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PubMed2026

Gout and allopurinol adherence in newly diagnosed patients and the risk of fractures: a nationwide cohort study.

INTRODUCTION / OBJECTIVES: The association between gout and fractures remains controversial due to the competing effects of uric acid's antioxidant properties and gout-induced chronic inflammation. Our study aimed to evaluate the risk of fractures in newly diagnosed gout patients and to analyze the impact of Allopurinol medication adherence on this risk. METHODS: This nationwide cohort study utilized the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database (2002-2019). We identified 4,107 patients newly diagnosed with gout who remained on continuous allopurinol therapy during the 24-month medication assessment period and matched them 1:3 with 12,321 non-gout controls using propensity score matching. Allopurinol adherence was assessed via the Medication Possession Ratio (MPR) over a 24-month period and categorized into three groups: MPR < 0.3, 0.3 ≤ MPR < 0.8, and MPR ≥ 0.8. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for fractures (vertebral, hip, and distal radius). RESULTS: Gout patients demonstrated a significantly higher risk of overall fractures compared to the non-gout group (aHR 5.52; 95% CI 4.19-7.26). A significant inverse linear relationship was observed between allopurinol adherence and fracture risk (P for trend < .001). The risk was highest in the low-adherence group (MPR < 0.3; aHR 5.91; 95% CI 4.40-7.93) and relatively lower in the high-adherence group (MPR ≥ 0.8; aHR 4.77; 95% CI 2.94-7.72). Consistent trends were observed for vertebral (aHR 5.68) and hip (aHR 4.22) fractures. These associations remained consistent across all subgroups, including age, sex, and comorbidities. CONCLUSION: Newly diagnosed gout is associated with a substantially increased risk of fractures. Higher adherence to Allopurinol therapy is correlated with a significant reduction in this risk, suggesting that consistent urate-lowering therapy may mitigate gout-related bone fragility. Key Points • Newly diagnosed gout patients have a significantly higher risk of major osteoporotic fractures compared to the non-gout population. • A significant inverse linear relationship exists between Allopurinol adherence and fracture risk, with the highest adherence group (MPR ≥ 0.8) showing a relatively lower risk. • Consistent urate-lowering therapy (ULT) may mitigate bone fragility in gout patients by reducing systemic inflammatory burden caused by urate crystal deposition.

Humans↗

PubMed2026

Robotic-assisted transbronchial biopsy versus computed tomography-guided transthoracic needle biopsy for peripheral pulmonary lesions: a systematic review and meta-analysis of direct comparative studies.

Robotic-assisted bronchoscopy (RAB) and computed tomography-guided transthoracic biopsy (CTTB) are competing strategies for sampling peripheral pulmonary lesions (PPLs). Whether they differ in yield or safety is uncertain. To our knowledge, this is the first systematic review restricted to direct comparisons. We searched MEDLINE, Europe PMC, Scopus, Web of Science and ClinicalTrials.gov from inception to 7 July 2026 for studies directly comparing RAB with CTTB in adults with PPLs. The primary outcome was strict 2024 American Thoracic Society/American College of Chest Physicians diagnostic yield. Risk of bias was assessed with ROBINS-I and certainty with GRADE. A cohort-genealogy step identified, per outcome, the largest set of cohorts sharing no patients; only that set was pooled, with Hartung-Knapp and Mantel-Haenszel sensitivity analyses. Five retrospective studies from one US health system were eligible. Four share patients; at most three cohorts are mutually independent. Across those three, diagnostic yield was comparable (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; I²=24%; Hartung-Knapp 0.87-1.13), with an identical relative effect under strict and intermediate definitions although absolute yields fell from 88% to 74-84% under strict criteria. Pneumothorax requiring a chest tube and/or admission was about three-quarters less frequent with RAB across all three cohorts (RR 0.25, 95% CI 0.14-0.46; I²=0%; Hartung-Knapp 0.07-0.96). Strict yield (RR 0.99) and any pneumothorax (RR 0.06) were reported by two cohorts each and neither survives the few-studies correction. RAB took about 50 min longer than CTTB where same-session staging endobronchial ultrasound was counted in the robotic time, but only about 8 min longer than CTTB where it was not. Only one cohort reported yield by lesion size category and none reported yield by bronchus sign or lung zone, so lesion-level subgroups could not be pooled. Certainty was low for pleural complications and very low elsewhere. Low-certainty evidence indicates that RAB is associated with fewer pleural complications, with no statistically detectable difference in diagnostic yield; equivalence was not formally established. Because all evidence is retrospective, confined to one health system, and almost never stratified by lesion size or accessibility, these findings are hypothesis-generating and require a multicenter randomized trial.

