Diagnostic and Prognostic Value of C1q in Sepsis-Induced Coagulopathy.

Early identification of biomarkers that can predict the onset of sepsis-induced coagulopathy (SIC) in septic patients is clinically important. This study endeavors to examine the diagnostic and prognostic utility of serum C1q in the context of SIC. Clinical data from 279 patients diagnosed with sepsis at the Departments of Intensive Care, Respiratory Intensive Care, and Infectious Diseases at the Renmin Hospital of Wuhan University were gathered spanning from January 2022 to January 2024. These patients were categorized into two groups: the SIC group comprising 108 cases and the non-SIC group consisting of 171 cases, based on the presence of SIC. Within the SIC group, patients were further subdivided into a survival group (43 cases) and non-survival group (65 cases). The concentration of serum C1q in the SIC group was significantly lower than that in the non-SIC group. Furthermore, A significant correlation was observed between serum C1q levels and both SIC score and coagulation indices. C1q demonstrated superior diagnostic and prognostic performance for SIC patients, as indicated by a higher area under the curve (AUC). Notably, when combined with CRP, PCT, and SOFA score, C1q displayed the most robust diagnostic efficacy for SIC. Moreover, the combination of C1q with the SOFA score heightened predictive value concerning the 28-day mortality of SIC patients.

Acute kidney injury in nonagenarians: clinical characteristics and mortality.

INTRODUCTION: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. METHODS: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85, p = 0.001) were associated with mortality. CONCLUSION: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

SOFA in sepsis: with or without GCS.

PURPOSE: Sepsis is a global public health burden. The sequential organ failure assessment (SOFA) is the most commonly used scoring system for diagnosing sepsis and assessing severity. Due to the widespread use of endotracheal intubation and sedative medications in sepsis, the accuracy of the Glasgow Coma Score (GCS) is the lowest in SOFA. We designed this multicenter, cross-sectional study to investigate the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis. METHODS: First, 3048 patients with sepsis admitted to Peking Union Medical College Hospital (PUMCH) were enrolled in this survey. The data were collected from June 8, 2013 to October 12, 2022. Second, 18,108 patients with sepsis in the eICU database were enrolled. Third, 2397 septic patients with respiratory system ≥ 3 points in SOFA in the eICU database were included. We investigated the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis in various ICUs of PUMCH, and then we validated the results in the eICU database. MAIN RESULTS: In data of ICUs in PUMCH, the predictive efficiency of SOFA without GCS (AUROC [95% CI], 24 h, 0.724 [0.688, 0.760], 48 h, 0.734 [0.699, 0.769], 72 h, 0.748 [0.713, 0.783], 168 h, 0.781 [0.747, 0.815]) was higher than that of SOFA with GCS (AUROC [95% CI], 24 h, 0.708 [0.672, 0.744], 48 h, 0.721 [0.685, 0.757], 72 h, 0.735 [0.700, 0.757], 168 h, 0.770 [0.736, 0.804]) on ICU mortality in patients with sepsis, and the difference was statistically significant (P value, 24 h, 0.001, 48 h, 0.003, 72 h, 0.004, 168 h, 0.005). In septic patients with respiratory system ≥ 3 points in SOFA in the eICU database, although the difference was not statistically significant (P value, 24 h, 0.148, 48 h, 0.178, 72 h, 0.132, 168 h, 0.790), SOFA without GCS (AUROC [95% CI], 24 h, 0.601 [0.576, 0.626], 48 h, 0.625 [0.601, 0.649], 72 h, 0.639 [0.615, 0.663], 168 h, 0.653 [0.629, 0.677]) had a higher predictive efficiency on ICU mortality than SOFA with GCS (AUROC [95% CI], 24 h, 0.591 [0.566, 0.616], 48 h, 0.616 [0.592, 0.640], 72 h, 0.628 [0.604, 0.652], 168 h, 0.651 [0.627, 0.675]). CONCLUSIONS: In severe sepsis, it is realistic and feasible to discontinue the routine GCS for SOFA in patients with a respiratory system ≥ 3 points, and even better predict ICU mortality.

