The elevated lactate dehydrogenase to albumin ratio is a risk factor for developing sepsis-associated acute kidney injury: a single-center retrospective study.

BACKGROUND: There is no evidence to determine the association between the lactate dehydrogenase to albumin ratio (LAR) and the development of sepsis-associated acute kidney injury (SAKI). We aimed to investigate the predictive impact of LAR for SAKI in patients with sepsis. METHODS: A total of 4,087 patients with sepsis from the Medical Information Mart for Intensive Care IV (MIMIC IV) database were included. Logistic regression analysis was used to identify the association between LAR and the risk of developing SAKI, and the relationship was visualized using restricted cubic spline (RCS). The clinical predictive value of LAR was evaluated by ROC curve analysis. Subgroup analysis was used to search for interactive factors. RESULTS: The LAR level was markedly increased in the SAKI group (p < 0.001). There was a positive linear association between LAR and the risk of developing SAKI (p for nonlinearity = 0.867). Logistic regression analysis showed an independent predictive value of LAR for developing SAKI. The LAR had moderate clinical value, with an AUC of 0.644. Chronic kidney disease (CKD) was identified as an independent interactive factor. The predictive value of LAR for the development of SAKI disappeared in those with a history of CKD but remained in those without CKD. CONCLUSIONS: Elevated LAR 12 h before and after the diagnosis of sepsis is an independent risk factor for the development of SAKI in patients with sepsis. Chronic comorbidities, especially the history of CKD, should be taken into account when using LAR to predict the development of AKI in patients with sepsis.

M1 cholinergic signaling in the brain modulates cytokine levels and splenic cell sub-phenotypes following cecal ligation and puncture.

BACKGROUND: The contribution of the central nervous system to sepsis pathobiology is incompletely understood. In previous studies, administration of endotoxin to mice decreased activity of the vagus anti-inflammatory reflex. Treatment with the centrally-acting M1 muscarinic acetylcholine (ACh) receptor (M1AChR) attenuated this endotoxin-mediated change. We hypothesize that decreased M1AChR-mediated activity contributes to inflammation following cecal ligation and puncture (CLP), a mouse model of sepsis. METHODS: In male C57Bl/6 mice, we quantified basal forebrain cholinergic activity (immunostaining), hippocampal neuronal activity, serum cytokine/chemokine levels (ELISA) and splenic cell subtypes (flow cytometry) at baseline, following CLP and following CLP in mice also treated with the M1AChR agonist xanomeline. RESULTS: At 48 h. post-CLP, activity in basal forebrain cells expressing choline acetyltransferase (ChAT) was half of that observed at baseline. Lower activity was also noted in the hippocampus, which contains projections from ChAT-expressing basal forebrain neurons. Serum levels of TNFα, IL-1ß, MIP-1α, IL-6, KC and G-CSF were higher post-CLP than at baseline. Post-CLP numbers of splenic macrophages and inflammatory monocytes, TNFα+ and ILß+ neutrophils and ILß+ monocytes were higher than baseline while numbers of central Dendritic Cells (cDCs), CD4+ and CD8+ T cells were lower. When, following CLP, mice were treated with xanomeline activity in basal forebrain ChAT-expressing neurons and in the hippocampus was significantly higher than in untreated animals. Post-CLP serum concentrations of TNFα, IL-1ß, and MIP-1α, but not of IL-6, KC and G-CSF, were significantly lower in xanomeline-treated mice than in untreated mice. Post-CLP numbers of splenic neutrophils, macrophages, inflammatory monocytes and TNFα+ neutrophils also were lower in xanomeline-treated mice than in untreated animals. Percentages of IL-1ß+ neutrophils, IL-1ß+ monocytes, cDCs, CD4+ T cells and CD8+ T cells were similar in xanomeline-treated and untreated post-CLP mice. CONCLUSION: Our findings indicate that M1AChR-mediated responses modulate CLP-induced alterations in serum levels of some, but not all, cytokines/chemokines and affected splenic immune response phenotypes.

