Objective Acute kidney injury (AKI) is a frequent complication in critically ill patients, affecting up to 50% of patients in the intensive care units. The lack of standardized and open-source tools for applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria to time series, requires researchers to implement classification algorithms of their own which is resource intensive and might impact study quality by introducing different interpretations of edge cases. This project introduces pyAKI, an open-source pipeline addressing this gap by providing a comprehensive solution for consistent KDIGO criteria implementation. Materials and methods The pyAKI pipeline was developed and validated using a subset of the Medical Information Mart for Intensive Care (MIMIC)-IV database, a commonly used database in critical care research. We constructed a standardized data model in order to ensure reproducibility. PyAKI implements the Kidney Disease: Improving Global Outcomes (KDIGO) guideline on AKI diagnosis. After implementation of the diagnostic algorithm, using both serum creatinine and urinary output data, pyAKI was tested on a subset of patients and diagnostic accuracy was compared in a comparative analysis against annotations by physicians. Results Validation against expert annotations demonstrated pyAKI’s robust performance in implementing KDIGO criteria. Comparative analysis revealed its ability to surpass the quality of human labels with an accuracy of 1.0 in all categories. Discussion The pyAKI pipeline is the first open-source solution for implementing KDIGO criteria in time series data. It provides a standardized data model and a comprehensive solution for consistent AKI classification in research applications for clinicians and data scientists working with AKI data. The pipeline’s high accuracy make it a valuable tool for clinical research and decision support systems. Conclusion This work introduces pyAKI as an open-source solution for implementing the KDIGO criteria for AKI diagnosis using time series data with high accuracy and performance.

BACKGROUND:Remote ischaemic preconditioning (RIPC) might reduce acute kidney injury after cardiac surgery. Protective effects appear to be restricted to patients with early and transient increases in two cell cycle arrest markers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), in urine. Studies suggest that propofol can attenuate the preconditioning effect on the myocardium. This study investigated whether propofol diminishes the renoprotective effect associated with the early transient increases in TIMP-2 and IGFBP7. METHODS:This was a single-centre, prospective randomised double-blind 2×2 factorial clinical trial of high-risk patients undergoing cardiac surgery. Patients were randomised to receive either propofol+sham-RIPC, propofol+RIPC, sevoflurane+sham-RIPC, or sevoflurane+RIPC. The primary outcome measure was the change in the product of urinary concentrations of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]) from before to after the intervention. RESULTS:We enrolled 160 participants in the trial (propofol+sham-RIPC: n=20, propofol+RIPC: n=60, sevoflurane+sham-RIPC: n=20, sevoflurane+RIPC: n=60). The median change in [TIMP-2]·[IGFBP7] as an indicator of response to RIPC was greater in participants receiving sevoflurane (0.070; interquartile range, -0.120 to 0.418) compared with those receiving propofol (-0.015; interquartile range, -0.138 to 0.068; P=0.022). Conversely, elevated [TIMP-2]·[IGFBP7] as a sign of renal stress in response to surgery was detected in all groups except for sevoflurane+RIPC (P=0.001). There were no statistically significant differences in patient-centred outcomes between groups. CONCLUSIONS:Transient increases in [TIMP-2]·[IGFBP7] induced by RIPC, which were associated with renoprotective effects, were only seen with sevoflurane anaesthesia, but not when propofol was used. The association of biomarker concentrations and choice of anaesthetic agent suggests that propofol can attenuate the renoprotective effects of remote ischaemic preconditioning. CLINICAL TRIAL REGISTRATION:DRKS00014989.

Acute kidney disease (AKD) is a significant health care burden worldwide. However, little is known about this complication after major surgery. We conducted an international prospective, observational, multi-center study among patients undergoing major surgery. The primary study endpoint was the incidence of AKD (defined as new onset of estimated glomerular filtration rate (eCFR) < 60 ml/min/1.73 m2 present on day 7 or later) among survivors. Secondary endpoints included the relationship between early postoperative acute kidney injury (AKI) (within 72 h after major surgery) and subsequent AKD, the identification of risk factors for AKD, and the rate of chronic kidney disease (CKD) progression in patients with pre-existing CKD. We studied 9510 patients without pre-existing CKD. Of these, 940 (9.9