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.

Prophylactic use of standardized extract of propolis of Apis mellifera (EPP-AF®) reduces lung inflammation and improves survival in experimental lethal sepsis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. OBJECTIVE: This study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). METHODS: Initially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. RESULTS: We show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. CONCLUSION: Thus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

Diastolic/systolic blood pressure ratio for predicting febrile children with sepsis and progress to septic shock in the emergency department.

OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.

The prognostic value of platelet aggregation in patients with sepsis.

BACKGROUND: This study aims to investigate the relevance of platelet aggregation markers, specifically arachidonic acid (AA) and adenosine diphosphate (ADP), in relation to the prognosis of sepsis patients. METHODS: A cohort of 40 sepsis patients was included and stratified, based on their 28-day post-treatment prognosis, into two groups: a survival group (n = 31) and a severe sepsis group (n = 9. Then, their various clinical parameters, including patient demographics, platelet counts (PLT), inflammatory markers, and platelet aggregation rates (PAR) induced by AA and ADP between the two groups, were compared. Long-term health implications of sepsis were assessed using the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score, and logistic regression analysis was conducted to evaluate the prognostic significance of PAR in sepsis patients. RESULTS: Patients with severe sepsis exhibited significantly elevated levels of procalcitonin (PCT), platelet adhesion rates, and PAR induced by ADP (P < 0.05), but having lower PLT (P < 0.05), compared to those in the survival group. Logistic regression analysis demonstrated that PAR induced by ADP was a protective factor in predicting prognosis in sepsis patients (P < 0.01). CONCLUSIONS: Activation of platelets in sepsis intensifies inflammatory response. Patients with sepsis whose ADP-induced PAR was < 60% displayed significant impairment in platelet aggregation function, and had higher mortality rate. Monitoring ADP-induced PAR is crucial for management of sepsis.

Association between the stress hyperglycemia ratio and 28-day all-cause mortality in critically ill patients with sepsis: a retrospective cohort study and predictive model establishment based on machine learning.

BACKGROUND: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. METHODS: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. RESULTS: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322). CONCLUSION: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis.

Cell-free DNA in patients with sepsis: long term trajectory and association with 28-day mortality and sepsis-associated acute kidney injury.

Introduction: Outcome-prediction in patients with sepsis is challenging and currently relies on the serial measurement of many parameters. Standard diagnostic tools, such as serum creatinine (SCr), lack sensitivity and specificity for acute kidney injury (AKI). Circulating cell-free DNA (cfDNA), which can be obtained from liquid biopsies, can potentially contribute to the quantification of tissue damage and the prediction of sepsis mortality and sepsis-associated AKI (SA-AKI). Methods: We investigated the clinical significance of cfDNA levels as a predictor of 28-day mortality, the occurrence of SA-AKI and the initiation of renal replacement therapy (RRT) in patients with sepsis. Furthermore, we investigated the long-term course of cfDNA levels in sepsis survivors at 6 and 12 months after sepsis onset. Specifically, we measured mitochondrial DNA (mitochondrially encoded NADH-ubiquinone oxidoreductase chain 1, mt-ND1, and mitochondrially encoded cytochrome C oxidase subunit III, mt-CO3) and nuclear DNA (nuclear ribosomal protein S18, n-Rps18) in 81 healthy controls and all available samples of 150 intensive care unit patients with sepsis obtained at 3 ± 1 days, 7 ± 1 days, 6 ± 2 months and 12 ± 2 months after sepsis onset. Results: Our analysis revealed that, at day 3, patients with sepsis had elevated levels of cfDNA (mt-ND1, and n-Rps18, all p<0.001) which decreased after the acute phase of sepsis. 28-day non-survivors of sepsis (16%) had higher levels of cfDNA (all p<0.05) compared with 28-day survivors (84%). Patients with SA-AKI had higher levels of cfDNA compared to patients without AKI (all p<0.05). Cell-free DNA was also significantly increased in patients requiring RRT (all p<0.05). All parameters improved the AUC for SCr in predicting RRT (AUC=0.88) as well as APACHE II in predicting mortality (AUC=0.86). Conclusion: In summary, cfDNA could potentially improve risk prediction models for mortality, SA-AKI and RRT in patients with sepsis. The predictive value of cfDNA, even with a single measurement at the onset of sepsis, could offer a significant advantage over conventional diagnostic methods that require repeated measurements or a baseline value for risk assessment. Considering that our data show that cfDNA levels decrease after the first insult, future studies could investigate cfDNA as a "memoryless" marker and thus bring further innovation to the complex field of SA-AKI diagnostics.

