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PubMed2026

Wearable Sleep Monitoring in Pediatric Acute Lymphoblastic Leukemia: Associations With Subjective Sleep Ratings and Neurocognitive Functioning.

BACKGROUND: Sleep disturbances are associated with increased fatigue, reduced quality of life, and neurocognitive dysfunction and have emerged as a common complication among pediatric cancer survivors. Sleep disturbances are particularly concerning given their potential to exacerbate existing neurocognitive impacts of cancer treatments. This pilot study examined the feasibility and acceptability of a home-wearable EEG-based sleep device (Sleep ProfilerTM) for acute lymphoblastic leukemia (ALL) survivors as well as associations between specific sleep parameters and neurocognitive functioning. PROCEDURE: Children (ages 8-12; M = 10 years, SD = 1.6; N = 23) >6 months post-treatment for ALL were enrolled at clinical visits and wore the Sleep ProfilerTM for two consecutive nights at home, followed by neurocognitive testing of attention, inhibitory control, working memory, and processing speed. Parents completed subjective measures of child sleep, anxiety, depression, and acceptability. Feasibility reflected the percentage of children wearing the device at least one night and the percentage of nights with good EEG quality data. RESULTS: All participants wore the device both nights, with 84% meeting the threshold for good quality measurement. Few children met recommended quantity and quality sleep thresholds based on objective measurement, including 5 patients with elevated snoring levels; 43.5% of subjective ratings fell above the threshold for sleep disturbance. Greater sleep latency was associated with worse inhibitory control (r = -0.42, p = 0.046), and total sleep time was positively associated with inhibitory control and attention. CONCLUSIONS: Findings confirm the feasibility and acceptability of home EEG sleep monitoring in school-age survivors, and associations of sleep latency and snoring with reduced neurocognitive functioning may offer modifiable risk factors for aspects of neuropsychological dysfunction common in pediatric survivorship. CLINICAL TRIAL REGISTRATION: At the time this study was conducted, we were not required to register the study on ClinicalTrials.gov. It was a single-institution feasibility study without intervention, which was not considered a clinical trial.

Humans↗

PubMed2026

Estimated prevalence and distribution of causes of immune-mediated hypertrophic pachymeningitis in São Paulo, Brazil.

BACKGROUND: The prevalence of hypertrophic pachymeningitis (HP) remains poorly defined worldwide. In Japan, the estimated prevalence is 0.949 cases per 100,000 inhabitants, with most cases related to ANCA-associated vasculitis or IgG4-related disease. In contrast, epidemiological data from other regions, including Latin America, are scarce. METHODS: This study was conducted at a tertiary referral center in the city of São Paulo, Brazil. The prevalence of HP was estimated by comparison with the known prevalence of multiple sclerosis (MS), based on the number of patients with each condition followed at our institution. The etiological distribution of HP was also analyzed. In addition, HP prevalence was compared with that of tuberculous meningoencephalitis, a compulsory notifiable disease and a well-established cause of chronic meningitis in Brazil, using data from the national surveillance system (SINAN). RESULTS: We identified 55 patients with HP: 36 (65%) idiopathic, 10 (18%) IgG4-related disease, 4 (7%) ANCA-associated pachymeningitis, 4 (7%) probable or definite neurosarcoidosis, and 1 (2%) secondary to rheumatoid arthritis. Among 968 registered MS patients and assuming an MS prevalence of 15 per 100,000 inhabitants in São Paulo, the estimated HP prevalence was 0.85 per 100,000 inhabitants. This estimate was comparable to the prevalence of tuberculous meningoencephalitis in the same region. CONCLUSION: The estimated prevalence of HP in São Paulo (0.85 per 100,000) is consistent with reports from other regions and is comparable to that of tuberculous meningeal disease, although with a distinct etiological profile. IgG4-related disease was the most frequent systemic association, differing from previous reports. ANCA-associated HP appears to be less frequent than in other geographic regions, possibly reflecting differences in disease phenotype. Key Points • The estimated prevalence of HP in São Paulo was 0.85 per 100,000 inhabitants. • IgG4-related disease was the most common systemic disease identified among patients with HP. • ANCA-associated HP was less common than reported in Asian and European cohorts. • The prevalence of HP was comparable to that of tuberculous meningoencephalitis in São Paulo.

