Prognostic and diagnostic utility of pancreatic stone protein in pediatric sepsis and mortality.

Background/aim: Early detection and prognosis of sepsis in critically ill children is crucial. The aim of this research was to investigate the prognostic ability of pancreatic stone protein (PSP) in validating sepsis and predicting mortality in a prospective observational study. Materials and methods: In a single-center study, pediatric intensive care unit patients were divided into cohorts of confirmed and suspected sepsis, as well as survivors and nonsurvivors. Patients with positive blood culture growth were considered to have confirmed sepsis, while their negative counterparts were considered to have suspected sepsis. Comparisons were made between complete blood counts, laboratory parameters, mortality indices, and C-reactive protein (CRP), procalcitonin (PCT), and PSP levels. The correlations between PSP and alternative inflammatory markers and mortality indices were then analyzed. The diagnostic and prognostic applicability of PSP for sepsis confirmation and mortality prediction was assessed using receiver operating characteristic curve analysis. Results: PSP levels were significantly elevated in patients with confirmed sepsis and within the nonsurvivor segment. In confirming sepsis and predicting mortality, PSP outperformed CRP and PCT in terms of sensitivity. It had sensitivity of 95% in diagnosing sepsis at a cut-off level of 50 ng/L, with an area under the curve (AUC) of 0.67 (95% CI: 0.52-0.81), and sensitivity of 92% in predicting mortality, with an AUC of 0.71 (95% CI: 0.56-0.83). In addition, PSP showed significant correlations with CRP, PCT, and mortality scores. Conclusion: PSP is emerging as a highly sensitive marker for confirming sepsis and predicting mortality in critically ill pediatric patients. Incorporating the PSP biomarker into routine clinical practice could potentially improve the management of pediatric sepsis.

Contributions of individual qSOFA elements to assessment of severity and for prediction of mortality.

BACKGROUND: The quick sequential [sepsis-related] organ failure assessment (qSOFA) acts as a prompt to consider possible sepsis. The contributions of individual qSOFA elements to assessment of severity and for prediction of mortality remain unknown. METHODS: A total of 3974 patients with community-acquired pneumonia were recruited to an observational prospective cohort study. The area under the receiver operating characteristic curve (AUROC), odds ratio, relative risk and Youden's index were employed to assess discrimination. RESULTS: Respiratory rate ≥22/min demonstrated the most superior diagnostic value, indicated by largest odds ratio, relative risk and AUROC, and maximum Youden's index for mortality. However, the indices for altered mentation and systolic blood pressure (SBP) ≤100 mm Hg decreased notably in turn. The predictive validities of respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg were good, adequate and poor for mortality, indicated by AUROC (0.837, 0.734 and 0.671, respectively). Respiratory rate ≥22/min showed the strongest associations with SOFA scores, pneumonia severity index, hospital length of stay and costs. However, SBP ≤100 mm Hg was most weakly correlated with the indices. CONCLUSIONS: Respiratory rate ≥22/min made the greatest contribution to parsimonious qSOFA to assess severity and predict mortality. However, the contributions of altered mentation and SBP ≤100 mm Hg decreased strikingly in turn. It is the first known prospective evidence of the contributions of individual qSOFA elements to assessment of severity and for prediction of mortality, which might have implications for more accurate clinical triage decisions.

Respiratory rate ≥22/min demonstrated the most superior diagnostic value.Respiratory rate ≥22/min showed the strongest association with severity.Respiratory rate ≥22/min, altered mentation and SBP ≤100 mm Hg predicted mortality well, adequately and poorly, respectively.

Increased serum albumin corrected anion gap levels are associated with poor prognosis in septic patients with liver cirrhosis.

