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PubMed2026

Direct Oral Anticoagulants as Primary or Secondary Treatment for Heparin-Induced Thrombocytopenia (HIT) and Associated Thromboembolism (HITT)-A Meta-Analysis.

INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is associated with a high risk for thrombosis. The role of direct oral anticoagulants (DOACs) is still emerging and data are limited considering efficacy and safety among patients with HIT. The aim of this review is to evaluate current data on DOACs as primary or secondary treatment among patients with HIT. METHODS: This is a systematic review utilising Pubmed, Scopus and Embase online databases. Eligible studies were published up to December 2024 evaluating DOACs as primary or secondary treatment among patients with HIT and/or associated thrombosis (HITT). Primary outcomes included thrombosis rate (TR) and bleeding rate (BR) during follow-up. RESULTS: A total of 44 publications were included (29 case reports, 5 case studies and 10 cohort studies [n > 10 patients]). Regarding treatment, 19 articles evaluated only rivaroxaban, 7 articles only apixaban, 11 articles only dabigatran and 7 articles more than one regimen. A total of 352 patients were included. Overall, 190 patients (53.8%) were given DOAC as primary treatment whereas 162 patients were given a parenteral treatment first and continued with a DOAC. Mean nadir platelet count at diagnosis was 63 000/μL. HITT rate was 190/352 (53.9%; 8% had arterial thrombosis). Mean follow-up was 7.6 months. TR was 20/352 (Pooled proportion = 0.064 [95% CI = 0.042-0.092]) (30% of them were new thromboses without initial thrombosis), and BR was 9/352 (Pooled proportion = 0.039 [95% CI = 0.022-0.062]). Finally, there was no difference found regarding TR and BR between primary or secondary treatment, and among different regimens. CONCLUSIONS: DOACs are associated with low rates of thrombosis and major bleeding among patients treated for HIT or HITT, either as primary or secondary treatment. However, the certainty of evidence is very low because of the quality and limitations of the available studies.

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PubMed2026

Socioeconomic differences in the effectiveness of oral health programs for dental caries prevention in Europe: A systematic review and meta-analysis.

AIM: The meta-analysis systematically summarized evidence on how socioeconomic status (SES), access to dental care, and oral health programs (OHP) affect caries prevalence and severity among children and adults in Europe. METHODS: Four electronic databases (PubMed, Scopus, Cochrane Library and Embase) were systematically screened from 1947-2026, supplemented by cross-referencing and manual searches, without language restrictions. Study selection, data extraction and quality assessment were done in duplicate. Methodological quality was assessed using the NHLBI Study Quality Assessment Tools according to study design. Certainty of evidence was graded using GRADE Profiler 3.6. Mean differences (MD) were calculated for changes in DMFT, and odds ratios (OR) for the presence of dental caries in individuals using fixed-or random-effects models. RESULTS: Electronic searching identified 1800 articles; 23 studies were included in the review (>169,000 participants) and 14 in the meta-analyses (>88,000). Nine studies evaluated the effectiveness of OHP stratified by SES, and ten examined OHP in low-SES populations. Among low-SES individuals, participation in OHP was associated with a significantly lower increase in DMFT (MD[95% CI]=-0.63[-0.94;-0.31];very low certainty) and significantly lower odds of having dental caries (OR[95% CI]=0.61[0.52;0.73];very low) compared with non-participation. Among program participants, individuals with low SES showed a significantly greater increase in DMFT than those with high SES (MD[95% CI]=0.79[0.30;1.21];very low) and had significantly higher odds of having dental caries (OR[95% CI]= 2.88[1.97;4.22];very low). CONCLUSION: Participation in OHP may be associated with reducing dental caries in European populations, but benefits are unequally distributed and increase with higher SES. However, this conclusion is based on a limited number of well-conducted trials.

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PubMed2026

Low-carbohydrate diet score subtypes and all-cause mortality in general and chronic disease populations: a systematic review and meta-analysis of prospective cohort studies.

