Procalcitonin (PCT) is an acute-phase protein and widely used marker for diagnosing bacterial infection and sepsis, but its physiological role remains incompletely defined. Interleukin-1β (IL-1β) is a critical mediator of the immune response to infection, whose excessive release can drive remote organ injury and dysfunction. Its secretion is therefore tightly controlled. Because other acute-phase proteins have been shown to regulate IL-1β secretion, we investigated whether PCT exerts a similar immunomodulatory effect and whether this influences sepsis severity, particularly in Gram-negative urosepsis. Primary human mononuclear leukocytes were stimulated to induce IL-1β release in the presence or absence of increasing PCT concentrations. In parallel, peak PCT levels, infection source, and causative pathogen were analyzed retrospectively in uroseptic patients in comparison to other septic sources, and related to Sepsis-related Organ Failure Assessment (SOFA) scores and serum lactate concentrations. PCT significantly inhibited IL-1β secretion from primary mononuclear leukocytes across the 2.5–75 µg/L concentration range. Clinically, the highest PCT peaks occurred in patients with Gram-negative urosepsis. Among these, those with peak PCT values within 2.5–75 µg/L had significantly lower SOFA scores and lactate levels—established indicators of sepsis severity and prognosis—compared with patients outside this range. Within a defined concentration range, PCT down-regulates IL-1β secretion and is associated with reduced markers of disease severity in Gram-negative urosepsis, compared to other sepsis entities. These findings suggest that pronounced PCT elevations in this setting may represent a protective host response rather than a worse prognosis, pointing to a novel immunomodulatory role of PCT in urosepsis that warrants further investigation. DRKS00037950, retrospectively registered on 22 September 2025.

Background Tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, reduces exacerbations across asthma phenotypes, but its role in status asthmaticus and near-fatal exacerbations requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) is unclear.Methods and Results We report three patients (17, 22, 57 years) with therapy-refractory hypercapnic respiratory failure initiated on VV-ECMO who received tezepelumab 210 mg within 24 h. Tidal volume and minute ventilation increased within 24-72 h, permitting decannulation by days 12-15 and ventilator weaning by days 17-28. Two patients had elevated IgE; one had normal blood eosinophils/IgE. No immediate drug-related adverse events occurred. Follow-up demonstrated lung-function recovery; one patient required escalation of maintenance therapy for persistent symptoms.Conclusion In this small series, adjunctive tezepelumab during VV-ECMO-supported status asthmaticus appeared safe and potentially beneficial adjunctive therapy during near-fatal asthma requiring VV-ECMO. Randomized controlled studies are needed to determine the impact of TSLP inhibition on recovery time, ventilation duration, and mortality in this setting.

Introduction The perioperative management of patients undergoing major surgical interventions is a dynamic field, continually striving for advancements in quality, reduction of complications, and cost-effectiveness. The implementation of Enhanced Recovery After Surgery (ERAS) pathways has demonstrated remarkable success in various surgical disciplines, particularly in colorectal procedures. This study investigates whether the implementation of an ERAS protocol for radical cystectomy for bladder cancer at our institution results in a reduced complication rate compared to traditional standards.DRKS00035673 (retrospective) on 13th December 2024. Methods This prospective observational case-control pilot study was conducted at the University Hospital Giessen, Germany. Following ethics committee approval, 30 patients were enrolled: 15 patients received perioperative management based on prevailing standard operating procedures, and the subsequent 15 patients were managed according to the newly developed ERAS protocol. The multidisciplinary team included urologists, anaesthesiologists, nursing staff, ICU staff, pharmacists, physiotherapists, dietitians, and administrative staff. Key components of the ERAS protocol included optimized pain management, early nutrition, thrombosis prophylaxis, intraoperative goal directed therapy and early mobilization. The primary outcome was the complication rate until the 30th postoperative day, while secondary outcomes included ICU and hospital mortality, length of stay, and quality of life assessed by the EQ-5D-5L questionnaire. Results Thirty patients were included in the final analysis. Patients in the control group underwent radical cystectomy between September 2018 and December 2019, and those in the ERAS group between July 2020 and March 2021. There were no significant differences in basic characteristics between the groups. The primary outcome showed numeric but no statistically significant difference in complication rates (86.7% in the control group vs. 60% in the ERAS group, p=0.21). However, the cumulative POMS score was significantly higher in the control group (7.87 vs. 2.87, p<0.01), and the Clavien-Dindo score was significantly lower in the ERAS group (p=0.02). Quality of life was significantly improved in the ERAS group on the 7th and 30th postoperative day. Conclusion Our pilot study suggests feasibility of ERAS implementation in radical cystectomy. The primary endpoint (overall complication rate) did not differ significantly between groups; however, ERAS was associated with lower complication severity and improved early postoperative quality of life, which should be interpreted as exploratory given the small, non-randomised sequential design. Larger multicentre prospective implementation studies are warranted to confirm these findings and to evaluate the influence of protocol adherence and individual ERAS elements. Trial registration DRKS00035673 (retrospective) on 13th December 2024

