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PubMed2026

Risk of neurodevelopmental disorders associated with paternal use of valproate during spermatogenesis: a living meta-analysis-version 1.

OBJECTIVE: To evaluate the association of paternal use of valproate during spermatogenesis compared with paternal use of lamotrigine or levetiracetam on offspring risk of neurodevelopmental disorders (NDDs). METHODS: Eligibility criteria: observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate vs lamotrigine or levetiracetam during spermatogenesis. INFORMATION SOURCES: the databases PubMed, Embase, Cochrane Library and Web of Science were systematically searched from January 1995 to October 2025.Synthesis of results and risk of bias: a random-effects model was used to estimate pooled HRs and 95% CI, with heterogeneity assessed using I2 statistic for any NDD.We present a meta-analysis of observational, peer-reviewed studies reporting neurodevelopmental outcomes of children exposed to paternal monotherapy use of valproate versus lamotrigine or levetiracetam during spermatogenesis. Given the major regulatory implications of paternal valproate safety, the recent emergence of new population-based data, and the expectation of further large studies, we designed this work as a living systematic review and meta-analysis that will be updated as new eligible evidence becomes available. RESULTS: We identified three eligible studies based on data from (1) Norway and Sweden, (2) Norway and Taiwan and (3) Denmark. As two studies included Norwegian data, their results are referred to as 'Norway 1' and 'Norway 2' for clarity. In the meta-analysis of data from Denmark, Sweden and Norway 1, the pooled HR of offspring NDDs was 1.05 (95% CI 0.87 to 1.27; I2=0.0%), and in meta-analysis of data from Denmark, Sweden and Norway 2, it was 1.03 (95% CI 0.85 to 1.24; I2=0.0%).In the meta-analysis including Taiwan, Denmark, Sweden and Norway 1, the pooled HR was 1.06 (95% CI 0.88 to 1.27; I2=0.0%), and when including data from Taiwan, Denmark, Sweden and Norway 2, the pooled HR was 1.04 (95% CI 0.87 to 1.25; I2=0.0%). CONCLUSIONS: In this living meta-analysis, we found no evidence that paternal exposure to valproate compared with lamotrigine/levetiracetam during spermatogenesis was associated with increased risk of NDDs in offspring.

Humans↗

PubMed2026

Dietary approaches for glycemic management in type 1 diabetes: A systematic review of Mediterranean and low-carbohydrate diets.

BACKGROUND/OBJECTIVES: Specific dietary approaches for better management of type 1 diabetes (T1D) have not been thoroughly investigated. We conducted a systematic review to evaluate the Mediterranean and low-carbohydrate diets for glycemic management in people with T1D. METHODS: We examined longitudinal studies (cohort studies and clinical trials) including individuals with T1D who followed low-carbohydrate diets (<26% calories from carbohydrates and/or <130 g of carbohydrates per day) and/or a Mediterranean diet, while hemoglobin A1c (HbA1c) and/or time in range (TIR) were measured. Additional eligibility criteria included publication in English and availability of a full-text primary research article. Non-longitudinal studies, abstracts, and studies published in languages other than English were excluded. Results were synthesized narratively, and the GRADEpro Guideline Development Tool was used to assess article quality. RESULTS: A total of 565 studies were identified from PubMed, the Web of Science, and citation chasing. After removal of duplicates and further evaluation, 22 studies (6 cohort studies and 16 clinical trials; total n = 3284) were included in this review. The search was initially completed in May 2024, and updated February 2026. Low-carbohydrate diets were associated with better glycemic management when compared to usual diets or baseline glycemic parameters. Studies using CGM were overall underpowered. The impact of Mediterranean diets was less clear, but generally appeared to be less effective at improving glycemic management than low-carbohydrate diets. DISCUSSION: Although structured dietary interventions for T1D hold promise for improving glycemic outcomes, further research is needed to determine exactly which dietary intervention is most beneficial for this population. The evidence provided by included studies is limited by small sample sizes and short durations; better powered, longer-term studies are required to inform clinical recommendations.

