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PubMed2026

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

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

Humans↗

PubMed2026

The Childhood Cancer and Leukemia International Consortium (CLIC): Expanding global collaboration in pediatric cancer etiology research.

Childhood cancers are rare, but incidence has risen modestly in countries with robust registration, partly reflecting improved diagnosis. In high-income countries, cancer is the leading cause of disease-related death in children. Marked inequities in incidence, survival, and research capacity underscore the need for large-scale collaboration to identify environmental, genetic, and contextual determinants of risk. The Childhood Cancer and Leukemia International Consortium (CLIC) was established in 2007 to study the etiology of childhood leukemia and later expanded in 2019 to include other childhood cancers, principally solid tumors. CLIC pools harmonized, individual-level data from case-control and cohort studies, obtained through interviews, record linkage (insurance claims, registries), or geographic information systems, and integrates germline genomic data where available. Membership has grown from 13 studies in 9 countries to 57 studies in 21 countries; recruitment spans the early 1960s to the present and encompasses approximately 150,000 cases across all tumor types and 300,000 controls with clinical, demographic, and exposure data, centralized via harmonized data dictionaries at the Data Coordination Center, established in 2014 at the International Agency for Research on Cancer, and supported by a secure analysis platform. Pooled analyses across diverse populations have implicated parental age, prenatal vitamin or folic acid use, mode of delivery, fetal growth, selected congenital anomalies, occupational or household exposures (e.g., pesticides), paternal smoking, and markers of early-life immune modulation (e.g., breastfeeding, daycare attendance) in leukemia risk, informing carcinogen evaluation and prevention. The integration of genetic ancestry and germline susceptibility data is clarifying ancestry-related differences in leukemia biology and outcomes, while confirming risk loci with population-specific effects. CLIC is now adding polygenic risk scores and exposomic data to refine etiologic subtyping and identify modifiable pathways, while broadening representation from underserved regions through partnership-building and capacity-strengthening.

Humans↗

PubMed2026

10-year outcome of fractional flow reserve-guided complete revascularization in patients with ST-segment elevation myocardial infarction - A DANAMI-3 PRIMULTI substudy.

BACKGROUND: Complete revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. However, whether the non-culprit lesions should be evaluated using angiography or fractional flow reserve (FFR) remains uncertain. The aim of this study was to evaluate the long-term outcome of patients with STEMI and multivessel disease who had non-culprit FFR-values >0.80 and thus deferred PCI. METHODS: Of the 627 patients included in the DANAMI-3-PRIMULTI trial, 314 patients were randomized to FFR-guided complete revascularization and 280 were included in this substudy. Patients were divided into a PCI-deferral group who had no PCI of non-culprit lesions (FFR > 0.80) (n = 106) and a PCI group encompassing patients treated with PCI of at least one non-culprit lesion (FFR ≤ 0.80 or an angiographical diameter stenosis of ≥90%) (n = 174). The combined endpoint included all-cause mortality, myocardial infarction, or urgent revascularization. RESULTS: During a median follow-up of 10.5 years (IQR 9.8-11.4), the composite outcome occurred in 62 (36%) patients in the PCI group and in 50 (47%) patients in the PCI-deferral group (adjusted HR 0.64, 95% CI: 0.44-0.95, p = 0.025). PCI-deferral was associated with a significantly higher risk of cardiovascular mortality (adjusted HR 0.48, CI 95% 0.24-0.97, p = 0.040) compared to the PCI group. CONCLUSION: In patients with STEMI and multivessel disease, deferring PCI of non-culprit lesions based on FFR > 0.80 was associated with an increased risk of the combination of all-cause mortality, myocardial infarction, or urgent revascularization as well as cardiovascular mortality compared to patients treated with PCI of FFR-positive non-culprit lesions.

Humans↗

PubMed2026

Ibuprofen versus acetaminophen for acute mild-to-moderate pain management in pediatric populations: a systematic review and meta-analysis of their efficacy.

