The Circulating CDC42 Expression in Sepsis: Relation to Disease Susceptibility, Inflammation, Multiple Organ Dysfunctions and Mortality Risk.

OBJECTIVE: Cell division cycle 42 (CDC42) modulates inflammation and multiple organ dysfunction by regulating T-cell differentiation and macrophage polarization. This research intended to explore the association of blood CDC42 expression with septic risk, multi-organ dysfunctions, and mortality. METHODS: 145 sepsis patients and 50 health controls were recruited, then CDC42 expression in peripheral blood mononuclear cell (PBMC) from them was measured by RT-qPCR. RESULTS: CDC42 was decreased in sepsis patients versus health controls (P<0.001); meanwhile, the receiver operating characteristic (ROC) curve showed that CDC42 had a certain value to predict sepsis risk with an area under the curve (AUC) (95% confidence interval (CI): 0.797 (0.725-0.869). Furthermore, CDC42 was negatively correlated with C-reactive protein (P<0.001), tumor necrosis factor-alpha (P<0.001) and interleukin-17A (P<0.001) but less with interleukin-6 (P=0.056). Moreover, CDC42 was negatively related to the SOFA score (P<0.001) and its several subscales (respiratory system, liver, cardiovascular, and renal system) (P<0.05). Furthermore, CDC42 was lower in septic deaths versus survivors (P<0.001); meanwhile, the ROC curve exhibited a certain ability of CDC42 in estimating 28-day mortality with an AUC (95%CI) of 0.766 (0.676-0.855). CONCLUSION: Circulating CDC42 exhibits potency to be a prognostic biomarker reflecting multi-organ dysfunctions and higher mortality risk in sepsis.

Evaluating the prognostic performance of the novel ERAP score in Vietnamese acute pancreatitis patients.

Early recognition of severe acute pancreatitis (AP) is crucial for timely intervention. This study aims to evaluate the prognostic accuracy of the Emergency Room Assessment of AP (ERAP) score and compare it with the Bedside Index for Severity in AP (BISAP) score in predicting severe AP, mortality, and persistent multiple organ failure (MOF) in Vietnamese patients. This prospective cohort study included AP patients admitted to Cho Ray Hospital between August 2021 and May 2022. Patient data, including demographics, clinical presentations, and laboratory results, were collected upon admission. The ERAP and BISAP scores were calculated from these admission data. The prognostic accuracy for severe AP, mortality, and persistent MOF was assessed via the area under the receiver-operating characteristic curve (AUC). Among 167 AP patients (mean age 41.5 ±â€…12.0 years), hypertriglyceridemia (34.7%) and alcohol (22.2%) were the most prevalent etiologies. Severe AP accounted for 33.5% of the patients. Mortality rates were higher in persistent MOF patients (42.9%) than in persistent single-organ failure patients (3.6%), with a P value <.001. The ERAP score had AUCs for predicting severe AP, mortality, and persistent MOF of 0.899, 0.817, and 0.867, respectively, with an optimal cutoff of ≥2. The ERAP score had a better prognostic value than the BISAP score in predicting severe AP (AUC: 0.899 vs 0.820; P = .0072) and persistent MOF (AUC: 0.867 vs 0.785; P = .0193) but had a similar prognostic value for mortality (AUC: 0.817 vs 0.728; P = .0628). The ERAP score has strong predictive value for severe AP and persistent MOF, surpassing the BISAP score in these categories while maintaining similar accuracy for mortality prediction in the Vietnamese population. The ERAP score can be a valuable tool for the early identification of high-risk AP patients, enabling timely and appropriate clinical interventions.

Iloprost and Organ Dysfunction in Adults With Septic Shock and Endotheliopathy: A Randomized Clinical Trial.

