Risk Of Sepsis Research Articles

Does Gastroesophageal Reflux Disease Increase the Risk of Sepsis and Its 28-day Mortality? A Causal Study Using a Mendelian Randomization Approach.

Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder. Recent studies indicate that GERD may exert systemic effects, potentially elevating the risk of severe infections, including sepsis. Nevertheless, the causal relationship between GERD and sepsis, as well as sepsis-related 28-day mortality, remains uncertain. The aim of this study is to investigate the causal relationship between GERD and the risk of sepsis, including 28-day mortality of sepsis. This study utilized a two-sample Mendelian Randomization (MR) approach to analyze data from publicly available genome-wide association studies (GWAS) databases ( https://gwas.mrcieu.ac.uk/ ). The analysis comprised 129,080 cases and 473,524 controls for GERD; 11,643 patients and 474,841 controls for sepsis; and 1,896 patients and 484,588 controls for 28-day mortality from sepsis. The objective was to evaluate the causal impact of GERD on the risk of sepsis and 28-day sepsis mortality. Genetic variation data pertinent to GERD were obtained from the most recent genome-wide association studies (GWAS). The primary analysis employed the Inverse Variance Weighted (IVW) method. Sensitivity and pleiotropy analyses were performed to validate the robustness of the findings. MR analysis revealed a notable link between genetically predicted GERD and increased sepsis risk (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.24-1.52; p = 2.79 × 10-9). Moreover, GERD correlated with elevated 28-day mortality of sepsis (OR 1.44, 95% CI 1.11-1.85; p = 5.34 × 10-3). These results remained consistent throughout various sensitivity analyses, indicating their resilience against potential pleiotropy and other biases. This study indicates that genetic predisposition to GERD may be linked to an elevated risk of sepsis and its associated 28-day mortality. However, the study does not establish a direct causal relationship for GERD itself, nor does it assess the impact of GERD treatment. Further research is needed to explore the underlying mechanisms and potential therapeutic interventions involved.

Comparison of Modified Early Warning Score (MEWS), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) for early prediction of septic shock in diabetic patients in Emergency Departments

IntroductionSepsis is a severe medical condition that can be life-threatening. If sepsis progresses to septic shock, the mortality rate increases to around 40%, much higher than the 10% mortality observed in sepsis. Diabetes increases infection and sepsis risk, making management complex. Various scores of screening tools, such as Modified Early Warning Score (MEWS), Simplified Acute Physiology Score (SAPS II), Sequential Organ Failure Assessment Score (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE II), are used to predict the severity or mortality rate of disease. Our study aimed to compare the effectiveness and optimal cutoff points of these scores. We focused on the early prediction of septic shock in patients with diabetes in the Emergency Department (ED).MethodsWe conducted a retrospective cohort study to collect data on patients with diabetes. We collected prediction factors and MEWS, SOFA, SAPS II and APACHE II scores to predict septic shock in these patients. We determined the optimal cutoff points for each score. Subsequently, we compared the identified scores with the gold standard for diagnosing septic shock by applying the Sepsis-3 criteria.ResultsSystolic blood pressure (SBP), peripheral oxygen saturation (SpO2), Glasgow Coma Scale (GCS), pH, and lactate concentrations were significant predictors of septic shock (p < 0.001). The SOFA score performed well in predicting septic shock in patients with diabetes. The area under the receiver operating characteristics (ROC) curve for the SOFA score was 0.866 for detection within 48 h and 0.840 for detection after 2 h of admission to the ED, with the optimal cutoff score of ≥ 6.ConclusionSBP, SpO2, GCS, pH, and lactate concentrations are crucial for the early prediction of septic shock in patients with diabetes. The SOFA score is a superior predictor for the onset of septic shock in patients with diabetes compared with MEWS, SAPS II, and APACHE II scores. Specifically, a cutoff of ≥ 6 in the SOFA score demonstrates high accuracy in predicting shock within 48 h post-ED visit and as early as 2 h after ED admission.

