Early detection of acute lung injury (ALI) remains challenging, as conventional diagnostics rarely capture initial molecular changes. We therefore examined whether extracellular vesicles (EVs) in bronchoalveolar lavage fluid (BALF) can detect early regional injury and distinguish initial stress mechanisms in a porcine ALI model. Unilateral ALI was induced using Triton X-100, followed by six hours of mechanical ventilation with either fixed positive end-expiratory pressure (PEEP) at 5 cmH2O or transpulmonary-pressure (TPP)-guided PEEP. Spatially separated BALF sampling allowed direct comparison between injured and contralateral mechanically stressed lungs. EV concentration and size distribution were quantified by nano-flow cytometry, while vesicular identity was confirmed by transmission electron microscopy and tetraspanin dot blot analyses. Furthermore, EV metrics were related to corresponding histologic injury scores. Across both PEEP strategies, EV concentration was markedly higher in both directly injured and contralateral mechanically stressed lungs compared with sham controls, indicating alveolar stress beyond the primary injury site. Median EV size differed significantly by injury type and correlated inversely with histologic injury, particularly with alveolar neutrophil infiltration. BALF-derived EV concentration and size may therefore provide complementary, spatially resolved molecular readouts of early ALI.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is one of the more recently described biomarkers for sepsis and currently of great interest, as an inhibitor called nangibotide (Inotrem, Paris, France) for TREM-1 has made it into a phase 3 study for the treatment of sepsis. TREM-1, as a pattern recognition receptor (PRRs), plays a crucial role in the immune defense of the host. Several studies revealed promising results for soluble TREM-1 (sTREM-1) as a biomarker for outcome prediction. However, its usefulness in different subgroups of sepsis and the cut-off threshold at which patients are exposed to a higher risk of mortality have not yet been sufficiently investigated. This study is a secondary analysis of data and sTREM-1 measurements from plasma samples obtained in the prospective, observational, non-interventional, multicentric Next GeneSiS-Trial (DRKS00011911). We aimed to characterize the role of sTREM-1 in septic and septic shock patients in a large cohort with regard to different pre-existing factors, infectious aspects and outcome parameters. Furthermore, we investigated the influence of sTREM-1 cut-offs previously described from Francois et al. on different outcome parameters. Therefore, data from 500 patients were analyzed. Median sTREM-1 values were statistically significant higher in patients with septic shock than in septic patients (406 (IQR;270–650) pg/mL vs. 293 (IQR;189–489) pg/mL; p < 0.001). Non-survivors, patients with the need of renal replacement therapy, mechanical ventilation or a positive Sepsis-Induced-Coagulopathy (SIC) score presented with statistically significant higher sTREM-1 values (p < 0.001). sTREM-1 levels were significantly higher in patients in the highest quartile for fluid balance and Sequential Organ Failure Assessment score, and significantly lower in those in the highest quartile for Horowitz Index and platelet count (PSSC). sTREM-1 levels showed slight but statistically significant differences based on the site of infection or blood culture results on day one; however, these differences were no longer detectable by day three. The best cut-off of sTREM-1 values to differentiate between survival and non-survival on day 28 was 408 (CI;297–505) pg/ml in our study. Elevated sTREM-1 concentrations particularly occur in patients with a high degree of organ damage, who are at high risk for adverse outcomes. In addition, the primary site of infection may be of relevance for the sTREM-1 increase. These characteristics support its suitability as a biomarker across different causes of sepsis and highlights its potential as a therapeutic target. A cut-off value exceeding 400 pg/mL has shown robust diagnostic performance across multiple studies. Our results support this observation, indicating that this threshold may be useful for future clinical and research applications.

