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Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5&#x2009;mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p&#x2009;=&#x2009;0.567), MVO (54.0% vs. 70.9%; p&#x2009;=&#x2009;0.059), MVO extent (0.70% vs. 1.90%; p&#x2009;=&#x2009;0.101) and IS (21.30% vs. 24.50%; p&#x2009;=&#x2009;0.079). Post-PCI angio-IMR was positively correlated with MVO extent (&#x3c1;&#x2009;=&#x2009;0.347; p&#x2009;<&#x2009;0.001) and IS (&#x3c1;&#x2009;=&#x2009;0.324; p&#x2009;<&#x2009;0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p&#x2009;<&#x2009;0.001), MVO&#x2009;>&#x2009;2.6% (AUC&#x2009;=&#x2009;0.735; p&#x2009;<&#x2009;0.001) and IS&#x2009;>&#x2009;25% (AUC&#x2009;=&#x2009;0.712; p&#x2009;<&#x2009;0.001). The exploratory optimal cut-off values for these endpoints were approximately 40&#x2009;U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans

Assessment of the safety and efficacy of sodium pentaborate pentahydrate in individuals with overweight and obesity: a randomized, double-blind, placebo-controlled, phase 1/2 dose-finding trial.

The present study aimed to examine the short-term safety and tolerability of sodium pentaborate pentahydrate (NaB) and to explore preliminary efficacy and dose selection as secondary objectives in individuals with overweight or obesity. In this randomized, double-blind, placebo-controlled, phase 1/2 trial, conducted from July 2024 to January 2025, 177 adults with overweight or obesity were randomized, of whom 116 completed the 12-week trial. Participants received placebo or NaB at doses of 200, 400, 600, 800, or 1,000&#x2009;mg for 12&#x2009;weeks, alongside a standardized diet and exercise programme. The primary safety objective was to investigate short-term safety and tolerability through adverse events, hypoglycaemic episodes, gastrointestinal adverse events, and changes in haematological and biochemical parameters. The primary exploratory efficacy outcome was percentage change in body weight from baseline to week 12. Secondary and exploratory efficacy outcomes included body weight, body mass index (BMI), waist and hip circumferences, waist-to-hip ratio, glycaemic markers, lipid parameters, and blood pressure. Baseline characteristics were broadly similar across groups (all p&#x2009;&#x2265;&#x2009;0.05), and no major short-term safety signal was observed. Mean body weight decreased in the 400&#x2009;mg (-2.6&#x2009;kg), 600&#x2009;mg (-1.2&#x2009;kg), and 1,000&#x2009;mg groups (-3.1&#x2009;kg). Compared with placebo, the 1,000&#x2009;mg dose resulted in the largest reductions in body weight (mean difference, -2.30&#x2009;kg; p&#x2009;=&#x2009;0.01) and BMI (mean difference, -0.85&#x2009;kg/m2; p&#x2009;=&#x2009;0.02). The 1,000&#x2009;mg dose showed preliminary efficacy for reducing body weight and BMI over 12&#x2009;weeks compared with placebo, with no major short-term safety signal and no clinically meaningful changes in renal, hepatic, or haematological markers. All reported adverse events were mild. These short-term findings are exploratory and require confirmation in future phase 3 trials with extended follow-up to investigate long-term safety and efficacy.

Humans

Efficacy and safety of thulium fiber laser versus conventional holmium:YAG laser in anatomical endoscopic enucleation of the prostate: a systematic review and pairwise meta-analysis.