Humans↗

PubMed2026

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS × RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans↗

PubMed2026

Cochlear Implantation in Sickle Cell Disease: A Systematic Review of Feasibility and Outcomes.

INTRODUCTION: Sickle cell disease (SCD) is associated with systemic complications, including sensorineural hearing loss (SNHL) from microvascular occlusion and chronic inflammation. Although reports link SCD to higher rates of SNHL, current evidence is limited by small sample size, varied audiologic methods, and lack of standardized screening. This systematic review summarizes available literature on SNHL and cochlear implantation (CI) in SCD. METHODS: A literature search of PubMed MEDLINE, Embase, Scopus, Web of Science, and CINAHL identified 79 citations. After removal of duplicates, 35 records were screened in Rayyan. Studies published between January 1, 2000, and June 30, 2025, were eligible if they reported patients with SCD who developed hearing loss and underwent CI. Nine full texts were reviewed, and 4 met the inclusion criteria. Screening and review were performed independently by 2 authors per PRISMA guidelines. RESULTS: Across 4 case reports, a total of 5 patients with SCD underwent CI, ranging in age from 2 to 42 years. Four presented with bilateral severe-to-profound SNHL and one with unilateral loss. Implantation was technically feasible in all cases, including patients with cochlear fibrosis or ossification requiring modified insertion techniques. Postoperative outcomes were favorable: all patients demonstrated reliable device function and low impedances. Only 60% showed meaningful auditory benefit, characterized by improved functional speech perception in 2 patients (40%) and access to the speech frequency range with hearing testing going from moderate/profound hearing loss to mild hearing loss in 3 patients (60%). Complications occurred in 2 patients (40%): one developed unilateral middle ear infection leading to meningitis, and another experienced a postoperative pulmonary embolism requiring anticoagulation. The remaining 3 patients (60%) had uncomplicated recoveries with reported improved hearing from moderate/profound hearing loss to mild hearing loss post implantation. CONCLUSION: While CI appears feasible in SCD, our findings suggest that additional data are needed to assess its effectiveness in this patient population. However, evidence is limited to case reports, and complications such as thromboembolism and rapid cochlear fibrosis highlight the need for close perioperative management. More comprehensive studies with larger sample size are required to define surgical risk, optimize management, and establish best practices for timely implantation in this population.

Humans↗

PubMed2026

Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.

BACKGROUND: Triazole resistance in Aspergillus fumigatus is a global public health concern associated with treatment failure, notably in invasive aspergillosis. However, population-level data on triazole resistance from India remain limited, with most reports originating from single-center studies. METHODS: We conducted a multicenter surveillance study to assess the prevalence of triazole resistance among clinical A. fumigatus isolates across India. Antifungal susceptibility testing was performed using the CLSI broth microdilution method (M38-Ed3), and molecular characterization was conducted on resistant isolates. A total of 518 isolates were analyzed: 115 prospectively collected from 13 tertiary-care hospitals from 2015-2020, and 403 archived isolates obtained from the National Culture Collection of Pathogenic Fungi (1994-2020). RESULTS: The overall pooled prevalence of non-wildtype isolates was 4.1% for itraconazole (95% CI: 2.54-6.17%), 3.9% for posaconazole (95% CI: 2.39-5.94%), while 1.4% were resistant to voriconazole (95% CI: 0.55-2.77%). One multi-azole-resistant isolate from an immunocompromised, mold-active triazole-naïve patient carried the TR34/L98H mutation, suggesting environmental acquisition. Prevalence of resistance did not differ significantly across geographic regions or between public and private sector hospitals. Linear regression analysis revealed a significant temporal increase in median MICs of all three licensed triazoles between 1994 and 2020. Approximately 29% of isolates exhibited amphotericin B MICs exceeding the epidemiological cutoff value; however, the clinical significance of this finding remains uncertain. CONCLUSIONS: Azole resistance among clinical A. fumigatus isolates in India remains uncommon (<5%), supporting the continued use of triazoles as first-line therapy. However, the observed temporal increase in triazole MICs underscores the need for sustained national surveillance to detect emerging resistance trends.

Aspergillus fumigatus↗

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

Endovascular treatment after stroke beyond 24 h vs 6-24 h: a propensity score-matched cohort study.

