Postoperative complications are of great relevance in daily clinical practice, and the gut microbiome might play an important role by preventing pathogens from crossing the intestinal barrier. The two aims of this prospective clinical pilot study were: (1) to examine changes in the gut microbiome following pancreatic surgery, and (2) to correlate these changes with the postoperative course of the patient. In total, 116 stool samples of 32 patients undergoing pancreatic surgery were analysed by 16S-rRNA gene next-generation sequencing. One sample per patient was collected preoperatively in order to determine the baseline gut microbiome without exposure to surgical stress and/or antibiotic use. At least two further samples were obtained within the first 10 days following the surgical procedure to observe longitudinal changes in the gut microbiome. Whenever complications occurred, further samples were examined. Based on the structure of the gut microbiome, the samples could be allocated into three different microbial communities (A, B and C). Community B showed an increase in Akkermansia, Enterobacteriaceae and Bacteroidales as well as a decrease in Lachnospiraceae, Prevotella and Bacteroides. Patients showing a microbial composition resembling community B at least once during the observation period were found to have a significantly higher risk for developing postoperative complications (B vs. A, odds ratio = 4.96, p < 0.01**; B vs. C, odds ratio = 2.89, p = 0.019*). The structure of the gut microbiome is associated with the development of postoperative complications.

Acute kidney injury (AKI) secondary to sepsis results in poor outcomes and conventional kidney function indicators lack diagnostic value. Soluble urokinase plasminogen activator receptor (suPAR) is an innate immune–derived molecule implicated in inflammatory organ damage. We characterized the diagnostic ability of longitudinal serum suPAR levels to discriminate severity and course of sepsis-induced AKI (SI-AKI) in 200 critically ill patients meeting Sepsis-3 criteria. The pathophysiologic relevance of varying suPAR levels in SI-AKI was explored in a polymicrobial sepsis model in WT, (s)uPAR-knockout, and transgenic suPAR-overexpressing mice. At all time points studied, suPAR provided a robust classification of SI-AKI disease severity, with improved prediction of renal replacement therapy (RRT) and mortality compared with established kidney biomarkers. Patients with suPAR levels of greater than 12.7 ng/mL were at highest risk for RRT or death, with an adjusted odds ratio of 7.48 (95% CI, 3.00–18.63). suPAR deficiency protected mice against SI-AKI. suPAR-overexpressing mice exhibited greater kidney damage and poorer survival through inflamed kidneys, accompanied by local upregulation of potent chemoattractants and pronounced kidney T cell infiltration. Hence, suPAR allows for an innate immune–derived and kidney function–independent staging of SI-AKI and offers improved longitudinal risk stratification. suPAR promotes T cell–based kidney inflammation, while suPAR deficiency improves SI-AKI.

Introduction: The role of reactive carbonyl species, such as methylglyoxal (MG), has been overlooked within the context of the sepsis syndrome. The aims of this study were to assess the impact of MG formation in different inflammatory settings and to evaluate its use for early diagnosis as well as prognosis of the sepsis syndrome. Methods: In total, 120 patients in three groups were enrolled in this observational clinical pilot study. The three groups included patients with septic shock (n = 60), postoperative controls (n = 30), and healthy volunteers (n = 30). Plasma samples from patients with septic shock were collected at sepsis onset and after 24 hours and 4, 7, 14, and 28 days. Plasma samples from postoperative controls were collected prior to surgery, immediately following the end of the surgical procedure as well as 24 hours later and from healthy volunteers once. Plasma levels of MG were determined by high-performance liquid chromatography. Additionally, plasma levels of procalcitonin, C-reactive protein, soluble CD14 subtype, and interleukin-6 were determined. Results: Patients with septic shock showed significantly higher plasma levels of MG at all measured times, compared with postoperative controls. MG was found to identify patients with septic shock more effectively—area under the curve (AUC): 0.993—than procalcitonin (AUC: 0.844), C-reactive protein (AUC: 0.791), soluble CD14 subtype (AUC: 0.832), and interleukin-6 (AUC: 0.898) as assessed by receiver operating characteristic (ROC) analysis. Moreover, plasma levels of MG in non-survivors were significantly higher than in survivors (sepsis onset: *P = 0.018 for 90-day survival; **P = 0.008 for 28-day survival). Plasma levels of MG proved to be an early predictor for survival in patients with septic shock (sepsis onset: ROC-AUC 0.710 for 28-day survival; ROC-AUC 0.686 for 90-day survival). Conclusions: MG was identified as a marker for monitoring the onset, development, and remission of sepsis and was found to be more useful than routine diagnostic markers. Further studies are required to determine the extent of MG modification in sepsis and whether targeting this pathway could be therapeutically beneficial to the patient. Trial registration: German Clinical Trials Register DRKS00000505. Registered 8 November 2010.