Importance: Soluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality. Objective: To assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble thrombomodulin higher than 10 ng/mL. Design, Setting, and Participants: This investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included. Interventions: Patients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng/kg/min (n = 142), or placebo (n = 137) for 72 hours. Main Outcomes and Measures: The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days. Results: Of 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, -0.8 to 1.2]; P = .70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P = .33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P = .52). Only 1 serious adverse reaction was observed. Conclusions and Relevance: In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04123444.

Ulinastatin shortens the length of ICU stay in critical patients with organ failure: A 7-year real-world study.

BACKGROUND: Ulinastatin has been applied in a series of diseases associated with inflammation but its clinical effects remain somewhat elusive. OBJECTIVE: We aimed to investigate the potential effects of ulinastatin on organ failure patients admitted to the intensive care unit (ICU). METHODS: This is a single-center retrospective study on organ failure patients from 2013 to 2019. Patients were divided into two groups according to using ulinastatin or not during hospitalization. Propensity score matching was applied to reduce bias. The outcomes of interest were 28-day all-cause mortality, length of ICU stay, and mechanical ventilation duration. RESULTS: Of the 841 patients who fulfilled the entry criteria, 247 received ulinastatin. A propensity-matched cohort of 608 patients was created. No significant differences in 28-day mortality between the two groups. Sequential organ failure assessment (SOFA) was identified as the independent risk factor associated with mortality. In the subgroup with SOFA ≤ 10, patients received ulinastatin experienced significantly shorter time in ICU (10.0 d [interquartile range, IQR: 7.0∼20.0] vs 15.0 d [IQR: 7.0∼25.0]; p = .004) and on mechanical ventilation (222 h [IQR:114∼349] vs 251 h [IQR: 123∼499]; P = .01), but the 28-day mortality revealed no obvious difference (10.5% vs 9.4%; p = .74). CONCLUSION: Ulinastatin was beneficial in treating patients in ICU with organ failure, mainly by reducing the length of ICU stay and duration of mechanical ventilation.

Understanding Causes of Death in Patients With Acute Respiratory Distress Syndrome: A Narrative Review.

OBJECTIVES: To provide a comprehensive summary of the published data on cause of death in patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: PubMed (January 2015 to April 2024), bibliographies of relevant articles, and ARDS Network and Prevention & Early Treatment of Acute Lung Injury (PETAL) network websites. STUDY SELECTION: Observational studies and clinical trials that reported on cause of death in greater than or equal to 30 patients with ARDS, not obtained from death certificates. Animal studies, case reports, review articles, study protocols, and studies in pediatrics were excluded. DATA EXTRACTION: Causes of death among ARDS patients who died were extracted and tabulated along with other pertinent study characteristics. DATA SYNTHESIS: We identified 15 observational studies (nine non-COVID ARDS, five COVID-related ARDS; one both) and five clinical trials (all non-COVID ARDS). Mutually exclusive prespecified categories were used for recording the cause of death in only eight studies although studies differed in the categories included and their definitions. When multiple organ failure was a predetermined category, it was the most common cause of death recorded (~50% of deaths), followed by respiratory causes with proportions varying from 16% to 42% depending on nomenclature (e.g., refractory hypoxemia, pulmonary causes) and definitions. However, the largest observational study in non-COVID ARDS (964 deaths), did not include multiple organ failure as a predetermined category, and found that pulmonary failure (42%) and cardiac failure (37%) were the most common causes of death. In COVID-related ARDS observational studies, pulmonary reasons were the most reported cause of death (up to 88%). CONCLUSIONS: Few studies have reported cause of death in patients with ARDS. In those that do, cause of death categories and definitions used are heterogeneous. Further research is needed to see whether a more rigorous and unified approach to assigning and reporting cause of death in ARDS would help identify more relevant endpoints for the assessment of targeted treatments in clinical trials.

Exploring the Mediating Role of Multiple Organ Dysfunction in Sepsis-Induced Disseminated Intravascular Coagulation and Its Impact on Worsening Prognosis.

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.

Validating the performance of organ dysfunction scores in children with infection: A cohort study.