UNLABELLED: Ibuprofen and acetaminophen are the most widely used analgesics in pediatric practice for the management of acute mild-to-moderate pain. Despite their widespread use, the comparative analgesic efficacy of these two agents in children remains a subject of ongoing debate, with existing evidence largely derived from heterogeneous clinical settings and small individual trials. Therefore, this study aimed to systematically review and meta-analyze randomized controlled trials comparing the analgesic efficacy of ibuprofen versus acetaminophen in pediatric populations with acute mild-to-moderate pain. A systematic literature search was conducted up to May 2026 in PubMed, Scopus, and Web of Science. The review was conducted and reported in accordance with the PRISMA-Children and Adolescents (PRISMA-C) 2026 reporting guideline. Eligible studies were randomized controlled trials comparing ibuprofen with acetaminophen in children and adolescents (defined as individuals aged 0 to < 18 years) with acute pain, reporting at least one extractable efficacy outcome. Continuous outcomes were synthesized as standardized mean differences (Hedges' g) using random-effects models; dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2 tool and certainty of evidence was evaluated using the GRADE framework. Eight randomized controlled trials enrolling 1325 participants were included. Three pediatric trials contributed to the primary continuous pain outcome meta-analysis (n = 196 analyzable participants), yielding a pooled SMD of - 0.28 (95% CI - 0.57 to 0.00; p = 0.052; I2 = 0%), indicating a small effect favoring ibuprofen that did not reach conventional statistical significance. Given the small number of contributing studies (k = 3), the I2 statistic should be interpreted with caution as it has limited power to detect heterogeneity in this context. For the dichotomous pain freedom outcome (2 trials, n = 114), no significant difference was observed (pooled RR 1.03, 95% CI 0.53-1.99; p = 0.93; I2 = 0%). A prespecified sensitivity analysis including an adult soft-tissue injury trial attenuated the pooled effect toward the null (SMD - 0.15, 95% CI - 0.38 to 0.09; p = 0.23; I2 = 36.6%). Narrative synthesis of additional studies generally demonstrated comparable analgesic efficacy between the two agents across postoperative and outpatient pediatric settings. The overall certainty of evidence was rated as low for both primary outcomes, primarily due to imprecision and indirectness. CONCLUSION: Current evidence from randomized controlled trials does not demonstrate a superiority of ibuprofen over acetaminophen for acute mild-to-moderate pain management in children. Both agents appear to provide clinically meaningful analgesia across heterogeneous pediatric pain settings. The clinical choice between agents should be guided by individual patient factors, including contraindications to NSAIDs, the inflammatory nature of the pain etiology, and patient-specific characteristics. The low certainty of evidence underscores the need for adequately powered, methodologically rigorous trials to definitively establish the comparative efficacy of these two analgesics in the pediatric population. WHAT IS KNOWN: • Ibuprofen and acetaminophen are the two most widely used non-opioid analgesics for acute mild-to-moderate pain in children, and both are recommended as first-line agents by major international guidelines. • Prior meta-analyses in mixed pediatric-adult populations have suggested a modest analgesic advantage of ibuprofen over acetaminophen, but pediatric-specific evidence has remained limited and methodologically heterogeneous. WHAT IS NEW: • This systematic review and meta-analysis, restricted to randomized controlled trials in pediatric populations, found that ibuprofen showed a small effect favoring pain reduction compared with acetaminophen (SMD - 0.28, p = 0.052), although this did not reach conventional statistical significance. • The analgesic advantage of ibuprofen may be more pronounced in pain etiologies with a significant inflammatory component (e.g., fractures). At the same time, both agents appear broadly equivalent in most other acute pediatric pain settings, supporting individualized analgesic selection based on clinical context and patient-specific factors.

Humans↗

PubMed2026

Efficacy and safety of pantoprazole for stress-ulcer prophylaxis in critically ill patients: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Stress-related mucosal damage (SRMD) is common in critically ill patients, and pharmacologic prophylaxis remains essential. This study evaluated the efficacy and safety of pantoprazole for stress-ulcer prophylaxis in ICU patients. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted per PRISMA-2020 guidelines. PubMed, Scopus, and CENTRAL were searched for studies comparing pantoprazole with placebo in adult and pediatric ICU patients. The primary outcome was clinically important gastrointestinal (GI) bleeding; secondary outcomes included mortality, ventilator-associated pneumonia (VAP), and Clostridioides difficile infection. RESULTS: Seven RCTs (n ≈ 9127; pantoprazole = 4575; placebo = 4552) were included. Pantoprazole significantly reduced clinically important GI bleeding (RR = 0.53; 95% CI 0.29-0.94; p = 0.03) without affecting overall mortality (RR ≈ 0.99 [95% CI 0.92-1.05]; p = 0.68). Infection rates were similar between groups (VAP: RR = 0.99; p = 0.78; C. difficile: RR = 1.11; p = 0.73). Sensitivity analyses confirmed robustness. CONCLUSIONS: Pantoprazole effectively reduces clinically important GI bleeding without increasing infection or overall mortality.