BACKGROUND: Endovascular thrombectomy (EVT) is the standard treatment for acute ischemic stroke due to anterior circulation large vessel occlusion (LVO) within 6-24 h. However, the safety and feasibility of EVT for anterior circulation strokes beyond 24 h remain uncertain. METHODS: We conducted a retrospective cohort study of consecutive patients with anterior circulation LVO who underwent EVT at Changhai Hospital from 2018 to 2023. Patients were stratified into late (6-24 h) and very late (>24 h) windows. Propensity score matching (PSM) was performed to adjust for baseline imbalances, including age, sex, NIHSS, ASPECTS, occlusion location, perfusion parameters, and vascular risk factors. The primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2) at 3 months. Secondary outcomes included successful reperfusion (TICI 2b-3) and symptomatic intracranial hemorrhage (sICH). RESULTS: Among 1043 screened patients, 429 patients with anterior circulation LVO were included after exclusions, comprising 373 in the late window and 56 in the very late window. PSM yielded 42 matched pairs. Compared with the late window group, the very late window group showed no statistically significant differences in functional independence (54.8% vs. 57.1%; OR = 0.908, 95% CI 0.382-2.153, p = 0.830), successful reperfusion (88.1% vs. 92.9%; OR = 1.800, 95% CI 0.481-7.096, p = 0.460), sICH (2.4% vs. 9.5%; OR = 0.232, 95% CI 0.012-1.652, p = 0.200), intraprocedural complications (26.2% vs. 19.0%; OR = 1.508, 95% CI 0.540-4.362, p = 0.440), or postoperative complications (33.3% vs. 35.7%; OR = 0.900, 95% CI 0.363-2.219, p = 0.820). CONCLUSIONS: In this selected, single-center cohort of anterior circulation LVO patients undergoing EVT, treatment initiated beyond 24 h appeared to have comparable effectiveness and safety to treatment initiated within 6-24 h. Definitive evidence requires confirmation from adequately powered randomized controlled trials.

Humans↗

PubMed2026

Timing and Dose Matter: Late High-Speed Exposure and Higher High-Intensity Acceleration Volumes Reduce Hamstring Reinjury Risk in Elite Male Football (Soccer).

OBJECTIVES: The aims of this study were to (a) investigate whether the timing and magnitude of exposure to high-speed running (HSR), sprinting, and high-intensity accelerations during on-field rehabilitation after hamstring strain injury were associated with reinjury risk and (b) examine changes in match running performance upon return to play (RTP). DESIGN: Retrospective cohort study. METHODS: Data from 95 elite male football (soccer) players from five professional clubs competing in major European and Middle Eastern leagues were analyzed. Players with complete rehabilitation load profiles were included in the 2-month and 6-month reinjury analysis. Modified Poisson regression assessed associations between rehabilitation load characteristics and reinjury risk. Match running performance (HSR distance, sprint distance, and high-intensity accelerations per minute) during the five matches before injury and the first five matches after RTP was compared using paired t-tests for the entire cohort. RESULTS: Late introduction of HSR, sprinting, and high-intensity accelerations during rehabilitation (ie, ≥ 60% of rehabilitation progression) was associated with a significantly lower reinjury risk at 2 months (relative risk [RR] range = 0.948-0.969; P < .01) and 6 months (RR range = 0.964-0.979; P < .05). Higher daily exposure to high-intensity accelerations once introduced was protective (RR = 0.861 (0.778-0.951)). There were no meaningful associations between total volume of HSR or sprinting and reinjury. Match running performance metrics did not differ between pre-injury and post-RTP matches (all P > .05). Changes in performance were not correlated with rehabilitation load characteristics. CONCLUSION: The timing of high-intensity running exposure during on-field rehabilitation appeared associated with a lower hamstring reinjury risk. Delaying the introduction of HSR, sprinting, and accelerations, followed by a structured and progressive build-up, was associated with lower risk of reinjury without compromising the subsequent match performance of elite male football players. J Orthop Sports Phys Ther 2026;56(9):611-621. Epub 7 Jul 2026. doi:10.2519/jospt.2026.14077.

Humans↗

PubMed2026

Presentation, management, and outcomes of anterior inferior cerebellar artery dissecting and fusiform aneurysms: a systematic review and institutional case series.

