Risk Factors for New Neurologic Diagnoses in Hospitalized Patients With COVID-19: A Case-Control Study in New York City.

BACKGROUND AND OBJECTIVES: There have been numerous reports of neurologic manifestations identified in hospitalized patients infected with SARS-CoV-2, the virus that causes COVID-19. Here, we identify the spectrum of associated neurologic symptoms and diagnoses, define the time course of their development, and examine readmission rates and mortality risk posthospitalization in a multiethnic urban cohort. METHODS: We identify the occurrence of new neurologic diagnoses among patients with laboratory-confirmed SARS-CoV-2 infection in New York City. A retrospective cohort study was performed on 532 cases (hospitalized patients with new neurologic diagnoses within 6 weeks of positive SARS-CoV-2 laboratory results between March 1, 2020, and August 31, 2020). We compare demographic and clinical features of the 532 cases with 532 controls (hospitalized COVID-19 patients without neurologic diagnoses) in a case-control study with one-to-one matching and examine hospital-related data and outcomes of death and readmission up to 6 months after acute hospitalization in a secondary case-only analysis. RESULTS: Among the 532 cases, the most common new neurologic diagnoses included encephalopathy (478, 89.8%), stroke (66, 12.4%), and seizures (38, 7.1%). In the case-control study, cases were more likely than controls to be male (58.6% vs 52.8%, p = 0.05), had baseline neurologic comorbidities (36.3% vs 13.0%, p < 0.0001), and were to be treated in an intensive care unit (62.0% vs 9.6%, p < 0.0001). Of the 394 (74.1%) cases who survived acute hospitalization, more than half (220 of 394, 55.8%) were readmitted within 6 months, with a mortality rate of 23.2% during readmission. DISCUSSION: Hospitalized patients with SARS-CoV-2 and new neurologic diagnoses have significant morbidity and mortality postdischarge. Further research is needed to define the effect of neurologic diagnoses during acute hospitalization on longitudinal post-COVID-19-related symptoms including neurocognitive impairment

Unintended effects of cardiovascular drugs on the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is rapidly becoming one of the leading causes of disability and mortality in the elderly. As life-expectancy increases, an increasing number of people will rely on modern medicines to treat age-associated disorders. Among these medications, some might benefit, while others might exacerbate, the pathogenesis of AD. We screened 1,600 FDA approved drugs for β-amyloid (Aβ)-modifying activity and identified drugs that can potentially influence amyloid precursor protein processing. In this study, we focused on cardiovascular drugs and demonstrated that some hypertensive medication can differentially modulate Aβ, both in vitro and in vivo. Our study suggests that some commonly prescribed drugs might exert unintended effects and modulate AD and provides the basis for continuing investigation of the role of individual drugs on a case-by-case basis. This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to AD as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population

Effect of Caprylic triglyceride on food intake and lifespan of SOD1-G93A animals.

<p>(A) Food intake in SOD1-G93A animals treated with caprylic triglyceride (n = 18) or an isocaloric control diet (n = 17); (B) Mice in the two treatment groups (n = 11) were monitored daily and survival curve was plotted in GraphPad Prism.</p

Mitochondrial bioenergetic profile in the spinal cord of WT and SOD1 G93A mice on control or caprylic triglyceride diet.

<p>Mitochondria were isolated by differential centrifugation from the whole spinal cord of SOD1-G93A mice on control or caprylic triglyceride diet and oxygen consumption rates were analyzed using Seahorse XF24 extracellular flux analyzer. (A) A representative trace of OCR in the presence of pyruvate and malate. Adenosine diphosphate (ADP), oligomycin (O), carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and a mixture of rotenone, antimycin A, N,N,N’,N’-tetramethylphenylenediamine and ascorbate (RATA) were injected at the indicated time points to measure basal, state 3, state 4o, maximal and complex IV OCR as indicated. OCR in the presence of pyruvate and malate in (B) SOD1-G93A (ALS) and (D) wild type (WT) mice. (C) Spare respiratory capacity of mitochondria from WT and ALS mice on control or caprylic triglyceride diet. Data are mean ± SEM, n = 3 for all groups, *p<0.05 as compared to control by two-tailed student t-test.</p

Glucose tolerance, ketone, triglyceride and corticosterone levels following caprylic triglyceride treatment.

<p>(A) Fasting serum glucose level and (B) glucose tolerance test in SOD1-G93A animals on control or caprylic triglyceride; (C) Blood ketone level at pre-symptomatic (10 weeks) or post-symptomatic (17 weeks) stage; (D) Plasma total triglyceride levels. (E) Plasma corticosterone level. All data are mean ± SEM, n = 4–5 for (A, B), n = 5 for (C) and n = 6–7 for (D, E) *p<0.05 by two-tailed t-test).</p

Nissl-stained motor neuron count in the lumbar spinal cord.

<p>(A) Representative photomicrographs of Nissl-stained sections at the ventral horn area of the lumbar spinal cord; (B) Motor neuron counts. Data are mean ± SEM, n = 3–4 per group, *p<0.05 by two-tailed t-test.</p

Effect of Aβ -promoting drugs treatment on blood pressure and amyloid neuropathology in Tg2576 mice.

<p>(A and D) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) in response to ∼4 weeks of drug treatments. (B and E) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice <i>vs.</i> the control mice. (C and F) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice <i>vs.</i> the control mice. Values represents group mean values (±SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.</p

Effect of Aβ-lowering drug treatment on blood pressure and amyloid neuropathology in Tg2576 mice.

<p>(A–F) Measurements of systolic, diastolic blood pressure, and mean arterial blood pressure (MAP) and heart beat (pulse) in response to ∼4 weeks of drug treatments. (G-L) Assessment of Aβ1-42 and Aβ1-40 peptide concentrations in the brain of drug treated mice <i>vs.</i> the control mice. (M-R) Assessment of Aβ1-42 and Aβ1-40 in peripheral blood of drug treated mice <i>vs.</i> the control mice. Blood pressure determination for each animal was calculated as the mean of 10 individual measurements. Values represents group mean values (<u>+</u>SEM); n = 3–5 mice per group. **P<0.01, *P<0.05, 2-tailed student t-test.</p

Effect of short-term in vivo on body weight and liquid consumption in Tg2576 mice.

<p>Animals were treated with the anti-hypertensive drugs for four weeks and body weight and liquid consumption were monitored weekly. Data presented here are the end point body weight and the average liquid consumption throughout the study.</p>*<p>P<0.05, 2-tailed student t-test, n = 3–5 for each treatment group.</p