PURPOSE: We aimed to validate the performance of six available scoring models for predicting hospital mortality in children with suspected or confirmed infections. METHODS: This single-center retrospective cohort study included pediatric patients admitted to the PICU for infection. The primary outcome was hospital mortality. The six scores included the age-adapted pSOFA score, SIRS score, PELOD2 score, Sepsis-2 score, qSOFA score, and PMODS. RESULTS: Of the 5,356 children admitted to the PICU, 9.1% (488) died, and 25.1% (1,342) had basic disease with a mortality rate of 12.7% (171); 65.3% (3,499) of the patients were younger than 2 years, and 59.4% (3,183) were male. The discrimination abilities of the pSOFA and PELOD2 scores were superior to those of the other models. The calibration curves of the pSOFA and PELOD2 scores were consistent between the predictions and observations. Elevated lactate levels were a risk factor for mortality. CONCLUSION: The pSOFA and PELOD2 scores had superior predictive performance for mortality. Given the relative unavailability of items and clinical operability, the pSOFA score should be recommended as an optimal tool for acute organ dysfunction in pediatric sepsis patients. Elevated lactate levels are related to a greater risk of death from infection in children in the PICU.

Organ Involvement Related to Death in Critically Ill Patients With Leptospirosis: Unsupervised Analysis in a French West Indies ICU.

OBJECTIVES: To identify distinct phenotypes of critically ill leptospirosis patients upon ICU admission and their potential associations with outcome. DESIGN: Retrospective observational study including all patients with biologically confirmed leptospirosis admitted to the ICU between January 2014 and December 2022. Subgroups of patients with similar clinical profiles were identified by unsupervised clustering (factor analysis for mixed data and hierarchical clustering on principal components). SETTING: All patients admitted to the ICU of the University Hospital of Guadeloupe on the study period. PATIENTS: One hundred thirty critically ill patients with confirmed leptospirosis were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At ICU admission, 34% of the patients had acute respiratory failure, and 26% required invasive mechanical ventilation. Shock was observed in 52% of patients, myocarditis in 41%, and neurological involvement in 20%. Unsupervised clustering identified three clusters-"Weil's Disease" (48%), "neurological leptospirosis" (20%), and "multiple organ failure" (32%)-with different ICU courses and outcomes. Myocarditis and neurological involvement were key components for cluster identification and were significantly associated with death in ICU. Other factors associated with mortality included shock, acute respiratory failure, and requiring renal replacement therapy. CONCLUSIONS AND RELEVANCE: Unsupervised analysis of critically ill patients with leptospirosis revealed three patient clusters with distinct phenotypic characteristics and clinical outcomes. These patients should be carefully screened for neurological involvement and myocarditis at ICU admission.

The effect of high-dose selenium on mortality and postoperative organ dysfunction in post-cardiotomy cardiogenic shock patients supported with mechanical circulatory support - A post-hoc analysis of the SUSTAIN CSX trial.

PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.

Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery.

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12-48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.

Trends in the Utilization of Multiorgan Support Among Adults Undergoing High-risk Cardiac Surgery in the United States.