The prognosis of septic patients with cirrhosis is worse compared to septic patients without cirrhosis. Early and accurate prognosis determination in patients with cirrhosis and sepsis is pivotal for guiding treatment decisions. The aim of this study was to investigate the association between albumin-corrected anion gap (ACAG) and clinical prognosis of patients with sepsis and cirrhosis. This study extracted data of patients with sepsis and cirrhosis from the Medical Information Mart for Intensive Care (MIMIC-IV) database. A total of 1340 patients (64.6% male) were enrolled. After confounders adjusting, elevated ACAG had a significant association with 28-day mortality (HR1.604; 95% CI 1.258-2.048; P < 0.001). Restricted cubic spline revealed that a linear relationship between ACAG and 28-day mortality (P-nonlinear = 0.089, P-overall = 0.001). According to the ROC curve analysis, the ACAG demonstrated a higher area under the curve (AUC) of 0.703 compared to AG (0.675). Kaplan-Meier analysis revealed higher 28-day mortality in high ACAG group (log-rank test, χ^2 = 175.638, P < 0.001). Furthermore, subgroup analysis showed a significant interaction between ACAG and etiology of cirrhosis (P for interaction = 0.014). Therefore, ACAG could provide clinicians with valuable insights for guiding interventions in this high-risk population.

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.

Machine learning-based prognostic model for 30-day mortality prediction in Sepsis-3.

BACKGROUND: Sepsis poses a critical threat to hospitalized patients, particularly those in the Intensive Care Unit (ICU). Rapid identification of Sepsis is crucial for improving survival rates. Machine learning techniques offer advantages over traditional methods for predicting outcomes. This study aimed to develop a prognostic model using a Stacking-based Meta-Classifier to predict 30-day mortality risks in Sepsis-3 patients from the MIMIC-III database. METHODS: A cohort of 4,240 Sepsis-3 patients was analyzed, with 783 experiencing 30-day mortality and 3,457 surviving. Fifteen biomarkers were selected using feature ranking methods, including Extreme Gradient Boosting (XGBoost), Random Forest, and Extra Tree, and the Logistic Regression (LR) model was used to assess their individual predictability with a fivefold cross-validation approach for the validation of the prediction. The dataset was balanced using the SMOTE-TOMEK LINK technique, and a stacking-based meta-classifier was used for 30-day mortality prediction. The SHapley Additive explanations analysis was performed to explain the model's prediction. RESULTS: Using the LR classifier, the model achieved an area under the curve or AUC score of 0.99. A nomogram provided clinical insights into the biomarkers' significance. The stacked meta-learner, LR classifier exhibited the best performance with 95.52% accuracy, 95.79% precision, 95.52% recall, 93.65% specificity, and a 95.60% F1-score. CONCLUSIONS: In conjunction with the nomogram, the proposed stacking classifier model effectively predicted 30-day mortality in Sepsis patients. This approach holds promise for early intervention and improved outcomes in treating Sepsis cases.

Impact of the timing of invasive mechanical ventilation in patients with sepsis: a multicenter cohort study.

BACKGROUND: The potential adverse effects associated with invasive mechanical ventilation (MV) can lead to delayed decisions on starting MV. We aimed to explore the association between the timing of MV and the clinical outcomes in patients with sepsis ventilated in intensive care unit (ICU). METHODS: We analyzed data of adult patients with sepsis between September 2019 and December 2021. Data was collected through the Korean Sepsis Alliance from 20 hospitals in Korea. Patients who were admitted to ICU and received MV were included in the study. Patients were divided into 'early MV' and 'delayed MV' groups based on whether they were on MV on the first day of ICU admission or later. Propensity score matching was applied, and patients in the two groups were compared on a 1:1 ratio to overcome bias between the groups. Outcomes including ICU mortality, hospital mortality, length of hospital and ICU stay, and organ failure at ICU discharge were compared. RESULTS: Out of 2440 patients on MV during ICU stay, 2119 'early MV' and 321 'delayed MV' cases were analyzed. The propensity score matching identified 295 patients in each group with similar baseline characteristics. ICU mortality was lower in 'early MV' group than 'delayed MV' group (36.3% vs. 46.4%; odds ratio, 0.66; 95% confidence interval, 0.47-0.93; p = 0.015). 'Early MV' group had lower in-hospital mortality, shorter ICU stay, and required tracheostomy less frequently than 'delayed MV' group. Multivariable logistic regression model identified 'early MV' as associated with lower ICU mortality (odds ratio, 0.38; 95% confidence interval, 0.29-0.50; p < 0.001). CONCLUSION: In patients with sepsis ventilated in ICU, earlier start (first day of ICU admission) of MV may be associated with lower mortality.

