such as asthma and COPD. In this multicenter randomized trial (NCT05764343, registration date: 2023-03-01), we previously reported that immediately scheduled appointments to smoking cessation clinics improved access and quit rates at 1-week and 3-month follow-ups. The present study evaluated whether these effects were sustained at 12 months. This prospective, parallel-arm, multicenter randomized trial included 397 adult people who smoke diagnosed with asthma, COPD, or bronchiectasis. Participants were allocated to either usual support (brief advice only) or immediate support (brief advice plus an appointment scheduled at a smoking cessation clinic). Smoking status was assessed by telephone at 12 months. Self-reported quitters were invited for exhaled carbon monoxide (CO) testing. The primary outcome was continuous abstinence at 12 months, analyzed on an intention-to-treat basis. Of 397 randomized patients, 330 (83.1%) completed the 12-month follow-up, with similar loss to follow-up between groups. In the intention-to-treat analysis, the 12-month smoking cessation rate was significantly higher in the immediate support group compared with the usual support group (20.7% vs. 11.6%, p = 0.019). Among non-quitters, quit attempts, smoking cessation clinic admission, and pharmacotherapy use were significantly more common in the immediate support group (p < 0.05). Immediate scheduling of smoking cessation clinic appointments resulted in significantly higher 12-month quit rates compared to usual care. These findings support the integration of proactive referral strategies into routine management of patients with chronic airway diseases.

Evaluation of the diagnostic value of the Modified Evan's Blue Dye Test for assessing aspiration in tracheostomized critically ill patients: A systematic review and meta-analysis.

Dysphagia and aspiration are common complications in tracheostomized critically ill patients. The Modified Evan's Blue Dye Test (MEBDT) is a non-invasive, bedside, adjunctive rule-in signal for aspiration when positive. However, its diagnostic accuracy compared to the gold standard Fiberoptic Endoscopic Evaluation of Swallowing (FEES) in these patients remains unclear. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of the MEBDT for the detection of aspiration in tracheostomized critically ill patients. Study protocol was prospectively registered on PROSPERO (CRD:42023479920). A systematic search was performed across three databases (PubMed, Cochrane Central, and Embase), followed by a systematic screening process against predetermined selection criteria and included studies that provided data on the sensitivity and specificity of MEBDT versus FEES. The risk of bias and the level of evidence certainty in the included papers were assessed by the QUADAS-2 tool and GRADE approach respectively. Six out of 2227 screened studies were included. We found that MEBDT had a high specificity 95.42% (95% CI [67.38%, 99.53%]) and positive predictive value 95% (95% CI [81, 100]). In conclusion, the MEBDT can serve as a bedside adjunctive tool that indicates a potential aspiration risk when the result is positive. However, if the result is negative, further diagnostic assessments, like FEES, are recommended for high-risk patients.

PloS one

Risk factors of inflammatory bowel disease complicating anemia: A systematic review and meta-analysis.

Inflammatory bowel disease (IBD) frequently complicates with anemia, which worsens disease prognosis and quality of life. However, the risk factors for IBD complicating anemia remain unclear. This study aims to systematically evaluate the risk factors of anemia in patients with IBD, and provide evidence for clinical practice. We systematically searched PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang Data, Cqvip, and SinoMed databases up to December 1, 2024. Literature screening, data extraction, and quality assessment were independently performed by 2 reviewers. Meta-analysis was conducted using Review Manager (RevMan) version 5.3. Fourteen studies, involving 111,940 patients, were included. Six significant risk factors were identified: advanced age (odds ratio [OR] = 1.07), smoking history (OR = 1.88), active disease (OR = 2.11), elevated C-reactive protein levels (ulcerative colitis: OR = 2.20; Crohn disease: OR = 2.06), decreased albumin levels (ulcerative colitis: OR = 0.78; Crohn disease: OR = 0.88), and penetrating disease behavior (B3) (OR = 6.08). Multiple factors are associated with an increased risk of anemia in patients with inflammatory bowel disease. The early identification of these factors may facilitate timely risk stratification, closer monitoring, and targeted interventions.

1 min12 May 2026

Symptom burden and treatment patterns in primary biliary cholangitis: A systematic review and meta-analysis.

Patients with primary biliary cholangitis (PBC) often suffer from debilitating symptoms, yet the overall symptom burden has not been systematically quantified. This study aims to systematically review the prevalence and severity of the symptom burden in PBC patients. We conducted a systematic search of 3 electronic databases to include studies that reported the prevalence and severity of PBC symptoms. Subgroup analyses were performed based on study type, publication year, risk of bias, study location, sex, and latitude. A total of 25 studies involving 13,178 patients were included. Fatigue was the most common symptom, affecting 51% of patients, followed by pruritus at 33%. Severe fatigue and severe pruritus were reported in 23% and 10% of patients, respectively. The prevalence of fatigue was significantly higher in more recent studies, those with smaller sample sizes, and studies published as abstracts. Fatigue score was significantly higher in female patients compared with males. Severe fatigue was more prevalent in studies conducted in North America/Europe than those from Asia (26% vs. 8%, p=0.0005), and in studies with a higher proportion of patients with cirrhosis (28% vs. 8%, p=0.0005). Despite the high burden, only 36% of PBC patients with pruritus received anti-pruritic treatment, with antihistamines being the most frequently prescribed medication. Over half of PBC patients experience significant symptom burden, with substantial ethnic disparities identified. The proportion and quality of appropriate symptom management in PBC are suboptimal. There remains an unmet need for standardized assessment, consistent reporting, and improved management strategies for PBC-related symptoms in future research.

Anti-neutrophil cytoplasmic antibodies in interstitial lung disease: results from a cross-sectional study and meta-analysis.

This study aims to investigate the prevalence, clinical characteristics, and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) across different subtypes of interstitial lung disease (ILD), specifically idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD) without ANCA-associated vasculitis (AAV), and AAV-ILD. A cross-sectional study was conducted to evaluate the positivity rate and clinical characteristics of ANCA in ILD. In the following meta-analysis, PubMed, Web of Science and Scopus were searched for eligible studies reporting positivity rate of ANCA in ILD. The pooled positivity rates of ANCA, MPO and PR3 in ILD were calculated, and survival outcome between ANCA-positive and ANCA-negative ILD patients were compared. Sensitivity analyses, subgroup analyses and meta-regression was also conducted. A total of 217 ILD patients were enrolled in this cross-sectional study, with an ANCA positivity rate of 7%. In the meta-analysis, with 24 studies and 4,424 patients, the pooled positivity rate of ANCA in IPF, CTD-ILD without AAV, and AAV-ILD were 9%, 15% and 97%, respectively. In patients with IPF, patients with ANCA positivity were more likely to develop honeycombing (OR 2.70, 95%CI 1.09, 6.70, p = 0.03). No significant difference was observed in survival time between IPF patients with or without ANCA positivity (HR 1.18, 95%CI 0.73, 1.90). The positivity rate of ANCA varies significantly across different subtypes of ILD. Future research should focus on the characteristics and prognostic value of ANCA positivity in other ILD subtypes.

Immunologic research

A meta-analysis of the efficacy and safety of Janus kinase inhibitors in patients with ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing intestinal inflammation and substantial impairment of quality of life. Janus kinase (JAK) inhibitors are orally administered small-molecule agents that interfere with intracellular cytokine signaling pathways central to UC pathogenesis. This systematic review and meta-analysis aimed to assess the therapeutic benefits and safety profile of JAK inhibitors in adults with moderate-to-severe UC. A systematic literature search was conducted in PubMed (from inception to November 2025), Embase, the Cochrane Library, and Web of Science to identify placebo-controlled RCTs evaluating JAK inhibitors in adult patients with UC. The primary efficacy outcomes were clinical remission and clinical response. Secondary outcomes included endoscopic remission, endoscopic response, and mucosal healing. Safety was assessed by the incidence of any adverse events (AEs). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models as appropriate. Statistical heterogeneity was evaluated using the I2 statistic, and subgroup analyses were performed according to treatment phase. Nine publications encompassing 14 placebo-controlled RCT datasets met the inclusion criteria. Compared with placebo, JAK inhibitors significantly increased rates of clinical remission (RR = 2.48, 95% CI: 1.64-3.73) and clinical response (RR = 2.53, 95% CI: 1.73-3.70), although moderate-to-high heterogeneity was observed. Endoscopic outcomes were also markedly improved, with higher rates of endoscopic remission (RR = 3.52, 95% CI: 2.55-4.86) and mucosal healing (RR = 2.60-2.79 across models). Safety analyses demonstrated no significant difference in the overall incidence of adverse events between JAK inhibitors and placebo. Subgroup analyses revealed consistent efficacy during both induction and maintenance phases, with comparable safety profiles across treatment periods. JAK inhibitors provide significant improvements in both clinical and endoscopic outcomes for patients with moderate-to-severe UC without increasing the overall risk of adverse events in short-term trials. These findings support the clinical utility of JAK inhibitors in UC management, while highlighting the need for long-term studies to better characterize rare and delayed safety signals.

Effects of an action research-based nursing program on rheumatoid arthritis patients on long-term hormone therapy: A randomized controlled trial.

This study aims to evaluate the impact of an action research-based nursing program on patients with rheumatoid arthritis (RA) undergoing long-term hormone therapy. Eighty RA patients admitted to the Department of Rheumatology and Immunology from January 1, 2023, to May 31, 2024, and receiving long-term hormone therapy were recruited. Patients were randomized into 2 groups of 40 each: a control group receiving conventional care and an intervention group receiving care based on the action research method. Evaluations included daily measurements of fasting and 2-hour postprandial blood glucose levels, compliance assessed via a self-developed compliance scale with established reliability and validity, pain via a Visual Analog Scale, joint activity using the 28-joint Disease Activity Score, and anxiety and depression levels using self-rating scales. Baseline measurements showed no significant differences between the groups in fasting blood glucose, 2-hour postprandial blood glucose, pain, joint mobility, and anxiety and depression scores (P > .05). Post-intervention, both groups exhibited improvements in compliance, pain, joint mobility, and anxiety and depression scores, with the intervention group showing significantly greater improvements. The intervention group showed significantly smaller increases in fasting and 2-hour postprandial blood glucose than the control group. The action research-based nursing program significantly enhances compliance and joint mobility, controls blood glucose increases, and reduces pain, anxiety, and depression in RA patients on long-term hormone therapy. This method provides a practical reference for clinical nursing intervention in such patients.

Iranian journal of allergy, asthma, and immunology

Evaluating the Efficacy of Intranasal Montelukast in Pediatric Acute Asthma Attacks: A Single-blinded, Placebo-controlled Clinical Trial.

Asthma is a common chronic respiratory disease in children, often leading to acute exacerbations marked by dyspnea, cough, and wheezing, which frequently necessitate emergency medical care. While standard therapies are effective, the exploration of novel drug delivery routes continues. Oral montelukast is a recognized treatment, but the efficacy of its intranasal formulation for acute attacks remains underexplored. This study aimed to evaluate the clinical effectiveness of intranasal montelukast as an adjunct therapy for pediatric asthma exacerbations. A single-blinded, placebo-controlled, single-center trial was conducted involving children aged 2-12 years hospitalized with moderate to severe acute asthma. Participants were randomized to receive either intranasal montelukast or a placebo alongside standard care. Key outcomes, including the Pulmonary Index Score (PIS), respiratory rate, oxygen saturation, and length of hospital stay, were systematically assessed. The analysis of 25 patients in each group revealed no significant baseline differences. The intranasal montelukast group demonstrated a statistically significant and sustained reduction in PIS scores at critical intervals (8, 12, and 24 hours) compared to the placebo group. Improvements in respiratory rate and oxygen saturation were also more pronounced with the active treatment. Notably, the mean hospital stay was significantly shorter for the montelukast group (2.16 days) than the placebo group (3.12 days). In conclusion, intranasal montelukast shows significant promise as an effective adjunct therapy for acute pediatric asthma, correlating with accelerated clinical improvement and a reduced duration of hospitalization. These encouraging results justify further investigation through larger, multicenter trials to definitively establish its efficacy and safety profile.

A molecular systems architecture of asthma.