OBJECTIVES: To examine trends in the prevalence of multiorgan dysfunction (MODS), utilization of multi-organ support (MOS), and mortality among patients undergoing cardiac surgery with MODS who received MOS in the United States. DESIGN: Retrospective cohort study. SETTING: 183 hospitals in the Premier Healthcare Database. PARTICIPANTS: Adults ≥18 years old undergoing high-risk elective or non-elective cardiac surgery. INTERVENTIONS: none. MEASUREMENTS AND MAIN RESULTS: The exposure was time (consecutive calendar quarters) January 2008 and June 2018. We analyzed hospital data using day-stamped hospital billing codes and diagnosis and procedure codes to assess MODS prevalence, MOS utilization, and mortality. Among 129,102 elective and 136,190 non-elective high-risk cardiac surgical cases across 183 hospitals, 10,001 (7.7%) and 21,556 (15.8%) of patients developed MODS, respectively. Among patients who experienced MODS, 2,181 (22%) of elective and 5,425 (25%) of non-elective cardiac surgical cases utilized MOS. From 2008-2018, MODS increased in both high-risk elective and non-elective cardiac surgical cases. Similarly, MOS increased in both high-risk elective and non-elective cardiac surgical cases. As a component of MOS, mechanical circulatory support (MCS) increased over time. Over the study period, risk-adjusted mortality, in patients who developed MODS receiving MOS, increased in high-risk non-elective cardiac surgery and decreased in high-risk elective cardiac surgery, despite increasing MODS prevalence and MOS utilization (p<0.001). CONCLUSIONS: Among patients undergoing high-risk cardiac surgery in the United States, MODS prevalence and MOS utilization (including MCS) increased over time. Risk-adjusted mortality trends differed in elective and non-elective cardiac surgery. Further research is necessary to optimize outcomes among patients undergoing high-risk cardiac surgery.

Dapagliflozin for Critically Ill Patients With Acute Organ Dysfunction: The DEFENDER Randomized Clinical Trial.

Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

Clinical presentation and outcomes of patients with rhabdomyolysis: A tertiary care center experience.

OBJECTIVES: To evaluate the clinical and laboratory features, complications, and outcomes of patients with rhabdomyolysis in the Saudi population. METHODS: Retrospectives descriptive study of adult patients who presented to King Abdulaziz Medical City (KAMC) withrhabdomyolysis between January 2016 and December 2022. RESULTS: Most of the participants (84.5%) were male, with a median age of 41 years and a body mass index of 26.5 kg/m2. Medications, mainly statins (22.4%) and illicit drugs (15.5%), constituted the root causes of rhabdomyolysis in the cohort (44.8%). The most common presenting complaints were myalgia (63.8%) and fatigue (37.9%). More than one-third of the participants (32.8%) developed AKI, with 3 patients requiring temporary hemodialysis, and only 8.6% developed acute liver failure (ALF). Intensive care unit (ICU) admission was required for 10 patients (17.2%), and the overall mortality rate was 8.6%. Patients who developed complications (composite outcomes of AKI, ALF, multiorgan failure, or death) had significantly reduced kidney function and higher levels of blood urea nitrogen, anion gap, and uric acid upon admission than those who did not. CONCLUSION: This study offers a thorough understanding of clinical and laboratory features, causes, complications, and outcomes of rhabdomyolysis among Saudi patients. The insights gained enhance our understanding of rhabdomyolysis within this population, providing a foundation for future research and improvements in clinical management.

Disseminated intravascular coagulation is associated with poor prognosis in patients with COVID-19.

This study aimed to investigate the incidence and significance of disseminated intravascular coagulation (DIC) in coronavirus disease 2019 (COVID-19). A multicenter cohort study was conducted using large-scale COVID-19 registry data. The patients were classified into DIC and non-DIC groups based on the diagnosis on admission (day 1) and on any of the days 1, 4, 8, and 15. In total, 23,054 patients were divided into DIC (n = 264) and non-DIC (n = 22,790) groups on admission. Thereafter, 1654 patients were divided into 181 patients with DIC and 1473 non-DIC patients based on the DIC diagnosis on any of the days from 1 to 15. DIC incidence was 1.1% on admission, increasing to 10.9% by day 15. DIC diagnosis on admission had moderate predictive performance for developing multiple organ dysfunction syndrome (MODS) on day 4 and in-hospital death and was independently associated with MODS and in-hospital death. DIC diagnosis on any of the days from 1 to 15, especially days 8 and 15, was associated with lower survival probability than those without DIC and showed significant association with in-hospital death. In conclusion, despite its low incidence, DIC, particularly late-onset DIC, plays a significant role in the pathogenesis of poor prognosis in patients with COVID-19.