PURPOSE: Anatomical endoscopic enucleation is an established treatment for benign prostatic obstruction. Whether thulium fiber laser enucleation (ThuFLEP) improves outcomes over conventional holmium:YAG laser enucleation (HoLEP) remains uncertain. We compared the efficacy and safety of ThuFLEP versus non-MOSES-modulated HoLEP. METHODS: We performed a PRISMA-compliant systematic review and pairwise meta-analysis of randomised and comparative cohort studies comparing ThuFLEP and conventional HoLEP in adult men. Six databases were searched. Outcomes included International Prostate Symptom Score (IPSS), IPSS quality-of-life score, maximum urinary flow rate (Qmax), post-void residual volume, hospital stay, and complications. Risk of bias and certainty of evidence were assessed with RoB 2/ROBINS-I and GRADE. RESULTS: Seven non-overlapping comparative populations in eight publications included 3,509 patients. ThuFLEP was associated with a small statistically significant reduction in IPSS at 3&#xa0;months (mean difference [MD] -1.04 points, 95% confidence interval [CI] -1.81 to -0.28) of uncertain clinical relevance. Qmax differences were small and directionally inconsistent across follow-up (favouring HoLEP at 3&#xa0;months and ThuFLEP at 6 and 12&#xa0;months) and derived mainly from retrospective cohorts, with neutral randomised subgroups. Stress and urge urinary incontinence were less frequent overall (RR 0.75, 95% CI 0.58 to 0.96, and RR 0.39, 95% CI 0.22 to 0.68), but both estimates depended on one large registry cohort and were not robust to its exclusion. Most other complications and hospital stay showed no clear between-group difference. Limitations include few studies per outcome, heterogeneity, sparse safety events, inconsistent prostate-specific antigen reporting, and mostly low/very low certainty evidence. CONCLUSION: ThuFLEP and conventional HoLEP are clinically comparable with no definitive superiority of either laser. Platform selection should be individualised according to surgeon expertise, institutional resources, and patient characteristics. Future trials should standardise cost-effectiveness outcomes and investigate whether the distinct laser-tissue interactions impact adenoma clearance, PSA reduction, enucleation completeness, and long-term durability.

Humans

Interfacial engineering of cobalt tungstate-halloysite nanotube nanocomposite for electrochemical detection of synthetic vanillin in food matrices.

In processed foods and medicine, synthetic vanillin is widely used, although excessive intake poses toxicological risks. Due to the rising usage of synthetic vanillin in food products and associated health hazards, quick, sensitive, and reliable analytical methods are needed to precisely measure vanillin in complex food matrices. This work introduces a CoWO4@F-HNT/GCE nanocomposite as an efficient electrocatalytic modifier for glassy carbon electrodes aimed at trace-level synthetic vanillin detection. Structural and microscopic analyses confirmed phase-pure monoclinic CoWO4, preservation of the tubular aluminosilicate framework, and homogeneous nanoparticle anchoring on F-HNT. Differential pulse voltammetry provided a broad linear range from 0.01 to 372.14&#xa0;&#x3bc;M and a low detection limit of 4.3&#xa0;nM, together with excellent selectivity against common interferents, good cycling stability, and high inter-electrode reproducibility. These characteristics position the CoWO4@F-HNT-modified electrode as a cost-effective and reliable platform for on-site quality control of synthetic vanillin in complex food matrices.

Benzaldehydes

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans

Exercise Snacks Are Feasible to Perform in the Real World and Improve Physical Capacity for Adults Living With Non-Insulin Treated Type 2 Diabetes: A Randomised Trial.

AIMS: To investigate the feasibility and preliminary efficacy of a 12-week remotely-delivered exercise snacks (ES) intervention in adults with type 2 diabetes. MATERIAL AND METHODS: Insufficiently active adults with type 2 diabetes (N&#x2009;=&#x2009;69; 46 females; mean age&#x2009;&#xb1;&#x2009;SD: 58&#x2009;&#xb1;&#x2009;11&#x2009;years) were randomised to an ES or mobility/stretching comparator group (CON), which involved 4&#x2009;&#xd7;&#x2009;1-min bouts of either vigorous or low intensity exercise, respectively, on &#x2265;&#x2009;5&#x2009;days/week. The primary outcome was feasibility based on adherence. Secondary outcomes included exercise enjoyment (1-7 scale), rating of perceived exertion (RPE; 0-10 scale), heart rate (HR), haemoglobin A1c (HbA1c), blood biomarkers of cardiometabolic health, 30-s sit-to-stand capacity, grip strength, estimated maximal oxygen uptake, and anthropometrics. RESULTS: Weekly adherence (estimated marginal mean [95% confidence interval]: 18 bouts [16-21] for both groups; p&#x2009;=&#x2009;0.99) and total enjoyment (ES: 4.5 [4.1-4.8] vs. CON: 4.3 [4.0-4.7]; p&#x2009;=&#x2009;0.64) were high and not different between groups. Despite higher RPE (5.7 [5.4-6.1]) and peak HR (73 [70-77] % of age-predicted HR maximum) in ES versus CON (2.0 [1.7-2.4] and 61 [58-64] % of age-predicted HR maximum, respectively) (all p&#x2009;<&#x2009;0.001), there were no between-group differences in the change in any secondary outcome (all p&#x2009;>&#x2009;0.05) except for greater sit-to-stand capacity in ES after training (between-group effect estimate [95% confidence interval]: 1.9 repetitions [0.3-3.4]; p&#x2009;=&#x2009;0.02). CONCLUSIONS: Exercise snacks were feasible to perform in the real world and improved sit-to-stand capacity to a greater extent than CON in adults living with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06407245.