Acute Kidney Injury (AKI) is a frequent complication in critically ill patients, affecting up to 50% of patients in the intensive care units. The lack of standardized and open-source tools for applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria to time series data has a negative impact on workload and study quality. This project introduces pyAKI, an open-source pipeline addressing this gap by providing a comprehensive solution for consistent KDIGO criteria implementation. The pyAKI pipeline was developed and validated using a subset of the Medical Information Mart for Intensive Care (MIMIC)-IV database, a commonly used database in critical care research. We defined a standardized data model in order to ensure reproducibility. Validation against expert annotations demonstrated pyAKI's robust performance in implementing KDIGO criteria. Comparative analysis revealed its ability to surpass the quality of human labels. This work introduces pyAKI as an open-source solution for implementing the KDIGO criteria for AKI diagnosis using time series data with high accuracy and performance.

BACKGROUND:Vasoplegia is common after cardiac surgery, is associated with hyperreninemia, and can lead to acute kidney stress. We aimed to conduct a pilot study to test the hypothesis that, in vasoplegic cardiac surgery patients, angiotensin-II (AT-II) may not increase kidney stress (measured by [TIMP-2]*[IGFBP7]). METHODS:We randomly assigned patients with vasoplegia (cardiac index [CI] > 2.1l/min, postoperative hypotension requiring vasopressors) and Δ-renin (4-hour postoperative-preoperative value) ≥3.7 µU/mL, to AT-II or placebo targeting a mean arterial pressure ≥65 mm Hg for 12 hours. The primary end point was the incidence of kidney stress defined as the difference between baseline and 12 hours [TIMP-2]*[IGFBP7] levels. Secondary end points included serious adverse events (SAEs). RESULTS:We randomized 64 patients. With 1 being excluded, 31 patients received AT-II, and 32 received placebo. No significant difference was observed between AT-II and placebo groups for kidney stress (Δ-[TIMP-2]*[IGFBP7] 0.06 [ng/mL] 2 /1000 [Q1-Q3, -0.24 to 0.28] vs -0.08 [ng/mL] 2 /1000 [Q1-Q3, -0.35 to 0.14]; P = .19; Hodges-Lehmann estimation of the location shift of 0.12 [ng/mL] 2 /1000 [95% confidence interval, CI, -0.1 to 0.36]). AT-II patients received less fluid during treatment than placebo patients (2946 vs 3341 mL, P = .03), and required lower doses of norepinephrine equivalent (0.19 mg vs 4.18mg, P < .001). SAEs were reported in 38.7% of patients in the AT-II group and in 46.9% of patients in the placebo group. CONCLUSIONS:The infusion of AT-II for 12 hours appears feasible and did not lead to an increase in kidney stress in a high-risk cohort of cardiac surgery patients. These findings support the cautious continued investigation of AT-II as a vasopressor in hyperreninemic cardiac surgery patients.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with increased morbidity and mortality. However, no specific treatment options are available, emphasizing the need for preventive measures. The aim of this study was to clarify the effect of glutamine on [TIMP2]*[IGFBP7] levels at the end of the intervention period. METHODS: In a randomized clinical, double-blind pilot study, 64 eligible cardiac surgery patients at high risk for AKI identified by high urinary [TIMP2]*[IGFBP7] were randomized, and body weight–adapted intravenous glutamine or saline-control was administered continuously for 12 hours postoperatively. The primary outcome was urinary [TIMP2]*[IGFBP7] at the end of the 12-hour study period. Secondary outcomes included kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) at 12 hours, overall AKI rates at 72 hours, free days through day 28 of mechanical ventilation and vasoactive medication, renal recovery at day 90, requirement of renal replacement therapy and mortality each at days 30, 60, and 90, length of intensive care unit (ICU) and hospital stay, and major adverse kidney events consisting of mortality, dialysis dependency, and persistent renal dysfunction (serum creatinine ≥2× compared to baseline value) at day 90 (major adverse kidney event; MAKE90). RESULTS: Sixty-four patients (mean age, 68.38 [standard deviation {SD} ± 10.48] years; 10 of 64 women) were enrolled and randomized. Patients received coronary artery bypass graft surgery (32/64), valve surgery (18/64), coronary artery bypass graft and valve surgery (6/64), or other procedures (8/64). Mean on-pump time was 68.38 (standard deviation ± 10.48) minutes. After glutamine administration, urinary [TIMP-2]*[IGFBP7] was significantly lower in the glutamine compared to the control group (primary end point, intervention: median, 0.18 [Q1, Q3; 0.09, 0.29], controls: median, 0.44 [Q1, Q3; 0.14, 0.79]; P = .01). In addition, [KIM-1] and [NGAL] were also significantly lower in the glutamine group. The overall AKI rate within 72 hours was not different among groups: (intervention 11/31 [35.5%] versus control 8/32 [25.0%]; P = .419; relative risk [RR], 0.86% [95% confidence interval {CI}, 0.62–1.20]). There were no differences regarding secondary end points. CONCLUSIONS: Glutamine significantly decreased markers of kidney damage in cardiac surgery patients at high risk for AKI. Future trials have to be performed to investigate whether the administration of glutamine might be able to reduce the occurrence of AKI after cardiac surgery.

