Citations

Background: Tumefactive demyelination (TD) is a rare variant of multiple sclerosis (MS) characterized by tumor-like lesions that often require aggressive management. Genome-wide association studies (GWAS) identified variants associated with MS; similar analyses in TD are lacking. Objective: A GWAS was performed to identify variants associated with TD. Methods: The case–control study included 142 TD cases and 293 controls. TD patients were required to have a demyelinating event and magnetic resonance imaging (MRI) showing one or more lesions. Controls were patients without a neurologic or systemic inflammatory disease or cancer. Logistic regression was used to compare cases versus controls for each variant; age, sex, and principal components were included as covariates. A p -value threshold of 5 × 10 −8 was GWAS significant and 5 × 10 −6 nominally significant. A polygenic risk score (PRS) was compared across TD and controls. Results: Variants on chromosome 14 (rs117797734, p = 2.06 × 10 −11 , odds ratio (OR) = 13.14) and chromosome 6 (most significant rs6936540, p = 5.5 × 10 −7 , OR = 2.61) near DCBLD1 were significant. Seven non-MHC and two MHC variants associated with MS were associated with TD. The PRS was significantly higher in TD versus controls. Conclusion: We identified novel regions associated with TD, demonstrating the importance of performing GWAS in homogeneous subtypes of MS. Further validation and functional experiments are necessary.

Abstract Valvular heart disease (VHD) is emerging as the next major epidemic in cardiovascular care, driven by the ageing population. The advent of less invasive alternatives to surgery—namely, transcatheter therapies—has revolutionized patient management, while simultaneously introducing new layers of complexity. Artificial intelligence (AI) holds significant promise to transform the care of patients with VHD across all dimensions, including diagnosis, prognostication, disease progression, and therapeutic decision-making. In this review, we provide a comprehensive overview of the current evidence, and discuss the challenges, risks, and future directions associated with the integration of AI in the management of VHD.

ABSTRACT Objective To compare maternal and neonatal adverse outcomes between women who are English proficient (EP) and those who have limited English proficiency (LEP). Design Retrospective cohort study. Setting Single US academic medical centre with interpreter services. Population All pregnant women with deliveries during the study period. Methods We retrospectively identified EP and LEP individuals (categorised by self‐report) who delivered at Mayo Clinic, Rochester, Minnesota, USA, from 2015 to 2019. Overall composite adverse outcomes, as well as maternal and neonatal composite outcomes, were measured with generalised linear models and logistic regression, reporting estimates and 95% CIs. Multivariable logistic regression analysis was used to assess associations between language proficiency and outcome measures while controlling for other clinical factors. Main Outcome Measures Composite overall, maternal and neonatal adverse outcomes. Results Among 10 427 EP and 900 LEP participants, the LEP group had a higher incidence of gestational diabetes, unplanned intensive care unit admission, uterine rupture, postpartum haemorrhage with transfusion, neonatal death and 5‐min Apgar score less than 7. The composite overall, maternal and neonatal adverse outcomes were more prevalent in the LEP group than the EP group in unadjusted analysis. Of these, the composite adverse outcome remained significant when the model was adjusted (odds ratio, 1.40; 95% CI, 1.03–1.90). Conclusions Pregnant women with LEP had increased incidence of adverse delivery outcomes, even in a setting with universal availability of medical interpreters.

Abstract Obesity is a major and growing driver of cardiovascular disease (CVD) in the United States, contributing to hypertension, diabetes, dyslipidemia, and structural cardiac changes that elevate the risk of ischemic heart disease, heart failure, and stroke. After decades of declining CVD mortality, recent national trends show a concerning reversal, coinciding with record-high obesity prevalence. We quantified national trends and disparities in obesity-related CVD mortality from 1999–2020 using de-identified death certificate data from the CDC WONDER database for U.S. residents aged 15–84 years, including deaths with circulatory disease (ICD-10 I00–I99) as the underlying cause and obesity (E66.0–E66.9) as a contributing cause. Age-adjusted mortality rates (AAMR) standardized to the 2000 U.S. population were analyzed using joinpoint regression to estimate annual percent change (APC) and detect inflection points. From 1999–2018, AAMR rose from 2.75 to 6.61 per 100,000 (APC 4.79%; 95% CI 4.60–4.98), followed by a significant post-2018 acceleration (APC 11.05%; 95% CI 6.76–15.51) to 8.36 in 2020. Mortality was highest among adults 65–74 years, males, Black Americans, and nonmetropolitan residents, with a 5.1-fold state variation. Young adults (15–24 years) had the largest relative increase (+210%). The 2020 surge was independent of COVID-19 mortality, indicating gaps in chronic disease management. These results highlight a growing obesity-related CVD mortality burden, with widening disparities by age, sex, race, and geography, emphasizing urgent, equity-focused prevention and targeted interventions.

