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PubMed2026

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5 years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult↗

PubMed2026

Effects of different resistance exercise programs on upper limb functional recovery in postoperative breast cancer patients.

PURPOSE: To investigate the effects of grip strength exercise combined with upper limb resistance exercise on upper limb functional rehabilitation in patients after breast cancer surgery. METHODS: A total of 111 patients who underwent either modified radical mastectomy with ALND or breast-conserving surgery with ALND were randomly assigned to a control group, an upper limb resistance exercise group, and a combined grip and upper limb resistance exercise group. Grip strength was measured at baseline, 16 weeks after intervention, and at 3- and 6-month follow-ups, while shoulder function was assessed using the Constant-Murley Scale (CMS). RESULTS: There were no statistically significant differences in grip strength or CMS scores among the groups before intervention (P > 0.05). At the post-intervention, 3-month, and 6-month follow-ups, compared with the control group, both resistance training protocols significantly improved patients' joint range of motion, pain, muscle strength, total CMS score, and grip strength (P < 0.05). Compared with the upper limb resistance exercise group, the combined grip and upper limb resistance exercise group demonstrated superior grip strength at the 6-month follow-up (P < 0.05), as well as more significant improvements in joint range of motion, pain, muscle strength, and total CMS scores (P < 0.05). CONCLUSION: A 16-week resistance exercise program effectively improves upper limb function in post-surgical breast cancer patients, with the combined grip and upper limb resistance exercise program yielding superior outcomes.

Humans↗

PubMed2026

Incidence of silent cerebral lesions during pulsed field ablation for paroxysmal atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is a first-line treatment for paroxysmal atrial fibrillation (PAF). Complications such as silent cerebral lesion (SCL) may occur during ablation. Pulsed field ablation (PFA) is a non-thermal method thatablates cardiac tissue via irreversible electroporation. Limited studies have reported the incidence of SCL during PFA, with highly variable results. However, randomized controlled trials (RCTs) remain scarce. The objective of this study was to compare perioperative SCL incidence between PFA and RFCA, and to identify risk factors for SCL during PFA. METHODS: In this prospective pilot RCT (ChiCTR2400088774), 62 patients with PAF were randomized 1:1 to undergo PFA or RFCA. Cerebral MRI (3.0 T) was performed preoperatively and 24-48h postoperatively. SCL was defined as a new acute brain lesion on MRI without neurological deficits. Baseline and surgical data of the patients were collected. RESULTS: SCL was detected post-procedure in 6.45% (2/31) in the RFCA group, 12.90% (4/31) in the PFA group. No statistically significant difference in the incidence of postoperative SCL was detected between the two groups (p = 0.67). Left atrium dimension (LAD), left atrial operation time (LAOT), left ventricular end-diastolic dimension (LVEDD), and total operation time (TOT) were significantly higher in SCL group than those in no-SCL group (p < 0.05) through univariate analyses. CONCLUSIONS: SCL incidence was 12.90% in the PFA group versus 6.45% in the RFCA group. While no statistically significant difference was detected between two groups, the numerically higher rate in the PFA group warrants larger studies to evaluate cerebral safety associated with PFA.

Humans↗

PubMed2026

The Acute Effects of Blood Flow Restriction on Ankle Muscle Reaction Time and Proprioception in Healthy Individuals.