Using weight loss to predict outcome and define a humane endpoint in preclinical sepsis studies.

Preclinical mouse models are critical for understanding the pathophysiological response to infections and developing treatment strategies for sepsis. In keeping with ethical values, researchers follow guidelines to minimize the suffering of the mice. Weight loss is a criteria used as a humane end point, but there is no official recommendation for a maximum weight loss leading to euthanasia. To evaluate whether the thresholds used in daily practice are optimal, we performed a comprehensive retrospective analysis of data generated over 10 years with > 2300 mice used in models of infection with Listeria monocytogenes, Streptococcus pneumoniae, Candida albicans and H1N1 influenza virus. Weight loss segregated mice that survived from those that did not. Statistical analyses revealed that lowering the weight loss thresholds used (none, 30% or 20%) would have increased mortality rates due to the sacrifice of mice that survived infections (p < 0.01-0.001). Power calculations showed high variability and reduction of power as weight loss thresholds approached 20% for S. pneumoniae and L. monocytogenes models. Hence, weight loss thresholds need to be adapted to each model of infection used in a laboratory. Overall, weight loss is a valuable predictor of mortality that contributes to the robustness of composite scores. To our knowledge, this is the most extensive study exploring the relationship between weight loss threshold and sepsis outcome. It underscores the importance of the infection-model-specific evaluation of weight loss for use in clinical scores defining humane endpoints to minimize mouse suffering without compromising statistical power and scientific objectives.

The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) Trial: A Trial Protocol.

Importance: Intravenous fluids are an essential part of treatment in sepsis, but there remains clinical equipoise on which type of crystalloid fluids to use in sepsis. A previously reported sepsis subphenotype (ie, group D) has demonstrated a substantial mortality benefit from balanced crystalloids compared with normal saline. Objective: To test the hypothesis that targeting balanced crystalloids to patients with group D sepsis through an electronic health record (EHR) alert will reduce 30-day inpatient mortality. Design, Setting, and Participants: The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) trial is a parallel-group, multihospital, single-blind, pragmatic randomized clinical trial to be conducted at 6 hospitals in the Emory Healthcare system. Patients with suspicion of group D infection in whom a clinician initiates an order for normal saline in the emergency department (ED) or intensive care unit (ICU) will be randomized to usual care and intervention arms. Intervention: An EHR alert that appears in the ED and ICUs to nudge clinicians to use balanced crystalloids instead of normal saline. Main Outcomes and Measures: The primary outcome is 30-day inpatient mortality. Secondary outcomes are ICU admission, in-hospital mortality, receipt of vasoactive drugs, receipt of new kidney replacement therapy, and receipt of mechanical ventilation (vasoactive drugs, kidney replacement therapy, and mechanical ventilation are counted if they occur after randomization and within the 30-day study period). Intention-to-treat analysis will be conducted. Discussion: The PRECISE trial may be one of the first precision medicine trials of crystalloid fluids in sepsis. Using routine vital signs (temperature, heart rate, respiratory rate, and blood pressure), available even in low-resource settings, a validated machine learning algorithm will prospectively identify and enroll patients with group D sepsis who may have a substantial mortality reduction from used of balanced crystalloids compared with normal saline. Results: On finalizing participant enrollment and analyzing the data, the study's findings will be shared with the public through publication in a peer-reviewed journal. Conclusions: With use of a validated machine learning algorithm, precision resuscitation in sepsis could fundamentally redefine international standards for intravenous fluid resuscitation. Trial Registration: ClinicalTrials.gov Identifier: NCT06253585.