Abstract Background The use of antibiotic therapy in acute pancreatitis remains controversial and is currently recommended only for confirmed infections of peripancreatic necrosis. However, reliable early predictors of septic complications and unfavorable outcomes are substantially lacking. Methods Patients with acute pancreatitis were retrospectively reviewed and divided into two groups: one with a septic course defined by pathogen detection [GERM(+)] and one without [GERM(-)]. After propensity score matching, both groups were compared regarding clinical outcomes. Early predictors of pathogen detection were evaluated by multivariate analysis. Results 424 patients with acute pancreatitis were included. After propensity score matching 123 GERM(-) patients were compared to 74 GERM(+) patients. GERM(+) patients demonstrated significantly worse clinical outcomes with higher rate of intensive care treatment (59.5% vs. 35.0%; p = 0.0011) and consecutive longer stay in intensive care unit (11.5 ± 25.2d vs. 3.0 ± 7.9d; p = 0.0007), longer in-hospital stay (26.8 ± 22.0d vs. 14.7 ± 15.0d; p = 0.0003) as well as worse results in the composite outcome length of in-hospital stay > 15d or death (67.6% vs. 31.7%; p < 0.0001). Prescence of ascites and elevated white blood cell count at the onset of acute pancreatitis were identified as significant predictive factors in the early disease associated with invasive infection and pathogen detection. The most frequently detected pathogens were commensals of the gastrointestinal tract, observed in 70.7% of the examined body fluids and 50.7% of the examined blood cultures. Conclusions Detection of pathogens is associated with unfavorable clinical outcomes in acute pancreatitis. The presence of ascites and elevated white blood cell count at onset of acute pancreatitis are significant predictive factors indicating the risk of invasive infection with relevant bacterial load. Thus, an aggressive, early anti-infective strategy against pathogens of intestinal origin should be considered in these cases and may improve patient outcomes.

BackgroundNucleated red blood cells (nRBC) are precursor cells of the erythropoiesis that are absent from the peripheral blood under physiological conditions. Their presence is associated with adverse outcomes in critically ill patients. This study aimed to evaluate the predictive value of nRBC on mortality in intensive care unit (ICU) patients with COVID-19 acute respiratory distress syndrome (ARDS).Material and methodsThis retrospective, observational cohort study analyzed data on 206 ICU patients diagnosed with COVID-19 ARDS between March 2020 and March 2022. The primary endpoint was ICU mortality, and secondary endpoints included ICU and hospital stay lengths, ventilation hours, and the time courses of disease severity scores and clinical and laboratory parameters.ResultsAmong the included patients, 68.9% tested positive for nRBC at least once during their ICU stay. A maximum nRBC of 105 µl-1 had the highest accuracy in predicting ICU mortality (area under the curve of the receiver operating characteristic [AUCROC] 0.780, p < 0.001, sensitivity 69.0%, specificity 75.5%). Mortality was significantly higher among patients with nRBC >105 µl-1 than ≤105 µl-1 (86.5% vs. 51.3%, p = 0.008). Compared to patients negative for nRBC in their peripheral blood, those positive for nRBC required longer mechanical ventilation (127 [44 - 289] h vs. 517 [255 - 950] h, p < 0.001), ICU stays (12 [8 – 19] vs. 27 [13 – 51] d, p < 0.001), and hospital stays (19 [12 - 29] d vs. 31 [16 - 58] d, p < 0.001). Peak Sepsis-related Organ Failure Assessment (SOFA), Simplified Acute Physiology Score, PaO2/FiO2, interleukin-6, and procalcitonin values were reached before the peak nRBC level. However, the predictive performance of the SOFA (AUCROC 0.842, p < 0.001) was considerably improved when a maximum SOFA score >8 and nRBC >105 µl-1 were combined.DiscussionnRBC predict ICU mortality and indicate disease severity among patients with COVID-19 ARDS, and they should be considered a clinical alarm signal for a worse outcome. nRBC are a late predictor of ICU mortality compared to other established clinical scoring systems and laboratory parameters but improve the prediction accuracy when combined with the SOFA score.