Comparison of Sepsis-1, 2 and 3 for Predicting Mortality in Septic Patients of a Middle-Income Country: A Retrospective Observational Cohort Study.

INTRODUCTION: The diagnosis of sepsis is based on expert consensus and does not yet have a "gold standard." With the aim of improving and standardizing diagnostic methods, there have already been three major consensuses on the subject. However, there are still few studies in middle-income countries comparing the methods. This study describes the characteristics of patients diagnosed with sepsis and evaluates and compares the performance of Sepsis-1, 2, and 3 criteria in predicting 28 days, and in-hospital mortality. PATIENTS AND METHODS: A retrospective observational cohort study was conducted in the intensive care unit of a tertiary hospital. All admissions between January 1, 2018, and December 31, 2019, were reviewed. Patients diagnosed with sepsis were included. RESULTS: During the study period, 653 patients diagnosed with sepsis (by any of the studied criteria) were included in the study. The 28 days mortality rate was 45.8%, and the in-hospital mortality rate was 59.7%. We observed that 72.1% of patients met the minimum criteria for diagnosing sepsis according to the three protocols, and this group also had the highest mortality rate. Age and comorbidities such as cancer and liver cirrhosis were significantly associated with in-hospital mortality. The most common microorganisms were Escherichia coli, Klebsiella spp., and Staphylococcus spp. CONCLUSIONS: The study found that most patients met the diagnostic criteria for sepsis using the three methods. Sepsis-2 showed greater sensitivity to predict mortality, while Sequential Organ Failure Assessment showed low accuracy, but was the only significant one. Furthermore, quick Sequential Organ Failure Assessment (qSOFA) had the highest specificity for mortality. Overall, these findings suggest that, although all three methods contribute to the diagnosis and prognosis of sepsis, Sepsis-2 is particularly sensitive in predicting mortality. Sepsis-3 shows some accuracy but requires improvement, and qSOFA exhibits the highest specificity. More research is needed to improve predictive capabilities and patient outcomes.

Development and Validation of Deep-Learning-Based Sepsis and Septic Shock Early Prediction System (DeepSEPS) Using Real-World ICU Data.

BACKGROUND: Successful sepsis treatment depends on early diagnosis. We aimed to develop and validate a system to predict sepsis and septic shock in real time using deep learning. METHODS: Clinical data were retrospectively collected from electronic medical records (EMRs). Data from 2010 to 2019 were used as development data, and data from 2020 to 2021 were used as validation data. The collected EMRs consisted of eight vital signs, 13 laboratory data points, and three demographic information items. We validated the deep-learning-based sepsis and septic shock early prediction system (DeepSEPS) using the validation datasets and compared our system with other traditional early warning scoring systems, such as the national early warning score, sequential organ failure assessment (SOFA), and quick sequential organ failure assessment. RESULTS: DeepSEPS achieved even higher area under receiver operating characteristic curve (AUROC) values (0.7888 and 0.8494 for sepsis and septic shock, respectively) than SOFA. The prediction performance of traditional scoring systems was enhanced because the early prediction time point was close to the onset time of sepsis; however, the DeepSEPS scoring system consistently outperformed all conventional scoring systems at all time points. Furthermore, at the time of onset of sepsis and septic shock, DeepSEPS showed the highest AUROC (0.9346). CONCLUSIONS: The sepsis and septic shock early warning system developed in this study exhibited a performance that is worth considering when predicting sepsis and septic shock compared to other traditional early warning scoring systems. DeepSEPS showed better performance than existing sepsis prediction programs. This novel real-time system that simultaneously predicts sepsis and septic shock requires further validation.

Predictors and Outcomes of Infections in ICU Patients With Cirrhosis: A Single-Center Observational Study.

