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Abstract Background Data describing outcome of extracorporeal membrane oxygenation (ECMO) support in Tuberculosis (Tbc)-associated acute respiratory distress syndrome (ARDS) remain sparce and are mostly confined to singular case reports. The aim of this case series was to analyze intensive care unit (ICU) survival in patients with Tbc-associated ARDS receiving veno-venous (vv-) ECMO support and to compare those to patients not receiving ECMO. Case presentation ICU survival was analyzed retrospectively in 14 patients treated for Tbc-associated ARDS at three ECMO-referral university hospitals (Hannover Medical School, University Hospital Bonn (both Germany) and University Hospital Zurich (Switzerland)) during the last 14 years, of which eight patients received additional vv-ECMO support and six standard care only. ICU survival was significantly higher in patients receiving additional vv-ECMO support (62.5%, n = 5/8) compared to those that did not (16.7%, n = 1/6) (p = 0.021). ECMO support was associated with reduced ICU mortality (Hazard ratio adjusted for baseline SOFA score [adj. HR] 0.125 (95% confidence interval (CI): 0.023–0.689), p = 0.017). Median (IQR) time on ECMO and invasive ventilation in the vv-ECMO group were 20 (11–26) and 37 (27–53) days, respectively. Major bleeding defined as transfusion requirement of 4 units of blood or more or surgical and/or radiologic intervention occurred only in one patient, in whom pulmonary bleeding was fatal. Thromboembolic events occurred in none of the vv-ECMO patients. Discussion and conclusions This retrospective analysis from three large ECMO centers with similar SOPs suggests vv-ECMO support as a feasible approach in patients with severe Tbc-associated ARDS. Although affiliated with extended runtimes, vv-ECMO might be associated with improved survival in those patients. Vv-ECMO support should thus be considered in Tbc-associated ARDS to enable lung protective strategies during prolonged lung recovery.

Introduction Previous studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysis The BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and dissemination The BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration number NCT04647396.

Sepsis is associated with a strong inflammatory reaction triggering a complex and prolonged immune response. Septic patients have been shown to develop sustained immunosuppression due to a reduced responsiveness of leukocytes to pathogens. Changes in cellular metabolism of leukocytes have been linked to this phenomenon and contribute to the ongoing immunological derangement. However, the underlying mechanisms of these phenomena are incompletely understood. In cell culture models, we mimicked LPS tolerance conditions to provide evidence that epigenetic modifications account for monocyte metabolic changes which cause immune paralysis in restimulated septic monocytes. In detail, we observed differential methylation of CpG sites related to metabolic activity in human PBMCs 18 h after septic challenge. The examination of changes in immune function and metabolic pathways was performed in LPS-tolerized monocytic THP-1 cells. Passaged THP-1 cells, inheriting initial LPS challenge, presented with dysregulation of cytokine expression and oxygen consumption for up to 7 days after the initial LPS treatment. Proinflammatory cytokine concentrations of TNFα and IL1β were significantly suppressed following a second LPS challenge (p