Outcome Of Sepsis Research Articles

A nationwide study on new onset atrial fibrillation risk factors and its association with hospital mortality in sepsis patients

Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01–1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

Sex or gender differences in treatment outcomes of sepsis and septic shock.

Gender disparities in intensive care unit (ICU) treatment approaches and outcomes are evident. However, clinicians often pay little attention to the importance of biological sex and sociocultural gender in their treatment courses. Previous studies have reported that differences between sexes or genders can significantly affect the manifestation of diseases, diagnosis, clinicians' treatment decisions, scope of treatment, and treatment outcomes in the intensive care field. In addition, numerous reports have suggested that immunomodulatory effects of sex hormones and differences in gene expression from X chromosomes between genders might play a significant role in treatment outcomes of various diseases. However, results from clinical studies are conflicting. Recently, the need for customized treatment based on physical, physiological, and genetic differences between females and males and sociocultural characteristics of society have been increasingly emphasized. However, interest in and research into this field are remarkably lacking in Asian countries, including South Korea. Through this review, we hope to enhance our awareness of the importance of sex and gender in intensive care treatment and research by briefly summarizing several principal issues, mainly focusing on sex and sex hormone-based outcomes in patients admitted to the ICU with sepsis and septic shock.

Impact of premorbid use of beta‑blockers on survival outcomes of patients with sepsis: A systematic review and meta‑analysis.

It is unclear if premorbid use of beta-blockers affects sepsis outcomes. The present systematic review aimed to assess the impact of premorbid beta-blocker use on mortality and the need for mechanical ventilation in patients with sepsis. Embase, Scopus, PubMed and Web of Science were searched for studies comparing outcomes of patients with sepsis based on the premorbid use of beta-blockers. The primary outcome was mortality, and the secondary outcome was the need for mechanical ventilation. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A total of 17 studies including 64,586 patients with sepsis were included. Of them, 8,665 patients received premorbid beta-blockers and 55,921 patients were not treated with premorbid beta-blockers and served as a control group. Pooled analysis of mortality rates revealed that premorbid use of beta-blockers did not affect in-hospital mortality (OR: 0.96; 95% CI: 0.78, 1.18; and I2=63%) but significantly reduced one-month mortality rates (OR: 0.83; 95% CI: 0.72, 0.96; and I2=63%). Combined analysis of adjusted data showed that premorbid beta-blockers were associated with a significant survival advantage in patients with sepsis (OR: 0.81; 95% CI: 0.72, 0.92; and I2=70%). However, there was no effect of premorbid use of beta-blockers on the need for mechanical ventilation (OR: 0.93; 95% CI: 0.66, 1.30); and I2=72%). The results of the present study indicated that premorbid use of beta-blockers is associated with improved survival in patients with sepsis. However, it does not impact the need for mechanical ventilation. The results should be interpreted with caution as the data is observational and unadjusted.

#807 Presepsin and procalcitonin levels are associated with acute kidney injury in sepsis patients

Abstract Background and Aims Acute kidney injury (AKI) is a leading cause of death in patients with sepsis. Presepsin is a novel biomarker which has been used to predict sepsis and the outcomes of sepsis. Presepsin was also demonstrated in a small clinical trial to be associated with AKI in sepsis patients. Procalcitonin is a biomarker which was well-studied in sepsis and AKI patients. We aimed to study the association of presepsin and procalcitonin with AKI and outcomes of AKI in sepsis patients. Method We conducted a multicenter prospective trial in eight tertiary-care hospitals in Thailand. We included suspected sepsis patients aged 18 years or older who entered the emergency room during January 2021 to July 2022. We excluded patients with pregnancy, previous trauma, and postcardiac arrest. We also excluded dialysis patients and patients with estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m2 from our study. We measured blood presepsin and procalcitonin at day 0, 3 and 7 along with other investigation for usual intensive care of sepsis. We calculated the level of presepsin and procalcitonin that could distinguish between sepsis patients with and without AKI. We also analyzed whether presepsin and procalcitonin were associated between severity of AKI determined by Kidney Disease: Improving Global Outcomes (KDIGO) staging of AKI. Results We recruited 621 patients who was diagnosed sepsis at emergency department. AKI was diagnosed in 246 patients (39.6%). Of these AKI patients, maximal KDIGO stage of AKI were stage 1, 2 and 3 in 140 (56.9%), 64 (26.0%) and 42 (17.1%) patients, respectively. The median age was 70.1 years with 54.6% was male patients. The median BMI was 21.9 kg/m2. The median Charlson comorbidity index (CCI) was 5 (IQR 4-7). The median presepsin level in AKI patients was 1012 pg/mL (IQR 528-1719 pg/mL), which was significantly higher (P < 0.001) than the median presepsin level in non-AKI patients, which was 594 pg/mL (IQR 337-1138 pg/mL). The median procalcitonin level in AKI patients was 1.24 ng/mL (IQR 0.22-6.06 ng/mL), which was significantly higher (P < 0.001) than the median presepsin level in non-AKI patients, which was 0.50 ng/mL (IQR 0.09-2.34 ng/mL). The cut-point of presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively. The higher level of presepsin and procalcitonin also significantly associated with higher KGIDO staging of AKI as shown in Fig. 1. However, the mortality rate in both groups were not significantly different (24.0% in AKI group vs. 21.1% in non-AKI group, P = 0.39) Conclusion To date, this is one of the largest studies to evaluate the association between presepsin level, procalcitonin level and AKI in sepsis patients. The presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively.

