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Abstract Background Ventricular arrhythmias (VA) are common complications of acute coronary syndromes (ACS) and can cause cardiac arrest and adverse outcomes. However, the prognostic impact of VA according to their timing in relation to percutaneous coronary intervention (PCI) remains unclear. Purpose To assess the prognostic significance of VA in patients with ACS undergoing PCI according to the timing of occurrence (before, during, or after PCI). Methods We performed a systematic review and meta-analysis of observational studies reporting all-cause mortality with and without VA (sustained VT/VF) in ACS patients undergoing PCI. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects models for short-term (30 days/in-hospital) and long-term (1 year) mortality. Between-study heterogeneity was assessed using the I² statistic. We conducted subgroup analyses for studies that stratified VA according to timing, defined as VA before PCI (prior to arrival in the catheterization laboratory), VA during PCI (in the catheterization laboratory or immediately after reperfusion), VA after PCI (following completion of PCI). Each timing category was compared to patients who did not develop VA within the same time window (before, during or after PCI). Results Twelve studies comprising 49306 patients were included, of whom 4320 (8.76%) experienced VA. The mean age of the patients ranged from 60 to 70 years, and the follow-up ranged from hospital discharge to 8 years. VA was associated with increased short-term (OR 5.02 [3.91-6.44]) and long-term mortality (OR 3.00 [2.86-3.82]). However, in patients alive at discharge/30 days, subsequent long-term mortality risk did not differ between those with and without VA (OR 1.21 [0.70-2.09]) (Figure 1). The subgroup analyses showed that patients with VA were associated with higher short-term mortality compared to patients without VA within each time window: before (OR 4.32 [3.29-5.66]), during (OR 4.29 [2.08-8.84]), and after PCI (OR 9.29 [3.12-27.63]) (Figure 2). VA after PCI was associated with the highest OR for short-term mortality. Conclusions VA significantly worsens short-term outcomes in ACS patients undergoing PCI. Subgroup analysis shows that VA increases mortality in each timing category, before, during and after PCI, with the poorest prognosis observed for arrhythmias developed after reperfusion, in whom reversible acute ischemia may play a lesser role and underlying arrhythmic substrate may predominate.Figure 1Figure 2

Abstract Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort ( n = 5136) and transcriptomic data from a prospective cohort ( n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “ TP53 ‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML‐like, bi TET2 , SF3B1 , and TP53 ‐complex subgroups. Further integration of multi‐omics data may refine MDS classification, improving clinical decision‐making and guiding the development of targeted therapies.