Humans↗

PubMed2026

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30 years;40.0 ± 7.1 mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90 min of steady-state cycle ergometry (ExSS; 60 ± 5%) followed by a 5 km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment < 0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14 µmol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n = 0.613) or TT performance (5 s [95%CI: -44, 54], Ptreatment = 0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans↗

PubMed2026

Structured robotic colorectal training in a non-tertiary NHS hospital: a 502-case consecutive cohort implementation study.

Robotic-assisted colorectal surgery has expanded rapidly across NHS practice in the UK. Structured unit-wide training pathways are essential for safe technology adoption, yet published outcome data from non-tertiary hospitals remain limited. This study describes the implementation and feasibility of a unit-wide robotic colorectal program at a high-volume non-tertiary hospital, reporting outcomes across 502 consecutive resections performed by eight consultant surgeons and presenting these in the context of nationally published benchmarks. A retrospective cohort study of 502 consecutive robotic colorectal resections performed at York Teaching Hospital between May 2022 and December 2025. Eight consultant surgeons (A-H) participated in a structured four-phase training pathway incorporating simulation training, proctored cases, complexity-based case progression, and formal credentialing. Primary outcomes were 30-day mortality, unplanned return to theatre (RTT), and anastomotic leak (AL). Anastomotic leak was calculated using only patients who underwent anastomosis as the denominator. Procedure-stratified and individual surgeon outcomes with 95% confidence intervals were reported. Risk-adjusted cumulative sum (RA-CUSUM) analysis was performed to evaluate learning curves. Outcomes are presented descriptively alongside nationally published reference data; no formal statistical comparison against national benchmarks was performed. 502 robotic colorectal resections were performed. Mean patient age was 70.0 ± 11.3 years; 58.4% were male. Median ASA grade was III. The indication was malignancy in 89.2% of cases. Length of stay was non-normally distributed and is therefore reported using median and interquartile range in the revised analysis. Key outcomes: - 30-day mortality: 1.0% (5/502; 95% CI 0.4-2.3%) - Unplanned return to theatre (RTT): 5.2% (26/502; 95% CI 3.6-7.5%) - Anastomotic leak (AL): 3.3% (15/450; 95% CI 2.0-5.5%; denominator = patients with anastomosis) - 30-day unplanned readmission: 5.0% (25/502; 95% CI 3.4-7.2%) - Conversion to open surgery: 3.6% (18/502; 95% CI 2.3-5.6%) - Lymph node yield ≥12: 91.3% of cancer resections - R0 resection rate: 95.1% of cancer resections All primary outcomes fell within or below the published reference ranges used for descriptive context. RA-CUSUM trajectories were heterogeneous: no surgeon crossed the predefined upper control limit, but several curves showed later upward movement. Accordingly, the analysis is interpreted as safety surveillance rather than evidence of uniform performance improvement. RA-CUSUM monitoring showed that no surgeon crossed the predefined upper control limit; however, heterogeneous trajectories precluded a claim of uniform performance improvement.

Humans↗

PubMed2026

Prognostic Value of Circulating Tumor DNA-Based Minimal Residual Disease for Recurrence-Free Survival in Resectable Gastric Cancer: A Systematic Review and Meta-Analysis with Serial Monitoring Analysis.

