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PubMed2026

Complete Revascularization Guided by Functional Coronary Angiography in STEMI.

BACKGROUND: Complete coronary-artery revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the preferred strategy for identifying nonculprit lesions that warrant treatment remains uncertain. METHODS: In this international, randomized trial, we assigned patients with STEMI and multivessel disease in whom the culprit lesion had been successfully treated to undergo complete coronary-artery revascularization guided by functional coronary angiography (physiology-guided group) or by conventional angiography (angiography-guided group). The primary outcome was a composite of death from any cause, myocardial infarction, cerebrovascular accident (stroke or transient ischemic attack), or ischemia-driven revascularization, assessed in a time-to-event analysis. The primary safety outcome was a composite of contrast-associated acute kidney injury or major bleeding. RESULTS: A total of 1823 patients underwent randomization; 913 were assigned to the physiology-guided group and 910 assigned to the angiography-guided group. The median age of the patients was 66 years (interquartile range, 58 to 76), and 24% were women. At a median follow-up of 17.9 months, a primary-outcome event had occurred in 81 patients (8.9%) in the physiology-guided group and in 125 patients (13.7%) in the angiography-guided group (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.83; P<0.001). A primary-safety-outcome event occurred in 42 patients (4.6%) in the physiology-guided group and in 65 patients (7.1%) in the angiography-guided group (hazard ratio, 0.63; 95% CI, 0.43 to 0.93; P = 0.02). CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease, a strategy of complete coronary-artery revascularization guided by functional coronary angiography resulted in a lower risk of a primary-outcome event (death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization) than a strategy guided by conventional angiography. (Funded by the Italian Health Ministry and others; AIR-STEMI ClinicalTrials.gov number, NCT05818475.).

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PubMed2026

Prevalence of Breastfeeding in Infants With Down Syndrome: A Systematic Review and Meta-Analysis.

AIM: To estimate the prevalence of breastfeeding-overall, exclusive, partial and depending on infants' age-in infants with Down syndrome, and to investigate associated factors. METHODS: A systematic literature search was conducted in Medline, Cochrane Library, Web of Science, Embase, CINAHL and SciELO up to 1 August 2024. Original articles that estimated the prevalence of breastfeeding in infants with Down syndrome, written in French, English or Spanish, were included. Study quality was assessed using the Joanna Briggs Institute (JBI) scale. Meta-analyses were performed for breastfeeding outcomes and meta-regression explored heterogeneity. The review was registered in PROSPERO (CRD42021278019). RESULTS: Twenty-six studies (3463 infants) were included. The estimated prevalence of overall breastfeeding regardless of duration was 71.6% (95% CI [60.3; 80.7]; 25 studies, 3351 infants) with high heterogeneity, I2 = 94%. The estimated prevalence of exclusive breastfeeding was 38.4% (95% CI [22.4; 57.3]; 10 studies, 1099 infants). No factor assessed in meta-regression was significantly associated with overall breastfeeding. CONCLUSION: The estimated breastfeeding prevalence in infants with Down syndrome is similar to that reported in the general population, despite high heterogeneity. Further studies using standardised methodology to assess breastfeeding barriers and facilitators in the context of Down syndrome would allow us to improve support for breastfeeding.

Humans↗

PubMed2026

Characterizing Caregiver-Child Interactions Through a Transactional Lens: A Baseline Analysis of a Caregiver-Implemented Intervention.