BACKGROUND: Surgical management of Crohn’s disease of the colon and rectum frequently requires total proctocolectomy with end ileostomy. There are limited data on the need for Crohn’s disease–directed therapy and the prevalence of recurrence after surgery. OBJECTIVE: To determine the risk of small-bowel Crohn’s disease recurrence and evaluate risk factors for postoperative recurrence after total proctocolectomy with end ileostomy. DESIGN: Retrospective cohort study. SETTINGS: Multistate tertiary health care system. PATIENTS: Adult patients with Crohn’s disease undergoing total proctocolectomy with end ileostomy between 2014 and 2023. MAIN OUTCOME MEASURES: The primary outcome was small-bowel Crohn’s disease recurrence. RESULTS: A total of 193 patients with a median age of 45 years (interquartile range, 34–61) were included. More than half of the patients (n = 102; 52.9%) had a history of small-bowel Crohn’s disease, and the majority (n = 134; 69.4%) received biologic therapy before surgery. The median follow-up time was 4.8 years (interquartile range, 2.0–7.6). Postoperatively, 30.6% of patients (n = 59) received biologic therapy. Thirty-five patients (18.1%) had small-bowel Crohn’s disease recurrence for an estimated 5-year recurrence-free rate of 80.2% (95% CI, 73.0–85.7). Seven patients (3.6%) developed small-bowel Crohn’s disease recurrence requiring surgery for an estimated 5-year surgical recurrence-free rate of 94.7% (95% CI, 89.0–97.5). On multivariable analysis, history of small-bowel Crohn’s disease (HR 2.17; 95% CI‚ 1.04–4.54) and diagnosis at age younger than 18 years (HR 2.31; 95% CI‚1.1–4.86) were associated with small-bowel Crohn’s disease recurrence. LIMITATIONS: Retrospective design and nonstandardized follow-up. CONCLUSIONS: Patients undergoing total proctocolectomy with end ileostomy for Crohn’s disease have approximately a 20% risk of small-bowel recurrence at 5 years but a low risk of requiring surgical intervention. Patients with a history of small-bowel Crohn’s disease and younger age at diagnosis have a higher risk of recurrence and may warrant consideration of more frequent surveillance and medical prophylaxis. See Video Abstract . FACTORES DE RIESGO DE RECURRENCIA DE LA ENFERMEDAD DE CROHN DEL INTESTINO DELGADO DESPUÉS DE UNA PROCTOCOLECTOMÍA TOTAL ANTECEDENTES: El tratamiento quirúrgico de la enfermedad de Crohn del colon y el recto frecuentemente requiere proctocolectomía total con ileostomía terminal. Existe información limitada sobre la necesidad de terapia dirigida a la enfermedad de Crohn y la prevalencia de recurrencia tras la cirugía. OBJETIVO: Determinar el riesgo de recurrencia de la enfermedad de Crohn del intestino delgado y evaluar los factores de riesgo de recurrencia posoperatoria tras proctocolectomía total con ileostomía terminal. DISEÑO: Estudio de cohorte retrospectivo. ÁMBITO: Sistema de atención médica terciaria multiestatal. PACIENTES: Pacientes adultos con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2014 y 2023. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la recurrencia de la enfermedad de Crohn del intestino delgado. RESULTADOS: Se incluyeron un total de 193 pacientes con una mediana de edad de 45 años (RIC, 34-61). Más de la mitad de los pacientes (n = 102, 52,9 %) tenían antecedentes de enfermedad de Crohn del intestino delgado y la mayoría (n = 134, 69,4 %) recibieron terapia biológica antes de la cirugía. El tiempo medio de seguimiento fue de 4,8 años (RIC, 2,0-7,6). Después de la cirugía, el 30,6 % de los pacientes (n = 59) recibieron terapia biológica. Treinta y cinco pacientes (18,1 %) tuvieron recurrencia de la enfermedad de Crohn del intestino delgado para una tasa estimada libre de recurrencia a 5 años del 80,2 % (IC del 95 %, 73,0-85,7). Siete pacientes (3,6 %) desarrollaron recurrencia de la enfermedad de Crohn del intestino delgado que requirió cirugía para una tasa estimada libre de recurrencia quirúrgica a 5 años del 94,7 % (IC del 95 %, 89,0-97,5). En el análisis multivariable, los antecedentes de enfermedad de Crohn del intestino delgado (HR 2,17; IC del 95%: 1,04-4,54) y el diagnóstico antes de los 18 años (HR 2,31; IC del 95%: 1,1-4,86) se asociaron con la recurrencia de la enfermedad de Crohn del intestino delgado. LIMITACIONES: Diseño retrospectivo y seguimiento no estandarizado. CONCLUSIONES: Los pacientes sometidos a proctocolectomía total con ileostomía terminal por enfermedad de Crohn tienen aproximadamente un 20% de riesgo de recurrencia en el intestino delgado a los 5 años, pero un bajo riesgo de requerir intervención quirúrgica. Los pacientes con antecedentes de enfermedad de Crohn del intestino delgado y menor edad al diagnóstico tienen un mayor riesgo de recurrencia y podrían requerir una vigilancia más frecuente y profilaxis médica. (AI-generated translation )