BACKGROUND: Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) is an emerging biomarker, but its utility in resectable gastric cancer remains incompletely characterized. METHODS: We conducted a systematic review and meta-analysis of eight studies (520 patients) to evaluate the prognostic value of ctDNA-based MRD for recurrence-free survival (RFS) and overall survival (OS) in resectable gastric cancer. RESULTS: In localized resectable gastric cancer (Stage I-III), the setting in which postoperative ctDNA most coherently represents true molecular residual disease after curative-intent surgery, postoperative ctDNA positivity was associated with diminished recurrence-free survival (RFS: HR 12.26, 95% CI 3.30-45.52) and overall survival (OS: HR 8.57, 95% CI 3.06-23.98). The test for subgroup differences between localized and mixed-stage cohorts was not statistically significant (P = 0.57), and the numerically higher HR in the localized subgroup should therefore not be interpreted as evidence of a quantitatively stronger prognostic effect. Postoperative ctDNA detection demonstrated substantially stronger prognostic value (overall RFS: HR 10.00, 95% CI 4.53-22.10) compared to preoperative assessment (HR 2.17, 95% CI 1.10-4.28). Both tumor-informed and tumor-agnostic strategies effectively stratified high-risk patients. However, these effect sizes should be interpreted cautiously given the small number of studies and substantial heterogeneity (I2 = 65-72%). Results from mixed-stage cohorts including Stage IV disease are supportive but should not be considered equivalent to localized-disease findings, as ctDNA in metastatic disease reflects persistent systemic burden rather than minimal residual disease in the postoperative sense. CONCLUSIONS: Postoperative ctDNA-based MRD shows a consistent adverse prognostic association in resectable gastric cancer, with localized disease (Stage I-III) representing the most biologically and clinically coherent setting for interpretation. However, the large pooled hazard ratios (HR 10.00-12.26) should be interpreted as a directionally consistent signal rather than precise quantitative estimates, given the small number of studies, wide confidence intervals, and substantial heterogeneity (I2 = 65-73%). This heterogeneity is largely driven by substantial variation in postoperative sampling timing (4 days to 16 weeks) and ctDNA assay characteristics (platform, sensitivity, coverage, variant filtering, and positivity thresholds), which require standardization in future studies. While ctDNA is prognostically valuable, its clinical utility remains unestablished. Prospective randomized trials are needed to determine whether ctDNA-guided strategies improve patient outcomes before routine clinical implementation can be recommended.

Humans↗

PubMed2026

Maternal anemia and the risk of preterm birth: a meta-analysis.

BACKGROUND: Globally, preterm birth continues to be a primary contributor to neonatal complications and fatalities. Anemia among the most common nutritional disorders in pregnancy has been proposed as a potential contributor to early delivery. Although extensively studied, the available evidence does not yet provide a clear consensus. This study aimed to conduct a meta-analysis to quantitatively assess the relationship between maternal anemia and the risk of preterm birth. METHODS: This meta-analysis was conducted and reported in accordance with the PRISMA guidelines and the MOOSE checklist. A systematic and exhaustive search was performed across multiple electronic databases PubMed, Scopus, Web of Science, Embase, and the Cochrane Library to identify relevant studies published from inception to 1 January 2025. Effect sizes were combined using a random-effects meta-analysis. RESULTS: A total of 45 articles, reporting 60 independent study populations comprising 2,119,392 pregnant individuals were included. Considerable heterogeneity was found across the included studies (I2 = 95.54%, p < 0.001), which justified the application of a random-effects model for pooling effect sizes. Maternal anemia was significantly associated with an increased risk of preterm birth (pooled odds ratio[OR] = 1.28, 95% confidence interval [CI]: 1.20-1.36, p < 0.001). Despite substantial heterogeneity, sensitivity analyses confirmed the robustness of this association. The relationship was strongest in studies conducted in Asia (OR = 1.30, 95% CI: 1.22-1.40; p < 0.001) and the Europe (OR = 1.24, 95% CI: 1.08-1.41; p = 0.001) and reached statistical significance when anemia was assessed during the first trimester (OR = 1.12, 95% CI: 1.03-1.51; p = 0.007) and the third trimester (OR = 1.65, 95% CI: 1.42-1.91; p < 0.001), while no significant associations were found in the second trimesters (OR = 1.10, 95% CI: 0.99-1.22; p = 0.05). Funnel plot asymmetry and a significant Egger's test (p = 0.001) indicated potential publication bias, although Begg's test was not significant (p = 0.425). CONCLUSIONS: The current evidence suggests that maternal anemia, particularly in the third trimester, is significantly associated with an increased risk of preterm birth. These findings emphasize the clinical imperative for comprehensive and timely anemia screening during the third trimester. Integrating targeted interventions such as iron and micronutrient supplementation, is essential to mitigate the risk of preterm delivery and improve neonatal outcomes.