Dissecting and fusiform aneurysms of the anterior inferior cerebellar artery (AICA) are rare and poorly characterized lesions. This study provides a comprehensive patient-level synthesis to date, combining a systematic review with institutional data to describe their clinical presentation, diagnostic workup, management strategies, and outcomes. A systematic review was conducted according to PRISMA guidelines. Studies were included if they reported on dissecting or fusiform AICA aneurysms. Individual patient data were extracted and supplemented with a single-institution case series. Outcomes, complications, and radiological evolution were analyzed descriptively. Forty-nine patients from 36 studies and 6 patients from our institution were included in this study. In the systematic review cohort, most aneurysms presented with subarachnoid hemorrhage (n = 38/49, 77.6%). Compressive cranial neuropathies, particularly including the vestibulocochlear system, were common in patients with unruptured aneurysms. Diagnosis often required digital subtraction angiography after the initial non-invasive imaging. Endovascular treatment, most commonly parent artery occlusion, was employed in 61.2% (n = 30/49) of cases. However, ischemic complications occurred in 23.3% (n = 7/30), especially in proximal (A1-A2) lesions. Bypass surgery was reported selectively for proximal aneurysms with inadequate collateral flow. As an alternative surgical approach, decompression or trapping was pursued based on aneurysm morphology or clinical context. Conservative management was typically reserved for select patients with poor-grade SAH, high procedural risk, or patient refusal of intervention. Overall, 81.4% (n = 35/43) of patients with available follow-up achieved good functional outcomes. Management of AICA dissecting and fusiform aneurysms is highly individualized. Endovascular approaches were frequently used to secure ruptured lesions or lesions considered at high risk, but periprocedural ischemic risk in perforator-rich segments remains a notable concern. Bypass procedures were reported in selected proximal aneurysms with limited collateralization. Conservative management was reserved for highly selected high-risk or anatomically inaccessible cases. Clinical trial registration: This study is not a clinical trial.

Humans↗

PubMed2026

Intravesical mitomycin-C administered immediately before transurethral resection of bladder tumor in non-muscle-invasive bladder cancer: Clinical outcomes and molecular predictors from over 3 years of extended follow-up in a phase II trial.

PURPOSE: To evaluate the long-term outcomes and molecular correlates of response after immediate preoperative intravesical chemotherapy (IPeIC) with mitomycin-C (MMC) in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In this single-center, open-label, randomized phase II trial, 33 patients received two split doses of IPeIC/MMC (40 mg/20 mL), whereas 38 patients underwent transurethral resection of bladder tumor (TURBT) alone. The primary endpoint was 3-year recurrence-free survival (RFS), and secondary endpoints included progression-free survival (PFS). Exploratory RNA sequencing was performed on IPeIC-treated patients (three with recurrence, 25 without) using a Monte Carlo-based resampling strategy. RESULTS: The median follow-up durations were comparable between the intervention (60.0 months) and control arms (60.4 months). IPeIC/MMC reduced recurrence risk by 76.8% versus TURBT alone (p=0.024), yielding a 3-year RFS rate of 90.7% versus 78.6%. On multivariable analysis, IPeIC/MMC independently improved RFS (hazard ratio [HR] 0.266, p=0.044). IPeIC was associated with superior PFS, with 3-year and 5-year rates of 100% versus 92.1% and 85.8%, respectively, in the controls (HR 0.078, p=0.014). Exploratory transcriptomics identified low Glutathione S-transferase Mu 1 (GSTM1) expression as the factor most strongly associated with recurrence. CONCLUSIONS: IPeIC/MMC is associated with improved long-term oncological outcomes compared with TURBT alone and represents a safe prophylactic option for patients with NMIBC who are unable to receive standard immediate postoperative intravesical chemotherapy because of safety concerns or practical constraints. The GSTM1 findings are hypothesis-generating and support future biomarker-driven validation studies.

Aged↗

PubMed2026

Open repairs with biceps rerouting does not impact retears in large to massive rotator cuff tears compared to conventional open repair: a randomized clinical trial.