PURPOSE: This study was motivated by the transactional model of development and examined the reciprocal influences that children and caregivers have on caregiver-child interactions (CCXs) prior to a caregiver-implemented intervention. We tested whether child communication characteristics were associated with caregiver strategy use and whether these strategies, in turn, influenced children's communication to understand how caregivers and children mutually shaped the language learning environment. METHOD: Caregiver-child dyads (N = 105) were participants in a randomized controlled trial. CCXs were collected when children were approximately 30 months of age, transcribed, and coded for four caregiver language facilitation strategies and child communication variables. RESULTS: Least Absolute Shrinkage and Selection Operator regression and postselection inference indicated that child communication characteristics in CCXs were associated with both the frequency and type of strategies caregivers used. Children's overall communication acts were significantly associated with caregiver use of vocabulary strategies, whereas children's vocabulary diversity was significantly associated with caregiver use of sentence strategies. Mixed-effects logistic regression demonstrated that all four caregiver strategies significantly increased the likelihood of spontaneous lexical overlap in subsequent child turns. CONCLUSIONS: Prior to the intervention, caregivers and children reciprocally shaped the language environment. This supports a transactional perspective and warrants further consideration of reciprocal influences when assessing the impact of caregiver-implemented interventions. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.32995796.

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PubMed2026

Bivalirudin Versus Heparin in Low and Non-Low Bleeding Risk Patients Undergoing Primary PCI for STEMI: The BRIGHT-4 Trial.

BACKGROUND: In the BRIGHT-4 trial, among 6,016 patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with a radial artery approach, procedural anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2 to 4 hours reduced the 30-day primary composite outcome of all-cause death or Bleeding Academic Research Consortium (BARC) types 3 to 5 bleeding, as well as death and bleeding individually, compared with heparin monotherapy. OBJECTIVES: We sought to determine whether the benefits of bivalirudin apply principally to patients who are at low bleeding risk (LBR) as well as non-LBR. METHODS: In a prespecified analysis from BRIGHT-4, outcomes were examined by baseline bleeding risk, with LBR defined as a CRUSADE score <30. RESULTS: At baseline, 4,581 patients (76.1%) were categorized as LBR. Non-LBR patients had higher rates of the 30-day primary endpoint (8.6% vs 2.2%; HR: 4.08 [95% CI: 3.14-5.31]; P < 0.0001), driven by both greater mortality and BARC types 3 to 5 bleeding. In non-LBR patients, the primary outcome occurred in 8.1% of patients randomized to bivalirudin vs 9.2% of those randomized to heparin (difference: -1.1% [95% CI: -4.0% to 1.8%]; HR: 0.88 [95% CI: 0.62-1.26]). In LBR patients, the primary outcome occurred in 1.4% of patients randomized to bivalirudin vs 2.9% of those randomized to heparin (difference: -1.5% [95% CI: -2.3% to -0.6%]; HR: 0.49 [95% CI: 0.32-0.75]) (Pabsolute interaction = 0.81; Prelative interaction = 0.04). The effects of bivalirudin compared with heparin in reducing all-cause death were as robust in LBR patients compared with non-LBR patients (Pabsolute interaction = 0.67; Prelative interaction = 0.06). CONCLUSIONS: Among patients with STEMI undergoing primary PCI with radial artery access, procedural anticoagulation with bivalirudin plus a high-dose post-PCI infusion for 2 to 4 hours reduced the 30-day risk of all-cause death and major bleeding in patients at low bleeding risk as well as in patients at higher-risk of bleeding. (Bivalirudin With Prolonged Full Dose Infusion Versus Heparin Alone During Emergency PCI [BRIGHT-4; NCT03822975]).

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PubMed2026

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24 hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125 mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95% CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

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PubMed2026

Second-Generation ELZA-sub400 Protocol: Individualized High-Fluence Cross-Linking for Ultra-Thin Keratoconus Corneas.