Humans↗

PubMed2026

Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis.

AIM: To assess the effects of mazdutide on body weight, HbA1c, metabolic outcomes, and adverse events in adults with overweight/obesity and/or type 2 diabetes (T2D). METHODS: This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing mazdutide with placebo or active comparators in adults with overweight/obesity and/or T2D, identified through PubMed, Scopus, Web of Science, and ClinicalTrials.gov to 20 February 2026. Co-primary outcomes were percent change in body weight and change in HbA1c. Secondary outcomes included other weight-related and metabolic outcomes, as well as safety. Random-effects models were used to generate pooled mean differences (MDs) or risk ratios with 95% confidence intervals, and the certainty of the evidence (COE) was assessed using GRADE. RESULTS: Nine RCTs (N = 2292; most with low risk of bias) were included. In overweight/obesity without diabetes, mazdutide 3, 4, and 6 mg reduced body weight more than placebo (MDs -6.56%, -9.92%, and -11.1%, respectively; very low COE due to substantial heterogeneity and few trials). In T2D, mazdutide 4 and 6 mg reduced body weight and HbA1c versus placebo (moderate COE) and also outperformed dulaglutide for both outcomes. Mazdutide also improved waist circumference, lipids, liver enzymes, and uric acid levels. Gastrointestinal adverse events were more frequent, but serious adverse events and treatment discontinuation rates were comparable with those of the comparators. CONCLUSIONS: Mazdutide was associated with dose-dependent reductions in body weight and HbA1c, with broader metabolic benefits in predominantly Chinese adults with obesity and/or T2D. Longer-term, multi-ethnic studies are needed to confirm durability, generalizability, and cardiovascular safety.

Humans↗

PubMed2026

Deucravacitinib 5-Year Safety and Efficacy Results in Plaque Psoriasis: A Phase 3 Open-Label Extension of Randomized Clinical Trials.

BACKGROUND: Deucravacitinib, an oral, selective, tyrosine kinase 2 inhibitor, is approved for adults with moderate to severe plaque psoriasis who are candidates for systemic therapy and for adults with active psoriatic arthritis. OBJECTIVE: We evaluated deucravacitinib safety and efficacy over 5 years in the phase 3 POETYK PSO-1, PSO-2, and long-term extension (LTE) trials in patients with moderate to severe plaque psoriasis. METHODS: PSO-1 and PSO-2 (parent trials) randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At 52 weeks, patients enrolled in the LTE trial received open-label deucravacitinib. Safety was reported as exposure-adjusted incidence rates (EAIRs) per 100 person-years (PY). Clinician- and patient-reported outcomes were analyzed using modified nonresponder imputation in patients receiving continuous deucravacitinib from day 1 (PSO-1/PSO-2) through 5 years. RESULTS: Overall, 1519 patients received one or more deucravacitinib dose; total exposure was 5046.7 PY through data cutoff (September 2, 2024). EAIRs/100 PY were comparable or decreased from the 1-year to 5-year cumulative period for adverse events (AEs) (229.23, 127.40, respectively), serious AEs (5.68, 5.06), discontinuation due to AEs (4.38, 2.09), deaths (0.20, 0.22), serious infections excluding coronavirus disease 2019 (COVID-19) (1.53, 0.94), malignancies (1.02, 0.92), major adverse cardiovascular events (0.30, 0.34), and venous thromboembolism (0.20, 0.06). Clinical outcomes were well-maintained in patients receiving continuous deucravacitinib (n = 513) from 1 through 5 years, including achievement of a ≥ 75% reduction from baseline in the Psoriasis Area and Severity Index (1 year, 72.1% [95% CI 68.2-76.1]; 5 years, 67.3% [62.0-72.6]) and a static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (1 year, 57.5% [53.1-61.9]; 5 years, 52.6% [47.0-58.1]). Dermatology Life Quality Index 0 or 1 was well-maintained from 1 year (52.5% [48.0-57.1]) through 5 years (45.4% [40.0-50.8]). CONCLUSIONS: These findings demonstrate a consistent safety profile with no new safety signals and durable clinical response through 5 years of treatment with deucravacitinib. CLINICAL TRIAL REGISTRATION: NCT03624127, NCT03611751, NCT04036435.