BACKGROUND: Patients with cirrhosis are susceptible to infections, especially by multidrug-resistant organisms (MDROs). There are limited data on the incidence of culture-positive infections and the validity of Sepsis 3-criteria in patients with cirrhosis admitted to the intensive care unit (ICU) in India, which we aimed to assess. METHODS: In this prospective study, we included consecutive patients with cirrhosis admitted to the ICU between November 1, 2021, and April 30, 2022. The primary objective was to compare the outcomes of patients with microbiologically proven infections with those without proven infections. The secondary objective was to assess the predictors of infections and mortality and the impact of drug-resistant organisms. RESULTS: A total of 298 patients (9.4% women) were included. The incidence of microbiologically proven infection was 34% (101/298; 95%CI=27.6-41.2). Most patients (61%) had healthcare-associated infections, Gram-negative organisms accounted for 75.3%, and bacteremia was the commonest site. Drug-resistant organisms accounted for 52.5% (53/101; 95%CI=39.3-68.7), of which 39.6% were multidrug-resistant (MDR) and 12.8% were extensively drug-resistant (XDR). Mortality was significantly higher in patients with proven infections than those without (61.4% vs. 44.2%; P=0.007). The sequential organ failure assessment (SOFA) score (OR=1.91; 95%CI=1.04-3.52; P<0.001) and presence of fever and/or positive quick SOFA (qSOFA; OR=1.91;1.04-3.52; P=0.03) were associated with an increased risk of infections. The SOFA score (OR=1.06;95%CI=1.002-1.12; P=0.04), MELD NA score (OR=1.08;95%CI=1.05-1.12; P<0.001), and presence of fever and/or positive qSOFA (OR=2.19; 95%CI=1.27-3.76; P=0.005) predicted mortality. CONCLUSIONS: One-third of the patients with cirrhosis admitted to the ICU had microbiologically proven infection, and the mortality rate in such patients was high. SOFA, qSOFA, and fever can predict microbiologically proven infections and mortality in patients with cirrhosis.

Epidemiology of sepsis in a Japanese administrative database.

Sepsis is the leading cause of death worldwide. Considering regional variations in the characteristics of patients with sepsis, a better understanding of the epidemiology in Japan will lead to further development of strategies for the prevention and treatment of sepsis. To investigate the epidemiology of sepsis, we conducted a systematic literature review of PubMed between 2003 and January 2023. Among the 78 studies using a Japanese administrative database, we included 20 that defined patients with sepsis as those with an infection and organ dysfunction. The mortality rate in patients with sepsis has decreased since 2010, reaching 18% in 2017. However, the proportion of inpatients with sepsis is increasing. A study comparing short-course (≤7 days) and long-course (≥8 days) antibiotic administration showed lower 28-day mortality in the short-course group. Six studies on the treatment of patients with septic shock reported that low-dose corticosteroids or polymyxin B hemoperfusion reduced mortality, whereas intravenous immunoglobulins had no such effect. Four studies investigating the effects of treatment in patients with sepsis-associated disseminated intravascular coagulation demonstrated that antithrombin may reduce mortality, whereas recombinant human soluble thrombomodulin does not. A descriptive study of medical costs for patients with sepsis showed that the effective cost per survivor decreased over an 8-year period from 2010 to 2017. Sepsis has a significant impact on public health, and is attracting attention as an ongoing issue. Further research to determine more appropriate prevention methods and treatment for sepsis should be a matter of priority.

M1 Cholinergic Signaling Modulates Cytokine Levels and Splenocyte Sub-Phenotypes Following Cecal Ligation and Puncture.