OBJECTIVES: To examine associations of overall, healthy and unhealthy low-carbohydrate diet (LCD) scores with all-cause mortality in general and chronic disease populations. Healthy and unhealthy subtypes were compared with assess whether the observed associations depend on macronutrient quality rather than carbohydrate restriction alone. DESIGN: Systematic review and pairwise category meta-analysis. DATA SOURCES: PubMed, MEDLINE, ProQuest Medical Database and Web of Science Core Collection were searched from inception to 12 May 2026. ELIGIBILITY CRITERIA: Prospective cohort studies of adults assessing LCD adherence using a validated three-macronutrient composite score and reporting HRs for all-cause mortality were eligible. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa Scale (NOS). Random-effects meta-analyses compared each higher reported LCD category with the lowest category, stratified by LCD score subtype and population type. Certainty of evidence was assessed using NutriGrade. RESULTS: 18 prospective cohort studies included 779 158 participants and 219 457 deaths; all scored 7-9/9 on the NOS. In chronic disease populations, the highest healthy LCD category was associated with lower mortality than the lowest category (HR 0.72, 95% CI 0.69 to 0.76; I²=0%; high certainty), as was the highest overall LCD category (HR 0.85, 95% CI 0.75 to 0.96; I²=68%; high certainty). In the general population, the highest healthy LCD category was not associated with lower mortality than the lowest category (HR 0.93, 95% CI 0.85 to 1.01; I²=69%; moderate certainty), and neither was the highest overall LCD category (HR 0.96, 95% CI 0.90 to 1.03; I²=87%; low certainty). Unhealthy LCD scores were not associated with mortality in either population. CONCLUSIONS: Healthy LCD adherence was associated with lower all-cause mortality, particularly among individuals with chronic diseases. Unhealthy LCD scores were not associated with mortality in either population, suggesting that macronutrient quality and source may matter more than carbohydrate reduction alone.

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PubMed2025

The impact of the COVID-19 pandemic on osteoporotic fractures: a systematic review and meta-analysis.

BACKGROUND: Recent reports suggest that the COVID-19 pandemic and associated lockdowns may have influenced the epidemiology of osteoporotic fractures, but results vary across regions and fracture types. The aim of this study was to provide evidence-based insights into the impact of the pandemic on osteoporotic fracture incidence. METHODS: We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) up to August 2025 for observational or retrospective studies comparing osteoporotic fracture incidence during the COVID-19 pandemic (2020) with the pre-pandemic period (2019). The primary outcome of interest was the change in fracture incidence, analysed using risk ratios (RR) with 95% confidence intervals (CI) in Review Manager 5.4. Subgroup analyses were performed by sex, geographic region, and fracture type. RESULTS: Nine studies meeting the inclusion criteria were analysed. Overall, "all types" of osteoporotic fractures showed a significant decrease during the pandemic (RR = 0.85, 95% CI 0.80-0.91, p < 0.0001). Specifically, forearm fractures decreased significantly (RR = 0.87, 95% CI 0.79-0.96, p = 0.002). However, for the most clinically significant fractures, no statistically significant global change was found for hip fractures (RR = 0.93, 95% CI 0.76-1.15, p = 0.14) or vertebral fractures (RR = 1.35, 95% CI 0.85-2.15, p = 0.20). In regional subgroup analysis, hip fracture incidence decreased significantly in South America (RR = 0.79, p = 0.0004) and in both males and females, but no significant change was observed in Europe (RR = 0.92, 95% CI 0.81-1.04, p = 0.17). CONCLUSION: During the COVID-19 pandemic, there was a decrease in the incidence of minor fractures, such as those of the forearm, likely due to reduced outdoor activity. However, the incidence of major osteoporotic fractures (hip and vertebral) remained stable globally, with significant reductions observed only in specific regions like South America.

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PubMed2026

Autologous bone grafts versus alloplastic implants for orbital floor reconstruction: a systematic review and meta-analysis.