Asthma is a heterogeneous inflammatory disease driven by complex genetic, immunological, environmental, and neuro-immune interactions. Modern therapeutic strategies increasingly target distinct molecular mechanisms underlying specific asthma endotypes. Emerging evidence highlights the role of psychological stress in modulating the neuro-immune axis, contributing to allergic airway inflammation. Systems biology offers a powerful framework to understand the multi-cellular and cross-organ interactions between lung and brain microenvironments that drive asthma pathogenesis. To develop a molecular systems architecture of asthma using the CytoSolve® systems biology platform and process. This approach enables a multi-layered, systems-level analysis of molecular pathway interactions across thirty-one pulmonary, immune, and neuronal cell types involved in allergic-eosinophilic and non-allergic asthma phenotypes, and identifies potential therapeutic targets. A systematic bioinformatics literature review was conducted using Medical Subject Headings (MeSH) across PubMed, Medline, and Google Scholar, covering peer-reviewed publications from January 2008 to August 2025. Relevant full-length articles were curated and analyzed using the CytoSolve® platform to construct a molecular systems architecture of asthma. The relevant literature was critically analyzed to understand the link between environmental and psychological stress triggers that drive asthma pathogenesis and disease exacerbations. The systems architecture identified biomolecular interactions across thirty-one cell types spanning bronchial, immune, stromal, vascular, endocrine, and neuronal compartments, including airway epithelial cells, T-cells, eosinophils, mast cells, fibroblasts, microglia, hypothalamic and brainstem neurons, vagal sensory neurons, and autonomic airway neurons. Environmental triggers such as pollutants and infections initiate cascades that promote three core pathobiological processes: airway inflammation, hyperresponsiveness, and remodeling. Psychological comorbidities, including anxiety and depression, further amplify airway inflammation through brain-lung cross-talk, contributing to neuronal inflammation and asthma exacerbations. This system architecture generated a multilayered visual map that shows the associations between various triggers and biomolecular interactions across airway and neuronal cell types in the lung and brain microenvironment, respectively. The architecture may be utilized for target identification, discovery of single and combination therapeutics, biomarkers, and clinical strategies to treat asthma endotypes.

Effects of traditional Chinese medicine polysaccharides on rheumatoid arthritis through gut microbiota modulation: a systematic review in animal models.

Traditional Chinese medicine polysaccharides (TCMPs) are promising therapeutic candidates for rheumatoid arthritis (RA), known for their efficacy and low toxicity. Acting as potent gut microbiota modulators, TCMPs may alleviate RA by reshaping microbial communities and their metabolic outputs. This systematic review followed PRISMA guidelines. We searched PubMed, Web of Science, and Embase up to April 7, 2025, for relevant animal studies. From an initial pool of 282 records, nine studies meeting the inclusion criteria were analyzed, involving polysaccharides from six single herbs and one compound formula. The results demonstrated that TCMPs significantly alleviated RA symptoms, including paw swelling and arthritis scores, and improved bone quality metrics. Regarding gut microbiota modulation, TCMPs induced changes in nine phyla (e.g., Patescibacteria, Desulfobacterota, Firmicutes) and 65 genera. At the genus level, 37 taxa (including Dubosiella, Faecalibaculum, Bifidobacterium) increased in abundance post-treatment, while 20 decreased. The results for 8 genera were inconsistent across studies. Notably, the abundance of Lactobacillus was reported to increase in four of the included studies. These microbial shifts correlated with reduced pro-inflammatory cytokines (e.g., IL-1β, TNF-α), improved RA clinical and bone parameters, and elevated levels of short-chain fatty acids (SCFAs), particularly butyrate and propionate. Correlation analyses identified Romboutsia and Lactobacillus as negatively associated with RA severity. Mechanistically, TCMPs enriched beneficial genera, enhanced SCFA production, suppressed NF-κB and JAK/STAT3 pathways, upregulated tight junction-related genes, and inhibited NLRP3 inflammasome activation via microbiota-derived metabolites, collectively forming a "microbiota-metabolite-host" regulatory network. This review demonstrates that TCMPs alleviate RA in animal models by modulating gut microbiota to enrich beneficial bacteria, suppress pathogens, enhance intestinal barrier function, and regulate immune homeostasis via the gut-joint axis, with SCFAs playing a pivotal role. Given the low methodological quality and high heterogeneity of included studies, future research should prioritize rigorous design, multi-omics integration, and clinical translation. https://www.crd.york.ac.uk/prospero/, identifier CRD420251053482.

Identification of new overlapping and disease-specific genetic risk factors for rheumatoid arthritis and radiographic axial spondyloarthritis: a meta-analysis of three large European populations and functional characterization.

This study conducted a meta-analysis across three large European cohorts (UKBB, FinnGen, and REPAIR), including 12,660 rheumatoid arthritis (RA) cases, 2,446 radiographic axial spondyloarthritis (r-axSpA) cases, and over 530,000 shared controls. Ten independent SNPs in CARMIL1, GRM4, ITPR3, PRSS16, ZNF322, HTT, IKZF1, MANEA, and MGAM2 were analyzed, and functional characterization was performed through cytokine and protein assessments as well as eQTL analyses. Ten independent SNPs were significantly associated with both RA and r-axSpA. Risk alleles included HTT rs363075A, IKZF1 rs12718261A, MANEA rs72920280T, and MGAM2 rs73158426G, while CARMIL1 rs72831267C, GRM4 rs2495964G, ITPR3 rs77601296A, ITPR3 rs9469540T, PRSS16 rs72843633T, and ZNF322 rs6901425G had protective effects. Functional analysis showed that GRM4 rs2495964G was linked to decreased CCL25 levels (p = 0.00030), and ITPR3 rs9469540T to reduced IL10 production after LPS stimulation (p = 1.3×10-4). The ZNF322rs6901425G allele was associated with reduced TNFB and increased TGM2 levels (p = 9.60×10-4 and p = 3.00×10-4), both involved in immune signaling and tissue remodeling. Disease-specific associations were found in BTN2A1, BTN3A2, and H2BC11. The BTN2A1 rs1977199A allele was protective in RA (OR = 0.93) but increased r-axSpA risk (OR = 1.23), and was associated with reduced IL22 (p = 0.00016) and elevated HO-1 in obese individuals (p = 6.73×10-6). In contrast, BTN3A2 rs9393716G and H2BC11 rs66462181C increased RA risk but were protective in r-axSpA, linked to decreased HO-1 and IL6 (p = 2.43×10-5, 3.287times;10-4, 1.18×10-4). These SNPs also acted as eQTLs for immune-related genes such as BTN3A2, HMGN4, and TRIM38. Our findings highlight novel shared and disease-specific variants and key immunoregulatory mediators-IL10, IL22, IL6, CCL25, and HO-1-offering insights for disease stratification and therapeutic targeting.

Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis.

Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.

Annals of medicine

Enpatoran, a Toll-like receptor 7/8 inhibitor, in moderate-to-severe systemic lupus erythematosus: findings from Cohort B of a multicentre, international, double-blind, placebo-controlled dose-finding phase 2 trial.

Toll-like receptors (TLR) 7 and 8 (TLR7/8) are activators of innate and adaptive immunity contributing to lupus pathogenesis. In Cohort B of WILLOW, a phase 2, randomised, placebo-controlled, double-blind, basket, dose-finding study, enpatoran, an oral small molecule inhibitor of TLR7/8, was evaluated in participants with active systemic lupus erythematosus (SLE). Participants were eligible if they were aged 18-75 years with moderate-to-severe SLE, with or without cutaneous manifestations, had a disease duration of at least 6 months, and were receiving a stable dose of medication before the screening period. Participants were recruited from 132 centres in 22 countries. In Part 1, participants were randomly allocated in a 1:2 ratio to receive either placebo or 100 mg enpatoran, both twice-daily. Following the enrolment of 60 participants, Part 2 was activated and additional participants were randomly allocated in a 1:1:1:1 ratio to 25 mg, 50 mg, or 100 mg of enpatoran or placebo, all twice-daily, for 24 weeks. Random allocation was stratified by region, biomarker status, and hybrid Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index score. The primary objective was to evaluate the dose-response relationship of enpatoran, using British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate at week 24, based on multiple comparison procedure-modelling analysis. Study visits were scheduled from week 0 to week 24, followed by a 2-week safety follow-up period for participants who chose not to enter the long-term extension. From weeks 2 to 12, glucocorticoid doses were tapered to a prednisone-equivalent dose of no more than 5 mg/day, as clinically tolerated. Adverse events were monitored continuously throughout the study; safety parameters (including physical examination, vital signs, and routine chemistry and haematology) were assessed at all study visits. The trial was registered at ClinicalTrials.gov (NCT05162586) and a long-term extension study is ongoing. Between May 4, 2022, and Feb 6, 2024, participants were screened for eligibility for WILLOW cohorts A and B; 715 participants were screened and 354 were randomly allocated and included in the Cohort B safety population (95 to placebo, 71 to 25 mg enpatoran, 74 to 50 mg enpatoran, and 114 to 100 mg enpatoran). One patient allocated to the placebo group was found to be ineligible and was excluded from the full analysis set for the efficacy analyses. 335 (95%) of 353 participants were female, 18 (5%) were male, and median age was 41 years (IQR 33-51). At week 24, the study did not meet its primary objective of identifying a statistically significant dose-response relationship for enpatoran in BICLA response rate (p=0·14). BICLA response rates at week 24 were higher with all doses of enpatoran (25 mg: 41 [58%] of 71; odds ratio [OR] vs placebo 2·2 [95% CI 1·1-4·0], 50 mg: 36 [49%] of 74; OR 1·5 [95% CI 0·8-2·8], and 100 mg: 56 [49%] of 114; OR 1·6 [95% CI 0·9-2·8]) versus placebo (37 [39%] of 94). The most common treatment-emergent adverse event was diarrhoea, in four (6%) of 71, two (3%) of 74, and two (2%) of 114 participants in the 25 mg, 50 mg, and 100 mg enpatoran groups, respectively, and seven (7%) of 95 participants in the placebo group. Serious adverse events were reported in one (1%) of 71, three (4%) of 74, five (4%) of 114, and three (3%) of 95 participants treated with 25 mg, 50 mg, and 100 mg enpatoran and placebo, respectively. In this study of participants with moderate-to-severe SLE, enpatoran improved BICLA response rates versus placebo; however, the primary objective of a statistically significant dose-dependent effect on disease activity based on BICLA response was not met. Enpatoran was well tolerated across all dose groups. Merck Healthcare (Darmstadt, Germany).

Lancet (London, England)

4 min11 May 2026

Mirikizumab is associated with rapid and sustained improvements in novel measures of bowel urgency in moderately-to-severely active ulcerative colitis: 28-week results from the LUCENT-URGE trial.

LUCENT-URGE (NCT05767021) was a Phase 3b, multicenter, open-label, single-arm study investigating bowel urgency (BU) in patients with moderately-to-severely active ulcerative colitis (UC) and BU at baseline, treated with mirikizumab. Patients without prior mirikizumab exposure received intravenous mirikizumab 300 mg at weeks (W)0, 4, and 8, followed by subcutaneous mirikizumab 200 mg at W12, 16, 20, and 24. The primary objective was improvement in the validated BU severity measure (Urgency Numeric Rating Scale [UNRS]) at W12. Secondary objectives included improvement in BU at W28, novel measures of stool deferral time (SDT), bowel urgency frequency (BUF), and associations between BU measures. UNRS, BUF, and SDT were collected using a daily diary; the shortest weekly SDT was used for analysis. Baseline observation carried forward was used as the response for the corresponding visit for all missing observations. Missing continuous data were treated as having no change from baseline. All three BU measures at W12 were sustained or improved through W28. With mirikizumab treatment, 52.2% improved BU severity, 55.1% improved BUF, and 40.7% improved shortest weekly SDT. Patients with shortest weekly SDT ≥ 15 min or no urgency increased from 4.1% at baseline to 29.7% at W28. At W12, 36 (20.9%) achieved clinical remission and 54 (31.4%) achieved endoscopic remission, improving to 62 (36.1%) and 76 (44.2%) at W28, respectively. The safety profile was generally consistent with the known profile. In the first comprehensive approach assessing complex BU symptoms in UC, mirikizumab was associated with improvements in several BU and clinically related measures through W28. ClinicalTrials.gov, NCT05767021. Mirikizumab treatment was associated with improved bowel urgency severity, frequency, and stool deferral time in patients with moderately-to-severely active ulcerative colitis, showing better patient-reported quality of life outcomes, improved endoscopic appearance, and fewer symptoms over a 28-week trial.

Effects of exercise training on depression, anxiety, and physical health-related quality of life in end-stage renal disease patients receiving maintenance hemodialysis: a systematic review and meta-analysis of randomized controlled trials.

Maintenance hemodialysis patients commonly have adverse emotional states of depression and anxiety, leading to a serious decline in their quality of life. Exercise therapy acts as a supplementary measure that has the potential to relieve negative emotions. However, gaps remain in the current literature. To explore the effect of exercise intervention on depression, anxiety, and physical health-related quality of life in maintenance hemodialysis patients, and analyze the influence of population characteristics and intervention plans on the curative effect of exercise therapy. A literature search was conducted across 12 databases from inception to November 14, 2025. Two researchers independently screened literature and extracted data based on PICOS framework. R software and Stata software were utilized for data analysis to evaluate intervention effects by calculating standardized mean differences (SMD) and 95% confidence intervals (CI). Sensitivity analysis was done by the leave-one-out method. Egger's test and trim-and-fill method were used to explore potential publication bias. The revised Cochrane risk-of-bias tool was used to assess the methodological quality of included studies, and the GRADE method assessed the overall quality of evidence. A total of 27 studies involving 1,597 participants were included. Meta-analysis results demonstrated that exercise improved depression and physical health-related quality of life in maintenance hemodialysis patients, while its effect on anxiety remains uncertain. Subgroup analyses indicated that exercise therapy yielded better outcomes in patients under 60 years of age. Intervention durations exceeding 24 weeks, the adoption of combined aerobic and strength training protocols, and a total weekly exercise volume of more than 120 min were associated with significant improvements in depression. Implementing exercise therapy with specialized equipment could better enhance physical health-related quality of life. The findings of this study demonstrate that exercise significantly ameliorates depression and modestly improves physical health-related quality of life in maintenance hemodialysis patients. However, due to the small number of included studies, high statistical heterogeneity, and limited assessment of publication bias, the ameliorating effect on anxiety cannot be definitively confirmed, necessitating future large-scale and rigorously designed randomized controlled trials for further verification. Furthermore, this study revealed that the intervention effects are moderated by variables including age, equipment utilization, exercise type, intervention duration, and total weekly exercise volume. Future research should prioritize the development of tailored exercise prescriptions for hemodialysis patients while concurrently enhancing the methodological rigor of study designs. Healthcare professionals should pay attention to improving the mental health of this group by implementing exercise therapy. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251196880, Identifier: CRD420251196880.

