Citations

ABSTRACT Background Obesity is an important risk factor associated with atrial fibrillation (AF). The impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on recurrent AF among patients undergoing catheter ablation is not well described. Objective This study aimed to evaluate the effect of GLP‐1 RA on the recurrence of AF among obese patients after catheter ablation. Methods Utilizing the TriNetX research network, we identified patients aged over 18 with obesity (BMI ≥ 30) who underwent AF ablation from January 1, 2015, to December 1, 2022, using Current Procedural Terminology codes. Patients were categorized based on their baseline GLP‐1 RA use. Through propensity‐score matching, each cohort comprised 1558 patients. The primary outcome encompassed a composite of cardioversion, initiation of new antiarrhythmic drug (AAD) therapy, or redo AF ablation. Additional outcomes during the 12‐month follow‐up included AF readmission, heart failure readmissions, readmissions due to ischemic stroke, and mortality, with a separate analysis done for patients with BMI > 40. Results GLP‐1 RA use in patients with obesity undergoing AF ablation was linked to a significantly reduced risk of cardioversion, new AAD therapy, and the need for redo AF ablation (hazard ratio [HR] 0.72 [0.65–0.80]; p < 0.001). At 12 months, individuals on GLP‐1 agonists exhibited a lower likelihood of mortality (HR 0.61 [0.40–0.93]; p < 0.001). Although all other secondary outcomes were lower in the GLP‐1 RA group, there was no significant difference in ischemic stroke between the groups. These results were consistent among patients with BMI > 40, although apart from ischemic stroke, there was no difference in mortality between the two groups. Conclusion The utilization of GLP‐1 RA in individuals with obesity is linked to a decreased likelihood of arrhythmia recurrence following AF ablation, leading to a reduced requirement for cardioversion, AAD therapy, or redo AF ablation.

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Abstract Objectives To compare the efficacy and safety of antibiotic lock therapy (ALT) versus catheter removal in managing central vascular catheter–associated bloodstream infection (CVC-BSI). Methods We conducted a single-centre, retrospective cohort study of adult patients treated with ALT or catheter removal for management of CVC-BSI between 2018 and 2022. The primary outcome was a composite of 90 day microbiological relapse or recurrent BSI. Secondary outcomes included 30 day mortality, CVC-associated complications and Clostridioides difficile infection (CDI). Logistic regression with propensity score-adjustment was used to evaluate differences in outcomes and identify predictors of relapse. Results During the study period, 106 participants received ALT and 181 underwent catheter removal. Patients treated with ALT received shorter courses of systemic antimicrobials (11 versus 14 days; P &lt; 0.001) and had shorter hospital stays (4 versus 10 days; P &lt; 0.001). Median duration of catheter salvage in patients receiving ALT was 28 days (IQR 7–80). Primary composite outcome was similar between both groups, but ALT was associated with a significantly higher risk of microbiological relapse within 90 days (20% versus 7%; adjusted odds ratio 3.93, 95% CI 1.64–9.40; P = 0.002). No significant difference in 30 day mortality, CVC-related complications or CDI was observed. CoNS BSI was an independent predictor of microbiological relapse in patients treated with ALT (OR 2.28; P = 0.05). Conclusions Although ALT offers a non-invasive catheter salvage strategy, its association with higher relapse rates, particularly in CoNS BSI, suggests catheter removal should remain the preferred approach when feasible. ALT could be considered a short-term catheter salvage strategy for pathogens with low virulence when used with close surveillance.

ABSTRACT Background Advancements in organ transplant technology are pushing global transplant capabilities to new heights. However, challenges persist in pediatric surgical and medical transplant fellowship training, primarily due to a limited number of adequate training programs and gaps in education. Addressing these gaps is essential for improving patient outcomes and advancing the field of pediatric transplantation. Methods An international survey was distributed to 416 pediatric transplant fellows via multiple global transplant associations. The 29‐question survey, available in English and Spanish, assessed current clinical knowledge, training satisfaction, and preferred learning formats. The survey received responses from 237 pediatric transplant fellows. Results One of the key findings was that respondents felt most confident in their pre‐transplantation clinical knowledge. About 75.5% of fellows reported being extremely or very aware of pre‐transplant workups and assessments. However, significant gaps were identified in other areas of training. Notably, 24% of respondents felt extremely knowledgeable about the side effects of immunosuppression, and only 22.8% were very confident in managing acute rejection. Fellows expressed strong interest in dynamic educational formats, particularly clinical case discussions (88.8%). Preferred methods to enhance training included continuing medical education (64.6%), hands‐on workshops, and support for transition protocols and psychosocial counseling. Conclusion This global survey highlights critical educational gaps in pediatric transplant fellowship training and identifies preferred learning methods among fellows. Targeted improvements such as standardized curricula, case‐based learning, interdisciplinary collaboration, and accessible continuing education are essential to enhance training. These strategies will ensure that future transplant professionals are well‐equipped to deliver high‐quality care across diverse healthcare settings.