Validation and comparison of triage-based screening strategies for sepsis

ObjectiveThis study sought to externally validate and compare proposed methods for stratifying sepsis risk at emergency department (ED) triage. MethodsThis nested case/control study enrolled ED patients from four hospitals in Utah and evaluated the performance of previously-published sepsis risk scores amenable to use at ED triage based on their area under the precision-recall curve (AUPRC, which balances positive predictive value and sensitivity) and area under the receiver operator characteristic curve (AUROC, which balances sensitivity and specificity). Score performance for predicting whether patients met Sepsis-3 criteria in the ED was compared to patients' assigned ED triage score (Canadian Triage Acuity Score [CTAS]) with adjustment for multiple comparisons. ResultsAmong 2000 case/control patients, 981 met Sepsis-3 criteria on final adjudication. The best performing sepsis risk scores were the Predict Sepsis version #3 (AUPRC 0.183, 95 % CI 0.148–0.256; AUROC 0.859, 95 % CI 0.843–0.875) and Borelli scores (AUPRC 0.127, 95 % CI 0.107–0.160, AUROC 0.845, 95 % CI 0.829–0.862), which significantly outperformed CTAS (AUPRC 0.038, 95 % CI 0.035–0.042, AUROC 0.650, 95 % CI 0.628–0.671, p < 0.001 for all AUPRC and AUROC comparisons). The Predict Sepsis and Borelli scores exhibited sensitivity of 0.670 and 0.678 and specificity of 0.902 and 0.834, respectively, at their recommended cutoff values and outperformed Systemic Inflammatory Response Syndrome (SIRS) criteria (AUPRC 0.083, 95 % CI 0.070–0.102, p = 0.052 and p = 0.078, respectively; AUROC 0.775, 95 % CI 0.756–0.795, p < 0.001 for both scores). ConclusionsThe Predict Sepsis and Borelli scores exhibited improved performance including increased specificity and positive predictive values for sepsis identification at ED triage compared to CTAS and SIRS criteria.

Wandering Spleen Complicated by Thrombocytopenia, Acute Appendicitis, and Sepsis: A Case Report and Literature Review

Wandering spleen (WS) is a rare condition often linked with torsion or infarction, but its association with Bochdalek hernia, acute appendicitis, and thrombocytopenia is exceptionally rare. We present a case of a nine-year-old girl who was admitted with acute abdominal pain, later diagnosed with WS, Bochdalek hernia, and acute appendicitis. A literature search was performed on PubMed and Google Scholar on 30 May 2024 with keywords including “Wandering spleen” and (“Bochdalek Hernia” OR “Sepsis” OR “Acute Appendicitis” OR “Thrombocytopenia”). The management was complicated by severe thrombocytopenia and post-operative sepsis, with Klebsiella pneumoniae as the causative agent. Imaging revealed an abnormally located spleen and significant splenic enlargement over time. The patient’s condition was managed non-operatively concerning the WS, avoiding splenectomy due to the risks of post-splenectomy sepsis. Instead, laparotomy was performed to address the appendicitis and diaphragmatic hernia. The patient experienced post-operative complications, including a seizure and persistent fever, which resolved with appropriate antibiotic therapy. This case underscores the complexity of managing WS with concurrent severe conditions, highlighting the importance of individualised treatment strategies. It also emphasises the need for further studies to explore optimal treatment modalities for such rare and complex presentations. This case serves as an educational example in clinical settings, demonstrating the challenges and considerations when treating multiple rare pathologies simultaneously.