Humans↗

PubMed2026

Dynamics and virulence of Enterobacteriaceae reservoirs harboring blaCTX-M group 1 in community wastewater.

UNLABELLED: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are ubiquitous and can cause serious infections. Here, we examined untreated community wastewater influent as a reservoir for blaCTX-M group 1 organisms and their virulence potential. Raw influent samples (n = 268) were collected from four wastewater treatment plants (WWTPs) representing dense urban populations. We observed that blaCTX-M group 1 levels were high at all WWTPs and only ~1-2 log10 lower and not correlated to common human-specific microbiome fecal markers, Lachno3 and HF183, indicating a lack of connection to human fecal inputs. Concentrations of blaCTX-M group 1 genes and markers for presumptive host organisms Escherichia coli and Klebsiella pneumoniae were influenced by travel time and season. Amplicon sequencing revealed high diversity of blaCTX-M group 1-9 genes, with 63% belonging to group 1. Selective culture and 16S rRNA gene sequencing showed blaCTX-M group 1 isolates were 26% E. coli, 26% K. pneumoniae, 40% other Enterobacteriaceae, and 8% Aeromonas. Overall, E. coli averaged 3.6E7 cells/L, with 3% of all E. coli found to contain blaCTX-M group 1. Whole-genome sequencing of blaCTX-M group 1 E. coli from wastewater revealed resistance and virulence gene profiles similar to clinical isolates and distinct from other wastewater ESBL-resistant and non-resistant E. coli. Interpretation of wastewater data needs to consider both the existence of environmental reservoirs that contain potentially pathogenic organisms and the strong influence the dynamics of the conveyance system can have on final concentrations measured at the WWTP. IMPORTANCE: The CTX-M enzyme family is highly abundant in nosocomial, community, and environmental settings and is leading to treatment of infections with carbapenem antibiotics, a last-line therapeutic option. The progressive increase of the clinically relevant blaCTX-M group 1 resistance genes in the human population warrants investigation, particularly to understand the establishment and dynamics of environmental reservoirs. This study utilized molecular and culture methods to gain insight into the possible origin, abundance, and dynamics of blaCTX-M group 1 genes in untreated wastewater influent samples. We found extremely high levels of these genes, with Escherichia coli as a major host organism that closely resembled clinical strains, suggesting they are seeded and propagate in sewer pipe systems. The significance of our research is in developing approaches to monitor antimicrobial resistance reservoirs in community wastewater, which could shed light on global burdens and potential transmission cycles and indicate increasing inputs of clinically relevant strains originating from human populations.

E. coli↗

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

Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r=0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

blood glucose↗

PubMed2026

A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans↗

PubMed2026

Early Worsening of Diabetic Retinopathy Following Initiation of Hybrid Closed-Loop/Automated Insulin Delivery Systems in Type 1 Diabetes: A Systematic Review and Structured Study-Level Synthesis.

