Background Despite the intensive efforts to improve the diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock. Methods This prospective pilot study was performed at the university hospital Charité–Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 h over a 24-h period to isolate CD14-positive monocytes and to measure the expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. A rhythmicity score SP was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic), and expression data were compared to data of a healthy study population additionally. Results 77% of the measured clock genes showed inconclusive rhythms, i.e., neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 ± 0.26) compared to the control group (12 healthy young men, 0.70 ± 0.18). In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls. Conclusion Molecular rhythms in immune cells of septic shock patients were substantially altered and decreased compared to healthy young men. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and down-regulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms. Trail registration Clinical trial registered with www.ClinicalTrials.gov (NCT02044575) on 24 January 2014.

Background: Although intensive efforts to improve diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock.Methods: This prospective pilot study was performed at the university hospital Charité – Universitätsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 hours over a 24-hour period to isolate CD14-positive monocytes and to measure expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. Expression data were compared to data of a healthy study population and a rhythmicity score SP was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic). Results: Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 ± 0.26) compared to the control group (12 healthy young men, 0.70 ± 0.18). 77% of the measured clock genes were classified as having inconclusive rhythms, i.e. neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls.Conclusion: Compared to young healthy men, molecular rhythms in immune cells of septic shock patients were substantially decreased. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and downregulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms.Clinical trial registered with www.ClinicalTrials.gov (NCT02044575) on 24 January 2014.

Purpose The management of patients with an anticipated difficult airway remains challenging. We evaluated laryngeal visualization with the recently introduced Vie Scope® as a straight blade laryngoscope consisting of an illuminated tube necessitating bougie-facilitated intubation vs Macintosh videolaryngoscopy. Methods We conducted a prospective randomized controlled noninferiority trial. Patients undergoing elective ear, nose, and throat or oral and maxillofacial surgery with an anticipated difficult airway were randomized 1:1 to receive tracheal intubation with the Vie Scope or Macintosh videolaryngoscope (C-MAC®). The primary outcome measure was laryngeal visualization by the percentage of glottis opening (POGO) scale. Secondary outcome measures were the time to successful intubation (TTI) and first-attempt and overall success rates. Results We included two sets of 29 patients in our analysis. For visualization, the Vie Scope was noninferior to videolaryngoscopy (VL) with mean (standard deviation [SD]) POGO scores of 71 (31)% vs 64 (30)% in the VL group [difference in means, 7 (8)%; 95% confidence interval, –9 to 23; P = 0.38]. Mean (SD) TTI was 125 (129) sec in the Vie Scope and 51 (36) sec in the VL group (difference in means, 75 sec; 95% confidence interval, 25 to 124; P = 0.005). The first-attempt and overall success rates were 22/29 (76%) and 27/29 (93%) in both groups. Two patients per group were switched to a different device. Four accidental esophageal intubations occurred in the Vie Scope group, these were presumably due to bougie misplacement. Conclusion Visualization with the Vie Scope was noninferior to VL in patients with an anticipated difficult airway, but TTI was longer in the Vie Scope group. Study registration ClinicalTrials.gov (NCT05044416); registered 5 September 2021. Supplementary Information The online version of this article contains supplementary material available 10.1007/s12630-023-02534-y.

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