Criteria For Sepsis Research Articles

Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study.

Two risk variants in the apolipoprotein L1 gene (APOL1) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients hospitalized with infections, independent of their association with pre-existing severe renal disease. A retrospective cohort study of 2242 Black patients hospitalized with infections. We assessed whether carriage of APOL1 high-risk genotypes was associated with the risk of sepsis and sepsis-related phenotypes in patients hospitalized with infections. The primary outcome was sepsis; secondary outcomes were short-term mortality, and organ failure related to sepsis. Of 2242 Black patients hospitalized with infections, 565 developed sepsis. Patients with high-risk APOL1 genotypes had a significantly increased risk of sepsis (odds ratio [OR]=1.29 [95% CI, 1.00-1.67; p=0.047]); however, this association was not significant after adjustment for pre-existing severe renal disease (OR = 1.14 [95% CI, 0.88-1.48; p=0.33]), nor after exclusion of those patients with pre-existing severe renal disease (OR = 0.99 [95% CI, 0.70-1.39; p=0.95]). APOL1 high-risk genotypes were significantly associated with the renal dysfunction component of the Sepsis-3 criteria (OR = 1.64 [95% CI, 1.21-2.22; p=0.001]), but not with other sepsis-related organ dysfunction or short-term mortality. The association between high-risk APOL1 genotypes and sepsis-related renal dysfunction was markedly attenuated by adjusting for pre-existing severe renal disease (OR = 1.36 [95% CI, 1.00-1.86; p=0.05]) and was nullified after exclusion of patients with pre-existing severe renal disease (OR = 1.16 [95% CI, 0.74-1.81; p=0.52]). APOL1 high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing severe renal disease. This study was supported by R01GM120523 (QF), R01HL163854 (QF), R35GM131770 (CMS), HL133786 (WQW), and Vanderbilt Faculty Research Scholar Fund (QF). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center's BioVU which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the CTSA grant UL1TR0004from NCATS/NIH. Additional funding provided by the NIH through grants P50GM115305 and U19HL065962. The authors wish to acknowledge the expert technical support of the VANTAGE and VANGARD core facilities, supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485) and Vanderbilt Vision Center (P30 EY08126). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study

Background:Two risk variants in the apolipoprotein L1 gene (APOL1) have been associated with increased susceptibility to sepsis in Black patients. However, it remains unclear whether APOL1 high-risk genotypes are associated with occurrence of either sepsis or sepsis-related phenotypes in patients hospitalized with infections, independent of their association with pre-existing severe renal disease.Methods:A retrospective cohort study of 2242 Black patients hospitalized with infections. We assessed whether carriage of APOL1 high-risk genotypes was associated with the risk of sepsis and sepsis-related phenotypes in patients hospitalized with infections. The primary outcome was sepsis; secondary outcomes were short-term mortality, and organ failure related to sepsis.Results:Of 2242 Black patients hospitalized with infections, 565 developed sepsis. Patients with high-risk APOL1 genotypes had a significantly increased risk of sepsis (odds ratio [OR]=1.29 [95% CI, 1.00–1.67; p=0.047]); however, this association was not significant after adjustment for pre-existing severe renal disease (OR = 1.14 [95% CI, 0.88–1.48; p=0.33]), nor after exclusion of those patients with pre-existing severe renal disease (OR = 0.99 [95% CI, 0.70–1.39; p=0.95]). APOL1 high-risk genotypes were significantly associated with the renal dysfunction component of the Sepsis-3 criteria (OR = 1.64 [95% CI, 1.21–2.22; p=0.001]), but not with other sepsis-related organ dysfunction or short-term mortality. The association between high-risk APOL1 genotypes and sepsis-related renal dysfunction was markedly attenuated by adjusting for pre-existing severe renal disease (OR = 1.36 [95% CI, 1.00–1.86; p=0.05]) and was nullified after exclusion of patients with pre-existing severe renal disease (OR = 1.16 [95% CI, 0.74–1.81; p=0.52]).Conclusions:APOL1 high-risk genotypes were associated with an increased risk of sepsis; however, this increased risk was attributable predominantly to pre-existing severe renal disease.Funding:This study was supported by R01GM120523 (QF), R01HL163854 (QF), R35GM131770 (CMS), HL133786 (WQW), and Vanderbilt Faculty Research Scholar Fund (QF). The dataset(s) used for the analyses described were obtained from Vanderbilt University Medical Center’s BioVU which is supported by institutional funding, the 1S10RR025141-01 instrumentation award, and by the CTSA grant UL1TR0004from NCATS/NIH. Additional funding provided by the NIH through grants P50GM115305 and U19HL065962. The authors wish to acknowledge the expert technical support of the VANTAGE and VANGARD core facilities, supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA068485) and Vanderbilt Vision Center (P30 EY08126). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction. We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015. Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland. Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old. None. We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores, measured at blood culture sampling, to predict 30-day mortality. We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Percentage with organ dysfunction ranged from 32.7% (IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy for identification of 30-day mortality was area under the curve (AUC) 0.87 (95% CI, 0.82-0.92) for IPSCC, 0.83 (0.76-0.89) for PELOD-2, 0.85 (0.78-0.92) for pSOFA, and 0.85 (0.78-0.91) for PODIUM. When restricting scores to neurologic, respiratory, and cardiovascular dysfunction, the adjusted AUC was 0.89 (0.84-0.94) for IPSCC, 0.85 (0.79-0.91) for PELOD-2, 0.87 (0.81-0.93) for pSOFA, and 0.88 (0.83-0.93) for PODIUM. IPSCC, PELOD-2, pSOFA, and PODIUM performed similarly to predict 30-day mortality. Simplified scores restricted to neurologic, respiratory, and cardiovascular dysfunction yielded comparable performance.