Humans↗

PubMed2026

Risk Factors for Long-Term Health-Related Quality-of-Life and Mental Health Outcomes in Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury (TBI) often leads to long-term disability, including persistent mental health issues and lower health-related quality of life (HRQoL). Early interventions can improve recovery, but because resources limit routine monitoring of all patients, trauma care remains largely symptom-driven. The combination of long-term disability and limited capacity for routine follow-up highlights the need for risk-stratified follow-up care and reliable evidence on early prognostic factors. However, the existing literature is sparse and methodologically heterogeneous, limiting the clinical applicability of findings. We therefore conducted a systematic review and meta-analysis to identify early risk factors for poorer long-term mental health and HRQoL outcomes. A systematic search of seven electronic databases identified studies of adult patients with TBI, with outcomes assessed at least 6 months postdischarge. Two authors independently screened the studies, assessed the risk of bias, and extracted the data. We pooled effect estimates using a random-effects meta-analysis and calculated 95% prediction intervals. A narrative synthesis was applied when meta-analysis was not feasible. The review was registered with PROSPERO (CRD42024576912) and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of the 8,104 articles screened, 64 studies met the inclusion criteria (n = 334,672). Most studies (58%) had a low risk of bias. Female sex, socioeconomic disadvantage, psychiatric history, assaultive-related injuries, and previous TBI were consistently associated with worse long-term outcomes. Across meta-analyses, assault-related injuries more than doubled the odds of post-traumatic stress disorder (odds ratio [OR] = 2.72; 95% confidence interval [CI]: 2.01-3.66, I2 = 0%). Higher odds were also observed among females (OR = 1.33; 95% CI: 1.11-1.59, I2 = 0%), individuals with prior TBI (OR = 1.56; 95% CI: 1.07-2.27, I2 = 0%), and those with psychiatric history (OR = 2.38; 95% CI: 1.83-3.10, I2 = 48%). We found that female sex (OR = 1.72; 95% CI: 1.38-2.16, I2 = 58%), prior TBI (OR = 1.52; 95% CI: 1.25-1.85, I2 = 0%), and psychiatric history (OR = 3.25; 95%CI: 1.86-5.69, I2 = 98%) were associated with higher odds of depression. Furthermore, higher pooled anxiety scores were observed in females and in individuals with a psychiatric history. The study identified several readily available factors present before or at discharge that are associated with poor long-term HRQoL and mental health outcomes. Leveraging these factors in follow-up protocols, prediction modeling, and clinical decision support systems may facilitate risk-stratified postdischarge care for TBI patients.

Humans↗

PubMed2026

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent↗

PubMed2026

Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial.

OBJECTIVES: To evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures. MATERIALS AND METHODS: Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs). RESULTS: PREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p < 0.05). PWV decreased after multiple doses (-0.87 m/s, 95% CI: -1.26 to -0.48 m/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (ρ = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios. CONCLUSION: PREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation. KEY POINTS: Question Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

Humans↗

PubMed2026

Ultra-high-frequency ECG quantifies residual electrical dyssynchrony during left bundle branch area pacing in patients with wide QRS: a paired within-patient study.

