Tuberculosis (TB) treatment is often associated with adverse drug reactions (ADRs) of varying severity, which may negatively affect treatment adherence and outcomes. This study aimed to identify ADRs related to first-line anti-TB drugs, determine associated factors, and evaluate treatment outcomes among TB patients in the Laâyoune-Sakia El Hamra region of Morocco. A retrospective study was conducted in southern Morocco from January 1, 2023 to December 31, 2024. Data were collected from clinical charts of TB patients treated at the Center for Tuberculosis and Respiratory Diseases of Laâyoune (CDTMRL). Adverse drug reactions were evaluated by a specialist clinician throughout treatment, and outcomes were assessed according to World Health Organization guidelines. Among 354 TB patients, 26.55% experienced ADRs, most commonly during the intensive treatment phase. ADRs were significantly associated with gender, age, smoking status, and comorbidities, particularly diabetes and HIV infection. The majority of ADRs were hepatic (13.87%) and gastrointestinal (9.83%). Cutaneous (6.36%), articular (6.07%), and renal (5.78%) ADRs occurred at similar frequencies. Neurological, immunoallergic, cardiovascular, and urogenital ADRs were comparatively less frequent. Most reactions were mild to moderate and managed symptomatically, with few requiring treatment modifications and no ADR-related deaths. Treatment success outcomes were achieved in 81.1% of patients and unsuccessful treatment accounted for 10.73%. Adverse reactions to first-line anti-TB medications are relatively common and highlight the need for close clinical monitoring throughout the treatment period. Strengthening pharmacovigilance and improving patient education may help enhance treatment adherence and reduce complications.

The current single-center, retrospective, observational cohort study with a cross-sectional design was conducted to evaluate the association between androgenic profile and metabolic cardiovascular risk (mCVR) factors and to explore whether testosterone deficiency was associated with an unfavourable cardiometabolic profile in a large community-recruited cohort of 659 young men aged 18-35 years.

Participants underwent comprehensive assessment of anthropometric, biochemical, clinical, and hormonal parameters.

Body mass index (BMI), expression of generalized obesity, waist circumference (WC), expression of abdominal/visceral obesity, diastolic blood pressure (DBP) and triglycerides (TG) significantly and progressively decreased and high-density lipoprotein (HDL)-cholesterol significantly increased across total testosterone (TT) tertiles. Similarly, weight, BMI, WC, systolic blood pressure (SBP), DBP and TG significantly decreased and HDL-cholesterol significantly increased across SHBG tertiles. Weight and adiposity-related anthropometric parameters, namely BMI and WC, significantly and progressively decreased across calculated free testosterone (cFT) tertiles. Spearman correlation analysis showed that TT and SHBG were significantly and negatively correlated with weight (r=-0.149, r=-0.154), BMI (r=-0.204, r=-0.165), WC (r=-0.234, r=-0.225), SBP (r=-0.112, r=-0.142) and TG (r=-0.117, r=-0.204), and significantly and positively correlated with HDL-cholesterol (r = 0.167, r = 0.251). Additionally, SHBG was significantly and negatively correlated with DBP (r=-0.173). cFT was significantly and negatively correlated with age (r=-0.108) and BMI (r=-0.132). In a multiple linear regression analysis in models adjusted for age, BMI and WC, TT and SHBG were independently associated with HDL-cholesterol (β = 0.151, β = 0.186), and SHBG was independently associated with SBP (β=-0.177) and DBP (β=-0.204). Men with testosterone below the normal range (Hypo-T group) showed a significantly higher prevalence of generalized obesity and abdominal obesity than men with testosterone within the normal range (Normal-T group). Conversely, Overweight/Obese men exhibited significantly lower TT and a significantly higher prevalence of testosterone deficiency than Normal-Weight men.

In young adult men, androgenic profile was found to be robustly associated with mCVR factors; however, causality and temporal directionality cannot be inferred because of the cross-sectional design of the study.