Blood flow restriction (BFR) induces hypoxic and metabolic stress, which may alter afferent feedback and neuromuscular control. However, its acute effects on ankle sensorimotor function remain unclear. The aim of the study was to investigate the acute effects of lower-limb BFR on multidimensional ankle sensorimotor function in healthy adults. Twenty-four participants (12 females, 12 males) completed two conditions in randomized order and a crossover design: BFR at 60% arterial occlusion pressure (AOP) and a control condition (20 mmHg). All measurements were performed during occlusion. Outcomes included joint position sense (active and passive), kinesthesia, static and dynamic balance, lower-limb muscle activation (surface electromyography), and muscle reaction time during sudden ankle inversion. BFR impaired active joint position sense at 20 degrees of inversion (p = 0.011), with no changes at other angles or in kinesthesia. Static balance deteriorated, with increases in sway area (p = 0.017), sway distance (p = 0.029), and sway velocity (p < 0.001), particularly under eyes-closed single-leg stance. Posterolateral reach distance decreased (p = 0.023), accompanied by reduced lower-limb muscle activation. Tibialis anterior muscle reaction time during 30 degrees of inversion in the ankle neutral position was shortened (p < 0.001), whereas peroneus longus muscle responses were unchanged. Acute lower-limb BFR impairs ankle sensorimotor control by reducing proprioceptive accuracy, balance performance, and muscle activation, while shortening reaction time. These findings suggest caution when applying BFR during tasks that require high postural demands or end-range control. Registration number and date: NCT07307339, 12/26/2025.

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 Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans↗

PubMed2026

Secretory Phospholipase A2 in Patients With Sickle Cell Disease Hospitalized for Vaso-Occlusive Pain Episodes.

BACKGROUND: Secretory phospholipase A2 (sPLA2) is an inflammatory mediator linked to acute chest syndrome (ACS) in sickle cell disease (SCD), a serious complication that can develop during an acute vaso-occlusive pain episode (VOE). Plasma sPLA2 levels have been proposed as a potential biomarker for predicting ACS onset. OBJECTIVE: To assess serial plasma sPLA2 levels in 105 pediatric patients hospitalized for SCD-VOE and determine the effects of arginine therapy compared to placebo. PROCEDURES: This is a pharmacokinetics/pharmacodynamics and randomized controlled trial of intravenous arginine therapy. Statistical methods included t-tests, chi-square, and correlation analyses. RESULTS: Mean age was 12.7 ± 3.7 years, 48% were male, 67% had Hb-SS, and 70% were prescribed hydroxyurea. Using a previously established SCD-specific cutoff of 48 ng/mL, presenting sPLA2 levels were elevated in 33% of patients (mean sPLA2 level 85.7 ± 32.9 ng/mL). SPLA2 elevation in the emergency department was more common in patients with ACS compared to those without ACS (64% vs. 30%; p = 0.02; negative predictive value of 94%). Peak sPLA2 levels were significantly higher in febrile (n = 34) versus afebrile patients (n = 71;101.0 ± 45.3 vs. 48.7 ± 35.4 ng/mL; p < 0.0001). Among subjects with elevated baseline sPLA2, arginine therapy resulted in a significant reduction in sPLA2 levels by discharge compared to placebo (-27.8 ± 38.1 ng/mL; p = 0.002; n = 23 vs. -15.0 ± 41.2 ng/mL; p = 0.23; n = 12). CONCLUSIONS: SPLA2 is an underutilized biomarker of ACS given accumulating evidence of its role. In particular, low levels may identify patients at low risk for ACS. Arginine therapy may modulate inflammation in patients with SCD during VOE and/or ACS. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02447874; NCT02536170.

Humans↗

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

Effects of exercise on muscle strength and characteristics in rheumatic diseases and sarcopenia: Protocol for the Care for Muscle (C4M) Study.