Comparing the Predictive Value of SOFA and SIRS for Mortality in the Early Hours of Hospitalization of Sepsis Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Sepsis, a deadly infection causing organ failure and Systemic Inflammatory Response Syndrome (SIRS), is detected early in hospitalization using the SIRS criteria, while sequential organ failure (SOFA) assesses organ failure severity. A systematic review and meta-analysis was evaluated to investigate the predictive value of the SIRS criteria and the SOFA system for mortality in early hospitalization of sepsis patients. METHODS: Inclusion criteria were full reports in peer-reviewed journals with data on sepsis assessment using SOFA and SIRS, and their relationship with outcomes. For quality assessment, we considered study population, sepsis diagnosis criteria, and outcomes. The area under the curve (AUC) of these criteria was extracted for separate meta-analysis and forest plots. RESULTS: Twelve studies met the inclusion criteria. The studies included an average of 56.1% males and a mean age of 61.9 (±6.1) among 32,979 patients. The pooled AUC was 0.67 (95% CI: 0.60-0.73) for SIRS and 0.79 (95% CI: 0.73-0.84) for SOFA. Significant heterogeneity between studies was indicated by an I2 above 50%, leading to a meta-regression analysis. This analysis, with age and patient number as moderators, revealed age as the major cause of heterogeneity in comparing the predictive value of the SOFA score with SIRS regarding the in-hospital mortality of sepsis patients (P<0.05). CONCLUSION: The SOFA score outperformed the SIRS criteria in predicting mortality, emphasizing the need for a holistic approach that combines clinical judgment and other diagnostic tools for better patient management and outcomes.

In sepsis or septic shock, prolonged vs. intermittent infusion of ß-lactam antibiotics reduces mortality at 90 d.

SOURCE CITATION: Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs intermittent infusions of ß-lactam antibiotics in adults with sepsis or septic shock: a systematic review and meta-analysis. JAMA. 12 June 2024. [Epub ahead of print.] 38864162.

In sepsis, continuous and intermittent infusion of ß-lactam antibiotics did not differ for mortality at 90 d.

SOURCE CITATION: Dulhunty JM, Brett SJ, De Waele JJ, et al; BLING III Study Investigators. Continuous vs intermittent ß-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial. JAMA. 12 June 2024. [Epub ahead of print.] 38864155.

Endothelial glycocalyx degradation in critically ill foals.

BACKGROUND: Endothelial glycocalyx (EG) degradation occurs in septic humans and EG products can be used as biomarkers of endothelial injury. Information about EG biomarkers and their association with disease severity is lacking in hospitalized foals. OBJECTIVES: Measure serum syndecan-1 (SDC-1), heparan sulfate (HS), angiopoietin-2 (ANG-2), aldosterone (ALD), and plasma atrial natriuretic peptide (ANP) concentrations and to determine their association with disease severity and death in hospitalized foals. ANIMALS: Ninety foals ≤3 days old. METHODS: Prospective, multicenter, longitudinal study. Foals were categorized into hospitalized (n = 74; 55 septic; 19 sick nonseptic) and 16 healthy foals. Serum ([SDC-1], [HS], [ANG-2], [ALD]) and plasma (ANP) were measured over 72 hours using immunoassays. RESULTS: Serum ([SDC-1], [HS], [ANG-2], [ALD]) and plasma (ANP) were significantly higher in hospitalized and septic than healthy foals (P < .05). Serum (ANG-2) and plasma (ANP) were significantly higher in hospitalized nonsurvivors than in survivors (P < .05). On admission, hospitalized foals with serum (HS) > 58.7 ng/mL had higher odds of nonsurvival (odds ratio [OR] = 6.1; 95% confidence interval [CI] = 1.02-36.7). Plasma (ANP) >11.5 pg/mL was associated with the likelihood of nonsurvival in hospitalized foals (OR = 7.2; 95% CI = 1.4-37.4; P < .05). Septic foals with serum (ANG-2) >1018 pg/mL on admission had higher odds of nonsurvival (OR = 6.5; 95% CI =1.2-36.6; P < .05). CONCLUSION AND CLINICAL IMPORTANCE: Critical illness in newborn foals is associated with EG degradation and injury, and these biomarkers are related to the severity of disease on admission and the outcome of sick foals.