Aged

Alterations in Spatiotemporal Parameters in Patients With Lower-Limb Amputation: A Systematic Review With Meta-Analysis.

OBJECTIVES: To evaluate differences in spatiotemporal gait parameters in individuals with transfemoral (TFA) and transtibial amputation (TTA) compared with physically able individuals. METHODS: This systematic review with meta-analysis was conducted according to the MOOSE guidelines. Cross-sectional studies or clinical trials that assessed spatiotemporal gait parameters in adults with unilateral TFA or TTA were included. Searches were performed in Medline (via PubMed), CINAHL, Scopus, LILACS, Cochrane Library, and Embase using descriptors related to amputation and gait. Risk of bias was assessed using the Joanna Briggs Institute scale for cross-sectional studies, whereas the meta-analysis was performed using quantitative data for the following outcomes: walking speed, step length, stride length, step width, cadence, stance time, swing time, step time, or stride time. RESULTS: A total of 12 cross-sectional studies involving 150 individuals with amputation (86 TTA and 64 TFA) and 138 healthy controls were included. Meta-analysis demonstrated a significant reduction in walking speed (mean difference of -0.24; 95% CI -0.32 to -0.17; p&#xa0;<&#xa0;0.0001; I2&#xa0;=&#xa0;61%) and cadence (mean difference of -6.01; 95% CI -9.69 to -2.34; p&#xa0;=&#xa0;0.001; I2: 54%) in patients with amputation compared with healthy individuals. A reduction in stride length (mean difference of -11.71; 95% CI -23.37 to -0.04; p&#xa0;=&#xa0;0.05; I2: 85%) and an increase in step width (mean difference of 5.22; 95% CI 2.99 to 7.45; p&#xa0;<&#xa0;0.0001; I2: 71%) were also observed. Step time showed no significant difference between groups (mean difference of 0.06; 95% CI -0.01 to 0.14; p&#xa0;=&#xa0;0.11; I2: 93%). Patients with TFA amputation exhibited greater impairment in gait variables, particularly cadence, when compared with a healthy individual. CONCLUSIONS: Patients with lower limb amputation present with functionally compromised gait, characterized by reduced walking speed. Increased step width and reduced stride length are findings that may suggest compensatory strategies during gait and improved balance, which are important requirements for amputee patients. These findings reinforce the need for rehabilitation interventions focused on improving propulsion and postural safety. TRIAL REGISTRATION: PROSPERO: CRD42024620098.

Humans

Efficacy and Safety of iGlarLixi Versus IDegAsp by Baseline Age, Disease Duration and HbA1c in Chinese People With Type 2 Diabetes: Post Hoc Analyses of the Soli-D Study.

AIMS: To compare the efficacy and safety of insulin glargine 100&#x2009;U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS: In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24&#x2009;weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (<&#x2009;65, &#x2265;&#x2009;65&#x2009;years), T2D duration (<&#x2009;10, &#x2265;&#x2009;10&#x2009;years) and HbA1c (&#x2265;&#x2009;7% to &#x2264;&#x2009;8% [&#x2265;&#x2009;53 to &#x2264;&#x2009;64&#x2009;mmol/mol], >&#x2009;8% to &#x2264;&#x2009;9% [>&#x2009;64 to &#x2264;&#x2009;75&#x2009;mmol/mol], >&#x2009;9% [>&#x2009;75&#x2009;mmol/mol]). RESULTS: Among 582 participants (iGlarLixi n&#x2009;=&#x2009;291; IDegAsp n&#x2009;=&#x2009;291), baseline age was <&#x2009;65&#x2009;years in 442 and &#x2265;&#x2009;65&#x2009;years in 140; T2D duration was <&#x2009;10&#x2009;years in 366 and &#x2265;&#x2009;10&#x2009;years in 216; and HbA1c was &#x2265;&#x2009;7% to &#x2264;&#x2009;8% in 205, >&#x2009;8% to &#x2264;&#x2009;9% in 209 and >&#x2009;9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS: iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

Humans

A novel neoadjuvant immunotherapy confers improved overall survival in oral cancer patients with low tumor PD-L1 expression The IT-MATTERS Clinical trial - Prognostic role of tumor PD-L1 expression.