OBJECTIVE: Muscle weakness is prevalent in rheumatoid arthritis (RA), osteoarthritis (OA) and sarcopenia (SARC). Endurance exercises may improve mitochondrial function and oxidative capacity, while strength exercises are thought to stimulate myofibrillar protein synthesis. This study aims to compare the effects of strength and endurance exercise and explore the association between muscle characteristics and exercise outcomes in patients with RA, OA and SARC. We hypothesize that responses to endurance and strength exercises in patients with muscle weakness are influenced by intramuscular pathology including muscle morphology, mitochondrial function, and systemic inflammation, based on their disease pathology, potentially requiring personalized training schedules. METHODS: This two-arm, parallel-group exploratory trial will enroll 69 patients (23 RA, 23 OA, 23 SARC), randomized to endurance (n = 35) or muscle strength exercises (n = 34), using minimization to balance disease type and gender. The 8-week intervention includes two supervised sessions per week using a controlled cable pulley device (Reforter™) and fitness equipment, plus one weekly home-based session. The primary outcome is isokinetic muscle strength (peak torque), measured with the Biodex system®. Secondary outcomes include muscle morphology, mitochondrial function, systemic inflammation and muscle endurance (by Biodex and 6 Minute Walk test). Muscle morphology will be assessed via 3D ultrasound imaging of the vastus lateralis. Mitochondrial function will be analyzed using high-resolution respirometry on muscle biopsies. Systemic inflammation will be measured using multiplex assays or ELISA on serum samples. DISCUSSION: This study will explore differential responses to muscle endurance and muscle strength exercises in patients with RA, OA, and SARC, offering novel insights into the molecular mechanisms of muscle weakness. The findings may help identify potential mechanisms underlying variability in exercise response and provide effect size estimates to guide future confirmatory studies and more targeted exercise interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT06480643 (date of registration28-06-24).

Humans↗

PubMed2026

Effects of Progressive Inspiratory Muscle Training on Lung Volume and Respiratory Strength in Patients With Pre-Dialysis Chronic Kidney Disease.

INTRODUCTION: Chronic kidney disease can present changes in thoracic cavity volume and respiratory muscle weakness, even in the pre-dialysis stage. However, there is little evidence on the effects of inspiratory muscle training in these patients. METHODS: This was a randomized clinical trial which comprised patients with Chronic Kidney Disease in stages 3, 4, and 5 undergoing conservative treatment, allocated experimental group (EG) with progressive loading (up to 50% of maximal inspiratory pressure [MIP]) and control group (CG) with a fixed load (5 cmH2O) and no load progression performed daily for 8 weeks. The outcomes assessed were thoracic cavity volumes, as measured by optoelectronic plethysmography, and inspiratory and expiratory respiratory muscle strength. RESULTS: A total of 30 patients completed the study. All volumes significantly increased at the end of the protocol with a large effect size, but only the pulmonary thoracic cavity volume showed a significant interaction (F = 3.698; p = 0.042). There was an increase in inspiratory muscle strength in the EG (73.88-90.35 cmH2O; p < 0.001) and in the CG (70.85-86.92 cmH2O; p = 0.001), as well as in expiratory muscle strength in the EG (97.71-108.53 cmH2O; p = 0.001) and in the CG (80.69-94.77 cmH2O; p = 0.004). CONCLUSION: Daily IMT increased thoracoabdominal volumes, particularly pulmonary rib cage volume in the progressive-load group, as well as respiratory muscle strength in patients with pre-dialysis CKD. However, progressive-load IMT was not superior to minimal-load training.

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

Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.

OBJECTIVE: To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug (NSAID) celecoxib. STUDY DESIGN: Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids. DATA SOURCES: Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov. DATA SYNTHESIS: Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome. RESULTS: Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS. REGISTRATION: PROSPERO-CRD42025642152.

Journal Article↗

PubMed2026

Early infantile developmental and epileptic encephalopathy: clinical spectrum, diagnosis, outcomes, and evolving treatment strategies.