BACKGROUND: The treatment of large to massive rotator cuff tears leads to a high failure rate and several techniques have been proposed to improve these results. Rerouting the long head of the biceps tendon (LHBT) appears to be a biological reinforcement to increase tendon healing. Therefore, this study aimed to compare the clinical and radiological outcomes of open repair for large and massive rotator cuff tears reinforced with the LHBT to conventional open repair. METHODS: A prospective randomized study was conducted with patients diagnosed with large to massive rotator posterosuperior rotator cuff tear and intact LHBT, randomized into 2 groups: biceps rerouting and conventional open repair. The functional outcomes were assessed by the American Shoulder and Elbow Surgeon score, University of California at Los Angeles score, and SF-12 questionnaire preoperatively and at 6, 12, and 24 months postoperatively. Pain level was also assessed by the visual analog scale including the first day and 2 weeks postoperatively. Structural outcomes were rotator cuff and LHBT healing with magnetic resonance imaging and acromiohumeral distance (AHD) through radiography. RESULTS: We evaluated 58 patients, 29 in each group. At the end of the follow-up there were no statistically significant differences between groups in American Shoulder and Elbow Surgeon (76.1 vs. 80.4, P = .761), University of California at Los Angeles (27.1 vs. 29.1, P = .634), or visual analog scale scores (1.3 vs. 1.1, P = .781). Additionally, rotator cuff healing rates (48.3% vs. 44.8%, P = .402) and LHBT healing rates (79.3% vs. 82.7%, P = .738) were similar. AHD increased in both groups, with no significant difference in delta AHD (P = .513). Both groups showed significant clinical improvement over time in all evaluated outcomes (P < 0,01). No postoperative complications were reported. CONCLUSIONS: We could not identify an advantage of open repair with LHBT rerouting as reinforcement over conventional open repair. Nonetheless, all clinical scores improved at the end of the 24 months of follow-up in both groups.

Humans↗

PubMed2026

Pairwise Comparative Safety and Effectiveness of Anti-TNF Blockers, Vedolizumab, and Ustekinumab During Pregnancy: A Systematic Review and Meta-Analysis.

PURPOSE: Biologic therapies, including tumor necrosis factor (TNF) blockers, vedolizumab (VDZ), and ustekinumab (UST), are generally considered safe during pregnancy in patients with inflammatory bowel disease (IBD), though comparative data remain limited. This meta-analysis examines their safety and effectiveness. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science was conducted through July 2025. Eligible studies reported maternal or neonatal outcomes in pregnant IBD patients treated with biologics. Studies were pooled using a random-effects model to calculate risk ratios (RRs) with 95% confidence intervals. Heterogeneity was assessed using I2. Primary outcomes were preterm birth and disease activity; secondary outcomes included pregnancy and neonatal outcomes. RESULTS: Nine observational studies (n = 6,054) were included. Compared to TNF blockers, VDZ was associated with a higher risk of preterm delivery (RR = 1.35, 95% CI 1.04-1.75, I2 = 0%) and active disease (RR = 1.55, 95% CI 1.01-2.40, I2 = 50%). UST was associated with a higher risk of active disease (RR = 1.30, 95% CI 1.06-1.60, I2 = 0%) and congenital anomalies (RR = 2.08, 95% CI 1.30-3.32, I2 = 0%) compared to TNF blockers. Compared to UST, VDZ was linked to increased risks of preterm birth (RR = 2.60, 95% CI 1.03-6.57, I2 = 0%) and low birth weight (RR = 2.38, 95% CI 1.01-5.60, I2 = 0%). No significant differences were observed for live births, abortions, hospitalizations, or neonatal infections. CONCLUSION: TNF blockers showed a favorable safety and effectiveness profile, VDZ and UST performed broadly similar, and all three biological classes appeared compatible with safe use in pregnancy to maintain effective disease control. Observed differences reflect that VDZ and UST cohorts likely had longer disease duration, prior biologic exposure, and more active disease. The results of this meta-analysis support the continuation of biologic therapy for disease control in pregnant patients with IBD. Treatment decisions should be individualized and tailored to each patient's clinical context.

Female↗

PubMed2026

Electro-clinical efficacy and safety of midazolam in neonatal seizures: a systematic review with individual level exploratory analysis of gestational age-related treatment response.