The role of colonization with resistant Gram-negative bacteria in the treatment of febrile neutropenia after stem cell transplantation

Febrile neutropenia (FN) is one of the most common complications of stem cell transplantation. The aim of this analysis was to evaluate the frequency of sepsis in patients with FN colonized with resistant Gram negative bacteria (Extended spectrum β-lactamase positive, multidrug resistant (MDR) P. aeruginosa) and the choice of primary antibiotic in colonized patients. This was a retrospective study analyzed data from patients who underwent hematopoietic stem cell transplantation from 01/2018 to 09/2022. Data were extracted from the hospital information system. Carbapenem as the primary antibiotic of choice was chosen in 10.9% of non-colonized +/-AmpC patients, 31.5% of ESBL+ patients, and 0% of MDR P. aeruginosa patients. Patients with FN and MDR P. aeruginosa colonization had a high prevalence of sepsis (namely 100%, p = 0.0197). The spectrum of sepsis appeared to be different, with Gram negative bacilli predominating in the ESBL+ group (p = 0.0123, OR 5.39 [95% CI 1.55-18.76]). Colonizer sepsis was present in 100% of sepsis with MDR P. aeruginosa colonization (p=0.002), all in allogeneic transplantation (p=0.0003), with a mortality rate of 33.3% (p=0.0384). The incidence of sepsis in patients with ESBL+ colonization was 25.9% (p=0.0197), with colonizer sepsis in 50% of sepsis cases (p=0.0002), most in allogeneic transplantation (p=0.0003). The results show a significant risk of sepsis in FN with MDR P. aeruginosa colonization, this state is almost exclusively caused by the colonizer. At the same time, a higher risk of Gram negative sepsis has been demonstrated in patients colonized with ESBL+ bacteria.

378. LAPAROSCOPIC PRIMARY CLOSURE OF ESOPHAGEAL RUPTURE CAUSED BY BALLOON DILATATION FOR ACHALASIA AND HELLER'S MYOTOMY WITH DOR FUNDOPLICATION

Abstract Background Achalasia is a Primary motor disorder of the esophagus cased by Insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Major clinical presentations are Dysphagia, regurgitation, and occasional chest pain with or without weight loss. One of most commonly performed conservative treatment is pneumatic dilatation and its most serious complication is esophageal perforation. In this presentation we will introduce a case of esophageal perforation caused by pneumatic dilatation for esophageal achalasia treated with laparoscopic primary closure of perforation and simultaneous Heller’s myotomy with Dor Fundoplication. Methods Esophageal perforation occurred during endoscopic pneumatic dilatation occurred in 61-year-old female patient with achalasia. Initially endoscopic clipping was performed but the patient showed leukocytosis, tachycardia and decreased oxygen saturation with dyspnea. Chest CT showed intraabdominal and mediastinal free air and defect in distal esophagus. Then the patient was referred for surgery. During laparoscopic exploration, 3cm mucosal and 6cm muscle tearing at distal esophagus 2cm proximal to the esophagogastric junction at 3 o’clock direction. After removal of endoscopic clips, primary closure of esophageal rupture in 2-layed method and simultaneous Heller’s Myotomy with Dor fundoplication at 12 o’clock direction was performed. Results The patient showed rapid recovery from septic condition. Nasogastric tube was removed 4 days after surgery. Upper GI series checked with gastrografin 5 days after surgery showed no leakage and no delayed passage in distal esophagus. Chest tube and abdominal drain were removed and the patient was discharged 10 days after surgery. There was no dysphagia and reflux during follow-up afterwards. Conclusion Primary closure for esophageal rupture occurred during balloon dilatation for achalasia and simultaneous Heller’s myotomy with Dor fundoplication by approaching the esophagus from a different direction were successfully performed reducing not only the risk of fulminant sepsis but also the burden of the surgery for achalasia that would be needed to be performed later.

Readmissions in Sepsis Survivors: Discharge Setting Risks.