BACKGROUND:Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). METHODS:In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72 h of onset, respectively. RESULTS:AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p = 0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p = 0.005). CONCLUSION:Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT03039959, NCT03046277.

Einleitung Procalcitonin (PCT) ist ein Akutphasenprotein und ein regelmäßig verwendeter Parameter in der Diagnostik bakterieller Infektionen und deren kritischen Formen wie die Sepsis und der septische Shock. Während einer Sepsis kann die PCT-Ausschüttung das 10000fache seines Normalwertes übersteigen. Die physiologische Rolle dieses ausgeprägten PCT-Anstiegs wurde bislang nicht geklärt. Interleukin-1β (IL-1β) ist ein potentes proinflammatorisches Zytokin, unabdingbar für die Immunabwehr. Im Überschuss kann IL-1β eine lebensbedrohliche systemische Inflammation mit Multiorgandysfunktion auslösen. Entsprechend unterliegt die Ausschüttung von IL-1β strikten regulatorischen Mechanismen, in die auch andere Akutphasenproteine involviert sind.

BACKGROUND:COVID-19 can induce acute respiratory distress syndrome (ARDS). In patients with congenital heart disease, established treatment strategies are often limited due to their unique cardiovascular anatomy and passive pulmonary perfusion.CASE PRESENTATION:We report the first case of an adult with single-ventricle physiology and bidirectional cavopulmonary shunt who suffered from severe COVID-19 ARDS. Treatment strategies were successfully adopted, and pulmonary vascular resistance was reduced, both medically and through prone positioning, leading to a favorable outcome.CONCLUSION:ARDS treatment strategies including ventilatory settings, prone positioning therapy and cannulation techniques for extracorporeal oxygenation must be adopted carefully considering the passive venous return in patients with single-ventricle physiology.

The early administration of fibrinogen has gained wide acceptance for the treatment of major hemorrhage, whereas the substitution of coagulation factor XIII (FXIII) is only supported by a low level of evidence. This study aimed to answer the question of whether a combined therapy of fibrinogen/FXIII substitution performs superiorly to sole fibrinogen administration in the treatment of dilutional coagulopathy. An in-vitro model of massive transfusion was used to compare the effect of combined fibrinogen/FXIII administration to that of sole fibrinogen therapy for the treatment of dilutional coagulopathy. For this purpose, the blood of red blood cell concentrates, fresh frozen plasma, and platelet concentrates were reconstituted in a ratio of 4:4:1, and then diluted with gelatin by 20% and 40%, respectively. Clot formation and stability were analyzed by thrombelastography. Both sole fibrinogen therapy (equivalent to 50 mg/kg) and the combined administration of fibrinogen (equivalent to 50 mg/kg) and FXIII (equivalent to 75 International Units (IU)/kg) increased fibrinogen-dependent mean clot firmness independently of the degree of dilution (20% dilution: 7 (6.3–7.8) mm; 20% dilution fibrinogen: 13.5 (13–17.3) mm; 20% dilution fibrinogen/FXIII: 16.5 (15.3–18.8) mm; 40% dilution: 3 (2–3.8) mm; 40% dilution fibrinogen: 8 (7–11.3) mm; 40% dilution fibrinogen/FXIII: 10 (8.3–11.8) mm; all p < 0.01). However, no differences were identified between the two treatment arms. Compared to fibrinogen therapy, no beneficial effect of the combined administration of fibrinogen and FXIII for the treatment of dilutional coagulopathy was detected in this in-vitro massive transfusion model. The result was independent of the degree of dilution.

