COVID-19-associated leukoencephalopathy in the absence of severe hypoxia with subsequent improvement: a case report.

BACKGROUND: Several cases of coronavirus disease 2019 (COVID-19)-associated leukoencephalopathy have been reported. Although most cases involve hypoxia, the pathophysiological mechanism and neurologic outcomes of COVID-19-associated leukoencephalopathy remain unclear. CASE PRESENTATION: We report a case of COVID-19-associated leukoencephalopathy without severe hypoxia in a 65-year-old woman diagnosed with pyelonephritis. After the initiation of intravenous ceftriaxone, her fever resolved, but she developed an altered state of consciousness with abnormal behavior and, subsequently, a relapse fever. She was diagnosed with COVID-19 pneumonia and was intubated. Lung-protective ventilation with deep sedation and neuromuscular blockade were used for treatment. After cessation of sedative administration, her mental status remained at a Glasgow Coma Scale score of 3. COVID-19 was assumed to have caused leukoencephalopathy due to the absence of severe hypoxia or other potential causes. She subsequently showed gradual neurologic improvement. Three months after the COVID-19 diagnosis, she regained alertness, with a Glasgow Coma Scale score of 15. CONCLUSION: Clinicians should consider leukoencephalopathy in the differential diagnosis of consciousness disorders in patients with severe COVID-19, even in the absence of severe hypoxia. Gradual neurologic improvement can be expected in such cases.

Critically ill patients with COVID-19 in Tokyo, Japan: A single-center case series.

INTRODUCTION: We reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan. METHODS: This is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected. RESULTS: Between February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure. CONCLUSIONS: As in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.

Changes in temporal muscle dimensions and their clinical impact in out-of-hospital cardiac arrest survivors.

Objective: This study investigates temporal muscle atrophy in out-of-hospital cardiac arrest patients post-resuscitation, seeking associations with neurological outcomes and factors associated with atrophy. Methods: Using data from six Japanese intensive care units, adult patients' post-resuscitation who underwent head computed tomography scans on admission and two to five days post-admission were assessed. Temporal muscle area, thickness, and density were quantified from a single cross-sectional image. Patients were categorized into 'atrophy' or 'no atrophy' groups based on median daily temporal muscle atrophy rates. The primary outcome was changes in temporal muscle dimensions between admission and follow-up two to five days later. Secondary outcomes included assessing the impact of temporal muscle atrophy on 30-day survival, as well as identifying any clinical factors associated with temporal muscle atrophy. Results: A total of 185 patients were analyzed. Measurements at follow-up revealed significant decreases in temporal muscle area (214 vs. 191 mm2, p < 0.001), thickness (4.9 vs. 4.7 mm, p < 0.001), and density (46 vs. 44 HU, p < 0.001) compared to those at admission. The median daily rate for temporal muscle area atrophy was 2.0% per day. There was no significant association between temporal muscle atrophy and 30-day survival (hazard ratios, 0.71; 95% CI, 0.41-1.23, p = 0.231). Multivariable logistic regression found no clinical factors significantly associated with temporal muscle atrophy. Conclusions: Temporal muscle atrophy in post-resuscitation patients occurs rapidly at 2.0% per day. However, there was no significant association with 30-day mortality or any identified clinical factors. Further investigation into its long-term functional implications is warranted.

Human eosinophils are activated by cysteine proteases and release inflammatory mediators.

BACKGROUND: Recent studies suggest that serine proteases are involved in various biological responses through activation of protease-activated receptors (PARs). However, the functions of other proteases, such as cysteine proteases, are poorly understood and need elucidation. OBJECTIVE: We examined the effects of an authentic cysteine protease, papain, and a protease derived from the mite allergen, Der f 1, on functions of human eosinophils. METHODS: Purified eosinophils were incubated with papain or Der f 1. Eosinophil activation was monitored by superoxide anion generation and by degranulation. Intracellular signaling pathways were investigated through use of pharmacologic approaches. RESULTS: We found that papain potently induces human eosinophils to degranulate and to produce superoxide anion. A cysteine protease inhibitor, E-64, abolished the stimulatory effects of papain, which suggests that the protease activity of papain is necessary to trigger eosinophil responses. The eosinophil's response to papain was enhanced by IL-5 and mediated by activation of the phosphatidylinositol 3-kinase/Akt pathway. Interestingly, whereas a serine protease, trypsin, activated eosinophils through PAR2, the effects of papain were not inhibited by an antibody to PAR2, which suggests another novel mechanism for the eosinophils' response to cysteine proteases. It is likely that these observations are clinically important, because eosinophils were activated by a natural cysteine protease allergen, Der f 1, and released granule proteins. CONCLUSION: Human eosinophils are probably equipped with machineries that recognize and respond to cysteine proteases, such as those found at allergic inflammation sites; the result is active release of proinflammatory mediators.