Trauma-induced coagulopathy (TIC) is a complex hemostatic disturbance that can develop early after a major injury. There is no universally accepted definition of TIC. However, TIC primarily refers to the inability to achieve sufficient hemostasis in severely injured trauma patients, resulting in diffuse microvascular and life-threatening bleeding. Endogenous TIC is driven by the combination of hypovolemic shock and substantial tissue injury, resulting in endothelial damage, glycocalyx shedding, upregulated fibrinolysis, fibrinogen depletion, altered thrombin generation, and platelet dysfunction. Exogenous factors such as hypothermia, acidosis, hypokalemia, and dilution due to crystalloid and colloid fluid administration can further exacerbate TIC. Established TIC upon emergency room admission is a prognostic indicator and is strongly associated with poor outcomes. It has been shown that patients with TIC are prone to higher bleeding tendencies, increased requirements for allogeneic blood transfusion, higher complication rates such as multi-organ failure, and an almost fourfold increase in mortality. Thus, early recognition and individualized treatment of TIC is a cornerstone of initial trauma care. However, patients who survive the initial insult switch from hypocoagulability to hypercoagulability, also termed “late TIC,” with a high risk of developing thromboembolic complications.

Background: The ultimate goal of haemodynamic therapy is to improve microcirculatory tissue and organ perfusion. Hyperspectral imaging (HSI) has the potential to enable noninvasive microcirculatory monitoring at bedside. Methods: HSI (Tivita^® Tissue System) measurements of tissue oxygenation, haemoglobin, and water content in the skin (ear) and kidney were evaluated in a double-hit porcine model of major abdominal surgery and haemorrhagic shock. Animals of the control group (n = 7) did not receive any resuscitation regime. The interventional groups were treated exclusively with either crystalloid (n = 8) or continuous norepinephrine infusion (n = 7). Results: Haemorrhagic shock led to a drop in tissue oxygenation parameters in all groups. These correlated with established indirect markers of tissue oxygenation. Fluid therapy restored tissue oxygenation parameters. Skin and kidney measurements correlated well. High dose norepinephrine therapy deteriorated tissue oxygenation. Tissue water content increased both in the skin and the kidney in response to fluid therapy. Conclusions: HSI detected dynamic changes in tissue oxygenation and perfusion quality during shock and was able to indicate resuscitation effectivity. The observed correlation between HSI skin and kidney measurements may offer an estimation of organ oxygenation impairment from skin monitoring. HSI microcirculatory monitoring could open up new opportunities for the guidance of haemodynamic management.

Zusammenfassung: Hintergrund: Sepsis ist eine akut lebensbedrohliche multiple Organdysfunktion, ausgelöst durch eine Infektion. Methodik: Bei der vorliegenden Leitlinie handelt es sich um ein Update der S3-Leitlinie „Sepsis – Prävention, Diagnose, Therapie und Nachsorge“ (AMWF-Register-Nr.: 079–001) der Deutschen Sepsis-Gesellschaft (DSG) vom 31.12.2018. Dabei wurde das Update der „Surviving sepsis campaign (SSC): international guidelines for management of sepsis and septic shock 2021“ vom 04.10.2021 als Referenzleitlinie zugrunde gelegt. Die DSG-Leitlinienkommission verglich jede Empfehlung zu den zugrunde liegenden PICO-Fragen der DSG-Leitlinie 2018 (Literaturrecherche bis 12/2018) mit denen der SSC-Leitlinie 2021 (Literaturrecherche bis 07/2019) und bewertete die in der Zwischenzeit neu verfügbare publizierte Datenlage (Literaturrecherche bis 12/2024) mittels systematischer Aktualisierungsrecherchen und Literaturbewertungen unter Befolgung des Regelwerkes des GRADE-Systems und der AWMF. Ergebnisse: Insgesamt wurden 88 PICO-Fragen u. a. zur Diagnose und Therapie der Infektion und des Organversagens adressiert. Davon wurden 2 als Statements, 29 als Expertenkonsens und 57 als evidenzbasierte Empfehlungen (26 mit starkem und 31 mit schwachem Empfehlungsgrad) konsentiert. Im Vergleich zur Vorgänger-Leitlinie 2018 wurden 43 Empfehlungen überprüft, aber beibehalten. 16 Empfehlungen wurden geändert, und 29 Empfehlungen wurden neu ausgesprochen. Schlussfolgerung: Angesichts fehlender Evidenz für zahlreiche Maßnahmen zur stationären Versorgung von Patienten mit Sepsis oder septischem Schock wurden alte und neue Wissenslücken offenbart. Bei den evidenzbasierten Empfehlungen war die zugrunde liegende Evidenzqualität nach GRADE nur bei 5 Empfehlungen hoch, bei 18 Empfehlungen moderat, bei 17 Empfehlungen niedrig und bei 16 sehr niedrig. Diese Evidenzlücken können nur durch zukünftige multizentrische, nichtkommerzielle klinische Prüfungen geschlossen werden. Das Update der S3-Leitlinie Sepsis beinhaltet einige Aktualisierungen zu Empfehlungen der Vorgängerleitlinie. Diese Aktualisierungen werden in einige der fall- und einrichtungsbezogenen QS-Indikatoren des QS-Verfahrens 2025 einfließen müssen. Beeinträchtigungen in der gesundheitsbezogenen Lebensqualität müssen bei Überlebenden mehr in den Fokus der ambulanten Versorgung gerückt werden.