Background: The contribution of the central nervous system to sepsis pathobiology is incompletely understood. In previous studies, administration of endotoxin to mice decreased activity of the vagus anti-inflammatory reflex. Treatment with the centrally-acting M1/M4 muscarinic acetylcholine (ACh) receptor (M1/M4AChR) attenuated this endotoxin-mediated change. We hypothesize that decreased M1/M4AChR-mediated activity contributes to inflammation following cecal ligation and puncture (CLP), a mouse model of sepsis. Methods: Basal forebrain cholinergic activity (immunostaining), serum cytokine/chemokine levels (ELISA) and splenocyte subtypes (flow cytometry) were examined at baseline and following CLP in male C57BL/6 male mice. Rersults: At 48hrs. post-CLP, activity in basal forebrain cells expressing choline acetyltransferase (ChAT) was half of that observed at baseline. Lower activity was also noted in the hippocampus, which contains projections from ChAT-expressing basal forebrain neurons. Serum levels of TNFα, IL-1ß, MIP-1α, IL-6, KC and G-CSF were higher post-CLP than at baseline. Post-CLP numbers of splenic macrophages and inflammatory monocytes, TNFa+ and ILb+ neutrophils and ILb+ monocytes were higher than baseline while numbers of central Dendritic Cells (cDCs), CD4+ and CD8+ T cells were lower. When, following CLP, mice were treated with xanomeline, a central-acting M1AChR agonist, activity in basal forebrain ChAT-expressing neurons and in the hippocampus was significantly higher than in untreated animals. Post-CLP serum concentrations of TNFα, IL-1ß, and MIP-1α, but not of IL-6, KC and G-CSF, were significantly lower in xanomline-treated mice than in untreated mice. Post-CLP numbers of splenic neutrophils, macrophages, inflammatory monocytes and TNFα+ neutrophils also were lower in xanomeline-treated mice than in untreated animals. The effects of CLP on percentages of IL-1ß+ neutrophils, IL-1ß+ monocytes, cDCs, CD4+ T cells and CD8+ T cells were similar in xanomeline - treated and untreated post-CLP mice. Conclusion: Our findings indicate that M1/M4AChR-mediated responses modulate CLP-induced alterations in the distribution of some, but not all, leukocyte phenotypes and certain cytokines and chemokines.

Bacteremia in Patients with Sepsis in the ICU: Does It Make a Difference?

Sepsis (and septic shock) is on of the most common causes of death worldwide. Bacteremia often, but not necessarily, occurs in septic patients, but the impact of true bacteremia on a patient's clinical characteristics and outcome remains unclear. The main aim of this study was to compare the characteristics and outcome of a well-defined cohort of 258 septic patients with and without bacteremia treated in the intensive care unit (ICU) of a tertiary center hospital in Prague, Czech Republic. As expected, more frequently, bacteremia was present in patients without previous antibiotic treatment. A higher proportion of bacteremia was observed in patients with infective endocarditis as well as catheter-related and soft tissue infections in contrast to respiratory sepsis. Multivariant analysis showed increased severity of clinical status and higher Charlson comorbidity index (CCI) as variables with significant influence on mortality. Bacteremia appears to be associated with higher mortality rates and length of ICU stay in comparison with nonbacteremic counterparts, but this difference did not reach statistical significance. The presence of bacteremia, apart from previous antibiotic treatment, may be related to the site of infection.

Predictability of Pediatric Sepsis Outcome Using SEPSIS-3 Definition in a Single Tertiary Pediatric Institution.

Sepsis is a syndrome of dysregulated response to infection and is associated with high morbidity and mortality. Sepsis was initially defined as a host's systemic inflammatory response syndrome (SIRS) to infection. In 2016, the importance of dysregulated response was incorporated into the definition of sepsis; adult sepsis was redefined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, with organ function being evaluated by the Sequential Organ Failure Assessment (SOFA) score (Sepsis-3 definition). However, the definition of pediatric sepsis remains the same, based on the original, SIRS-based criteria. In this study, we examined the relationship between mortality and sepsis in pediatric patients in our institution using the Sepsis-3 definition by incorporating the pediatric SOFA (pSOFA) score system, which was reported in 2017. We found that sepsis mortality was better correlated with the pSOFA score in our pediatric cohort. We also found that patients who did not have identified microbes were associated with better survival. In the future, we need to determine the relationship between mortality and Sepsis-3 definition-based pediatric sepsis worldwide to further define the utility of this new definition.

Population sepsis incidence, mortality, and trends in Hong Kong between 2009-2018 using clinical and administrative data.