UNLABELLED: Neonatal seizures are the most common neurological emergency during the neonatal period and are associated with increased mortality and adverse neurodevelopmental outcomes. Despite current recommendations supporting phenobarbital as first-line therapy, seizure control remains suboptimal in a large proportion of neonates, prompting the use of second-line antiseizure medications. Midazolam is increasingly administered in refractory neonatal seizures but evidence regarding its electro-clinical efficacy and safety remains limited and heterogeneous. To systematically review the available evidence on the electro-clinical efficacy and safety of midazolam in neonatal seizures and to perform an exploratory individual-level analysis investigating the association between gestational age and treatment response. A systematic review was conducted according to PRISMA 2020 guidelines. Studies including neonates with EEG- or aEEG-confirmed seizures treated with midazolam were included. Binary logistic regression was performed to assess the individual-level association between gestational age and treatment response. Eleven studies involving 146 neonates treated with midazolam were included. Electro-clinical response was observed in 101/146 neonates (69.2%), while seizure cessation was achieved in 61/146 neonates (41.8%). In an exploratory complete-case logistic regression analysis, higher gestational age appeared to be associated with a greater probability of electro-clinical response. The predicted probability curve crossed the 50% response probability at approximately 36.5 weeks of gestation. Hypotension was the most frequently reported adverse event, while respiratory depression, sedation-related effects, and transient EEG/aEEG suppression were reported less frequently. CONCLUSIONS: Midazolam may have a role as an add-on antiseizure medication in neonatal seizures, particularly in refractory cases. However, the evidence remains limited by heterogeneity in study design, EEG monitoring strategies, outcome definitions, and incomplete individual-level data. The observed association between gestational age and response is hypothesis-generating and requires prospective validation. WHAT IS KNOWN: • Phenobarbital often provides incomplete seizure control in neonates, making second-line antiseizure therapies necessary in refractory cases. • Evidence supporting midazolam for neonatal seizures remains limited and heterogeneous. WHAT IS NEW: • This systematic review summarizes the electro-clinical efficacy and safety of midazolam and includes an exploratory patient-level analysis suggesting that higher gestational age may be associated with improved treatment response. • These findings support further prospective studies on developmental determinants of response to GABAergic therapy.

Humans↗

PubMed2026

Robot-assisted versus freehand cannulated-screw fixation for femoral neck fractures: a systematic review of technical, clinical and adoption outcomes.

Robot-assisted guidance may improve the technical precision of percutaneous cannulated-screw fixation for femoral neck fractures. Whether these procedural advantages translate into better clinical outcomes remains uncertain. We compared robot-assisted and conventional freehand fixation in adults with femoral neck fractures. MEDLINE, Embase and CINAHL were searched from inception to 15 July 2026 without language restrictions. Google Scholar was used only as a supplementary search source, together with forward and backward citation searching. Comparative studies of robot-assisted versus freehand fluoroscopy-guided cannulated-screw fixation were included. Risk of bias was assessed using RoB 2 and ROBINS-I, with the Newcastle-Ottawa Scale used as a complementary appraisal of non-randomised studies. Random-effects meta-analyses included prediction intervals and prespecified sensitivity analyses. The protocol was registered prospectively (PROSPERO CRD420261465038). Sixteen comparative studies involving 1,293 participants were included. Of these, 597 underwent robot-assisted fixation and 696 underwent freehand fixation. Two studies reporting random allocation and 14 non-randomised studies were included in the study. Robot-assisted fixation was associated with fewer guide-wire manipulations, greater screw-placement accuracy and 13.9 fewer fluoroscopic acquisitions per procedure (95% confidence interval [CI] -20.3 to -7.5). Earlier radiographic healing and modestly higher final Harris Hip Scores were also observed. Pooled estimates suggested lower risks of union failure, avascular necrosis and composite complications. Fluoroscopy duration, overall operative time and reoperation did not differ significantly. Heterogeneity was substantial for several continuous outcomes, with prediction intervals crossing the null for several estimates, indicating that the magnitude of benefit varied considerably between studies. Some clinical associations were also sensitive to eligibility-restricted analyses. Robot-assisted cannulated-screw fixation improves technical execution compared with freehand fixation. Patient-important clinical superiority and economic value have not been established, and evidence concerning learning curves, operator acceptability and system reliability remains insufficient. Current evidence does not support routine widespread adoption; adequately powered multicentre randomised trials incorporating economic and implementation evaluation are required.

Humans↗

PubMed2026

The Effectiveness of Passive Half-Time Interventions on Simulated Second-Half Performance in Elite Youth Soccer Players.