Introduction Treatment of high-risk pulmonary embolism (PE) in perioperative patients remains challenging. Systemic thrombolysis is associated with a high risk of major bleedings and intracranial haemorrhage. High mortality rates are reported for open pulmonary embolectomy. Therefore, postoperative surgical patients may benefit substantially from catheter-directed ultrasound-accelerated thrombolysis (USAT). Case presentation We report two cases of high-risk perioperative PE. Both patients developed severe haemodynamic instability leading to cardiac arrest. After the implantation of a veno-arterial extracorporeal membrane oxygenation (ECMO), they were both successfully treated with USAT. Adequate improvement of right ventricular function was achieved; thus, ECMO could be successfully weaned after 3 and 4 days, respectively. Both patients showed favourable outcomes and could be discharged to rehabilitation. Conclusion Current guidelines on treatment of PE offer no specific therapies for perioperative patients with high-risk PE. However, systemic thrombolysis is often excluded due to the perioperative setting and the risk of major bleeding. Catheter-directed thrombolysis was shown to utilise less thrombolytic agent while obtaining comparable thrombolytic effects. The risk for major bleeding (including intracranial haemorrhage) is also significantly lowered. Until further trials determining the value of adopted treatment strategies of high-risk PE in perioperative patients are available, USAT should be considered in similar cases.

Echinocandins are known as effective and safe agents for the prophylaxis and treatment of different cohorts of patients with fungal infections. Recent studies revealed that certain pharmacokinetics of echinocandin antifungals might impact clinical efficacy and safety in special patient populations. The aim of our study was to evaluate echinocandin-induced aggravation of cardiac impairment in septic shock. Using an in vivo endotoxemic shock model in rats, we assessed hemodynamic parameters and time to hemodynamic failure (THF) after additional central-venous application of anidulafungin (2.5 mg/kg of body weight [BW]), caspofungin (0.875 mg/kg BW), micafungin (3 mg/kg BW), and control (0.9% sodium chloride). In addition, echinocandin-induced cytotoxicity was evaluated in isolated rat cardiac myocytes. THF of the animals in the caspofungin group (n = 7) was significantly reduced compared to that in the control (n = 6) (136 min versus 180 min; P = 0.0209). The anidulafungin group (n = 7) also showed a trend of reduced THF (136 min versus 180 min; log-rank test P = 0.0578). Animals in the micafungin group (n = 7) did not show significant differences in THF compared to those in the control. Control group animals and also micafungin group animals did not show altered cardiac output (CO) during our experiments. In contrast, administration of anidulafungin or caspofungin induced a decrease in CO. We also revealed a dose-dependent increase of cytotoxicity in anidulafungin- and caspofungin-treated cardiac myocytes. Treatment with micafungin did not cause significantly increased cytotoxicity. Further studies are needed to explore the underlying mechanism.

ABSTRACT Echinocandins have become the agents of choice for early and specific antifungal treatment in critically ill patients. In vitro studies and clinical case reports revealed a possible impact of echinocandin treatment on cardiac function. The aim of our study was to evaluate echinocandin-induced cardiac failure. Using an in vivo rat model, we assessed hemodynamic parameters and time to hemodynamic failure after central venous application (vena jugularis interna) of anidulafungin (low-dose group, 2.5 mg/kg body weight [BW]; high-dose group, 25 mg/kg BW), caspofungin (low-dose group, 0.875 mg/kg BW; high-dose group, 8.75 mg/kg BW), micafungin (low-dose group, 3 mg/kg BW; high-dose group, 30 mg/kg BW), and placebo (0.9% sodium chloride). Left ventricular heart tissue was collected to determine mitochondrial enzyme activity via spectrophotometric measurements. mRNA expression of transcriptional regulators and primary mitochondrial transcripts, mitochondrial DNA (mtDNA) content, and citrate synthase activity were also explored. Animals receiving high-dose anidulafungin or caspofungin showed an immediate decrease in hemodynamic function. All of the subjects in these groups died during the observation period. Every animal in the untreated control group survived ( P < 0.001). Hemodynamic failure was not noticed in the anidulafungin and caspofungin low-dose groups. Micafungin had no impact on cardiac function. In analyzing mitochondrial enzyme activity and mitochondrial transcripts, we found no association between echinocandin administration and the risk for hemodynamic failure. Further experimental studies are needed to elucidate the underlying mechanisms involved in cardiotoxic echinocandin effects. In addition, randomized controlled clinical trials are needed to explore the clinical impact of echinocandin treatment in critically ill patients.