BACKGROUND: Hybrid closed-loop (HCL) systems achieve rapid, algorithm-driven improvements in glycaemia in type 1 diabetes (T1D). Paradoxically, rapid improvement in glycaemic control is associated with early worsening of diabetic retinopathy (EWDR), a phenomenon established in the intensive insulin therapy era. Whether HCL initiation carries a clinically meaningful EWDR risk is unknown. No systematic review has previously addressed this question. METHODS: A systematic review and structured quantitative synthesis was performed using study-level estimates only (PROSPERO CRD:420261391951). MEDLINE, SCOPUS and Web of Science were searched to 14th May 2026. Studies reporting retinal outcomes in people with T1D initiating any HCL system were eligible. Two reviewers independently screened studies and extracted data. Risk of bias was assessed using ROBINS-I and certainty of evidence using the GRADE framework. EWDR incidence was summarised using study-level proportions, and comparative studies were summarised using study-specific risk ratios for HCL versus control therapy. Given substantial heterogeneity in EWDR definitions, retinal assessment timing, follow-up duration, and comparator groups, no pooled or meta-analytic estimates were derived. RESULTS: Eight studies (n = 1487 participants; 860 HCL users) were included; all were observational and six were retrospective. EWDR varied markedly with the timing of retinal assessment. In studies assessing the retina within ≤ 12 months of HCL initiation, EWDR rates ranged from 8.9% to 26.5%. Studies with longer follow-up reported lower rates of retinal worsening or incident DR, 6.7% at 24 months and 6.1% over a mean follow-up of 4.9 years, suggesting that these studies may capture background DR progression rather than true early worsening. Three comparative studies included 177 HCL users and 315 controls; EWDR study-specific risk ratios were directionally inconsistent, ranging from 0.32 to 1.51, and were therefore not pooled. The most consistently identified risk factors were higher baseline HbA1c and older age. The magnitude of HbA1c reduction was not a consistent predictor of EWDR in the HCL context, in contrast to pre-HCL era evidence. Risk of bias ranged from moderate to critical and certainty of evidence was very low for all outcomes. CONCLUSIONS: Study-defined retinal worsening was reported in a minority of participants. The current evidence base is dominated by retrospective studies, variable retinal assessment timing, and inconsistent EWDR definitions. Well-designed prospective studies with protocol-specified retinal surveillance anchored to HCL initiation are required to generate reliable incidence estimates, identify risk factors, determine visual consequences, and inform standardised screening guidance.

Humans↗

PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗

PubMed2026

Public health, public protest: The role of health burdens and healthcare access in protest mobilisation.

Health and politics are intertwined, yet few studies have examined the association between health and protest. This study examined whether population health burdens were associated with protest incidence and whether healthcare access modified these associations. Analysis was based on an unbalanced 2004-2023 country-year panel, combining protest counts from ACLED with rates for 22 GBD causes. Mixed-effects negative-binomial models estimated incidence-rate ratios (IRRs) with interactions for healthcare access (±1 SD). Two-way fixed-effects Poisson models were estimated as a benchmark to distinguish cross-national associations from within-country dynamics. Health burdens were systematically, but heterogeneously, associated with protest. Rates for several non-communicable burdens were associated with protest, notably musculoskeletal disorders (IRR 1.72, 95% CI 1.37-2.15), neoplasms (1.24, 1.06-1.44), substance-use disorders (1.32, 1.12-1.56) and HIV/AIDS and other STIs (1.24, 1.12-1.38). Higher healthcare access generally attenuated health-protest associations. Fixed-effects models confirmed several associations (e.g. HIV/AIDS, neoplasms) but revealed that others (e.g. maternal/neonatal disorders, enteric infections) were driven primarily by cross-national differences. Population health burdens were associated with cross-national variation in protest mobilisation. Chronic, non-communicable burdens were associated with heightened protest, whereas poverty-linked and early-life burdens were associated with lower mobilisation. Healthcare access was associated with attenuation of these relationships.

