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PubMed2026

Intravenous Nicorandil in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary PCI: The CLEAN Randomized Clinical Trial.

BACKGROUND: Nicorandil, an adenosine triphosphate-sensitive potassium-channel opener with nitrate-like properties, may reduce reperfusion injury and microvascular obstruction in ST-segment elevation myocardial infarction (STEMI), but large-scale randomized evidence on long-term clinical outcomes is inconclusive. OBJECTIVES: The CLEAN trial aimed to assess whether adjunctive intravenous nicorandil improves 12-month clinical outcomes in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial conducted at 49 hospitals in China, patients aged 18 to 80 years with STEMI within 12 hours of symptom onset were randomly assigned (1:1) to receive intravenous nicorandil (6 mg bolus before reperfusion followed by 6 mg/h infusion for 48 h) or matching placebo. Oral nicorandil was prohibited during follow-up. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, target vessel revascularization, or unplanned hospitalization for heart failure within 12 months. RESULTS: Between January 2021 and December 2023, 1,503 patients were enrolled and randomly assigned to nicorandil (n = 748) or placebo (n = 755). The primary composite outcome occurred in 98 patients (13.1%) in the nicorandil group (113 events over 717.2 person-years) and 99 (13.1%) in the placebo group (136 events over 710.3 person-years), with no significant difference between groups (rate ratio: 0.869; 95% CI: 0.650-1.162; P = 0.3429). Among secondary outcomes, nominal reductions were observed in cardiovascular death (1.9% vs 3.6%; HR: 0.515; 95% CI: 0.269-0.983) and target-vessel revascularization (1.1% vs 3.0%; HR: 0.322; 95% CI: 0.143-0.727), whereas rates of nonfatal myocardial infarction and unplanned hospitalization for heart failure were similar between groups. Adverse events did not differ between groups. CONCLUSIONS: In patients with STEMI undergoing primary percutaneous coronary intervention, adjunctive intravenous nicorandil did not significantly reduce the 12-month primary composite outcome. These findings do not support routine use of intravenous nicorandil in unselected patients with STEMI. (Clinical Efficacy and sAfety of Intravenous Nicorandil; NCT04665648).

Humans↗

PubMed2026

An Overview of Red Breast Syndrome: A Qualitative Systematic Review of the Literature and a Single-Center Case Series.

Red breast syndrome (RBS) is an uncommon inflammatory complication that may occur following implant-based breast reconstruction and can clinically mimic surgical-site infection. This qualitative systematic review, based on comprehensive PubMed and Scopus searches, summarizes the existing literature on RBS, focusing on its etiology, clinical presentation, diagnostic characteristics, and therapeutic approaches following breast reconstruction using acellular dermal matrices (ADMs). A management protocol is proposed based on available data, and a single-center case series is presented from our Hospital, including patients who developed RBS after direct-to-implant reconstruction with ADM between January 2022 and December 2024. Twenty-nine studies met the inclusion criteria, comprising case reports, case series, and retrospective or prospective cohort studies. The reported incidence of RBS ranged from 0% to 29.6%. Proposed etiologies include endotoxin contamination, residual cellular debris, delayed hypersensitivity reactions, and lymphatic or vascular impairment of mastectomy flaps. Most reports described localized erythema confined to the area of the ADM, with normal inflammatory markers and negative imaging findings, whereas antibiotic therapy frequently failed to achieve improvement. Corticosteroids represented the most consistently effective treatment, although some cases required ADM removal or replacement. In our institutional case series (n = 8), symptom onset occurred between 4 weeks and 7 months postsurgery. Inflammatory markers remained within normal limits, imaging rarely demonstrated fluid collections, and symptoms resolved within days to weeks with corticosteroid therapy or conservative management. This review consolidates current evidence, proposes a diagnostic-therapeutic algorithm and highlights the need for prospective investigations and manufacturer-level endotoxin testing to elucidate pathogenesis and optimize clinical management. Level of Evidence: 2 (Risk) For image description, please refer to the figure legend and surrounding text.

Humans↗

PubMed2026

A New Highly Concentrated Insulin Aspart AT278 (500 U/mL) Demonstrates Ultra-Rapid Pharmacokinetic and Pharmacodynamic Properties in Type 2 Diabetes Regardless of BMI.