Cerebral ischemic stroke (CIS) leads to high mortality and disability due to cerebrovascular obstruction. Current therapeutic approaches such as thrombolysis have limitations, and many patients suffer from long-term functional impairments, so new treatment strategies are urgently needed. Both low-intensity pulsed ultrasound (LIPUS) and mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated some therapeutic potential for CIS, but their efficacy is less pronounced when used alone. Therefore, this study aims to evaluate whether the combination of MSC-EXOs and LIPUS exerts an additive effect in the treatment of cerebral ischemic stroke. Adult rats subjected to middle cerebral artery occlusion (MCAO) were randomly assigned to sham, MCAO, MSC-EXO, LIPUS, or combination groups. Outcomes were assessed using the modified Neurological Severity Score (mNSS), corner and Y-maze tests, histological staining (HE and immunofluorescence), transmission electron microscopy (TEM), and quantitative real-time polymerase chain reaction (q-PCR). The combination group showed notable improvements in neurological function, with the highest proportion of cluster of differentiation 31 (CD31)/alpha-smooth muscle actin (α-SMA)/doublecortin (DCX)-positive immunofluorescence area, up-regulation of circular RNA SCMH-1(circSCMH-1), and the best restoration of synaptic ultrastructure. Compared with MSC-EXOs or LIPUS alone, the combined treatment appeared to have an additive effect, supporting neurovascular regeneration and functional recovery after cerebral ischemic stroke.

Pathological thrombosis is a major cause of cardiovascular and cerebrovascular diseases. Current anticoagulants increase bleeding risk by impairing physiological hemostasis. Because coagulation factor XIIa (FXIIa) drives pathological thrombosis but is dispensable for normal hemostasis, inhibiting FXIIa may offer antithrombotic efficacy with reduced bleeding risk. However, the marked flexibility of its active site hampers the discovery of small-molecule inhibitors. Here, we developed an integrated computational workflow to address this challenge and screened a library of approximately 21 million compounds. Four structurally distinct hits (DR1-DR4) were identified. Microsecond-scale molecular dynamics simulations suggested stable binding of all four compounds to FXIIa, and binding free energy calculations suggested that DR1 and DR3 exhibited more favorable binding free energies than the reference inhibitor 1303. These compounds also showed favorable predicted pharmacokinetic properties, providing structurally distinct hits for FXIIa-targeted anticoagulant discovery.

The crystal structure of the FXIIa catalytic domain (PDB ID: 6B74) was prepared in PyMOL 3.1, and missing regions were modeled with MODELLER. To capture active-site flexibility, apo-FXIIa was subjected to three independent 1-µs molecular dynamics simulations, and a representative conformation selected by clustering was used for virtual screening. A hierarchical screening workflow was carried out in DrugFlow using KarmaDock for primary screening, CarsiDock for redocking, and RTMScore for rescoring. Drug-likeness and pharmacokinetic properties were predicted with SwissADME. Selected complexes were simulated in Amber18 using ff19SB for the protein, GAFF2 for ligands, OPC water, and AM1-BCC ligand charges, and trajectories were analyzed with CPPTRAJ in AmberTools. Binding free energies were estimated with MMPBSA.py using the MM/GBSA method, with entropy contributions evaluated by normal mode analysis. Structural visualization was performed with PyMOL and Discovery Studio Visualizer 2016.

Up to 50% of pulmonary embolism (PE) survivors experience long-term functional limitations and reduced quality of life (QoL). Reperfusion strategies can rapidly relieve right-ventricular (RV) dysfunction and prevent clinical deterioration or hemodynamic collapse; however, these approaches have never been evaluated in a randomized trial against anticoagulation alone using patient-centered outcomes.

This study sought to evaluate whether mechanical thrombectomy with anticoagulation improves functional, QoL, and safety outcomes compared with anticoagulation alone in patients with acute intermediate-high risk PE over 90 days.

STORM-PE enrolled 100 PE patients randomized 1:1 to computer-assisted vacuum thrombectomy (CAVT) with anticoagulation or anticoagulation alone across 22 international sites, with RV-to-left-ventricular (RV/LV) ratio change at 48 hours as the primary endpoint. Secondary endpoints included major adverse events within 7 days, functional and QoL outcomes, mortality, and symptomatic PE recurrence through 90 days.