Umbilical cord blood hematological parameters in predicting early onset neonatal sepsis (EOS)- a prospective cohort study.

In low and middle income countries, there is a need for affordable and accurate biomarkers to identify neonates at risk of early onset neonatal sepsis (EOS). Cord blood hematological parameters if reliable and accurate for the detection of EOS are cost effective and can reduce the need for repeated venipuncture in the neonate. In this prospective cohort study, the umbilical cord parameters of newborns with gestational age>34weeks were collected. These neonates were followed up for 72 h and septic screen was employed in those babies who had risk factors or developed clinical features of sepsis. The cord blood parameters of the normal newborn and those who had sepsis were analyzed. A total of 513 neonates were enrolled for the study, 32 required septic screening of whom 13 neonates were found to meet the criteria for sepsis: either blood culture positive or sepsis screen positive with clinical features. Cord blood parameters were analyzed using independent t test. Red cell distribution width (RDW) and band cells were statistically significant (p 0.007 and 0.009 respectively) between the septic and normal neonates. Increased RDW had a sensitivity of 61.54 %, specificity of 54.60 %. Increased band cells with a cut off of>15 cells had a sensitivity of 7.7 % with specificity of 100 % with higher numbers in septic neonates. Increased RDW and band cells in combination had sensitivity of 61.54 % and specificity of 54.6 %. RDW and band cell can be potential markers of EOS in cord blood but require further study in a larger population.

Low lymphocyte to high-density lipoprotein ratio predicts mortality in sepsis patients.

The lymphocyte-to-high-density lipoprotein (HDL) ratio (LHR) is associated with both inflammation and immunity, and may have the potential to predict the prognosis of sepsis. Our study aimed to evaluate the relationship between LHR and sepsis-related mortality. We collected data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.2) database by targeting patients who met the Sepsis-3 criteria and recorded the absolute values of lymphocytes and HDL after admission. We then used restricted cubic splines based on logistic regression to simulate the relationship between the LHR and 90-day mortality. Subsequently, the hazardous threshold was derived based on the mortality curve, and further evaluations were performed using different methods and data sources for hazardous threshold. We ultimately included 1027 eligible patients from the MIMIC-IV database and described the nonlinear relationship between LHR and 90-day mortality. Based on the curve, an LHR of ≤ 0.6 indicated harmful threshold, and the odds ratio for mortality was 1.74 (P=0.001). The outperforming hazard was particularly marked in patients with chronic lung disease and remained consistent after adjusting for baseline data and validating multiple data sources. The LHR has prognostic value in patients with sepsis, and an LHR ≤ 0.6 is a deleterious load that increases mortality.

Substantial heterogeneity of inflammatory cytokine production and its inhibition by a triple cocktail of toll-like receptor blockers in early sepsis.