AIMS: To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 [500 U/mL]; AT278-U500) compared with standard concentration insulin aspart (InsAsp [100 U/mL]; InsAsp-U100) and U500 human regular insulin (HumIns [500 IU/mL]; HumIns-U500). MATERIALS AND METHODS: This single-centre, randomised, double-blind crossover 12-h euglycaemic clamp study was conducted in 41 overweight and obese people with type 2 diabetes (BMI 25.0-38.7 kg/m2) receiving a single subcutaneous dose (0.5 U/kg) of AT278-U500 and InsAsp-U100. HumIns-U500 was consecutively studied open label in a 24-h clamp. RESULTS: AT278-U500 exhibited a significantly faster insulin absorption than InsAsp-U100 and HumIns-U500 (t Early50%Cmax: 9 min vs. 35 min vs. 55 min), leading to a significantly higher glucose-lowering effect within the first hour (AUCGIR,0-60min) compared with both InsAsp-U100 (treatment ratio 2.02 [95% CI 1.64; 2.50]) and HumIns-U500 (3.91 [2.89; 5.27]). When divided by median BMI (29.7 kg/m2), AUCGIR,0-60min was significantly higher with AT278-U500 in both the low-BMI and high-BMI subgroup compared to InsAsp-U100. Linear regression showed a significant inverse relationship between BMI and AUCGIR,0-60min for InsAsp-U100 (slope -0.142, p < 0.0001), whereas AT278-U500 showed no such relationship. Overall insulin exposure was similar for AT278-U500 and InsAsp-U100, while overall glucose-lowering effect was comparable across all three treatments. CONCLUSIONS: AT278-U500 maintains its ultra-rapid onset characteristics independent of BMI, representing the first ultra-rapid U500 option for prandial dosing in insulin-resistant people with type 2 diabetes requiring high-dose therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05754424.

Humans↗

PubMed2026

Effect of Local Anesthetic Solution at Different Temperatures for Epidural Labor Analgesia on Intrapartum Fever: A Randomized Clinical Trial.

BACKGROUND: Whether heating local anesthetic solutions to core body temperature (37°C) for epidural labor analgesia reduces intrapartum fever incidence remains undefined in the current literature. METHODS: This double-blind randomized controlled trial (RCT) enrolled 220 nulliparous parturients (18-35 years, American Society of Anesthesiologists [ASA] physical status II, term singleton pregnancy). Participants were randomized to receive epidural labor analgesia with 0.075% ropivacaine + 0.5 µg/mL sufentanil at 37°C (warmed group) or 22°C (room-temperature group). Epidurals were placed at L3-L4 with a test dose of 3 mL of 1.5% lidocaine at room temperature, followed by programmed bolus epidural analgesia (initial 10 mL, 10 mL/h) and patient-controlled epidural analgesia (PCEA) 5 mL (30-minute lockout). Tympanic temperature was measured every 30 minutes from epidural initiation to delivery, defining intrapartum fever as ≥38°C. The primary outcome was fever incidence, on which the power analysis was based, and also maximum temperature and shivering. Secondary outcomes comprised analgesia onset, block level, labor durations, neonatal Apgar scores, umbilical cord blood pH and BE, and maternal adverse events. RESULTS: A total of 220 parturients were included (warmed group, n = 110; room-temperature group, n = 110). The warmed group had a lower intrapartum fever incidence (15.5% [17/110] vs 30.9% [34/110], relative risk [RR] 0.5 [95% confidence interval {CI}, 0.298-0.840]; P = .007); however, the reduction of 49.8% did not reach the preset clinically meaningful difference of 60% reduction proposed in the power analysis. The maximum body temperature was also lower in the warmed group: median (interquartile range [IQR]) 37.4 (IQR, 37.2-37.7) °C vs 37.6 (IQR, 37.3-38.0) °C, median difference -0.2 (95% CI, -0.3 to -0.1) °C ( P = .006). Shivering incidence was not different between groups (10.9% [12/110] vs 14.5% [16/110]; P = .418). No statistically significant differences were observed between groups in any of the secondary outcomes assessed, including block characteristics, local anesthetic consumption, labor duration, neonatal outcomes, and maternal adverse events. CONCLUSION: Although we found a 50% reduction in the incidence of temperature rise using warmed (37°C) local anesthetics for epidural labor analgesia, this did not reach our preset threshold of 60% reduction.

Humans↗

PubMed2026

Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.