Humans↗

PubMed2026

Endoscopic Ultrasound-Guided Franseen Fine-Needle Biopsy for Solid Pancreatic Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Accurate tissue acquisition (TA) of solid pancreatic lesions is essential for guiding treatment with endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) being the preferred method. Among FNB designs, the three-pronged Franseen-tip needle demonstrates strong diagnostic performance, though direct head-to-head comparisons with other FNB designs remain limited. METHODOLOGY: This meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251123856). Eligible studies enrolled patients with solid pancreatic lesions who underwent EUS-guided FNB, directly compared the Franseen-tip with other FNB needles. Six databases were systematically searched through July 2025, and study selection, data extraction, and risk of bias assessment (QUADAS-2 tool) were performed independently by two reviewers. Pooled estimates were generated using random-effects and bivariate hierarchical models. RESULTS: Sixteen studies (2,010 Franseen vs. 2,811 comparator) were included. Bivariate analysis showed that sensitivity and specificity of the Franseen needle were comparable to newer-generation comparator needles (sensitivity 91.3% vs. 94.0%; specificity 99.99% vs. 99.15%), whereas older-generation needles demonstrated lower sensitivity (80.8%) and inferior discriminatory performance (Negative Likelihood Ratio [LR⁻] 0.19 vs. 0.09). Diagnostic accuracy was higher with the Franseen needle (RR 1.07, 95% CI 1.01-1.14; I2 = 69%). Sample adequacy was similar overall (RR 1.04, 95% CI 0.95-1.14) but superior to older-generation needles (RR 1.19, 95% CI 1.02-1.41) and in lesions > 30 mm (RR 1.14, 95% CI 1.02-1.28, I2 = 81.2%). The Franseen needle achieved nominally strong diagnostic performance (DOR 116.6), although small-study effects were observed. Primary procedural outcomes were comparable between Franseen and comparator needles, including technical success (RR 1.00, 95% CI 0.98-1.02) and histological core procurement (RR 1.04, 95% CI 0.92-1.17). The Franseen needle had fewer low-cellularity samples (RR 0.56, 95% CI 0.45-0.69) and lower specimen bloodiness (RR 0.48, 95% CI 0.25-0.90) but a slightly higher overall adverse event rate (RR 1.29, 95% CI 1.06-1.57). CONCLUSION: The Franseen needle provides superior diagnostic accuracy and sample adequacy compared to older-generation FNB needles with comparable performance to newer-generation designs. It reduces low-cellularity samples and specimen bloodiness, although adverse events are slightly increased, with other primary procedural outcomes remaining comparable. TRIAL REGISTRATION: PROSPERO (Registration No. CRD420251123856).

Humans↗

PubMed2026

Structural and physicochemical characterisation of branched dextrans produced by an active α-(1→2) branching sucrase from Apilactobacillus kunkeei PDER37.

Recently, branching sucrases encoded in the genomes of certain Lactic Acid Bacteria (LAB) strains have become novel enzymes to obtain branched α-glucans. In this study an active α-(1 → 2) branching sucrase from Apilactobacillus kunkeei PDER37 was expressed, characterised and distinct branched dextrans was obtained with reactions under different sucrose: dextran ratio. Structural characterisation by 1H and 13C NMR analysis demonstrated the branching of the dextran with (1 → 2)-linked α-d-glucose units with no alteration in the final structure depending on sucrose: dextran ratio (D0) but this ratio was effective for the determination of the molecular weights of the branched dextrans (D1, D2 and D3). FTIR analysis further supported the dextran structures and suggested the higher accumulation of the α-Glc units in the branched dextrans. Thermal characterisation of the branched dextrans obtained by TGA and DSC analysis suggested the increased hygroscopicity of the branching units. Both SEM and AFM analysis demonstrated more porous chain like structures in the branched dextrans. This study provides valuable information on the role of active α-(1 → 2) branching sucrase (BS37) for the production of branched dextrans with potential increased physicochemical status applicable for food and other industries.

Dextrans↗

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

Efficacy and safety of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with active psoriatic arthritis: 52-week results from the randomised, double-blind, placebo-controlled phase 3 POETYK PsA-1 trial.