Clinical biomarker profiles reveals gender differences and mortality factors in sepsis.

Sepsis is a major contributor to global morbidity and mortality, affecting millions each year. Notwithstanding the decline in sepsis incidence and mortality over decades, gender disparities in sepsis outcomes persist, with research suggesting higher mortality rates in males. This retrospective study aims to delineate gender-specific clinical biomarker profiles impacting sepsis progression and mortality by examining sepsis cases and related clinical data from the past three years. Propensity score matching was used to select age-matched healthy controls for comparison. Among 265 sepsis patients, a significantly higher proportion were male (60.8%, P<0.001). While mortality did not significantly differ by gender, deceased patients were significantly older (mean 69 vs 43 years, P=0.003), more likely to have hypertension (54% vs 25%, P=0.019), and had higher SOFA scores (mean ~10 vs 4, P<0.01) compared to survivors. Principal Component Analysis (PCA) showed clear separation between sepsis patients and healthy controls. 48 serum biomarkers were significantly altered in sepsis, with Triiodothyronine, Apolipoprotein A, and Serum cystatin C having the highest diagnostic value by ROC analysis. Gender-stratified comparisons identified male-specific (e.g. AFP, HDLC) and female-specific (e.g. Rheumatoid factor, Interleukin-6) diagnostic biomarkers. Deceased patients significantly differed from survivors, with 22 differentially expressed markers; Antithrombin, Prealbumin, HDL cholesterol, Urea nitrogen and Hydroxybutyrate had the highest diagnostic efficiency for mortality. These findings enhance our understanding of gender disparities in sepsis and may guide future therapeutic strategies. Further research is warranted to validate these biomarker profiles and investigate the molecular mechanisms underlying these gender differences in sepsis outcomes.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism. We here provide the mechanistic evidence in support of the relevance for these observations. Angiopoetin-1 (Ang-1), which promotes vascular integrity, was decreased in blood plasma of human and murine septic newborns. In preclinical models, administration of Ang-1 provided prophylactic protection from septic death. Arachidonic acid metabolism appears to be functionally connected to Ang-1 via reactive oxygen species (ROS) with a direct role of nitric oxide (NO). Strengthening this intersection via oral administration of arachidonic acid and/or the NO donor L-arginine provided prophylactic as well as therapeutic protection from septic death while also increasing plasma Ang-1 levels among septic newborns. Our data highlight that targeting angiogenesis-associated pathways with interventions that increase Ang-1 activity directly or indirectly through ROS/eNOS provide promising avenues to prevent and/or treat severe neonatal sepsis.

Multimodal Quality Initiatives in Sepsis Care: Assessing Impact on Core Measures and Outcomes.