Early sepsis is a life-threatening immune dysregulation believed to feature a "cytokine storm" due to activation of pattern recognition receptors by pathogen and danger associated molecular patterns. However, treatments with single toll-like receptor (TLR) blockers have shown no clinical benefit. We speculated that sepsis patients at the time of diagnosis are heterogeneous in relation to their cytokine production and its potential inhibition by a triple cocktail of TLR blockers. Accordingly, we analyzed inflammatory cytokine production in whole blood assays from early sepsis patients and determined the effects of triple TLR-blockade. Whole blood of 51 intensive care patients sampled within 24h of meeting Sepsis-3 criteria was incubated for 6h without or with specific TLR2, 4, and 7/8 stimuli or suspensions of heat-killed S. aureus or E. coli bacteria as pan-TLR challenges, and also with a combination of monoclonal antibodies against TLR2 and 4 and chloroquine (endosomal TLR inhibition), subsequent to dose optimization. Concentrations of tumor necrosis factor (TNF), Interleukin(IL)-6, IL-8, IL-10, IL-1α and IL-1β were measured (multiplex ELISA) before and after incubation. Samples from 11 sex and age-matched healthy volunteers served as controls and for dose-finding studies. Only a fraction of sepsis patient samples revealed ongoing cytokine production ex vivo despite sampling within 24h of first meeting Sepsis-3 criteria. In dose finding studies, inhibition of TLR2, 4 and endosomal TLRs reliably suppressed cytokine production to specific TLR agonists and added bacteria. However, inflammatory cytokine production ex vivo was only suppressed in the high cytokine producing samples but not in the majority. The suppressive response to TLR-blockade correlated both with intraassay inflammatory cytokine production (r=0.29-0.68; p<0.0001-0.04) and cytokine baseline concentrations (r=0.55; p<0.0001). Upon meeting Sepsis-3 criteria for less than 24h, a mere quarter of patient samples exhibits a strong inflammatory phenotype, as characterized by increased baseline inflammatory cytokine concentrations and a stark TLR-dependent increase upon further ex vivo incubation. Thus, early sepsis patient cohorts as defined by Sepsis-3 criteria are very heterogeneous in regard to inflammation. Accordingly, proper ex vivo assays may be useful in septic individuals before embarking on immunomodulatory treatments.

Validating the performance of 3 sepsis screening tools in patients with clinical chorioamnionitis

Maternal sepsis is a leading cause of maternal death in the United States. Approximately two-thirds of maternal deaths because of sepsis are related to delayed recognition or treatment. New early warning systems using a 2-step approach have been developed for the early recognition of sepsis in obstetrics; however, their performance has not been validated. This study aimed to assess the performance of 3 primary screening tools introduced by the Society of Obstetric Medicine Australia and New Zealand and the California Maternal Quality Care Collaborative for use in the first step of their 2-step early warning systems. The obstetrically modified quick Sequential (sepsis-related) Organ Failure Assessment score tool, the obstetrically modified Systemic Inflammatory Response Syndrome tool, and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool were evaluated for the early detection of sepsis in patients with clinically diagnosed chorioamnionitis. This was a retrospective cohort study using prospectively collected clinical data at a tertiary care center and an affiliated healthcare system. The electronic health records were searched to identify and verify cases with clinically diagnosed chorioamnionitis between November 2017 and September 2022. The flow sheet for every patient was reviewed to determine when criteria were met for any of the 3 tools. The performance of these tools was analyzed using their sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curve for the identification of sepsis. There were 545 cases that had the requisite data for inclusion in the analysis. Of note, 11 patients met the criteria for sepsis. Both the obstetrically modified Systemic Inflammatory Response Syndrome and obstetrically modified Systemic Inflammatory Response Syndrome 1 tools had overall similar test characteristics, which were notably different from the obstetrically modified quick Sequential Organ Failure Assessment tool. The screen-positive rate of the obstetrically modified quick Sequential Organ Failure Assessment tool (1.5%; 95% confidence interval, 0.6%-2.9%) was lower than that of the obstetrically modified Systemic Inflammatory Response Syndrome tool (60.0%; 95% confidence interval, 55.7%-64.1%) and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool (50.0%; 95% confidence interval, 45.8%-54.3%). The sensitivities of the obstetrically modified Systemic Inflammatory Response Syndrome tool (100.0%; 95% confidence interval, 71.5%-100.0%) and the obstetrically modified Systemic Inflammatory Response Syndrome 1 tool (100.0%; 95% confidence interval, 71.5%-100.0%) were higher than that of the obstetrically modified quick Sequential Organ Failure Assessment tool (18.0%; 95% confidence interval, 2.3%-51.8%). All 3 tools had high negative predictive values; however, their positive predictive values were poor. This study demonstrated that all 3 tools had limitations in screening for sepsis among patients with a clinical diagnosis of chorioamnionitis. The obstetrically modified quick Sequential Organ Failure Assessment tool missed more than half of the sepsis cases and, thus, had poor performance as a primary screening tool for sepsis. Both the obstetrically modified Systemic Inflammatory Response Syndrome and obstetrically modified Systemic Inflammatory Response Syndrome 1 tools captured all sepsis cases; however, they tended to overdetect sepsis.