Identifying depression's genetic role as a precursor to sepsis and increased mortality risk: Comprehensive insights from mendelian randomization analysis.

BACKGROUND: Previous retrospective studies have shown a correlation between depression and increased risk of infections, including a moderate rise in sepsis likelihood associated with severe depression and anxiety. To investigate the potential causal links between depression, sepsis, and mortality risks, while considering confounding factors, we employed a Mendelian randomization (MR) approach. METHODS: In this two-sample Mendelian randomization study, we analyzed data from a large-scale genome-wide association study on depression, involving 807,553 European individuals (246,363 cases, 561,190 controls). We extracted SNP associations with sepsis and 28-day mortality from UK Biobank GWAS outcomes. The correlation analysis primarily employed the inverse-variance weighted method, supplemented by sensitivity analyses for heterogeneity and pleiotropy assessment. RESULTS: Our analysis revealed a potential causal link between depression and an increased risk of sepsis (OR = 1.246, 95% CI: 1.076-1.442, P = 0.003), but no causal association was found with sepsis-induced mortality risk (OR = 1.274, 95% CI: 0.891-1.823, P = 0.184). Sensitivity analyses confirmed the robustness of these findings. CONCLUSIONS: We identified a potential causal association between depression and heightened sepsis risk, while no link was found with sepsis-induced mortality. These findings suggest that effective management of depression could be important in preventing sepsis.

Mendelian randomization analysis reveals causal associations of serum metabolites with sepsis and 28-day mortality.

Metabolic disorder has been found to be an important factor in the pathogenesis and progression of sepsis. However, the causation of such an association between serum metabolites and sepsis has not been established. We conducted a two-sample Mendelian randomization (MR) study. A genome-wide association study of 486 human serum metabolites was used as the exposure, whereas sepsis and sepsis mortality within 28 days were set as the outcomes. In MR analysis, 6 serum metabolites were identified to be associated with an increased risk of sepsis, and 6 serum metabolites were found to be related to a reduced risk of sepsis. Furthermore, there were 9 metabolites positively associated with sepsis-related mortality, and 8 metabolites were negatively correlated with sepsis mortality. In addition, "glycolysis/gluconeogenesis" (p = 0.001), and "pyruvate metabolism" (p = 0.042) two metabolic pathways were associated with the incidence of sepsis. This MR study suggested that serum metabolites played significant roles in the pathogenesis of sepsis, which may provide helpful biomarkers for early disease diagnosis, therapeutic interventions, and prognostic assessments for sepsis.