Providing timely and effective care for patients with sepsis is challenging due to delays in recognition and intervention. The Surviving Sepsis Campaign has developed bundles that have been shown to reduce sepsis mortality. However, hospitals have not consistently adhered to these bundles, resulting in suboptimal outcomes. To address this, a multimodal quality improvement sepsis program was implemented from 2017 to 2022 in a large urban tertiary hospital. The aim of this program was to enhance the Severe Sepsis and Septic Shock Management Bundle compliance and reduce sepsis mortality. At baseline, the Severe Sepsis and Septic Shock Management Bundle compliance rates were low, at 25%, with a sepsis observed/expected mortality ratio of 1.14. Our interventions included the formation of a multidisciplinary committee, the appointment of sepsis champions, the implementation of sepsis alerts and order sets, the formation of a Code Sepsis team, real-time audits, and peer-to-peer education. By 2022, compliance rose to 62%, and the observed/expected mortality ratio decreased to 0.73. Our approach led to improved outcomes and hospital rankings. These findings underscore the efficacy of a comprehensive sepsis care initiative, emphasizing the importance of interdisciplinary collaboration. A multimodal hospital-wide sepsis performance program is feasible and can contribute to improved outcomes. However, further research is necessary to determine the specific impact of individual strategies on sepsis outcomes.

Comparison between platelets to lymphocytes ratio, procalcitonin serum level, and SOFA score for outcome prediction in patients with sepsis

ABSTRACT Background Sepsis is a fatal condition with high treatment costs, early identification of sepsis is mandatory to avoid lethal complications. The objective of this study was to compare the predictive capabilities of platelets to lymphocytes ratio (PLR) and procalcitonin (PCT) in determining the outcome of sepsis. Methods This study was a prospective cross-sectional study and fifty-four individuals diagnosed with sepsis were involved. The participants were between the ages of twenty-one and sixty-five and had been admitted to ICU for more than twenty-four hours. The measurement of whole blood count and PCT serum levels was conducted at time of diagnosis, as well as on days three, seven, and fourteen following the onset of sepsis while SOFA score was conducted at time of admission. Results There was important elevation in platelet to lymphocytes ratio value and PCT in non survivors group compared to survivors group at day one, three, and seven of diagnosis of sepsis (p value ≤ 0.05), and day fourteen there were no data in non survivors group. The Sequential Organ Failure Assessment (SOFA) score was found to be the most effective in mortality prediction [area under the curve (AUC) = 0.982] second effective was PCT (AUC = 0.977) and PLR was third (AUC = 0.945). Conclusions In adult patients diagnosed with sepsis PLR with cutoff value > 228.89 demonstrates efficacy as a reliable prognostic indicator for predicting outcomes in sepsis. Although PLR may have a lower predictive power compared to PCT and SOFA score, it possesses the advantage of being a readily available and cost-effective technology.

Estradiol contributes to sex differences in resilience to sepsis-induced metabolic dysregulation and dysfunction in the heart via GPER-1-mediated PPARδ/NLRP3 signaling

Background and aimClinically, septic males tend to have higher mortality rates, but it is unclear if this is due to sex differences in cardiac dysfunction, possibly influenced by hormonal variations. Cardiac dysfunction significantly contributes to sepsis-related mortality, primarily influenced by metabolic imbalances. Peroxisome proliferator-activated receptor delta (PPARδ) is a key player in cardiac metabolism and its activation has been demonstrated to favor sepsis outcomes. While estradiol (E2) is abundant and beneficial in females, its impact on PPARδ-mediated metabolism in the heart with regards to sex during sepsis remains unknown. Methods and resultsHere, we unveil that while sepsis diminishes PPARδ nuclear translocation and induces metabolic dysregulation, oxidative stress, apoptosis and dysfunction in the heart thereby enhancing mortality, these effects are notably more pronounced in males than females. Mechanistic experiments employing ovariectomized(OVX) mice, E2 administration, and G protein-coupled estrogen receptor 1(GPER-1) knockout (KO) mice revealed that under lipopolysaccharide (LPS)-induced sepsis, E2 acting via GPER-1 enhances cardiac electrical activity and function, promotes PPARδ nuclear translocation, and subsequently ameliorates cardiac metabolism while mitigating oxidative stress and apoptosis in females. Furthermore, PPARδ specific activation using GW501516 in female GPER-1−/− mice reduced oxidative stress, ultimately decreasing NLRP3 expression in the heart. Remarkably, targeted GPER-1 activation using G1 in males mirrors these benefits, improving cardiac electrical activity and function, and ultimately enhancing survival rates during LPS challenge. By employing NLRP3 KO mice, we demonstrated that the targeted GPER-1 activation mitigated injury, enhanced metabolism, and reduced apoptosis in the heart of male mice via the downregulation of NLRP3. ConclusionOur findings collectively illuminate the sex-specific cardiac mechanisms influencing sepsis mortality, offering insights into physiological and pathological dimensions. From a pharmacological standpoint, this study introduces specific GPER-1 activation as a promising therapeutic intervention for males under septic conditions. These discoveries advance our understanding of the sex differences in sepsis-induced cardiac dysfunction and also present a novel avenue for targeted interventions with potential translational impact.