Sepsis is a complex condition with high morbidity and mortality. Prompt treatment can improve survival, but for survivors the risk of deterioration and readmission remains high. Little is known about the association between discharge setting and readmission among sepsis survivors. To examine 30-day hospital readmission rates in adult sepsis survivors by the type of setting to which patients were discharged. The Medical Information Mart for Intensive Care database was used to identify adult sepsis survivors and evaluate 30-day readmission by discharge setting. A χ2 contingency analysis was used with each factor and presence/absence of readmission. The Kruskal-Wallis test was used to compare readmissions across discharge settings. From our sample (N = 7107; mean age 66.5 years; 46.2% women), 23.6% (n = 1674) were readmitted within 30 days and of those readmitted, 30% were readmitted between 1 and 3 times. Discharge setting (P < .001) and age (P = .02) were significantly associated with readmission, but sex, ethnicity, and insurance type were not. High numbers of readmissions were seen in patients discharged to skilled nursing facilities (29.6%), home health care (26.9%), and home (15.0%). Similar high comorbidity burden and acuteness of illness were seen in patients discharged to these settings. Sepsis survivors discharged to skilled nursing facilities, home health care, and home are at high risk for 30-day readmission. The rates of readmission from home health care and home settings were alarming. Often patients are discharged to inappropriate settings, placing them at risk for residual sepsis and readmission. Future research should focus on appropriate timing of hospital discharge and transition to the most appropriate discharge setting.

Outpatient Management of Fever and Neutropenia in Low-risk Children with Solid Tumors: A Quality Improvement Initiative.

Management of febrile neutropenia in pediatric oncology usually requires inpatient parenteral antibiotics after initial evaluation, but some patients at lower risk of sepsis could be safely managed outpatient. We describe a quality improvement project to increase outpatient management of fever and neutropenia. We designed a standardized algorithm for children with a solid tumor diagnosis and low risk for bacteremia. The aim was to achieve outpatient management for at least 80% of eligible patients within 20 months of project initiation. We used plan-do-study-act cycles to improve algorithm compliance, including optimizing medical record decision support, developing targeted educational materials and outreach, and restructuring outpatient processes to allow for close follow-up. We surveyed patients (age ≥12 y) and parents/caregivers to assess the impact of outpatient management. The initiative led to 71% (n = 34) of eligible patients being managed as outpatients. Six percent (n = 2) of patients developed bacteremia, resulting in hospital admission. Fifteen of 26 parents/caregivers and five of 11 patients approached completed the survey. For the preferred setting of febrile neutropenia management, 83% of patients preferred to be home versus 40% of parents/caregivers. No patient expressed any of the three highest ratings in the question exploring fear regarding outpatient febrile neutropenia management versus 67% of parents/caregivers. Some children with a solid tumor diagnosis at low risk for bacteremia are safely managed for febrile neutropenia as outpatients. Targeted efforts to engage parents/caregivers early in this practice change are necessary for success.

Examining Sepsis Incidence, Risk Factors, and Mitigation Efforts at PKU Muhammadiyah Gamping Hospital, Yogyakarta: A Retrospective Analysis

Sepsis poses a significant challenge in healthcare settings due to its association with heightened morbidity and mortality rates, prolonged hospitalizations, and increased healthcare expenditures. This study aims to investigate the incidence of sepsis, its associated risk factors, and the efficacy of various mitigation efforts implemented at PKU Muhammadiyah Gamping Hospital in Yogyakarta. Employing a cross-sectional, analytical observational design, this study examined a sample comprising patients diagnosed with sepsis at the hospital between January 2019 and December 2022, meeting predefined inclusion and exclusion criteria. Inclusion criteria encompassed patients diagnosed with sepsis in accordance with hospital protocols and those admitted between January 2019 and December 31, 2022, while exclusion criteria included patients with incomplete bacteremia diagnoses. Consecutive sampling was utilized for sample selection, with data extracted from patient records maintained in the hospital's medical archives. This study was conducted with the approval of PKU Muhammadiyah Gamping Hospital's ethical committee (permit number: 051/KEP-PKU/III/2023). Analysis of four years' worth of data revealed a total of 210 cases of sepsis, comprising 112 male and 98 female patients.