PURPOSE: The choice of reconstructive material for orbital floor fractures remains a subject of debate. While autologous bone has historically been considered the "gold standard," alloplastic implants offer potential advantages in reducing surgical morbidity. This meta-analysis aimed to compare the safety and efficacy of autologous bone grafts versus alloplastic implants in orbital floor reconstruction. METHODS: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251140583). Electronic databases (PubMed, Scopus, Web of Science, Cochrane Library) were searched from inception to August 2025. Randomized controlled trials and comparative cohort studies evaluating functional outcomes (diplopia, enophthalmos) and complications (ectropion, infection, malposition) were included. Data were synthesized using a random-effects model, with risk ratios (RR) and 95% confidence intervals (CI) calculated. RESULTS: Twenty studies comprising 2,119 patients were included. Alloplastic implants demonstrated statistically significant superiority in periocular safety, with a reduced risk of postoperative ectropion compared to autologous grafts (RR = 2.245; p = 0.020). In an exploratory sensitivity analysis excluding one outlier study, autologous grafts were associated with a significantly higher risk of implant malposition (RR = 2.074; p = 0.004). Autologous reconstruction was associated with a strong trend toward increased postoperative pain (p = 0.052) and inherent donor-site morbidity. No statistically significant differences were observed regarding infection (p = 0.402), enophthalmos (p = 0.201), or diplopia (p = 0.221). CONCLUSION: Alloplastic implants were associated with a lower risk of ectropion and implant malposition, with functional outcomes statistically comparable to autologous bone. Given the elimination of donor-site morbidity, alloplastic biomaterials represent a safe and effective alternative for orbital floor reconstruction; however, the predominance of retrospective, heterogeneous studies in the current evidence base means these findings should inform, rather than replace, individualized surgical decision-making pending further high-quality randomized trials.

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PubMed2026

The impact of prehabilitation on postoperative outcomes in patients undergoing radical prostatectomy for prostate cancer: a systematic review and meta-analysis.

PURPOSE: Preoperative rehabilitation training can optimize functional reserve before radical prostatectomy (RP), thereby improving postoperative outcomes. However, its effects on urinary incontinence, erectile function, and quality of life (QoL) remain controversial. This study systematically evaluated these outcome measures. METHODS: Data from randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, Embase, and CINAHL databases. The risk of bias was assessed using the RoB-2 tool, and meta-analysis was performed using Stata 18.0 software. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Meta-analyses were conducted using fixed- or random-effects models according to heterogeneity. Outcomes included urinary incontinence incidence, urinary incontinence severity, erectile function, and QoL at different postoperative follow-up time points. RESULTS: 16 randomized controlled trials involving 1,542 participants were included. Prehabilitation significantly reduced the incidence of urinary incontinence at 1 month (OR = 0.58, 95% CI 0.39-0.84) and 6 months (OR = 0.52, 95% CI 0.28-0.96) after RP, with a non-significant borderline reduction at 3 months, and no significant benefit at 12 months. No significant improvement was observed in urinary incontinence severity or erectile function at any follow-up time point. Prehabilitation significantly improved QoL within 3 months (SMD = -0.70, 95% CI -1.08 to -0.32) and 6 months (SMD = -0.45, 95% CI -0.74 to -0.16) postoperatively. However, within 12 months, the effect size attenuated, showing only a marginal trend that did not reach statistical significance (SMD = -0.33, 95% CI -0.66 to 0.00). Risk of bias was generally moderate. CONCLUSION: Prehabilitation reduces early incontinence and improves QoL post-RP, but its effects on severity and erectile function remain unclear. SYSTEMATIC REVIEW REGISTRATION: PROSPERO [CRD420251183407].

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PubMed2026

Comparative efficacy of LDL-C-lowering therapies in first-time vs. recurrent myocardial infarction prevention: a meta-analysis of large-scale randomized controlled trials.