OBJECTIVE: Five-year overall survival (OS) remains&#xa0;<&#xa0;50% for patients with resectable, locally advanced (LA) primary oral squamous cell carcinoma (OSCC) and soft palate, receiving current standard of care (SOC). The aim of our study was to examine neoadjuvant Leukocyte Interleukin Injection (LI) with CIZ (intravenous low dose cyclophosphamide, indomethacin and zinc multivitamins) effect on OS, in low-risk (LR) OSCC patients. PATIENTS AND METHODS: In a randomized, controlled Phase 3 trial, treatment-na&#xef;ve locally advanced patients, with stage III/IVa OSCC and soft-palate cancer, had surgical tumor samples assessed for pre-defined thresholds of PD-L1 tumor proportion score (TPS). OS was analyzed using proportional hazard models for LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC, in the intention-to-treat (ITT) population. RESULTS: OS was superior in low risk (LR) patients receiving LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC compared to SOC; OS advantage hazard ratio (HR) 0.64, p&#xa0;=&#xa0;0.0569 (without selecting for N0, PD-L1 TPS&#xa0;<&#xa0;10%), and the Kaplan-Meier (K-M) lifetable achieved significance (log rank p&#xa0;=&#xa0;0.0340) favoring LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC. Applying the selection criteria (cN0 and TPS&#xa0;<&#xa0;10%) to ITT, OS reached HR 0.34p&#xa0;=&#xa0;0.0012, Kaplan-Meier log rank p&#xa0;=&#xa0;0.0015. The ITT LR cohort (cN0 and TPS&#xa0;<&#xa0;10%) achieved a HR 0.26 (p&#xa0;=&#xa0;0.0023), Kaplan-Meier log rank p&#xa0;=&#xa0;0.0013, supported by progression free survival (PFS) HR 0.43, p&#xa0;=&#xa0;0.0178, Kaplan-Meier log rank p&#xa0;=&#xa0;0.0431, with 32% absolute survival advantage over control at 60&#xa0;months. CONCLUSIONS: Significant OS prolongation was observed in ITT population for LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC, in LR and in ITT LR cN0, PD-L1TPS&#xa0;<&#xa0;10% cohort having locally advanced squamous cell carcinoma tumors in oral cavity/soft-palate. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01265849; EudraCT (Identifier: 2010-019952-35).

Humans

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, &#x2265; 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

Exploring the role of successful exercise-induced body weight loss on cardiometabolic health in individuals with metabolic syndrome.

BACKGROUND AND AIM: High-intensity interval training (HIIT) is known to improve cardiorespiratory fitness (i.e., VO2MAX), a key marker of cardiometabolic health in individuals with metabolic syndrome (MetS). Nonetheless, body weight loss is widely recognized as a crucial factor in reducing insulin resistance and improving metabolic risk factors. Thus, we aimed to determine the importance of body weight loss following exercise training on improving MetS. METHODS AND RESULTS: Two hundred and twenty-eight adults (55.3&#xa0;&#xb1;&#xa0;7.9&#xa0;yr) with overweight/obesity (32.5&#xa0;&#xb1;&#xa0;4.6&#xa0;kg&#xb7;m-2) and MetS were randomized to: a) standard health care non-exercise group (CONTROL group, N=58) or b) standard health care plus 16 weeks of HIIT (EXER group, N=170). MetS (MetS z-score), insulin resistance (HOMA-IR), cardiorespiratory fitness (VO2PEAK), maximal cycling power (WPEAK), and body weight/composition were assessed. After intervention, EXER group participants were divided according to their weight loss response to training: i) those achieving the weight loss predicted from estimated exercise energy expenditure (-BW group, n=78; -3.3&#xa0;&#xb1;&#xa0;2.2&#xa0;kg); ii) those not reaching the expected weight loss (=BW group, n=38; -0.7&#xa0;&#xb1;&#xa0;0.5&#xa0;kg); iii) and those who gained weight (+BW group, n=54; 1.1&#xa0;&#xb1;&#xa0;1.0&#xa0;kg). VO2PEAK significantly improved regardless of body weight loss response (-BW, 0.3&#xa0;&#xb1;&#xa0;0.3; =BW, 0.2&#xa0;&#xb1;&#xa0;0.3; +BW, 0.3&#xa0;&#xb1;&#xa0;0.2&#xa0;L&#xb7;min-1; all p&#xa0;<&#xa0;0.001) compared to CONTROL group (0.0&#xa0;&#xb1;&#xa0;0.3&#xa0;L&#xb7;min-1). However, significant improvements in MetS z-score (-0.31&#xa0;&#xb1;&#xa0;0.41) and HOMA-IR (-0.7&#xa0;&#xb1;&#xa0;1.6) were observed only in the -BW group (both p&#xa0;<&#xa0;0.001). CONCLUSIONS: Exercise recommendations should consider that greater improvements in MetS are observed when interventions are accompanied by successful body weight loss. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05120778.