United European gastroenterology journal

Effect of Mirikizumab on Clinical and Endoscopic Outcomes Based on Prior Advanced Therapy Failure in Patients With Moderately to Severely Active Ulcerative Colitis.

Mirikizumab demonstrated efficacy in moderately-to-severely active ulcerative colitis, including in patients with prior advanced therapy failure (PATF) (Phase 3: LUCENT-1 [NCT03518086], LUCENT-2 [NCT03524092]). This post hoc analysis evaluates mirikizumab efficacy by number/mechanism of PATF. LUCENT-1 patients received 300 mg mirikizumab or placebo; mirikizumab induction responders entered LUCENT-2 and received 200 mg mirikizumab or placebo until week (W)52. Mirikizumab induction non-responders received extended induction with open-label 300 mg mirikizumab between W12 and W24. Extended induction responders received open-label 200 mg mirikizumab between W24 and W52. In each population, efficacy was analyzed by subgroups based on PATF number (0, 1, ≥ 2 [2-3]) and mechanism (including difficult-to-treat [DTT]: anti-TNF plus tofacitinib and/or vedolizumab). At baseline, 479/1162 patients (41.2%) had (≥ 1) PATF, of which 177 (37.0%) had DTT. Among mirikizumab-treated patients (n = 868), W12 clinical response was achieved by 69.8%, 63.9%, 45.3%, and 41.9% of the 0-PATF, 1-PATF, ≥ 2-PATF, and DTT subgroups, respectively. 42.1% (365/868) continued with maintenance treatment. Among W12 responders, 51.9% (0-PATF), 44.2% (1-PATF), 49.0% (≥ 2-PATF), and 42.9% (DTT) achieved clinical remission at W52. Over half of the patients (54.0% [147/272]) in the extended induction population had PATF; 51.0% (75/147) were DTT. At W24, clinical response was achieved by 62.4%, 41.4%, 49.5%, and 49.3% of the 0-PATF, 1-PATF, ≥ 2-PATF, and DTT subgroups. Of this 49.3% of the DTT subgroup (extended induction responders), 38.9% (14/36) achieved W52 clinical remission. Mirikizumab induction and maintenance is efficacious in moderately-to-severely active ulcerative colitis with or without prior failure of advanced therapy, including difficult-to-treat disease. LUCENT-1: NCT03518086; LUCENT-2: NCT03524092.

2 min10 May 2026

Ventilatory ratio as a predictor of mortality in acute respiratory distress syndrome: a systematic review and Bayesian meta-analysis of observational studies.

The ventilatory ratio (VR) has been proposed as a simple and accessible index to estimate ventilatory inefficiency and physiological dead space in critically ill patients with acute respiratory distress syndrome (ARDS). However, its association with mortality remains controversial, partly due to the methodological heterogeneity of the published studies. A systematic review and Bayesian random-effects meta-analysis were conducted to assess the association between VR and mortality in patients with ARDS. Observational studies reporting crude or adjusted odds ratios (OR) that analysed the association between VR and mortality were included. The search was performed in PubMed, Embase, Scopus, Cochrane, and LILACS databases up to April 2025. Bayesian model, subgroup analyses, meta-regression, and sensitivity analyses were applied. Publication bias was assessed using a funnel plot and Egger's test. Risk of bias was evaluated using the Quality In Prognosis Studies (QUIPS) tool, and the certainty of evidence was assessed using the GRADE approach. The protocol was registered in PROSPERO (CRD42024538654). A total of 23 studies were identified, of which 17 were included in the systematic review and meta-analysis of observational studies. The pooled OR for the association between VR and mortality was 1.55 (95% credible interval: 1.27-1.96), with moderate-to-high heterogeneity (τ = 0.41, I2 = 71.9%). Sensitivity and meta-regression analyses confirmed the robustness of the findings across different model specifications and study characteristics. Risk of bias was rated as moderate in 3 studies and low in 20, according to the QUIPS tool, and the overall certainty of the evidence was rated as low using the GRADE approach. Higher VR values were associated with increased mortality risk in patients with ARDS. However, moderate-to-high heterogeneity across studies indicates that these findings should be interpreted cautiously. VR may represent a complementary prognostic marker, but prospective studies are needed to validate its performance and determine its incremental value over established indices such as PaO2/FiO2.

Respiratory medicine

2 min9 May 2026

Effect of a mobile application-delivered educational video on interest in and uptake of contraception among patients with systemic lupus erythematosus in Thailand: A randomized controlled trial.

To evaluate the impact of contraceptive education delivered via the mobile application (LINE) compared with in-person counseling among women with systemic lupus erythematosus (SLE). In this randomized controlled trial at a university hospital in Thailand, 156 sexually active women with SLE aged 18-45 were randomized to LINE-based video education (intervention) or standard in-person counseling (control). Intervention participants were referred for same-day initiation of desired contraceptives, while controls received them immediately. The primary outcome was the contraceptive method selected immediately after the session, categorized by effectiveness. Secondary outcomes included contraceptive knowledge, attitudes, and method use at four weeks. Immediately after the intervention, intention to use long-acting reversible contraception (LARC) and any effective method was higher in the LINE group than in the control group (RR 1.58, 95% CI 1.08-2.30; and RR 1.36, 95% CI 1.01-1.83, respectively). However, at four weeks, actual LARC uptake and overall effective contraceptive use were lower in the LINE group (RR 0.59, 95% CI 0.38-0.91; and RR 0.66, 95% CI 0.47-0.92, respectively), largely due to non-attendance at health facilities to obtain the chosen methods. Knowledge scores improved in both groups. Fear of side effects remained the most frequently reported barrier. Both LINE-based and face-to-face counseling improved contraceptive knowledge among women with SLE. LINE-based counseling enhanced intention but was less successful in translating intention into actual use, whereas in-person counseling with immediate method provision more effectively facilitated uptake of effective contraception. Mobile interventions may be a useful adjunct to increase contraceptive intention among women with SLE, but additional support is needed to ensure translation into actual uptake.

Contraception

2 min9 May 2026

Frontiers in cellular and infection microbiology

The therapeutic potential of epimedium and its bioactive flavonoids in hepatitis and cirrhosis: an integrative review.

Hepatitis and cirrhosis constitute a substantial global health burden, with therapeutic options remaining largely confined to antiviral agents and liver transplantation. Traditional Chinese medicine has long employed Epimedium species (Berberidaceae) for hepatoprotective indications, with contemporary investigations identifying prenylated flavonoids-principally icariin and its active metabolite icaritin-as the principal bioactive constituents. This integrative review systematically examined 33 high-impact studies published up to March 2026, selected based on a comprehensive search of PubMed, Web of Science, Scopus, Embase, Cochrane Library, CNKI, Wanfang, and Google Scholar. Included investigations were critically evaluated for mechanistic sophistication, translational validity, methodological rigor, and pharmacokinetic relevance. Preclinical evidence, derived predominantly from toxin-induced (e.g., CCl4, TAA), metabolic, and acute injury models, demonstrates that icaritin exerts consistent anti-fibrotic activity through dual inhibition of HIF-1α and TGF-β/Smad signaling, selective induction of hepatic stellate cell apoptosis, and suppression of angiogenesis via VEGF/VEGFR2 blockade. Immunomodulatory properties observed in preclinical tumor models and early-phase clinical trials in advanced HBV-related hepatocellular carcinoma, encompass reduction of myeloid-derived suppressor cells (-43%), regulatory T cells (-31%), and enhancement of CD8+ T-cell function (+2.8-fold) providing proof-of-concept for immune modulation in an HBV-endemic population. Clinical data in liver disease remain limited to small, non-randomized studies (primarily in HCC), with no phase III trials specifically targeting fibrosis or cirrhosis endpoints. Critical evidence gaps-including the absence of validation in viral hepatitis models, undefined pharmacokinetics in cirrhosis, and lack of drug-drug interaction data with antivirals-currently preclude routine clinical application in hepatitis and cirrhosis. Safety analyses reveal dose-dependent hepatotoxicity at concentrations exceeding 50 μM icaritin and substantial inter-individual variability in gut microbiota-mediated bioactivation. Epimedium flavonoids exhibit multi-target therapeutic potential that bridges traditional botanical medicine and modern pharmacology, though critical translational gaps persist. Future investigations must prioritize phase III fibrosis trials, pharmacokinetic optimization in cirrhotic populations, and comprehensive drug-drug interaction studies with direct-acting antivirals to establish evidence-based clinical protocols.

2 min8 May 2026

Acute Kidney Injury and Risk of Adverse Neurocognitive Outcomes: A Systematic Review and Meta-Analysis.

Chronic kidney disease is a recognized risk factor for adverse neurocognitive outcomes, but the effect of acute kidney injury (AKI) on brain health remains less well defined. We conducted a systematic review and meta-analysis to evaluate associations between AKI and subsequent risk of stroke, delirium, and dementia. Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until April 2025. Studies were included if they reported quantitative estimates with measures of precision for the association between AKI and delirium, stroke, or dementia in adult populations. Two reviewers independently screened and extracted data, and study quality was assessed using standardized criteria. Study characteristics, participant demographics, and adjusted effect estimates (hazard ratios [HRs] or odds ratios [ORs]) with 95% CIs were extracted. Pooled HRs and ORs with 95% CIs were calculated using random-effects models. Heterogeneity was evaluated with the χ2 test and I2 statistic, and sources of heterogeneity were explored through prespecified subgroup analyses and meta-regression. We identified 49 studies comprising 11,253,825 participants with 1,279,145 events. Individuals with AKI were at increased risk of stroke (pooled adjusted HR 1.35, 95% CI 1.20-1.52), delirium (pooled adjusted OR 1.76; 1.42-2.17), and dementia (pooled adjusted HR 1.64, 1.41-1.89). A gradient of risk across increasing AKI stages was demonstrated for stroke (stage 1: HR 1.11; 1.00-1.23; combined stages 2 and 3: HR 1.57; 1.35-1.81). AKI was also associated with higher in-hospital and 90-day mortality poststroke (pooled HR 2.13, 1.56-2.90, and 4.81, 2.55-9.08, respectively) and with 90-day disability (pooled adjusted OR 1.47, 1.22-1.76). Associations between AKI and all outcomes were directionally consistent across sensitivity analyses and pooled propensity score-matched studies. In this systematic review and meta-analysis, AKI was consistently associated with increased short-term and long-term neurocognitive risk, including stroke, delirium, and dementia. These findings suggest that AKI may identify individuals vulnerable to both acute and chronic brain injury. Further studies are needed to clarify mechanisms linking AKI to brain injury and to identify strategies to mitigate neurocognitive risk in this high-risk population.

Neurology

2 min7 May 2026

NephrologyReview

Post-asphyxia acute kidney injury in neonates: a systematic review.

Perinatal asphyxia is a major cause of neonatal morbidity and mortality globally. It affects multi-systems and has significant renal consequences. Acute kidney injury (AKI) is a frequent complication of perinatal asphyxia; however, its burden, diagnosis, and outcomes remain variably characterized. This study employed a scoping review approach to map and synthesize the existing evidence on post-asphyxia AKI in neonates. A total of 30 studies published between 1995 and 2025 were included, encompassing different geographic regions, study designs, and diagnostic criteria. The review demonstrates a clear growth in scholarly attention to post-asphyxia AKI, particularly in the last 25 years, coinciding with the introduction of neonatal-modified KDIGO definitions and advances in neonatal nephrology. Reported incidence of AKI varied widely, ranging from 20% to over 60%, reflecting non-homogeneity in study populations, differing case definitions of acute kidney injury in neonates, the severities of hypoxic-ischemic encephalopathy, and varied methodological approaches. Findings consistently indicate that AKI is strongly associated with severe forms of perinatal asphyxia, the presence of multi-organ dysfunction, prolonged neonatal intensive care stay, and mortality.  Despite emerging interest in novel biomarkers and standard definitions, important gaps persist in early detection, long-term renal outcome data, and evidence from low- and middle-income countries. Addressing these gaps through standardized monitoring, biomarker validation, and longitudinal follow-up will improve renal survival in neonates affected by perinatal asphyxia. • The newborn kidneys are susceptible to the hemodynamic changes that follow ischemia/asphyxia due to a poor functioning capacity and oftentimes an inadequate structural potential. • Neonatal AKI is closely linked to severe forms of asphyxia, increased length of hospital stay and increased mortality. its reported incidence is widely varied. • The emergence of novel biomarkers in the identification and diagnosis of neonatal AKI, and the uptake and application of standard definitions (modified neonatal KDIGO) in the identification of neonatal AKI. • The availabiltiy of specialized kidney support therapy (continuous kidney replacement therapy; the carpadiem) in the management of neonatal AKI.