AIMS: Reducing elevated low-density lipoprotein cholesterol (LDL-C) is central to global efforts to prevent myocardial infarction (MI). While many studies have evaluated LDL-C-lowering therapies in first-time and recurrent MI prevention, direct comparisons of their relative efficacy are lacking. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy of LDL-C-lowering therapies in first-time vs. recurrent MI prevention. METHODS AND RESULTS: We searched three databases until 30 November 2024, for randomized controlled trials (RCTs) with at least 1000 patient-years of follow-up. Efficacy was quantified as relative risk (RR) with 95% confidence intervals (CIs). Differences in benefit magnitude were assessed using Cochran's Q test. Data were pooled with a random-effects model, and heterogeneity was measured using the I2 statistic. Additionally, we applied the Cochrane Risk of Bias Tool to evaluate study quality and utilized the GRADE method to assess the certainty of the evidence. This study included 22 large-scale RCTs involving 180 304 participants. In first-time MI prevention, LDL-C-lowering therapies achieved a remarkable 38% reduction in MI risk [12 RCTs; 79 604 participants; RR, 0.62 (95% CI, 0.55-0.69); P < 0.001]. In recurrent MI prevention, these therapies were associated with a more modest but significant 16% risk reduction [11 RCTs; 100 700 participants; RR, 0.84 (95% CI, 0.80-0.88); P < 0.001]. Importantly, the benefit magnitude between the two groups was significantly different (Q = 22.63; P < 0.001), highlighting the greater relative benefit in first-time MI prevention. Furthermore, the robustness of our findings was consistently supported by leave-one-out analyses, the absence of publication bias, high-quality GRADE evidence, and subgroup and sensitivity analyses. CONCLUSION: Our findings suggest that LDL-C-lowering therapies may offer a greater benefit in preventing first-time MI compared with recurrent MI.

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PubMed2026

EffectS of Lifestyle Interventions in Older PEople With Obesity (Effective SLOPE): a Systematic Review With Network Meta-Analyses.

BACKGROUND/AIM: We conducted a systematic review with network meta-analyses (NMA) summarizing the effects and safety of lifestyle interventions containing nutrition (NUT; e.g., calorie restriction), exercise (EX; e.g., aerobic/resistance exercise) and behavior change interventions (BCI; e.g., behavioral therapy) on physical function, body composition, quality of life, psychosocial outcomes, health and adverse events in community-dwelling older adults with obesity. METHODS: We used the methodology proposed by Cochrane and searched six databases and one trial registry for eligible randomized controlled trials (RCTs; intervention duration ≥ 12 weeks) up to May 2022 with a full new search in MEDLINE and a re-assessment of previously identified eligible trial registry entries in October 2025. Random-effects NMA ((standardized) mean difference ((S)MD), 95% confidence intervals) were conducted if possible. RESULTS: We included 72 RCTs (n = 6716) for descriptive summaries and 54 RCTs (n = 4249) for NMA. NUT+EX+BCI improved physical function (performance batteries) compared to control (SMD 3.37 [1.76;4.97]; high certainty of evidence). NUT+EX+BCI may reduce body (MD -8.69 [-13.14;-4.25]) and fat mass (MD -6.58 [-10.44;-2.73]) while not negatively affecting fat-free mass (MD -1.38 [-3.52;0.76]) or bone mineral density (MD -0.01 [-0.05;0.02]) (evidence very uncertain). Other interventions (single/combined) may also be effective; however, effects were often imprecise. For psychosocial outcomes, quality of life, and health events, data were insufficient or too heterogeneous to derive clear results. CONCLUSION: The evidence suggests that NUT+EX+BCI interventions are most suitable for the management of obesity in older adults. Nevertheless, further RCTs-especially in frail populations and on patient-relevant outcomes-are needed.

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PubMed2026

Effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia: a systematic review and meta-analysis.

BACKGROUND: Despite the burden of tobacco use, access to cessation support in South Asia remains scarce. OBJECTIVE: This review evaluates the effectiveness of tobacco cessation interventions delivered in clinical settings in South Asia. METHODS: Five relevant databases were searched from inception to February 2025. Eligibility criteria included randomized and non-randomized studies evaluating behavioral, pharmacotherapy, and multicomponent interventions delivered in clinical settings in South Asia. Data on study setting and design, participant information, intervention, comparator, and outcomes were extracted. Meta-analyses using random-effect models were conducted where possible. Certainty of evidence was assessed using GRADE. RESULTS: Thirty-seven studies were included (22 randomized and 15 non-randomized). Interventions involved pharmacotherapy (n = 6; 16.2%), nicotine replacement therapy (n = 7; 18.9%), behavioral counseling (n = 12; 32.4%), or combined/multicomponent interventions (n = 12; 32.4%). Most studies were conducted in India (n = 26; 70.3%), followed by Pakistan (n = 6; 16.2%), Nepal (n = 3; 8.1%), and two studies (5.4%) were multi-country in India, Pakistan, and Bangladesh. Pooled analyses demonstrated higher quit rates among intervention versus control for continuous abstinence at 0-3 months (RR: 1.21, 95%CI: 1.06 to 1.37) and >3 months (RR: 1.68, 95%CI: 1.1.4 to 2.47), and for point abstinence at >3 months post-intervention (RR: 2.03, 95%CI:1.35 to 3.08). Heterogeneity was high for all analyses (I2 range: 94% to 97%). Combined behavioral and pharmacotherapy interventions were most effective (RR: 1.70, 95%CI: 0.98 to 2.92), although not statistically significant (p = 0.06). CONCLUSION: Tobacco cessation interventions delivered in clinical settings in South Asia are effective, particularly when combining behavioral support with pharmacotherapy. However, evidence is limited by methodological weaknesses.