Construction and evaluation of short-term and long-term mortality risk prediction model for patients with sepsis based on MIMIC-IV database. / 基于MIMIC-IVæž„å»ºåŠè¯„ä¼°è„“æ¯’ç—‡æ‚£è€ è¿‘æœŸå’Œè¿œæœŸæ­»äº¡é£Žé™©é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: Given the high incidence and mortality rate of sepsis, early identification of high-risk patients and timely intervention are crucial. However, existing mortality risk prediction models still have shortcomings in terms of operation, applicability, and evaluation on long-term prognosis. This study aims to investigate the risk factors for death in patients with sepsis, and to construct the prediction model of short-term and long-term mortality risk. METHODS: Patients meeting sepsis 3.0 diagnostic criteria were selected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and randomly divided into a modeling group and a validation group at a ratio of 7꞉3. Baseline data of patients were analyzed. Univariate Cox regression analysis and full subset regression were used to determine the risk factors of death in patients with sepsis and to screen out the variables to construct the prediction model. The time-dependent area under the curve (AUC), calibration curve, and decision curve were used to evaluate the differentiation, calibration, and clinical practicability of the model. RESULTS: A total of 14 240 patients with sepsis were included in our study. The 28-day and 1-year mortality were 21.45% (3 054 cases) and 36.50% (5 198 cases), respectively. Advanced age, female, high sepsis-related organ failure assessment (SOFA) score, high simplified acute physiology score II (SAPS II), rapid heart rate, rapid respiratory rate, septic shock, congestive heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, diabetes, malignant tumor, high white blood cell count (WBC), long prothrombin time (PT), and high serum creatinine (SCr) levels were all risk factors for sepsis death (all P<0.05). Eight variables, including PT, respiratory rate, body temperature, malignant tumor, liver disease, septic shock, SAPS II, and age were used to construct the model. The AUCs for 28-day and 1-year survival were 0.717 (95% CI 0.710 to 0.724) and 0.716 (95% CI 0.707 to 0.725), respectively. The calibration curve and decision curve showed that the model had good calibration degree and clinical application value. CONCLUSIONS: The short-term and long-term mortality risk prediction models of patients with sepsis based on the MIMIC-IV database have good recognition ability and certain clinical reference significance for prognostic risk assessment and intervention treatment of patients.

Sepsis mortality among patients with haematological malignancy admitted to intensive care 2000-2022: a binational cohort study.

BACKGROUND: Sepsis occurs in 12-27% of patients with haematological malignancy within a year of diagnosis. Sepsis mortality has improved in non-cancer patients in the last two decades, but longitudinal trends in patients with haematological malignancy are not well characterised. We aimed to compare outcomes, including temporal changes, in patients with and without a haematological malignancy admitted to ICU with a primary diagnosis of sepsis in Australia and New Zealand over the past two decades. METHODS: We performed a retrospective cohort study of 282,627 patients with a primary intensive care unit (ICU) admission diagnosis of sepsis including 17,313 patients with haematological malignancy, admitted to 216 intensive care units (ICUs) in Australia or New Zealand between January 2000 and December 2022. Annual crude and adjusted in-hospital mortality were reported. Risk factors for in-hospital mortality were determined using a mixed methods logistic regression model and were used to calculate annual changes in mortality. RESULTS: In-hospital sepsis mortality decreased in patients with haematological malignancy, from 55.6% (95% CI 46.5-64.6%) in 2000 to 23.1% (95% CI 20.8-25.5%) in 2021. In patients without haematological malignancy mortality decreased from 33.1% (95% CI 31.3-35.1%) to 14.4% (95% CI 13.8-14.8%). This decrease remained significant after adjusting for mortality predictors including age, SOFA score and comorbidities, as estimated by adjusted annual odds of in-hospital death. The reduction in odds of death was of greater magnitude in patients with haematological malignancy than those without (OR 0.954, 95% CI 0.947-0.961 vs. OR 0.968, 95% CI 0.966-0.971, p < 0.001). However, absolute risk of in-hospital mortality remained higher in patients with haematological malignancy. Older age, higher SOFA score, presence of comorbidities, and mechanical ventilation were associated with increased mortality. Leukopenia (white cell count < 1.0 × 109 cells/L) was not associated with increased mortality in patients with haematological malignancy (p = 0.60). CONCLUSIONS: Sepsis mortality has improved in patients with haematological malignancy admitted to ICU. However, mortality remains higher in patients with haematological malignancy than those without.

Urosepsis 30-day mortality, morbidity, and their risk factors: SERPENS study, a prospective, observational multi-center study.