Multinational trends in sepsis mortality between 1985 and 2019: a temporal analysis of the WHO Mortality Database.

OBJECTIVES: Understanding the burden of disease of sepsis is essential for monitoring the effectiveness of international strategies to improve sepsis care. Our objective was to describe the multinational trend of sepsis-related mortality for the period 1985-2019 from the WHO Mortality Database. DESIGN: Retrospective analysis of the WHO Mortality Database. SETTING: We included data from all countries defined by the WHO as having 'high usability data' and at least 10 years of total available data. PARTICIPANTS: From the WHO list of 50 countries with high usability data, 14 (28%) were excluded due to excessive missingness. We included and analysed data separately for male and female. PRIMARY AND SECONDARY OUTCOME MEASURES: We analysed age-standardised mortality rates (ASMR) (weighted average of the age-specific mortality rates per 100 000 people, where the weights are the proportions of people in the corresponding age groups of the WHO standard population). RESULTS: We included 1104 country-years worth of data from 36 countries with high usability data, accounting for around 15% of the world's population. The median ASMR for men decreased from 37.8 deaths/100 000 (IQR 28.4-46.7) in 1985-1987 to 25.8 deaths/100 000 (IQR 19.2-37) in 2017-2019, an approximately 12% absolute (31.8% relative) decrease. For women, the overall ASMR decreased from 22.9 deaths/100 000 (IQR 17.7-32.2) to 16.2 deaths/100 000 (IQR 12.6-21.6), an approximately 6.7% absolute decrease (29.3% relative decrease). The analysis of country-level data revealed wide variations in estimates and trends. CONCLUSIONS: We observed a decrease in reported sepsis-related mortality across the majority of analysed nations between 1985 and 2019. However, significant variability remains between gender and health systems. System-level and population-level factors may contribute to these differences, and additional investigations are necessary to further explain these trends.

Analysis of the diagnostic value of coagulation markers and coagulation function indices on the occurrence of DIC in sepsis and its prognosis.

Sepsis is a life-threatening condition that has the potential to multiple organ dysfunction and mortality. One of its frequent complications is disseminated intravascular coagulation (DIC), characterized by hyperactive clotting mechanisms that cause widespread clot formation and tissue damage. This study aimed to investigate early diagnostic markers of sepsis-associated DIC by comparing inflammatory factor levels, 28-day survival rates, coagulation function, and markers between patients with sepsis (non-DIC group) and those with sepsis-induced DIC (DIC group). The study analyzed the diagnostic efficacy of coagulation function and markers in predicting the occurrence and prognosis of sepsis-associated DIC, presenting survival curves. Results indicated significantly increased levels of APTT, TAT, tPAIC, PIC, and sTM in the DIC group compared to the non-DIC group. Sequential Organ Failure Assessment (SOFA) scores on days 1, 3, and 7 were notably lower in the non-DIC group. Correlation analysis revealed positive associations between PT, APTT, TAT, tPAIC, PIC, sTM levels, and SOFA scores, as well as negative associations with Fib and SOFA scores. Survival curves showed substantially lower mortality rates in the non-DIC group, highlighting significant survival disparities between groups. Combining all four coagulation indicators (TAT+ tPAIC + PIC + sTM) showed promising diagnostic value in evaluating disease severity, early DIC diagnosis, and sepsis prognosis.