Impact of timing of antimicrobial therapy on outcome and mortality in severe sepsis and septic shock

Even though new antimicrobial treatments have been available for over 60 years, the fatality rate from septic shock has not decreased. Evolutionary pressure on microbial pathogens has, as expected, led to selection towards resistant species as a consequence of the creation of ever more broad-spectrum and strong antimicrobials. The ineffectiveness of antibiotic treatment of septic shock un the decades that followed may have been a result of this phenomena. The treatment of septic shock has traditionally focused on resuscitative measures. The management of these serious illnesses has not prioritised the prompt provision of effective antibiotic treatment.

Trajectories of State-Level Sepsis-Related Mortality by Race and Ethnicity Group in the United States.

Background: Recent reports on the national temporal trends of sepsis-related mortality in the United States (US) suggested improvement of outcomes in several race and ethnicity groups. However, it is unknown whether national data reflect state-level trajectories. Methods: We used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death data set to identify all decedents with sepsis in the US during 2010-2019. Negative binomial regression models were fit to estimate national and state-level trends of age-adjusted sepsis-related mortality rates within race and ethnicity groups. Results: There were 1,852,610 sepsis-related deaths in the US during 2010-2019. Nationally, sepsis-related mortality rates decreased among Blacks and Asians, were unchanged among Hispanics and Native Americans, and rose among Whites. The percent of states with similar trends were 30.0% among Blacks, 32.1% among Asians, 74.3% among Hispanics, 75.0% among Native Americans, and 66.7%% among Whites, while trending in opposite direction from 3.6% among Asians to 15.0% among Blacks. Conclusions: National trends in sepsis-related mortality in the US did not represent state-level trajectories in race ethnicity groups. Gains in sepsis outcomes among race and ethnicity groups at the national level were not shared equitably at the state level.

Exploring the relationship between HCMV serostatus and outcomes in COVID-19 sepsis.

Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19. A multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis. The prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival. These findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management. This study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.

Bacteriological profile and their antimicrobial susceptibility pattern among clinical suspected adult septicemia admitted patients: A study from tertiary care and teaching hospital

Objectives: The objective of this study is to determine the bacteriological profile and their antimicrobial susceptibility pattern among clinically suspected adult septicemia admitted patients and to study the correlation between the clinical presentation and inflammatory biomarkers (C-reactive protein [CRP] and Procalcitonin [PCT]) in the final outcomes of nosocomial sepsis in adult septicemia patients. Material and Methods: This is a descriptive cross-sectional study of 1-year duration from November 2022 to November 2023. The study has been approved from the Institutional Ethical Committee. Adult patients with a clinical suspected diagnosis of sepsis were admitted to the medicine ward of the tertiary hospital. Blood samples of adult sepsis suspected patients samples were taken for as a part of septicemia screening. Blood culture and sensitivity were performed according to standard guidelines. The sepsis inflammatory prognostic markers CRP and PCT test were evaluated according to manufactures instruction. Results: Out of 300 clinically suspected adult septicemia patients, 93 (31%) patients were isolated culture-positive sepsis while 207 (69%) patients were culture-negative sepsis. Gram-positive organisms were more (69%) as compared to Gram-negative organisms (31%). Staphylococcus aureus was predominant among Gram-positive organisms while Acinetobacter baumanii complex (9%) followed by Enterobacter spp. (8%) isolated in Gram-negative bacilli. Culture-positive sepsis patients have CRP level ≥3.2 mg/dL (80%) and the majority (80%) of these patients have reactive PCT. Conclusions: Successful treatment of bloodstream infection depends on early diagnosis and appropriate use of antimicrobial agents. Rapid identification results and antimicrobial susceptibility tests are essential for guiding clinicians in the selection of the most appropriate treatment for patients with bloodstream infections.