2 min7 May 2026

Revista medica del Instituto Mexicano del Seguro Social

[Lifestyle pattern and therapeutic adherence in patients on hemodialysis].

Chronic kidney disease (CKD) is a common complication of hypertension and diabetes mellitus. Hemodialysis (HD) is a renal replacement therapy that requires self-care and therapeutic adherence (TA), which if not performed increase the risk of associated complications. Therefore, it is essential to adopt self-care practices and implement modifications in lifestyle patterns (LP). To determine changes in LP and TA in patients with CKD undergoing HD following educational interventions (EIs). Quasi-experimental, longitudinal, non-randomized study. Sociodemographic and clinical-therapeutic variables were analyzed. Evaluation tools were applied to identify changes in LP and TA before and after a 6-month period of EIs. The EIs consisted of 7 individualized sessions provided in the HD unit. Measures of central tendency, chi-square test, and Student's t test were used for data analysis. The sample included 39 patients, with a mean age of 52.87 years; 53% were male. Initially, 100% of participants were classified as "at risk" in LP, and 0% had "full adherence" in TA. After the EIs, 43.6% of patients achieved a "protective" LP, and 38.5% reached "full adherence" in TA (p = 0.00). Patients who received 7 individualized educational sessions showed significant improvements in self-care practices as measured by LP, as well as notable improvement in TA. la enfermedad renal crónica (ERC) es una complicación común de la hipertensión arterial y la diabetes mellitus. La hemodiálisis (HD) es un tratamiento sustitutivo de la función renal que requiere de autocuidado y de adherencia terapéutica (AT), las cuales al no realizarse aumentan el riesgo de complicaciones asociadas. Por lo tanto, es necesaria la toma de prácticas de autocuidado y modificaciones del patrón de vida (PV). determinar los cambios en el PV y AT en pacientes con ERC en HD posterior a intervenciones educativas (IE). estudio cuasi-experimental, longitudinal, no aleatorizado. Se estudiaron variables sociodemográficas y clínico-terapéuticas. Se aplicaron pruebas de evaluación para identificar los cambios de PV y AT antes y después de 6 meses de IE. Las IE consistieron en 7 sesiones individualizadas en el servicio de HD. Se emplearon medidas de tendencia central, chi cuadrada y t de Student. la muestra fue de 39 pacientes, edad media de 52.87 años y el 53% fue del sexo masculino. En cuanto al PV, 100% estaban “en riesgo” y en relación con la AT, 0% estaba en “adherencia total”. Después de la IE, el 43.6% resultó en PV “protector” y el 38.5% logró “adherencia total” de AT (p < 0.001). aquellos pacientes que recibieron 7 sesiones individualizadas de IE demostraron mejoras significativas en relación con las prácticas de autocuidado evaluadas mediante el PV y también se demostró una mejora en la AT.

3 min6 May 2026

Yi-Shen-Hua-Shi granule added to supportive care reduces proteinuria in IgA nephropathy: a multicenter randomized controlled trial.

IgA nephropathy is the most common primary glomerulonephritis globally. Current management relies on supportive care, but many patients remain at risk for progressive disease, especially those with persistent proteinuria. This study evaluated the efficacy of Yi-Shen-Hua-Shi granule in adult patients with IgA nephropathy and persistent proteinuria. We conducted a multicenter, randomized, controlled trial involving adults with biopsy-confirmed IgA nephropathy, estimated glomerular filtration rate ≥30 mL/min/1.73 m2, and persistent proteinuria despite optimized supportive therapy. Participants were randomized 1:1 to receive Yi-Shen-Hua-Shi granule (10 g, orally, twice daily) plus best supportive care, or best supportive care alone, for 8 weeks. The primary endpoint was change in 24-hour urinary protein from baseline to week 8. Secondary endpoints included changes in renal function and safety assessments. Data were analyzed using linear mixed-effects models according to the intention-to-treat principle. A total of 97 patients were included. At 8 weeks, the Yi-Shen-Hua-Shi group showed a significantly greater reduction in 24-hour proteinuria compared with controls, with an estimated mean difference of ≈340 mg (95% CI 89.59 to 588.62; p = 0.01). The benefit was most pronounced among participants with baseline proteinuria >1000 mg, whose reduction was approximately 505 mg greater than controls (95% CI 152.45 to 859.42; p = 0.01). No significant differences in estimated glomerular filtration rate or adverse event rates were observed between groups. Yi-Shen-Hua-Shi granule, added to best supportive care, safely produced a greater short-term reduction in proteinuria, particularly in patients with high baseline proteinuria. Adjunctive benefit: Yi-Shen-Hua-Shi granule added to optimized supportive care further reduced 24-hour proteinuria over 8 weeks in adults with IgA nephropathy.Target population: The effect appeared most clinically meaningful in patients with persistent proteinuria >1000 mg/day despite supportive care including RAS inhibition.Steroid-sparing potential: This herbal formulation may be considered as an adjunct option for patients who are unsuitable for or reluctant to use systemic corticosteroids.Safety/tolerability: No significant between-group differences in adverse events were observed, supporting acceptable short-term tolerability.Renal function stability: eGFR remained stable during the 8-week intervention period.Need for long-term data: Longer follow-up is required to confirm durability and effects on hard renal outcomes.

American journal of otolaryngology

The intriguing condition of eosinophilic sialodochitis: insights into an emerging type 2 disorder.

Eosinophilic sialodochitis is a rare and increasingly recognized inflammatory disorder of the salivary glands, characterized by eosinophil-rich mucus plugs, periductal eosinophilic infiltration, and frequent association with type 2 disorders. A systematic search was conducted on PubMed, Embase, Scopus, and Web of Science for papers reporting on eosinophilic sialodochitis. PRISMA 2020 guidelines were followed, and the study protocol was registered in PROSPERO with registration number CRD42023433994. Data was summarized descriptively and presented as percentages or medians with interquartile range. A total of 157 studies were identified and 21 met the inclusion criteria of the present review, comprising 179 patients. The majority were female (73%) and their ages ranged from 15 to 80 years old. Eosinophilic sialodochitis often presented with multiglandular involvement of the parotid glands. Allergic rhinitis (72%) and asthma (28%) were the most common associated type 2 comorbidities, while elevated serum IgE and blood eosinophil count were frequently reported. Diagnosis was based on different examinations, ranging from ultrasonography to MRI, fine-needle or core-needle biopsy, and conventional sialography. Therapeutic interventions included antihistamines, montelukast, and oral corticosteroids. Sialendoscopy and sialadenectomy were used in refractory cases, while biologics such as dupilumab, benralizumab and mepolizumab were employed only in 4 patients. This review highlights the diagnostic complexity, therapeutic challenges, and potential role of targeted biologic therapies in managing eosinophilic sialodochitis.

Soluble Thrombomodulin Links Viremia and Mortality During COVID-19: Results From the ACTIV-4a Trial.

COVID-19 and other respiratory viral infections can cause cardiovascular complications. SARS-CoV-2 virions are found in the blood, and circulating viral RNA levels are associated with death. We hypothesized that viremia can induce thrombotic endotheliopathy that contributes to death and studied this relationship in patients hospitalized for COVID-19 and enrolled in the ACTIV-4a (Accelerating COVID-19 Therapeutic Interventions and Vaccines) randomized trial of antithrombotic therapy. We quantified SARS-CoV-2 nucleocapsid RNA and protein in plasma and measured their associations with clinical outcomes and biomarkers of thromboinflammation and endotheliopathy. We used Cox regression and Fine-Gray competing risk models to analyze survival and thrombosis. We conducted causal mediation analysis to explore whether thrombotic endotheliopathy mediates the relationship between viral RNA and death. In 93 patients, SARS-CoV-2 RNA and N-antigen were higher in nonsurvivors. Baseline viral RNA levels were associated with increased 90-day death (hazard ratio [HR], 1.31 [95% CI, 1.17-1.46]) and thrombosis (HR, 1.35 [95% CI, 1.24-1.47]). Viral RNA more effectively predicted survivorship than N-antigen levels. Soluble thrombomodulin, a biomarker of thrombotic endotheliopathy, positively correlated with viral RNA levels. Mediation analysis revealed that soluble thrombomodulin accounts for 12.2% (95% CI, 0.1%-32.3%; P=0.048) after adjustment for age and sex of the relationship between viral RNA and the 90-day mortality rate. Elevated plasma SARS-CoV-2 RNA levels are associated with death in ACTIV-4a, which is causally mediated in part by soluble thrombomodulin. We propose that lung-blood viral dissemination is a potential mechanism for cardiovascular complications of respiratory viruses. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04505774.

Association of preadmission metformin use and prognosis in patients with sepsis with diabetes: a systematic review and meta-analysis.

Preadmission metformin may lower mortality in diabetic sepsis patients, but evidence is conflicting, necessitating a systematic review and meta-analysis for confirmation. We systematically searched MEDLINE (via PubMed), EMBASE, and Cochrane CENTRAL from inception to September 1, 2025, for cohort studies evaluating metformin use in septic patients with diabetes. Study quality was assessed using the Newcastle-Ottawa Scale. Two reviewers independently screened studies, extracted data, and evaluated methodological quality. Meta-analysis was conducted using STATA statistical software and Review Manager software, calculating pooled odds ratios with 95% confidence intervals via the inverse variance random-effects model. The MET group included diabetic sepsis patients with preadmission metformin exposure, and the NM group included those without. This meta-analysis of 14 studies (12,687 patients), all with low bias risk, demonstrated that preadmission metformin use in sepsis-diabetes patients was associated with reduced overall mortality (OR 0.58, 95% CI 0.44-0.75, P < 0.00001). Significant reductions were observed in 28-day (OR 0.61, P = 0.002), 90-day (OR 0.48, P = 0.001), 365-day (OR 0.33, P = 0.0005), and in-hospital mortality (OR 0.43, P < 0.02). However, 30-day (OR 0.71, P = 0.06), 60-day (OR 0.72, P = 0.22), and ICU mortality (OR 0.76, P = 0.25) showed no significant differences. Notably, metformin also significantly improved serum creatinine (MD -0.32, P = 0.04) and metformin usage was associated with elevated serum lactate levels. This meta-analysis links preadmission metformin use in diabetic sepsis patients to reduced mortality-particularly 28-day, 90-day, 365-day, and in-hospital-along with decreased serum creatinine. Clinically and from a public health standpoint, these data support the integration of metformin history as a favorable prognostic indicator into updated clinical guidelines, thereby informing future antimicrobial stewardship and sepsis bundle strategies. These findings support further evaluation of metformin's benefits in large-scale, multicenter randomized controlled trials.

American journal of respiratory and critical care medicine

Increasing protein dose does not further augment muscle protein synthesis in critical illness: a randomized, controlled clinical trial.

Critical illness impairs the muscle protein synthetic response to protein administration. Whether increased protein dose can overcome this anabolic resistance is unknown. To assess the impact of a single intraduodenal bolus of 40 g protein compared to 20 g of protein in mechanically ventilated critically ill patients on the primary outcome of postprandial muscle protein synthesis rates. Mechanically ventilated patients were randomized to 40 or 20 g of whey protein isolate delivered intraduodenally over 1 h. Primed continuous intravenous L-[ring-13C6]-phenylalanine and L-[3,5-2H2]-tyrosine infusions were applied with repeated arterial blood and skeletal muscle tissue sampling over 2 h fasting and 6 h postprandial periods to assess plasma amino acid responses and rates of fasting and postprandial muscle protein synthesis (primary outcome). Data are mean ± SD and area under the curve (AUC), analyzed with ANCOVA adjusted for fasting rate and paired t-tests (P < .05). Twenty patients (n = 10/group: 40 g: 90% male, 49 ± 21 y and 20 g: 80% male, 51 ± 13 y) were studied. Postprandial muscle protein synthesis rates (primary outcome) did not differ between groups (40 g vs 20 g: 0.030 ± 0.012 vs 0.025 ± 0.010%·h-1; adjusted mean difference 0.007 (95% CI, -0.003 to 0.016) %·h-1; P = .152). Postprandial plasma leucine and tyrosine availability (AUC) were higher following 40 g vs 20 g protein (leucine: 263 ± 87 vs 194 ± 54 µmol·L-1, P = .005; tyrosine: 92 ± 24 vs 63 ± 17 µmol·L-1, P = .006). Fasting muscle protein synthesis rates did not differ between groups (40 g vs 20 g: 0.020 ± 0.012 vs 0.025 ± 0.023%·h-1; P = .558). The post hoc uncontrolled analysis of muscle protein synthesis rates from fasting to postprandial periods increased in the 40 g group only (P = .005). Higher enteral protein does not further augment postprandial muscle protein synthesis rates to overcome -anabolic resistance during critical illness, despite increased plasma amino acid availability. Australia New Zealand Clinical Trials Registry Identifier: ACTRN12620000776909.