BACKGROUND: Sepsis surveillance using electronic health record (EHR)-based data may provide more accurate epidemiologic estimates than administrative data, but experience with this approach to estimate population-level sepsis burden is lacking. METHODS: This was a retrospective cohort study including all adults admitted to publicly-funded hospitals in Hong Kong between 2009-2018. Sepsis was defined as clinical evidence of presumed infection (clinical cultures and treatment with antibiotics) and concurrent acute organ dysfunction (≥2 point increase in baseline SOFA score). Trends in incidence, mortality, and case fatality risk (CFR) were modelled by exponential regression. Performance of the EHR-based definition was compared with 4 administrative definitions using 500 medical record reviews. RESULTS: Among 13,550,168 hospital episodes during the study period, 485,057 (3.6%) had sepsis by EHR-based criteria with 21.5% CFR. In 2018, age- and sex-adjusted standardized sepsis incidence was 759 per 100,000 (relative +2.9%/year [95%CI 2.0, 3.8%] between 2009-2018) and standardized sepsis mortality was 156 per 100,000 (relative +1.9%/year [95%CI 0.9,2.9%]). Despite decreasing CFR (relative -0.5%/year [95%CI -1.0, -0.1%]), sepsis accounted for an increasing proportion of all deaths (relative +3.9%/year [95%CI 2.9, 4.9%]). Medical record reviews demonstrated that the EHR-based definition more accurately identified sepsis than administrative definitions (AUC 0.91 vs 0.52-0.55, p < 0.001). CONCLUSIONS: An objective EHR-based surveillance definition demonstrated an increase in population-level standardized sepsis incidence and mortality in Hong Kong between 2009-2018 and was much more accurate than administrative definitions. These findings demonstrate the feasibility and advantages of an EHR-based approach for widescale sepsis surveillance.

Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study.

Introduction: We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio. Methods: Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI). Results: In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated (p < 0.001) admission PSEP:GSN ratios were found in non-septic and septic patients. Regarding 10-day mortality prediction, PSEP:GSN ratios were lower (p < 0.05) in survivors than in non-survivors during follow-up, while the prognostic performance of PSEP:GSN ratio was similar to widely used clinical scores (APACHE II, SAPS II, SOFA). PSEP:GSN ratios were also higher (p < 0.001) in patients with sepsis-related AKI than septic non-AKI patients during follow-up, especially in sepsis-related AKI patients needing renal replacement therapy. Furthermore, increasing PSEP:GSN ratios were in good agreement (p < 0.001) with the dosage and the duration of vasopressor requirement in septic patients. Moreover, PSEP:GSN ratios were markedly greater (p < 0.001) in patients with septic shock than in septic patients without shock. Compared to septic patients requiring oxygen supplementation, substantially elevated (p < 0.001) PSEP:GSN ratios were observed in septic patients with demand for mechanical ventilation, while higher PSEP:GSN ratios (p < 0.001) were also associated with extended periods of mechanical ventilation requirement in septic patients. Conclusion: PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis. Clinical trail registration: NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.

Unsupervised clustering identifies sub-phenotypes and reveals novel outcome predictors in patients with dialysis-requiring sepsis-associated acute kidney injury.

INTRODUCTION: Heterogeneity exists in sepsis-associated acute kidney injury (SA-AKI). This study aimed to perform unsupervised consensus clustering in critically ill patients with dialysis-requiring SA-AKI. PATIENTS AND METHODS: This prospective observational cohort study included all septic patients, defined by the Sepsis-3 criteria, with dialysis-requiring SA-AKI in surgical intensive care units in Taiwan between 2009 and 2018. We employed unsupervised consensus clustering based on 23 clinical variables upon initializing renal replacement therapy. Multivariate-adjusted Cox regression models and Fine-Gray sub-distribution hazard models were built to test associations between cluster memberships with mortality and being free of dialysis at 90 days after hospital discharge, respectively. RESULTS: Consensus clustering among 999 enrolled patients identified three sub-phenotypes characterized with distinct clinical manifestations upon renal replacement therapy initiation (n = 352, 396 and 251 in cluster 1, 2 and 3, respectively). They were followed for a median of 48 (interquartile range 9.5-128.5) days. Phenotypic cluster 1, featured by younger age, lower Charlson Comorbidity Index, higher baseline estimated glomerular filtration rate but with higher severity of acute illness was associated with an increased risk of death (adjusted hazard ratio of 3.05 [95% CI, 2.35-3.97]) and less probability to become free of dialysis (adjusted sub-distribution hazard ratio of 0.55 [95% CI, 0.38-0.8]) than cluster 3. By examining distinct features of the sub-phenotypes, we discovered that pre-dialysis hyperlactatemia ≥3.3 mmol/L was an independent outcome predictor. A clinical model developed to determine high-risk sub-phenotype 1 in this cohort (C-static 0.99) can identify a sub-phenotype with high in-hospital mortality risk (adjusted hazard ratio of 1.48 [95% CI, 1.25-1.74]) in another independent multi-centre SA-AKI cohort. CONCLUSIONS: Our data-driven approach suggests sub-phenotypes with clinical relevance in dialysis-requiring SA-AKI and serves an outcome predictor. This strategy represents further development toward precision medicine in the definition of high-risk sub-phenotype in patients with SA-AKI.Key messagesUnsupervised consensus clustering can identify sub-phenotypes of patients with SA-AKI and provide a risk prediction.Examining the features of patient heterogeneity contributes to the discovery of serum lactate levels ≥ 3.3 mmol/L upon initializing RRT as an independent outcome predictor.This data-driven approach can be useful for prognostication and lead to a better understanding of therapeutic strategies in heterogeneous clinical syndromes.