STUDY OBJECTIVES: To evaluate the effect of daridorexant on nighttime respiratory function and sleep in adults with severe obstructive sleep apnea (OSA) without insomnia. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, two-period, crossover trial was conducted at a single sleep center in 16 adults (≥18 years) with severe OSA without insomnia. In each period, daridorexant 50 mg or placebo was administered every evening for 5 days. Primary and secondary endpoints were the treatment differences (daridorexant-placebo) for apnea/hypopnea index (AHI) and oxygen saturation (SpO2) during total sleep time (TST), respectively, after last dosing. A mean increase in AHI ≥10 events/h and mean decrease in nocturnal SpO2 ≤-2% were the minimum changes considered to be clinically meaningful negative effects. Other endpoints included TST, latency to persistent sleep (LPS), and wake after sleep onset (WASO). RESULTS: Mean baseline AHI was 51.2 events/h (range 30.8, 82.2) and mean SpO2 during TST was 92.1% (range 88.5, 94.3). No clinically meaningful effect of daridorexant on AHI or SpO2 during TST was detected. Treatment differences were -3.7 events/h (one-sided 95% CI ≤ +4.2) and - 0.12 % (one-sided 95% CI ≥ -0.6), respectively. Compared with placebo, daridorexant increased TST by 32.5 min (90% CI: 6.9, 58.2), associated with shorter LPS (-10.3 min [90% CI: -20.6, -0.02]) and a trend towards reduced WASO (-15.2 min [-31.2, 0.9]). Four adverse events were reported (daridorexant n = 3; placebo n = 1), all of mild intensity and none related to respiratory function. CONCLUSION: Short-term treatment with daridorexant does not impair sleep-disordered breathing and may improve sleep in patients with severe OSA. CLINICAL TRIAL: ClinicalTrials.gov, https://clinicaltrials.gov/study/NCT05458193, NCT05458193. Statement of Significance Obstructive sleep apnea (OSA) is highly prevalent and associated, in 30%-50% of cases, with insomnia-related symptoms, yet the safety of insomnia medications in OSA remains unclear. Daridorexant, a dual orexin receptor antagonist for the treatment of adults with insomnia disorder, previously showed no negative effect on sleep-disordered breathing in participants with mild/moderate OSA. This randomized, double-blind, placebo-controlled, crossover trial evaluates daridorexant 50 mg (maximum therapeutic dose) in participants with severe OSA without insomnia. Repeated dosing (5 nights) did not impair nighttime respiratory function, as assessed by apnea/hypopnea index and nocturnal oxygen saturation. Moreover, improvements in sleep characteristics were observed with daridorexant, extending evidence that daridorexant 50 mg is safe and well-tolerated and may improve sleep in adults with severe OSA.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2025

Examining Behavioral Interventions for Infancy and Early Toddlerhood: A Systematic Review of Intervention Effects, Parameters, and Participants.

Rapid advancement is paving the way to identify children who would likely benefit from early intervention during the first years of life, prior to the onset of significant delays in development. With the widely acknowledged benefits of early intervention, key questions arise: Does behavioral intervention targeted to infancy and early toddlerhood improve developmental outcomes? What procedures might be used, and under what circumstances? Who do these interventions work for? The current review comprehensively examined the literature on behavioral interventions based in operant learning, focused on key developmental areas with children in the first two years of life. We located and synthesized 69 studies with unique participant cohorts that included 1735 children. The search revealed many studies focused on the first year of life, of which a large proportion investigated approaches to increase communication. We provide implications, limitations, and future directions on how behavioral interventions for infants and young toddlers can inform current practice and future intervention research this population.

Humans↗

PubMed2026

Valproate vs levetiracetam in juvenile myoclonic epilepsy: systematic review and meta-analysis.