2 min5 May 2026

Impact of protocolized restrictive versus liberal/usual maintenance fluid strategy on fluid overload among mechanically ventilated children: an open-label randomized trial (ReLiSCh-II trial).

Fluid overload (FO) is associated with poor clinical outcomes among critically ill children. The objective of this trial was to assess the impact of a protocolized restrictive maintenance fluid strategy on FO among mechanically ventilated children. This open-label randomized controlled trial was conducted in the pediatric intensive care unit (PICU) of a tertiary care hospital in North India over 13 months (November 2023-November 2024). Hemodynamically stable mechanically ventilated children were randomized to protocolized restrictive (n = 64) (40-50% of maintenance fluids with diuretic infusion if FO% > 10%); and liberal/usual (n = 66) (70-80% of maintenance fluid) groups. The primary outcome was the proportion of children with cumulative FO% > 10% through day 5. Secondary outcomes were daily cumulative FO%; inferior vena cava variability index (∆IVC) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at 48 h; safety parameters (requirement of fluid boluses or vasoactive drugs); 28-day ventilator and PICU-free days (VFDs and PFDs), and mortality. Significantly fewer children in the protocolized restrictive group had cumulative FO% > 10% than in the liberal/usual group (22% vs. 47%, p = 0.003). Also, the restrictive group had significantly lower daily cumulative FO% on the first 5 days. ∆IVC and NT-proBNP levels at 48 h, as well as safety parameters, were similar between the two groups. Protocolized restrictive and liberal/usual groups had similar VFDs [20 (8-24) vs. 16 (0-23), p = 0.076], PFDs [16 (3-21) vs. 13 (0-19), p = 0.071], and mortality (14% vs. 24%, p = 0.14).  A protocolized restrictive maintenance fluid strategy resulted in significantly lower FO among hemodynamically stable, mechanically ventilated children without a measurable impact on short-term clinical outcomes. • Fluid overload (FO) is associated with poor clinical outcomes among critically ill mechanically ventilated children. • Among hemodynamically stable, mechanically ventilated children, a restrictive maintenance fluid strategy may be a useful intervention to limit FO and improve clinical outcomes in LMICs.

2 min4 May 2026

Pathogens (Basel, Switzerland)

The Role of Microbiota and Fecal Transplantation in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and therapeutic modulation. We conducted a systematic review to synthesize current evidence on microbiota alterations in IBD and the clinical application of fecal microbiota transplantation (FMT). A total of 118 studies were included (76 focused on microbiota profiling and 42 evaluated FMT as therapy). Across heterogeneous study designs and microbial characterization methods, reduced microbial diversity was the most consistently reported alteration, generally more pronounced in CD than in UC. Depletion of Faecalibacterium prausnitzii-a key butyrate producer with anti-inflammatory properties-was commonly reported, often accompanied by functional impairment in short-chain fatty acid production. Microbial patterns were frequently associated with mucosal inflammation and varied across disease phenotypes; these patterns have been increasingly explored as predictors of treatment response and relapse, although mechanistic interpretation remains limited and causal relationships are difficult to establish. Evidence from randomized controlled trials suggests potential efficacy of FMT in UC, particularly with intensive or repeated protocols, whereas data in CD remain limited and heterogeneous, with signals of benefit often appearing transient. FMT was generally well tolerated, but long-term safety data remain scarce. Emerging multi-omic approaches are reshaping the field by integrating taxonomic and functional insights, with potential implications for risk stratification, diagnosis, prognosis, and therapeutic optimization. Further standardized, longitudinal, and mechanistically oriented studies are required to translate microbiome research into clinically actionable strategies in IBD.

2 min4 May 2026

Microcirculation (New York, N.Y. : 1994)

Microvascular Effects of Endocannabinoid Signaling in Sepsis: A Mechanistic and Systematic Review.

Microvascular dysfunction is a central determinant of organ failure in sepsis, reflecting early endothelial activation, increased permeability, and impaired capillary perfusion. Experimental evidence suggests that the endocannabinoid system (ECS) modulates these immunovascular processes, yet mechanistic insights remain dispersed across heterogeneous models. We conducted a PRISMA-guided systematic review of experimental studies assessing pharmacological modulation of ECS components under sepsis or endotoxemia conditions. Eleven studies met inclusion criteria, encompassing in vivo microcirculatory preparations and in vitro endothelial or immune-cell systems. Across models, three mechanistic domains consistently emerged: leukocyte-endothelial adhesion, endothelial barrier integrity, and vascular reactivity. Among these, cannabinoid receptor 2 (CB2) activation produced the most reproducible effects, reducing adhesion molecule expression and attenuating leukocyte recruitment. Endocannabinoid-endovanilloid signaling contributed to the stabilization of endothelial junctions and limitation of inflammatory hyperpermeability, whereas cannabinoid receptor 1 (CB1) signaling showed context-dependent influences on vascular tone and microvascular flow. These findings outline a coherent framework in which ECS activity-particularly through CB2-shapes early microvascular responses to sepsis. Standardized and clinically relevant models will be essential to determine whether targeting ECS pathways can yield effective strategies to protect the microcirculation during sepsis.

1 min2 May 2026

Validation and minimum important difference of the chronic respiratory disease questionnaire in patients with interstitial lung disease.

The Chronic Respiratory Disease Questionnaire (CRQ) was developed to measure health-related quality of life (HRQoL) in patients with chronic obstructive pulmonary disease (COPD), with a minimum clinically important difference (MCID) of 0.5 points per item. It has been used in clinical trials of patients with interstitial lung disease (ILD), however its validity and MCID in this population is unknown. Is the CRQ a valid measure of HRQoL in people with ILD and what is the MCID in this population? Data from a multicentre randomised controlled trial of pulmonary rehabilitation (PR) in 142 patients with ILD were analysed. Concurrent validity with the St George's Respiratory Questionnaire for IPF (SGRQ-I), known groups validity between patients of varying TLCO and GAP Index, and responsiveness to change after PR were assessed. MCID was calculated using anchor- and distribution-based methods. Analyses were repeated for the idiopathic pulmonary fibrosis (IPF) subgroup. There was a strong association between CRQ and SGRQ-I scores (r = -0.786, p < 0.05). CRQ scores differed significantly between patients in the highest and lowest TLCO quartile (effect sizes -0.49 to -0.64) and between GAP Index groups (p < 0.05), except for the emotional function domain. The CRQ was responsive to PR (effect size -0.53). The MCID ranged from 0.45 to 0.65 points per item. Results were similar in the IPF subgroup. The CRQ is a valid and responsive measure of HRQoL in patients with ILD, including those with IPF, with an MCID of around 0.5 points per item. These findings support the use of the CRQ in ILD.

Respiratory medicine

2 min2 May 2026

Efficacy of fluoroquinolone prophylaxis during induction phase in children with acute lymphoblastic leukemia: a systematic review and meta-analysis.

The role of infection prevention with fluoroquinolone prophylaxis specifically, during induction chemotherapy in pediatric acute lymphoblastic leukemia (ALL), remains unclear. Therefore, we conducted a systematic review and meta-analysis to assess its efficacy. PubMed, Scopus, and Cochrane databases were systematically searched for randomized controlled trials and observational studies. The main outcome was febrile neutropenia (FN) 26 and secondary outcomes were bloodstream infection (BSI), Clostridioides difficile infection (CDI) and all-cause mortality (ACM). A random-effects meta-analysis was conducted. We included 7 studies with 991 patients; 439 (44.3%) used fluoroquinolone prophylaxis, of whom 255 used levofloxacin and 184 used ciprofloxacin. The B-cell immunophenotype was the most frequent. Fluoroquinolone prophylaxis reduced the risk of FN (46.1% vs 64.9%; OR 0.44; 95% CI 0.33-0.59; I2 = 0%). Fluoroquinolone prophylaxis also significantly reduced the risk of BSI (OR 0.50; 95% CI 0.32-0.81; I2 = 0%). Risks of CDI (OR 0.43; 95% CI 0.00-42.30; I2 = 39.6%) and ACM (OR 1.04; 95% CI 0.20-5.38; I2 = 54.3%) were not significantly altered. Fluoroquinolone prophylaxis during induction chemotherapy for pediatric ALL significantly reduces FN and BSI without increasing C. difficile risk. While overall mortality is unchanged, reducing infectious morbidity may enhance treatment tolerance. • Febrile neutropenia and bloodstream infections are major causes of treatment-related morbidity and mortality during induction chemotherapy in pediatric acute lymphoblastic leukemia and fluoroquinolone prophylaxis has shown inconsistent results across studies. • Prior evidence suggests potential reduction in infectious complications, but is limited by heterogeneous populations and lack of analyses specific for induction phase. • This systematic review and meta-analysis focused specifically on the induction phase of pediatric acute lymphoblastic leukemia and demonstrates that fluoroquinolone prophylaxis significantly reduces febrile neutropenia and bloodstream infections with consistent effect across study designs. • The study provides pooled estimate from an specific phase showing no clear increase in Clostridioides difficile infection, demonstrating the risk-benefit profile of fluoroquinolone prophylaxis.

2 min1 May 2026

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology

Exclusive enteral nutrition for induction of remission in Crohn's disease in adults: A systematic review and meta-analysis of randomized trials and real-world studies.

Exclusive enteral nutrition (EEN) is an established induction therapy in pediatric Crohn's disease (CD); however, its role in adults remains less well defined. A systematic search was performed through December 2025. Eligible studies included randomized controlled trials (RCTs) and non-randomized studies evaluating EEN in adults (≥ 18 years) with active CD. The primary outcome was clinical remission, defined by validated disease activity indices. Risk of bias was assessed using RoB 2 and the Newcastle-Ottawa Scale. Random-effects models were applied to estimate pooled remission rates and relative risks. Forty studies, comprising 2459 patients, were included. In 23 real-world cohort studies (n = 1269), the pooled clinical remission rate with EEN was 66% (95% CI = 0.60-0.71, I2 = 69.9%, p < 0.0001). In five RCTs (n = 315) comparing corticosteroids with EEN, corticosteroids achieved higher remission rates compared with EEN (RR 0.65, 95% CI = 0.50-0.84; p = 0.0009). In eight RCTs (n = 301), remission rates did not differ significantly between elemental and non-elemental formulations (RR 1.04, 95% CI = 0.88-1.23). Sub-group analyses by protein type and lipid composition showed no differences in efficacy. In two studies, combination therapy with biologics plus EEN was associated with a higher clinical remission compared with biologics alone (RR 0.75; 95% CI = 0.67-0.84; p < 0.0001). Adverse events were generally mild, with poor palatability being most frequent. EEN induces clinical remission in adults with CD. It is less efficacious than corticosteroids to induce clinical remission. The efficacy of EEN is independent of formula composition. Given its favorable safety profile, EEN may represent a therapeutic option in select adult patients. PROSPERO registration number: CRD42023445039.

2 min1 May 2026

Mineralocorticoid receptor antagonists in dialysis patients after ACHIEVE and ALCHEMIST: updated systematic review and meta-analysis of 14 randomized trials.

End-stage kidney disease (ESKD) patients receiving dialysis bear a heavy burden of cardiovascular disease (CVD), the leading cause of mortality. Mineralocorticoid receptor antagonists (MRAs) have cardiovascular protective effects in non-dialysis patients, but their efficacy and safety in dialysis-dependent individuals remain controversial. This study aimed to clarify their clinical value via an updated systematic review and meta-analysis. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we systematically searched PubMed, EMBASE, and The Cochrane Library up to 25 August 2025. Eligible studies were parallel-design randomized controlled trials (RCTs) enrolling adults (≥18 years) on maintenance dialysis, comparing MRAs with placebo or no intervention. Two reviewers independently screened studies, extracted data, and assessed quality using the Cochrane Risk of Bias Tool 2.0. Meta-analysis was performed with Cochrane Review Manager 5.4. The results showed that a total of 14 RCTs involving 4,525 patients were included (13 used spironolactone, one used eplerenone; follow-up: 3-40.8 months). MRAs significantly reduced nonfatal CVD events (RR 0.68, p = 0.04) but had no significant effect on cardiovascular mortality (RR 0.75, p = 0.14) or all-cause mortality (RR 0.76, p = 0.05). They significantly elevated risks of severe hyperkalemia (RR 1.35, p = 0.009) and gynecomastia and breast pain (RR 4.23, p < 0.001). In conclusion, MRAs can reduce the incidence of nonfatal cardiovascular events in dialysis patients; however, clinicians also need to be mindful of the risks of severe hyperkalemia as well as gynecomastia and breast pain in men when prescribing them. Across 14 randomized trials in dialysis patients, mineralocorticoid receptor antagonists did not reduce cardiovascular or all-cause mortality. They lowered non-fatal cardiovascular events but increased severe hyperkalemia and gynecomastia. Routine use in unselected dialysis populations is not supported and requires careful monitoring.

