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Background Disease‐causative variants in LMNA ‐encoded lamin A/C cause a genetic cardiomyopathy characterized by atrioventricular block, atrial fibrillation, ventricular arrhythmias, and systolic dysfunction. The influence of LMNA variant type/localization on late gadolinium enhancement (LGE) patterns and clinical outcomes remains unclear. Methods Retrospective analysis of 822 genotype‐positive patients with arrhythmogenic/dilated cardiomyopathy was used to identify those with disease‐causative variants in LMNA . Data on LGE distribution and prevalence of advanced heart failure, thromboembolic and sudden cardiac death/major ventricular arrhythmia events were extracted from the electronic record and analyzed by variant type/localization. Results Among the 72/116 (62%) LMNA variant‐positive patients with cardiac magnetic resonance imaging data, LGE was observed in 40/72 (56%) cases. Most exhibited a nonischemic, midmyocardial or subepicardial pattern (73%), and 6/40 (15%) showed a unique “pseudo‐infarct” transmural pattern, predominantly affecting the apical segments. All 6 patients with this distinct LGE pattern harbored C‐terminal IgD (immunoglobulin‐like domain) variants (p.Arg471His or p.Arg541His). In patients with clinically manifest disease (76/116), those with IgD‐localizing variants had a lower prevalence of atrioventricular block (25% versus 72%, P =0.002) and atrial fibrillation (50% versus 81%, P =0.019) but higher rates of thromboembolic events (42% versus 16%, P =0.038). During a median follow‐up of 37 months, IgD variant presence independently predicted sudden cardiac death/major ventricular arrhythmia (hazard ratio, 2.391 [95% CI, 1.046–5.464]; P =0.039). Conclusions LMNA missense variants localizing to IgD present a distinct apical pseudo‐infarct LGE pattern associated with increased risk of ventricular arrhythmias and thromboembolic events but reduced atrioventricular block and atrial fibrillation. Multicenter studies are warranted to develop variant‐specific risk‐stratification strategies in cardiac laminopathy.

Objectives: To analyze variations in patient characteristics, treatment patterns, clinical manifestations, clinical outcomes (i.e., response, flares and flare-free survival in HES; remission, relapses and relapse-free survival in EGPA; and overall survival), and healthcare resource utilization (HCRU) in patients with hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) across five European countries. Methods: In two parallel, retrospective, non-interventional, longitudinal chart review studies (GSK ID: 214661 [EGPA] and 214657 [HES]), physicians collected data of patients they treated in France, Germany, Italy, Spain, and the UK from January 2015 to December 2019, with follow-up until August 2021. Country-level results are presented for each study; HES and EGPA data were pooled in a post hoc exploratory analysis. Results: Per-country, 22–26 HES- and 38–45 EGPA-treating physicians collected data from 52–62 (total 280) patients with HES and 80–85 (total 407) with EGPA. Patient sex and age at diagnosis differed across countries. Pooled HES/EGPA data revealed high oral corticosteroid (OCS) use in all countries (94.9% of patients; median [IQR] duration 20.7 [9.0, 33.8] months); immunosuppressive treatments and biologics use varied between countries (43.7–61.5% and 25.6–59.8%, respectively). The most frequent clinical manifestations were constitutional (51.6–78.8%) and lung (43.5–55.8%) in HES, and lung (41.3–67.9) and ENT (43.8–61.2) in EGPA. Pooled HCRU data showed country-level variation; 70.7–91.2% of patients had disease-related outpatient visits and 36.1–52.6% had ER visits or hospitalizations. Conclusions: Results demonstrate substantial disease burden, including high HCRU and extensive OCS use among patients with HES and EGPA in five European countries. The findings highlight the need for improved treatment strategies such as optimizing use of biologics to mitigate the reliance on corticosteroids.

This review describes approaches for encapsulation of pluripotent stem cells, the biomaterials used, strategies for differentiation into hepatocytes and β cells, and the impact of microencapsulation on cellular therapy.

Acute ischaemic stroke remains a leading cause of disability and mortality worldwide. Treatments include systemic fibrinolysis and more recently, endovascular thrombectomy (EVT). The presence of incidental intracranial aneurysms may increase procedural risk during EVT, particularly given their potential higher prevalence in patients with stroke due to shared risk factors such as smoking and hypertension. We present the case of an elderly woman who experienced rupture of an unrecognised intracranial aneurysm during EVT. This case underscores the importance of meticulous preprocedural imaging review, awareness of high-risk anatomical locations and cautious selection of EVT techniques. We also provide a brief review of the literature regarding the incidence, mechanisms and management of intraprocedural aneurysm rupture.