Missing data is a common problem in the intensive care unit as a variety of factors contribute to incomplete data collection in this clinical setting. This missing data has a significant impact on the accuracy and validity of statistical analyses and prognostic models. Several imputation methods can be used to estimate the missing values based on the available data. Although simple imputations with mean or median generate reasonable results in terms of mean absolute error, they do not account for the currentness of the data. Furthermore, heterogeneous time span of data records adds to this complexity, especially in high-frequency intensive care unit datasets. Therefore, we present DeepTSE, a deep model that is able to cope with both, missing data and heterogeneous time spans. We achieved promising results on the MIMIC-IV dataset that can compete with and even outperform established imputation methods.

OBJECTIVES: Optimal timing of renal replacement therapy (RRT) initiation in severe acute kidney injury (AKI) remains controversial. Initiation of treatment early in the course of AKI may lead to some patients undergoing unnecessary RRT, whereas delayed treatment is associated with increased mortality. This study aims to investigate whether the combination of the furosemide stress test (FST) and AKI-associated biomarkers can predict the development of indications for RRT. DESIGN: Single-center, prospective, observational study. SETTING: University Hospital of Muenster, Germany. PATIENTS: Critically ill, postoperative patients with moderate AKI (Kidney Disease: Improving Global Outcomes stage 2) and risk factors for further progression (vasopressors and/or mechanical ventilation) receiving an FST. INTERVENTIONS: Sample collection and measurement of different biomarkers (chemokine [C-C motif] ligand 14 [CCL14], neutrophil gelatinase-associated lipocalin, dipeptidyl peptidase 3). MEASUREMENT AND MAIN RESULTS: The primary endpoint was the development of greater than or equal to one predefined RRT indications (hyperkalemia [≥ 6 mmol/L], diuretic-resistant hypervolemia, high urea serum levels [≥ 150 mg/dL], severe metabolic acidosis [pH ≤ 7.15], oliguria [urinary output < 200 mL/12 hr], or anuria). Two hundred eight patients were available for the primary analysis with 108 having a negative FST (urine output < 200 mL in 2 hr following FST). Ninety-eight patients (47%) met the primary endpoint, 82% in the FST negative cohort. At the time of inclusion, the combination of a negative FST test and high urinary CCL14 levels had a significantly higher predictive value for the primary endpoint with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.82–0.92) compared with FST or CCL14 alone (AUC, 0.79; 95% CI, 0.74–0.85 and AUC, 0.83; 95% CI, 0.77–0.89; p < 0.001, respectively). Other biomarkers showed lower AUCs. CONCLUSIONS: The combination of the FST with the renal biomarker CCL14 predicts the development of indications for RRT.

Background Acute respiratory distress syndrome (ARDS) results in significant hypoxia, and ARDS is the central pathology of COVID-19. Inhaled prostacyclin has been proposed as a therapy for ARDS, but data regarding its role in this syndrome are unavailable. Therefore, we investigated whether inhaled prostacyclin would affect the oxygenation and survival of patients suffering from ARDS. Methods We performed a prospective randomized controlled single-blind multicenter trial across Germany. The trial was conducted from March 2019 with final follow-up on 12th of August 2021. Patients with moderate to severe ARDS were included and randomized to receive either inhaled prostacyclin (3 times/day for 5 days) or sodium chloride (Placebo). The primary outcome was the oxygenation index in the intervention and control groups on Day 5 of therapy. Secondary outcomes were mortality, secondary organ failure, disease severity and adverse events. Results Of 707 patients approached 150 patients were randomized to receive inhaled prostacyclin (n = 73) or sodium chloride (n = 77). Data from 144 patients were analyzed. The baseline PaO 2 /FiO 2 ratio did not differ between groups. The primary analysis of the study was negative, and prostacyclin improved oxygenation by 20 mmHg more than Placebo (p = 0.17). Secondary analysis showed that the oxygenation was significantly improved in patients with ARDS who were COVID-19-positive (34 mmHg, p = 0.04). Mortality did not differ between groups. Secondary organ failure and adverse events were similar in the intervention and control groups. Conclusions The primary result of our study was negative. Our data suggest that inhaled prostacyclin might be beneficial treatment in patients with COVID-19 induced ARDS. Trial registration: The study was approved by the Institutional Review Board of the Research Ethics Committee of the University of Tübingen (899/2018AMG1) and the corresponding ethical review boards of all participating centers. The trial was also approved by the Federal Institute for Drugs and Medical Devices (BfArM, EudraCT No. 2016003168-37) and registered at clinicaltrials.gov (NCT03111212) on April 6th 2017.