PURPOSE: To evaluate the safety and efficacy of a second-generation individualized corneal cross-linking (CXL) protocol (ELZA-sub400) using high-fluence UV-A irradiation in ultrathin ectatic corneas. DESIGN: Retrospective, single-center, consecutive interventional case series. METHODS: Twenty-nine eyes of 24 patients with progressive keratoconus or post-LASIK ectasia and a post-soak intraoperative thinnest stromal thickness <400 µm were included. After epithelial removal and riboflavin soaking, continuous UV-A irradiation (365 nm) at 3 or 9 mW/cm² was delivered with total fluence titrated up to 10 J/cm² based on intraoperative ultrasound pachymetry and a previously published nomogram targeting an uncross-linked stromal margin of approximately 70 µm above the endothelium. Outcomes were assessed at baseline and up to 12 months using corrected distance visual acuity (CDVA) and corneal parameters measured using Scheimpflug tomography and anterior segment OCT (AS-OCT) with Placido-based topography. The main outcome measure was the proportion of eyes without progression at 12 months, defined as <1.0 D increase in maximum keratometry (Kmax). Secondary outcomes included changes in CDVA, refraction, Kmax, stromal thickness, demarcation line depth, densitometry, and safety parameters. RESULTS: At 12 months, 22/29 eyes (76%; 95% CI, 57.9%-87.8%) met the nonprogression criterion. Mean change in Kmax was -0.77 ± 5.10 D (95% CI, -2.71 to 1.17; P = .418). Mean demarcation line-to-anterior stroma distance was 205 ± 64 µm (95% CI, 180.7-229.3), and demarcation line-to-endothelium distance was 64 µm (IQR, 49-152). All demarcation lines remained within the stromal layer; 15/29 eyes (51.7%) had a demarcation line located ≤70 µm from the endothelium. Median CDVA changed from 0.10 to 0.32 logMAR (P = .142). Minimum stromal thickness showed a median change of -4.0 µm (P = .309). No significant change was observed in densitometry, and no eye developed deep stromal haze or endothelial decompensation. CONCLUSIONS: Second-generation ELZA-sub400 CXL halted ectasia progression in 76% of ultrathin corneas at 12 months and was associated with an acceptable short-term safety profile, including stromal-confined demarcation line formation and no observed endothelial decompensation. The numerical decline in spectacle CDVA observed in this severely affected cohort did not reach statistical significance but is clinically important and warrants confirmation in larger prospective studies.

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PubMed2025

Evaluation of Prevalence of Obstetric Violence and its Associated Factors: A Systematic Review and Meta-Analysis.

Obstetric violence (OV) begins with a woman's initial contact with a health institution and can persist throughout pregnancy, labor, and the postpartum period. Despite this, previous research has largely focused on the labor process. This systematic review and meta-analysis aimed to determine the prevalence and associated factors of OV experienced by women during pregnancy, labor, or the postpartum period. We conducted systematic searches in five electronic databases (Web of Science, Scopus, CINAHL Ultimate, MEDLINE Ultimate, and OVID) between April 27 and August 7, 2024. Studies were included if they involved women aged 18 and above who experienced mistreatment, abuse, disrespect, or OV during pregnancy, childbirth, or the postpartum period; employed quantitative cohort, descriptive, or cross-sectional designs; were written in English; reported the prevalence of OV and/or associated factors; and were published between January 1, 2007 and December 31, 2023. Data synthesis involved meta-analysis, meta-regression, and narrative synthesis methods. A total of 41 studies, including 43,977 participants from 17 countries, were included. The meta-analysis revealed that the pooled prevalence of OV was 61.7% (95% CI [0.549, 0.680]; I²: 99.258%). The meta-regression analysis showed that variables such as the country of study, income level of countries, study setting, study design, and risk of bias had statistically significant effects on OV. In addition, 40 risk factors and 14 protective factors were identified through narrative synthesis. This highlights the high prevalence of OV and the need to address the associated factors.

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PubMed2026

Associations between multiple essential trace metal concentrations and risk of hyperuricemia: insights from a central Chinese population.