The early use of bisoprolol in patients with severe sepsis and its impact on the patients outcome

Objectives To explore the hypothesis that beta 1 adrenergic receptor blockage might be protective through attenuation of destructive sympathetic activity and catecholaminergic inflammatory effects in severe sepsis patients. Design Prospective, randomized, controlled study. Settings Critical care department in Alexandria main university hospital. Patients and methods The study was conducted on 50 adult patients who were admitted to the Department of Critical Care Medicine in the Alexandria Main University Hospital who fulfilled the criteria for severe sepsis according to The American College Of Chest Physicians, patients were randomly assigned into two groups, group I: Included 25 patients receiving Bisoprolol 2.5 to 10 mg enterally for a target heart rate 80–90 beat/minute within the first 24 h according to the effect on hemodynamic stabilization and group II: Included 25 patients, as a control group, who received routine management of severe sepsis. Both groups were followed up and compared regarding the primary end points (discharge from the intensive care unit after recovery, septic shock or death) and the secondary end points (length of ICU stay, days of mechanical ventilation and need for inotropes). Results The heart rate at the end of the study was significantly lower in survived patients in group I with mean value of 80.06+9.05 beats/minute compared to mean value of 102.22+7.58 beats/minute in the died patients in the same group (P=0.003). The mean arterial blood pressure (mmHg) in studied patients, was not significantly different between the two groups on admission (P=0.099) and on the 1st day (P=0.172) the significant differences started to appear on the 2nd day (P=0.003), and over the whole period of observation till the end point of the study as the mean value of 83.31+16.90 in group I compared to mean value of 72.0+16.07 in group II (P=&lt;0.021), regarding the comparison between the survived and died patients in group I, on admission there was no statistically significant difference between them (p 0.213) while by the end point of the study, there was a statistically significant difference being higher in survived patients with mean value of 95.38+3.38 compared to mean value of 61.44+2.70 in died patients (P&lt;0.001). Regarding the occurrence of septic shock, it was less in group I as 40% compared to 72% in group II (P=0.023), group I had longer ICU stay (5.0 to 24.0 days) compared to group II (7.0 to 20.0 days), with a statistically significant difference (P=0.029). The duration of mechanical ventilation days (P=0.001), as longer in group II compared group I (group I= 8.37±3.43 days, group II=12.0±3.21 days). The mortality was lower in group I about 36% compared to 68% in group II with a statistically significant difference between the two groups (P= 0.024). Conclusion The administration of bisoprolol to patients with severe sepsis decrease the mortality, length of stay in ICU, days of mechanical ventilation and improves tissue perfusion without significant effect on hemodynamics.

Potential Role and Prognostic Value of Interleukin-15 for Mortality Among Elderly Patients with Sepsis.

To investigate the potential role and prognostic value of interleukin-15 (IL-15) in predicting 28-day mortality in elderly patients with sepsis. According to the Sepsis-3.0 diagnostic criteria for sepsis, elderly patients with sepsis who were admitted to the emergency department of the Shi jingshan branch of Beijing Chaoyang Hospital between October 2021 and June 2022 were enrolled in this retrospective cohort study. After observation for 28 days, patients were divided into a survival group and a nonsurvival group. Samples for laboratory tests, baseline characteristic data, and SOFA and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were collected or recorded within 24 h after admission to the emergency department. Quantitative detection of IL-15 was performed with a Luminex assay. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were conducted for comparison. In total, 220 elderly patients with sepsis were enrolled, 69 of whom were in the survival group and 151 of whom were in the nonsurvival group at the 28-day interval. Systolic pressure, high-density lipoprotein (HDL), platelets (PLT) and albumin (ALB) were significantly higher in the survival group (P<0.05), while IL-15, SOFA, and APACHE II were significantly higher in the nonsurvival group (P<0.05). IL-15 was an independent risk factor associated with 28-day mortality (OR=1.842, 95% CI [1.323, 2.565]). The area under the receiver operating characteristic curve (AUROC) of IL-15 alone was 0.691 (95% CI [0.618, 0.764]), with a sensitivity of 46.67% and a specificity of 85.81%. The AUROC of the combined IL-15 and SOFA reached 0.880 (95% CI [0.672, 0.812]), for which the sensitivity and specificity were 80.95% and 85.08%, respectively. IL-15 possesses the prognostic value for predicting 28-day mortality in elderly patients with sepsis.