Epidemiology of sepsis in Internal Medicine Units of Apulia: results of SEMINA (SEpsis Management in INternal medicine Apulia) study.

Background: The prevalence and mortality of sepsis in Internal Medicine Units (IMUs) is poorly understood as most of the data derive from studies conducted in Intensive Care Units. Aim of SEpsis Management in INternal medicine Apulia (SEMINA) study was to determine the prevalence of sepsis and the characteristics and outcomes of patients with Sepsis-3 criteria admitted in Apulia's Internal Medicine Units for over six months. Methods: The SEpsis Management in INternal medicine of Apulia study was a prospective, multicentre, observational study. Adult admissions to the 13 Apulia Region's Internal Medicine Units between November 15, 2018 and May 15, 2019 were screened for sepsis according to the Sepsis-3 criteria. Medical data were collected in electronic case report form. Results: Out of 7,885 adult patients of the Internal Medicine Units, 359 (4.55%) fulfilled the inclusion criteria, and 65 of them (18.1%) met the septic shock criteria. The patients enrolled were elderly, suffering from chronic poly-pathologies and from cognitive and functional impairment. The respiratory system was the most common site of infection and the most common pathogens isolated from blood cultures were Staphylococcus spp., E. coli, Klebsiella spp., Enterococcus spp. and Acinetobacter spp. The in-hospital fatality rate was 31.2% and was significantly higher for septic shock. Sequential Organ Failure Assessment score, dementia and infections from Acinetobacter spp. were independent risk factors for mortality. Conclusions: A high prevalence of sepsis and a high fatality rate were detected in Apulia Region's Internal Medicine Units. The high fatality rate observed in our study could be related to the underlying diseases and to the vulnerability of elderly patients admitted to our Internal Medicine Units.

Quick Sequential Organ Failure Assessment Score, Lactate, and Neutrophil-Lymphocyte Ratio Help in Diagnosis and Mortality Prediction during Golden Hour of Sepsis in Emergency Department.

Introduction: Sepsis is a life-threatening condition with a very narrow golden period in which confirmatory diagnosis may change the outcome dramatically. No confirmatory biomarker is available till date for early diagnosis of sepsis. This study aimed to evaluate the combined and independent role of quick sequential organ failure assessment (qSOFA) score, lactate, and neutrophil-lymphocyte ratio (NLR) in diagnosis and mortality prediction in early sepsis. Methods: This was a hospital-based, single-center, prospective cohort study conducted in a tertiary care institute, Karnataka, India. Three hundred adult sepsis patients were recruited during 10-month period, and demographic data, qSOFA score, lactate, NLR, and culture samples were collected in ED within 1 h of admission. Outcome groups (survivor and nonsurvivor) were statistically analyzed with relative frequencies (%), median, mean ± standard deviation with 95% confidence interval (CI), univariate, bivariate, and multivariate logistic regression analysis, and Receiver -operating characteristic curve (ROC) curve to test the predictive ability of initial levels of three biomarkers. Results: Sepsis was more prevalent among middle-aged male patients. Male gender (odds ratio [OR], 6.9; 95% CI: 1.61-30.1), qSOFA (OR, 154; 95% CI: 15-1565), and lactate (OR, 1.36; 95% CI: 22-833) show 97% (area under the curve) predictive accuracy of the model for sepsis on bivariate and multivariate logistic regression analysis. A significant rise in NLR was a poor outcome indicator on univariate analysis (P = 0.773). Conclusion: All three biomarkers are good outcome predictors whereas qSOFA and lactate have diagnostic significance in early sepsis. These markers can be used for patient triaging, minimizing culture report dependence for treatment and ultimately the outcome.