Previous studies have indicated that levels of individual essential trace metals are related to hyperuricemia (HUA), but evidence on their combined effects is limited. To address this gap, the associations of individual and joint levels of 12 essential trace metals (manganese, selenium, nickel, chromium, cobalt, tin, iron, molybdenum, zinc, strontium, vanadium, and copper) with the risk of HUA were investigated in 2,021 adults recruited from Hunan Province, China. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to determine urinary metal concentrations. Logistic regression, Bayesian kernel machine regression (BKMR), and quantile g calculation (Qgcomp) were applied to evaluate the associations of single and mixture metal concentrations with HUA. Of the participants, 516 (25.53%) were diagnosed with HUA. Inverse associations were found between vanadium, chromium, manganese, iron, cobalt, selenium, strontium, and molybdenum levels and HUA, with ORs ranging from 0.63 to 0.91. Conversely, a positive association was observed between zinc concentration and HUA [OR (95% CI): 1.17 (1.01, 1.37)]. Both BKMR and Qgcomp models showed a negative overall effect of essential trace metals on HUA risk, with strontium (- 43.6%) and vanadium (- 27.8%) being the main contributors. In addition, formal interaction tests revealed significant effect modification by age for tin and by BMI for zinc. In conclusion, the levels of essential trace metals were linked to a decreased risk of HUA, and these associations were modified by age and BMI only for specific metals.

Humans↗

PubMed2025

Enhanced fracture detection on radiographs with AI assistance for clinicians: a systematic review and meta-analysis.

BACKGROUND: Emergency radiographic interpretation for fractures is prone to missed or misdiagnoses. Artificial intelligence (AI) is expected to become a powerful tool to assist clinicians in fracture detection. PURPOSE: A systematic review and meta-analysis was performed to assess whether AI improves clinicians' ability to detect fractures on radiographs. MATERIALS AND METHODS: A literature search was conducted in PubMed, Web of Science, and Cochrane Library for studies published between January 1, 2010, and October 10, 2025. A meta-analysis of diagnostic accuracy studies was performed using a Summary Receiver Operating Characteristic (SROC) curve. The quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Subgroup analysis and meta-regression were conducted to explore potential sources of heterogeneity. RESULTS: A total of 26 studies were included . The pooled sensitivity of clinicians increased from 77% (95% CI: 72-81) to 87% (95% CI: 83-90) with AI assistance, while the pooled specificity improved from 88% (95% CI: 85-90) to 92% (95% CI: 89-94). The corresponding AUC values were 0.90 (95% CI: 0.87-0.92) before and 0.95 (95% CI: 0.93-0.97) after AI assistance. Eight studies were rated as high risk of bias. Subgroup analysis and meta-regression identified potential sources of heterogeneity, including fracture location, AI model type, high risk of bias, and reference standards. CONCLUSION: AI assistance significantly improves clinicians' diagnostic performance in detecting fractures on radiographs for extremity and trunk fractures.

Humans↗

PubMed2026

Prevalence of psychosis in South Asia: A systematic review and meta-analysis.

BACKGROUND: Psychotic disorders are a major contributor to global disability, yet prevalence data from South Asia which inhabits a quarter of the world's population, remain limited. Reliable estimates are essential for health service planning, policy, and closing the substantial treatment gap. This review provides the first comprehensive synthesis of psychosis prevalence across South Asia. METHODS: We searched PubMed, Embase, Web of Science, Global Health, and Medline to 18 December 2024 for DSM- or ICD-based prevalence studies in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. Cross-sectional and longitudinal studies in community or clinical populations were included. Study quality was assessed using the Joanna Briggs Institute checklist. Random-effects meta-analyses estimated pooled prevalence using the logit transformation. Heterogeneity was explored with meta-regression of key methodological variables (publication year, diagnostic system, residential setting). FINDINGS: Thirty-one studies from five countries were included. Among community-dwelling adults, pooled point prevalence was 0.85% and lifetime prevalence was 1.40%, with inter-country differences (India 1.18%, Pakistan 2.13%, Nepal 2.90%). Clinical samples showed substantially higher proportions of individuals with psychosis in service settings (11.44%), reflecting concentration of cases in treatment-seeking samples. Data for children and adolescents were limited and summarised narratively. Heterogeneity was high across meta-analyses, and exploratory meta-regression did not identify any significant moderators. INTERPRETATION: Psychosis prevalence estimates in South Asia appear higher than global averages but should be interpreted cautiously due to substantial heterogeneity and methodological variation; nevertheless, they highlight the need for culturally sensitive screening, improved detection, and strengthened mental health services.