INTRODUCTION: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome with onset typically in adolescence and a chronic course requiring long-term antiseizure medications (ASMs). Valproate (VPA) is the most effective treatment for seizure control in JME but use is limited by metabolic, cognitive, and teratogenic adverse effects (AEs). Levetiracetam (LEV) is an alternative ASM when VPA is contraindicated or not tolerated. Comparisons of the efficacy and long-term tolerability of VPA and LEV remain limited. METHODS: We conducted a systematic review and meta-analysis using PRISMA guidelines and the Cochrane Handbook. We searched PubMed, Embase, and the Cochrane Library from inception through January 2026 for studies in JME patients comparing LEV and VPA, and included randomized controlled trials and comparative observational studies with ≥ 6 months of follow-up. Primary outcomes were seizure remission and ASM failure or treatment discontinuation. Secondary outcomes included, memory impairment, weight gain or obesity, dizziness, and overall AEs. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Heterogeneity was assessed using the I2 statistic. RESULTS: Seven studies encompassing 1,009 patients were included. VPA was associated with higher pooled seizure remission rates compared with LEV (344 of 574 vs. 169 of 390; RR 1.44, 95% CI 1.27-1.63); however, substantial heterogeneity (I2 = 88.4%) limits confidence in this finding. VPA was associated with a lower risk of drug failure or treatment discontinuation (RR 0.68, 95% CI 0.54-0.86), with no heterogeneity (I2 = 0.0%). VPA was also associated with a higher risk of memory impairment (RR 5.37, 95% CI 2.05-14.04; I2 = 74.5%) and weight gain or obesity (RR 6.40, 95% CI 3.64-11.26; I2 = 35.9%). No significant differences were observed between treatments regarding dizziness (RR 0.91, 95% CI 0.61-1.37; I2 = 21.2%). Sensitivity analyses confirmed the robustness of the pooled estimates. CONCLUSION: VPA was associated with higher seizure remission rates and lower treatment discontinuation compared with LEV; however, these findings must be interpreted with caution given the substantial heterogeneity, the predominance of observational studies, and the serious risk of bias identified in most included studies VPA also demonstrated lower rates of treatment discontinuation, despite a higher burden of cognitive impairment and weight gain. No relevant differences were observed regarding dizziness. Large-scale randomized trials with standardized outcome definitions and longer follow-up are needed to define the comparative risk-benefit profiles of LEV and VPA in JME.

Humans↗

PubMed2026

Umbilical Cord-Derived Cell-Based Interventions for Bronchopulmonary Dysplasia and Related Complications in Preterm Infants: A Bayesian Sparse-Data Meta-Analysis.

Bronchopulmonary dysplasia (BPD) is a major complication of prematurity with limited disease-modifying therapies. We evaluated umbilical cord-derived cell-based interventions for BPD and related complications in preterm infants. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-based systematic review and meta-analysis were registered in PROSPERO. PubMed, Cochrane Library, Web of Science, CNKI, and Wanfang were searched from inception to June 14, 2026. Comparative clinical studies of umbilical cord-derived cell-based interventions in preterm infants at risk of or diagnosed with BPD were included. Outcomes included BPD, BPD severity, death, persistent pulmonary hypertension of the newborn (PPHN), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), late-onset sepsis (LOS), and adverse events (AEs). Bayesian random-effects meta-analysis used a binomial-normal hierarchical model to estimate pooled odds ratios (ORs), 95% credible intervals (CrIs), prediction intervals, and heterogeneity. Twelve studies were included. Umbilical cord-derived cell-based interventions showed a possible protective effect on overall BPD (OR, 0.48; 95% CrI, 0.14-1.20). Stronger associations were observed for severe BPD (OR, 0.17; 95% CrI, 0.01-0.85), moderate or severe BPD (OR, 0.28; 95% CrI, 0.09-0.70), and ROP stage ≥3 (OR, 0.17; 95% CrI, 0.02-0.65). No conclusive benefit or harm was observed for death, PPHN, PDA, IVH, NEC, or LOS. No treatment-related serious AEs were identified. However, prediction intervals were generally wide, and the certainty of evidence was low to very low for most outcomes. Umbilical cord-derived cell-based interventions may reduce the risk of moderate or severe BPD in preterm infants, with an additional potential benefit for ROP stage ≥3. Current evidence remains limited, and larger randomized trials with standardized outcomes and long-term follow-up are needed.

Humans↗

PubMed2026

Clinical features and outcomes of patients with anti-neutrophil cytoplasmic antibody-positive systemic lupus erythematosus from a single-center retrospective study.