OBJECTIVES: The randomised, double-blind, placebo-controlled, phase 3 Program fOr Evaluation of TYK2 inhibitor Psoriatic Arthritis-1 (POETYK PsA-1) trial evaluated the efficacy, safety, and tolerability of deucravacitinib, an oral, selective tyrosine kinase 2 inhibitor, in patients with PsA naïve to biologic disease-modifying antirheumatic drugs. METHODS: Adults with active PsA, high-sensitivity C-reactive protein concentration ≥ 3 mg/L, and ≥ 1 PsA-related hand and/or foot erosion detectable via radiograph were randomised 1:1 to oral deucravacitinib 6 mg once daily or placebo through week (W) 16. At W16, patients continued receiving deucravacitinib or switched from placebo to deucravacitinib through W52. The primary endpoint was American College of Rheumatology 20% improvement in response (ACR20) at W16. Nonresponder imputation was used for missing data. Efficacy and safety were evaluated through W52. Post hoc rank analysis of covariance was used to evaluate structural damage with no missing data imputation. RESULTS: In 670 patients, a significantly greater proportion of those receiving deucravacitinib vs placebo achieved ACR20 at W16 (54.2% vs 34.1%, P < .001). Responses with deucravacitinib were increased at W52. Patients who switched from placebo to deucravacitinib achieved improvements similar to those in patients who received continuous deucravacitinib. Inhibition of structural damage was observed at W16 and W52. At W16, incidences of serious adverse events (AEs) (deucravacitinib, 1.8%; placebo, 2.4%) and discontinuations due to AEs (2.4%; 1.8%) were low and remained low through W52, without imbalances in cardiovascular events, malignancies, or opportunistic infections. No new safety signals were detected; no deaths occurred. CONCLUSIONS: Deucravacitinib demonstrated superiority vs placebo for clinical responses, patient-reported outcomes, and structural damage inhibition in patients with PsA, with favourable tolerability and safety.

Humans↗

PubMed2026

Lateral Femoral Condyle Angle Is an Anatomic Risk Factor for Anterior Cruciate Ligament Primary Injury and Secondary Graft Rerupture.

PURPOSE: To define the lateral femoral condylar angle (LFCA)-a parameter measuring condylar inclination-and assess its predictive capacity for primary and recurrent anterior cruciate ligament (ACL) injuries. METHODS: Patients aged 18 to 50 years who underwent primary ACL reconstruction between 2017 and 2022 were screened. Those with graft rerupture were matched 1:1:1 by sex, age, body mass index, and meniscal status to ACL-intact controls and patients without graft failure during a minimum 48-month follow-up. LFCA was measured as the angle between the long axis of the distal femur and the axis of the lateral femoral condyle, alongside 38 established parameters using preoperative 3.0-T magnetic resonance imaging scans. Intergroup differences were assessed with one-way analysis of variance; multivariate regression and receiver operating characteristic analyses identified independent predictors and evaluated predictive performance. RESULTS: The study included 540 patients (180 per group: primary ACL injury, rerupture, controls). One-way analysis of variance revealed a significant gradient in LFCA across controls (81.3°, 95% CI: 80.8-81.8°), primary injuries (81.9°, 95% CI: 81.5-82.3°), and reruptures (84.2°, 95% CI: 83.7-84.6°) (P < .001). In multivariate models adjusted for baseline factors, LFCA independently predicted primary injury (odds ratio [OR] = 1.27, 95% CI: 1.13-1.42, P < .001; area under the curve [AUC] = .576) and rerupture (OR = 1.46, 95% CI: 1.21-1.76, P < .001; AUC = .704). Combined models incorporating LFCA with tibial slopes, notch angle, and notch height achieved an AUC of .847 for primary injury prediction, whereas models with LFCA, lateral condylar flexion curvature radius, slope asymmetry, and tibial AP distance reached an AUC of .817 for rerupture. LFCA alone with lateral condylar flexion curvature radius yielded an AUC of .777 for rerupture prediction. Sex-stratified analyses confirmed LFCA predicted rerupture in both male patients (OR = 1.44, 95% CI: 1.19-1.75) and female patients (OR = 1.49, 95% CI: 1.16-1.92), and primary injury in male patients (OR = 1.30, 95% CI: 1.15-1.48). CONCLUSIONS: LFCA is an independent predictor of ACL injury, showing particular strength in identifying Asian patients at high risk for graft rerupture. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Humans↗

PubMed2026

Risk of mortality and complications in people with depressive disorder and co-occurring diabetes mellitus: a systematic review and meta-analysis.