BACKGROUND:Optimal ventilator strategies for septic patients remain uncertain, particularly regarding positive end-expiratory pressure (PEEP). While PEEP may affect hemodynamics through changes in intrathoracic pressure, its impact on clinical outcomes in sepsis is not well understood. This multi-cohort study explores the impact of higher versus lower PEEP settings on mortality and hemodynamics in sepsis. METHODS:We conducted a secondary analysis of 844 septic patients requiring mechanical ventilation across three cohorts (one multicentric prospective = Hyspec ICU, one monocentric prospective = SepDataNet, one monocentric retrospective = RetroSep). Patients were stratified into low PEEP groups according to the ARDSnet low PEEP table and high PEEP groups with PEEP levels above mentioned table. Primary endpoint was ICU or 30-day mortality depending on reported outcome data. Secondary endpoints included vasopressor requirement, lactate levels and fluid balance. RESULTS:In two cohorts, higher PEEP was associated with significantly lower mortality (RetroSep: 39.4% vs. 50.4% for ICU-mortality, p = 0.008; Hyspec-ICU: 22% vs. 41.7% for 30-day mortality, p = 0.029). The difference persisted after propensity score matching in the RetroSep cohort (38.4% vs. 49.4%; p = 0.046). Hemodynamic parameters such as lactate and vasoactive-inotropic scores were similar or improved in high PEEP groups. Hyperspectral imaging showed no adverse microcirculatory effects. CONCLUSION:In this multi-cohort analysis, higher PEEP (above ARDSnet low PEEP table) was associated with improved survival without evidence of hemodynamic deterioration. However, due to the observational nature of this analysis and possible confounders, the results should be considered hypothesis-generating and warrant confirmation in randomized trials.

Abstract Objectives Ventilator-associated pneumonia (VAP) is driven in part by microaspiration along the endotracheal tube cuff, a process difficult to measure directly in ventilated patients. Because microbial communities differ between airway compartments, changes in their similarity over time may serve as an indirect readout of microaspiration. We assessed whether the Venner PneuX ® Tube (VT) system, combining cuff-pressure monitoring, subglottic suction, and a biofilm-resistant coating, reduces microbial exchange between airway compartments compared with a standard endotracheal tube (ST). Methods In a prospective, randomized, single-center pilot study, 50 adults with acute respiratory failure received an ST or VT intubation. Microbial communities from five airway niches (throat, tracheal secretions, right upper, right lower, and left lower lung lobes) were sampled by 16 S rRNA sequencing at intubation (T1), after four days of ventilation (T2) and, for the tube tip, at extubation (T3). The primary outcome was the change in beta diversity (Morisita–Horn distances) between tube-associated, upper-airway, and lower-airway communities from T1 to T2. Results Twenty-one of 50 randomized patients had complete microbiota data sets (9 ST, 12 VT) and were comparable in demographics, comorbidities, severity, and ventilation duration. In the ST group, tube-associated communities became more similar to tracheal and lower-airway communities from T1 to T2 (e.g. TS–Tube Morisita–Horn 0.55 → 0.30, p = 0.001), while lung regions diverged from each other and from the throat (LLL–LRL 0.08 → 0.31, p = 0.003; LLL–Throat 0.30 → 0.61, p < 0.001). None of these distances changed significantly in the VT group. Lower-airway Shannon diversity declined in both groups, more in the VT group. Conclusions Standard intubation produced progressive microbial convergence between airway compartments, while the VT system did not. The findings provide biological plausibility for previously reported VAP reductions with the VT system and show that microbiota sampling can detect device-related differences in airway community structure, warranting further investigation as an endpoint for evaluating airway devices. Trial registration The study is registered in the German Clinical Trials Register (DRKS- Deutsches Register für klinische Studien) under the clinical trial number: DRKS00029176. The Date of Trial Registration was 07.07.2022.

Background:Utility of serum creatinine (SCr) and urine output (UO) is limited for real-time assessments of functional integrity and guiding kidney replacement therapy (KRT) decisions in acute kidney injury (AKI). Proenkephalin A 119-159 (PENK) may overcome these limitations. We evaluate PENK's use for AKI staging, assessment of residual kidney function during KRT, and assessment of liberation failure. Methods:Prospective, real-world study in 1,436 critically ill patients at Heidelberg University Hospital, including a subgroup of 138 patients receiving KRT for liberation analyses. Plasma PENK was measured from admission to discharge. AKI was defined by KDIGO criteria; biomarker kinetic, ROC analyses and binary logistic regression models were performed. KRT liberation was considered successful if no re-initiation occurred within >5 days. Results:Of 1,436 patients, 621 (43.2%) developed AKI. Acute KRT was required in 12.6%, 40.9% of whom were successfully liberated, 24.3% failed, and 31.5% underwent no liberation attempt (3.3% lost to follow up). PENK rose with AKI stages and, unlike SCr/UO, distinguished stage 3 AKI with versus without acute KRT requirements, and differentiated acute from chronic KRT patients even under ongoing KRT. From KRT start, mean PENK levels increased progressively whereas SCr decreased under treatment. Later, PENK declined around successful liberation, with lower values compared to cases with liberation failure. PENK was the strongest, independent predictor of KRT liberation failure, outperforming SCr. A PENK cut-off of ≥250 pmol/L provided >90% specificity for liberation failure. Combining PENK and UO, further improved risk stratification. Conclusions:PENK may reflect kidney integrity independent of KRT, enhance residual kidney function assessment, and may aid prediction of KRT liberation failure, warranting multicenter validation.