Outcome of sepsis in a Spanish sample of patients: A modest approach

Outcome of sepsis in a Spanish sample of patients: A modest approach

Trial of labour following two previous caesarean sections – A UK cohort study

ObjectivesTo assess the (i) predictors of and associated rates of success and; (ii) maternal and perinatal outcomes of women undergoing trial of labour after two previous caesarean sections (TOLA2C). Study designThis retrospective cohort study collected data from two regional obstetric centres with 12,000 deliveries per annum collectively. The population included singleton pregnancies undergoing (i) TOLA2C, (ii) elective repeat caesarean section following two caesarean sections (ERCS) and (iii) trial of labour after one caesarean section (TOLA1C). Data was collected electronically from 2013 to 2021. Statistical analysis included Fisher exact and Kruskal-Wallis test to compare unpaired samples alongside univariate and multivariable logistic regression. The primary outcome measure was maternal and perinatal outcome. ResultsThe three groups included; n = 146 TOLA2C, n = 206 ERCS and n = 99 TOLA1C. TOLA2C had a success rate of 65 % compared to 74 % for TOLA1C (p = 0.16). The optimal predictor of successful TOLA2C was previous successful TOLA1C OR 8.65 (95 % CI 2.75–38.41). TOLA2C was associated with greater risk of endometritis and/or sepsis postnatally compared to the other two groups [10.3 % (n = 15) versus 0.5 % (n = 1) and 3 % (n = 3) for ERCS and TOLA1C respectively p < 0.01]. It was also associated with longer maternal hospital stay [2.4 days (+/-1.8) versus 1.8 (+/-0.8) and 1.8 (+/-1.7) p < 0.01], a greater proportion of neonates with Apgar scores less than 7 (p=<0.01) and higher rates of neonatal unit admission [14 % (n = 20) versus 5 % (n = 11) versus 4 % (n = 4) (p=<0.01)]. ConclusionWomen considering trial of labour following two caesarean sections should be counselled regarding the potential increased risk of endometritis, sepsis and adverse neonatal outcome.

Anti-inflammatory effect of melatonin therapy in sepsis

Background The biggest cause of illness and death in children across the globe is sepsis. Melatonin, which is an endogenous lipophilic indoleamine that is primarily made from serotonin inside the pineal gland, has been shown in clinical research to be useful as an adjuvant treatment in septic newborns, improving outcomes and reducing complications, because of its strong antioxidant and immunological activities. Aim The goal of the present study is to evaluate the anti-inflammatory effects of melatonin as an additional treatment to antibiotics in children with sepsis, on laboratory markers and inflammatory cytokines: interleukin 6 (IL-6) and IL-8 as well as to study its impact on the outcome of these children. Patients and methods Our research is a prospective randomized controlled double-blinded trial from February 2017 to February 2018 at Mansoura University Children’s Hospital. This was accomplished by examining 30 children who were diagnosed with sepsis according to the Third International Consensus Definitions for Sepsis and Septic Shock. The study’s subjects were divided into two groups: group A (cases group) 15 children with sepsis in which antibiotics as well as a total oral dosage of 20 mg melatonin were given. Group B (control group) 15 matched septic children who received antibiotics as well as a cumulative oral dosage of 20 mg of a placebo. Results The research showed that melatonin administration as an adjuvant treatment was associated with a significant decrease in the C-reactive protein after treatment in group A than in group B (P=0.031). While there was a statistically insignificant decrease in white blood cells and an increase in hemoglobin as well as in platelets. Furthermore, serum IL-6 and IL-8 levels were significantly lower in the melatonin receiving group when matched with the control group 72 h after treatment (P=&lt;0.001, 0.021, respectively). Melatonin administration improved the outcome in melatonin-treated group better than the control group (P=0.01). Conclusion Melatonin can be used as an adjuvant treatment for children with sepsis as it significantly reduced the C-reactive protein, serum IL-6, and IL-8 levels as well as it improves the outcome of sepsis in these children.