INTRODUCTION: The role of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus (SLE) remains unclear. ANCA positivity has been linked to more severe disease and possible overlap with ANCA-associated vasculitis, but available data are inconsistent. METHODS: We conducted a retrospective single-center study of SLE patients treated at the University Hospital in Kraków (2012-2022). Patients fulfilled the 2019 EULAR/ACR criteria. ANCA positivity (anti-MPO or anti-PR3) was confirmed by ELISA. Clinical features, laboratory findings, treatment, and outcomes were analyzed. RESULTS: Among 1039 SLE patients, 18 (1.73%) were ANCA-positive (anti-MPO, 72.22%; anti-PR3, 27.78%). Most ANCA-positive SLE patients were female (88.89%), with a median age at disease onset of 35.5 years. The most common manifestations in ANCA-positive cases were hematological abnormalities (100%), constitutional symptoms (88.89%), and joint involvement (88.89%). Renal involvement was observed in 72.22% (n = 13) of ANCA-positive SLE patients; however, lupus nephritis was confirmed by kidney biopsy in only seven cases. Vasculitis was rare (5.56%). Anti-dsDNA (61.11%) and anti-SSA (50%) were the most frequent autoantibodies. No significant differences were found between anti-MPO and anti-PR3 subgroups. Most ANCA-positive patients received glucocorticoids (94.44%), cyclophosphamide (61.11%), and antimalarials (61.11%). No statistically significant differences were observed between the ANCA-positive and ANCA-negative groups (p > 0.05 for all parameters). CONCLUSIONS: ANCA positivity in SLE is rare and predominantly associated with anti-MPO antibodies. It is linked to frequent renal involvement but infrequent vasculitis. No differences were observed between ANCA subtypes, suggesting no distinct clinical phenotype. Key Points • ANCA positivity was rare in this systemic lupus erythematosus cohort (1.73%) and was predominantly associated with anti-MPO antibodies rather than anti-PR3 antibodies. • No significant differences in demographic characteristics, clinical manifestations, comorbidities, or autoantibody profiles were observed between ANCA-positive and ANCA-negative patients. Similarly, no significant differences were identified between the anti-PR3-positive and anti-MPO-positive groups. • ANCA-positive SLE was commonly associated with the need for intensive immunosuppressive treatment, highlighting its potential relevance as a marker of severe disease course.

Humans↗

PubMed2026

Circular RNAs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of motor neurons, with most cases lacking a clear genetic basis. Emerging evidence highlights the involvement of non-coding RNAs, particularly circular RNAs (circRNAs), in disease onset and progression. Here, we investigated circRNAs implicated in ALS and related motor neuron diseases (MNDs). Here, we provide a general overview of circular RNA metabolism and cellular functions. We then present our systematic literature review that identified ALS-associated circRNAs, followed by in silico analyses of 15 circular RNA candidates that were selected based on the most compelling data regarding ALS. Our results revealed that several circular RNAs regulate ALS-related genes, such as unfolded protein response, oxidative stress, cell cycle regulation, and apoptosis. Protein-RNA interaction analysis further showed that ALS-related circRNAs can sponge 20 RNA-binding proteins. Additionally, molecular docking analysis demonstrated that ALS-associated FUS variants significantly alter its binding affinity to circular RNAs. RNA-seq data from ALS patients confirmed significant alterations in the expression of host genes of ALS-related circRNAs and hub proteins in ALS-affected CNS tissues. Collectively, our findings identify circRNAs as potential key contributors to ALS pathogenesis.

Amyotrophic Lateral Sclerosis↗

PubMed2026

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R²=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans↗

PubMed2026

To longevity and beyond: A systems view of aging and stress resilience.

Aging is a dynamic and time-dependent process characterized by progressive functional decline across biological systems. Key hallmarks, including genomic instability, telomere attrition, loss of proteostasis, mitochondrial dysfunction, and immunosenescence, have been widely described, each reflecting distinct yet interconnected mechanistic frameworks. Rather than acting in isolation, these processes arise from complex interactions among cellular stressors, impaired repair mechanisms, and the cumulative burden of maladaptive responses. This system-level perspective explains the inter-individual variability in aging trajectories. Centenarians represent an extreme and informative model of successful aging, in which the balance between damage accumulation and repair is shifted toward the maintenance of physiological function. Their exceptional longevity is supported by coordinated genetic, epigenetic, metabolic, and immunological adaptations that enhance resilience to age-related stressors. Here, we summarize the biological drivers and theoretical frameworks of aging within an integrative context, focusing on mechanisms associated with extended healthspan in centenarians. We also examine the contribution of major animal models, highlighting their complementary roles in elucidating conserved and species-specific aging pathways. Overall, aging outcomes reflect a dynamic equilibrium between damage and repair processes. Understanding how this balance is modulated in long-lived individuals may inform strategies to promote healthy aging and delay the onset of age-related diseases.

Humans↗

PubMed2026

Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis.

BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1·0 mg [FLOW], once-weekly subcutaneous 2·4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1·73 m2, or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39·5-47·5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0·84 [95% CI 0·77-0·91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0·80 [0·69-0·92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk.