Humans

Hyper-oncotic albumin administration reduces mortality in acute Respiratory Distress Syndrome compared to crystalloid: a systematic review and meta-analysis.

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (&#x2265;20%) and the iso-oncotic albumin subgroup (4%&#x223c;5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with &#x3b1;&#x2009;=&#x2009;0.05 and &#x3b2;&#x2009;=&#x2009;0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85, p&#x2009;=&#x2009;0.004). RCTs (n&#x2009;=&#x2009;204) showed no benefit (OR = 0.83, p&#x2009;=&#x2009;0.54), but NRSs (n&#x2009;=&#x2009;384) demonstrated reduced mortality (OR = 0.52, p&#x2009;=&#x2009;0.002). Hyper-oncotic albumin was associated with lower mortality in NRSs (OR = 0.40, p&#x2009;=&#x2009;0.02) but not in RCTs (OR = 0.74, p&#x2009;=&#x2009;0.57). Iso-oncotic albumin showed no benefit (OR = 0.88, p&#x2009;=&#x2009;0.72). Regarding the impact of albumin on oxygenation, significant improvements in oxygenation were observed only on the first (p&#x2009;=&#x2009;0.05) and second days (p&#x2009;<&#x2009;0.0001). The TSA indicated a continued need for high-quality RCTs. CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.

Humans

'Sawa Aqwa' (Stronger Together): A multi-site randomized controlled trial of a brief family systemic intervention for adolescent mental health in Lebanon.

BACKGROUND: There are no evaluated family-based mental health and psychosocial support (MHPSS) interventions for adolescents in Southwest Asia (known as the Middle East), and few whole-family interventions in low- and middle-income countries, despite consistent evidence for the impact of family support on mental health and well-being. This study aims to evaluate the effectiveness of a brief family systemic mental health intervention, deliverable by non-specialists in mental health. METHODS: We conducted an assessor-blind type I hybrid effectiveness-implementation multi-site randomized controlled trial comparing the locally developed family intervention to a waitlist control group for randomly allocated families residing in North Lebanon and Beqa'a governorates. Eligible families presented with medium-to-high risk for child protection concerns (abuse, neglect, child labor, early marriage) and had at least one adolescent aged 12-17 who demonstrated psychological distress. Outcomes at the family, caregiver, and adolescent level were measured pre- and post-intervention, and at 3-month follow-up. RESULTS: Intent-to-treat analyses found a significant between-group effect of the intervention on adolescent-reported family functioning, caregiver mental health, and parenting. No change was found for adolescent psychological distress. Further analyses found effects on adolescent well-being for those who completed the intervention, and that father attendance was associated with better outcomes for adolescent well-being in the intervention group. No other significant moderators were found. At the 3-month follow-up for the intervention condition, family functioning and caregiver well-being significantly dropped from endline. CONCLUSIONS: The study demonstrates mixed results for a non-specialist-delivered family-systemic intervention developed in the context of humanitarian crises in Lebanon. While the intervention did not result in benefits in adolescent-reported symptoms of psychological distress, the intervention group did show greater improvements than the control group on a number of other outcomes, showing the potential impact of working with the wider family system to support adolescents in humanitarian settings.