The half-time period in soccer provides a potentially important window to implement short-duration interventions aimed at maintaining second-half performance. However, passive rest has been associated with a decline in subsequent physical and technical performance. While re-warm-up strategies are well studied, little is known about the efficacy of technology-based, passive recovery modalities, device-supported interventions that require minimal active movement or physical exertion from the athlete, during half-time intervals. This study examined whether percussive therapy, electrical muscle stimulation, and pneumatic compression can mitigate second-half performance decline in male adolescent soccer players. Forty-three academy-level players (17.5 ± 0.6 years) completed a simulated soccer protocol including the Loughborough Soccer Pass Test (LSPT), repeated 20-meter sprints, and completed Total Quality of Recovery (TQR) assessments before and after half-time. Participants were randomized into one of four intervention groups during the 15-minute half-time interval: Passive Rest (CON), Percussive Therapy (Theragun Pro; TG), EMS (PowerDot; PD), and Pneumatic Compression (RecoveryAir; COMP). Linear mixed-effects models assessed Time × Condition interactions for performance and recovery outcomes. Passive half-time rest led to significant deterioration in technical skill, sprint performance, and perceived recovery (p < .05) for the control group. TG and PD significantly improved technical performance (LSPT scores) compared to the control group (d = 0.65 and 0.72, respectively; p < .01). Furthermore, TG and COMP were effective at maintaining 20-meter sprint times (d = 0.58 and 0.49; p < .01), whereas the control group experienced significant slowing. Perceived recovery (TQR) scores significantly declined in the CON group from First Half to Second Half (16.5 ± 2.2 to 11.1 ± 2.3. However, this decline was significantly attenuated in all intervention groups: TG (17.5 ± 1.9 to 14.2 ± 1.9), PD (17.3 ± 1.9 to 15.1 ± 1.9), and COMP (17.6 ± 1.9 to 15.9 ± 2.0). Short-duration passive interventions during half-time can mitigate performance decline in adolescent soccer players. TG and EMS appear most effective for preserving technical skills, while COMP may support perceived recovery. These findings highlight practical strategies for optimizing in-game performance and inform evidence-based half-time protocols.

Humans↗

PubMed2026

Efficacy and safety of Janus kinase inhibitors in Behçet's disease: A systematic literature review.

INTRODUCTION: Behçet's disease e (BD) is a chronic, relapsing, multisystem inflammatory disorder that if not successfully treated can lead to severe, organ or life-threatening complications. Despite treatment with glucocorticoids, immunosuppressants, and tumor necrosis factor (TNF) inhibitors, some patients still have refractory disease that mandates additional therapeutic options. The pathogenesis of BD involves dysregulated innate and adaptive immune responses with multiple cytokines signaling through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway. By targeting multiple inflammatory pathways, JAK inhibitors have emerged as a promising therapeutic option. However, current evidence remains limited and heterogeneous. Therefore, we conducted this systematic review to evaluate their efficacy and safety in BD. METHODS: We conducted a systematic literature review in accordance with PRISMA 2020 guidelines (PROSPERO registration: CRD420261381955). PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched from inception to March 2026. Original clinical studies evaluating Janus kinase (JAK) inhibitors in BD were included. Two reviewers independently performed study selection, data extraction, and quality assessment using Joanna Briggs Institute tools. Due to heterogeneity, results were synthesized narratively, focusing on efficacy and safety outcomes. RESULTS: Seventeen studies (99 patients) were included, predominantly case reports and small observational cohorts with overall high methodological quality. All evaluated tofacitinib, baricitinib, or upadacitinib, with no data on other JAK inhibitors. Patients were highly treatment-refractory, with prior failure of conventional and biologic therapies. Upadacitinib was the most frequently studied agent and demonstrated an overall response rate of 85.2% and complete remission in 59.3% in a multi-center study. Efficacy was observed across multiple domains, with the most consistent responses in intestinal disease, including clinical and endoscopic remission, alongside frequent glucocorticoid-sparing effects. Safety findings were consistent with known JAK inhibitor safety profiles, with mainly mild to moderate infections and manageable laboratory abnormalities, and no clear signal for increased thrombotic events, although follow-up was limited. CONCLUSION: JAK inhibitors demonstrate promising efficacy in BD, particularly in refractory and multisystem disease. The most consistent evidence of efficacy was observed in gastrointestinal involvement, whereas data for other disease domains remain limited. Their safety profile appears consistent with existing data, although further follow up and validation is required. High-quality randomized controlled studies are an imminent need to study the potential role of JAK inhibitors in BD.

Humans↗

PubMed2026

Clinical effectiveness of transversus abdominis plane block versus local anaesthesia wound infiltration for postoperative pain relief after laparoscopic appendicectomy in children: A multicentre, double-blind, randomised, controlled phase III trial.