AIMS: People with depressive disorder have increased premature mortality and higher rates of diabetes mellitus than general population. Evidence shows that diabetes may further increase their risk of premature death from diabetes-related complications, especially cardiovascular diseases (CVDs). Earlier studies examining depression-associated outcomes in diabetes patients have shown mixed results and were hindered by important limitations, especially the use of self-reported questionnaires to ascertain depression, causing misclassification bias by identifying subclinical symptoms or diabetes distress. Associations of depression with specific diabetes complications have not been systematically evaluated. This meta-analysis aimed to investigate the risk of mortality and complications among patients with depression and co-occurring diabetes (depression-diabetes group) relative to patients with diabetes-only (diabetes-only group), on their all-cause mortality rates, and if applicable cause-specific mortality rates, and occurrence of specific diabetes complications. METHODS: We systematically reviewed and quantitatively synthesized diabetes-related outcomes in patients with depression by searching Embase, MEDLINE, PsycInfo and Web-of-Science from inception to 20 December 2024, and included studies that examined mortality and complication outcomes in depression-diabetes group relative to diabetes-only group. Results were synthesized by random-effects meta-analytic models, with stratified-analyses (subgroup analyses and meta-regression) by study-level characteristics, including age, gender, study period, geographic region, follow-up duration and nature of diabetes sample. The study was registered with PROSPERO (CRD42024595145). RESULTS: Twenty-six studies were identified from nine geographic regions. Regarding mortality risk, depression-diabetes group exhibited increased risks of all-cause mortality (RR = 1.30 [95% CI: 1.21-1.39]) and CVD-specific mortality (1.15 [1.02-1.29]) relative to diabetes-only group. Regarding complication risk, depression-diabetes group showed increased risk of complications (1.28 [1.18-1.40]) relative to diabetes-only group, especially in incident-diabetes sample signifying advanced disease stage upon presentation, with stratified-analyses showing higher risk of metabolic complications (1.63 [1.33-1.99]) and cardiovascular complications (1.20 [1.11-1.29]), and lower likelihood of retinopathy (0.84 [0.76-0.94]), albeit comparable rates of cerebrovascular complications (1.36 [0.99-1.87]), nephropathy (1.09 [0.93-1.27]) and peripheral-vascular complications (0.97 [0.79-1.18]). Both overall mortality and complication risks were present in various regions and persisted over time. Heterogeneities were noted and could not be entirely explained by stratified analyses. CONCLUSIONS: Our study demonstrated that patients with depression and co-occurring diabetes were associated with elevated overall mortality risk and complication risk (particularly metabolic and cardiovascular-complications) than non-depressed counterparts, suggesting an overall poorer glycemic control that might eventually drive their earlier death. Comprehensive and multipronged interventions are needed for individualized risk estimation of diabetes-related outcomes, with consequent early interventions to minimize the avoidable physical morbidity and premature mortality in this vulnerable population.

Humans↗

PubMed2026

Accelerated Diagnostic Pathways for Suspected Acute Coronary Syndrome in Practice: A Randomized Trial of 0/1-Hour vs 0/3-Hour Troponin Testing.

BACKGROUND: For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS: This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS: From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS: Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/1 Versus 0/3 Hour Troponin Pathway [MACROS2]; NCT05322395).

Acute Coronary Syndrome↗

Results for “GLP&#x2010;1”

Results for “GLP‐1”