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Abstract Background Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. Discussion In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Abstract Objectives To develop a novel laryngoscope device capable of dynamically measuring force and torque measurements in real‐time during intubation and to explore the efficacy of such a device through a face validation simulation. Methods The torque sensor laryngoscope is designed for use during intubation and is modeled after a standard, single‐use plastic laryngoscope. After device calibration, a face validation study was performed with intubation experts in the field. Quantitative data (intubation force metrics) and qualitative data (expert feedback on the device) were collected from three intubations using a Mac blade and three intubations with the Miller blade. Results Three experts (two anesthesiologists and one otolaryngologist) participated in the study. The mean maximum force exerted with the Mac blade was 24.5 N (95% confidence interval [CI], 22.3–26.8). The average force exerted was 13.6 N (95% CI, 11.7–15.5). The average total suspension time was 13.1 s (95% CI, 10.4–15.8). The average total impulse was 164.6 N·s (95% CI, 147.9–181.4). The mean maximum force exerted with the Miller blade was 31.6 N (95% CI, 26.4–36.8). The average force exerted was 15.8 N (95% CI, 13.8–17.9). The average total suspension time was 11.3 s (95% CI, 9.9–12.6). The average total impulse was 216.2 N·s (95% CI, 186.5–245.9). The mean maximum force (p = .0265) and total impulse (p = .009) were significantly higher in the Miller blade trials than in the Mac blade trials. Survey results found that this device, while bulky, intubated similarly to standard‐use models and has potential as an intubation teaching tool. Conclusion The torque sensor laryngoscope can measure and display real‐time intubation force metrics for multiple laryngoscope blades. Initial validation studies showed a significantly lower maximum force and total impulse when intubating with the Mac blade than with the Miller blade. Face validation survey results were positive and suggested the potential for this device as a teaching tool. Level of Evidence Level 5.

Introduction: Neutrophil extracellular traps (NETs) release (i.e., NETosis) has been recently implicated in the pathomechanism underlying severe end-organ damage in Coronavirus Disease 2019 (COVID-19) and could present a novel therapeutic target. We aimed to determine whether circulating levels of cell-free DNA (cfDNA), a surrogate for NETosis, may be associated with the development of acute kidney injury (AKI), a major contributor to poor outcomes and mortality in COVID-19. Methods: Blood samples were collected prospectively from adult patients infected with SARS-CoV-2 presenting to the emergency department (ED). Circulating levels of cfDNA were quantified from patients’ serum. Further assessment of correlations between cfDNA levels and markers of AKI (i.e., serum creatinine (SCr), cystatin C, neutrophil gelatinase–associated lipocalin (NGAL)), biomarkers of thrombotic microangiopathy and of inflammation in patients’ serum was performed. Results: Fifty-one COVID-19 patients were enrolled. cfDNA levels were found to be significantly higher in those who developed severe AKI (p

Abstract. Introduction:. Peripheral nerve stimulators have emerged as a new generation of advanced modalities to treat chronic pain and avoid opioids. They transmit electrical stimulation through implanted leads and wireless, wearable, external generators. Common complications include infection, nerve damage, and migration of stimulating leads. This article describes 2 cases of complications from lead migration. Methods:. Case 1 describes a 61-year-old man with chronic groin pain who underwent an uncomplicated ultrasound-guided ilioinguinal peripheral nerve lead implantation. Case 2 describes a 54-year-old woman with left shoulder pain who underwent an uncomplicated ultrasound-guided percutaneous lead placement near the axillary nerve through a deltoid approach. Both peripheral nerve stimulators were confirmed with fluoroscopy, and each patient was followed up every 2 months for the following 2 years. Results:. Both patients experienced lead migration to the skin resulting in erythema and need for lead removal. Initial unsuccessful removal by traction resulted in retained fragments and need for open surgical removal. Discussion:. Neurologic complications of peripheral nerve stimulator implantation are rare, but device-associated complications, specifically lead migration, remain a source of long-term problems that can result in decreased coverage of the intended neural target. Conclusion:. Thorough patient education, early postimplantation assessment, and extended routine follow-up are necessary to decrease lead-associated complications. If migration does occur, the potential impact of scar tissue on removal should be considered.

Background: Host proteases have been suggested to be crucial for dissemination of MERS, SARS-CoV, and SARS-CoV-2 coronaviruses, but the relative contribution of membrane versus intracellular proteases remains controversial. Transmembrane serine protease 2 (TMPRSS2) is regarded as one of the main proteases implicated in the coronavirus S protein priming, an important step for binding of the S protein to the angiotensin-converting enzyme 2 (ACE2) receptor before cell entry. Methods: We developed a cell-based assay to identify TMPRSS2 inhibitors. Inhibitory activity was established in SARS-CoV-2 viral load systems. Results: We identified the human extracellular serine protease inhibitor (serpin) alpha 1 antitrypsin (A1AT) as a novel TMPRSS2 inhibitor. Structural modeling revealed that A1AT docked to an extracellular domain of TMPRSS2 in a conformation that is suitable for catalysis, resembling similar serine protease inhibitor complexes. Inhibitory activity of A1AT was established in a SARS-CoV-2 viral load system. Notably, plasma A1AT levels were associated with COVID-19 disease severity. Conclusions: Our data support the key role of extracellular serine proteases in SARS CoV-2 infections and indicate that treatment with serpins, particularly the FDA-approved drug A1AT, may be effective in limiting SARS-CoV-2 dissemination by affecting the surface of the host cells.