Elevated Circulating Cell-Free Hemoglobin Drives Endothelial Glycocalyx Destruction and Inflammation in Sepsis

Rationale: Endothelial injury is a hallmark of sepsis-induced acute respiratory distress syndrome (ARDS). Endothelial barrier integrity is regulated by the endothelial glycocalyx, a matrix of proteoglycans and glycosaminoglycans (GAGs) that lines the vascular lumen. In sepsis, this glycocalyx is degraded by heparanase, which cleaves heparan sulfate, the primary glycocalyx GAG. Glycocalyx breakdown is linked to worse sepsis outcomes, but the mechanisms inducing heparanase activity in sepsis are unknown. We previously found that plasma levels of hemoglobin released from red blood cells (cell-free hemoglobin, CFH) are elevated in clinical sepsis and correlate with higher rates of ARDS and death. CFH also worsens endothelial injury and microvascular permeability in murine sepsis. We therefore hypothesized that CFH upregulates heparanase production to drive glycocalyx shedding and inflammation in sepsis. Methods: To test the association between CFH levels, heparanase expression, and glycocalyx degradation, circulating levels of heparanase, heparan sulfate, and total GAGs were measured in 77 sepsis patients and compared across CFH quartiles. In mice with intraabdominal polymicrobial sepsis with elevated CFH (CS [cecal slurry] + intravenous [IV] CFH), plasma heparanase, total GAGs, and syndecan-1 were quantified. Whole lung and plasma pro-inflammatory cytokines were also determined to investigate the impact of CFH on inflammation in sepsis. Results: In sepsis patients, higher circulating CFH levels were associated with increased plasma heparanase (p=0.0304), total GAGs (p=0.0178), and heparan sulfate (p=0.0112). CFH also exacerbated glycocalyx degradation in murine sepsis; circulating syndecan-1 (p=0.0152) and total GAGs (p=0.0094) were elevated in animals that received CS+IV CFH compared to CS alone. This effect may be mediated by upregulation of active heparanase, which was higher in the plasma of CS+IV CFH treated animals (p=0.1333). CFH also worsened illness severity, as CS+IV CFH animals had worse sepsis severity scores (p=0.0074). Whole lung tumor necrosis factor-alpha (TNF-a; p=0.0129) and interferon-gamma (IFN-g; p=0.0264) transcript levels were increased in the CS+IV CFH group, indicating greater lung inflammation. Systemic inflammation was also enhanced in the CS+IV CFH animals, demonstrated by higher plasma TNF-a (p&lt;0.001) and IFN-g (p=0.0221) concentrations. Conclusions: In sepsis, CFH is associated with upregulation of heparanase and endothelial glycocalyx degradation, which may disrupt the endothelial barrier, causing downstream organ injury. Future studies to define the molecular pathways that underlie these findings and their effect on endothelial permeability will be an important next step towards identifying novel treatment targets to improve outcomes for patients with sepsis-associated ARDS. Funding F30HL170483, R01HL164937, R01HL158906, R01HL150783, R01HL125371. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparison of Neutrophil Lymphocyte Ratio combined SOFA versus APACHE IV in assessing the Prognosis of Sepsis Patients admitted to Medical Intensive Care Unit

Background Sepsis poses a significant threat in the Medical Intensive Care Unit (MICU), with high morbidity and mortality rates. Accurate prognostic tools are essential for guiding patient management. This study aims to compare the effectiveness of Neutrophil–Lymphocyte Ratio with Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) in predicting sepsis outcomes. A prospective cross-sectional design will enrol septic MICU patients, collecting baseline data and scoring systems. Patient outcomes, including mortality and length of MICU stay, will be analyzed using correlation and ROC curve analyses. This study addresses the current gap in direct comparisons of these tools. Results The results of this study are anticipated to reveal significant correlations between the Neutrophil Lymphocyte Ratio combined with SOFA and APACHE IV scores and patient outcomes. Specifically, we expected to observe strong associations between the combined scoring system and mortality rates, length of MICU stay, and the need for organ support. Furthermore, we anticipate that the Neutrophil Lymphocyte Ratio combined with SOFA will demonstrate higher predictive accuracy than APACHE IV to assess prognosis in sepsis patients admitted to the MICU. Conclusion Based on the results obtained from this prospective cross-sectional study, we can draw conclusions regarding the comparative effectiveness of NLR (Neutrophil Lymphocyte Ratio) combined with SOFA and APACHE IV in assessing the prognosis of sepsis in the MICU. We anticipate that the combined scoring system will provide a more accurate prognostic assessment and enable healthcare professionals to make well-informed choices regarding patient care and the distribution of resources. These findings will contribute to building evidence on sepsis and may have implications for improving patient outcomes in the MICU setting.

The causality of gut microbiota on onset and progression of sepsis: a bi-directional Mendelian randomization analysis.