Clinical decision support tools for paediatric sepsis in resource-poor settings: an international qualitative study

ObjectiveNew paediatric sepsis criteria are being developed by an international task force. However, it remains unknown what type of clinical decision support (CDS) tools will be most useful for dissemination...

Use of Electronic Clinical Data to Track Incidence and Mortality for SARS-CoV-2–Associated Sepsis

Efforts to quantify the burden of SARS-CoV-2-associated sepsis have been limited by inconsistent definitions and underrecognition of viral sepsis. To describe the incidence and outcomes of SARS-CoV-2-associated sepsis vs presumed bacterial sepsis using objective electronic clinical criteria. This retrospective cohort study included adults hospitalized at 5 Massachusetts hospitals between March 2020 and November 2022. SARS-CoV-2-associated sepsis was defined as a positive SARS-CoV-2 polymerase chain reaction test and concurrent organ dysfunction (ie, oxygen support above simple nasal cannula, vasopressors, elevated lactate level, rise in creatine or bilirubin level, and/or decline in platelets). Presumed bacterial sepsis was defined by modified US Centers for Disease Control and Prevention adult sepsis event criteria (ie, blood culture order, sustained treatment with antibiotics, and organ dysfunction using identical thresholds as for SARS-CoV-2-associated sepsis). Trends in the quarterly incidence (ie, proportion of hospitalizations) and in-hospital mortality for SARS-CoV-2-associated and presumed bacterial sepsis were assessed using negative binomial and logistic regression models. This study included 431 017 hospital encounters from 261 595 individuals (mean [SD] age 57.9 [19.8] years, 241 131 (55.9%) females, 286 397 [66.5%] from academic hospital site). Of these encounters, 23 276 (5.4%) were from SARS-CoV-2, 6558 (1.5%) had SARS-CoV-2-associated sepsis, and 30 604 patients (7.1%) had presumed bacterial sepsis without SARS-CoV-2 infection. Crude in-hospital mortality for SARS-CoV-2-associated sepsis declined from 490 of 1469 (33.4%) in the first quarter to 67 of 450 (14.9%) in the last (adjusted odds ratio [aOR], 0.88 [95% CI, 0.85-0.90] per quarter). Crude mortality for presumed bacterial sepsis was 4451 of 30 604 patients (14.5%) and stable across quarters (aOR, 1.00 [95% CI, 0.99-1.01]). Medical record reviews of 200 SARS-CoV-2-positive hospitalizations confirmed electronic health record (EHR)-based SARS-CoV-2-associated sepsis criteria performed well relative to sepsis-3 criteria (90.6% [95% CI, 80.7%-96.5%] sensitivity; 91.2% [95% CI, 85.1%-95.4%] specificity). In this retrospective cohort study of hospitalized adults, SARS-CoV-2 accounted for approximately 1 in 6 cases of sepsis during the first 33 months of the COVID-19 pandemic. In-hospital mortality rates for SARS-CoV-2-associated sepsis were high but declined over time and ultimately were similar to presumed bacterial sepsis. These findings highlight the high burden of SARS-CoV-2-associated sepsis and demonstrate the utility of EHR-based algorithms to conduct surveillance for viral and bacterial sepsis.