Pantoprazole↗

PubMed2026

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans↗

PubMed2026

A reanalysis of the Hitachi cohort study evaluating the effectiveness of low-dose CT screening for lung cancer.

The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.

epidemiology/public health↗

PubMed2026

Comparative Efficacy of Insulin and Alternative Therapies for Hypertriglyceridemia-Associated Acute Pancreatitis: A Systematic Review and Network Meta-Analysis.

BACKGROUND AND AIMS: Hypertriglyceridemia-induced acute pancreatitis is associated with high triglyceride levels and may lead to significant clinical complications. Rapid TG-lowering strategies, including insulin, therapeutic plasma exchange (TPE), heparin, hemofiltration, and conservative management, are used in clinical practice; however, their comparative efficacy and impact on clinical outcomes remain uncertain. METHODS: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines and International Prospective Register of Systematic Reviews (PROSPERO) registration (CRD420251239674), we searched PubMed, Embase, Web of Science, Scopus, CINAHL, Google Scholar, and Cochrane. Primary outcomes included TG reduction, C-reactive protein (CRP), length of stay, mortality, and organ failure. Secondary outcomes included renal and respiratory failure. Random-effects network meta-analyses estimated mean differences or relative risks with 95% confidence intervals; treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA). Predefined sensitivity analyses were conducted according to study design (RCTs) and risk of bias (ROB). RESULTS: Across predominantly observational evidence, no intervention demonstrated statistically significant superiority over insulin-based therapy for mortality, organ failure, or length of stay, and no consistent clinical benefit was observed despite differences in biochemical TG reduction. Although some interventions showed relatively favorable SUCRA rankings across selected outcomes, these findings were not consistently supported by statistically significant or high-certainty evidence. In RCT-restricted analyses, therapeutic plasma exchange (TPE) significantly reduced TG levels versus insulin (MD - 620.0; p = 0.03) and CRP versus conservative therapy (MD - 0.80; p < 0.01), while insulin plus heparin was associated with shorter hospital stay (MD - 1.60 days; p < 0.01). However, faster triglyceride reduction did not consistently translate into improved mortality, organ failure, ICU-related outcomes, or length of stay. CONCLUSION: Despite improvements in biochemical markers, the clinical significance of rapid TG reduction in HTG-AP remains uncertain, as these effects were not consistently associated with improvements in mortality, organ failure, ICU-related outcomes, or hospital length of stay. Given that most available evidence was derived from nonrandomized studies and that the certainty of evidence was predominantly low or very low, adequately powered randomized controlled trials are needed to determine whether accelerated triglyceride lowering improves clinically meaningful patient outcomes.

Humans↗

PubMed2026

Prognostic Value of Frailty in Aortic Surgery: A Systematic Review and Meta-Analysis Comparing Frailty Assessment Tools.

BACKGROUND: Frailty is increasingly recognized as an important determinant of outcomes after aortic vascular surgery, but assessment methods vary substantially and the optimal tool for risk stratification remains uncertain. This systematic review and meta-analysis evaluated the prognostic value of preoperative frailty and compared the predictive performance of different frailty instruments in aortic surgery. METHODS: PubMed, Embase, and Cochrane Library were searched from inception to April 27, 2026. Eligible studies included patients undergoing open, endovascular, or hybrid aortic procedures involving abdominal, thoracic, thoracoabdominal, arch, and proximal aortic diseases, including aneurysms and dissections, assessed frailty preoperatively, and reported postoperative outcomes. RESULTS: Thirty studies comprising 419,459 patients were included. Frailty was associated with higher early mortality (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.54-3.14) and late mortality (hazard ratio 2.18; 95% CI 1.64-2.90). Frail patients also had increased risks of major complications (OR 2.52; 95% CI 1.22-5.19), acute kidney injury (OR 1.64; 95% CI 1.34-2.02), and nonhome discharge (OR 5.50; 95% CI 3.05-9.92). Associations were consistent across surgical approaches and aortic segments. Judgment-based or phenotype-like tools yielded higher effect estimates than deficit-accumulation indices, although differences were not statistically significant; among index-based tools, Modified Frailty Index (mFI)-11 outperformed mFI-5. CONCLUSION: Preoperative frailty strongly predicts mortality, morbidity, and loss of functional independence after open, endovascular, and hybrid aortic surgery across different aortic segments and pathologies, including aneurysmal and dissecting aortic disease. Routine frailty assessment may improve risk stratification and perioperative decision-making.