Paper-Based procalcitonin and Interleukin-6 test strip with Spectrum-Based optical reader for enterovirus severity differentiation in children

Infectious diseases significantly impact global health, necessitating prompt diagnosis to mitigate life-threatening sepsis risk. Identifying patients at risk of severe neurological complications from enterovirus infections is challenging due to nonspecific initial presentations. Point-of-care testing (POCT) has emerged as a transformative tool, with low-cost lateral-flow colorimetric assays showing promise in deployable POCT devices. We developed a PCT/IL-6 rapid diagnostic system integrating lateral flow assay (LFA) test strips and a portable optical spectrum reader, allowing simultaneous semi-quantitative measurement of serum PCT and IL-6 within 30 min at the point of care. The system demonstrated a strong correlation with traditional ELISA and effectively differentiated severe pediatric enterovirus cases using serum samples. IL-6 showed superior discriminatory ability over PCT in identifying patients with severe neurological complications. This novel diagnostic platform holds great potential for early sepsis recognition and infectious disease management, especially in resource-limited settings.

Plasma Proteome, Metabolome Mendelian Randomization Identifies Sepsis Therapeutic Targets.

The interrelation between the plasma proteome and plasma metabolome with sepsis presents a multifaceted dynamic that necessitates further research to elucidate the underlying causal mechanisms. Our investigation used public genome-wide association study (GWAS) data to explore the relationships among the plasma proteome, metabolome, and sepsis, considering different sepsis subgroup. Initially, two-sample MR established causal connections between the plasma proteome and metabolome with sepsis. Subsequently, multivariate and iterative MR analyses were performed to understand the complex interactions in plasma during sepsis. The validity of these findings was supported by thorough sensitivity analyses. The study identified 25 plasma proteins that enhance risk and 34 that act as protective agents in sepsis. Post p-value adjustment (0.05/1306), ICAM5 emerged with a positive correlation to sepsis susceptibility (p-value = 2.14E-05, OR = 1.10, 95% CI = 1.05-1.15), with this significance preserved across three sepsis subgroup examined. Additionally, 29 plasma metabolites were recognized as risk factors, and 15 as protective factors for sepsis outcomes. Following p-value adjustment (0.05/997), elevated levels of 1,2,3-benzenetriol sulfate (2) was significantly associated with increased sepsis risk (p-value = 3.37E-05, OR = 1.18, 95% CI = 1.09-1.28). Further scrutiny revealed that this plasma metabolite notably augments the abundance of ICAM5 protein (p-value = 3.52E-04, OR = 1.11, 95% CI = 1.04-1.17), devoid of any detected heterogeneity, pleiotropy, or reverse causality. Mediated MR revealed ICAM5 mediated 11.9% of 1,2,3-benzenetriol sulfate (2)'s total effect on sepsis progression. This study details the causal link between the plasma proteome and metabolome with sepsis, highlighting the roles of ICAM5 and 1,2,3-benzenetriol sulfate (2) in sepsis progression, both independently and through crosstalk.

U-shaped correlation of lymphocyte count with all-cause hospital mortality in sepsis and septic shock patients: a MIMIC-IV and eICU-CRD database study

BackgroundIn sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients.MethodsThis retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients.ResultsOur study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P < 0.01; HR = 1.06, P < 0.01). RCS regression analysis revealed a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients (P for overall < 0.001, P for nonliner < 0.01; P for overall = 0.002, P for nonliner = 0.014). Subgroup analyses revealed that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease and requiring renal replacement therapy (P for overall = 0.021, P for nonliner = 0.158; P for overall = 0.025, P for nonliner = 0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets of critically ill sepsis patients.ConclusionOur findings demonstrate that lymphocyte counts are a significant independent predictor of hospital mortality in sepsis and septic shock patients. We observed a U-shaped association between lymphocyte levels and mortality risk, indicating that high and low counts are linked to increased mortality. This result highlights the complex role of lymphocytes in sepsis outcomes and suggests the need for further investigation into the underlying mechanisms and potential therapeutic approaches. Integrating lymphocyte count assessment into risk stratification algorithms and clinical decision support tools could enhance the early identification of high-risk sepsis patients.