PURPOSE: To provide a descriptive report of mortality and morbidity in the first 30 days of diagnosis of urosepsis. Secondary aim is to identify risk factors of unfavourable outcomes. METHODS: Prospective observational multicentre cohort study conducted from September 2014 to November 2018 in European hospitals. Adult patients (≥ 18 years) diagnosed with acute urosepsis according to Sepsis-2 criteria with confirmed microbiological infection were included. Outcomes were classified in one of four health states: death, multiple organ failure, single organ failure, and recovery at day 30 from onset of urosepsis. Descriptive statistics and ordinal logistic regression analysis was performed. RESULTS: Three hundred and fifty four patients were recruited, and 30-day mortality rate was 2.8%, rising to 4.6% for severe sepsis. All patients who died had a SOFA score of ≥ 2 at diagnosis. Upon initial diagnosis, 79% (n = 281) of patients presented with OF. Within 30 days, an additional 5% developed OF, resulting in a total of 84% affected. Charlson score (OR 1.14 CI 1.01-1.28), patients with respiratory failure at baseline (OR 2.35, CI 1.32-4.21), ICU admission within the past 12 months (OR 2.05, CI 1.00-4.19), obstruction causative of urosepsis (OR 1.76, CI 1.02-3.05), urosepsis with multi-drug-resistant(MDR) pathogens (OR 2.01, CI 1.15-3.53), and SOFA baseline score ≥ 2 (OR 2.74, CI 1.49-5.07) are significantly associated with day 30 outcomes (OF and death). CONCLUSIONS: Impact of comorbidities and MDR pathogens on outcomes highlights the existence of a distinct group of patients who are prone to mortality and morbidity. These findings underscore the need for the development of pragmatic classifications to better assess the severity of UTIs and guide management strategies. STUDY REGISTRATION: Clinicaltrials.gov registration number NCT02380170.

Causes and attributable fraction of death from ARDS in inflammatory phenotypes of sepsis.

BACKGROUND: Hypoinflammatory and hyperinflammatory phenotypes have been identified in both Acute Respiratory Distress Syndrome (ARDS) and sepsis. Attributable mortality of ARDS in each phenotype of sepsis is yet to be determined. We aimed to estimate the population attributable fraction of death from ARDS (PAFARDS) in hypoinflammatory and hyperinflammatory sepsis, and to determine the primary cause of death within each phenotype. METHODS: We studied 1737 patients with sepsis from two prospective cohorts. Patients were previously assigned to the hyperinflammatory or hypoinflammatory phenotype using latent class analysis. The PAFARDS in patients with sepsis was estimated separately in the hypo and hyperinflammatory phenotypes. Organ dysfunction, severe comorbidities, and withdrawal of life support were abstracted from the medical record in a subset of patients from the EARLI cohort who died (n = 130/179). Primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: The PAFARDS was 19% (95%CI 10,28%) in hypoinflammatory sepsis and, 14% (95%CI 6,20%) in hyperinflammatory sepsis. Cause of death differed between the two phenotypes (p < 0.001). Respiratory failure was the most common cause of death in hypoinflammatory sepsis, whereas circulatory shock was the most common cause in hyperinflammatory sepsis. Death with severe underlying comorbidities was more frequent in hypoinflammatory sepsis (81% vs. 67%, p = 0.004). CONCLUSIONS: The PAFARDS is modest in both phenotypes whereas primary cause of death among patients with sepsis differed substantially by phenotype. This study identifies challenges in powering future clinical trials to detect changes in mortality outcomes among patients with sepsis and ARDS.

Lactate dynamics in paediatric patients with severe sepsis: insights from a prospective cohort study.