Hyperspectral imaging (HSI) is a non-invasive technology capable of assessing microcirculatory impairment. This study evaluated whether HSI can detect early microcirculatory alterations in trauma patients and differentiate between those with hemodynamic instability or stability during initial trauma resuscitation. In this prospective single-center observational study at a German level I trauma center (01/2023-10/2024), patients underwent HSI (TIVITA® 2.0) at three time points: during the primary survey, after resuscitation room care, and 24 h after admission. HSI approximates four microcirculatory parameters: tissue oxygenation saturation (StO₂), tissue water index (TWI), tissue hemoglobin index (THI), and near-infrared perfusion index (NIR). Hemodynamic instability was defined as systolic blood pressure < 90 mmHg for > 10 min, catecholamine use > 10 min, or pronounced clinical signs of hypoperfusion. The primary outcome was the difference in StO₂ between patients with and without hemodynamic instability at the initial HSI measurement. Secondary outcomes included comparison of all HSI parameters between groups, correlations with Injury Severity Score (ISS), biomarkers (lactate, bicarbonate, base excess), and mortality. Statistical analyses comprised t-tests, receiver operator curve (ROC) analyses, diagnostic accuracy, and DeLong's test. A total of 163 patients were analyzed (18 hemodynamic instability, 145 hemodynamic stability). No significant difference in initial StO₂ was observed between groups (hemodynamic instability: 56.50 (SD 17.08) vs. hemodynamic stability: 59.48 (SD 10.92); p = 0.311). Likewise, TWI, THI, and NIR showed no significant differences. Initial elevated lactate levels (≥ 2 mmol/L) were associated with significantly lower StO2 levels (p = 0.002). ROC analysis of StO₂ for predicting in-hospital mortality showed an area under the curve of 0.677 (95% CI 0.529-0.825). The optimal mortality cut-off (StO₂ ≤ 54%) demonstrated a sensitivity of 0.70, specificity of 0.66, positive predictive value of 0.22, and negative predictive value (NPV) of 0.94. AUCs of StO₂, lactate, bicarbonate, and base excess overlapped, with no significant pairwise differences. HSI did not discriminate between hemodynamically unstable and stable patients at initial trauma assessment but correlated well with high lactate levels. However, its high NPV for mortality suggests potential value as an objective, non-invasive tool for early trauma team downgrading.Trial registration: German Clinical Trials Register (DRKS ID DRKS00030986) on 27th December 2022.

BACKGROUND:Neonatal sepsis is a leading cause of morbidity and mortality in neonates. The underdeveloped neonatal immune system, particularly innate immune cells such as monocytes, plays a critical role in susceptibility to infection. Monocyte-mediated regulation of iron metabolism, a key component of "nutritional immunity," is known to influence sepsis outcomes in adults. In this study, we investigated differences in iron sensing, iron-regulated gene expression, and intracellular iron content between neonatal and adult monocytes. METHODS:Monocytes were isolated from human umbilical cord blood and adult peripheral blood and stimulated in vitro with lipopolysaccharide (LPS), ferric nitrilotriacetate (FeNTA), or the iron chelator deferoxamine (DFO). Transferrin receptor 1 (TfR1) and differentiation markers were analyzed by flow cytometry, intracellular iron content by atomic absorption spectrometry, and metabolic and inflammatory responses via lactate and cytokine measurements. RESULTS:Neonatal monocytes exhibited lower basal TfR1 expression with a trend toward higher intracellular iron. LPS induced TfR1 upregulation exclusively in adult monocytes, while neonatal cells maintained consistently low expression. Although FeNTA increased intracellular iron in both groups, neonatal monocytes accumulated iron less efficiently. CONCLUSION:These findings indicate fundamental developmental differences in monocyte iron handling and immunometabolic adaptation, which may underlie the distinct immune profile observed in neonatal sepsis. IMPACT:Neonatal sepsis is a leading cause of morbidity and mortality in neonates. Particularly innate immune cells such as monocytes, play a critical role in susceptibility to infection. Monocyte-mediated regulation of iron metabolism, a key component of "nutritional immunity," is known to influence sepsis outcomes in adults. Our findings indicate fundamental developmental differences in monocyte iron handling and immunometabolic adaptation, which may play a role in both the distinct immune profile observed in neonatal sepsis and, consecutively, sepsis outcome. These findings imply that host-directed iron modulation could be a viable strategy to counteract immunoparalysis in neonatal sepsis without compromising cellular activation.