Humans↗

PubMed2026

Who Is the Ideal Candidate for High-Definition Liposuction? A Systematic Review and Meta-Analysis.

BACKGROUND: High-definition liposuction (HDL) enhanced muscular definition by selectively removing superficial subcutaneous fat. Despite its growing popularity and high satisfaction rates, no consensus exists regarding the ideal candidate. This systematic review evaluates demographic factors, patient selection criteria, and complication rates associated with HDL. METHODS: A systematic review and meta-analysis were conducted utilizing PRISMA-P guidelines. PubMed, Cochrane Library, Embase, and Web of Science were searched for studies published within the past 10 years. Seventeen studies met inclusion criteria, comprising 9570 patients. Study designs included randomized controlled trials, cohort studies, and observational analyses reporting demographics, procedural details, and complications. Standardized data extraction was performed. Pooled analyses were conducted for hematoma and seroma, and univariable meta-regression assessed associations between mean age, BMI, and proportion of female patients with complication rates. RESULTS: Mean age was 36.0 years and mean BMI was 25.8 kg/m 2 (range: 18 to 66); 55% of patients were female. Selection criteria varied; most studies applied BMI thresholds (≤30 to 34 kg/m 2 ) and excluded poorly controlled diabetes, heavy smoking, and thromboembolic history. The abdomen, flanks, and chest were most treated. Mean fat removal was 4268.8 mL, with an average operative time of 235 minutes. Complication rates were low; the pooled incidence of seroma was 7% and hematoma was 1%. Meta-regression showed no significant associations between complications and age, BMI, or sex. Patient satisfaction was high. CONCLUSION: HDL is safe and effective across diverse populations; however, variability in selection criteria and reporting limits evidence-based definitions of ideal candidates. Further prospective studies with standardized reporting are needed.

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PubMed2025

Parent-Mediated Interventions for ASD Under 3 Years: A Systematic Review, Meta Analysis, and Moderator Analyses.

This study aimed to assess the effectiveness of PMIs for ASD under 3 years, and explore potential moderators influencing the effectiveness through moderator analyses. The study searched five English databases for randomized controlled trials (RCTs). The meta-analysis was conducted using a random-effects model to calculate Hedges's g. Subgroup analyses and meta regression assessed the effects of potential moderators on PMIs effectiveness, with evidence quality evaluated using GRADE. A total of 31 RCTs were included in the systematic review, with 26 included in the meta-analysis. The results showed a small overall beneficial effect of PMIs on ASD under 3 years (g = 0.20). Small to trivial positive effects were found in several subdomains, including adaptive skills (g = 0.29), parent responsiveness (g = 0.23), parent-child interaction (g = 0.35), social communication (g = 0.18), and symptoms (g =  - 0.22). However, PMIs did not show statistically significant effects on children's cognitive competence, language, or motor skills domains. Subgroup analysis and meta-regression explored potential moderators, but none significantly influenced the effectiveness of PMIs. The GRADE assessment showed that the certainty of the evidence ranged from moderate to low. This study confirmed that PMIs demonstrate positive effects on children under 3 years old with ASD, and showed beneficial outcomes in most subdomains. However, the evidence was of moderate to low certainty, so these findings should be interpreted with caution. In the future, broader databases and more large-scale, multicenter, high-quality clinical studies are needed to confirm these effects.

