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PubMed2026

Single-slice Functional Lung MRI During Metronome-Paced Tachypnea Detects Changes in Regional Ventilation Dynamics After a Single Dose of Dual Bronchodilator Treatment in COPD.

Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.

Humans↗

PubMed2026

Gonadal function and fertility outcomes after orchiopexy versus orchiectomy for testicular torsion: A systematic review and meta-analysis.

PURPOSE: To review the early and late changes in hormonal profiles, semen parameters, and clinical outcomes in patients treated with orchiopexy versus orchiectomy for testicular torsion. METHODS: A systematic search was conducted across MEDLINE, Scopus, Web of Science, Cochrane Library, and other databases, following PRISMA guidelines. PRIMARY OUTCOMES: FSH, LH, testosterone, inhibin-B, and semen parameters. Quality was assessed using the Newcastle-Ottawa Scale. Certainty of evidence was evaluated using the GRADE framework. Statistical analysis was performed using the random-effects model. RESULTS: Eleven studies involving 538 participants (197 orchiectomy, 341 orchiopexy) were included. Orchiectomy was associated with a significant increase in FSH (SMD: 1.63, P < 0.0001) and LH (SMD: 1.31, P < 0.0001) compared to orchiopexy. However, testosterone (MD: 0.31 ng/mL; P = 0.4) and inhibin-B (SMD: -0.14; P = 0.87) levels were comparable between groups. Regarding semen parameters, orchiectomy resulted in a significant reduction in sperm concentration (MD: -18 million/mL, P = 0.01). No significant differences were found in sperm count (MD: 13.9 million; P = 0.43), normal morphology (MD: 4.97%; P = 0.12), or total motility (MD: 4.05%; P = 0.49). The pooled rate for ipsilateral atrophy following orchiopexy was 38%, which likely depends on ischemia duration. CONCLUSION: Surgical choice in testicular torsion does not significantly affect the overall hormonal balance or most semen parameters due to compensatory mechanisms of the hypothalamic-pituitary-gonadal axis. Clinical decisions should consider individual case factors, as we lack reliable data on subsequent paternity rates.

Male↗

PubMed2026

Evaluation of one-step amplicon-based targeted enrichment for SARS-CoV-2 whole-genome sequencing using the Midnight amplicon scheme.

Genomic surveillance proved invaluable during the COVID-19 pandemic for tracking SARS-CoV-2 variants and guiding outbreak responses, underscoring the ongoing need to reduce whole-genome sequencing (WGS) costs and improve workflow efficiency to ensure accessibility in resource limited settings. Here, we evaluated a one-step reverse transcription polymerase chain reaction (RT-PCR) approach using the Midnight V2 primer scheme for targeted amplification of the SARS-CoV-2 genome, assessed its compatibility with Illumina sequencing, and compared its performance to a well-established two-step method. Initially, we determined optimal RT-PCR reaction conditions using the Midnight V2 primer panel for the one-step RT-PCR kit and scaled reaction volumes for both RT-PCR and library preparation. Clinical specimens (n = 53) that had undergone routine WGS for surveillance purposes using the established two-step RT-PCR method were compared using the one-step RT-PCR assay. For samples with genome completeness greater than 70%, both methods gave comparable results with similar sequence coverage and 100% concordance for lineage assignment. Further investigation revealed a higher percentage of reads aligning to the SARS-CoV-2 genome with a greater depth of coverage using the one-step method compared to the two-step method. Finally, analysis of scaled one-step and library reaction volumes revealed significant cost savings for samples undergoing WGS. Overall, the results presented here verify the accuracy and reproducibility of one-step targeted amplification and offer an efficient and cost-effective workflow for routine SARS-CoV-2 genomic surveillance.

Humans↗

PubMed2026

Extender-dependent effects of reduced glutathione on post-thaw boar sperm quality: A systematic review and meta-analysis.