Humans↗

PubMed2026

Safety and efficacy of immune checkpoint inhibitors as a bridge to allogeneic hematopoietic stem cell transplantation in classical Hodgkin lymphoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for relapsed or refractory classical Hodgkin lymphoma (cHL); however, a substantial subset of patients ultimately requires allogeneic hematopoietic stem cell transplantation (allo-HCT) to achieve long-lasting disease control. The use of ICIs as a bridge to allo-HCT has therefore gained increasing clinical interest, though concerns persist regarding post-transplant complications and incompletely-defined safety profiles. Accordingly, this systematic review and meta-analysis was conducted to evaluate outcomes of ICIs administered prior to allo-HCT in cHL. Following PRISMA guidelines, a comprehensive literature search was conducted across online databases through January 2026. Eligible studies included observational designs reporting survival and transplant-related outcomes in cHL patients treated with ICIs followed by allo-HCT. Pooled proportions for overall survival, progression-free survival, non-relapse mortality, and graft-versus-host disease (GVHD) incidence were calculated using a random-effects model. Seven studies comprising 739 patients were included. Post-transplant survival outcomes were favorable, with high pooled estimates across timepoints. Transplant-related mortality remained low, with NRM rates consistently within an acceptable range through long-term follow-up. Acute GVHD was observed at a meaningful frequency, including a smaller subset of severe cases, while chronic GVHD occurred in approximately one-quarter of patients at follow-up. Overall, these findings suggest that ICI therapy prior to allo-HCT in cHL is associated with encouraging survival and disease control and does not appear to confer excessive non-relapse mortality, supporting its use as a feasible and effective bridging strategy, while underscoring the need for future prospective studies to clarify optimal timing, risk mitigation strategies, and patient selection.

Humans↗

PubMed2026

Efficacy of sodium-glucose cotransporter 2 inhibitors after acute myocardial infarction: Are the benefits limited to patients with diabetes? A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction remains one of the leading causes of death worldwide. Recently, studies have focused on evaluating the effectiveness of SGLT2 inhibitors in this scenario. Objectives We aimed to perform a meta-analysis comparing the efficacy of SGLT2 inhibitors vs standard care. METHODS: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and observational studies comparing patients with acute myocardial infarction using iSGLT2 inhibitors and standard care. Statistical analyses were conducted using R software (v 4.3.2) and a random-effects model was employed for all outcomes. RESULTS: A total of 31,378 patients were included, with 10,897 (34.7%) assigned to the SGLT2 inhibitor group. Among these studies, three were randomized controlled trials (RCTs). There was a significant difference in reduction of HF readmissions (OR 0.61; p < 0.01), all-cause mortality (OR 0.62; p < 0.01;) and stroke (OR 0.67; p < 0.01;). However, there was no significant difference in cardiovascular death, rehospitalization for any cause and recurrence of acute MI. Meta regression and subgroup analysis showed a trend toward better outcomes in the diabetic and non-STEMI population. CONCLUSIONS: SGLT2 inhibitors were associated with lower HF rehospitalization, stroke, and all-cause mortality after acute MI, mainly in observational studies. Benefits appeared greater in diabetic and non-STEMI patients. Dedicated RCTs focusing on diabetic, particularly non-STEMI, populations are needed to confirm these findings. KEY POINTS: What is already known on this topic: SGLT2 inhibitors have demonstrated cardiovascular and renal benefits in patients with heart failure and type 2 diabetes mellitus. However, their role in the acute myocardial infarction (AMI) setting remains uncertain, particularly regarding post-AMI outcomes such as heart failure readmissions, mortality, and recurrent ischemic events, with current evidence derived from heterogeneous and predominantly observational studies. WHAT THIS STUDY ADDS: This meta-analysis, including over 31,000 patients, suggests that SGLT2 inhibitors are associated with reductions in heart failure readmissions, all-cause mortality, and stroke following AMI. These associations were more consistently observed in patients with type 2 diabetes and in non-ST-segment elevation myocardial infarction (NSTEMI) populations. However, randomized controlled trials showed neutral results, and the observed benefits were mainly driven by observational studies. Meaning: These findings should be interpreted as hypothesis-generating. While SGLT2 inhibitors may represent a potential therapeutic strategy in selected post-AMI populations, particularly patients with diabetes and NSTEMI, current evidence does not support routine early in-hospital initiation. Dedicated randomized trials specifically enrolling diabetic post-AMI patients are required to clarify optimal timing and clinical benefit.

