Tissue-resident memory-like T _H 17 cells are clonally expanded in bronchoalveolar lavage fluid of patients with severe COVID-19.

Background: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. Methods: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. Results: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79–1.40]; P =0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86–1.46, P =0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78–1.44]; P =0.822). The study was prematurely terminated because of futility. Conclusions: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT00457431.

Jaundice and cholestatic hepatic dysfunction are frequent findings in critically ill patients associated with increased mortality. Cholestasis in critically ill patients is closely associated with stimulation of pro-inflammatory cytokines resulting in impaired bile secretion and subsequent accumulation of bile acids. Aim of this study was to evaluate the clinical role of circulating bile acids in critically ill patients. Total and individual serum bile acids were assessed via high-performance liquid chromatography in 320 critically ill patients and 19 controls. Total serum bile acids were threefold higher in septic than cardiogenic shock patients and sixfold higher than in post-surgical patients or controls (p < 0.001). Elevated bile acid levels correlated with severity of illness, renal dysfunction and inflammation (p < 0.05). Total bile acids predicted 28-day mortality independently of sex, age, serum bilirubin and severity of illness (HR 1.041, 95% CI 1.013–1.071, p < 0.005). Best prediction of mortality of total bile acids was seen in patients suffering from septic shock. Individual and total BAs are elevated by various degrees in different shock conditions. BAs represent an early predictor of short-term survival in a mixed cohort of ICU patients and may serve as marker for early risk stratification in critically ill patients. Future studies should elucidate whether modulation of BA metabolism and signalling influences the clinical course and outcome in critically ill patients.