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PubMed2026

The association of 25-hydroxyvitamin D deficiency with neuroinflammation and prognosis in HIV-negative cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) in HIV-negative individuals is increasing, yet the role of vitamin D remains unclear. This study investigates serum 25-hydroxyvitamin D [25(OH)D] levels and their clinical implications in HIV-negative CM patients. METHODS: We conducted a retrospective case-control study of 93 HIV-negative CM patients and 191 healthy controls (HCs). Serum 25(OH)D levels, cerebrospinal fluid (CSF) fungal burden, cytokine profiles, the incidence of postinfectious inflammatory response syndrome (PIIRS), and one-year mortality were assessed. Bivariate logistic regression models identified predictors of mortality. RESULTS: CM patients had significantly lower serum 25(OH)D levels than HCs (18.33 vs. 23.69 ng/mL, p < 0.001), with a higher rate of deficiency (<20 ng/mL) in the CM group (59.14% vs. 34.03%, p < 0.001). Lower 25(OH)D levels were associated with elevated CSF levels of IL-6 and IL-8 (p < 0.05). Deficiency was linked to increased PIIRS incidence (43.64% vs. 21.05%, p = 0.028). Bivariate logistic regression showed a protective trend for 25(OH)D levels (OR 0.939, 95% CI 0.877-1.006, p = 0.075), although deficiency was not associated with higher mortality. CONCLUSIONS: Serum 25(OH)D deficiency is prevalent in HIV-negative CM patients and linked to neuroinflammation and increased risk of PIIRS. Serum 25(OH)D levels may serve as a useful prognostic marker, although further research is needed.

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PubMed2026

Maternal prior pregnancy outcome subtype and offspring cryptorchidism: A retrospective case-control study.

OBJECTIVE: To determine whether maternal prior pregnancy outcome subtype and frequency are associated with cryptorchidism in male offspring, and whether first-trimester exogenous progesterone exposure mediates any observed association. MATERIALS AND METHODS: We conducted a hospital-based retrospective case-control study of 1220 mother-son pairs (610 cryptorchidism cases; 610 controls). Maternal prior pregnancy outcome subtype was defined using a prespecified proximal-event approach based on the most recent qualifying pregnancy event before the index pregnancy: no prior pregnancy loss or termination, miscarriage, or pregnancy termination. Subtype-specific frequency was categorized as 0, 1, or ≥2. Adjusted odds ratios (aORs) were estimated using multivariable logistic regression; robustness was examined using 1:1 propensity score matching with conditional logistic regression. Exploratory mediation analysis estimated indirect effects through first-trimester exogenous progesterone exposure. RESULTS: In fully adjusted models, miscarriage was associated with higher odds of cryptorchidism compared with no prior pregnancy loss or termination (aOR 1.97; 95% CI 1.26-3.09), whereas pregnancy termination was not (aOR 1.14; 95% CI 0.86-1.52). In joint subtype-frequency analyses, odds increased with the number of miscarriages (one: aOR 1.74; 95% CI 1.07-2.83; two or more: aOR 3.77; 95% CI 1.22-11.66) and were higher for two or more pregnancy terminations (aOR 1.77; 95% CI 1.10-2.84). Matched analyses were directionally consistent. Mediation analyses suggested a modest indirect effect through first-trimester progesterone exposure for the miscarriage association. CONCLUSIONS: Maternal prior miscarriage was associated with cryptorchidism in male offspring, whereas pregnancy termination showed higher odds only among women with two or more prior procedures. First-trimester exogenous progesterone exposure may account for a modest proportion of the miscarriage-cryptorchidism association.

Humans↗

PubMed2026

Retinal microstructural alterations as early phenotypes of depression in radiogenomics analysis.

BACKGROUND: With the increasing prevalence of depression, there is an urgent clinical need for early screening in depression. The retina offers a promising window for early screening in depression due to its rapid, non-invasive, objective, eye-brain correlated characteristics, but previous research has yielded conflicting alterations in retinal microstructure in depression. METHODS: We screened retinal optical coherence tomography and brain magnetic resonance imaging data in the UK Biobank to enroll 23,225 participants for retinal study of depression occurrence, and 1475 participants for the eye-brain association study. We also used genetic data (ID: ebi-a-GCST90014267 and ukb-d-20,448) from the Integrative Epidemiology Unit Open Genome-Wide Association Study for Mendelian randomization analysis. We used Cox regression to assess the association between retinal microstructure and depression risk, Mendelian randomization to infer causality, and mediation analysis to explore retina-brain pathway association. RESULTS: The Cox regression analysis showed that retinal ganglion cell-inner plexiform layer (GCIPL) thickness remained a significant predictor of depression. The Mendelian randomization analysis indicated a positive statistical association between GCIPL thickness and depression. Moreover, there was a significant positive correlation (all p < 0.001) between the volume of specific depression-related brain regions and the GCIPL thickness. Adjusting for age, sex, and head size, the mediation analysis provided preliminary evidence for a potential anatomical pathway linking retinal GCIPL thickness to depression-related brain regions through primary visual cortex and secondary visual cortex volumes. CONCLUSION: Thickened retinal GCIPL is a potential early phenotype of depression and has a potential association pathway with depression-related brain regions using a radiogenomics approach.