Humans↗

PubMed2026

Tranexamic acid in spontaneous intracerebral hemorrhage: an updated systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Tranexamic acid (TXA) is a well-established antifibrinolytic medication in the general population. However, its efficacy and safety for patients with spontaneous intracerebral hemorrhage (ICH) remain inconclusive. Consequently, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of TXA for spontaneous ICH. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) following established methodological standards. Our search encompassed eight electronic databases from inception to April 25, 2024. The primary outcome was a reduction in all-cause mortality. The secondary outcomes included improvements in functional independence, neurological impairment, activities of daily living, and reduction in hematoma expansion (HE). Fixed-effects or random-effects model were performed for pooled data where eligible. RESULTS: A total of 9 RCTs that initially enrolled 3,124 patients were included. There were no significant differences observed concerning all-cause mortality (RR, 1.03; 95% CI [0.89-1.18]), hematoma expansion (RR, 0.90; 95% CI [0.80-1.00]), improvement of functional independence (RR, 1.02; 95% CI [0.92-1.12], neurological impairment (MD, -0.88 [95% CI, -2.22-0.45]), or activities in daily living (MD, -0.83 [95% CI, -29.25-12.59]). The pooled data indicated that TXA for ICH was associated with a decrease in hematoma volume from baseline (MD, -1.74; 95% CI [-2.47 to -1.02]). No significant difference in adverse events was observed between the TXA group and the control group. CONCLUSIONS: In summary, TXA does not affect all-cause mortality, functional outcomes, or neurological impairment, nor does it reduce HE, despite reducing hematoma volulume. TXA use for ICH requires careful clinical consideration.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Excimer laser angioplasty for acute coronary occlusion: a stratified meta-analysis of efficacy against aspiration thrombectomy and conventional PCI.

Primary percutaneous coronary intervention (PCI) achieves epicardial reperfusion in most STEMI patients, yet microvascular obstruction persists in up to 60% of patients. Excimer laser coronary angioplasty (ELCA) vaporizes thrombus in situ and may reduce distal embolization, but the evidence base has not been systematically synthesized. This systematic review and meta-analysis (PROSPERO CRD420261422463) included comparative studies of adjunctive ELCA versus aspiration thrombectomy (Stratum A) or PCI alone (Stratum B) in acute coronary occlusion. Primary outcomes were final TIMI-3 flow and myocardial blush grade (MBG) 3; secondary outcomes were short-term mortality, MACCE, and slow-flow/no-reflow. A random-effects model with Hartung-Knapp-Sidik-Jonkman confidence intervals was applied to all outcomes. Certainty was assessed with GRADE. Ten studies (1 RCT, 9 observational) were included, from a total enrolled population exceeding 3,500. In Stratum A, no outcome reached significance: MBG-3 (OR 3.57, 95% CI 0.07-185.10), mortality (OR 0.31, 0.02-4.04), MACCE (OR 0.22, 0.04-1.26), TIMI-3 flow (OR 1.58, 0.67-3.75) and slow-flow/no-reflow (OR 0.78, 0.22-2.78). In Stratum B, using each study's propensity-matched data, no outcome differed significantly (TIMI-3 OR 0.88, 0.38-2.03; MBG-3 OR 1.06, 0.13-8.43; slow-flow/no-reflow OR 0.93, 0.29-3.02; mortality OR 0.44, 0.05-3.80). Composite endpoints were not pooled across incompatible follow-up horizons, and all outcomes were of very low certainty. Adjunctive ELCA-containing strategies during primary PCI were not associated with improved angiographic or short-term clinical outcomes against either comparator. Multicenter randomized trials are required before recommending clinical adoption.