Lasers in medical science

Effects of resistance training with/without Photobiomodulation on muscle and respiratory function in difficult-to-control asthma: a randomized trial.

Difficult-to-Control Asthma (DTCA) is characterized by persistent symptoms, frequent exacerbations, and reduced functional capacity despite optimized pharmacological therapy. Patients with DTCA commonly exhibit peripheral muscle dysfunction, making strategies that may potentiate the effects of resistance training clinically relevant. Photobiomodulation therapy (PBMT) has been investigated as a modality capable of improving muscle performance and exercise tolerance. The aim of this study was to determine whether combining resistance training with LED-based PBMT (RT+LEDT) results in greater improvements in peripheral muscle strength and functional exercise capacity compared with resistance training alone in adults with DTCA. This randomized, triple-blind controlled trial included 30 adults with DTCA who met predefined inclusion and exclusion criteria. Participants were allocated equally to an experimental group (RT+LEDT; n = 15) or a control group (RT; n = 15). Both groups completed supervised resistance training twice weekly for 12 weeks. The experimental group received active PBMT before each session, while the control group received placebo PBMT. The primary outcome was peripheral muscle strength assessed by one-repetition maximum (1RM). Secondary outcomes included cardiopulmonary exercise test variables, shuttle walk test performance, spirometry, physical activity level, and asthma control. Post-intervention group comparisons were performed using independent t-tests. Compared with RT alone, RT+LEDT produced greater post-treatment gains in 1RM strength across major muscle groups, along with significant improvements in oxygen consumption at the anaerobic threshold and shuttle walk test distance. No between-group differences were observed in pulmonary function or asthma control. PBMT combined with resistance training yielded clinically meaningful improvements in muscle strength and functional capacity, suggesting its potential as an adjunctive strategy in rehabilitation programs for DTCA.

Journal of the International Association of Providers of AIDS Care

Self-Care Practices for Puerperal Sepsis Prevention and Associated Factors Among Postnatal Women in Africa: A Systematic Review and Meta-Analysis.

BackgroundPuerperal sepsis remains a preventable contributor to maternal illness. Pregnancy-related sepsis is responsible for ∼10% to 15% of maternal deaths. Despite this burden, no comprehensive review has examined self-care practices related to its prevention. Therefore, this review sought to evaluate self-care behaviors aimed at preventing puerperal sepsis and to explore associated factors among postnatal women in Africa.Data Sources and MethodsWe conducted a systematic review and metaanalysis of 17 eligible studies on the prevalence of self-care practices for puerperal sepsis prevention and their associations among postnatal mothers. Searched PubMed, Web of Science, Wiley Online Library, ScienceDirect, African Journals Online, and Google Scholar from December 10, 2023 to January 15, 2024. A Joanna Briggs Institute adapted tool was used to assess the quality of the studies. Forest plot, Cochran's Q test, subgroup analysis, sensitivity analysis, and metaregression model were used to test heterogeneity between included studies. Funnel plots and Egger's test were used to examine publication bias.ResultsA total of 17 studies that meet the inclusion criteria were included. The pooled prevalence of self-care for puerperal sepsis prevention practices among postpartum women was 36.09% (95% CI: 26.35, 45.82). Among postpartum women, urban dwellers (AOR: 3.23, 95% CI: 1.86, 5.63), those who were above tertiary education status (AOR: 2.81, 95% CI: 1.11, 4.67), those who had a good level of knowledge (AOR: 2.45, 95% CI: 1.11, 4.67), and those who had ≥4 ANC contacts (AOR: 3.75, 95% CI: 2.23, 6.31) were identified as associated factors.ConclusionsOnly 36.09% of postpartum women practiced self-care practices to prevent puerperal sepsis at home. It would be better to design a new healthcare system during maternal healthcare to scale up mothers' self-care puerperal sepsis prevention practices to reduce maternal morbidity and mortality caused by puerperal sepsis. In addition, all healthcare providers recognize the need to foster new thinking and to apply greater action to address identified factors of poor self-care and puerperal sepsis prevention practices.PROSPERO RegistrationCRD420251042794. Self-care practices for puerperal sepsis prevention and associated factors among postnatal women in Africa: A systematic review and meta-analysisPuerperal sepsis remains a preventable contributor to maternal illness. Pregnancy-related sepsis is responsible for ∼10% to 15% of maternal deaths. Although some primary studies have been conducted on self-care prevention practices and related factors, the findings have been inconsistent, making it difficult to generalize their results across Africa. Therefore, this systematic review aimed to evaluate the overall self-care prevention practices and their associated factors among postpartum mothers. I hope our findings will help to identify relevant gaps and contribute to improving self-care practices to prevent complications of puerperal sepsis and encourage early self-reporting about the condition. In addition, all healthcare providers recognize the need to foster new thinking and to apply greater action to address identified factors of poor self-care and puerperal sepsis prevention practices.

3 min30 Apr 2026

Acta odontologica Scandinavica

Association of Crohn's disease with periodontal disease risk and severity: a meta-analytic study.

Crohn's disease (CD) is a chronic inflammatory disorder with systemic manifestations, including potential effects on oral health. Evidence regarding its association with periodontal disease remains inconsistent. We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Library, CNKI, and WanFang Data up to August 28, 2025, for observational studies comparing periodontal -outcomes in adults with CD and non-inflammatory bowel diseases controls. Random-effects meta--analyses were -performed to estimate pooled odds ratios (ORs) for prevalence and standardized mean differences (SMDs) for clinical parameters. Subgroup and sensitivity analyses were conducted. Thirty-four studies, including 6482 CD patients and 9137 controls, were analyzed. CD was -associated with a higher risk of periodontitis (OR = 2.14, 95% confidence interval [CI]: 1.65-2.77). Clinical periodontal parameters were also significantly worse in CD patients: probing depth (SMD = 0.42), clinical attachment loss (CAL) (SMD = 0.50), bleeding on probing (SMD = 0.47), plaque index (SMD = 0.39), and gingival index (SMD = 0.31). Associations were stronger in European populations and in studies using CAL criteria. Sensitivity analyses confirmed the robustness of results. CD is associated with increased prevalence and severity of periodontal disease. These -findings support routine periodontal screening and integrated multidisciplinary management for CD patients, highlighting shared inflammatory pathways as potential therapeutic targets.

A prospective, randomized, double-blind, placebo-controlled, multicenter study of thiamin plus folic acid in the treatment of cognitive impairment in patients undergoing maintenance hemodialysis.

This prospective, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of thiamin and folic acid for cognitive impairment in maintenance hemodialysis (MHD) patients. A total of 215 MHD patients aged 18-75 with cognitive impairment were randomized to receive either oral thiamin (90 mg/day) plus folic acid (30 mg/day) or a placebo for 96 weeks. The primary endpoint was the change in the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog) score. After 96 weeks, the treatment group showed a significant improvement in ADAS-Cog scores (from 21.25 ± 9.2 to 15.07 ± 8.38, p < 0.001), whereas the placebo group showed a non‑significant improvement (from 24.53 ± 11.01 to 26.53 ± 14.43, p = 0.077). The treatment group also demonstrated significantly increased blood levels of thiamin (from 5.59 ± 0.95 to 18.21 ± 3.91 ng/mL) and folate (from 12.37 ± 4.62 to 63.33 ± 16.02 ng/mL), and a reduction in homocysteine levels (from 4709.06 ± 353.15 to 2962.68 ± 158.87 ng/mL, p < 0.001), with no significant changes in the placebo group. While mortality was similar between the two groups (12.1% vs. 12.0%, p = 0.978), the incidence of adverse events was significantly lower in the treatment group (31.8% vs. 62.0%, p = 0.0017), particularly cardiovascular and cerebrovascular events (13.1% vs. 25.9%, p = 0.001). The study concludes that combined thiamin and folic acid supplementation improves cognitive function in MHD patients with a favorable safety profile.

1 min30 Apr 2026

European respiratory review : an official journal of the European Respiratory Society

Oscillometry for the diagnosis of asthma in children: a systematic review.

Diagnosing asthma in children and young people (CYP) remains challenging. Oscillometry is a promising tool and is feasible from 2 years of age. European Respiratory Society (ERS) technical standards and bronchodilator response (BDR) oscillometry thresholds have been published, but diagnostic accuracy is not established. We systematically reviewed studies comparing oscillometry and spirometry in CYP under investigation for asthma. Reference standards were positive BDR or positive methacholine challenge test (MCT). Primary aims were to investigate the sensitivity and specificity of current ERS oscillometry thresholds (>40% decrease in resistance at 5 Hz (R 5), >50% increase in reactance at 5 Hz (X 5) or >80% decrease in the area under the reactance curve); secondary aims were to identify oscillometry threshold values optimising both sensitivity and specificity. 11 studies were included; six (n=992 CYP) utilised BDR and five (n=531 CYP) MCT as reference standard. Meta-analysis was not possible due to heterogeneity of results reported. In two studies using current ERS BDR thresholds, zero sensitivity and high specificity (>85%) were observed. In weighted regression analyses of BDR studies, a 17.0% decrease in resistance at 5-6 Hz had sensitivity and specificity of 71.6% (95% CI 69.7-73.7%); a 20.2% increase in X 5 had sensitivity and specificity of 68.6% (95% CI 66.6-70.8%). Similarly, 27.7% increase in R 5 had sensitivity and specificity of 73.6% (95% CI 71.9-75.3%) for MCT. Currently recommended ERS thresholds for oscillometry BDR have low sensitivity. Proposed thresholds for defining positive BDR and MCT by oscillometry require prospective validation and adoption of standards for measuring and reporting oscillometry parameters in future diagnostic comparative studies.

Recombinant human interleukin-7 for patients with infection-associated lymphopenia: a systematic review and meta-analysis.

This study aims to evaluate the efficacy of recombinant human interleukin-7 (rhIL-7) in treating lymphopenia and related clinical outcomes in patients with infection-associated lymphopenia through a meta-analysis. A Literature retrieval was conducted across databases, including the Cochrane Library, Web of Science, PubMed, Embase, SinoMed, CNKI, Wanfang, and VIP from the inception until October 2025. Randomized controlled trials of rhIL-7 for the treatment of lymphopenia were screened and identified for eligibility. Primary outcomes included absolute lymphocyte counts (ALC), mortality, intensive care unit (ICU) length of stay, and incidence of secondary infections. Four studies were included, covering sepsis and COVID-19. In septic patients, rhIL-7 significantly increased ALC (MD = 1.33 at 3 weeks; 95% CI [0.29, 2.38]; MD = 1.14 at 4 weeks; 95% CI [0.02, 2.25]), CD4+ T-cell counts (MD = 0.56 at 3 weeks; 95% CI [0.08, 1.05]) and CD8+ T-cell counts (MD = 0.40 at 2 weeks; 95% CI [0.05, 0.76]). However, rhIL-7 failed to reduce mortality (RR = 1.01; 95% CI [0.36, 2.81]) or the incidence of secondary infections (RR = 1.05; 95% CI [0.48, 2.30]) in patients with sepsis. In patients with COVID-19, rhIL-7 did not significantly increase ALC at 30 days (MD = 0.46; 95% CI [-0.15, 1.08]) or reduce mortality (RR = 0.85; 95% CI [0.55, 1.33]), but it did significantly reduce the incidence of secondary infections (RR = 0.58; 95% CI [0.46, 0.74]; p < 0.0001). A combined analysis revealed that rhIL-7 significantly increased ALC (MD = 1.15 at 3 weeks; 95% CI [0.47, 1.84]; MD = 0.80 at 4 weeks; 95% CI [0.24, 1.36]) and reduced the risk of secondary infections (RR = 0.64; 95% CI [0.50, 0.81]), but had no effect on mortality or ICU length of stay. RhIL-7 effectively ameliorates sepsis-associated lymphopenia but does not improve prognosis. Although rhIL-7 reduces the incidence of secondary infections in COVID-19 patients, confounding factors related to the pandemic context must be taken into account.

Respiratory medicine

American journal of physiology. Endocrinology and metabolism

Muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICU-acquired weakness.