BACKGROUND: Left bundle branch area pacing (LBBAP) may restore a more physiological pattern of ventricular activation in patients with conduction delay; however, QRS narrowing alone may incompletely characterize electrical resynchronization. Ultra-high-frequency ECG (UHF-ECG) provides quantitative markers of ventricular activation timing and dyssynchrony. OBJECTIVE: To quantify paired OFF-to-ON changes in conventional ECG and UHF-ECG metrics during LBBAP in patients with baseline wide QRS and to assess the relationship between paced R-wave peak time (RWPT) and residual UHF-ECG dyssynchrony. METHODS: In this prospective single-center paired study, 21 patients with bradycardia and baseline wide QRS underwent standard ECG and UHF-ECG assessment during intrinsic rhythm (pacing OFF) and during LBBAP (pacing ON). Endpoints included QRS duration, signed VED16, absolute VED16 (|VED16|), mean ventricular delay (meanVD), and a clinically interpretable distance-to-normal metric defined as dist = max(|VED16|-20, 0). Paired changes were summarized as medians with bootstrap 95% confidence intervals and tested using the Wilcoxon signed-rank test. Associations between paced RWPT and residual dyssynchrony during pacing were evaluated using Pearson and Spearman correlation coefficients. RESULTS: LBBAP significantly narrowed QRS duration from 136.8 [130.2-153.6] ms during intrinsic rhythm to 116.0 [107.8-125.6] ms during pacing (median Δ -21.0 ms; 95% CI -33.9 to -18.6; p < 0.001). Signed VED16 did not change significantly (median Δ 0.4 ms; p = 1.000), consistent with the mixed conduction-phenotype composition of the cohort. In contrast, severity-oriented UHF-ECG endpoints improved: |VED16| decreased numerically (median Δ -5.2 ms; p = 0.070), whereas dist decreased significantly (median Δ -0.7 ms; 95% CI -14.4 to 0.0; p = 0.015). The proportion of patients within the normal dyssynchrony band (|VED16| ≤ 20 ms) increased from 7/21 (33.3%) to 12/21 (57.1%). Median paced RWPT was 66.6 [58.6-74.6] ms, and shorter RWPT correlated with lower residual |VED16| during pacing (Pearson r = -0.45, p = 0.038). CONCLUSIONS: In patients with baseline wide QRS, LBBAP produces marked QRS narrowing, whereas UHF-ECG provides complementary quantification of residual electrical dyssynchrony. Severity-oriented UHF-ECG endpoints, particularly a distance-to-normal metric, may offer an interpretable mechanistic framework beyond conventional ECG alone. Shorter paced RWPT was associated with lower residual dyssynchrony during pacing, supporting physiological coherence between procedural and high-resolution electrocardiographic markers.

Humans↗

PubMed2026

Azacitidine-Venetoclax or Induction Chemotherapy for Acute Myeloid Leukemia.

BACKGROUND: Induction chemotherapy has long been a key component of curative therapy for fit patients with acute myeloid leukemia (AML), despite its frequently severe side effects and substantial health care utilization. For patients who are ineligible for induction chemotherapy, hypomethylating therapy plus venetoclax is the standard treatment owing to its efficacy and side-effect profile. METHODS: In this multicenter, phase 2 trial, we randomly assigned, in a 1:1 ratio, previously untreated adults with AML who were eligible for induction chemotherapy to receive either azacitidine plus venetoclax or induction chemotherapy. Patients with core binding factor fusions, mutations in the gene encoding FMS-like tyrosine kinase 3 (FLT3), or mutations in the gene encoding nucleophosmin-1 (NPM1; unless the patient was ≥60 years of age) were excluded. The primary end point was event-free survival. RESULTS: A total of 172 patients underwent randomization, with 86 patients assigned to each group. The median age of the patients was 64 years. A total of 72% of the patients had adverse-risk disease according to the European LeukemiaNet 2022 classification. At a median follow-up of 21.9 months, the median event-free survival was 14.5 months (95% confidence interval [CI], 10.4 to 24.4) in the azacitidine-venetoclax group, as compared with 6.2 months (95% CI, 4.1 to 10.1) in the induction chemotherapy group, corresponding to a hazard ratio for event or death of 0.57 (95% CI, 0.39 to 0.84; P = 0.002 by the stratified log-rank test). Infection of grade 3 or higher occurred in 28% of the patients (95% CI, 19 to 39) receiving azacitidine-venetoclax and in 41% of those (95% CI, 30 to 52) receiving induction chemotherapy; hemorrhage of grade 3 or higher occurred in 2% (95% CI, 0.3 to 8) and 12% (95% CI, 6 to 20), respectively. CONCLUSIONS: In this phase 2, randomized trial, azacitidine-venetoclax therapy led to significantly longer event-free survival than induction chemotherapy among induction-eligible patients with AML. (Funded by AbbVie and others; PARADIGM ClinicalTrials.gov number, NCT04801797.).

Adult↗

PubMed2026

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans↗

PubMed2026

Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g = -0.84, 95% Confidence Interval, CI -1.42, -0.26, p < .01, I2 = 92.3%), reduced generic stress symptoms (g = -0.64, 95% CI -1.09, -0.20, p < .01, I2 = 87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g = -0.99, 95% CI -2.58, -0.60, p = .12, I2 = 84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (β = 0.13, p = .02) and a lower attrition rate (β = 0.03, p = .03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans↗

PubMed2026

Telmisartan-based monotherapy and combination regimens for blood pressure control in adults with hypertension: a systematic review, meta-analysis, and GRADE assessment.