Humans↗

PubMed2026

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n = 148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1·08, 95% CI 1·02-1·13; p = 0·004; I2 = 44%), driven by the observational studies group (1·08, 1·02-1·14; I2 = 61%); RCTs showed a directionally consistent but non-significant RR (1·12, 0·87-1·43; I2 = 0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans↗

PubMed2026

Intravenous thrombolysis for ischemic stroke in extended time window selected with CT perfusion: a systematic review and meta-analysis.

PURPOSE: Recent randomized controlled trials (RCTs) have provided new evidence regarding the efficacy and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) presenting within the extended time window (ETW). We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IVT, in patients treated within the ETW and selected with perfusion imaging criteria, predominantly computed tomography perfusion (CTP). METHODS: A systematic review and meta-analysis, registered in PROSPERO, was conducted including all available RCTs comparing IVT with best medical treatment (BMT) in patients with AIS within the ETW, selected using advanced perfusion imaging criteria. The predefined efficacy outcomes were excellent functional outcome and good functional outcome at 3 months. The safety endpoints included symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days. RESULTS: Six RCTs, including 1182 patients treated with IVT and 1176 patients receiving BMT, were included. IVT was associated with a higher likelihood of achieving excellent and good functional outcomes at 3 months. Exploratory subgroup analyses by treatment timing suggested consistent findings up to 24 hours. No significant difference in 90-day mortality was observed between groups, whereas IVT was associated with an increased risk of sICH. CONCLUSION: Treatment with IVT in the ETW (4.5-24 h) in patients selected using advanced perfusion imaging, predominantly CTP, may be associated with improved functional outcomes in patients with AIS. Although IVT was associated with an increased risk of sICH, no significant increase in 90-day mortality was observed. PROSPERO REGISTRATION: CRD420261304314.

Aged↗

PubMed2026

Efficacy and safety of middle meningeal artery embolization for chronic subdural hematoma: an updated systematic review and meta-analysis focusing on time of intervention.

INTRODUCTION: Chronic subdural hematoma (cSDH) is increasingly prevalent among older adults due to population aging and widespread antithrombotic use. Although burr-hole drainage remains the standard treatment, recurrence rates are substantial. Middle meningeal artery embolization (MMAE) has emerged as an adjunctive strategy to disrupt dural neovascularization and prevent rebleeding. OBJECTIVES: To assess the efficacy and safety of MMAE combined with standard therapy versus standard therapy alone, with stratification by timing of intervention. METHODS: Randomized controlled trials (RCTs) were searched in PubMed, Scopus, and Cochrane Central up to July 2025. Adults with confirmed cSDH were included. The primary outcome was hematoma recurrence or persistence. Secondary outcomes were reoperation, hematoma resorption, serious adverse events, neurological death, mortality, functional independence, and hospital stay. Risk of bias was assessed with RoB-2, and analyses followed PRISMA guidelines (PROSPERO CRD420251112841). RESULTS: Seven RCTs (1,889 patients) were included. Compared with standard therapy, MMAE significantly reduced recurrent or residual cSDH (RR 0.63; 95% CI 0.46-0.85) and reoperation (RR 0.39; 95% CI 0.28-0.56) without increasing serious adverse events (RR 0.87; 95% CI 0.72-1.06), neurological death, mortality, or poor functional outcomes. Hematoma resorption did not differ significantly. Subgroup and sensitivity analyses confirmed the robustness of the results across age, intervention timing, and follow-up duration. CONCLUSION: MMAE combined with standard therapy significantly reduces recurrence and reoperation in cSDH without increasing adverse events or mortality. Benefits appear independent of procedural timing, though larger RCTs with extended follow-up are warranted to define long-term outcomes and optimal use.

Humans↗

PubMed2026

Safety and outcomes of dapagliflozin initiation in critically ill patients with acute kidney injury: A post-hoc analysis of the defender trial.

BACKGROUND: SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS: Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS: Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS: Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.

Humans↗