Abstract Rationale: The 1-year double-blind period of the MANDARA trial (NCT04157348) demonstrated non-inferiority of benralizumab to mepolizumab for achieving remission, in adults with relapsing/refractory eosinophilic granulomatosis with polyangiitis (EGPA). Here, we report the 2-year combined double-blind and ongoing open-label extension (OLE) data. Methods: On completion of the double-blind period (n=136/140) comparing benralizumab 1x30mg versus mepolizumab 3x100mg subcutaneously every 4 weeks, patients were invited to enter the OLE where they continued benralizumab (benra/benra) or switched from mepolizumab to benralizumab (mepo/benra). Endpoints included remission (Birmingham Vasculitis Activity Score=0 and oral glucocorticoid [OGC[ dose ≤4 mg/day), OGC use, relapse, blood eosinophil count (bEOS), Asthma Control Questionnaire (ACQ-6), pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), and safety. Results: In total, 128 patients entered the OLE (n=66 benra/benra, n=62 mepo/benra; mean age 52.8 years; 60.2% female), and 119 completed OLE Year 1. Baseline characteristics of those entering the OLE were similar to the double-blind period. At Week 104, over 60% in both groups (41 [62.1%] benra/benra and 42 [67.7%] mepo/benra patients) achieved remission. During the OLE, 51 (77.3%) benra/benra and 42 (67.7%) mepo/benra patients had no relapses. The percentage of benra/benra patients who discontinued OGCs was similar at Weeks 49-52 (27 [40.9%]) and Weeks 101-104 (29 [43.9%]), while the percentage increased for mepo/benra patients between Weeks 49-52 (16 [25.8%]) and Weeks 101-104 (27 [43.5%]; Figure). The median (IQR) OGC dose at Weeks 101-104 was 0.5 (0,5) in benra/benra and 1.36 (0,5) mg/day in mepo/benra patients. The median (IQR) bEOS in benra/benra patients was 20 (10,40) cells/µL at both Weeks 52 and 100; bEOS were depleted in mepo/benra patients from 70 (40,90) cells/µL to 20 (10,50) cells/µL by 4 weeks after switching. Mean (SD) ACQ-6 scores were 0.64 (0.78) in benra/benra patients and 0.60 (0.76) in mepo/benra patients at Week 104 compared with 1.39 (1.18) and 1.11 (0.95) at baseline. Mean (SD) pre-BD FEV1 was 2.59 (0.90) L versus 2.62 (0.84) L in benra/benra versus mepo/benra patients at Week 52, and 2.61 (0.90) versus 2.63 (0.81) L, at Week 100. Safety of mepolizumab and benralizumab was consistent with their known profiles. Conclusions: In patients with EGPA receiving benralizumab, remission rates, OGC discontinuation, and bEOS depletion were durable over 104 weeks with low relapse rates, and without loss of asthma control or lung function decline. Additional bEOS depletion and OGC sparing was observed in patients switching from mepolizumab to benralizumab.

ABSTRACT LYRM7‐associated mitochondrial complex III deficiency has classically been described in the literature as a childhood‐onset episodic leukoencephalopathy with neuroimaging findings of cavitating periventricular and subcortical white matter loss. We describe the heterogeneous clinical and neuroimaging profile of six individuals from south India with the specific homozygous pathogenic variant in the LYRM7 gene (c.2T>C, (p.Met1?)). This is a retrospective case series featuring six cases (four pediatric, one adult, and one adolescent‐onset) with the pathogenic start loss LYRM7 variant. The spectrum of neurologic manifestations and brain imaging findings documented over multiple clinic visits was analyzed and described. Vision loss and lactic acidosis were seen in all but one individual. A novel phenotype with adult‐onset isolated bilateral simultaneous optic neuropathy was noted. Characteristic cavitating leukoencephalopathy in supratentorial white matter was seen in the brain MRI of three out of six individuals. A comprehensive description of our cases along with the previously published cases is provided in the table highlighting the clinical and imaging variability and the disease course. The phenotype of adult‐onset isolated acute optic neuropathy can be a manifestation of LYRM7‐related mitochondrial disorder. LYRM7‐associated Mitochondrial Complex III deficiency should be considered in the differential diagnosis of para‐ and post‐infectious demyelinating/inflammatory disorders, especially if there is a background of variable developmental delay, recurrence of the episodes, family history, cystic changes in cerebral white matter on imaging, or poor response to immunomodulation. The case series also exemplifies the intra‐and inter‐familial variability seen with this rare disorder.