Supplementation of reduced glutathione (GSH) in freezing media has been proposed to improve post-thaw boar sperm quality, although reported findings remain inconsistent. This study aimed to quantitatively evaluate the effects of reduced glutathione on post-thaw sperm quality through a systematic review and meta-analysis. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Scopus, PubMed, CAB Direct, EBSCOhost, and Google Scholar were systematically searched. Based on predefined inclusion and exclusion criteria, 15 in vitro studies comprising 19 experiments were included. Four outcomes were analyzed: total motility, progressive motility, viability, and acrosome integrity. Standardized mean differences (SMD) were calculated using random-effects models. Heterogeneity was assessed using Cochran's Q test, and the I2 statistic. Publication bias was evaluated using funnel plots, Egger's test, and trim-and-fill analysis, while sensitivity analyses were performed using Baujat plots and leave-one-out analysis. Reduced glutathione was positively associated with total motility (SMD = 0.74; 95% CI: 0.42-1.05; P<0.001), progressive motility (SMD = 0.90; 95% CI: 0.21-1.58; P=0.014), viability (SMD = 0.67; 95% CI: 0.11-1.23; P=0.022), and acrosome integrity (SMD = 0.72; 95% CI: 0.32-1.12; P=0.002). Low to high heterogeneity was observed across outcomes, indicating variability in the estimated effects across studies. Significant subgroup differences were identified according to GSH concentration, freezing media, and thawing media. Overall, the available evidence suggests a possible positive association between GSH supplementation and several post-thaw sperm quality parameters, although these subgroup findings are exploratory and require confirmation in well-standardized experimental studies.

Animals↗

PubMed2026

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets + vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans↗

PubMed2026

Comparative Efficacy of Non-opioid Analgesic Drugs for Chronic Cancer Pain: A Bayesian Network Meta-analysis.

PURPOSE: While opioids remain the primary pharmacological intervention for cancer pain management, their clinical utility is frequently compromised by dose-limiting toxicities. This study aimed to determine the comparative efficacy, opioid-sparing potential, and clinical hierarchy of non-opioid adjuvant drug classes. The study was structured around the PICO framework to evaluate the pharmacological strategies currently utilized in multimodal clinical oncology. METHODS: A systematic search of electronic databases (PubMed, Embase, Cochrane) was conducted for randomized controlled trials (RCTs) published between 2000 and 2025. The primary outcome was global analgesic efficacy (standardized mean difference [SMD]), while secondary outcomes included the opioid-sparing effect, defined as the percentage reduction in morphine equivalent daily dose (MEDD) and the incidence of treatment-emergent adverse events (Harms). A Bayesian network meta-analysis (NMA) was performed to rank treatments using SUCRA values. The methodological quality was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RESULTS: Twenty-three RCTs (n = 1845) met the inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (-1.10) and anticonvulsants (-1.06) demonstrated the most robust analgesic effects. The SUCRA ranking confirmed a clear hierarchy, with the combination of anticonvulsants and antidepressants showing the highest probability of efficacy. A significant opioid-sparing effect was observed for gabapentinoids and ketamine, facilitating MEDD reduction. While serious adverse events were rare, minor harms (somnolence, dizziness) were more frequent in the most effective classes. CONCLUSION: Our NMA provides a robust evidence base for a "Clinical Tier" system, ranking adjuvants by their balance of efficacy and safety. These findings support the early integration of Tier I agents (anticonvulsants and NSAIDs) to optimize pain control and reduce opioid-related toxicities in chronic cancer pain management.

Humans↗

PubMed2026

Interventions with a significant mortality difference in acute respiratory distress syndrome: A systematic review and comparison with Guidelines.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) has a high mortality rate. European Society of Intensive Care Medicine (ESICM) and American Thoracic Society (ATS) Guidelines are the worldwide reference for clinicians in management of ARDS. Mortality represents one of the most important outcomes in intensive care practice and randomized controlled trials (RCTs) the highest level of evidence. We compared Guidelines recommendations with RCT results to highlight differences and find potential new therapeutic opportunities. METHODS: We performed a systematic review of all RCTs reporting a statistically significant mortality difference in ARDS and a subsequent comparison with ESICM and ATS Guidelines recommendations. RESULTS: We identified 33 RCTs and 23 interventions with mortality difference in ARDS patients. Seven interventions relate to invasive ventilation strategies, two to noninvasive ventilation strategies, one to extracorporeal membrane oxygenation (ECMO), 12 to drugs and one to nutritional support. In 25/33 (76%) RCTs the intervention was associated with mortality reduction and in 8/33 with mortality increase (24%). Multicenter studies were 24/33 (73%) while blinding was adopted in 19/33 (58%) studies. Guidelines recommendations supported by RCTs with mortality impact include: the use of low tidal volume ventilation, prone positioning, venovenous ECMO, steroids and the avoidance of high frequency oscillatory ventilation. Eight of the interventions identified were not mentioned by Guidelines but demonstrated reduced mortality, and five further interventions demonstrated increased mortality. CONCLUSIONS: This systematic review highlights potential gaps between RCTs results and Guidelines that could be used to plan future research or highlight topics to be discussed in future Guidelines.

