The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time. Moreover, CLP induced an increase in LC3-II/LC3-I ratio at 6–8 hrs, demonstrated in western blots, as well as an increase in GFP-LC3 dots at 6–8 hrs and 24 hrs, using immunofluorescence and anti-LC3 and LAMP1 antibodies on tissue sections from GFP-LC3 transgenic mice. LC3-II/LC3-I ratio and the number of co-localized GFP-LC3 dots and LAMP1 signals (GFP LC3 + LAMP1 dots) in CLP mice at 24 hrs were significantly reduced compared with data obtained at 6–8 hrs. Notably, acceleration of autophagy by rapamycin resulted in improvement of renal function that was associated with improvement in the histologic severity of tubular epithelial injury in CLP treated animals. Autophagy in the kidney was significantly slowed in the kidney during the acute phase of sepsis; nonetheless, autophagy in kidney appears to play a protective role against sepsis.

Background Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. Methods This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). Results In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07–2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29–3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03–1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). Conclusions In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Background The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. Methods We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. Results A total of 1644 patients with OHCA were included in this study. The patient age was 18–93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45–66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. Conclusions In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

Background Non-occlusive mesenteric ischemia (NOMI) has a high mortality rate, but the analyses of preoperative prognostic factors for improving survival in patients suspected of having NOMI are scarce. We aimed to analyze the prognostic factors of preoperative examinations for NOMI. Methods The clinical data of 224 patients with NOMI were retrospectively collected for a multicenter survey. Clinicophysiological factors were compared between the survivors and non-survivors (N = 107/117) and between the operative and non-operative cases (N = 180/44) by univariate analysis using chi-square test and multivariate analysis using Cox proportional hazard models. In the operative cases, the prognostic operative factors were also analyzed. ResultsThe overall mortality rate for NOMI was 52.2%. There were 129 male and 95 female patients. The mean age was 71.23 (14-94) years. Univariate analysis showed that cardiovascular complication, shock, abdominal pain, average blood pressure, systemic inflammatory response syndrome, aspartic aminotransferase, alanine transaminase, creatine phosphokinase, lactate dehydrogenase, base excess, prothrombin time-international normalized ratio, D-dimer, and fibrinogen degradation products were independent prognostic factors. Multivariate analysis showed that average blood pressure and base excess were independent prognostic factors. Among patients undergoing surgery, those with bowel resection had better prognosis than those without bowel resection, but those with long bowel resection had worse prognosis than those with short resection. Additional postoperative treatment was not effective compared with operation alone (P = 0.011). Conclusions Prognostic factors of preoperative examinations for NOMI were average blood pressure and base excess. Patients with long bowel resection should be carefully monitored owing to their poor prognosis.

AimTo investigate the clinical utility of interleukin‐6 (IL‐6), procalcitonin (PCT), and C‐reactive protein (CRP) as predictive markers in consideration of the time‐course changes in critically ill patients with organ dysfunction.MethodsSerum levels of IL‐6, PCT, CRP, and Sequential Organ Failure Assessment (SOFA) scores were measured sequentially in 92 patients during their initial 5 days following admission to the intensive care unit. Maximum values were analyzed. Patients were assigned to a low ( ≤ 8), intermediate ( > 8 and ≤ 16), or high ( > 16 and ≤ 24) SOFA score group.ResultsThere were significant differences in the maximum serum levels of IL‐6 and PCT among the three SOFA score groups (IL‐6, P < 0.0001; PCT, P = 0.0004). Specifically, comparisons between the groups revealed significant differences in IL‐6 levels (low versus intermediate, P = 0.0007; intermediate versus high, P = 0.0010). The probability of patients with the maximum value was greatest on day 1 (56.5%) for IL‐6, on day 1 (39.1%) or day 2 (38.0%) for PCT, on day 3 (39.1%) for CRP, and on day 1 (43.5%) for SOFA score. The median (interquartile range) peak day of IL‐6 was day 1 (1–2), which was significantly earlier than that of SOFA score at day 2 (1–3) (P = 0.018).ConclusionSerum levels of IL‐6 reflected the severity of organ dysfunction in critically ill patients most accurately compared to PCT and CRP. Interleukin‐6 elevated soonest from the insult and reached its peak earlier than SOFA score.