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PubMed2026

The clinical value of adding immune checkpoint inhibitors to radiotherapy for cancer: a systematic review and meta-analysis.

BACKGROUND: While several randomized clinical trials (RCTs) have explored the addition of immune checkpoint inhibitor (ICI) treatment for patients undergoing radiotherapy, studies systematically assessing the clinical value of such interventions are lacking. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant RCTs of cancers that received ICIs plus radiotherapy or radiotherapy. Eligible studies were those published in English as of 14 April 2024. Two independent reviewers screened the included studies and extracted relevant data, then selected the random or fixed-effects model based on the I2 statistic. The main outcomes were hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS); Odds ratios (ORs) with 95% CIs for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stratified analysis was performed based on cancer type, ICI type, and the timing of ICI addition. The study was registered on PROSPERO (CRD42024551008). RESULTS: 15 RCTs with 7947 patients were included. Pooled HRs were 0.865 (95% CI, 0.730-1.000; I2 = 72.1%) for OS and 0.799 (0.677-0.922; I2 = 82.0%) for PFS in cancer patients. In cancer types, adding immunotherapy to radiotherapy significantly improved patients with non-small-cell lung cancer (OS: 0.544 [0.371-0.717]; PFS: 0.527 [0.438-0.617]) and cervical cancer (OS: 0.722 [0.578-0.867] and PFS: 0.754 [95%CI, 0.621-0.887]). Regarding the ICIs schedule, adjuvant ICI therapy with pooled HRs was 0.742 (0.649-0.834) for OS and 0.638 (0.579-0.697) for PFS. In addition, the pooled ORs for the incidence of grade 3 or higher treatment-related and immune-related adverse events were 1.227 (1.059-1.421; I2 = 71.9%) and 2.217 (1.743-2.821; I2 = 74.0%), respectively. CONCLUSION: Adding immunotherapy to radiotherapy can provide significant clinical benefits for patients with NSCLC and cervical cancer, and the addition of these ICIs in the adjuvant stage is supported.

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PubMed2026

Omics in hereditary optic neuropathies: A systematic review of clinical studies with an integrated point of view.

Hereditary optic neuropathies are characterized by bilateral visual loss due to the degeneration of retinal ganglion cells, resulting in optic nerve degeneration and atrophy. Although the genetic origin of the main isolated and syndromic hereditary optic neuropathies has been characterized, the clinical phenotypes exhibit significant and poorly understood variability in both penetrance and expressivity. Additionally, the genetic and environmental factors that influence the onset of these optic neuropathies remain poorly understood, with limited biomarkers to predict disease progression or as readouts for therapeutic trials. Data-driven omics strategies allow deep phenotyping to improve our understanding of pathophysiological mechanisms and to search for new biomarkers and therapeutic targets. We explore whether the omics strategies applied to patients with hereditary optic neuropathies have provided such new insights. MEDLINE, Web of Science and EMBASE databases were screened for studies with terms relating to hereditary optic neuropathies, transcriptomics, epigenomics, proteomics, metabolomics and lipidomics in clinical studies exploring patients' samples. Out of 1244 references identified, 22 articles were included after double-masked data curation. These articles focused only on the 3 main forms of hereditary optic neuropathies, namely, OPA1-related dominant optic atrophy (n = 4), Leber hereditary optic neuropathy (n = 13), and Wolfram syndrome (n = 5). While the methodological designs and results of these studies were highly heterogeneous, they revealed molecular alterations that we have attempted to discuss at the integrated multi-omics level. This data integration highlighted several common pathophysiological mechanisms such as energetic impairment, endoplasmic reticulum stress, proteotoxic and oxidative stresses, lipid remodeling and altered amino acid and purine metabolisms, while suggesting potential new biomarkers and therapeutic targets. These findings underscore the potential of integrated multi-omics approaches to deepen our understanding of the phenotypic complexity of hereditary optic neuropathies and to support the development of innovative diagnostic and therapeutic strategies.