Clinical evaluation of Sepsis-1 and Sepsis-3 in infective endocarditis

BackgroundSepsis is associated with poor survival outcomes in patients with infective endocarditis (IE). However, the prognostic value of the Sepsis-1 and Sepsis-3 criteria of sepsis for IE patients is unclear. MethodsA total of 1354 patients with IE was enrolled and classified into the sepsis and non-sepsis groups according to the Sepsis-1 and Sepsis-3. Multivariate regression analysis was performed to test the predictive performances of the Sepsis-1 and Sepsis-3 in assessing the risk of mortality in patients with IE. ResultsSepsis was diagnosed in 347 (25.6%) patients according to the Sepsis-1 and 496 (36.6%) patients with the Sepsis-3. The in-hospital mortality rate was 11.5% in the Sepsis-1 group and 14.3% in the Sepsis-3 group. Kaplan-Meier survival curve analysis showed that both Sepsis-1 (Log-rank = 17.2, p < 0.001) and Sepsis-3 (Log-rank = 94.3, p < 0.001) were significantly associated with 6-month mortality. Multivariate regression analysis demonstrated that the Sepsis-3 was independently associated with the in-hospital mortality (odds ratio = 2.89, 95% CI 1.68–4.97, p < 0.001) and the 6-month mortality (hazard ratio = 3.24, 95% CI 2.08–5.04, p < 0.001). ConclusionsSepsis-3 shows better predictive performance than Sepsis-1 criteria in assessing the risk of mortality in patients with IE.

Long-term clinical outcomes in critically ill patients with sepsis and pre-existing low muscle mass: a retrospective cohort study

PurposeCritically ill patients with sepsis account for significant disease morbidity and healthcare costs. Low muscle mass has been proposed as an independent risk factor for poor short-term outcomes, although its effect on long-term outcomes remains unclear.MethodsRetrospective cohort analysis of patients treated at a quaternary care medical center over 6 years (09/2014 - 12/2020). Critically ill patients meeting Sepsis-3 criteria were included, with low muscle mass defined by le 5th percentile skeletal muscle index, measured at the L3 lumbar level (L3SMI) on Computed-Tomography (CT) scan (le 41.6 cm2/m2 for males and le 32.0 cm2/m2 for females). L3SMI was calculated by normalizing the CT-measured skeletal muscle area to the square of the patient’s height (in meters). Measurements were taken from abdominal/pelvic CT scan obtained within 7 days of sepsis onset. The prevalence of low muscle mass and its association with clinical outcomes, including in-hospital and one-year mortality, and post-hospitalization discharge disposition in survivors, was analyzed. Unfavorable post-hospitalization disposition was defined as discharge to a location other than the patient’s home.ResultsLow muscle mass was present in 34 (23%) of 150 patients, with mean skeletal muscle indices of 28.0 ± 2.9 cm2/m2 and 36.8 ± 3.3 cm2/m2 in females and males, respectively. While low muscle mass was not a significant risk factor for in-hospital mortality (hazard ratio 1.33; 95% CI 0.64 – 2.76; p = 0.437), it significantly increased one-year mortality after adjusting for age and illness severity using Cox multivariate regression (hazard ratio 1.9; 95% CI 1.1 – 3.2; p = 0.014). Unfavorable post-hospitalization discharge disposition was not associated with low muscle mass, after adjusting for age and illness severity in a single, multivariate model.ConclusionLow muscle mass independently predicts one-year mortality but is not associated with in-hospital mortality or unfavorable hospital discharge disposition in critically ill patients with sepsis.

Two vicious circles associated with the aging of the immune system in the development of severe forms of COVID-19.

Background: The immune-inflammatory response is the basis of the pathophysiology of SARS-Cov-2 infection. In severe cases of COVID-19 uncontrolled systemic inflammatory response causes multiorgan dysfunction (MODS), as the most common immediate cause of death. Unfavorable outcome of the COVID-19 most often occurs in elderly patients. The aim of the study was to establish parameters with prognostic significance in severe cases of COVID-19 according to life years, laboratory markers of sepsis and MODS, as well as the number of peripheral CD4+ and CD8+T lymphocytes in 20 consecutively selected critically ill patients. Results: Eleven subjects were male, 9 female, mean age 73.45 ± 11.59, among which the oldest patient was 94 and the youngest 43years. All the patients met the sepsis and MODS criteria. Increased age and low CD4+ and CD8+T cell counts were identified as independent predictors of death. Only the two youngest patients (43 and 50years old) survived 28days, and they are the only ones with a CD4 lymphocyte count above 500 cells/mm3. Conclusion: Senescence of the immune system is mostly characterized by reduced regenerative capacity of adaptive immunity with diminished ability to respond to new antigens and a manifested proinflammatory phenotype. Additional reduction of protective capacity by further deterioration of T cell quantity and quality due to sepsis itself and mutual interaction of senescent T cells and vascular endothelial cells in the induction of cytokine storm represent two complementary vicious cycles in the development of sepsis-related multiorgan dysfunction.