BACKGROUND: Postoperative pain relief after laparoscopic appendicectomy in children provided by transversus abdominis plane (TAP) block and local anaesthesia wound infiltration (LAWI) of trocar insertion sites has never been compared. OBJECTIVE: To investigate whether TAP block could decrease postoperative opioid requirements after laparoscopic appendicectomy in children compared with LAWI. DESIGN: Multicentre, double-blind, phase III randomised trial. SETTING: Two tertiary paediatric surgery centres. PATIENTS: Children aged 3 to 15 years admitted for laparoscopic appendicectomy. MAIN OUTCOME MEASURES: The primary outcome was the total dose of nalbuphine delivered within 24 h after surgery. Secondary outcomes were the Face Legs Activity Cry Consolability (FLACC) scale values at 1, 2, 6, 12 and 24 h, the time from levobupivacaine injection to the first dose of nalbuphine, and the time from the end of surgery to the first mobilisation. Patients received either ultrasound-guided TAP block (TAP group) or LAWI of trocar insertion sites (infiltration group) with 0.6 ml kg -1 of levobupivacaine 2.5 mg ml -1 , combined with standardised systemic multimodal analgesia including paracetamol, ketoprofen, phloroglucinol and nalbuphine. RESULTS: Forty-six and 50 patients were analysed in the TAP and infiltration groups, respectively [age: 10 [7 to 12] versus 10 [8 to 12] years; females: 16 (35%) versus 25 (50%); duration of surgery: 71 [64 to 90] versus 69 [56 to 89] min]. The primary outcome (total nalbuphine dose) was 0.2 [0.0 to 0.2] and 0.2 [0.0 to 0.2] mg kg -1 in the TAP and infiltration groups, respectively ( P  = 0.95). FLACC scale values did not significantly differ between the two groups ( P  = 0.78). Time to the first dose of nalbuphine or to first mobilisation was not significantly different between groups ( P value for log-rank test = 0.095 and 0.18, respectively). CONCLUSION: TAP block does not appear to provide a greater opioid-sparing effect than LAWI of trocar insertion sites after laparoscopic appendicectomy in children, when combined with systemic multimodal analgesia including nonsteroidal anti-inflammatory drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04969133.

Humans↗

PubMed2026

Prognostic effect of serum glial fibrillary acidic protein and neurofilament light chain for predicting progression independent of relapse activity in multiple sclerosis: A systematic review.

BACKGROUND: Progression independent of relapse activity (PIRA) is increasingly appreciated as one of the important factors contributing to disability accumulation in MS. sGFAP and sNfL could represent markers reflecting two separate biological processes related to relapse-independent progression in MS. OBJECTIVE: To perform a systematic review of the literature on blood GFAP and/or NfL measured in relation to PIRA or other similar relapse-independent progression endpoints in people with MS. METHODS: PubMed, Scopus, and Web of Science databases were searched from inception to 1 June 2026. The eligible studies were original human studies measuring blood GFAP and/or NfL concentrations in serum, plasma, or any other type of blood-derived material and assessing PIRA, PIRMA, CDP/CDW without relapses, relapse-free EDSS progression, non-inflammatory progression, or comparable relapse-independent disability worsening outcomes. Methodological quality was assessed according to the Newcastle-Ottawa scale and the QUIPS instrument for bias detection in the body of evidence on prognostic factors. Due to heterogeneity of outcomes, biomarker measurements and effect estimates, results were synthesized qualitatively rather than quantitatively. RESULTS: After removing duplicates, 1206 records were screened, followed by full-text review of 120 reports. A total of 18 reports were included. Overall, sGFAP was associated more frequently with PIRA or PIRA-like disability progression, particularly in cohorts with suppressed or limited overt inflammatory activity. Evidence for sNfL was more variable and context-dependent: several studies reported associations with PIRA-like or relapse-independent disability worsening when acute inflammatory activity was absent, suppressed, or analytically separated, whereas other studies reported negative or inconclusive findings. Negative or inconclusive results were reported by several articles, particularly when broad outcomes were evaluated or the study population was small. CONCLUSION: Blood GFAP and NfL give complementary but non-interchangeable information concerning PIRA in MS patients. The existing evidence base does not allow us to perform meta-analysis because of heterogeneity in terms of outcomes, standardization of biomarkers, and treatment context. Further prospective investigations with uniform criteria will be necessary for their use as biomarkers of PIRA in clinical settings.

Humans↗