Background Exacerbated inflammatory response is considered one of the key elements of acute kidney injury (AKI). Interleukin-6 (IL-6) is an inflammatory cytokine that plays important roles in the inflammatory response and may be useful for predicting the clinical outcomes in patients with AKI. However, supporting evidence adapted to the current KDIGO criteria is lacking. Methods AKI patients admitted to the ICU between Jan 2011 and Dec 2015 were retrospectively screened. Patients were assigned to three groups by admission IL-6 tertiles. Associations between IL-6 on ICU admission and in-hospital 90-day mortality, short-term/long-term renal function were analyzed. Results Patients ( n = 646) were divided into low (1.5–150.2 pg/mL), middle (152.0–1168 pg/mL), and high (1189-2,346,310 pg/mL) IL-6 on ICU admission groups. Patients in the high IL-6 group had higher in-hospital 90-day mortality (low vs. middle vs. high, P = 0.0050), lower urine output (low vs. middle vs. high, P < 0.0001), and an increased probability of persistent of anuria for ≥12 h (low vs. middle vs. high, P < 0.0001) within 72 h after ICU admission. In contrast, the high IL-6 group had a lower incidence of persistent AKI at 90 days after the ICU admission in survivors (low vs. middle vs. high, P = 0.013). Conclusions Serum levels of IL-6 on ICU admission may predict short-term renal function and mortality in AKI patients and were associated with renal recovery in survivors.

The blood lactate level is used to guide the management of trauma patients with circulatory disturbance. We hypothesized that blood lactate levels at the scene (Lac scene) could improve the prediction for immediate interventions for hemorrhage. We prospectively measured blood lactate levels and assessed retrospectively in 435 trauma patients both at the scene and on arrival at the emergency room (ER) of a level I trauma center. Primary outcome was immediate intervention for hemorrhage defined as surgical/radiological intervention and/or blood transfusion within 24 h. Physiological variables plus Lac scene significantly increased the predictive value for immediate intervention (area under the curve [AUC] 0.882, 95% confidence interval [CI] 0.839–0.925) compared to that using physiological variables only (AUC 0.837, 95% CI 0.787–0.887, P = 0.0073), replicated in the validation cohort (n = 85). There was no significant improvement in predicting value of physiological variables plus Lac scene for massive transfusion compared to physiological variables (AUC 0.903 vs 0.895, P = 0.32). The increased blood lactate level per minute from scene to ER was associated with increased probability for immediate intervention (P < 0.0001). Both adding Lac scene to physiological variables and the temporal elevation of blood lactate levels from scene to ER could improve the prediction of the immediate intervention.

Background Heterogeneous respiratory system static compliance (CRS) values and levels of hypoxemia in patients with novel coronavirus disease (COVID-19) requiring mechanical ventilation have been reported in previous small-case series or studies conducted at a national level. Methods We designed a retrospective observational cohort study with rapid data gathering from the international COVID-19 Critical Care Consortium study to comprehensively describe CRS—calculated as: tidal volume/[airway plateau pressure-positive end-expiratory pressure (PEEP)]—and its association with ventilatory management and outcomes of COVID-19 patients on mechanical ventilation (MV), admitted to intensive care units (ICU) worldwide. Results We studied 745 patients from 22 countries, who required admission to the ICU and MV from January 14 to December 31, 2020, and presented at least one value of CRS within the first seven days of MV. Median (IQR) age was 62 (52–71), patients were predominantly males (68%) and from Europe/North and South America (88%). CRS, within 48 h from endotracheal intubation, was available in 649 patients and was neither associated with the duration from onset of symptoms to commencement of MV (p = 0.417) nor with PaO2/FiO2 (p = 0.100). Females presented lower CRS than males (95% CI of CRS difference between females-males: − 11.8 to − 7.4 mL/cmH2O p < 0.001), and although females presented higher body mass index (BMI), association of BMI with CRS was marginal (p = 0.139). Ventilatory management varied across CRS range, resulting in a significant association between CRS and driving pressure (estimated decrease − 0.31 cmH2O/L per mL/cmH20 of CRS, 95% CI − 0.48 to − 0.14, p < 0.001). Overall, 28-day ICU mortality, accounting for the competing risk of being discharged within the period, was 35.6% (SE 1.7). Cox proportional hazard analysis demonstrated that CRS (+ 10 mL/cm H2O) was only associated with being discharge from the ICU within 28 days (HR 1.14, 95% CI 1.02–1.28, p = 0.018). Conclusions This multicentre report provides a comprehensive account of CRS in COVID-19 patients on MV. CRS measured within 48 h from commencement of MV has marginal predictive value for 28-day mortality, but was associated with being discharged from ICU within the same period. Trial documentation: Available at https://www.covid-critical.com/study. Trial registration: ACTRN12620000421932.