Sepsis remains one of the leading causes of morbidity and mortality worldwide. Despite evolving supportive therapeutic strategies, outcomes, particularly in severe disease manifestations, remain unsatisfactory. In recent years, the conceptual understanding of sepsis has undergone a fundamental shift: from a uniform disease entity to a heterogeneous syndrome characterized by variable pathophysiology and diverse clinical trajectories. In parallel, key aspects of diagnosis and management have been re-evaluated in the context of recently updated guidelines as well as international consensus statements. This review integrates recent guideline updates and emerging concepts in sepsis management into a clinically oriented synthesis. Particular focus is placed on evolving approaches to infection control, hemodynamic stabilization, tissue perfusion–oriented resuscitation, individualized antimicrobial strategies, and the concept of refractory septic shock. In the early phase, sepsis management continues to rely predominantly on standardized interventions focused on rapid infection control and hemodynamic stabilization. As the disease progresses, however, therapeutic strategies increasingly require continuous reassessment and adaptation to the individual patient context. Recent guideline developments therefore reflect a broader shift from rigid protocol-driven algorithms toward more flexible, context-sensitive, and physiology-guided approaches. A central component of this evolution is the growing emphasis on tissue perfusion–oriented resuscitation, individualized hemodynamic management, and risk-adapted antimicrobial strategies. Another important recent development is the proposed definition of refractory septic shock, which aims to identify a subgroup of patients with persistent hemodynamic instability and tissue hypoperfusion despite guideline-based initial therapy. Beyond its prognostic relevance, this concept may provide a pragmatic framework for structured therapeutic escalation and phenotype-guided treatment strategies. Overall, contemporary sepsis care is evolving toward a staged management model in which standardized early interventions are increasingly complemented by individualized and dynamically adapted therapeutic decisions during later disease stages. Building on these developments, this review integrates recent guideline updates and emerging concepts into a clinically oriented synthesis and discusses their implications for personalized and phenotype-guided sepsis care.

OBJECTIVES:This exploratory pilot study was designed to evaluate the effectiveness of pulse contour analysis (PCA) for real-time hemodynamic monitoring in patients undergoing transcatheter edge-to-edge tricuspid valve repair (T-TEER). Additionally, it examined whether continuous PCA monitoring can identify indicators of procedural success and improve perioperative management. DESIGN:Prospective, hypothesis-generating pilot, single-center study. SETTING:Single tertiary care university hospital. PARTICIPANTS:A total of 12 patients undergoing T-TEER. INTERVENTIONS:Real-time PCA was used throughout the intervention period, from preoperative assessment up to 4 hours postprocedure, to monitor hemodynamic parameters (cardiac output [CO], cardiac index [CI], stroke volume, stroke volume variation, and blood pressure). MEASUREMENTS AND MAIN RESULTS:At 4 hours after T-TEER, CO-PCA had increased by 30% (p = 0.0124), accompanied by a 0.68-L/min/m² rise in CI (p = 0.008). T-TEER also resulted in a persistent reduction in stroke volume variation-PCA, with a sustained 3% decrease after the intervention (p = 0.009). Implantation of the first device triggered a notable peri-interventional increase in systolic arterial pressure of 17 mmHg (p = 0.026). In addition, the right atrial v-wave decreased by 8 mmHg (p = 0.034). No meaningful changes in central venous oxygen saturation or central venous pressure were detected during or following the procedure (p = 0.73 and p = 0.27, respectively). CONCLUSIONS:This study demonstrated that PCA using FloTrack monitoring can provide valuable continuous hemodynamic information and characterize acute hemodynamic responses to T-TEER. PCA detected meaningful hemodynamic improvements during T-TEER, characterized by increased CO, enhanced CI, and more stable preload conditions.

