Faculty Bibliography

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BACKGROUND AND PURPOSE/OBJECTIVE:While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS:We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS:During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION/CONCLUSIONS:We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.

OBJECTIVES/OBJECTIVE:Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear. MATERIALS AND METHODS/METHODS:We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis. RESULTS:Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02). CONCLUSION/CONCLUSIONS:SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.

BACKGROUND:Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS:We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS:Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS:Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.

OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

OBJECTIVES/OBJECTIVE:Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. DESIGN/METHODS:Retrospective, multicenter, observational cohort study. SETTING/METHODS:Four New York City hospitals that are part of the same health network. PATIENTS/METHODS:Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. INTERVENTIONS/METHODS:None. MEASUREMENTS AND MAIN RESULTS/RESULTS:Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). CONCLUSIONS:Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.

BACKGROUND AND PURPOSE/OBJECTIVE:Anticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH). METHODS:-VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer. RESULTS:We identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years. CONCLUSIONS:Patients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.

BACKGROUND AND PURPOSE/OBJECTIVE:The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). METHODS:We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). RESULTS:A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p = 0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 - 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.