The association of perturbed skeletal muscle metabolism with intensive care unit (ICU)-acquired weakness (ICUAW) is not clear. The objective of the present study was to characterize temporal changes in skeletal muscle mitochondrial function, ATP concentration, and substrate utilization during and up to 6 mo post-ICU admission in critically ill patients, and to delineate mechanisms underpinning ICUAW by comparing the expression of genes involved in skeletal muscle mitochondrial function and substrate utilization in the critically ill patients to control groups that had either undergone elective surgery or leg immobilization (i.e., muscle disuse). The study design was a randomized controlled trial of functional electrical stimulation-assisted cycle ergometry (FESCE) versus standard care, with skeletal muscle mitochondrial respirometry defined a priori in a nested subgroup of patients as the primary outcome. Mitochondrial respirometry did not change 7 days or 6 mo after ICU admission and was not impacted by FESCE. However, a 20% reduction in muscle ATP content by day 7 of ICU stay persisted after 6 mo and tended to associate with ICUAW (P = 0.078, R2 = 0.582). Moreover, a 40% lower muscle glycogen and 2.5-fold greater muscle lactate were observed earlier at day 1 compared with elective surgery patients. These changes reflected expression of genes related to glycogen metabolism when disuse was accounted for, and a greater expression of the gene encoding glycogen phosphorylase (PYGM) was predictive of mortality. We conclude that muscle glycogen metabolism is rapidly dysregulated in critical illness, which may have implications for muscle ATP resynthesis and ICUAW.NEW & NOTEWORTHY The association of skeletal muscle metabolism with intensive care unit (ICU)-acquired weakness (ICUAW) is not clear. We report for the first time that reduced muscle ATP content by day 7 of ICU stay persisted after 6 mo and tended to be associated with ICUAW. Moreover, lower muscle glycogen and greater muscle lactate were observed earlier at day 1 compared with elective surgery patients. These changes reflected the expression of genes related to glycogen metabolism, which were predictive of mortality.

2 min29 Apr 2026

Clinical nutrition (Edinburgh, Scotland)

Optimal delivery of enteral protein in the critically ill: A systematic review and meta-analysis of randomised controlled trials.

Critically ill patients experience acute muscle wasting, associated with impaired clinical outcomes. It has been suggested that greater dietary protein delivery may attenuate muscle wasting and improve outcomes, but the optimal dose is unknown. The aim of this systematic review and meta-analysis was to evaluate the effect of enteral protein delivered to achieve doses recommended within international guidelines (1.2-2.0 g/kg bodyweight/day) compared to enteral protein delivered below international guidelines (<1.2 g/kg/day) on mortality and clinical, patient-centred, and muscle outcomes. A systematic review of databases MEDLINE, EMBASE, CINAHL, and CENTRAL was performed from database inception through to 2 July 2025. Randomised controlled trials (RCTs) of adult critically ill patients comparing 'greater protein' delivery (1.2-2.0 g/kg/day) versus 'lesser protein' delivery (<1.2 g/kg/day) predominantly via enteral nutrition (EN), with similar energy delivery, were identified. Risk ratios were pooled for binary outcomes and mean differences or standardised mean differences for continuous outcomes using random-effects models. Subgroup analyses investigated the effect of exclusive EN; acute kidney injury (AKI) as defined within individual trials; and higher severity of illness (Sequential Organ Failure Assessment score ≥9) for the primary outcome (mortality). From a total of 10,414 citations, 14 RCTs were included, comprising n = 6553 patients (n = 3248 greater protein; n = 3305 lesser protein) from 13 individual patient RCTs and one cluster randomised cross-over trial. Greater protein delivery did not affect mortality (pooled RR 1.01, 95% CI 0.92, 1.12, p = 0.795; I2= 0%; τ2= 0.00; 12 RCTs: greater protein n = 3197; lesser protein n = 3243). Other clinical outcomes were not different; however, the point estimate suggested decreased quality of life for greater protein compared to lesser protein (pooled standardised mean difference -0.11, 95% CI -0.24, 0.01, p = 0.081; I2= 0%; τ2= 0.00; 2 RCTs, n = 921: greater protein n = 456; lesser protein n = 465). In patients with an AKI (as defined within individual trials), greater protein delivery was associated with increased mortality (pooled effect estimate 1.29, 95% CI 1.05, 1.58, p = 0.015; I2= 0%; τ2= 0.00; 3 RCTs, n = 755: greater protein n = 390; lesser protein n = 365), with ICEMAN evaluation suggesting that the evidence for effect modification was of moderate credibility. Greater protein delivery does not reduce mortality or improve any clinical outcomes compared with lesser protein, and may be associated with increased mortality in patients with AKI, though subgroup definitions varied across trials. CRD42025547923.

3 min29 Apr 2026

The western journal of emergency medicine

Advances in Patient Monitoring Systems for Prehospital and Resource-Limited Settings.

Vital sign monitoring is essential to the management of critically ill and injured patients. Recent advances in patient monitoring systems have the potential to improve outcomes by providing real-time data and predictive insights, which are particularly valuable in prehospital and resource-limited settings. We conducted a systematic review of the literature to assess the capabilities, performance, and clinical impact of patient monitoring technologies designed for these environments. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review using PubMed and Scopus search engines on studies published between 2018-2022 that proposed or tested novel patient monitorint systems with utility in prehospital or resource-limited settings. Two reviewers independently screened studies, and discrepancies were resolved by a senior author. Of 217 studies identified in the search, 40 met the proposed inclusion criteria. Compared to standard platforms, wearable and contactless systems for patient monitoring demonstrated high accuracy but with delayed responsiveness and less reliable temperature measurements. Artificial intelligence (AI)-based platforms consistently outperformed well-accepted scoring systems in predicting outcomes such as mortality, intensive care unit (ICU) admission, and clinical decompensation. In this review we summarize proposals for prototypes of integrated patient monitoring systems that combine biosensors, AI algorithms, global positioning system, and wireless communication designed to facilitate triage in prehospital settings, and we then compare their components. Various platforms were piloted and demonstrated minimal disruption to workflow and positive user feedback, although most lacked comprehensive cost analyses. Emerging patient monitoring system technologies may enhance remote triage and care delivery, particularly in resource-limited settings. However, significant barriers remain, including cost, limited testing in real-world environments, and the lack of higher tiers of evidence. Future efforts should prioritize field-based testing, usability in low-resource settings, and cost-effectiveness analyses to guide clinical adoption.

2 min29 Apr 2026

Risk Prediction Models for Frailty in Maintenance Hemodialysis Patients: A Systematic Review and Meta-Analysis.

The aim is to systematically evaluate the frailty risk prediction models for Chinese maintenance hemodialysis patients and to provide a reference for the construction and optimization of such models. Relevant studies on prediction models for frailty in Chinese maintenance hemodialysis patients were retrieved from PubMed, Embase, Web of Science, Cochrane Library, CINAHL, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Database, and VIP Database. The search period was from the inception of each database to October 23, 2024. Two researchers independently screened the literature, extracted data, and assessed the quality of the included models using the Prediction model Risk of Bias Assessment Tool (PROBAST). A meta-analysis of predictors was performed using Stata 18.0 software. A total of 13 studies from China were included, which developed 15 distinct prediction models. These models involved 4341 patients. The area under the receiver operating characteristic curve (AUC) for these models ranged from 0.722 to 0.998, indicating good predictive performance (AUC > 0.7). However, the overall risk of bias was high, primarily in the domain of data analysis. The meta-analysis identified the following significant predictors of frailty (p < 0.05): age (OR = 1.14, 95% CI 1.05-1.23), serum albumin (OR = 0.66, 95% CI 0.52-0.83), exercise (OR = 0.50, 95% CI 0.49-0.63), comorbidity (OR = 1.70, 95% CI 1.47-1.97), nutritional score (OR = 3.64, 95% CI 1.53-8.67), ADL score (OR = 0.77, 95% CI 0.68-0.88), female sex (OR = 6.24, 95% CI 1.97-19.80), and depression (OR = 1.26, 95% CI 1.04-1.53). Our results indicate the incidence of frailty among maintenance hemodialysis patients in China is as high as 39%. The identified predictors-advanced age, hypoalbuminemia, physical inactivity, comorbidities, poor nutritional status, impaired activities of daily living, female sex, and depression-form the basis for developing targeted preventive measures for frail patients on maintenance hemodialysis. The prediction model of frailty risk in maintenance hemodialysis patients in China is still in its infancy. Future research can refer to the model construction method of this study and the common predictors integrated by meta-analysis and select appropriate methods to develop and verify the frailty prediction model in combination with clinical practice. Targeted preventive measures should be given to maintenance hemodialysis patients with high risk in the early stage.

Seminars in dialysis

2 min28 Apr 2026

Clinical and translational science

Modulation of Inflammatory Indices by Omega-3 Fatty Acids Supplementation in Hemodialysis: A Clinical Trial Approach.

Chronic kidney disease (CKD) is closely associated with systemic inflammation. This randomized controlled trial aimed to evaluate the effects of omega-3 fatty acids supplementation on inflammatory markers in patients with CKD undergoing hemodialysis. Eligible participants with CKD receiving hemodialysis were randomly assigned to either an intervention group or a control group. The intervention group received three capsules of omega-3 fatty acids (3 g/day) for two months, while the control group received placebo capsules containing medium-chain triglyceride (MCT) oil. Inflammatory markers, including C-reactive protein (CRP) and interleukin-6 (IL-6), were measured both before and after the interventions. The results showed that CRP levels increased from 9.86 ± 12.64 to 11.46 ± 22.23 mg/L in the intervention group and from 5.24 ± 9.01 to 5.61 ± 7.93 mg/L in the control group (p = 0.11). Similarly, IL-6 levels increased from 17.84 ± 14.08 to 81.82 ± 66.22 pg/mL in the intervention group and from 14.96 ± 18.41 to 56.73 ± 115.45 pg/mL in the control group (p = 0.53). No statistically significant group differences were observed after adjusting for confounders such as age, sex, body mass index (BMI), smoking, dietary intake, and pre-existing diseases. The study findings showed that a two-month intake of omega-3 fatty acids supplements did not have a significant impact on reducing the levels of inflammatory markers in CKD patients undergoing hemodialysis. Larger trials with longer durations are warranted. Study Highlights What is the Current Knowledge on the Topic? ○ Omega-3 fatty acids have anti-inflammatory properties and are reported to be potentially beneficial in reducing inflammation associated with CKD, but the evidence regarding the effectiveness of omega-3 supplements in reducing inflammatory markers in this population remains inconsistent. What Question did this Study Address? ○ What is the effect of omega-3 fatty acids supplementation for 2 months on CRP and IL-6 levels in patients with CKD undergoing hemodialysis? What Does This Study Add to Our Knowledge? ○ Contrary to previous studies, this study found that omega-3 fatty acids supplementation did not significantly reduce CRP or IL-6 levels compared with placebo over 2 months and that short-term supplementation is not sufficient to reduce systemic inflammation in hemodialysis patients. How Might this Change Clinical Pharmacology or Translational Science? ○ These findings suggest that short-term omega-3 fatty acids supplementation may not be sufficient in reducing inflammatory markers in CKD patients undergoing hemodialysis and highlight the need for larger-scale clinical trials with different doses and longer durations to investigate nutritional or pharmacological strategies.

2 min28 Apr 2026

Time-Threshold Dose-Response Relationship Between Duration of Premature Rupture of Membranes and Maternal, Neonatal, and Laboratory Evidence of Infection: A Systematic Review and Meta-Analysis.

To identify the continuous dose-response relationship between the duration of premature rupture of membranes (PROM) and the probability of neonatal and maternal infectious morbidity. This meta-analysis and systematic review synthesise data from 15 studies worldwide involving more than 70,000 mother-neonate pairs. A two-step random-effects model of PROM duration as a continuous dose, using restricted cubic splines, was used to estimate specific risk thresholds. The analysis established a progressive, non-linear escalation of risk. The onset of statistical risks at 16 hours is the early-onset pneumonia (Adjusted OR 1.86, 95% CI: 1.152.99). At the age of 18 hours, the incidence of culture-proven sepsis in neonates was 4.0%, and the odds ratio for maternal fever was significantly higher (AOR 36.6). The analysis of the ROC curves revealed a critical mathematical pivot point at 37 hours, after which complications escalate exponentially. Latency greater than 48 hours was the most significant independent predictor of culture-proven sepsis, with an increased risk of 8.2 (p < 0.001). Histologic chorioamnionitis was detected in 39% of mothers, and in many cases, they are clinically silent. Considerable heterogeneity (I2 > 60%) was mainly caused by gestational age disparities in cohorts of extremely preterm and term babies. PROM latency risk is not a threat but accelerates with time. Although 18 hours will be an acceptable early warning level, the range of 37 to 48 hours is a high-risk period that needs aggressive treatment. International guidelines need to be reviewed to reflect this non-linear trend, especially regarding pregnancy, where the risks of delivery are low compared to the rising risk of latency.

La Clinica terapeutica

2 min28 Apr 2026

The Effect of Probiotic Use on Gut Leakage Measured by Zonulin and its Relation to P Cresyl Sulfate and Inflammation in Hemodialysis Patients: A prospective controlled clinical study.