The early identification of patients with sepsis among those presenting with suspected infection in the emergency department (ED) remains challenging. Delta-like canonical Notch ligand-1 (DLL-1), a Notch pathway ligand involved in immune and endothelial signaling, has been shown to reflect disease severity and outcomes in ICU-based sepsis cohorts. Its value for early risk stratification at ED presentation is less well defined. We analyzed DLL-1 concentrations in serum samples from a prospectively enrolled ED cohort of adults presenting with clinically suspected acute infection. Blood samples were obtained during the initial clinical assessment. Sepsis was defined according to Sepsis-3 criteria and adjudicated by an expert panel, including evaluation of organ dysfunction within 72 h after presentation. DLL-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and diagnostic performance was assessed using AUROC analysis. Among 300 enrolled patients, 74 (24.7

OBJECTIVES:To provide real-world evidence on piperacillin exposure and outcomes in critically ill patients after the implementation of pharmacokinetics/pharmacodynamics-guided dosing in routine care. METHODS:This retrospective observational study included critically ill adults who received continuous piperacillin/tazobactam infusion between 2011 and 2019. Empiric doses were individualized using dosing software based on renal function and subsequently adjusted according to therapeutic drug monitoring (TDM) results. Drug exposure was defined as subtherapeutic (<32 mg/L), therapeutic (32-64 mg/L), extended (64-96 mg/L), or supratherapeutic (>96 mg/L). RESULTS:A total of 1538 critically ill patients with severe infections and sepsis of varying severity were included, and 3089 piperacillin serum concentrations were analysed. Median daily piperacillin dose was 8 g (interquartile range [IQR], 6-12 g), median steady-state concentration 55 mg/L (IQR, 38-73 mg/L), and median clearance 6.25 L/h (IQR, 4.0-9.8 L/h). At the first measurement, individualized empiric dosing resulted in 45.7% (704 of 1538) of patients being within the therapeutic range; after TDM-guided adjustment, target attainment increased to 62.4% (968 of 1551). Subtherapeutic and supratherapeutic concentrations were uncommon among all TDM samples collected during individualized dosing (<32 mg/L: 12.8%, 395 of 3089; <16 mg/L: 0.8%, 26 of 3089; >96 mg/L: 11%, 340 of 3089). Twenty-eight-day mortality was 18.2% (131 of 718) in patients within the therapeutic range, 27.0% (107 of 396) in those within the extended range, and 40.9% (101 of 247) in those with supratherapeutic concentrations (p 0.05). Women were associated with 1.74-fold higher odds of supratherapeutic concentrations (OR, 1.74; 95% CI, 1.38-2.19; p < 0.001; 176 of 2022 male vs. 152 of 1067 female with concentrations >96 mg/L). CONCLUSIONS:A multimodal approach combining individualized empiric dosing, TDM, and continuous infusion ensured target attainment while reducing drug consumption. These findings support the integration of individualized, pharmacokinetics/pharmacodynamics-guided dosing into routine care for critically ill patients and warrant further exploration of sex-related differences in exposure.

Background: Osteoradionecrosis (ORN) following head and neck radiotherapy has been demonstrated to induce structural and functional alterations of the upper airway, with the potential to complicate the process of tracheal intubation. Despite its clinical relevance, there is a paucity of systematic evidence on airway characteristics in ORN and reliable predictors of difficult tracheal intubation. This study compares preoperative airway parameters and tracheal intubation outcomes in irradiated patients with and without ORN and introduces a novel preoperative ORN-Difficult-Airway Score for risk stratification. Methods: In this retrospective cohort study, airway assessments, tracheal intubation methods, and perioperative visualization parameters were evaluated in 105 patients following head and neck radiotherapy. Group differences between non-ORN and ORN were analyzed using chi-square tests. A preoperative ORN-Difficult-Airway Score was constructed using exclusively bedside parameters, based on statistically and clinically relevant predictors. Results: Patients with ORN showed significantly restricted mouth opening (p < 0.001), higher Mallampati classes, particularly Mallampati IV, and a greater need for fiberoptic tracheal intubation (p < 0.01). Direct laryngoscopy (DL) was significantly less feasible in ORN, while hyperangulated videolaryngoscopy (VL) yielded consistently positive visualization (first-pass success (FPS) 100% in both groups). Under DL, FPS was lower in ORN (54.2% vs. 79.5%), resulting in an odds ratio of 0.305. Based on observed predictors, ORN status, mouth opening <3 cm, Mallampati class, restricted neck reclination, and history of difficult intubation, a preoperative ORN-Difficult-Airway Score was developed. Conclusions: ORN has been associated with distinct alterations in airway anatomy and visualization, resulting in increased tracheal intubation complexity after head and neck radiotherapy. The proposed ORN-Difficult-Airway Score presents a clinically practical, bedside-applicable approach to stratifying the risk of tracheal intubation in this population. Prior to clinical implementation, prospective validation in larger cohorts is warranted.