Risk Factors of Sepsis-Associated Thrombocytopenia among Patients with Sepsis Induced Coagulopathy.

The study aims to evaluate the prognosis and risk factors of sepsis-associated thrombocytopenia (SAT) among patients with coagulopathy, and to provide evidence of the relationship between adverse outcomes and potential risks. Patients with sepsis-associated coagulopathy were included in the study from January 2014 to December 2022. The primary outcome was sepsis-associated thrombocytopenia (platelet count less than 100 *109/L), which was evaluated by logistic regression models adjusted for demographic characteristics and comorbidities. Among patients in the SAT group, 54% developed severe SAT, while 16% of these patients recovered from thrombocytopenia. The in-hospital mortality rate was significantly higher in the SAT group compared to the non-SAT group (31% in SAT group vs 23.9% in non-SAT group, p = 0.029). Even after adjusting for age, gender, Charlson comorbidity, white blood cell, and Sequential Organ Failure Assessment score, the differences in mortality rate persisted (Odds Ratio 0.72, [95% Confidence Interval 0.52-0.92]). Correlation analyses revealed that prothrombin time (r = 0.08, p = 0.50), international normalized ratio (r = 0.08, p = 0.42), prothrombin activity (r = -0.06, p > 0.999), D-dimer (r = -0.02, p > 0.999), and inflammatory parameters such as C-reactive protein (r = -0.11, p = 0.37) were not significantly correlated with platelet counts. According to subgroup analyses, patients with lung infection complicated by SAT had slightly higher mortality (OR 0.66, [95% CI, 0.46 to 0.94]). Sepsis-associated coagulopathy indicates a subset of critical ill patients, with those experiencing thrombocytopenia at greater risk for in-hospital death compared to those without it.

Metamizole outperforms meloxicam in sepsis: insights on analgesics, survival and immunomodulation in the peritoneal contamination and infection sepsis model.

Background: Limited availability and side effects of opioids have led to an increased use of non-opioid analgesia in animal disease models. However, by affecting the immune-inflammatory reactions, analgesia may disrupt the resolution of the host inflammation and modulate the survival in septic animals. This study used a clinically relevant sepsis mouse model of peritoneal contamination and infection (PCI) to investigate the antinociceptive and anti-inflammatory properties of two non-opioid analgesics. Methods: Adult C57BL/6J mice were intraperitoneally injected with a human feces suspension and received either no analgesics (Non-A), Meloxicam, or Metamizole orally. The mice were monitored for pain and illness. Mortality was assessed at 7 days post-PCI. A separate group of mice was sacrificed 24 hours after infection. Blood, peritoneal lavage fluid (PLF), liver, and spleen were harvested for pathogen load quantification via qPCR, macrophage phenotyping, neutrophil infiltration/activation, and systemic/tissue cytokine release by flow cytometry. Results: Meloxicam but not Metamizole reduced the mortality of septic mice by 31% on day 7 compared to the Non-A group. Both analgesics effectively alleviated pain but did not affect illness severity, body weight, and temperature. Meloxicam quadrupled the bacterial burden in the blood and PLF. In high IL-6 responders, Meloxicam treatment was associated with reduced circulating IL-10 and IL-1ß compared to the Non-A septic group. In low IL-6 responders, Meloxicam increased circulating MCP-1 levels and decreased PGE2 levels compared to Non-A septic mice. Notably, Meloxicam reduced spleen neutrophil infiltration by 20% compared to two other sepsis groups. Conclusion: Metamizole and Meloxicam effectively relieved pain and increased the animals' basal activity in the PCI sepsis model. Meloxicam prolonged survival yet triggered maladaptive responses due to its immunosuppressive features that decreased tissue bacterial clearance during sepsis. In contrast, Metamizole constitutes a safe and effective non-opioid alternative for analgesic control in the non-surgical PCI sepsis model.

Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival.

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel. We observed significantly increased levels of autoantibodies in 59% of the COVID-19-Sepsis group compared to 48% of the Sepsis group. Significant differences were identified between the groups for the levels of autoantibodies against gATPase. The cytokine levels of interferon (IFN)-λ1 and IP-10 were higher in the COVID-19-Sepsis group compared to the Sepsis group. Additional correlations between autoantibodies, cytokines and 30-day survival could be demonstrated, suggesting varied underlying pathological mechanisms. Elevated levels of cytokines and autoantibodies may serve as prognostic indicators for the survival probability of sepsis patients, highlighting the intricate relationship between immune responses and patient outcomes in the context of both sepsis and COVID-19.

Clinical Phenotyping for Prognosis and Immunotherapy Guidance in Bacterial Sepsis and COVID-19.

OBJECTIVES: It is suggested that sepsis may be classified into four clinical phenotypes, using an algorithm employing 29 admission parameters. We applied a simplified phenotyping algorithm among patients with bacterial sepsis and severe COVID-19 and assessed characteristics and outcomes of the derived phenotypes. DESIGN: Retrospective analysis of data from prospective clinical studies. SETTING: Greek ICUs and Internal Medicine departments. PATIENTS AND INTERVENTIONS: We analyzed 1498 patients, 620 with bacterial sepsis and 878 with severe COVID-19. We implemented a six-parameter algorithm (creatinine, lactate, aspartate transaminase, bilirubin, C-reactive protein, and international normalized ratio) to classify patients with bacterial sepsis intro previously defined phenotypes. Patients with severe COVID-19, included in two open-label immunotherapy trials were subsequently classified. Heterogeneity of treatment effect of anakinra was assessed. The primary outcome was 28-day mortality. MEASUREMENTS AND MAIN RESULTS: The algorithm validated the presence of the four phenotypes across the cohort of bacterial sepsis and the individual studies included in this cohort. Phenotype α represented younger patients with low risk of death, ß was associated with high comorbidity burden, and δ with the highest mortality. Phenotype assignment was independently associated with outcome, even after adjustment for Charlson Comorbidity Index. Phenotype distribution and outcomes in severe COVID-19 followed a similar pattern. CONCLUSIONS: A simplified algorithm successfully identified previously derived phenotypes of bacterial sepsis, which were predictive of outcome. This classification may apply to patients with severe COVID-19 with prognostic implications.

The Nonlinear Relationship Between Temperature and Prognosis in Sepsis-induced Coagulopathy Patients: A Retrospective Cohort Study from MIMIC-IV Database.

Background: The prognostic value of body temperature in sepsis-induced coagulopathy (SIC) remains unclear. In this study we aimed to investigate the association between temperature and mortality among SIC patients. Methods: We analyzed data for 9,860 SIC patients from an intensive care database. Patients were categorized by maximum temperature in the first 24 hours into the following: ≤36.0°C; 36.0-37.0°C; 37.0-38.0°C; 38.0-39.0°C; and ≥39.0°C. The primary outcome was 28-day mortality. We used multivariate regression to analyze the temperature-mortality association. Results: The 37.0-38.0°C, 38.0-39.0°C and ≥39.0°C groups correlated with lower 28-day mortality (adjusted HR 0.70, 0.76 and 0.72, respectively), while the <36.0°C group correlated with higher mortality compared to the 36.0-37.0°C group (adjusted HR 2.60). A nonlinear relationship was observed between temperature and mortality. Subgroup analysis found no effect modification except in cerebrovascular disease. Conclusion: A body temperature in the range of 37.0-38.0°C was associated with a significantly lower mortality compared to the normal temperature (36.0-37.0°C) group. Additionally, a gradual but statistically insignificant increase in mortality risk was observed when body temperature exceeded 38.0°C. Further research should validate these findings and elucidate involved mechanisms, especially in cerebrovascular disease subgroups.