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PubMed2026

Hysteroscopic platelet-rich plasma and medically assisted reproduction outcomes: a systematic review and SWOT analysis.

BACKGROUND: Platelet-rich plasma (PRP) has been proposed as an adjuvant treatment in reproductive medicine. While most evidence refers to blind intrauterine instillation, subendometrial administration under hysteroscopic guidance allows targeted delivery under direct visualisation. This systematic review aimed to synthesise the available evidence on hysteroscopic PRP administration and its impact on clinical medically assisted reproduction (MAR) outcomes. METHODS: A systematic search was conducted from inception to December 2025 across major databases. Studies were included if they evaluated hysteroscopic PRP administration in women undergoing MAR, comparing reproductive outcomes between treated and control groups. RESULTS: Out of 142 records, 3 studies met the inclusion criteria. Study populations were heterogeneous and included women with refractory thin endometrium and/or a history of implantation failure. Hysteroscopic PRP administration protocols varied in timing, technique, and dosage. In a prospective case-control study, hysteroscopic intraendometrial PRP injection at a depth of 2-3 mm in the four uterine walls, using an ovum aspiration needle, on days 11-13 of the cycle prior to euploid frozen embryo transfer (ET), was associated with higher implantation (IR), clinical pregnancy (CPR), and live birth rates (LBR) compared with standard therapy. Conversely, no significant differences in CPR, miscarriage rate, or LBR were observed in an observational study evaluating a single intraendometrial PRP injection (35-40 mL, 2-3 mm depth), administered via endoscopic needle on days 6-8 of the menstrual cycle preceding frozen ET, alone or after electrical impulse therapy. A randomised controlled trial in women undergoing intrauterine insemination reported a significant improvement in CPR following hysteroscopic subendometrial PRP instillation in the four uterine walls (1.0 mL each). CONCLUSIONS: Current literature on hysteroscopic PRP administration in reproductive medicine is limited, and robust conclusions cannot yet be drawn. Well-designed randomised controlled trials with standardised protocols are needed to clarify its clinical role.

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PubMed2026

Externally validated risk prediction models for gestational diabetes mellitus: A systematic review and meta-analysis.

INTRODUCTION: Risk prediction models for gestational diabetes mellitus (GDM) offer potential for early identification and targeted prevention. External validation is crucial to assess model performance across diverse populations. Despite the availability of numerous GDM prediction models, limited evidence exists on their external validation frequency, methodological quality, and clinical applicability. This systematic review evaluated externally validated GDM prediction models, focusing on methodological rigor, reporting standards, and clinical relevance to inform future research and implementation. MATERIAL AND METHODS: Databases including Ovid MEDLINE, Embase, Scopus, Emcare, and CINAHL were searched up to May 1, 2025. Studies reporting external validation of GDM risk prediction models were included. Two reviewers independently screened studies. Data were extracted using the CHARMS framework, and risk of bias and applicability were assessed using PROBAST+AI. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251125758). RESULTS: Twenty-six studies validated 33 models, with validation sample sizes ranging from 50 to 75 161. Over half used the IADPSG criteria to define GDM. Discrimination metrics were commonly reported, but calibration, overall performance, and clinical utility were often lacking. Meta-analysis was feasible for only four models: Teede et al., Nanda et al., Naylor et al., and Van Leeuwen et al., each showing fair discrimination. The Teede et al. model was the most widely validated, with 11 external validations across six continents and a pooled AUC of 0.72 (95% CI: 0.67-0.76). Despite fewer validations, the Nanda et al. model achieved the highest pooled discrimination (5 validations; pooled AUC 0.77, 95% CI: 0.74-0.80). The Naylor et al. and van Leeuwen et al. models also underwent meta-analysis, as sufficient external validation studies were available to support comparative performance assessment. Notably, 69.23% of studies had a high risk of bias. CONCLUSIONS: While many models showed acceptable predictive performance, most validations were methodologically weak. Future studies should follow best-practice guidelines and promote scalable validation strategies, such as algorithm sharing, to enhance clinical utility.