Humans↗

PubMed2026

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p < 0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2 = 50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans↗

PubMed2026

Microbial signal profiles and organism-level concordance between plasma metagenomic sequencing and blood culture in suspected bloodstream infection.

Plasma metagenomic next-generation sequencing (mNGS) and blood culture detect different components of the microbial signal and frequently produce discordant organism reports. We characterized microbial signal class, report-derived burden, organism-level concordance, and independent clinical attribution in a retrospective, single-center, episode-level cohort. Among 329 episodes with evaluable plasma mNGS reports, 315 had blood culture performed; 232 were mNGS positive/culture negative and 53 were positive by both methods. In the 232 discordant episodes, the recorded routine-care diagnosis classified 124 as bloodstream infection (BSI) and 108 as non-BSI. Nonviral signals were present in 78.2% and 42.6%, respectively (P < 0.001), and median maximum report-derived sequence counts were 98.5 and 11.5 (P < 0.001). Two laboratory physicians then independently reviewed source records using structured criteria while masked to the recorded BSI label and mNGS organism and sequence-count information. Initial agreement for the five-category BSI assessment was 97.6% (Cohen's kappa, 0.960). Within the mNGS-positive/culture-negative subgroup, adjudicated BSI likelihood showed a modest ordinal association with report burden (Spearman rho = 0.190; P = 0.004), while mNGS organisms were considered supported in 1 episode, plausible in 158, unlikely or contaminant in 72, and unresolved in 1. Among 53 dual-positive episodes, 33 (62.3%) shared at least one species, but only 5 (9.4%) had complete species-set concordance. Plasma mNGS and blood culture therefore frequently generated non-equivalent organism sets. Signal class and report burden contributed graded contextual evidence, but organism-level attribution required clinical review and orthogonal microbiology rather than binary positivity alone.

Humans↗

PubMed2026

Risk prediction models for blood transfusion in patients undergoing total hip and knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and evaluate published risk prediction models for perioperative blood transfusion in patients undergoing total hip or knee arthroplasty (THA/TKA). METHODS: We systematically searched PubMed, Web of Science, the Cochrane Library, and Embase from inception to May 31, 2025. Two researchers independently screened the literature, extracted data, and assessed the risk of bias and applicability using the Prediction model Risk Of Bias Assessment Tool (PROBAST). The area under the receiver operating characteristic curve (AUC) values were pooled via a meta-analysis using Stata 18.0. RESULTS: d Fourteen studies containing 36 prediction models were included. The incidence of blood transfusion among THA/TKA patients ranged from 3.2% to 30.8%. Preoperative hemoglobin (Hb) level, tranexamic acid (TXA) use, operative duration, intraoperative blood loss, and age were the most frequently incorporated predictors. Model sensitivity ranged from 58% to 94.5%, and specificity ranged from 71.3% to 94%. Meta-analysis showed that the pooled AUC value of the 13 validated models was 0.87 (95% CI: 0.85-0.90), suggesting good discriminatory performance. All models were rated as having a high risk of bias. The applicability of four studies was rated as unclear. CONCLUSION: Although the included studies demonstrated promising discriminative ability of prediction models for blood transfusion in THA/TKA, all were assessed as having a high risk of bias using the PROBAST tool. Therefore, future research should prioritize the development of models with larger sample sizes, rigorous study designs, and multicenter external validation.

Humans↗

PubMed2026

Should we consider excessive weights in pediatric kidney transplant recepient candidates?: A systematic review and meta-analysis of kidney transplantation outcomes.