Neutrophil CD64-a prognostic marker of sepsis in intensive care unit: a prospective cohort study.

Little is known about the prognostic ability of nCD64 in critically ill patients. This study aimed to assess the prognostic values of nCD64 in adult ICU patients with sepsis. A prospective cohort study was conducted at the ICU of Cho Ray Hospital in Vietnam between January 2019 to September 2020. All newly admitted 86 septic patients diagnosed based on sepsis-3 criteria were included. An evaluation of nCD64 was performed at admission (T0) and 48 h thereafter (T48). Delta nCD64 (nCD64 T48 - nCD64 T0), %delta nCD64 [(nCD64 T48 - nCD64 T0)/nCD64 T0 x 100%], APACHE II and SOFA scores were calculated and examined. Serum procalcitonin levels and white blood cell counts were documented. Spearman's rank correlation coefficient was used to test the correlation between nCD64 and severity scores. Receiver-operating characteristic (ROC) curve was performed to evaluate the predictive efficacy of the sepsis parameters. Patients with septic shock had significantly higher nCD64 levels than septic patients [3,568 (2,589; 5,999) vs. 1,514 (1,416;2,542) molecules/cell, p < 0.001]. nCD64 T0 and SOFA scores had a moderately positive linear correlation (R = 0.31, p = 0.004). In the survivor group, nCD64 levels significantly decreased within the first 48 h of admission (p < 0.001), while this trend was not statistically significant in the non-survivor group (p = 0.866). The area under the ROC curve (AUC) value of %delta nCD64 combined with APACHE II score (0.81) was higher than that of any other parameter alone or in combination with each other. The nCD64 index may serve as a valuable biomarker for predicting the course of sepsis. Monitoring changes in nCD64 during the initial 48 h of admission can aid in predicting the prognosis of septic patients. The use of a combination of the trends of nCD64 index in the first 48 h with APACHE II score would further enhance the predictive accuracy. More studies with longer follow-ups are needed to fully understand the implications of serial trend and kinetics of nCD64 in septic patients.

CLINICAL UTILITY OF INTERLEUKIN-1 INHIBITORS IN PEDIATRIC SEPSIS.

The pathophysiology of pediatric sepsis is characterized by increased innate immune activation earlier in life. Interleukin-1 is a proinflammatory cytokine implicated in the pathophysiology of sepsis, and ferritin is a stable surrogate biomarker for elevated IL-1 levels. Data in adult sepsis have shown that use of anakinra, an anti-IL-1 receptor antagonist, led to improved clinical outcomes in patients with features of macrophage activation and hyperferritinemia. However, data in pediatric sepsis are lacking. Our narrative review sought to highlight the current understanding of using IL-1 inhibitors in pediatric sepsis. We identified five studies including one case report and four retrospective case series that described clinical outcomes in relation to use of anakinra for secondary hemophagocytic lymphohistiocytosis (HLH). A few patients in this pooled heterogenous cohort of 72 patients had concomitant infection meeting the criteria for sepsis. All studies measured ferritin levels and reported a decrease in ferritin after initiating anakinra. Twelve patients died after treatment initiation. There was no clear comparison in clinical outcomes between infected and noninfected patients. The pathophysiology of pediatric sepsis suggests that there is a need for blinded clinical trials using targeted immunomodulation such as IL-1 inhibitors in pediatric sepsis cohort with an immunophenotype suggesting increased innate immune activation.

Multi-Clinical Factors Combined with an Artificial Intelligence Algorithm Diagnosis Model for HIV-Infected People with Bloodstream Infection.