Preoperative Hypoalbuminemia is Associated With Higher 30-day Mortality and Complications After Esophagectomy.

Serum albumin level is routinely screened during preoperative assessments as a biomarker for poor nutritional status and/or concurrent inflammation. In esophagectomy, while early postoperative hypoalbuminemia is associated with a higher risk of adverse surgical outcomes, the effects of preoperative hypoalbuminemia on esophagectomy outcomes were conflicting. This study aimed to examine the effect of preoperative hypoalbuminemia on 30-day outcomes following esophagectomy. National Surgical Quality Improvement Program (NSQIP) esophagectomy targeted database from 2016 to 2022 was used. Patients with preoperative serum albumin <3.4g/L were defined as having hypoalbuminemia. Patients with and without hypoalbuminemia were propensity-score matched (1:3 ratio) for demographics, baseline characteristics, neoadjuvant therapy, surgical approaches, tumor diagnosis, and pathologic staging of the malignancy. Thirty-day postoperative outcomes were examined. There were 803 (10.24%) and 7046 (89.76%) patients with and without preoperative hypoalbuminemia who underwent esophagectomy, respectively. After propensity-score matching, all patients with hypoalbuminemia were matched to 2170 controls. After propensity-matching, patients with hypoalbuminemia had higher risks of mortality (4.48% vs 3.00%, P = 0.04), sepsis (14.94% vs 10.92%, P < 0.01), and bleeding requiring transfusion (21.30% vs 13.50%, P < 0.01). Also, patients with hypoalbuminemia had a higher rate of discharge not to home (42.65% vs 34.81%, P < 0.01) and longer LOS (12.69 ± 9.09 vs 11.39 ± 8.16 days, P < 0.01). Patients with preoperative hypoalbuminemia had increased risks of mortality and complications after esophagectomy. Thus, preoperative hypoalbuminemia could be a useful and cost-effective tool for preoperative risk stratification for patients undergoing esophagectomy, and correcting the underlying cause of hypoalbuminemia may help decrease the risk of adverse postoperative outcomes.

Bleeding disorder increases the risks of complications following arthroscopic rotator cuff repair.

It is imperative to determine patients' risk factors prior to arthroscopic rotator cuff repair (ARCR), so that the physician and patient are both aware of the possible postoperative complications. However, the impact of bleeding disorders on a patient's short-term postoperative outcome has not yet been analyzed. A national database was queried for patients undergoing ARCR from 2006 to 2018. Two patient cohorts were defined: patients with a bleeding disorder and patients without a bleeding disorder. In this analysis, outcomes including postoperative complications, hospital admission, extended length of stay, and mortality were compared between the two cohorts using bivariate and multivariate analyses. Of 33,374 patients undergoing ARCR, 32,849 patients (98.4%) did not have a bleeding disorder whereas 525 patients (1.6%) had a bleeding disorder. Following adjustment on multivariate analyses, patients with a bleeding disorder had an increased risk of postoperative transfusion (OR 8.11; p = 0.044), sepsis (OR 11.86; p = 0.003), hospital admission (OR 1.41; p = 0.008), and mortality (OR 8.10; p = 0.019). Patients with documented bleeding disorder have an increased risk of postoperative complications compared to patients without a bleeding disorder. Consequently, it is essential to recognize these risk factors to decrease postoperative complications to optimize patient outcomes and costs. III.

Dissecting the mediating role of inflammatory factors in the interaction between metabolites and sepsis: insights from bidirectional Mendelian randomization.

Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine's protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

Platelet traits and sepsis risk and prognosis: a bidirectional two-sample Mendelian randomization study.