INTRODUCTION: In adult populations, excess body weight has been associated with an increased risk of adverse clinical outcomes and mortality following kidney transplantation. In contrast, the influence of obesity on transplantation outcomes among pediatric populations is not yet fully understood. This study aimed to evaluate the association between pre-transplant excess weight and post-transplant outcomes in pediatric kidney transplant recipients. MATERIAL & METHODS: A systematic literature search was performed across PubMed, ScienceDirect, and the Cochrane Library, covering publications up to December 31, 2025. The quality of the included studies was evaluated using the ROBINS-E tool. Statistical analysis was conducted using Review Manager version 5.4. RESULTS: From a total of 1465 records screened, six studies that included 65,483 participants were selected in the meta-analysis. The results indicated that pre-transplant excess weight was significantly associated with an increased risk of acute rejection (OR = 1.09; P = 0.009), delayed graft function (OR = 1.17; P < 0.00001), 1-year graft failure (OR = 1.16; P = 0.0002), and 5-year graft failure (OR = 1.13; P = 0.009). Although 5-year mortality was also higher among recipients with excess weight, this association was not statistically significant (OR = 1.08; P = 0.11). CONCLUSION: Pediatric patients with pre-transplant excess weight had higher post-transplant odds of acute rejection, delayed graft function, and both 1-year and 5-year graft failure compared to those without excess weight. These findings highlight the importance of assessing and managing excess weight prior to kidney transplantation to help prevent adverse outcomes in the future.

Humans↗

PubMed2026

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a ≥ 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans↗

PubMed2026

Granger connectivity and graph-theoretical analysis of scalp EEG across the preictal to ictal transition for presurgical evaluation.

OBJECTIVE: To assess the feasibility of estimating lateralization and localization of the epileptogenic zone (EZ) in temporal and extratemporal lobe epilepsy by combining Electric Source Imaging (ESI) with functional connectivity analysis of high-density EEG from the preictal to the ictal phase. METHODS: Adults with drug-resistant focal epilepsy and at least one recorded seizure during 40- or 64 channels EEG monitoring were retrospectively included. Granger causality and hubness centrality were computed over the 10-s preictal interval and the first 5 s of the ictal period, with ictal onset defined as the first EEG change identified by experienced epileptologists. The reference standard for EZ localization was based on resective surgical outcome or stereo-EEG findings. RESULTS: Thirteen patients (7 females; median age 35 years) were included. Connectivity analyses showed higher concordance with clinical findings during the preictal phase than during the ictal phase for both lateralization (91% vs 46%) and localization (73% vs 27%). Performance was highest in temporal (7/7 lateralization; 6/7 localization) and frontal lobe epilepsy (2/2 for both), and lower in parieto-occipital epilepsy (1/2 and 0/2, respectively). In two cases with poor surgical outcome or no surgical indication, connectivity findings were discordant with clinical estimates. CONCLUSIONS: Connectivity analysis across the preictal to ictal transition provides relevant lateralizing and localizing information, particularly in temporal and frontal lobe epilepsy, and may reveal clinically meaningful discordance. SIGNIFICANCE: Integrating high-density EEG, ESI, and functional connectivity during the phase preceding the first EEG change may support non-invasive presurgical evaluation.

Humans↗

PubMed2026

Positive conversion of latent tuberculosis screening in patients with inflammatory bowel disease on antitumor necrosis factor alpha drugs: a systematic review and meta-analysis.

Inflammatory bowel disease (IBD) patients undergoing antitumor necrosis factor-alpha (anti-TNF) therapy are at increased risk of developing tuberculosis (TB), making screening before anti-TNF initiation mandatory. Repeated screening during treatment is not yet recommended because of a lack of studies to support this practice. We aimed to determine the proportion of patients who develop latent TB during anti-TNF therapy. We systematically searched studies from MEDLINE, Embase, and Lilacs, and performed a single-arm meta-analysis investigating the positive conversion rate in IBD patients under anti-TNF therapy with previous negative TB screening. We calculated the combined proportion with 95% confidence interval, using the random-effects model. A P value less than 0.05 was considered statistically significant for subgroup differences. We included 13 studies from nine countries with 1153 patients. The overall positive conversion rate was 9.20%. Portugal had 18.01% of positive conversion, Spain 4.51%, and the USA 1.11%. Tests for subgroup differences were statistically significant for subgroup analysis by country and consistency of test used (performig same test as baseline). Subgroup analyses by continent, study design, or specific test (tuberculin skin test or interferon-gamma release assay) showed no statistical difference. Meta-regression analysis showed a significant positive association between positive conversion and TB incidence. In conclusion, IBD patients on anti-TNF therapy can have a positive conversion rate of 9.20%. Higher conversion rates were seen in European and Asian studies compared with those in the Americas (particularly the USA). TB prevention strategies should, therefore, be individualized and based on geographic location and risk factors.