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PubMed2026

Paediatric penile length: a systematic review and meta-analysis.

OBJECTIVE: To assess geographical variation in stretched penile length among prepubertal boys and evaluate temporal trends over the past two decades, as defining reference values for genital organ size remains crucial for early identification of development disorders. METHODS: The PubMed, Cochrane and Scopus databases (no deadlines for publishing were imposed) were searched according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Five authors independently extracted individual participant data and assessed the risk of bias. Studies with quantitative penile lengths were included; those involving congenital malformations were excluded. The review protocol was prospectively registered in the International Prospective Register of Systematic Reviews (registration number CRD42022335643). RESULTS: A total of 55 studies from 2000 to 2024 were evaluated, including data from 31 915 boys. Pooled mean stretched penile length estimates were 3.07 cm (95% confidence interval [CI] 2.88-3.26 cm) for the 1-week-old boys, 3.73 cm (95% CI 3.53-3.93 cm) for the 1-year-old boys, 4.69 cm (95% CI 4.49-4.88 cm) for the 2-5 year-old boys, and 5.43 cm (95% CI 5.20-5.66 cm) for the 5-10 year- old boys. When comparing data from the 2000s to the 2020s, stretched penile length decreased by 16.2% (from 3.46 to 2.90 cm), 16.3% (from 4.17 to 3.49 cm), 21.5% (from 5.31 to 4.17) and 26.2% (from 6.46 to 4.77 cm) in the 1-week-old, 1-year-old, 2-5-year-old and 5-10-year-old boys, respectively. Subgroup analysis for those aged >2 years showed significant variations by geographical region (P < 0.001). CONCLUSIONS: The present study observed large variations in penile length across geographical regions and among prepubescent boys of different ages, while also suggesting a possible decline over the past two decades.

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PubMed2026

Effect of adding umbilical cord blood derived stem cells to haploidentical stem cell transplant (haplo-cord) on post-transplant survival and graft-versus-host disease in patients with hematological malignancies: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Haploidentical stem cell transplantation (haplo-SCT) carries a substantial risk of graft-versus-host disease (GvHD), whereas umbilical cord blood (UCB) transplantation offers lower GvHD risk but slower engraftment. The haplo-cord approach combines both graft sources, aiming to mitigate GvHD while ensuring timely engraftment. This meta-analysis compares haplo-cord transplantation with haplo-SCT alone for the treatment of hematological malignancies. METHODS: Four electronic databases and two clinical trial registries were systematically searched. Effect sizes from eligible studies were pooled using odds ratios (ORs) for dichotomous outcomes and hazard ratios (HRs) for time-to-event outcomes. RESULTS: Twelve studies met the inclusion criteria. Haplo-cord was associated with a statistically significant reduction in chronic GvHD (OR = 0.62, 95%-CI: 0.42-0.93), while no significant difference was observed for grade II-IV acute GvHD (OR = 0.75, 95%-CI: 0.52-1.09). Survival outcomes favored haplo-cord, with lower HRs for overall survival (HR = 0.68, 95%-CI: 0.53-0.86) and event-free survival (HR = 0.61, 95%-CI: 0.52-0.72), while non-relapse mortality was not significant. Relapse at 3 years was significantly lower with haplo-cord (OR = 0.54, 95%-CI: 0.35-0.82). Haplo-cord also demonstrated higher day-30 engraftment, along with lower relapse-related and GvHD-related mortality, while CMV and EBV viremia showed no difference between groups. CD34 selection in the haplo graft significantly influenced effect sizes and heterogeneity in both subgroup analyses and meta-regression for acute GvHD. CONCLUSION: Haplo-cord transplantation improves GvHD outcomes, survival, and relapse risk compared with haplo-SCT alone. However, whether protocol optimization, possibly via CD34 selection, confers additional benefit remains uncertain and requires confirmation in future studies.