Introduction:Acute kidney injury (AKI) is a common complication in cardiac surgery patients and prevention is needed to improve clinical outcomes. Alpha-1-microglobulin (A1M) is a physiological antioxidant with strong tissue-protective and cell-protective properties that has demonstrated renoprotective effects. RMC-035, a recombinant variant of endogenous human A1M, is being developed for the prevention of AKI in cardiac surgery patients. Methods:In this phase 1b, randomized, double-blind, and parallel group clinical study, 12 cardiac surgery patients undergoing elective, open-chest, on-pump coronary artery bypass graft and/or valve surgery with additional predisposing AKI risk factors were enrolled to receive in total 5 intravenous doses of either RMC-035 or placebo. The primary objective was to evaluate the safety and tolerability of RMC-035. The secondary objective was to evaluate its pharmacokinetic properties. Results:RMC-035 was well tolerated. The nature and frequency of adverse events (AEs) were consistent with the expected background rates in the underlying patient population with no AEs reported as related to study drug. No clinically relevant changes were observed for vital signs or laboratory parameters except for renal biomarkers. Several established AKI urine biomarkers were reduced at 4 hours after first dose administration in the treatment group, indicating a reduced perioperative tubular cell injury following RMC-035 treatment. Conclusion:Multiple intravenous doses of RMC-035 were well tolerated in patients undergoing cardiac surgery. Observed RMC-035 plasma exposures were safe and in the range of expected pharmacological activity. Furthermore, urine biomarkers suggest reduced perioperative kidney cell injury, warranting further investigation of RMC-035 as a potential renoprotective treatment.

Abstract Purpose Chronic kidney disease (CKD) is a significant health care burden worldwide. However, little is known about its development after major surgery. Methods We conducted an international prospective, observational, multi-center study in 30 countries among patients undergoing major surgery. The primary study endpoint was the incidence of CKD (defined as new onset CKD with an eGFR < 60ml/min/1.73m2 at day 90). Secondary endpoints included the relationship between early postoperative-AKI (within 72h after major surgery) and development of postoperative CKD, the identification of risk factors for CKD, and the rate and risk factors for CKD progression in patients with pre-existing CKD. Results We studied 9,510 patients without pre-existing CKD. Of these, 940 (9.9%) developed CKD with 34.2% experiencing an episode of early postoperative-AKI. CKD rates significantly increased with the severity of early AKI (19.1% KDIGO1, 24.5% KDIGO2, 34.3% KDIGO3; P < 0.001) and duration (15.5% transient vs 38.3% persistent AKI; P < 0.001). Independent risk factors for CKD included early postoperative-AKI, exposure to perioperative nephrotoxic agents, and postoperative pneumonia. Early postoperative-AKI carried an independent odds ratio for CKD of 2.64 (95%-CI 2.21–3.15). Of 663 patients with pre-existing CKD, 42 (6.3%) had worsening CKD at day 90 as defined. In patients with CKD and an episode of early AKI, CKD progression occurred in 11.6%. Conclusion One in ten major surgery patients developed postoperative CKD, most of them without an episode of early postoperative-AKI. However, early postoperative-AKI severity and duration was associated with an increased rate of CKD with early postoperative-AKI being a major independent risk factor for CKD. Clinical trial number: The study was registered at ClinicalTrials.gov (NCT04165369).