Introduction Outcome after surgery depends on both patient-related as well as procedure-related risks. Complications after surgery are a significant burden to patients and to the health system. A vast amount of often unstructured data from different sources are generated during surgery, which contain valuable information associated with outcome. Advances in computer hardware and machine learning now increasingly facilitate the development of prediction models in standardised, parametric, information-rich areas such as the perioperative setting. For the development and validation of risk scores and prediction models, high-fidelity data sources are required to arrive at meaningful and reliable predictions. However, data quality standards in retrospective studies are rarely met. Therefore, the prospective Heidelberg Perioperative Deep Data Registry and Biomaterial Bank (HeiPoDD - Registry and Bio Bank) was started to implement a clinical data base and a corresponding biobank merging the entirety of available clinical records.Methods and analysis The HeiPoDD - Registry and Bio Bank is a study-driven, prospective, single-centre observational registry data base and biomaterial bank. It contains data and material from eligible patients who give informed consent and undergo elective non-cardiac high-risk surgery at the surgical centre of the Heidelberg University Hospital. The screening for eligibility started in January 2022, with no maximum sample size specified in advance. Routine data are recorded and stored during hospital stay and potential readmissions within 90 days after index surgery. The data are merged with the potentially available genome, proteome, flow cytometry, and bio signal data. Endpoints are obtained from routine observations, stored data in the hospital information system and follow-up visits. Further, data and biological specimens from separate perioperative studies with the patients’ consent can be transferred into the HeiPoDD - Registry and Bio Bank as well. This large-scale data collection will allow the calculation of endpoint-specific prediction models using logistic regression models as well as machine learning models. The first 1040 patients included in the HeiPoDD - Registry and Bio Bank are also included in the HeiPoDD study.Ethics and dissemination The trial protocol and subsequent amendments were approved by the ethics committee of the University of Heidelberg (S-745/2021). Participating patients’ data will be entered only in pseudonymised form. Data and biomaterials will be kept for up to 30 years. The findings will be disseminated in peer-reviewed academic journals.Trial registration number DRKS00025924, registered on 2021-11-12.

Die Versorgung von Sepsispatient*innen stellt eine anhaltende intensivmedizinische Herausforderung dar und führt selbst in medizinisch hochentwickelten Ländern zu inakzeptabel hohen Morbiditäts- und Mortalitätsraten. Wie steht es um die Qualität der frühzeitigen Sepsisversorgung auf deutschen Intensivstationen? Zur Bewertung der Qualität der frühen Sepsisbehandlung führten wir eine nationale, internetbasierte Umfrage unter den Mitgliedern der Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin (DIVI) durch. Insgesamt wurden 1935 Intensivmediziner*innen in ganz Deutschland befragt, von denen 459 erfahrene Fachärzt*innen geantwortet haben – darunter 38

Optimization of perioperative hemodynamic management during major pancreatic surgery can reduce postoperative complications. In this study, we aimed to investigate the effect of intraoperative hemodynamic management, in consideration of both anesthesiologic and surgery-related aspects on major short-term complications following partial pancreatoduodenectomy (PD). Data of 525 patients undergoing PD between January 2017 and December 2018 at the Heidelberg University Hospital were retrospectively analyzed. Primary outcome was a composite of 90-day mortality, pancreatic fistula and completion pancreatectomy. Logistic regression was performed to estimate the impact of anesthesiologic and surgical factors. Furthermore, patients were stratified by the amount of fluid administered intraoperatively and the maximum catecholamine dose to examine the impact on the primary endpoint. Using logistic regression analysis we demonstrated that epidural anesthesia was associated with a reduction in the occurrence of the combined endpoint (OR 0.568; CI 0.331–0.973), this effect was primarily driven by a lower rate of completion pancreatectomy. The intraoperative administration of fresh frozen plasma (FFP) doubled the odds of the occurrence of the primary endpoint (OR 2.238; CI 1.290–3.882). The comparison of patients with and without FFP transfusion showed that all components of the primary endpoint were more frequent in the FFP group. Complication rates in the stratified fluid groups showed a U-shaped curve with the least amount of complications in patients who received 6.5 to 8 ml/kg/h of intraoperative fluid. The comparison of maximum norepinephrine doses revealed the same pattern with the least complication rate in the low-intermediate dose range (0.05–0.08 µg/kg/min and 0.08–0.11 µg/kg/min). Epidural anesthesia had a beneficial effect on the rate of major surgical complications following PD, whereas intraoperative FFP transfusion showed a negative association. Intraoperative hemodynamic management appears to have a major impact on perioperative mortality and morbidity with a U-shaped relation for both fluid and vasopressor dose.