Early infantile developmental and epileptic encephalopathy (EIDEE) is among the most severe epilepsy syndromes, with onset before three months of age and an estimated incidence of approximately 10 per 100,000 live births. The 2022 International League Against Epilepsy classification unified the historically distinct Ohtahara syndrome and early myoclonic encephalopathy under a single diagnostic framework defined by frequent drug-resistant tonic and/or myoclonic seizures, an abnormal neurological examination, and an abnormal interictal electroencephalogram-most characteristically a burst-suppression pattern. This narrative review synthesizes the clinical, electrophysiological, neuroimaging, genetic, and therapeutic literature within the EIDEE framework. The clinical phenotype is characterized by central hypotonia, postnatal microcephaly, cortical visual impairment, and age-dependent syndromic evolution toward infantile epileptic spasms syndrome or Lennox-Gastaut syndrome in the majority of patients. Electroencephalography remains essential for syndromic classification, while systematic metabolic screening and early trio whole-exome or whole-genome sequencing are central to the etiologic workup, achieving diagnostic yields of 60-65%. The most commonly identified genetic causes include STXBP1, KCNQ2, and SCN2A variants. Outcomes are poor overall and strongly etiology-dependent: vitamin-responsive disorders carry a substantially more favorable prognosis, whereas mortality reaches 25% in genetic cohorts. Genotype-guided pharmacotherapy is now applicable to a clinically meaningful subset of patients, with sodium channel blockers, potassium channel openers, and emerging antisense oligonucleotide therapies representing important therapeutic advances. Gene therapy trials are underway but have encountered early safety signals, underscoring the vulnerability of this population. Critical unmet needs include earlier molecular diagnosis, precision therapies targeting developmental outcomes beyond seizure control, and prospective international registries to characterize the long-term natural history of EIDEE.

Humans↗

PubMed2026

Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial.

AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age ≥ 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p ≥ 0.11 and p ≥ 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38.

Aged↗

PubMed2026

Improved donor-site biomechanics and functional recovery with xenogeneic acellular dermal matrix after ALT flap harvest: A prospective randomized controlled study.

BACKGROUND: Donor-site management after anterolateral thigh (ALT) flap harvest is a significant yet underaddressed concern in reconstructive surgery for oral cancer. While xenogeneic acellular dermal matrix (Xeno-ADM) is common in soft-tissue repair, its efficacy for fascia lata reconstruction at the ALT donor site remains insufficiently characterized. This study aimed to assess the efficacy of xeno-ADM in fascia lata repair, focusing on compartment pressure, inflammatory and muscle injury biomarkers, and functional recovery. METHODS: In this prospective, randomized, single-blind trial, 200 patients undergoing ALT flap reconstruction were allocated to Xeno-ADM repair (n = 100) or primary closure (n = 100). Primary endpoints included compartment pressure, inflammatory markers in drainage fluid, serum muscle injury biomarkers, and functional outcomes. RESULTS: The xeno-ADM group showed significantly lower compartment pressures throughout postoperative days (POD) 1-5. Inflammatory markers in drainage fluid (CRP on POD 3 and 5) and serum muscle injury biomarkers (creatine kinase on POD 1 and 5) were significantly lower in xeno-ADM group. Functional outcomes were superior in the Xeno-ADM group, with faster gait recovery, lower pain scores at POD 7, and better lower-limb function at the 1- and 6-month follow-ups. Drainage duration did not differ between groups. Stratified analyses revealed that the benefits of xeno-ADM were more pronounced in patients with defect width >3 cm or a body mass index ≥24 kg/m2. CONCLUSION: Xeno-ADM provides a safe and effective approach for fascia lata repair, reducing biomechanical and inflammatory burdens while enhancing functional recovery. These findings support a transition from simple structural closure toward functional donor-site reconstruction.

Humans↗

PubMed2026

Response-adapted surgical de-escalation following neoadjuvant immunotherapy in resectable mucosal HNSCC A systematic review and meta-analysis.

INTRODUCTION: Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS: A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS: The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS: RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.

Humans↗

PubMed2026

The Efficacy of Erector Spinae Plane Block Versus Subcostal Transversus Abdominis Plane Block in Laparoscopic Nephrectomy: A Randomized Clinical Trial.