Soluble Neuropilin-1 Is Elevated in Sepsis and Correlates with Organ Dysfunction and Long-Term Mortality in Critical Illness.

Critical illness and sepsis may cause organ failure and are recognized as mortality drivers in hospitalized patients. Neuropilin-1 (NRP-1) is a multifaceted transmembrane protein involved in the primary immune response and is expressed in immune cells such as T and dendritic cells. The soluble form of NRP-1 (sNRP-1) acts as an antagonist to NRP-1 by scavenging its ligands. The aim of this study was to determine the value of sNRP-1 as a biomarker in critical illness and sepsis. We enrolled 180 critically ill patients admitted to a medical intensive care unit and measured serum sNRP-1 concentrations at admission, comparing them to 48 healthy individuals. Critically ill and septic patients showed higher levels of sNRP-1 compared to healthy controls (median of 2.47 vs. 1.70 nmol/L, p < 0.001). Moreover, sNRP-1 was also elevated in patients with sepsis compared to other critical illness (2.60 vs. 2.13 nmol/L, p = 0.01), irrespective of disease severity or organ failure. In critically ill patients, sNRP-1 is positively correlated with markers of kidney and hepatic dysfunction. Most notably, critically ill patients not surviving in the long term (one year after admission) showed higher concentrations of sNRP-1 at the time of ICU admission (p = 0.036), with this association being dependent on the presence of organ failure. Critically ill and septic patients exhibit higher serum concentrations of circulating sNRP-1, which correlates to organ failure, particularly hepatic and kidney dysfunction.

[Cause of Death after Severe Trauma: 30 Years Experience from TraumaRegister DGU]. / Woran stirbt der schwerverletzte Patient: eine Analyse aus 30 Jahren TraumaRegister DGU.

Every year, thousands of people in Germany succumb to severe injuries. But what causes the death of these patients? In addition to the trauma, pre-traumatic health status, age, and other influencing factors play a role in the outcome after trauma. This study aims to answer the question of what causes the death of a severely injured patient.For this publication, in addition to previously published results, we examined current data from patients in German hospitals from the years 2015-2022 (8 years) documented in the TraumaRegister DGU®. The feature "Presumed Cause of Death", introduced in 2015, was considered. Patients transferred out early (< 48 h) as well as patients with minor injuries were excluded from this analysis.The number of fatalities decreases over time and does not correspond to a traditionally postulated tri-modal mortality distribution. Instead, over time, the distribution of causes of death shows significant variation. In over half of the cases (54%), traumatic brain injury (TBI) was the presumed cause of death, followed by organ failure (24%) and haemorrhage (9%). TBI dominates, especially in the first week, haemorrhage in the first 24 h, and organ failure as a cause steadily increases over time.In summary, it can be observed that the risk of death due to trauma-related consequences is highest in the first minutes, hours, and days, decreasing steadily over time. Particularly, the extent of injuries, head injuries, and significant blood loss are early risk factors.

Therapeutic plasma exchange in critically ill children: A single center experience.

INTRODUCTION: Therapeutic plasma exchange (TPE) is used in a wide spectrum of diseases in critically ill pediatric patients. We aim to review the indications, complications, safety, and outcomes of critically ill children who received TPE. METHODS: All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 19 years (January 2013-January 2023) were evaluated retrospectively. A total of 154 patients underwent 486 TPE sessions. RESULTS: Median age was 6 years (2-12.5) and 35 children had a body weight of <10 kg (22.7%). Number of organ failure was 4 (2-6). Liver diseases were the most common indication for TPE (31.2%) followed by sepsis with multiorgan dysfunction syndrome (27.3%). Overall survival rate was 72.7%. The highest mortality was observed in hemophagocytic lymphohistiocytosis group. Non-survivors had significantly higher number of organ failure (p < 0.001), higher PRISM score (p < 0.001), and higher PELOD score on admission (p < 0.001). Adverse events were observed in 68 (13.9%) sessions. Hypotension (7.8%) and hypocalcemia (5.1%) were the most frequent adverse events. CONCLUSION: TPE is safe for critically ill pediatric patients with experienced staff. Survival rate may vary depending on the underlying disease. Survival decreases with the increase in the number of failed organs.