Humans↗

PubMed2026

Non-linear predictive modeling and comprehensive meta-analysis of rectal temperature in Santa Inês sheep: a systematic review of thermal challenges and biometerological trends.

A systematic and bibliometric review, combined with a meta-analysis, was used to adjust an equation for estimating the physiological responses of Santa Inês sheep subjected to different thermal challenges. The systematic review compiled data on physiological responses and the thermal environment, which were then used in the meta-analysis to adjust regression models. The bibliometric analysis mapped the relationships among studies, highlighting their usefulness in interpreting research findings and biases. Addressing prior methodological critiques, the core of this study involves replacing the linear approach with a non-linear segmented regression model to accurately define the Thermal Neutral Zone (TNZ). The Segmented Regression Model was crucial, establishing the upper limit of the Thermal Neutral Zone (TNZ) at an air temperature (tair) of 34.64 °C, where trectal begins to increase abruptly. The model, while identifying a biologically significant breakpoint, exhibited a moderate Multiple R-squared of 0.3529, highlighting the high heterogeneity and methodological variability in the current Santa Inês literature. This non-linear approach offers a biologically superior tool for identifying the onset of thermal distress.

Animals↗

PubMed2026

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans↗

PubMed2026

First evaluation of a novel recombinant eCG molecule in ewes reveals a discrepancy between ovulatory response and pregnancy outcome.

This study evaluated the reproductive performance and clinical safety of a novel recombinant eCG (r-eCG) in ewes. Two weeks prior to study onset (Day 0: intravaginal progesterone device insertion), 45 ewes were randomly assigned to negative control (NC; no eCG; n = 10), positive control (PC; 400IU commercial non-recombinant eCG; n = 20), or treatment group (T; 400IU r-eCG; n = 15). Ewes were inseminated with fresh-diluted semen (200 × 106 sperm). Ultrasonography assessed follicle count/diameter (days 11, 13), ovulation (day 13), corpus luteum (CL) number/characteristics (day 20), and pregnancy (day 44). Serum progesterone was measured on day 20; Group T underwent clinical/hematological evaluations (days 0, 20, and 44). Estrus signs were more frequent (P < 0.01) in T (100%) than NC (50%), while PC (85%) did not differ. Ovulation rates were similar between T (93%) and PC (95%), but higher than NC (50%; P < 0.05). On day 13, largest follicle diameter did not differ (P > 0.05) among groups; however, fewer follicles > 2 mm occurred in PC than NC and T (P < 0.05). CL number was higher in T than PC (2.0 ± 0.3 vs. 1.0 ± 0.0, P < 0.01), while NC did not differ (1.0 ± 0.25). Conversely, pregnancy rate was higher (P < 0.05) in PC (70%) than T (28.6%) and NC (20%). Among ovulated ewes, progesterone concentration and progesterone/CL ratio did not differ among groups (P = 0.92 and P = 0.08, respectively). No relevant r-eCG-related clinical or hematological alterations occurred. In conclusion, 400IU r-eCG effectively induces estrus and ovulation without adverse effects; however, the discrepancy between ovulatory response and pregnancy rate underscores the need for further study refinement to improve fertility.

Animals↗

PubMed2026

The Neurological Impact of Metabolic and Bariatric Surgery: A Systematic Review of Post-Operative Neuropathic and Non-Neuropathic Complications.

Metabolic and bariatric surgery achieves durable weight loss and meaningful improvement in obesity-related comorbidities yet carries a risk of neurological complications that remains under-recognised in routine clinical practice. This systematic review, registered with PROSPERO (CRD42024591611) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, searched MEDLINE, Embase, Emcare, CINAHL and Cochrane databases through September 2023 to evaluate the incidence, spectrum, timing, pathophysiology and management of post-operative neurological complications. Twelve studies comprising over 5000 patients were included. Reported incidence ranged from 1.4% to 16%, with peripheral neuropathy the most frequent manifestation. Mononeuropathies, particularly carpal tunnel syndrome, were prominent in several cohorts, while central complications including Wernicke encephalopathy occurred less commonly but with considerably greater severity. Thiamine deficiency was the predominant aetiological factor. Onset varied from days to several years postoperatively, with early presentations typically compression-related and later ones nutritionally mediated. Outcomes were generally favourable with early intervention, though severe or delayed cases were associated with persistent neurological deficits and occasional mortality. Neurological complications after bariatric surgery are heterogeneous and largely preventable, and structured post-operative follow-up with consistent adherence to nutritional supplementation remains central to reducing long-term harm.

Humans↗