BACKGROUND: Sepsis is an infection-related systemic inflammatory response that often leads to elevated lactate levels. Monitoring lactate levels during severe sepsis is vital for influencing clinical outcomes. The aim of this study was to assess the association between plasma lactate levels and mortality in children with severe sepsis or septic shock. METHODS: The current prospective study was conducted in the PICU of University Children's Hospital. The International Paediatric Sepsis Consensus Conference criteria for Definitions of Sepsis and Organ Failure in 2005 were used to diagnose patients with sepsis. We measured plasma lactate levels upon admission (Lac H0) and 6 h later (Lac H6). The static indices included the absolute lactate values (Lac H0 and Lac H6), while the dynamic indices included the delta-lactate level (ΔLac) and the 6-hour lactate clearance. The 6-hour lactate clearance was calculated using the following formula: [(Lac H0-Lac H6)100/Lac H0]. ΔLac was calculated as the difference between the Lac H0 and Lac H6 levels. Patient survival or death after a PICU stay was the primary outcome. RESULTS: A total of 46 patients were included in this study: 25 had septic shock, and 21 had severe sepsis. The mortality rate was 54.3%. The Lac H0 did not significantly differ between survivors and nonsurvivors. In contrast, the survivors had significantly lower Lac H6 levels, higher ΔLac levels, and higher 6-hour lactate clearance rates than nonsurvivors. Lactate clearance rates below 10%, 20%, and 30% were significantly associated with mortality. The best cut-off values for the lactate clearance rate and Lac H6 for the prediction of mortality in the PICU were < 10% and ≥ 4 mmol/L, respectively. Patients with higher Lac H6 levels and lower lactate clearance rates had significantly higher PICU mortality based on Kaplan-Meier survival curve analysis. CONCLUSIONS: This study highlights the significance of lactate level trends over time for the prediction of mortality in the PICU in patients with severe sepsis or septic shock. Elevated lactate levels and decreased lactate clearance six hours after hospitalisation are associated with a higher mortality rate.

Positive pathogens in stool could predict the clinical outcomes of sepsis-associated acute kidney injury in critical ill patient.

In this study, we sought to evaluate the influence of positive pathogens in stool (PPS) on clinical outcomes in critical ill patients with Sepsis-associated acute kidney injury (S-AKI) from intensive care unit. Our sample consisted of 7338 patients, of whom 752 (10.25%) had PPS. We found that the presence of Clostridium difficile (C. difficile) and protists in stool samples was correlated with survival during hospitalization, as well as 30-day and 90-day survival. Interestingly, there was no significant difference in overall survival and 30-day in-hospital survival between the PPS group and the negative pathogens in stool (NPS) control group. However, the cumulative incidence of 90-day infection-related mortality was significantly higher in the PPS group (53 vs. 48%, P = 0.022), particularly in patients with C. difficile in their stool specimens. After adjusting for propensity scores, the results also have statistical significance. These findings suggest that PPS may affect the 90-days survival outcomes of S-AKI, particularly in patients with C. difficile and protists in their stool samples. Further research is warranted to further explore these associations.

Blood calprotectin as a biomarker for infection and sepsis - the prospective CASCADE trial.

BACKGROUND: Early in the host-response to infection, neutrophils release calprotectin, triggering several immune signalling cascades. In acute infection management, identifying infected patients and stratifying these by risk of deterioration into sepsis, are crucial tasks. Recruiting a heterogenous population of patients with suspected infections from the emergency department, early in the care-path, the CASCADE trial aimed to evaluate the accuracy of blood calprotectin for detecting bacterial infections, estimating disease severity, and predicting clinical deterioration. METHODS: In a prospective, observational trial from February 2021 to August 2022, 395 patients (n = 194 clinically suspected infection; n = 201 controls) were enrolled. Blood samples were collected at enrolment. The accuracy of calprotectin to identify bacterial infections, and to predict and identify sepsis and mortality was analysed. These endpoints were determined by a panel of experts. RESULTS: The Area Under the Receiver Operating Characteristic (AUROC) of calprotectin for detecting bacterial infections was 0.90. For sepsis within 72 h, calprotectin's AUROC was 0.83. For 30-day mortality it was 0.78. In patients with diabetes, calprotectin had an AUROC of 0.94 for identifying bacterial infection. CONCLUSIONS: Calprotectin showed notable accuracy for all endpoints. Using calprotectin in the emergency department could improve diagnosis and management of severe infections, in combination with current biomarkers. CLINICAL TRIAL REGISTRATION NUMBER: DRKS00020521.

Effect of Intravenous Push and Piggyback Administration of Ceftriaxone on Mortality in Sepsis.