PURPOSE: To evaluate the efficacy, safety, and certainty of evidence for telmisartan-based antihypertensive regimens in adults with hypertension. METHODS: This systematic review and meta-analysis followed PRISMA 2020. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception to 2026. Eligible studies enrolled adults with hypertension and compared telmisartan monotherapy or telmisartan-containing combinations with placebo, usual care, non-telmisartan antihypertensive agents, or alternative telmisartan-based regimens. Continuous outcomes were pooled as mean differences (MDs) and dichotomous outcomes as risk ratios (RRs), both with 95% confidence intervals (CIs), using random-effects models, with additional subgroup analyses conducted by comparator type. Risk of bias was assessed using RoB 2, and certainty of evidence was evaluated using GRADE. RESULTS: Twenty-five included reports (24 unique trials, since two reports present secondary outcomes from the same underlying trial) involving 6,521 participants were included, spanning placebo-controlled, usual-care-controlled, active-comparator, and telmisartan-combination-versus-telmisartan-monotherapy designs. Telmisartan-based therapy significantly reduced office systolic blood pressure (MD - 6.39 mm Hg; 95% CI - 7.86 to - 4.93; low certainty) and office diastolic blood pressure (MD - 4.88 mm Hg; 95% CI - 6.67 to - 3.09; low certainty), although the magnitude of effect was comparator-dependent. Based on only two trials, 24-h ambulatory systolic blood pressure (MD - 7.16 mm Hg; 95% CI - 10.61 to - 3.72) and ambulatory diastolic blood pressure (MD - 4.42 mm Hg; 95% CI - 6.36 to - 2.48) were reduced with moderate certainty. Telmisartan-based regimens improved blood pressure response (RR 1.68; 95% CI 1.31 to 2.16; moderate certainty) but not blood pressure control achievement (RR 1.44; 95% CI 0.92 to 2.24; very low certainty). Overall adverse events, dizziness, and headache were comparable (very low to low certainty), while edema was less frequent with telmisartan-based therapy (RR 0.33; 95% CI 0.15 to 0.73; moderate certainty). CONCLUSION: Telmisartan-based regimens, particularly fixed-dose and multidrug combinations, effectively reduce office and ambulatory blood pressure and improve blood pressure response, with broadly comparable short-term safety and less edema. These effect sizes are comparator-dependent, and certainty of evidence for absolute blood pressure control achievement and for major adverse events is very low; heterogeneity, limited long-term data, and a predominance of Asian-population trials warrant cautious interpretation pending larger, higher-quality, and more geographically diverse confirmatory studies.

Humans↗

PubMed2026

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n = 65) or routine nursing only (n = 65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6 months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6 months ranged from small for resilience (D = 0.28) and avoidance coping (D = 0.26) to moderate for confrontation coping (D = 0.60) and resignation coping reduction (D = -0.51), and large for attributional style (D = 0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans↗

PubMed2026

Surgical management and outcomes of total colonic aganglionosis in children: A systematic review and meta-analysis.