OpenSep: a generalizable open source pipeline for SOFA score calculation and Sepsis-3 classification.

EHR-based sepsis research often uses heterogeneous definitions of sepsis leading to poor generalizability and difficulty in comparing studies to each other. We have developed OpenSep, an open-source pipeline for sepsis phenotyping according to the Sepsis-3 definition, as well as determination of time of sepsis onset and SOFA scores. The Minimal Sepsis Data Model was developed alongside the pipeline to enable the execution of the pipeline to diverse sources of electronic health record data. The pipeline's accuracy was validated by applying it to the MIMIC-IV version 1.0 data and comparing sepsis onset and SOFA scores to those produced by the pipeline developed by the curators of MIMIC. We demonstrated high reliability between both the sepsis onsets and SOFA scores, however the use of the Minimal Sepsis Data model developed for this work allows our pipeline to be applied to more broadly to data sources beyond MIMIC.

Septic shock 3.0 criteria application in severe COVID-19 patients: An unattended sepsis population with high mortality risk.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can be associated with life-threatening organ dysfunction due to septic shock, frequently requiring intensive care unit (ICU) admission, respiratory and vasopressor support. Therefore, clear clinical criteria are pivotal for early recognition of patients more likely to need prompt organ support. Although most patients with severe COVID-19 meet the Sepsis-3.0 criteria for septic shock, it has been increasingly recognized that hyperlactatemia is frequently absent, possibly leading to an underestimation of illness severity and mortality risk. AIM: To identify the proportion of severe COVID-19 patients with vasopressor support requirements, with and without hyperlactatemia, and describe their clinical outcomes and mortality. METHODS: We performed a single-center prospective cohort study. All adult patients admitted to the ICU with COVID-19 were included in the analysis and were further divided into three groups: Sepsis group, without both criteria; Vasoplegic Shock group, with persistent hypotension and vasopressor support without hyperlactatemia; and Septic Shock 3.0 group, with both criteria. COVID-19 was diagnosed using clinical and radiologic criteria with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive RT-PCR test. RESULTS: 118 patients (mean age 63 years, 87% males) were included in the analysis (n = 51 Sepsis group, n = 26 Vasoplegic Shock group, and n = 41 Septic Shock 3.0 group). SOFA score at ICU admission and ICU length of stay were different between the groups (P < 0.001). Mortality was significantly higher in the Vasoplegic Shock and Septic Shock 3.0 groups when compared with the Sepsis group (P < 0.001) without a significant difference between the former two groups (P = 0.713). The log rank tests of Kaplan-Meier survival curves were also different (P = 0.007). Ventilator-free days and vasopressor-free days were different between the Sepsis vs Vasoplegic Shock and Septic Shock 3.0 groups (both P < 0.001), and similar in the last two groups (P = 0.128 and P = 0.133, respectively). Logistic regression identified the maximum dose of vasopressor therapy used (AOR 1.046; 95%CI: 1.012-1.082, P = 0.008) and serum lactate level (AOR 1.542; 95%CI: 1.055-2.255, P = 0.02) as the major explanatory variables of mortality rates (R 2 0.79). CONCLUSION: In severe COVID-19 patients, the Sepsis 3.0 criteria of septic shock may exclude approximately one third of patients with a similarly high risk of a poor outcome and mortality rate, which should be equally addressed.