Although highly active antiretroviral therapy (HA-ART) can effectively suppress the disease process in patients with acquired immunodeficiency syndrome (AIDS), opportunistic infections, mainly bloodstream infections (BSI), are still the main cause of death in people living with HIV. There is no effective diagnostic strategy for HIV-infected people with BSI. This study aimed to develop an AI diagnostic model with high sensitivity to improve the early detection of HIV-infected people with BSI. This study retrospectively analyzed the 40 clinical factors of 498 HIV-infected people (171 with BSI positive and 327 with BSI negative) who admitted to Wenzhou Central Hospital from September 2014 to July 2021. This study used the hospital information management system to collect the clinical characteristics, laboratory and imaging examination results, and clinical diagnosis of the two groups. The diagnostic results of all patients were in line with the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of AIDS (2021 Edition), and the BSI diagnosis was in line with the diagnostic criteria of sepsis and bacteremia in Practical Internal Medicine (13th Edition). On this basis, various risk prediction models were established by combining 8 artificial intelligence (AI) algorithms in the training set and validating the diagnosis performance in the testing set. The model with the best diagnostic performance was selected as the final diagnostic model. The clinical characteristics of HIV-infected people with BSI are atypical, and the pathogens in this area are mainly fungi. Ten risk factors were selected: low level of hemoglobin, CD4+T cell and platelets, high level of lactate dehydrogenase and blood urea nitrogen, splenomegaly, without ART treatment, strip shadow, nodular shadow, and shock. The combination of the ten risk factors, age, gender and the "svmRadial" model can identify the HIV-infected people with BSI from the HIV-infected people without BSI with an area under the curve of 0.916 and a sensitivity and specificity of 0.824 and 0.855, respectively. The model showed excellent performance in diagnosing HIV-infected people with BSI. Internal and external validation showed that the diagnosis model had high clinical application value.

The value of right ventricular ultrasound assessment and cardiac biomarkers in the prognosis of sepsis.

The aim of this study was to explore the risk factors affecting the prognosis of patients with sepsis using a prospective design. From January 2022 to March 2023, a prospective study was conducted in the Intensive Care Unit (ICU) of Cangzhou Central Hospital, including 58 patients who met the diagnostic criteria for sepsis. Patients were divided into a survival group (39 cases) and a death group (19 cases) based on outcome. Within 24 hours, the following indicators were collected: gender, age, underlying diseases, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), lactate, procalcitonin, ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE), systolic velocity (S'), and global longitudinal strain/strain rate (GLS/GLSr) and global circumferential strain/strain rate (GCS/GCSr) by speckle tracking. Logistic regression analysis was used to evaluate the risk factors for mortality in septic patients, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of various risk factors for sepsis-related death. There was no significant difference in gender, age, underlying diseases, BNP, procalcitonin, EF, TAPSE, S', GLSr, GCS, or GCSr between the two groups (p>0.05). There were statistically significant differences in APACHE II score, SOFA score, cTnI, lactate, and GLS between the two groups (p<0.05). Logistic regression analysis showed that SOFA score (OR=2.32, 95% CI: 1.067-5.289, p<0.05), cTnI (OR=1.19, 95% CI: 1.001-1.312, p<0.05), and GLS (OR=1.58, 95% CI: 1.012-2.721, p<0.05) were risk factors for sepsis-related death (p<0.05). The areas under the ROC curves for SOFA score, cTnI, and GLS were 0.769, 0.757, and 0.846, respectively. SOFA score, cTnI, and GLS are independent risk factors for mortality in patients with sepsis. Among these factors, GLS has the highest predictive value for patient prognosis. Therefore, when predicting the prognosis of patients with sepsis, the assessment of right ventricular ultrasound can be used in clinical practice.

Antibiotic treatment of choice for urinary sepsis associated with ureteral lithiasis in Chile. Multicenter study

Inadequate antibiotic coverage in septic patients is associated with higher morbidity and mortality. This multicentric study reports antibiotic susceptibility in patients with ureterolithiasis-associated urosepsis, aiming to propose an optimal empirical therapy for this disease in the Chilean population. The prospective cohort study included patients from 7 Chilean hospitals who presented with ureterolithiasis and met sepsis criteria. We analyzed demographic data, vital signs at admission, and microbiological and radiological exams. We used descriptive statistics for the analysis of collected data. Initially, the study included 119 patients; 52 met the inclusion criteria. 77% were female, with a mean age of 52. 100% of the cohort had a urine culture taken at admission, whereas 48,7% had blood cultures. Escherichia Coli was the most common microorganism (73%), followed by Proteus Mirabilis (9.6%) and Klebsiella Pneumoniae (3.9%). Only two patients presented gram-positive pathogens. 100% of gram-negative bacteria were sensible to amikacin. The microorganisms found in our cohort were similar to those in international reports. Since the highest level of susceptibility was for amikacin, we propose its use as empirical therapy for urosepsis associated with ureterolithiasis in Chile. It is always necessary to consider the potential nephrotoxic effects of amikacin. An association of beta-lactams and glycopeptides should be considered in patients with risk factors for enterococcal infections.

Existing Data Sources in Clinical Epidemiology: Database of Community Acquired Infections Requiring Hospital Referral in Eastern Denmark (DCAIED) 2018-2021.

Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.