AIM: Total colonic aganglionosis (TCA) is a rare form of Hirschsprung disease, and there is no consensus regarding its optimal surgical management. This systematic review and meta-analysis aimed to evaluate different surgical approaches and outcomes in children with TCA. METHODS: A systematic search of PubMed/MEDLINE and Embase was performed for studies published between January 2000 and December 2025. The review followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251078401). Eligible studies included patients aged ≤18 years with TCA who underwent conventional pull-through procedures (CPT; Duhamel, Soave, Swenson, Rehbein, and Ikeda-Soper) or non-conventional techniques (NCPT; STATE procedure, J-pouch, right- or left-sided colonic patch pull-through, and ileocecal patch). A subgroup analysis comparing Duhamel and ileoanal pull-through procedures (IAPT) was also performed. Outcomes included fecal incontinence, Hirschsprung-associated enterocolitis (HAEC), requirement for additional interventions, postoperative intestinal obstruction, and mortality. Meta-analysis was performed using jamovi software, version 2.3.28, with p < 0.05 considered statistically significant. RESULTS: Seven studies including 134 patients compared CPT (n = 85) with NCPT (n = 49), and ten studies including 274 patients compared Duhamel (n = 143) with IAPT (n = 131). Across both comparisons, pooled odds ratios (ORs) showed no statistically significant differences in fecal incontinence, HAEC, requirement for additional interventions, postoperative intestinal obstruction (Duhamel vs IAPT only), or mortality. For CPT versus NCPT, the pooled ORs were 1.1 for fecal incontinence (95% CI, 0.44-2.73; p = 0.837), 1.1 for HAEC (95% CI, 0.49-2.71; p = 0.743), 4.3 for requirement for additional interventions (95% CI, 0.86-22.1; p = 0.074), and 3.4 for mortality (95% CI, 0.52-21.5; p = 0.198). For Duhamel versus IAPT, the pooled ORs were 1.4 for fecal incontinence (95% CI, 0.60-3.36; p = 0.423), 0.6 for HAEC (95% CI, 0.22-2.06; p = 0.503), 1.8 for requirement for additional interventions (95% CI, 0.62-5.50; p = 0.262), 1.1 for postoperative intestinal obstruction (95% CI, 0.21-6.01; p = 0.875), and 1.03 for mortality (95% CI, 0.25-4.20; p = 0.965). CONCLUSION: No statistically significant differences were identified between CPT and NCPT or between Duhamel and IAPT for the evaluated outcomes in children with TCA. However, the absence of statistically significant differences should not be interpreted as evidence of equivalence, particularly given the small sample sizes, wide confidence intervals, and clinical and methodological heterogeneity of the studies included. The choice of surgical approach should be individualized according to disease extent, patient-specific factors, institutional experience, and surgical expertise. TYPE OF STUDY: Meta-analysis. LEVEL OF EVIDENCE: III.

Humans↗

PubMed2026

Diagnostic performance of panfungal PCR on tissue specimens for the diagnosis of invasive fungal diseases: a systematic review and meta-analysis of the Fungal PCR Initiative (FPCRI).

UNLABELLED: Invasive fungal diseases are difficult to diagnose because of the limited sensitivity of culture. Panfungal PCR amplicon sequencing assays (targeting ribosomal RNA, such as 18S, 28S, ITS) are recommended for fungal identification in histopathology samples showing fungal elements. However, data describing its overall performance and consistency are lacking. This systematic literature review and meta-analysis assessed the performance of panfungal PCR on formalin-fixed paraffin-embedded (FFPE) and non-fixed (fresh or frozen) tissue samples. A systematic literature search was performed to include studies reporting the use of panfungal PCR for fungal identification in FFPE or non-fixed tissue samples. PCR sensitivity and specificity were assessed using the reference standard of histopathology showing fungal elements. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled estimates were obtained using random-effects meta-analysis. Twenty-eight studies were included. In FFPE samples (18 studies, 852 samples), sensitivity and specificity were 75.4% (95% confidence interval [CI], 59.2-86.6) and 93.5% (70.2-98.9), respectively. Sensitivity in non-fixed samples (13 studies, 207 samples) was 86.5% (74.7-93.3), while specificity could not be assessed (insufficient data). Comparative analyses showed a significantly higher sensitivity of panfungal PCR over culture (88.2%; 76-94.7 vs 52.2%; 39-65, P = 0.001). Sub-analyses could not demonstrate the superiority of one PCR target over another due to limited data. Panfungal PCR exhibited adequate sensitivity and good specificity in FFPE samples. Sensitivity was even higher in non-fixed samples and largely superior to culture. Nevertheless, large interstudy variability was observed, warranting interlaboratory studies to define the optimal PCR target and standardized protocols. IMPORTANCE: Invasive fungal diseases are difficult to diagnose because of the low sensitivity of culture. Panfungal PCRs are widely used for fungal identification in tissue specimens but suffer from heterogeneous procedures and performance. This meta-analysis shows an acceptable sensitivity (75.4% and 86.5% in fixed and non-fixed samples, respectively) and good specificity (93.5%) of panfungal PCR, supporting its use, not only on histopathology-positive fixed samples but also in non-fixed samples concomitantly with other diagnostic tools (cultures and fungal-specific PCRs if available). These results provide a strong basis for further standardization of panfungal PCR techniques via interlaboratory assays to assess reproducibility and optimize analytical protocols. CLINICAL TRIALS: This study is registered with PROSPERO as CRD42023461148.

Humans↗

PubMed2026

GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid® platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I2 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings.

Journal Article↗