OBJECTIVES: This study compared the efficacy and safety of erector spinae plane block (ESPB) versus subcostal transversus abdominis plane (TAP) block in reducing postoperative pain among patients undergoing laparoscopic nephrectomy. METHODS: This randomized clinical trial enrolled 70 adult patients, ASA physical status I or II, who underwent total (radical) laparoscopic nephrectomy under general anesthesia. Patients were randomly assigned to 2 groups. Group ESPB received an ultrasound-guided ESPB at the T7 transverse process level, while group TAP received an ultrasound-guided subcostal TAP block. The primary outcome was the total amount of morphine consumed at 6 and 24 hours postoperatively. Secondary outcomes included the incidence of patients requiring opioid analgesia, time to rescue analgesia, visual analog scale of pain intensity, time to postoperative ambulation, intraoperative and postoperative hemodynamics, arterial partial pressure of oxygen to fraction of inspired oxygen (PaO 2 /FiO 2 or P /F) ratio, and incidence of complications. RESULTS: Compared with the TAP group, the ESPB group exhibited significantly lower median morphine consumption at 24 hours ( P =0.032), prolonged time to first analgesic rescue ( P =0.049), and lower incidence of rescue morphine requirement (OR=0.23; 95% CI=0.06-0.94; P =0.031), with lower visual analog scale pain scores at 12, 18, and 24 hours postoperatively ( P <0.001). The mean arterial blood pressure and heart rates were comparable between groups. No significant adverse effects from either approach. DISCUSSION: In laparoscopic nephrectomy, ultrasound-guided ESPB may safely and effectively be used to improve pain management and reduce pain intensity, with stable hemodynamics and a comparable risk of postoperative complications to the ultrasound-guided subcostal TAP block.

Humans↗

PubMed2026

Relationships between cannabis and cocaine use in a randomized trial of combined buprenorphine and naltrexone for DSM-IV cocaine dependence.

BACKGROUND: Cannabis is the most commonly used drug in the United States, and among people who use cannabis, polysubstance use is common and understudied. We aimed to examine the association of tetrahydrocannabinol (THC) positive urine drug screen (+UDS) with the odds of submitting a cocaine + UDS during cocaine use disorder treatment. METHODS: We conducted a secondary data analysis of a previously reported double-blind, placebo-controlled clinical trial, CTN0048. Participants meeting criteria for opioid abuse/dependence were assigned to receive extended-release naltrexone and one of three conditions of buprenorphine (placebo, 4 mg/day, 16 mg/day) for 8 weeks. Generalized estimating equations (GEE) were used to analyze urine samples (Liu et al., 2018) collected over time, examining the association between THC + UDS and cocaine + UDS during treatment. RESULTS: Participants (n = 301) averaged 46 (SD = 8.64) years of age, were majority male (78.41 %), non-Hispanic (89.70 %), and African American (66.45 %). GEE results indicated that patients who submitted THC + UDS had significantly higher odds of submitting cocaine + UDS compared to participants who submitted THC-negative UDS across the 25 time points examined (OR = 1.47, 95 % CI = 1.21-1.79, p = 0.00). Time (OR = 0.9998, 95 % CI: 0.9997, 0.9999, p = 0.018) and the covariate of sex assigned at birth (OR = 1.77, 95 % CI = 1.13-2.77, p = 0.013) were also significant in the model, indicating very small decreases in the odds of submitting a cocaine + UDS over time for all patients and 77 % higher odds of submitting cocaine + UDS for females. CONCLUSION: THC + UDS was associated with increased odds of submitting a cocaine + UDS during treatment. Further investigation is needed to discern whether decreasing THC use will result in reduced cocaine use; however, these results suggest that it may be beneficial to counsel patients on cannabis use cessation both before and during treatment for cocaine use, as it is related to cocaine use treatment outcomes. TRIAL REGISTRATION: Secondary data analysis of ClinicalTrials.gov, TRN: NCT01402492 ("A randomized study to test the safety and effectiveness of buprenorphine in the presence of naltrexone for the treatment of cocaine dependence"; National Drug Abuse Treatment Clinical Trials Network (CTN) clinical trial: CTN0048), Registration date: 27 July 2011.

Humans↗