Abstract Objective Invasive presurgical evaluation plays a key role in pediatric epilepsy surgery, particularly in magnetic resonance imaging (MRI)‐negative cases, by guiding resective, disconnective, or ablative procedures. This International League Against Epilepsy (ILAE) Pediatric Epilepsy Surgery Taskforce study provides an updated global overview of current invasive evaluation practices. Methods Group‐level data were collected from 61 epilepsy surgery programs (49 pediatric‐only) in 29 countries across six continents. Included were children and adolescents who underwent presurgical evaluation and epilepsy surgery in 2023. The study was designed to enable comparison with the similar ILAE survey conducted in 2004. Results A total of 2427 patients were included. Invasive evaluations were performed in 21.1% of cases, most frequently in North America (33.7%, higher than Europe: 18.0%, p = .003). Among invasive cases, 32.3% had no detectable MRI abnormalities. The main indication for invasive evaluation was seizure onset localization (88.1%), followed by motor or sensory mapping (17.2%) and language mapping (14.2%). Stereoelectroencephalography (SEEG) was the predominant technique (19.8% overall, 93.6% of invasive cases), more common in North America (30.0%, p = .021) and less common in South America (7.4%, p < .001). Subdural electrodes were used in only 3.2% of invasive cases, and combined depth and subdural approaches in 3.2%. SEEG‐guided radiofrequency thermocoagulation (RF‐TC) was performed in 40.9% of SEEG cases, most commonly in Asia (63.8%). In 16.2% of invasive evaluations, patients did not proceed to resection, disconnection, or ablation, with the highest rate in Europe (28.5%). Significance This global survey provides the first broad overview of invasive evaluation practices in pediatric epilepsy surgery across participating centers worldwide. It highlights the widespread adoption of SEEG, declining use of subdural electrodes, and increasing application of SEEG‐guided RF‐TC. The high proportion of MRI‐negative cases and the considerable proportion of patients not proceeding to resection, disconnection, or ablation underscore the complexity of contemporary surgical candidates and the need for further refinement of selection strategies.

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of advanced spinal cord imaging techniques. Finally, we discuss spinal cord–specific processing pipelines and reproducibility challenges. Collectively, these insights underscore the need to integrate advanced and quantitative spinal cord imaging into clinical trials, research studies, and—when feasible—clinical care, to fully capture the extent of MS pathology, and ultimately improve patient outcomes.

Abstract Background and Aims A simple diagnostic method able to reliably exclude left main (LM) coronary artery disease (CAD) or LMCAD-equivalent would expand implementation of an initial non-invasive strategy in patients with chronic coronary syndrome (CCS). This study assessed the diagnostic utility of an approach using clinical and ECG stress testing (EST) variables in excluding LMCAD/LMCAD-equivalent in CCS patients. Methods In a multicentre case-control study, CCS patients undergoing invasive coronary angiography (CAG) after a maximal EST were evaluated. Cases were patients with angiographic ≥ 50% LM stenosis or ≥70% stenosis of both proximal left anterior descending and proximal circumflex arteries, matched with similar patients without them (controls) in a 1:3 ratio. A risk model developed through logistic regression was internally and externally validated. Results Three hundred and thirty-five cases were matched with 797 controls. The model area under the curve (AUC) was .78. Assuming LMCAD prevalence of 5% and a misclassification cost ratio of 1:100 (ratio of cost of performing CAG in a control to cost of not performing CAG in a case), negative predictive value was 98.2%. Thus, CAG could be safely avoided in 41% of patients, missing one LMCAD/LMCAD-equivalent diagnosis for every 58 CAGs safely spared in patients without them. Conclusions Among CCS patients, LMCAD/LMCAD-equivalent can be excluded with high negative predictive value through a model based on clinical and EST parameters, allowing initial non-invasive management of most patients able to exercise. This approach is potentially useful particularly in communities where access to computed tomography coronary angiography is limited.