Novel Damage Biomarkers of Sepsis-Related Acute Kidney Injury.

Sepsis-related acute kidney injury (AKI) is one of the most common complications of sepsis at the intensive care unit (ICU) with more adverse mortality rates. The early diagnosis and reliable monitoring of sepsis-related AKI are essential in achieving a favorable outcome. Novel serum and urinary biomarkers could yield valuable information during this process. Regarding the widely used Kidney Disease Improving Global Outcomes (KDIGO) classifications, the diagnosis of AKI is still based on the increase of serum creatinine levels and the decrease of urine output; however, these parameters have limitations in reflecting the extent of kidney damage, therefore more sensitive and specific laboratory biomarkers are needed for the early diagnosis and prognosis of sepsis-related AKI. Regarding this, several serum parameters are discussed in this review including presepsin and the most important actin scavenger proteins (gelsolin, Gc-globulin) while other urinary markers are also examined including cell cycle arrest biomarkers, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), Cystatin C and actin. Novel biomarkers of sepsis-related AKI could facilitate the early diagnosis and monitoring of sepsis-related AKI.

Presepsin and platelet to lymphocyte ratio predict the progression of septic subclinical acute kidney injury to septic acute kidney injury: a pilot study.

OBJECTIVE: This study aimed to determine whether presepsin and inflammation-based prognostic scores can predict the progression of septic subclinical acute kidney injury (AKI) to septic AKI among intensive care unit (ICU) patients. RESULTS: Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio (PLR), Prognostic Index, and Prognostic Nutritional Index were measured at baseline. Presepsin values and these indices were compared between septic AKI and septic subclinical AKI patients. There were 38 septic AKI patients and 21 septic subclinical AKI patients. Receiver operating characteristic curve analyses revealed the following cut-off values for AKI (relative to subclinical AKI): 708.0 (pg/ml) for presepsin on Day 1 (AUC, 0.69; sensitivity, 82%; specificity, 52%), 1283.0 (pg/ml) for presepsin on Day 2 (AUC, 0.69; sensitivity, 55%; specificity, 80%), and 368.66 for PLR (AUC, 0.67; sensitivity, 71%; specificity, 62%). Multivariate logistic regression analyses revealed PLR to be a predictor of septic subclinical AKI (odds ratio, 1.0023; 95% confidence interval, 1.0000-1.0046; p = 0.046). Presepsin and PLR predicted the progression of septic subclinical AKI to septic AKI and the prognosis of subclinical septic AKI patients.

Effect of Serum Phosphate on the Prognosis of Septic Patients: A Retrospective Study Based on MIMIC-IV Database.

Objective: To assess the effect of serum inorganic phosphate (Pi) on the prognosis of patients with sepsis. Methods: A retrospective analysis of patients with sepsis selected from the Medical Information Mart for Intensive Care (MIMIC)-IV database was performed. Sepsis was diagnosed according to the Third International Consensus Definition for sepsis and septic shock (Sepsis-3). The time-weighted values of the serum Pi measurements within the first 24 h of sepsis were analyzed. The association between serum Pi and in-hospital mortality was evaluated with a generalized linear model (log-binomial model). Results: The analysis of 11,658 patients from six intensive care units (ICUs) showed a nearly linear correlation between serum Pi and in-hospital mortality in all patients with sepsis, especially in those with acute kidney injury (AKI). The increase of serum Pi was related to a higher risk of AKI, higher norepinephrine doses, ICU mortality, and in-hospital mortality. The generalized linear model showed that serum Pi was an independent predictor for in-hospital mortality in all patients with sepsis even within the normal range. The adjusted risk ratios (RRs) were also significant in subgroup analyses according to kidney function, gender, respiratory infection, vasopressor use, and Sequential Organ Failure Assessment (SOFA) score. Conclusion: Higher levels of serum Pi, even within the normal range, were significantly associated with a higher risk of in-hospital mortality in patients with sepsis regardless of kidney function, gender, respiratory infection, vasopressor use, and SOFA score.