Humans↗

PubMed2026

Genetic evidence for a causal relationship between melatonin metabolism and depression.

To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR = 1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Melatonin↗

PubMed2026

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPARα, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPARα expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

Animals↗

PubMed2026

Current Concepts and Emerging Technologies in Aesthetic Outcome Assessment of Breast Reconstruction.

Aesthetic outcomes are a crucial determinant of the overall success of breast reconstruction. Recently, aesthetic assessment has evolved from relying mainly on subjective impressions to incorporating more quantitative methods. This systematic review summarizes current concepts and emerging technologies in aesthetic outcome assessment after breast reconstruction. A comprehensive search of studies evaluating aesthetic outcomes following implant-based, autologous or hybrid breast reconstruction was performed between 2000 and 2025. Assessments were classified as subjective or objective. Extracted variables included assessment characteristics, aesthetic outcome domains, and patient-centered outcomes. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Levels of evidence were classified according to the Oxford Centre for Evidence-Based Medicine. A total of 51 studies involving 7711 participants from 16 countries were included. Subjective tools were most frequently employed, led by the BREAST-Q (35/51, 69%), followed by expert- or panel-based evaluations (17/51, 33%) and the visual analog scale (2/51, 4%). Objective methods were applied in 19 studies and included 3-dimensional surface imaging (8/51, 16%), BCCT.core (7/51, 14%), eye tracking (3/51, 6%), and artificial intelligence-based analyses (3/51, 6%). Although subjective tools captured satisfaction with breast appearance, objective tools quantified morphological parameters and positional landmarks. BREAST-Q remains the cornerstone of outcome evaluation after breast reconstruction, providing patient-centered perspectives, including, but not limited to, aesthetic perception. A progressive shift toward multimodal evaluation was noticed, as no single modality comprehensively addressed all aesthetic domains. Future research should focus on integrating subjective and objective assessment methods within a unified framework. Level of Evidence: 3 (Therapeutic) For image description, please refer to the figure legend and surrounding text.

Humans↗

PubMed2026

Endoscopic Ultrasound-Guided Versus Transjugular Portal Pressure Measurements: Systematic Review and Meta-Analysis.

PURPOSE: Published reviews of endoscopic ultrasound-guided portal pressure gradient (EUS-PPG) have emphasized feasibility and safety. We performed a systematic review and meta-analysis specifically to evaluate how closely EUS-based portal pressure measurements track invasive comparator measurements in prospective paired studies and to summarize agreement, technical success, and adverse events. METHODS: We searched major databases through January 2026 for prospective cohorts reporting same-patient EUS-based portal pressure measurement and invasive hemodynamic measurements. Correlations were pooled with random-effects models and analyzed separately for studies comparing EUS-PPG with hepatic venous pressure gradient (HVPG) and studies comparing EUS-based portal measurements with direct portal venous pressure. Agreement and threshold discordance were summarized descriptively. RESULTS: Six prospective cohorts (127 attempted procedures) were included. In studies using HVPG as the comparator, the pooled correlation was 0.82 (95% CI, 0.72-0.89; I2 = 0%). In studies comparing EUS-based portal measurements with direct portal venous pressure, the pooled correlation was 0.86 (95% CI, 0.72-0.93; I2 = 16.9%). Technical success was 95.3%. EUS-PPG-attributed adverse events occurred in 2.4% of procedures, with no procedure-related deaths. Agreement data were limited. Reported limits of agreement were wide (approximately - 6 to + 7 mmHg), and discrepancies of 5 mmHg or greater occurred in 4 of 30 paired measurements. CONCLUSIONS: EUS-based portal pressure measurement is feasible and shows a strong association with invasive hemodynamic comparators, but the evidence base remains small (six cohorts, 127 attempted procedures). Further study will be necessary to establish patient-level agreement, procedural reproducibility, EUS-specific clinically significant portal hypertension thresholds, and whether HVPG-based decision thresholds can be transferred to EUS-derived measurements.

Humans↗