BackgroundThis study evaluates the use and clinical implications of prehospital packed red blood cells administered by a specialized physician-staffed Medical Intervention Car in a German emergency medical service system capable of advanced interventions such as thoracotomy and extracorporeal cardiopulmonary resuscitation.MethodsWe conducted a retrospective cohort study of all prehospital patients treated with at least one unit of packed red blood cells (pRBC) by the MIC team between August 2019 and September 2024. In the trauma cohort, we compared characteristics and interventions between those who were admitted to the hospital and those for whom resuscitation was commenced on scene. For in-hospital comparisons, patients were grouped into two categories: those who continued to receive pRBCs and those who did not. A modified blood transfusion need score (mBTNS) was retrospectively applied to assess the clinical appropriateness of transfusion.ResultsA total of 57 patients received pRBCs, including 45 with traumatic and 12 with non-traumatic hemorrhage. Among trauma patients, 78% were male, 49% sustained penetrating injuries, and 56% were in traumatic cardiac arrest. There were higher rates of primary dispatch by the dispatch center in patients admitted to the hospital (43% vs. 13%; p = 0.048). The mean number of prehospital pRBC units transfused did not differ between those admitted and those for whom resuscitation was commenced (mean 4 [2]). Patients admitted to the hospital received fibrinogen (90% vs. 47%; p = 0.003), tranexamic acid (93% vs. 47%; p < 0.001), and Calcium (67% vs. 33%; p = 0.028) significantly more often compared to those who died on the scene. A lower pH and higher glucose level were significantly linked to continuous pRBC transfusion during the first 24 h after hospital admission. In the non-trauma cohort, gastrointestinal bleeding was the predominant cause (54%).ConclusionPrehospital transfusion by a trained MIC team led to high survival rates in trauma and non-trauma patients. The frequent invasive procedures underline the need for integrated prehospital blood transfusion within advanced care. Broader adoption of structured protocols in high-acuity systems warrants prospective evaluation.

With sepsis remaining a leading cause of mortality, early identification of patients with sepsis and those at high risk of death is a challenge of high socioeconomic importance. Given the potential of hyperspectral imaging (HSI) to monitor microcirculatory alterations, we propose a deep learning approach to automated sepsis diagnosis and mortality prediction using a single HSI cube acquired within seconds. In a prospective observational study, we collected HSI data from the palms and fingers of more than 480 intensive care unit patients. Neural networks applied to HSI measurements predicted sepsis and mortality with areas under the receiver operating characteristic curve (AUROCs) of 0.80 and 0.72, respectively. Performance improved substantially with additional clinical data, reaching AUROCs of 0.94 for sepsis and 0.83 for mortality. We conclude that deep learning-based HSI analysis enables rapid and noninvasive prediction of sepsis and mortality, with a potential clinical value for enhancing diagnosis and treatment.

The main risk factor for developing transplant vasculopathy (TV) after solid organ transplantation is de-novo production of donor-specific antibodies (DSAs) binding to endothelial cells (ECs) within the graft’s vasculature. Diverse leukocyte populations recruited into the vessel wall via activated ECs contribute to vascular inflammation. Subsequent smooth muscle cell proliferation results in intima hyperplasia, the pathophysiological correlate of TV. We demonstrated that incubating aortic EC with anti-HLA-I antibodies led to increased monocyte adhesion to and transmigration across an EC monolayer. Both occurred in a CD62E-dependent fashion and were sensitive toward the anti-inflammatory enzyme heme oxygenase (HO)-1 modulation. Using a murine heterotopic aortic transplantation model, we demonstrated that anti-MHC I antibody-induced TV is ameliorated by pharmacologically induced HO-1 and the application of anti-CD62E antibodies results in a deceleration of developing TV. HO-1 modulation is a promising therapeutic approach to prevent leukocyte recruitment and subsequent intima hyperplasia in TV and thus precludes organ failure.