Sepsis is a critical medical condition characterized by a dysregulated host response to infection. Platelet abnormalities frequently manifest in sepsis patients, but the causal role of platelets in sepsis remains unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach to investigate the causal direction between platelets and sepsis. MR analysis was used to investigate the causal effect of four platelet traits - platelet count (PLT), platelet crit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW)- on sepsis risk and prognosis. Additionally, the study explored the reverse causality, assessing the impact of sepsis on these platelet traits. Genetic variants from large-scale genome-wide association studies (GWAS) served as instrumental variables to infer causality. Sensitivity analyses and heterogeneity tests were conducted to ensure the validity and robustness of the results. Genetically predicted decreased PCT (OR = 0.938, p = 0.044) and MPV (OR = 0.410, p = 0.006) were associated with an increased risk of sepsis. In the reverse direction, 28-day sepsis mortality was significantly associated with decreased PLT (OR = 0.986, p = 0.034). No significant causal relationships were observed between sepsis and other platelet traits. This study suggests a causal association between low PCT and MPV levels and increased risk of sepsis. Additionally, sepsis with a poor prognosis was causally linked to decreased PLT. These findings provide novel evidence for the causal relationship between platelet traits and sepsis.

The impact of butyrate on group B Streptococcus-induced intestinal barrier disruption.

Group B Streptococcus (Streptococcus agalactiae; GBS) is a leading cause of neonatal sepsis worldwide. As a pathobiont of the intestinal tract, it is capable of translocating across barriers leading to invasive disease. Neonatal susceptibility to invasive disease stems from immature intestinal barriers. GBS intestinal colonization induces major transcriptomic changes in the intestinal epithelium related to barrier function. Butyrate, a microbial metabolite produced by fermentation of dietary fiber, bolsters intestinal barrier function against enteric pathogens, and these effects can be transferred in utero via the placenta to the developing fetus. Our aim was to determine if butyrate mitigates GBS disruption of intestinal barriers. We used human intestinal epithelial cell (IEC) lines to evaluate the impact of butyrate on GBS-induced cell death and GBS adhesion and invasion. IECs and human fetal tissue-derived enteroids were used to evaluate monolayer permeability. We evaluated the impact of maternal butyrate treatment (mButyrate) using our established mouse model of neonatal GBS intestinal colonization and late-onset sepsis. We found that butyrate reduces GBS-induced cell death, GBS invasion, monolayer permeability, and translocation in vitro. In mice, mButyrate decreases GBS intestinal burden in offspring. Our results demonstrate the importance of bacterial metabolites, such as butyrate, in their potential to bolster epithelial barrier function and mitigate neonatal sepsis risk.IMPORTANCEGroup B Streptococcus (GBS) is a leading cause of neonatal morbidity and mortality. It is a commensal of the intestines that can translocate across barriers leading to sepsis in vulnerable newborns. With the rise in antibiotic-resistant strains and no licensed vaccine, there is an urgent need for preventative strategies. Butyrate, a short-chain fatty acid metabolized in the gut, enhances barrier function against pathogens. Importantly, butyrate is transferred in utero, conferring these benefits to infants. Here, we demonstrate that butyrate reduces GBS colonization and epithelial invasion. These effects were not microbiome-driven, suggesting butyrate directly impacts epithelial barrier function. Our results highlight the potential impact of maternal dietary metabolites, like butyrate, as a strategy to mitigate neonatal sepsis risk.

Hospitalization outcome of patients with lung cancer with COVID-19 infection: NIS 2020 analysis.