Post–liver transplant (LT) weight gain and metabolic dysfunction predispose to cardiovascular (CV) morbidity, allograft steatosis, and reduced long-term survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) promote weight loss and improve cardiometabolic health, yet evidence in liver transplant recipients (LTRs) is limited. We aimed to evaluate the safety, tolerability, and efficacy of GLP-1 RAs in post-LT weight management. We performed a multicenter retrospective cohort study of adult LTRs treated with GLP-1 RAs across 4 international centers (January 1, 2010–June 30, 2025). Regular GLP-1 RA users were compared with matched non-users by age, sex, obesity, and diabetes status, transplant year, and center. The primary outcome was the change in body weight 1-year post-exposure. Secondary outcomes included glycemic and lipid profiles, kidney and allograft function, immunosuppression effects, major adverse cardiovascular events (MACE), and adverse effects. Longitudinal analyses used linear mixed models with multiple imputation. Among 104 GLP-1 RA users, 68.3% initiated therapy for diabetes; subcutaneous semaglutide was most used at a median dose of 0.82±0.46 mg weekly. Treatment led to significant reductions in body weight (−3.8 kg; −3.9%, p <0.001), body mass index (BMI) (−1.6 kg/m 2 ; −5.0%, p <0.001), and glycated hemoglobin (HbA1c) (−0.48%, p =0.002), with modest lipid improvement. Liver function tests and immunosuppression trough levels remained stable, and no treatment-limiting adverse events occurred. In matched analyses (80 GLP-1 RA users vs. 116 non-users), GLP-1 RAs facilitated greater weight loss (−3.4 kg difference, p =0.009) and HbA1c reduction (−0.43% difference in HbA1c, p =0.042) without increased risk of allograft dysfunction, T-cell–mediated rejection (TCMR), or MACE. This multicenter, international study demonstrates GLP-1 RAs are safe and moderately effective in reducing weight and improving metabolic parameters post-LT, without adverse effects on allograft function or immunosuppression, despite limitations of low dosing. Prospective, randomized trials of GLP-1 RAs in LTRs are thus warranted.

Abstract Introduction Transthoracic echocardiography (TTE) identifies a hypercontractile phenotype (HP) in chronic coronary syndromes (CCS), characterized by elevated resting left ventricular (LV) elastance (force = systolic blood pressure/end-systolic volume). To evaluate the prognostic significance and functional correlates of HP. Methods In a prospective multicentre study, 10 677 patients with CCS underwent resting TTE to assess LV ejection fraction (EF), stroke volume, and force by quantitative volumetric echocardiography. All patients were followed for the endpoint of all-cause mortality. In a subset of 5834 patients, stress echocardiography (exercise or dobutamine) was performed for LV contractile reserve and heart rate reserve. Results Patients were stratified into Force quintiles (Q1–Q5). Patients with hypercontractile phenotype exhibited lower stroke volume at rest (Q5 = 34.8 ± 12.3 vs Q1–Q4 = 57.4 ± 19.1 mL; P &lt; .01) and higher EF at rest (Q5 = 64.8 ± 6.9% vs Q1–Q4 = 58.1 ± 8.7%, P &lt; .01). During a median follow-up of 24 months (interquartile range = 12–40 months), 509 deaths occurred. The exposure-adjusted death rate was lowest in Q3 (3.53–4.51 mmHg/mL; 1.03 per 100 person/years) and higher in Q1 (≤2.62 mmHg/mL, 2.88), Q2 (2.63–3.52 mmHg/mL, 1.86), Q4 (4.52–6.11 mmHg/mL, 1.56), and Q5 (HP, &gt;6.11 mmHg/mL; 1.88; P &lt; .0001 vs Q1 and Q3). Multivariable analysis identified HP (Q5; HR 1.531 vs Q3, 95% CI 1.116–2.099; P = .006) and EF (HR 0.963, 95% CI 0.953–0.972; P &lt; .0001) as independent predictors of death. During exercise or dobutamine stress, HP showed reduced LV contractile reserve (ΔEF: Q5 = 4.3 ± 9.4% vs Q1–Q4 = 7.0 ± 9.3%; P &lt; .001) and blunted heart rate reserve (Q5 = 1.77 ± 0.33 vs Q1–Q4 = 1.85 ± 0.39; P &lt; .01). All patients with force-based LV contractile reserve &gt;4.1 (present in 185, 3.2% of the population) survived. Conclusion Patients with CCS with HP assessed by resting TTE demonstrate higher mortality and multilayered functional impairment, including reduced LV contractile and chronotropic reserves. Hypercontractile phenotype improved the prediction of mortality by EF. A ‘stronger’ heart is, in fact, functionally and prognostically weaker.