In chronic kidney disease, gut dysbiosis increases intestinal permeability, allowing toxins to enter the bloodstream and causing inflammation. This study aimed to assess the impact of probiotic supplementation on serum Zonulin levels, P-cresyl sulfate and highly sensitive C-reactive protein (hs-CRP) in hemodialysis patients. Forty hemodialysis patients were enrolled and divided into either a probiotic group or a control group (20 patients per group). The probiotic group received supplements for 3 months. Serum Zonulin, hs-CRP and P-cresyl sulfate were measured at baseline and after the 3-month intervention. After 3 months of probiotic administration, the probiotic group showed a statistically significant decrease in serum Zonulin (p < 0.001), P-cresyl sulfate (p < 0.001) and hs-CRP (p = 0.037). Furthermore, a significant difference was observed between the two groups regarding post-intervention levels of Zonulin (p < 0.001), P-cresyl sulfate (p < 0.001), and hs-CRP (p < 0.001). Probiotic administration in hemodialysis patients improved intestinal barrier integrity, reduced gut-derived toxin levels, and lowered systemic inflammation.

La Clinica terapeutica

1 min28 Apr 2026

Prevalence and clinical impact of hepatic steatosis on autoimmune liver disease: A systematic review and meta-analysis.

The clinical impact of hepatic steatosis (HS) among patients with autoimmune liver disease (AILD) remains unclear. We aim to determine the prevalence of HS and its clinical impact on treatment response and outcomes in patients with AILD. We systematically searched 3 electronic databases until 17 December 2025, including all studies that reported the prevalence, clinical impact, and treatment response of AILD patients with concomitant HS. The temporal trend of HS prevalence was analyzed using a quasi-Poisson regression model, with annual percent changes (APC, %) calculated. Overall, 44 studies, comprising 19,898 patients with autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were included. The pooled prevalence of HS in patients with AIH, PBC, and PSC was 27.3%, 32.9%, and 21.6%, respectively. HS prevalence has significantly increased among PBC patients since 2010 (APC: +37.4%). While concomitant HS was associated with a higher risk of hepatic decompensation (OR: 1.6, 95% CI: 1.3-2.1, I2=0%) and hepatocellular carcinoma (OR: 1.8, 95% CI: 1.3-2.6, I2=0%) in patients with AIH, HS did not influence the clinical outcomes in patients with PBC. Treatment response in AIH and PBC was not influenced by concomitant HS. Available data on PSC with concomitant HS were insufficient to assess its association with clinical outcomes. AIH patients with concomitant HS had worse outcomes than those without HS; whereas HS did not influence the clinical outcomes in patients with PBC. Future research evaluating the impact of HS on PSC and overlap syndrome is much needed.

2 min27 Apr 2026

Rheumatology (Oxford, England)

Long-term efficacy and safety of belimumab in children with systemic lupus erythematosus: a meta-analysis of real-world data.

Belimumab is the first biologic approved for children aged over 5 years with systemic lupus erythematosus (SLE); however, evidence on its long-term efficacy and safety remains limited. This meta-analysis synthesized available data to provide quantitative evidence for clinical decision-making. PubMed, Embase, Cochrane Library and Wanfang databases were searched for studies reporting belimumab outcomes in pediatric SLE. Random-effects models were used for single-arm analyses, and risk ratios (RRs) and mean differences (MDs) were calculated for double-arm comparisons. Sixteen cohort studies and trials were included. Belimumab reduced the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score by 10.16 points at 6 months and 17.71 points at 12 months from baseline. LLDAS was achieved 42% at 6 months and 79% at 12 months. Mean glucocorticoid dose decreased by 19.88 mg/day at 6 months and 11.84 mg/day at 12 months. The 12-month flare rate was 7%, and adverse event (AE) rates were 12% and 46% at 6 and 12 months, respectively. In lupus nephritis (LN), complete remission occurred in 88% at 6 months and 94% at 12 months. Compared with standard immunotherapy, belimumab produced significant greater SLEDAI score reduction (MD, 2.86; P < 0.001), fewer AEs (RR, 0.37; P = 0.004) and higher LN remission rates (RR, 1.26; P = 0.03) at 6 months and lower flare risk at 12 months (RR, 0.44; P = 0.02). In pediatric SLE, add-on belimumab improves disease control and safety at 6 months and reduces flare risk at 12 months compared with standard immunotherapy. PROSPERO: https://www.crd.york.ac.uk/prospero, CRD420251142943.

2 min27 Apr 2026

A randomized controlled trial of L-taurine for fatigue in decompensated cirrhosis.

Fatigue affects 60%-80% of patients with cirrhosis, yet no universally effective pharmacologic therapy exists. Taurine, an amino sulfonic acid with antioxidant and membrane-stabilizing properties, may address metabolic mechanisms underlying fatigue. We hypothesized that L-taurine supplementation would significantly reduce fatigue severity compared to standard care in patients with decompensated cirrhosis. This single-center, parallel-arm, open-label randomized controlled trial enrolled adults with decompensated cirrhosis (Child-Turcotte-Pugh score 7-13) and clinically significant fatigue (Fatigue Assessment Scale score >22) at a tertiary care center in South India. Participants were randomized via block randomization to L-taurine (1000 mg/d) plus standard care or standard care alone for 12 weeks. The primary outcome was the change in the Fatigue Assessment Scale score. Analysis of covariance examined treatment-by-anaemia interactions. Effect sizes were calculated using Cohen's d. Of 220 randomized patients, 202 completed the study (standard care: n=100; taurine: n=102). The mean FAS change was -6.83±8.70 (standard care) versus -8.08±7.95 (taurine), with no significant difference (mean difference -1.25; 95% CI: -3.55 to 1.05; p=0.288; Cohen's d=-0.15). However, a significant treatment-by-anemia interaction was observed (p=0.009). In patients without anemia (n=41), taurine produced a large treatment effect (-11.90±4.04 vs. -4.57±9.23; p=0.002; Cohen's d=-1.02), whereas patients with anemia (n=161) showed no benefit (p=0.832). Adverse events occurred in 11.8% of patients treated with taurine, all of which were mild. L-taurine did not improve fatigue in unselected patients with decompensated cirrhosis. A post hoc subgroup analysis suggested potential benefit in patients without anemia; however, given the open-label design, small subgroup size, post hoc nature of the analysis, and the inherent limitations of unblinded patient-reported outcomes, this finding should be considered hypothesis-generating. A confirmatory, placebo-controlled trial enrolling patients without anemia is warranted (Clinical Trials Registry India number CTRI/2023/06/054455).

2 min27 Apr 2026

Journal of affective disorders

The influence of C-reactive protein on depression in inflammatory bowel disease: A systematic review and meta-analysis.

The comorbidity between inflammatory bowel disease (IBD) and depression has been widely recognized, but the role of C-reactive protein (CRP) as a key inflammatory marker in this context is controversial. Furthermore, there is a lack of an effective strategy for applying changes in CRP levels to the clinical diagnosis of IBD and depression comorbidity. A systematic search of relevant databases was conducted to include studies that met the criteria. A fixed-effects model was used to assess the association between the CRP levels and depressive status in IBD patients using the standardized mean difference (SMD) and its 95% confidence interval (CI). 10 case-control studies involving 2105 participants were included. The results showed that IBD patients with depression had significantly higher CRP levels than non-depressed patients (SMD = 0.18, 95% CI: 0.09-0.27). Subgroup analyses further showed that the association was more pronounced in the Asian region (SMD = 0.26, 95% CI: 0.11-0.41), in patients aged ≤40 years (SMD = 0.27, 95% CI: 0.15-0.39), and in studies with a higher proportion of male participants (SMD = 0.28, 95% CI: 0.12-0.43). Individuals with IBD exhibiting higher CRP concentrations face a substantially greater likelihood of developing depression, indicating that CRP potentially functions as an inflammatory marker for depression susceptibility in IBD patients.

1 min27 Apr 2026

Journal of clinical pharmacology

A Phase 1 Study Evaluating the Pharmacokinetics and Safety of Avacopan in Participants with End-Stage Kidney Disease on Hemodialysis.

The effect of end-stage kidney disease (ESKD) and hemodialysis (HD) on avacopan exposure is unknown. This Phase 1 study evaluated the pharmacokinetics (PK) and safety of avacopan and its active metabolite M1 in healthy participants and participants with ESKD requiring HD following a single 30-mg oral dose administered with food. Healthy participants (N = 6) received one dose of avacopan, while participants with ESKD (N = 7) received a single 30-mg oral dose during each treatment period 18 days apart: once 4 h before HD and once on a non-HD day. PK parameters included area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast), AUC from time 0-48 h (AUC0-48), and maximum concentration (Cmax). Comparisons were based on geometric least squares mean (GLSM) ratios with 90% confidence intervals. Relative to healthy participants, avacopan exposure on the non-HD day in participants with ESKD was similar, with GLSM ratios of 0.862 for AUC0-48, 1.12 for AUClast, and 1.03 for Cmax. Corresponding M1 exposures were lower in participants with ESKD, with GLSM ratios ranging from 0.639 to 0.658. Within the ESKD group, avacopan exposure on the HD day was lower than on the non-HD day (GLSM ratios: 0.699-0.914), while M1 exposure was comparable between periods. Adverse events were mild to moderate and consistent with the known safety profile of avacopan. These findings indicate that ESKD or HD has no clinically meaningful impact on avacopan or M1 exposure, and dose adjustment may not be necessary in this population.

2 min24 Apr 2026

Critical care (London, England)

Alternative net ultrafiltration rate strategies in acute kidney injury: a feasibility randomized clinical trial.

Observational studies link high net ultrafiltration (UFNET) rates during continuous kidney replacement therapy (CKRT) to increased mortality. The Restrictive versus Liberal Rate of Extracorporeal Volume Evaluation in Acute Kidney Injury trial evaluated the feasibility of a restrictive versus liberal UFNET rate strategy. This stepped-wedge cluster-randomized trial enrolled patients in ten ICUs across two healthcare systems from July 2022 to June 2024. Each ICU was a cluster, with 1 randomly transitioning from liberal (2.0-5.0 mL/kg/h) to restrictive (0.5-1.5 mL/kg/h) group every two months after the first six months. The coprimary outcomes included between-group separation in UFNET rates, protocol adherence, and recruitment rate. Of 97 patients (55 liberal, 42 restrictive) enrolled, the mean (SD) delivered UFNET rate did not differ between the groups (2.05 [0.83] vs. 1.81 [0.86] mL/kg/h; adjusted P = 0.4). In per-protocol analysis, there was a significant between-group separation in mean UFNET rates (2.24 [0.72] vs. 1.22 [0.32] mL/kg/h; P = 0.002). Protocol deviations were similar (9.1% vs.7.1%, P = 0.7), and the recruitment rate was 0.99 (0.27) patients per ICU per two months. The use of rescue UFNET was higher in the restrictive group (14.5% vs. 66.7%; P < 0.001). In conclusion, despite high protocol adherence, there was minimal separation in delivered UFNET rates. While both strategies were feasible in select patients, the high rates of hemodynamic instability, the need for rescue UFNET, and physician override orders suggest that UFNET is more often driven by dynamic patient physiology than fixed protocols. This makes it challenging to maintain distinct, alternative UFNET targets in clinical practice.Trial registration number: ClinicalTrials.gov Identifier: NCT05306964.

2 min23 Apr 2026

Factors influencing patency after percutaneous transluminal angioplasty for autogenous arteriovenous fistulae: a systematic review and meta-analysis.

This systematic review and meta-analysis identified factors influencing patency after percutaneous transluminal angioplasty (PTA) for autogenous arteriovenous fistulae (AVF) in hemodialysis patients. Literature through July 2025 was searched for observational and randomized trials. Two reviewers independently performed study selection, quality assessment (Newcastle-Ottawa Scale/Cochrane tool), and data extraction. Meta-analyses used fixed-/random-effects models in R (per I2 statistic), with sensitivity and publication bias analyses. Fifty-two studies (n = 6,407) were included, 45 of high quality. For primary patency, independent risk factors were diabetes (OR = 1.02, 95% CI 1.01-1.02), lesion length >2 cm (OR = 2.87, 1.38-5.96), previous intervention (OR = 3.13, 1.69-5.79), failed AVF history (OR = 1.69, 1.22-2.35), brachiocephalic configuration (vs. radiocephalic, OR = 1.73, 1.33-2.26), vascular calcification, and multiple comorbidities. High post-PTA flow was protective, and drug-coated balloons outperformed conventional angioplasty. Secondary patency was compromised by diabetes (OR = 1.05, 95% CI 1.02-1.08), longer lesions (OR = 1.01, 95% CI 1.01-1.02), and residual stenosis (OR = 1.02, 95% CI 1.01-1.04), with procedural success protective. Intimal hyperplasia strongly predicted failure. Restenosis risk was elevated by diabetes (OR = 1.72, 95% CI 1.28-2.31) and hypertension (OR = 1.59, 95% CI 1.04-2.44), while medical therapy with nitrates (OR = 0.20, 95% CI 0.05-0.79) and higher albumin were protective. Conventional biomarkers had limited value. Long-term AVF patency after PTA depends on anatomical, historical, and pathological factors, emphasizing the need to target modifiable procedural and hemodynamic variables in clinical practice.