Humans↗

PubMed2026

Diagnostic accuracy of bronchoalveolar lavage fluid-based testing for pulmonary cryptococcosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary cryptococcosis(PC) presents diagnostic challenges because of its non-specific clinical and radiological manifestations. Bronchoalveolar lavage fluid (BALF)-based testing, which includes latex agglutination (LA) and lateral flow assay (LFA), offers a minimally invasive diagnostic method, yet its pooled diagnostic accuracy remains unclear. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Scopus from inception to May 2026. Studies evaluating BALF-based testing for PC with extractable 2 × 2 data were included. The methodological quality of relevant studies was assessed by the QUADAS-2 tool. Pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) were estimated using a bivariate random-effects model. Subgroup analyses were performed by testing method and reference standard type. Heterogeneity was evaluated through paired forest plots, HSROC visualization, and exploratory bivariate meta-regression. RESULTS: The pooled sensitivity was 0.87 (95% CI: 0.81-0.91), and the specificity was 0.99 (95% CI: 0.982 - 0.995). The pooled positive likelihood ratio (PLR) was 88.00 (95% CI: 47.39 - 163.42), the negative likelihood ratio (NLR) was 0.13 (95% CI: 0.09 -0.20), and the DOR was 658.50 (95% CI: 285.36-1519.55). No significant threshold effect or publication bias was detected. Exploratory meta-regression suggested a possible assay-method effect in the joint model (P = 0.03), mainly driven by specificity (P = 0.01). CONCLUSIONS: The study demonstrates the high accuracy of CrAg in BALF for the diagnosis of pulmonary cryptococcosis, supporting its role as an important adjunctive diagnostic tool, particularly when tissue biopsy is not feasible or rapid results are needed. Larger prospective studies with standardized protocols are needed to validate these estimates.

Humans↗

PubMed2026

Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P < 0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

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PubMed2026

Adjunctive middle meningeal artery embolization for chronic subdural hematoma: A systematic review and meta-analysis of eight randomized trials.

BACKGROUND: Randomized trials suggest that adjunctive middle meningeal artery embolization (MMAE) may reduce recurrence in chronic subdural hematoma (CSDH), but potential sources of variability in treatment effects across studies remain poorly understood. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of MMAE and to explore potential study-level sources of between-study heterogeneity. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing MMAE plus surgery versus surgery alone, following PRISMA guidelines. Trial sequential analysis (TSA) was prespecified to assess the robustness of pooled findings. Exploratory mixed-effects meta-regression was performed to examine whether aggregate study-level mean age and anticoagulation use were associated with variability in recurrence outcomes. RESULTS: Eight trials including 1961 patients were analyzed. MMAE plus surgery was associated with a reduction in recurrence compared with surgery alone (RR 0.63, 95% CI 0.46-0.85; I² = 0%), and TSA supported this finding. Although conventional meta-analysis suggested a reduction in reoperation, the TSA findings were more sensitive to analytical assumptions and less robust. Exploratory study-level meta-regression analyses suggested possible associations between recurrence outcomes and mean age or anticoagulation use, although these findings should be interpreted as hypothesis-generating only. Safety outcomes were comparable between groups. CONCLUSIONS: Adjunctive MMAE was associated with reduced recurrence in CSDH. Exploratory analyses evaluating aggregate study-level characteristics were limited by the small number of included trials and the use of aggregate-level data, and should be considered hypothesis-generating only. Further prospective studies are needed to better understand variability in treatment effects.

Humans↗