For all patients, median time from randomization to last follow-up visit was 91.0 days [Q1-Q3: 80.5-100.0]. At 90 days, 66.0% (31/47) of CAVT and 64.2% (34/53) of anticoagulation patients completed the 6-min walk test. The CAVT arm exhibited a longer 6-min walk distance compared with anticoagulation alone (478.7 ± 159.5 m vs 368.0 ± 127.8 m, P = 0.003). More CAVT than anticoagulation patients were NYHA Functional Class I (97.4% [37/38] vs 75.6% [34/45], P = 0.005) at 90 days. Dyspnea and QoL scores were comparable between groups, with no differences between arms for all-cause mortality, PE-related mortality, and symptomatic PE recurrence within 90 days.

In STORM-PE, CAVT with anticoagulation resulted in improved functional outcomes at 90 days compared with anticoagulation alone, with equivalent safety rates. This trial supports CAVT as an effective and safe reperfusion strategy for intermediate-high risk PE.

https://clinicaltrials.gov Unique Identifier: NCT05684796.

As more adults with atrial septal defect (ASD) survive into older age and undergo atrial fibrillation (AF) ablation, evidence to guide post-ablation risk stratification remains limited.

To evaluate long-term outcomes after the first AF ablation across ASD management states compared with an intact interatrial septum.

This real-world cohort study included 27 675 patients undergoing their first AF ablation, classified by interatrial septal status as intact septum (n = 27 134), unrepaired ASD (n = 232), percutaneous closure (n = 119), or surgical repair (n = 190). Three pairwise comparisons with an intact septum were constructed. Propensity score overlap weighting was used to balance baseline characteristics, and Cox proportional hazards models were used to assess outcomes. The primary outcome was atrial arrhythmia recurrence after the 3-month blanking period; the secondary outcome was a composite cardiovascular outcome.

Compared with an intact septum, unrepaired ASD was associated with a higher recurrence risk (hazard ratio [HR], 1.27; 95% CI, 1.07-1.51; p = 0.006), with excess risk mainly observed between 3 months and 1 year after ablation. Surgical repair was also associated with higher recurrence risk (HR, 1.21; 95% CI, 1.01-1.46; p = 0.038), with differences emerging beyond 1 year. Percutaneous closure was not associated with increased recurrence risk (HR, 1.07; 95% CI, 0.83-1.38; p = 0.589). Composite cardiovascular outcomes did not differ significantly across groups.

ASD management status identified distinct temporal patterns of atrial arrhythmia recurrence after AF ablation, suggesting that ASD should not be treated as a single binary condition in post-ablation risk assessment.

AIM: To evaluate the potential neuroprotective effect of felbamate in a rat model of spinal cord ischemia-reperfusion injury. MATERIAL and METHODS: Twenty-one male Wistar albino rats were randomly assigned to three groups (n=7 each): control, ischemia, and felbamate-treated. Transient spinal cord ischemia was induced by abdominal aortic occlusion for 20 minutes, followed by reperfusion. Felbamate was administered via a nasogastric tube immediately after reperfusion at a dose of 20 mg/kg. Twenty-four hours after surgery, tissue caspase-3 levels were measured using an enzyme-linked immunosorbent assay, spinal cord sections were evaluated histopathologically using a semiquantitative composite injury score, and neurological function was assessed using the modified Tarlov scoring system. RESULTS: Tissue caspase-3 levels differed significantly across the three groups (ANOVA, F=205.19, p.

Acute myocarditis is an inflammatory disorder of the myocardium that can lead to severe cardiac dysfunction, arising from a broad spectrum of infectious and noninfectious etiologies. Ankylosing spondylitis, which primarily affects the axial skeleton, can involve the heart due to its systemic inflammatory nature, occasionally resulting in severe complications such as myocarditis.

We report an unusual case of acute myocarditis in a 49-year-old male with ankylosing spondylitis presenting with chest pain and systemic inflammatory symptoms. Diagnostic workup using the 2018 Lake Louise Criteria among cardiac MRI confirmed myocarditis in the absence of coronary artery disease or infectious etiology. The patient also demonstrated extraarticular manifestations with pulmonary and ocular involvement, consistent with an active ankylosing spondylitis flare. Management combined beta blockers, physical activity restriction, and re-introduction of anti-TNF alpha therapy, leading to both clinical and biological improvement.

Acute myocarditis represents a rare yet severe cardiac manifestation of ankylosing spondylitis, requiring a high clinical suspicion to prevent heart failure and dilated cardiomyopathy.