The incidence, patient features, risk factors and outcomes of surgery-associated postoperative acute kidney injury (PO-AKI) across different countries and health care systems is unclear. We conducted an international prospective, observational, multi-center study in 30 countries in patients undergoing major surgery (> 2-h duration and postoperative intensive care unit (ICU) or high dependency unit admission). The primary endpoint was the occurrence of PO-AKI within 72 h of surgery defined by the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Secondary endpoints included PO-AKI severity and duration, use of renal replacement therapy (RRT), mortality, and ICU and hospital length of stay. We studied 10,568 patients and 1945 (18.4

Objectives: Patients with COVID-19–associated acute respiratory distress syndrome (ARDS) have a high risk for developing acute kidney injury (AKI) which is associated with an increased risk of death and persistent renal failure. Early prediction of AKI is crucial in order to implement preventive strategies. The purpose of this study was to investigate the predictive performance of tissue inhibitor of metalloproteinases 2 and insulin like growth factor binding protein 7 (TIMP-2) × (IGFBP7) in critically ill patients with COVID-19–associated ARDS. Design: Multicenter, prospective, observational study. Setting: Twelve centers across Europe and United Kingdom. Patients: Patients with moderate or severe COVID-19–associated ARDS were included and serial measurements of (TIMP-2) × (IGFBP7) were performed. Interventions: None. Measurements and Main Results: The primary endpoint was the development of moderate or severe AKI according to the Kidney Disease: Improving Global Outcomes definition. Three hundred patients were available for the primary analysis, and 39 met the primary endpoint. At enrollment, urinary (TIMP-2) × (IGFBP7) had high predictive value for the primary endpoint with an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.84–0.93). (TIMP-2) × (IGFBP7) was significantly higher in endpoint-positive patients at enrollment and at 12 hours. Conclusions: Urinary (TIMP-2) × (IGFBP7) predicts the occurrence of AKI in critically ill patients with COVID-19–associated ARDS.

BACKGROUND: Hyperreninemia after cardiac surgery is associated with cardiovascular instability. Angiotensin II (AT-II) could potentially attenuate hyperreninemia while maintaining target blood pressure. This study assesses the association between AT-II usage and renin levels in cardiac surgery patients with postoperative hyperreninemia and vasoplegia. METHODS: Between September 2020 and March 2021, we retrospectively identified 40 cardiac surgery patients with high Δ-renin levels (4 hours after cardiopulmonary bypass [CPB] minus preoperative levels) (defined as higher than 3.7 µU/mL) and vasopressor use who received a vasopressor therapy with either AT-II or continued norepinephrine alone. The primary outcome was the renin plasma level at 12 hours after surgery, adjusted by the renin plasma level at 4 hours after surgery. RESULTS: Overall, the median renin plasma concentration increased from a baseline with median of 44.3 µU/mL (Q1–Q3, 14.6–155.5) to 188.6 µU/mL (Q1–Q3, 29.8–379.0) 4 hours after CPB. High Δ-renin (difference between postoperation and preoperation) patients (higher than 3.7 µU/mL) were then treated with norepinephrine alone (median dose of 3.25 mg [Q1–Q3, 1.00–4.75]) or with additional AT-II (norepinephrine dose: 1.33 mg [Q1–Q3, 0.78–2.04]; AT-II dose: 0.34 mg [Q1–Q3, 0.29–0.78]). At 12 hours after surgery, AT-II patients had lower renin levels than standard of care patients (71.7 µU/mL [Q1–Q3, 21.9–211.4] vs 130.6 µU/mL [Q1–Q3, 62.9–317.0]; P = .034 adjusting for the renin plasma level at 4 hours after surgery). CONCLUSIONS: In cardiac surgery patients with hypotonia and postoperative high Δ-renin levels, AT-II was associated with reduced renin plasma levels for at 12 hours and significantly decreased norepinephrine use, while norepinephrine alone was associated with increased renin levels. Further studies of AT-II in cardiac surgery appear justified.

Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with long-term complications and an increased mortality. This work presents preliminary findings from the first freely available European intensive care database released by Amsterdam UMC. A machine learning (ML) model was developed to predict AKI in the intensive care unit 12 hours before the actual event. Main features of the model included medications and hemodynamic parameters. Our models perform with an accuracy of 81.8% on moderate to severe AKI and 79.8% on all AKI patients. Those results can compete with models reported in the literature and introduce an ML model for AKI based on European patient data.

