Predictors of Transthoracic Impedance in Patients Who Underwent Elective Electrical Cardioversion.

Successful synchronized direct current cardioversion (DCCV) requires adequate current delivery to the heart. However, adequate current for successful DCCV has not yet been established. Transmyocardial current depends on 2 factors: input energy and transthoracic impedance (TTI). Although factors affecting TTI have been studied in animal models, factors affecting TTI in humans have not been well established. Herein, we explored the potential factors that affect TTI in humans. A retrospective review of patients who underwent DCCV at a large quaternary medical center between October 2019 and August 2021 was conducted. Pertinent clinical information, including demographics, echocardiography findings, laboratory findings, and body characteristics, was collected. Cardioversion details, including joules delivered and TTI, were recorded by the defibrillator for each patient's first shock. Predictors of thoracic impedance were assessed using regression analysis. A total of 220 patients (29% women) were included in the analysis; 143 of the patients (65%) underwent DCCV for atrial fibrillation and 77 (35%) underwent DCCV for atrial flutter. The mean impedance in our population was 73 ± 18 Ω. In a regression model with high impedance defined as the upper quartile of our cohort, body mass index (BMI), female sex, obstructive sleep apnea, and chronic kidney disease (all p values <0.05) were significantly associated with high impedance. According to a receiver operating characteristic analysis, BMI has a high predictive value for high impedance, with an area under the curve of 0.76. In conclusion, our study reveals that elevated BMI, female sex, sleep apnea, and chronic kidney disease were predictors of higher TTI. These factors may help determine the appropriate initial shock energy in patients who underwent DCCV for atrial fibrillation and flutter.

Analysis of SARS-CoV-2 RNA on surfaces in New York City.

BACKGROUND: This study sought to determine the presence of SARS-CoV-2 virus on surfaces that trainees and faculty of an academic eye clinic came into contact with during daily life at the time of the COVID-19 pandemic in New York City. METHODS: This cross-sectional analysis involved collection of at least two samples by teams on four different days (November 9, 2020 - December 18, 2020) using sterile swabs (Puritan HydraFlock, Garden Grove, CA). Collection sites were grouped into four zones depending on proximity and amount of time personnel spent there. Samples were transported to the laboratory in transport medium and RNA was extracted using the QIAamp DSP Viral RNA Mini Kit (Qiagen, Germantown, MD). Presence of viral RNA was investigated using the Luna Universal Probe One-step RT-qPCR kit (New England Biolabs, Ipwsich, MA). RESULTS: 834 samples were submitted. Two were positive for SARS-CoV-2 RNA. The first was a sample from a patient bathroom sink handle in the main emergency department. The second was a nasal swab sample from a staff member who had been assigned to collect samples. Prior to this positive result, this asymptomatic staff member had tested positive for COVID-19, had quarantined for two weeks, and had received a negative test. CONCLUSION: Though COVID-19 is currently widespread in the United States, this study shows that health care personnel working in New York City at the Columbia University Irving Medical Center have a low chance of encountering viral RNA on surfaces they are in close contact with during daily life.

The Intracerebral Hemorrhage Score: Changing Perspectives on Mortality and Disability.

BACKGROUND: Intracerebral hemorrhage (ICH) remains a devastating diagnosis. While the ICH Score continues to be used in the clinical setting to prognosticate outcomes, contemporary improvements in management have reduced mortality rates for each scoring tier. The aims of this study were to examine mortality rates within ICH Score strata and examine if these findings are stable when major disability is included in categorizing poor outcomes. METHODS: From a single-institution cohort built between 2009 and 2016, 582 patients were extracted based on the criteria for complete ICH Score, discharge mortality, and functional status for survivors. Mortality rates were stratified by ICH Score and compared with both historical and similar contemporary cohorts. Poor outcome was defined as severe disability (modified Rankin Scale score 5) in addition to death, stratified by ICH Score, and compared. A secondary analysis of patients with ICH Score of 2 was performed in light of the primary results. RESULTS: Mortality rates stratified by ICH Score were notably lower than expected for low- and moderate-grade ICH compared with the original cohort. However, when defining a poor outcome as including severe disability (modified Rankin Scale score 5) in addition to death, the rates for poor outcomes were higher for patients with ICH Score of 2 (51.16% vs. 26%, P = 0.017) and no different for any other score group compared with the original cohort. CONCLUSIONS: Though the original ICH Score overestimates mortality for low-grade and moderate-grade hemorrhages, it may underpredict severe disability.

Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity.

Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit off-target toxicity. Here, we mine disaggregase sequence space to safely enhance Hsp104 activity via single mutations in nucleotide-binding domain 1 (NBD1) or NBD2. Like MD variants, NBD variants counter TDP-43, FUS, and α-synuclein toxicity and exhibit elevated ATPase and disaggregase activity. Unlike MD variants, non-toxic NBD1 and NBD2 variants emerge that rescue TDP-43, FUS, and α-synuclein toxicity. Potentiating substitutions alter NBD1 residues that contact ATP, ATP-binding residues, or the MD. Mutating the NBD2 protomer interface can also safely ameliorate Hsp104. Thus, we disambiguate allosteric regulation of Hsp104 by several tunable structural contacts, which can be engineered to spawn enhanced therapeutic disaggregases with minimal off-target toxicity.