e20041 Background: Paraneoplastic syndromes (PNS) are caused by underlying malignancy but not due to metastasis, or treatment related side effects. Studies are lacking which target PNS seen in non small cell lung cancer (NSCLC) Methods: Systematic search of PubMed & Scopus was conducted to include all case reports & case series of adult NSCLC patients with PNS, published globally from inception upto July 7, 2024. Patient demographics, geographical distribution, NSCLC histology, clinical manifestations, diagnosis, treatment was extracted. Quality was assessed by JBI's critical appraisal checklist. Results: 138 publications (136 case reports, 2 case series) describing 142 patients published in 30 countries were included. Majority patients were male (69.7%) with mean age 57 years. Top publishing countries were USA (28.2%), Japan (13%), China (6.5%), Germany (5%), with publications (n=16) peak seen in 2020. Histological type of NSCLC with PNS was adenocarcinoma (39.8%), SCC (26.8%), unspecified histology (13%) & large cell (8.6%). Most common PNS seen in NSCLC were hypertrophic osteoarthropathy (7.2%), bilateral diffuse uveal melanocytic proliferation (5.7%), leukemoid reaction (4.3%) & limbic encephalitis (4.3%). Conclusions: Study provides bird’s eye view of all PNS found in NSCLC, aiding in timely diagnosis & treatment of NSCLC. Organ system PNS Cases Neurology Limbic encephalitisOpsoclonus myoclonus syndromeGBSSensorimotor peripheral neuropathyCerebellar degenerationEncephalomyelitisPerson in barrel syndromeMyoclonusPandysautonomiaNeuromyelitis opticaOpsoclonusAntiHu Ab neuropathyMononeuritis multiplexMorvan syndrome 63221111111111 Cardiology & haematology Leukemoid reactionLeukocytoclastic vasculitisHSPDICITPMyelofibrosisAcral vascular cyanosisHyper eosinophiliaHeart blockTrousseau syndromeHaemophilia ASVC syndromeChurg Strauss syndrome 6332211111111 Endocrinology SIADHCushing syndromeHypercalcemia of malignancyGynaecomastiaβ HCG secretionErectile dysfunction 433221 Rheumatology Hypertrophic osteoarthropathyPolyarthritisPolymyositisDermatomyositisMyasthenia gravisLambert Eaton syndromePolymyalgia rheumaticaSclerodermaRaynaud phenomenonAnti synthetase syndrome 10433311111 Dermatology Bazex syndromeBullous pemphigoidErythema gyratumLeser Trélat Tripe palmsErythrodermaIchthyosisAcanthosis nigricansRhinophymaGranuloma annularePityriasis rubria pilarisEczemaErythema induratumHyperhidrosis 42212111111111 Ophthalmology Bilateral diffuse uveal melanocytic proliferationCancer associated retinopathyCicatrizing conjunctivitisRetinal detachmentOrbital inflammationOcular flutterProptosis 8311111 Nephrology Nephrotic syndrome 3 Gastroenterology Pseudo achalasiaVerner Morrison syndromeGranulomatous visceral neuronopathy 111 Musculoskeletal Necrotizing myopathy 2

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.

Background The Woven EndoBridge (WEB) device is a prevalent treatment for intracranial aneurysms. While many studies have assessed the obliteration rate post-WEB embolization, few have focused on long-term outcomes in partially thrombosed aneurysms. Objective To assess whether partially thrombosed aneurysms are at higher risk of recurrence or retreatment following WEB embolization compared with non-thrombosed aneurysms. Methods We evaluated data from 22 academic institutions, focusing on previously untreated cerebral aneurysms treated with the WEB device. Logistic regression was utilized to analyze factors predicting long-term aneurysm obliteration and retreatment necessity. Results Among 1303 patients, 26 presented with a partially thrombosed aneurysm. In the partially thrombosed group, the mean aneurysm maximal diameter was 10.7±4 mm with a neck ratio of 1.99±1.19 mm, larger than in the control group where the mean aneurysm maximal diameter was 6.81±2.37 mm with a neck ratio of 1.64±0.51 mm (P<0.001 for both maximal diameter and neck ratio). At the final follow-up, partially thrombosed aneurysms treated by the WEB device had a 38.5% retreatment rate, compared with 7.0% for non-thrombosed aneurysms (P<0.001). Among partially thrombosed aneurysms, the Raymond-Roy type IIIa/b occlusion rate was higher (38.5% vs 9.9%, P<0.001). On multivariate analysis, partially thrombosed aneurysms compared with non-thrombosed aneurysms had an increased rate of retreatment (OR 3.64, 95% CI 1.28 to 10.1). Conclusion Partially thrombosed aneurysms are associated with a poorer occlusion rate and a higher rate of retreatment following WEB embolization. For partially thrombosed aneurysms, the WEB device appears suboptimal as a first-line treatment, and therefore alternative techniques should be prioritized.