Humans

Measurable Residual Disease and the Unresolved Biology of Leukemic Stem Cells.

Measurable residual disease (MRD) testing has transformed the management of hematologic cancers by enabling detection of residual malignant cells after therapy. Current approaches rely on qPCR and next-generation sequencing to monitor leukemia-associated somatic mutations, while multiparameter flow cytometry identifies aberrant leukemic immunophenotypes. Although these methods provide valuable prognostic and therapeutic information, MRD negativity remains an imperfect surrogate for cure. Most MRD platforms evaluate CD45+, rapidly dividing leukemic populations and fail to detect quiescent cells that may survive cytotoxic therapies which efficiently target proliferating hematopoietic cells. Relapse frequently occurs despite deep molecular remission, suggesting persistence of rare leukemic stem cells (LSCs) that are intrinsically resistant to chemotherapy and targeted therapies. The paradox of relapse despite molecular remission could be explained by the presence of very small embryonic-like stem cells (VSELs) which are pluripotent, quiescent stem cells sitting at the top of cellular hierarchy in multiple adult tissues including bone marrow. A pluripotent VSEL divides through asymmetrical cell division to give rise to two cells of different sizes and fates, smaller cell is to self-renew while the bigger is lineage-restricted and tissue-committed progenitor which undergoes extensive epigenetic changes, divides rapidly and undergoes clonal expansion before further differentiation. Dysfunctions of VSELs initiate both solid and hematologic cancers. Based on this view, somatic mutations monitored during MRD assessment possibly represent downstream consequences of clonal expansion rather than the initiating drivers of disease persistence. Thus, exclusive monitoring of somatic mutations and CD45&#x2009;+&#x2009;leukemic populations possibly overlook rare, small-sized, CD45- VSELs that contribute to therapeutic resistance and relapse.

Humans

Control of foreign DNA: emerging roles of xenogeneic silencers.

Bacteria continuously acquire foreign DNA through horizontal gene transfer, yet its successful integration depends on regulatory mechanisms that balance genome protection with evolutionary innovation. Xenogeneic silencers are central to this process: they preferentially bind AT-rich DNA, a common feature of many horizontally acquired genetic elements, and repress its transcription. Recent studies, however, reveal a much broader regulatory repertoire. Beyond transcriptional repression, these proteins contribute to chromosome organization by forming higher-order nucleoprotein complexes and phase-separated condensates that shape bacterial nucleoid architecture. Furthermore, they play roles in regulating bacteriophage infection cycles, including mechanisms by which phages hijack host silencing activities for their own benefit. Their extensive regulatory reach, spanning virulence genes, biofilm formation, specialized metabolite production, and mobile genetic elements (MGEs), underscores their central role in connecting environmental signals, including fluctuations in the second messenger c-di-GMP, with gene expression, and genome organization. The diversification of xenogeneic silencers across bacterial chromosomes, plasmids, phages, and other MGEs highlights their evolutionary significance. Together, these recent findings position xenogeneic silencers as dynamic regulatory modules that shape the fate of foreign DNA across the horizontal gene transfer network.