Background: The extent of aortic replacement for aneurysms of the distal ascending aorta remains controversial and opinions vary between standard cross-clamp resection and open hemiarch anastomosis in circulatory arrest and selective cerebral perfusion. As the deleterious effects of extended circulatory arrest are well-known, borderline indication for distal ascending aorta aneurysm repair must be outweighed against the potential risk of complications related to the open anastomosis. In the present study, we describe our own approach consisting of “transversal arch clamping” for exhaustive resection of aneurysms of the distal ascending aorta without open anastomosis and we present the postoperative outcomes. Methods: Between May 2017 and December 2019, 35 patients with aneurysm of the ascending aorta (20 male, 15 female) underwent replacement with repair of the lesser curvature without circulatory arrest. Pre-operative, intraoperative, and postoperative clinical outcomes were retrospectively withdrawn from our institutional database and analyzed. Results: Maximal diameter of distal ascending aorta was 47.5 mm. Patient median age was 66 years (IQR 14) (range 42–86). Preoperative logistic median EuroSCORE II was 17% (IQR 11.3). Median duration of cardiopulmonary bypass and cardiac arrest were 137 (IQR 64) and 93 (IQR 59) min, respectively. In-hospital and 30-day mortality were 0%. There were no cases with acute low output syndrome, surgical re-exploration for bleeding, kidney injury requiring dialysis, or wound infection. Disabling stroke was observed in one patient (2.9%). There was one case of major ventricular arrhythmia (2.9%). Conclusions: Our institutional experience suggests that this novel technique is safe and feasible. It facilitates complete resection of the aortic ascending aneurysm avoiding circulatory arrest, antegrade cerebral perfusion, additional peripheral cannulation, and all related complications.

Rationale: Capillary leakage frequently occurs during sepsis and after major surgery and is associated with microvascular dysfunction and adverse outcome. Procalcitonin is a well-established biomarker in inflammation without known impact on vascular integrity. Objectives: We determined how procalcitonin induces endothelial hyperpermeability and how targeting procalcitonin protects vascular barrier integrity. Methods: In a prospective observational clinical study, procalcitonin levels were assessed in 50 patients who underwent cardiac surgery and correlated to postoperative fluid and vasopressor requirements along with sublingual microvascular functionality. Effects of the procalcitonin signaling pathway on endothelial barrier and adherens junctional integrity were characterized in vitro and verified in mice. Inhibition of procalcitonin activation by dipeptidylpeptidase 4 (DPP4) was evaluated in murine polymicrobial sepsis and clinically verified in cardiac surgery patients chronically taking the DPP4 inhibitor sitagliptin. Measurements and Main Results: Elevated postoperative procalcitonin levels identified patients with 2-fold increased fluid requirements (P<0.01), 1.8-fold higher vasopressor demand (P<0.05), and compromised microcirculation (reduction to 63.5 +/- 2.8% of perfused vessels, P<0.05). Procalcitonin induced 1.4-fold endothelial and 2.3-fold pulmonary capillary permeability (both Ps<0.001) by destabilizing VE-cadherin. Procalcitonin effects were dependent on activation by DPP4, and targeting the procalcitonin receptor or DPP4 during sepsis-induced hyperprocalcitonemia reduced capillary leakage by 54 +/- 10.1% and 60.4 +/- 6.9% (both Ps<0.01), respectively. Sitagliptin before cardiac surgery was associated with augmented microcirculation (74.1 +/- 1.7% vs. 68.6 +/- 1.9% perfused vessels in non-sitagliptin-medicated patients, P<0.05) and with 2.3-fold decreased fluid (P<0.05) and 1.8-fold reduced vasopressor demand postoperatively (P<0.05). Conclusions: Targeting procalcitonin's action on the endothelium is a feasible means to preserve vascular integrity during systemic inflammation associated with hyperprocalcitonemia.

Importance Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality. Objective To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality. Design, Setting, and Participants This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours. Interventions A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol. Main Outcomes and Measures The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay. Results Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR, 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881 (33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5.9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 1.28; P = .91). None of the 19 prespecified secondary end points differed significantly. Conclusions and Relevance Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days. Trial Registration ClinicalTrials.gov Identifier: NCT04016454.

To investigate whether (1 → 3)-β-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI). Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality. 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80–1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0–2.2] days in the BDG group and 4.4 (IQR 2.0–9.1, p < 0.01) days in the control group. Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.