212 Background: Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths globally. Recent data showed the detrimental effects of COVID-19 infection on other neoplasm conditions, causing increased mortality rates and complications. However, data on the precise effects of COVID-19 on hospitalized individuals with lung cancer are scarce. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted due to lung and bronchus cancer. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Statistical significance was established at a p-value of 0.05. Results: We identified 103,334 patients with a primary discharge diagnosis of lung and bronchus cancer. The mean age was 68.9 years; 50.5% were female. In the non-COVID group, Caucasians accounted for 75%, followed by Hispanics (12%). Of these, 0.36% (374/103,334) had a concurrent diagnosis of COVID-19 infection. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality (aOR 5.39; 95% CI (3.01, 9.64), p &lt; 0.001), higher mean length of stay (b 5.51; 95% CI (2.59, 8.43) p &lt; 0.001), mean total hospital cost (b 10,683; 95% CI (784.32, 20,581.93) p = 0.034), shock (aOR 4.37; 95% CI (1.96, 9.91), p &lt; 0.001), acute respiratory failure (aOR 2.23; 95% CI (1.30, 3.85), p = 0.004), mechanical ventilation usage (aOR 3.12; 95% CI (1.46, 6.66), p = 0.003) and acute kidney injury (aOR 2.71; 95% CI (1.54, 4.74), p &lt; 0.001). We observed non-significant, but increased, risks of sepsis, SIRS, and coagulopathy in COVID-19-positive patients. Conclusions: In conclusion, our study underscores that COVID-19 infection is associated with higher in-hospital mortality and other major clinical outcomes in lung cancer, as well as increased economic burden and cost of stay. To definitively establish causal relationships between the observed factors and the reported clinical outcomes in this population, further longitudinal research is necessary.

Circulating inflammatory cytokines and the risk of sepsis: a bidirectional mendelian randomization analysis

BackgroundSepsis is a life-threatening condition that is characterized by multiorgan dysfunction and caused by dysregulated cytokine networks, which are closely associated with sepsis progression and outcomes. However, currently available treatment strategies that target cytokines have failed. Thus, this study aimed to investigate the interplay between genetically predicted circulating concentrations of cytokines and the outcomes of sepsis and to identify potential targets for sepsis treatment.MethodsData related to 35 circulating cytokines in 31,112 individuals (including 11,643 patients with sepsis) were included in genome-wide association studies (GWASs) from the UK Biobank and FinnGen consortia. A bidirectional two-sample Mendelian randomization (MR) analysis was performed using single nucleotide polymorphisms (SNPs) to evaluate the causal effects of circulating cytokines on sepsis outcomes and other cytokines.ResultsA total of 35 inflammatory cytokine genes were identified in the GWASs, and 11 cytokines, including Interleukin-1 receptor antagonist (IL-1ra), macrophage inflammatory protein 1 (MIP1α), IL-16, et al., were associated with sepsis outcome pairs according to the selection criteria of the cis-pQTL instrument. Multiple MR methods verified that genetically predicted high circulating levels of IL-1ra or MIP1α were negatively correlated with genetic susceptibility to risk of sepsis, including sepsis (28-day mortality), septicaemia, streptococcal and pneumonia-derived septicaemia (P ≤ 0.01). Furthermore, genetic susceptibility of sepsis outcomes except sepsis (28-day mortality) markedly associated with the circulating levels of five cytokines, including active plasminogen activator inhibitor (PAI), interleukin 7 (IL-7), tumour necrosis factor alpha (TNF-α), beta nerve growth factor (NGF-β), hepatic growth factor (HGF) (P < 0.05). Finally, we observed that the causal interaction network between MIP1α or IL-1ra and other cytokines (P < 0.05).ConclusionsThis comprehensive MR analysis provides insights into the potential causal mechanisms that link key cytokines, particularly MIP1α, with risk of sepsis, and the findings suggest that targeting MIP1α may be a potential strategy for preventing sepsis.

The Protective Effect of Octanoic Acid on Sepsis: A Review.

Sepsis, a systemic inflammation that occurs in response to a bacterial infection, is a significant medical challenge. Research conducted over the past decade has indicated strong associations among a patient's nutritional status, the composition of their gut microbiome, and the risk, severity, and prognosis of sepsis. Octanoic acid (OA) plays a vital role in combating sepsis and has a protective effect on both animal models and human patients. In this discussion, the potential protective mechanisms of OA in sepsis, focusing on its regulation of the inflammatory response, immune system, oxidative stress, gastrointestinal microbiome and barrier function, metabolic disorders and malnutrition, as well as organ dysfunction are explored. A comprehensive understanding of the mechanisms by which OA act may pave the way for new preventive and therapeutic approaches to sepsis.