BACKGROUND: There is a lack of evidence-based guidelines for the administration methods of ceftriaxone in emergency departments (EDs), resulting in the reliance on individual institutional protocols for decision-making. OBJECTIVE: This study was performed to compare the effects of administering ceftriaxone via intravenous push (IVP) and intravenous piggyback (IVPB) on 28-day mortality in patients with sepsis. METHODS: This was a retrospective study of patients aged 18 years or older with sepsis or septic shock who visited an ED and were treated with ceftriaxone as an initial antibiotic between March 2010 and February 2019. Patients were divided into the IVP group and the IVPB group based on the administration method. The primary outcome was 28-day mortality, and multivariable Cox proportional hazards regression analysis was performed to evaluate the relationship between antibiotic administration methods and 28-day mortality. RESULTS: During the study period, a total of 939 patients were included in the final analysis, and the overall mortality rate was 12.2%. The antibiotic administration time was significantly lower in the IVP group than in the IVPB group, and the rates of antibiotic administration within 1 h and within 3 h were higher in the IVP group than in the IVPB group (p < 0.05). However, there was no significant difference in 28-day mortality between the two groups (hazard ratio 1.07, 95% confidence interval 0.69-1.65). CONCLUSIONS: IVP administration of ceftriaxone reduced the time of antibiotic administration compared with IVPB, but there was no difference in 28-day mortality.

[Predictive value of left ventricular global longitudinal peak strain for the prognosis of septic patients].

OBJECTIVE: To investigate the predictive value of left ventricular global longitudinal peak strain (GLPS) for the prognosis of septic patients. METHODS: A prospective cohort study was conducted. Patients diagnosed with sepsis and admitted to the intensive care unit (ICU) of the First Affiliated Hospital, Sun Yat-sen University from December 2018 to November 2019 were enrolled. The patient characteristics, cardiac ultrasound parameters [left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), four-dimensional ejection fraction (4DEF), GLPS] and cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT)] within 24 hours of ICU admission, organ support therapies, severity of illness, and prognostic indicators were documented. The differences in clinical parameters between patients with varying outcomes during ICU hospitalization were assessed. Pearson correlation analysis was employed to explore the correlation between GLPS and other cardiac systolic parameters, as well as the associations between various cardiac systolic parameters and sequential organ failure assessment (SOFA) score. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive capacity of cardiac ultrasound parameters and cardiac biomarkers for death during ICU hospitalization in septic patients. RESULTS: A total of 50 septic patients were enrolled, with 40 surviving and 10 dying during ICU hospitalization, resulting in a mortality of 20.0%. All patients in the death group were male. Compared with the survival group, the patients in the death group were older, had a higher prevalence of diabetes mellitus, and received continuous renal replacement therapy (CRRT) more frequently, additionally, they exhibited more severe illness and had longer length of ICU stay. The levels of GLPS and cTnT in the death group were significantly elevated as compared with the survival group [GLPS: -7.1% (-8.5%, -7.0%) vs. -12.1% (-15.5%, -10.4%), cTnT (µg/L): 0.07 (0.05, 0.08) vs. 0.03 (0.02, 0.13), both P < 0.05]. However, no statistically significant difference was found in other cardiac ultrasound parameters or cardiac biomarkers between the two groups. Pearson correlation analysis revealed a negative correlation between GLPS and LVEF (r = -0.377, P = 0.014) and 4DEF (r = -0.697, P = 0.000), while no correlation was found with RVEF (r = -0.451, P = 0.069). GLPS demonstrated a positive correlation with SOFA score (r = 0.306, P = 0.033), while LVEF (r = 0.112, P = 0.481), RVEF (r = -0.134, P = 0.595), and 4DEF (r = -0.251, P = 0.259) showed no significant correlation with SOFA score. ROC curve analysis indicated that the area under the ROC curve (AUC) of GLPS for predicting death during ICU hospitalization in septic patients was higher than other cardiac systolic parameters, including LVEF, RVEF, and 4DEF, as well as cardiac biomarkers NT-proBNP and cTnT (0.737 vs. 0.628, 0.556, 0.659, 0.580 and 0.724). With an optimal cut-off value of -14.9% for GLPS, the sensitivity and negative predictive value reached to 100%. CONCLUSIONS: GLPS < -14.9% within 24 hours of ICU admission in septic patients indicated a reduced risk of death risk during ICU hospitalization, while also correlating with the severity of organ dysfunction in this patient population.