Genetically Determined Low-Density Lipoprotein Cholesterol and Risk of Subarachnoid Hemorrhage.

We evaluated whether genetically elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with lower risk of intracranial aneurysms and subarachnoid hemorrhage (IA/SAH). We conducted a 2-sample Mendelian randomization (MR) study. Our primary analysis used the inverse-variance weighted method. In secondary analyses, we implemented the MR-PRESSO method, restricted our analysis to LDL-C-specific instruments, and performed multivariate MR. A 1-mmol/l increase in genetically instrumented LDL-C levels was associated with a 17% lower risk of IA/SAH (odds ratio = 0.83, 95% confidence interval = 0.73-0.94, p = 0.004). Results remained consistent in secondary and multivariate analyses (all p < 0.05). Our results provide evidence for an inverse causal relationship between LDL-C levels and risk of IA/SAH. ANN NEUROL 2022;91:145-149.

Mononeuritis multiplex as a rare and severe neurological complication of immune checkpoint inhibitors: a case report.

BACKGROUND: Mononeuritis multiplex is a rare autoimmune peripheral neuropathy that typically presents in the context of vasculitis, diabetes, infection, or as a paraneoplastic syndrome. Adverse immune-related neurological conditions have been increasingly reported with the use of immune checkpoint inhibitors against cytotoxic T-lymphocyte antigen-4 and/or the programmed cell death protein 1/programmed death ligand-1 axis. Mononeuritis multiplex has only been reported twice from treatment of cancers with immunotherapy. CASE PRESENTATION: Here we report a case of mononeuritis multiplex as a complication of immune checkpoint inhibitor therapy for melanoma. An 80-year-old non-Hispanic white female with recurrent melanoma was treated with combination ipilimumab and nivolumab and subsequently presented with progressive leg weakness, back pain, and difficulty ambulating. The diagnosis of mononeuritis multiplex was made, which was resistant to steroid pulses, chronic steroids, intravenous immunoglobulin, and rituximab. She developed progressive neurologic dysfunction and elected for hospice care. We found only two other cases reported in the literature. CONCLUSIONS: Increased awareness, prompt recognition, and aggressive treatments are likely the best opportunity for improved outcomes in this severe side effect.

Cardiovascular Health Disparities in Racial and Other Underrepresented Groups: Initial Results From the All of Us Research Program.

Background All of Us is a novel research program that aims to accelerate research in populations traditionally underrepresented in biomedical research. Our objective was to evaluate the burden of cardiovascular disease (CVD) in broadly defined underrepresented groups. Methods and Results We evaluated the latest data release of All of Us. We conducted a cross-sectional analysis combining survey and electronic health record data to estimate the prevalence of CVD upon enrollment in underrepresented groups defined by race, ethnicity, age (>75 years), disability (not able to carry out everyday physical activities), sexual orientation and gender identity lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA+), income (annual household income <$35 000 US dollars) and education (less than a high school degree). We used multivariate logistic regression to estimate the adjusted odds ratio (OR) and product terms to test for interaction. The latest All of Us data release includes 315 297 participants. Of these, 230 577 (73%) had information on CVD and 17 958 had CVD (overall prevalence, 7.8%; 95% CI, 7.7-7.9). Multivariate analyses adjusted by hypertension, hyperlipidemia, type 2 diabetes mellitus, body mass index, and smoking indicated that, compared with White participants, Black participants had a higher adjusted odds of CVD (OR, 1.21; 95% CI, 1.16-1.27). Higher adjusted odds of CVD were also observed in underrepresented groups defined by other factors, including age >75 years (OR, 1.90; 95% CI, 1.81-1.99), disability (OR, 1.60; 95% CI, 1.53-1.68), and income <$35 000 US dollars (OR, 1.22; 95% CI, 1.17-1.27). Sex significantly modified the odds of CVD in several of the evaluated groups. Conclusions Among participants enrolled in All of Us, underrepresented groups defined based on race, ethnicity and other factors have a disproportionately high burden of CVD. The All of Us research program constitutes a powerful platform to accelerate research focused on individuals in underrepresented groups.

Prior Stroke and Age Predict Acute Ischemic Stroke Among Hospitalized COVID-19 Patients: A Derivation and Validation Study.

Objectives: Our objective was to identify characteristics associated with having an acute ischemic stroke (AIS) among hospitalized COVID-19 patients and the subset of these patients with a neurologic symptom. Materials and Methods: Our derivation cohort consisted of COVID-19 patients admitted to Yale-New Haven Health between January 3, 2020 and August 28, 2020 with and without AIS. We also studied a sub-cohort of hospitalized COVID-19 patients demonstrating a neurologic symptom with and without an AIS. Demographic, clinical, and laboratory results were compared between AIS and non-AIS patients in the full COVID-19 cohort and in the sub-cohort of COVID-19 patients with a neurologic symptom. Multivariable logistic regression models were built to predict ischemic stroke risk in these two COVID-19 cohorts. These 2 models were externally validated in COVID-19 patients hospitalized at a major health system in New York. We then compared the distribution of the resulting predictors in a non-COVID ischemic stroke control cohort. Results: A total of 1,827 patients were included in the derivation cohort (AIS N = 44; no AIS N = 1,783). Among all hospitalized COVID-19 patients, history of prior stroke and platelet count ≥ 200 × 1,000/µL at hospital presentation were independent predictors of AIS (derivation AUC 0.89, validation AUC 0.82), irrespective of COVID-19 severity. Among hospitalized COVID-19 patients with a neurologic symptom (N = 827), the risk of AIS was significantly higher among patients with a history of prior stroke and age <60 (derivation AUC 0.83, validation AUC 0.81). Notably, in a non-COVID ischemic stroke control cohort (N = 168), AIS patients were significantly older and less likely to have had a prior stroke, demonstrating the uniqueness of AIS patients with COVID-19. Conclusions: Hospitalized COVID-19 patients who demonstrate a neurologic symptom and have either a history of prior stroke or are of younger age are at higher risk of ischemic stroke.