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PubMed2026

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

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PubMed2026

Comparative efficacy and safety of bi-flanged metal stents versus lumen-apposing metal stents for endoscopic drainage of pancreatic fluid collections: a systematic review and meta-analysis.

INTRODUCTION: Pancreatic fluid collections (PFCs), particularly walled-off necrosis, are common complications of acute pancreatitis that often require endoscopic drainage. Bi-flanged metal stents (BFMS; NAGI; Taewoong Medical, Gyenoggi-do, Korea) and electrocautery-enhanced lumen-apposing metal stents (LAMS; AXIOS, Boston Scientific Corporation, Marlborough, Massachusetts, USA) are frequently used, but comparative data remain limited. This study aims to compare the efficacy and safety of BFMS and LAMS in the endoscopic drainage of PFCs. METHODS: This meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive database searches were conducted through November 2024 to identify studies comparing BFMS and LAMS for endoscopic ultrasound-guided drainage of PFCs. Outcomes were pooled using a random-effects model with RevMan Web, and statistical significance was defined as a P value less than 0.05. RESULTS: Three studies ( n  = 627; 329 BFMS and 298 LAMS) met inclusion criteria. No significant differences were observed between BFMS and LAMS for technical success [odds ratio (OR): 1.16; 95% confidence interval (CI): 0.55-2.43] or clinical success (OR: 0.97; 95% CI: 0.51-1.87). Similarly, there were no differences in walled-off necrosis recurrence (OR: 2.01; 95% CI: 0.17-24.02), number of direct endoscopic necrosectomy sessions (OR: 0.52; 95% CI: 0.05-5.12), or mean number of endoscopic procedures (mean difference: 0.18, 95% CI: 2.08-2.45). Adverse events were also comparable between groups, including bleeding (OR: 0.64), infection (OR: 1.18), stent migration (OR: 1.83), and stent occlusion/dysfunction (OR: 1.71). CONCLUSION: BFMS and LAMS provide equivalent efficacy and safety in the endoscopic ultrasound-guided drainage of PFCs. Either stent type represents a viable therapeutic option. Further large-scale prospective studies are warranted to refine stent selection strategies.

Humans↗

PubMed2026

Relationship Between Number of Acute Pancreatitis Episodes and Risk of New-onset Diabetes in the U.S.: A Real-world Data Analysis.

INTRODUCTION: Acute pancreatitis (AP) is a common inflammatory disorder that is associated with increased risk for diabetes mellitus (DM). It remains unclear whether recurrent acute pancreatitis (RAP) is associated with further increased risk of incident DM. This study aims to investigate the association between RAP and incident DM using real-world data. METHODS: We conducted a retrospective cohort study using the MerativeTM MarketScan® claims database (2016-2023), identifying patients with AP and no prior history of DM at baseline. The primary exposure of interest, RAP, was defined as one or more episodes of AP occurring ≥90 days after the index AP diagnosis, whereas one episode of AP referred to a single episode of AP (SAP) with no subsequent recurrence within 90 days following the index event. A multivariable stratified Cox proportional hazards regression models were used to determine the association between RAP and incident DM, identified using ICD-10 codes. RESULTS: In total, 16,184 individuals with AP (mean [SD] age: 45.8 [12.3]) contributed 40,712 person-years of follow-up, during which 1,477 incident cases of DM were documented. Individuals with RAP had an increased risk of incident DM compared with those with a SAP(adjusted HR, 1.92; 95% CI, 1.61-2.29). The risk increased significantly with the frequency of RAP. In comparing the modifying effect of patient demographics and comorbidities, a stronger association between RAP and incident DM was observed in females (adjusted HR, 2.44; 95% CI, 1.87-3.19) than in males (adjusted HR, 1.64; 95% CI, 1.30-2.07; Pinteraction=0.03). Also, stronger associations were observed among younger patients (18-46 y) (adjusted HR=2.56; 95% CI, 1.97-3.31) and among non-tobacco abuse (adjusted HR=2.19; 95% CI, 1.81-2.65), with significant interactions for all comparisons (Pinteraction<0.05. CONCLUSIONS: In this real-world study, RAP was associated with an increased risk of incident DM. Our findings highlight an opportunity for glycemic monitoring and proactive management of patients with RAP to mitigate their risk of developing DM.

AP↗