Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Various patterns of leukoencephalopathy have been described in coronavirus disease 2019 (COVID-19). In this article, we aimed to describe the clinical and imaging features of acute disseminated leukoencephalopathy in critically ill patients with COVID-19 and the imaging evolution during a short-term follow-up. MATERIALS AND METHODS/METHODS:We identified and reviewed the clinical data, laboratory results, imaging findings, and outcomes for 8 critically ill patients with COVID-19 with acute disseminated leukoencephalopathy. RESULTS:All patients demonstrated multiple areas of white matter changes in both cerebral hemispheres; 87.5% (7/8) of patients had a posterior predilection. Four patients (50%) had short-term follow-up imaging within a median of 17 days after the first MR imaging; they developed brain atrophy, and their white matter lesions evolved into necrotizing cystic cavitations. All (8/8) patients had inflammatory cytokine release syndrome as demonstrated by elevated interleukin-6, D-dimer, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, and ferritin levels. Most (7/8; 87.5%) patients were on prolonged ventilator support (median, 44.5 days; interquartile range, 20.5 days). These patients had poor functional outcomes (6/8 [75%] patients were discharged with mRS 5) and high mortality (2/8, 25%). CONCLUSIONS:Critically ill patients with COVID-19 can develop acute disseminated leukoencephalopathy that evolves into cystic degeneration of white matter lesions with brain atrophy during a short period, which we dubbed virus-associated necrotizing disseminated acute leukoencephalopathy. This may be the result of COVID-19-related endothelial injury, cytokine storm, or thrombotic microangiopathy.

Background/Objectives/UNASSIGNED:Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. Methods/UNASSIGNED:We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. Results/UNASSIGNED:= 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. Conclusion/UNASSIGNED:Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.

BACKGROUND:Venous thromboembolism (VTE) represents a significant source of morbidity and mortality in the inpatient population and is considered a leading preventable cause of death among inpatients. Neurosurgical inpatients are of particular interest because of the greater rates of immobility, steroid use, and potential consequences of postoperative hemorrhage. A consensus protocol for VTE screening in this population has not yet been developed, and institutional protocols vary widely. METHODS:We performed a retrospective review of lower extremity venous duplex ultrasonography (VDUS) usage at our institution and applied this information to the development of a neurosurgery department protocol, with consideration of high-risk patient risk factors and indications for VDUS ordering. We then implemented this protocol, which consisted of preoperative screening of patients at high risk of VTE and limited postoperative surveillance, for a 6-month period and compared VDUS usage and VTE occurrence. RESULTS:Preoperative VDUS screening before nonemergent neurosurgical procedures in high-risk patients with active cancer, an inability to ambulate, or a history of deep vein thrombosis (DVT) identified proximal DVTs that were then treated. Postoperative routine surveillance VDUS scans only diagnosed incidental isolated calf DVT for which no clinically relevant sequelae occurred. Overall, postoperative surveillance VDUS usage decreased significantly (66.9% vs. 13.5%; P = 0.001). CONCLUSIONS:Our findings lend support to preoperative screening of high-risk patients and suggest that routine postoperative VDUS surveillance of asymptomatic patients is unnecessary.

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: Zinc impairs replication of RNA viruses such as SARS-CoV-1, and may be effective against SARS-CoV-2. However, to achieve adequate intracellular zinc levels, administration with an ionophore, which increases intracellular zinc levels, may be necessary. We evaluated the impact of zinc with an ionophore (Zn+ionophore) on COVID-19 in-hospital mortality rates. Methods: A multicenter cohort study was conducted of 3,473 adult hospitalized patients with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) positive SARS-CoV-2 infection admitted to four New York City hospitals between March 10 through May 20, 2020. Exclusion criteria were: death or discharge within 24h, comfort-care status, clinical trial enrollment, treatment with an IL-6 inhibitor or remdesivir. Patients who received Zn+ionophore were compared to patients who did not using multivariable time-dependent cox proportional hazards models for time to in-hospital death adjusting for confounders including age, sex, race, BMI, diabetes, week of admission, hospital location, sequential organ failure assessment (SOFA) score, intubation, acute renal failure, neurological events, treatment with corticosteroids, azithromycin or lopinavir/ritonavir and the propensity score of receiving Zn+ionophore. A sensitivity analysis was performed using a propensity score-matched cohort of patients who did or did not receive Zn+ionophore matched by age, sex and ventilator status. Results: Among 3,473 patients (median age 64, 1947 [56%] male, 522 [15%] ventilated, 545[16%] died), 1,006 (29%) received Zn+ionophore. Zn+ionophore was associated with a 24% reduced risk of in-hospital mortality (12% of those who received Zn+ionophore died versus 17% who did not; adjusted Hazard Ratio [aHR] 0.76, 95% CI 0.60-0.96, P=0.023). More patients who received Zn+ionophore were discharged home (72% Zn+ionophore vs 67% no Zn+ionophore, P=0.003) Neither Zn nor the ionophore alone were associated with decreased mortality rates. Propensity score-matched sensitivity analysis (N=1356) validated these results (Zn+ionophore aHR for mortality 0.63, 95%CI 0.44-0.91, P=0.015). There were no significant interactions for Zn+ionophore with other COVID-19 specific medications. Conclusions: Zinc with an ionophore was associated with increased rates of discharge home and a 24% reduced risk of in-hospital mortality among COVID-19 patients, while neither zinc alone nor the ionophore alone reduced mortality. Further randomized trials are warranted.