Several observational studies have proposed a potential link between gut microbiota and the onset and progression of sepsis. Nevertheless, the causality of gut microbiota and sepsis remains debatable and warrants more comprehensive exploration. We conducted a two-sample Mendelian randomization (MR) analysis to test the causality between gut microbiota and the onset and progression of sepsis. The genome-wide association study (GWAS) summary statistics for 196 bacterial traits were extracted from the MiBioGen consortium, whereas the GWAS summary statistics for sepsis and sepsis-related outcomes came from the UK Biobank. The inverse-variance weighted (IVW) approach was the primary method used to examine the causal association. To complement the IVW method, we utilized four additional MR methods. We performed a series of sensitivity analyses to examine the robustness of the causal estimates. We assessed the causality of 196 bacterial traits on sepsis and sepsis-related outcomes. Genus Coprococcus2 [odds ratio (OR) 0.81, 95% confidence interval (CI) (0.69-0.94), p = 0.007] and genus Dialister (OR 0.85, 95% CI 0.74-0.97, p = 0.016) had a protective effect on sepsis, whereas genus Ruminococcaceae UCG011 (OR 1.10, 95% CI 1.01-1.20, p = 0.024) increased the risk of sepsis. When it came to sepsis requiring critical care, genus Anaerostipes (OR 0.49, 95% CI 0.31-0.76, p = 0.002), genus Coprococcus1 (OR 0.65, 95% CI 0.43-1.00, p = 0.049), and genus Lachnospiraceae UCG004 (OR 0.51, 95% CI 0.34-0.77, p = 0.001) emerged as protective factors. Concerning 28-day mortality of sepsis, genus Coprococcus1 (OR 0.67, 95% CI 0.48-0.94, p = 0.020), genus Coprococcus2 (OR 0.48, 95% CI 0.27-0.86, p = 0.013), genus Lachnospiraceae FCS020 (OR 0.70, 95% CI 0.52-0.95, p = 0.023), and genus Victivallis (OR 0.82, 95% CI 0.68-0.99, p = 0.042) presented a protective effect, whereas genus Ruminococcus torques group (OR 1.53, 95% CI 1.00-2.35, p = 0.049), genus Sellimonas (OR 1.25, 95% CI 1.04-1.50, p = 0.019), and genus Terrisporobacter (OR 1.43, 95% CI 1.02-2.02, p = 0.040) presented a harmful effect. Furthermore, genus Coprococcus1 (OR 0.42, 95% CI 0.19-0.92, p = 0.031), genus Coprococcus2 (OR 0.34, 95% CI 0.14-0.83, p = 0.018), and genus Ruminiclostridium6 (OR 0.43, 95% CI 0.22-0.83, p = 0.012) were associated with a lower 28-day mortality of sepsis requiring critical care. This MR analysis unveiled a causality between the 21 bacterial traits and sepsis and sepsis-related outcomes. Our findings may help the development of novel microbiota-based therapeutics to decrease the morbidity and mortality of sepsis.

Sepsis and Septic Shock in Patients Undergoing Thyroidectomy: Incidence, Risk Factors, and Outcomes

IntroductionPostoperative sepsis represents a rare complication following thyroidectomy. We aimed to explore the incidence, risk factors, sources, and outcomes of postoperative sepsis and septic shock among adult patients undergoing thyroidectomy. MethodsData from the American College of Surgeons National Surgical Quality Improvement Program were used in this retrospective cohort study. Patients aged ≥18 y who underwent elective thyroidectomy between 2005 and 2019 were included. Multivariable binary logistic regression models were computed to explore risk factors and outcomes of 30-d sepsis and septic shock. ResultsAmong the 180,373 included patients, 0.1% developed sepsis or septic shock. Male gender, low body mass index, American Society of Anesthesiologists classes 3-5, functional dependence, smoking, diabetes mellitus, pulmonary disease, inpatient surgery, malignant indication, clean-contaminated wound classification, and operation time ≥150 min were significant risk factors for development of sepsis or septic shock. Common infectious sources of sepsis included surgical site infections (29.6%), pneumonia (18.6%), urinary tract infections (16.2%), and multiple infections (6.9%). Patients with postoperative sepsis or septic shock were significantly more likely to develop complications, including wound disruption, stroke, cardiac and renal complications, thromboembolism, prolonged length of stay, unplanned reoperation, and mortality. ConclusionsSepsis is rare following thyroidectomy. Our study provides insight into risk factors and procedural characteristics which may contribute to the development of postoperative sepsis or septic shock in this population.