Gene Transfer, Horizontal

Extending the Treatment Window for Intravenous Thrombolysis in Acute Ischemic Stroke: An Updated Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Intravenous thrombolysis (IVT) is the standard treatment for acute ischemic stroke within 4.5 hours of onset. However, imaging-based selection may extend the treatment window. This systematic review and meta-analysis evaluated the efficacy and safety of IVT administered beyond 4.5 hours after stroke onset or last known well (LKW) in patients selected based on imaging findings. METHODS: A comprehensive search of PubMed, Scopus, and Cochrane Library was performed to identify randomized controlled trials comparing IVT with alteplase or tenecteplase (TNK) administered >4.5 hours after stroke onset/LKW vs standard care. Primary outcomes were 3-month excellent (modified Rankin Scale [mRS] 0-1) functional outcome and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included good (mRS 0-2) functional outcome, recanalization, and 3-month mortality. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analysis assessed differences between alteplase and TNK. RESULTS: Fourteen studies involving 4,944 patients were included. The mean age was 69.8 years, 58.2% were male, the median National Institutes of Health Stroke Scale score was 9, and 12.3% received preplanned endovascular thrombectomy (EVT). A total of 2,492 patients received IVT in an extended time window (4.5-24 hours). Compared with standard care, extended IVT was associated with higher odds of achieving an excellent functional outcome (OR: 1.43 [95% CI 1.25-1.63]), a good functional outcome (OR: 1.25 [95% CI 1.11-1.40]), and recanalization (OR: 3.28 [95% CI 2.09-5.16]). There was no difference in 3-month mortality (OR: 1.21 [95% CI 0.95-1.53]). However, IVT increased the risk of sICH (OR: 2.51 [95% CI 1.47-4.28]). Sensitivity analysis excluding patients who received EVT showed no impact on the outcomes. TNK exhibited similar efficacy to alteplase but showed potentially lower odds of sICH (OR: 1.96, 95% CI 1.06-3.64) compared with alteplase (OR: 5.29, 95% CI 1.80-15.57); however, the subgroup difference was not significant (p = 0.11). DISCUSSION: Among patients selected based on imaging, 4.5-24 hours after stroke onset/LKW, IVT improves outcomes despite an increased risk of sICH. TNK showed similar efficacy to alteplase, with a possible lower risk of sICH; however, direct comparisons in future trials are needed.

Humans

Transverse Tibial Transport for Limb Salvage in Ischemic Lower Extremity Disease: Technique, Mechanisms, and Clinical Outcomes-A Systematic Review.

Transverse tibial transport (TTT) is a surgical technique derived from Ilizarov's distraction osteogenesis principles that stimulates angiogenesis and microcirculatory regeneration in the ischemic lower limb without directly manipulating macrovascular anatomy. By creating a proximal tibial cortical bone window and distracting it transversely using an external fixator, TTT triggers converging cascades of growth factor release, endothelial progenitor cell mobilization, and immunomodulation that translate into improved distal limb perfusion and wound healing. Combined TTT plus endovascular therapy improves amputation-free survival versus endovascular therapy alone. Prospective randomized trials and standardized international protocols are needed to consolidate TTT's role in multidisciplinary limb salvage pathways.

Humans

Assessment of the role and effectiveness of nurse-led multimodal intervention in the rehabilitation of dysphagia in patients with brain tumors.

BACKGROUND: Dysphagia is a common complication in patients with brain tumors, which has a profound adverse impact on patients' health status and quality of life. However, there is a relative lack of research on the rehabilitation of dysphagia in brain tumor patients, especially regarding the role and effectiveness of nurse-led multimodal interventions in the rehabilitation of dysphagia in brain tumor patients, which lacks systematic assessment and in-depth discussion. AIM: This study aimed to evaluate the role and effectiveness of a nurse-led multimodal intervention in improving swallowing function and quality of life in brain tumor patients with dysphagia. METHODS: In this study, a randomized controlled trial (RCT) design was used to select 120 dysphagia patients among brain tumor patients admitted to our hospital during the period of January 2024 to May 2024 as the study subjects, and they were stratified and randomly divided into an intervention group (n&#x2009;=&#x2009;60) and a control group (n&#x2009;=&#x2009;60). While the control group received conventional nursing care and treatment protocols, the intervention group received a nurse-led multimodal intervention program, including personalized swallowing training, nutritional support, psychological care, and a family-participatory rehabilitation program, which was developed and dynamically adjusted by nurses, rehabilitation therapists, and dietitians. Differences in data before and after the intervention were analyzed using the paired t-test or Wilcoxon signed-rank test, and between-group comparisons were made using the independent samples t-test or Mann-Whitney U test. RESULTS: Both the intervention and control groups showed improvement in swallowing function among the patients. The Kubota drinking test score, Saito's swallowing function grading, and the quality of life scores for patients in the intervention group showed a significant enhancement compared to those in the control group (P&#x2009;<&#x2009;0.05), indicating that the intervention was more effective than the control. When compared within groups, all scores in both the intervention and control groups improved gradually with the time of intervention (P&#x2009;<&#x2009;0.05). The improvement was significantly higher in the intervention group than in the control group. CONCLUSION: This study demonstrates that a nurse-led multimodal intervention is significantly effective in improving swallowing function and quality of life in patients with brain tumors. The intervention provides comprehensive rehabilitation support for patients through multidisciplinary collaboration and personalized care and has certain clinical promotion value.

Humans