Automated Calculator for the Pediatric Sequential Organ Failure Assessment Score: Development and External Validation in a Single-Center 7-Year Cohort, 2015-2021.

OBJECTIVES: The pediatric Sequential Organ Failure Assessment (pSOFA) score summarizes severity of organ dysfunction and can be used to predict in-hospital mortality. Manual calculation of the pSOFA score is time-consuming and prone to human error. An automated method that is open-source, flexible, and scalable for calculating the pSOFA score directly from electronic health record data is desirable. DESIGN: Single-center, retrospective cohort study. SETTING: Quaternary 40-bed PICU. PATIENTS: All patients admitted to the PICU between 2015 and 2021 with ICU stay of at least 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used 77 records to evaluate the automated score. The automated algorithm had an overall accuracy of 97%. The algorithm calculated the respiratory component of two cases incorrectly. An expert human annotator had an initial accuracy of 75% at the patient level and 95% at the component level. An untrained human annotator with general clinical research experience had an overall accuracy of 16% and component-wise accuracy of 67%. Weighted kappa for agreement between the automated method and the expert annotator's initial score was 0.92 (95% CI, 0.88-0.95), and between the untrained human annotator and the automated score was 0.50 (95% CI, 0.36-0.61). Data from 9146 patients (in-hospital mortality 3.6%) were included to validate externally the discriminability of the automated pSOFA score. The admission-day pSOFA score had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77-0.82). CONCLUSIONS: The developed automated algorithm calculates pSOFA score with high accuracy and is more accurate than a trained expert rater and nontrained data abstracter. pSOFA's performance for predicting in-hospital mortality was lower in our cohort than it was for the originally derived score.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Modifiability of surgical timing in postinjury multiple organ failure patients.

BACKGROUND: Postinjury multiple organ failure (MOF) is the leading cause of late trauma deaths, with primarily non-modifiable risk factors. Timing of surgery as a potentially modifiable risk factor is frequently proposed, but has not been quantified. We aimed to compare mortality, hospital length of stay (LOS), and ICU LOS between MOF patients who had surgery that preceded MOF with modifiable timings versus those with non-modifiable timings. METHODS: Retrospective analysis of an ongoing 17-year prospective cohort study of ICU polytrauma patients at-risk of MOF. Among MOF patients (Denver score>3), we identified patients who had surgery that preceded MOF, determined whether the timing of these operation(s) were modifiable(M) or non-modifiable (non-M), and evaluated the change in physiological parameters as a result of surgery. RESULTS: Of 716 polytrauma patients at-risk of MOF, 205/716 (29%) developed MOF, and 161/205 (79%) had surgery during their ICU admission. Of the surgical MOF patients, 147/161 (91%) had one or more operation(s) that preceded MOF, and 65/161 (40%) of them had operation(s) with modifiable timings. There were no differences in age (mean (SD) 52 (19) vs 53 (21)years), injury severity score (median (IQR) 34 (26-41)vs34 (25-44)), admission physiological and resuscitation parameters, between M and non-M-patients. M patients had longer ICU LOS (median (IQR) 18 (12-28)versus 11 (8-16)days, p < 0.0001) than non-M-patients, without difference in mortality (14%vs16%, p = 0.7347), or hospital LOS (median (IQR) 32 (18-52)vs27 (17-47)days, p = 0.3418). M-patients had less fluids and transfusions intraoperatively. Surgery did not compromise patient physiology. CONCLUSION: Operations preceding MOF are common in polytrauma and seem to be safe in maintaining physiology. The margin for improvement from optimizing surgical timing is modest, contrary to historical assumptions.