Abstract Background & Aims Pregnancy can be a complex and risk-filled event for women with inflammatory bowel disease (IBD). High-quality studies in this population are lacking, with limited data on medications approved to treat IBD during pregnancy. For patients, limited knowledge surrounding pregnancy impacts pregnancy rates, medication adherence, and outcomes. Limited provider knowledge leads to highly varied practices in care affected by local dogma, available resources, individual interpretation of the literature, and fear of harming the fetus. The variations in guidelines by different societies and countries reflect this and lead to confusion for physicians and patients alike. The Global Consensus Consortium is a group of 39 IBD and content experts and 7 patient advocates from 6 continents who convened to review and assess current data and come to an agreement on best practices based on these data. Methods The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process was used when sufficient published data were available and the RAND (Research and Development) process in those instances where expert opinion was needed to guide consistent practice. Recommendations were informed by the guiding principle that maternal health best supports infant health. Results The topics were divided into ten categories with 34 GRADE recommendations and 35 consensus statements. Conclusions Overall, the goal of the group was to provide data-driven and practical guidance to improve the care of women with IBD around the globe based on the best available research.

Abstract Home parenteral nutrition (HPN) is a life‐sustaining therapy traditionally used as a bridge to enteral autonomy or intestinal transplantation. Increasingly, it is used for intractable feeding intolerance (IFI), which can occur near the end of life (EOL) in children with severe neurological impairment (SNI). In these cases, HPN use differs from its historical role and requires tailored outpatient planning. We report a retrospective case series of four children with SNI who developed IFI and received HPN as part of their EOL care. The pediatric palliative care team (PPCT) was involved in all cases during HPN decision‐making and planning. The pediatric nutrition support team (PNST) and PPCT collaborated to provide individualized, goal‐directed care. Patients ranged from 1 to 12 years old, with HPN durations between 5 weeks and 2 years. All were enrolled in hospice while receiving HPN. Plans were made through shared decision‐making, reflecting each family's values, and included tailored approaches to laboratory monitoring, febrile episodes, line care, growth assessment, and follow‐up. HPN at EOL requires careful ethical consideration, particularly of autonomy because families often find comfort in providing nutrition. IFI is often unanticipated, and prognoses are uncertain. With the combined expertise of PNST and PPCT, HPN can be used meaningfully at EOL, supporting family values, easing suffering, and creating space for peace and connection.

Background and Purpose Informed consent (IC) practices for endovascular thrombectomy (EVT) in acute stroke are not well elucidated. We investigated the roles and specialties of those obtaining EVT IC, aiming to provide insights for enhancing the process. Methods We conducted a survey from July- December 2023 among acute stroke care clinicians. Utilizing Qualtrics, we disseminated a questionnaire through various national and international online platforms. This analysis summarizes the characteristics of individuals who obtain IC at respondents’ institution. Results Among 168 respondents, 71% were staff physicians, 70% practiced in the US and 70% worked at academic centers. Neurology (77%) was the most common specialty obtaining EVT IC, followed by neurosurgery (41%), radiology (30%) and emergency medicine (EM) (10%). Staff physicians were the most frequently involved (61%), followed by fellows (43%), residents (48%) and advanced practice providers (APPs) (36%). Comparatvely, non-US institutions were more likely to utilize neurologists alone (50% vs 31%, P = 0.016) and staff physicians (76% vs 54%, P = 0.008), while US institutions more often utilized neurosurgeons (51% vs 18%, P < 0.001), APPs (43% vs 18%, P = 0.002) and residents (56% vs 28%, P = 0.001). Non-academic institutions used EM (25% vs 5%, P < 0.001) and APPs (50% vs 31%, P = 0.031), while academic institutions commonly utilized neurosurgeons (48% vs 18%, P = 0.001), residents (59% vs 13%, P < 0.001) and fellows (52% vs 18%, P < 0.001). Conclusion Neurologists and staff physicians are the primary providers obtaining EVT IC, with variations based on region and institution type. Future efforts to optimize the IC process should integrate various specialties and be widely adaptable.

ABSTRACT Beyond the arboviruses they transmit to humans and animals, mosquitoes harbour diverse viral communities that shape infection and immunity dynamics. Understanding how these communities shift within mosquito populations across time and space has important implications for how we anticipate and manage arboviral disease epidemics. Here, we examined the viromes of rural and sylvatic mosquito species sampled longitudinally across two years from countries representing South America, Africa, and Southeast Asian geographies to quantify the relative contributions of host and ecological factors in shaping their virome dynamics. We found that virus diversity and virome composition are strongly influenced by host phylogeny and spatial factors and show limited temporal variation. By examining virus similarity networks across mosquito species and biogeographies, we observed frequent instances of within- and cross-genus Culex - Anopheles virus sharing in Madagascar. Taken together, these findings inform the development and implementation strategies of any virome-based vector control technology and raise new evolutionary questions on how host generalism shapes the spatial prevalence of viruses and their potential for disease emergence.