ABSTRACT Complement protein 3 (C3) glomerulopathy (C3G) is a rare and progressive kidney disease primarily affecting young individuals and frequently advancing to end-stage kidney disease (ESKD). For ESKD, kidney transplantation remains the optimal treatment option; however, C3G has a high recurrence rate post-transplantation, affecting over two-thirds of transplanted patients. Despite advances in our understanding of C3G, significant gaps persist regarding the optimal timing for transplantation and the best strategies for peri-transplant management. Currently, no clear evidence links functional complement levels to the risk of post-transplant recurrence. Genetic counseling is also complex, due to variable gene penetrance and weak genotype–phenotype correlations, which limit predictive accuracy. Transplant-related factors are believed to significantly influence C3G recurrence, yet there are no established methods for preventing recurrence after transplantation. Eculizumab has shown inconsistent efficacy in managing recurrent C3G. However, new proximal complement inhibitors, such as factor B and C3 inhibitors, are under investigation in clinical trials and show promise. Some of these trials include kidney transplant patients with C3G, and their outcomes could potentially shape future treatment protocols.

Background Pineal parenchymal tumor of intermediate differentiation (PPTID) is a rare tumor. This study aims to evaluate patient outcomes and propose a treatment algorithm based on existing literature and our case series. Methods This prospective observational study includes seven patients diagnosed with PPTID through histopathology. We analyzed their clinical presentation, magnetic resonance imaging findings, surgical approaches, histopathological and immunohistochemical analysis, adjuvant treatments, and outcomes. We conducted univariate and multivariate statistical analyses. Results The mean patient age was 40 years, with a male predominance. All patients presented with hydrocephalus, four of which required cerebrospinal fluid diversion procedures. The average tumor size was 3.13cm, with 85.7% showing brain invasion. Surgical outcomes included one gross total resection, two near total resections, and four subtotal resections. The supracerebellar infratentorial (Krause) approach was used in 71.4% of cases. About 85.7% were diagnosed with grade 3 PPTID. Five patients received adjuvant radiotherapy. The analysis showed each additional mitosis unit decreased survival by 0.17 units, equating to roughly 2 months (P < 0.016). Follow-up ranged from 6 to 120 months, with a 5-year survival rate of 57.1%. Factors influencing survival included the extent of tumor resection, brain invasion, tumor grade, and adjuvant treatment, although it was not statistically significant due to the small sample size. Conclusion We propose a treatment algorithm for PPTID and highlight the importance of further research to understand its biological characteristics. Safe maximal resection appears beneficial for higher-grade PPTID, but the role of adjuvant treatment after complete resection of lower-grade tumors remains uncertain.

Hyperuricemia, characterized by elevated serum uric acid levels, has been linked to cardiovascular diseases such as hypertension, atrial fibrillation, chronic kidney disease, heart failure, metabolic syndrome, and coronary artery disease. This relationship, however, is complex; while some studies indicate a strong association, others suggest that it may be influenced by confounding factors. The rising global prevalence of hyperuricemia underscores the necessity for a deeper understanding of its cardiovascular implications. Hyperuricemia results from an imbalance in uric acid production and excretion, driven by dietary factors, obesity, insulin resistance, and other conditions. Elevated uric acid levels contribute to cardiovascular risk through mechanisms such as inflammation, oxidative stress, endothelial dysfunction, and activation of the renin-angiotensin-aldosterone system. This review highlights the importance of ongoing research to clarify hyperuricemia’s role in cardiovascular disease and suggests that urate-lowering therapies, such as xanthine oxidase inhibitors, may confer cardiovascular benefits; however, evidence remains conflicting. The Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES) trial indicated an increased risk of cardiovascular and all-cause mortality with febuxostat compared with allopurinol, raising safety concerns. In contrast, the Febuxostat versus Allopurinol Streamlined Trial (FAST) demonstrated that febuxostat was noninferior to allopurinol, with even lower all-cause mortality. These opposing findings emphasize the complexity of treatment decisions and the need for individualized management strategies for hyperuricemia. Clinical decisions should consider individual patient risks and characteristics. Ultimately, this comprehensive analysis aims to enhance prevention and management strategies for cardiovascular diseases related to hyperuricemia. The overview includes discussions on major studies such as the Framingham Heart Study, CARES, FAST, PRIZE, and FREED trials, examining their results. It explores whether hyperuricemia is a causal factor versus an associated risk factor and whether it serves as a marker or mediator of disease. Additionally, the review addresses novel biomarkers and predictive models, the management of hyperuricemia in the context of cardiovascular risk, the role of urate-lowering therapies in cardiovascular disease, variability in guidelines and recommendations, and the impact of hyperuricemia in special populations such as those with diabetes and chronic kidney disease. The cardiovascular risk associated with hyperuricemia across various demographics is also discussed. Furthermore, the review suggests that existing risk scores might be modified to include uric acid levels in patients with hyperuricemia.