In-hospital cardiac arrest (IHCA) is an acute event associated with high mortality. Although survival has improved in high-income countries, contemporary multicenter data from low- and middle-income countries remain scarce, limiting global benchmarking and the identification of system-level opportunities for improvement.

This cohort study used data from the BASIC-IHCA (Baseline Investigation of In-Hospital Cardiac Arrest) registry. Adult patients (≥18 years) who experienced IHCA and received cardiopulmonary resuscitation between July 1, 2019, and December 31, 2020, at 37 hospitals across 29 provinces in China were included. The primary outcome was survival to 30 days or hospital discharge. Secondary outcomes included return of spontaneous circulation, 6- and 12-month survival, and favorable neurological outcome (Cerebral Performance Category score 1-2). Process measures focused on the timeliness of resuscitation response and the implementation of postresuscitation interventions.

Among 17 602 patients (median age, 66 years; 65.5% male), the annual incidence of adult IHCA was 4.1 per 1000 admissions. Cardiac etiology was identified in 6569 (37.3%) patients, and 2380 (13.5%) presented with initial shockable rhythm. Among all patients, 16 872 (95.9%) received cardiopulmonary resuscitation within 1 minute; timely defibrillation or epinephrine was achieved in 71.4% and 84.4% of patients with initial shockable and nonshockable rhythms, respectively. Sustained return of spontaneous circulation was achieved in 6200 (35.2%) patients, of whom 222 (3.6%) received temperature control therapy and 320 (5.2%) underwent coronary angiography. Overall, 1610 (9.1%) patients survived to 30 days or discharge, with 1241 (7.1%) having a favorable neurological outcome. At 12 months, 1075 (6.1%) patients remained alive, and 986 (5.6%) had a favorable neurological outcome.

This multicenter registry highlights a substantial burden of IHCA in China, with markedly low survival rates. Despite prompt initial resuscitation, critical gaps persist in postresuscitation care. Systemic and cultural factors, including the infrequent use of do not attempt cardiopulmonary resuscitation orders, may further contribute to survival disparities. These findings suggest several system-level opportunities to improve IHCA outcomes, including structured response systems, optimized critical care resource allocation, and greater integration of advanced care planning.

Cardiometabolic diseases (CMDs) often manifest in the form of cardiometabolic multimorbidity. Traditional risk assessment methods that rely on single biomarkers fail to adequately characterise the heterogeneity among patients across various subtypes. This study seeks to utilise routine biomarkers to identify clinical subtypes with unique characteristics, thereby improving risk assessment.

We included 337 334 UK Biobank participants without type 2 diabetes (T2D), ischaemic heart disease (IHD) or stroke at baseline. Multi-task Deep LASSO selected 12 variables for K-means clustering. Multi-state Cox models assessed transitions to first cardiometabolic disease (FCMD), cardiometabolic multimorbidity (CMM) and death. Analyses of 251 plasma metabolic measures and circulating proteins characterised molecular correlates; metabolite panels were evaluated in held-out testing.

Four risk-informed phenotypes were identified: metabolically healthy (MH), older cardio-renal-metabolic (OCRM), lean hypercholesterolaemia (LHC) and early-onset metabolic syndrome (EO-MetS). During a median follow-up of approximately 13 years, OCRM showed the highest FCMD and FCMD-to-CMM risks. In primary models, OCRM and EO-MetS showed strong T2D associations, whereas LHC showed stronger relative associations with IHD and stroke than with T2D. Age adjustment attenuated several OCRM and LHC associations, particularly with IHD and stroke; T2D associations remained largely unchanged. Phenotypes exhibited differing metabolic profiles, and exploratory decomposition showed statistical overlap with phenotype-outcome associations without establishing causality. Protein enrichment highlighted complement/coagulation and vascular-remodelling processes. Metabolite panels modestly improved discrimination beyond full clinical models, increasing the 10-year CMM area under the receiver operating characteristic curve from 0.834 to 0.848; phenotype membership added little further improvement.

Routine biomarker-derived subtypes showed distinct cardiometabolic trajectories and multi-omic profiles. These risk-informed phenotypes support exploratory description of cardiometabolic heterogeneity, pending external validation.