Outcome Of Sepsis Research Articles

A simple electronic medical record-based predictors of illness severity in sepsis (sepsis) score.

Current scores for predicting sepsis outcomes are limited by generalizability, complexity, and electronic medical record (EMR) integration. Here, we validate a simple EMR-based score for sepsis outcomes in a large multi-centre cohort. A simple electronic medical record-based predictor of illness severity in sepsis (SEPSIS) score was developed (4 additive lab-based predictors) using a population-based retrospective cohort study. Internal medicine services across four academic teaching hospitals in Toronto, Canada from April 2010-March 2015 (primary cohort) and 2015-2019 (secondary cohort). We identified patients admitted with sepsis based upon receipt of antibiotics and positive cultures. The primary outcome was in-hospital mortality and secondary outcomes were ICU admission at 72 hours, and hospital length of stay (LOS). We calculated the area under the receiver operating curve (AUROC) for the SEPSIS score, qSOFA, and NEWS2. We then evaluated the SEPSIS score in a secondary cohort (2015-2019) of hospitalized patients receiving antibiotics. Our primary cohort included 1,890 patients with a median age of 72 years (IQR: 56-83). 9% died during hospitalization, 18.6% were admitted to ICU, and mean LOS was 12.7 days (SD: 21.5). In the primary and secondary (2015-2019, 4811 patients) cohorts, the AUROCs of the SEPSIS score for predicting in-hospital mortality were 0.63 and 0.64 respectively, which were similar to NEWS2 (0.62 and 0.67) and qSOFA (0.62 and 0.68). AUROCs for predicting ICU admission at 72 hours, and length of stay > 14 days, were similar between scores, in the primary and secondary cohorts. All scores had comparable calibration for predicting mortality. An EMR-based SEPSIS score shows a similar ability to predict important clinical outcomes compared with other validated scores (qSOFA and NEWS2). Because of the SEPSIS score's simplicity, it may prove a useful tool for clinical and research applications.

Osteopontin Depletion in Nonhematopoietic Cells Improves Outcomes in Septic Mice by Enhancing Antimicrobial Peptide Production.

Osteopontin (Opn) depletion can improve septic outcomes, but the underlying mechanism remains unknown. In this study, we demonstrated that nonhematopoietic but not hematopoietic Opn depletion improved septic outcomes. When compared with wild type mice, cohoused Opn-/- mice displayed enhanced production of antibacterial peptides (AMPs), decreased bacterial loads, and a distinct bacterial composition of gut microbiota. Fecal microbiota transplantation and OPN neutralization assay showed that Opn depletion could reduce bacterial loads and improve septic inflammation. By employing an intestinal organoid culture system, we proved that OPN neutralization in wild type organoids could inactivate AKT and decrease FOXO3a phosphorylation, resulting in enhanced AMP production, whereas OPN treatment in OPN-deficient organoids could activate AKT and increase FOXO3a phosphorylation, leading to reduced AMP production. Our findings identified OPN as a novel regulatory factor of AMP production to modulate bacterial loads and composition of gut microbiota, in turn affecting sepsis outcomes.

Diagnostic and prognostic value of heparin-binding protein in sepsis: A systematic review and meta-analysis.

Sepsis remains a leading cause of death worldwide. In this context, heparin-binding protein (HBP) has emerged as a possible biomarker, drawing significant attention for its diagnostic and prognostic usefulness in septic patients. Despite this advancement, the literature yields conflicting results. This study is intended to critically evaluate the diagnostic and prognostic value of HBP in critically ill septic patients. We searched multiple databases, including PubMed, SCOPUS, Web of Science, and EBSCO, to identify relevant studies on April 27, 2023. We included studies investigating sepsis or its severe outcomes that reported HBP levels and the required data to create 2 × 2 tables. We used R version 4.2.2 and R Studio to analyze the pooled diagnostic accuracy outcomes. The diagmeta package was utilized to calculate the optimum cutoff value. In our meta-analysis, we incorporated 28 studies including 5508 patients. The analysis revealed that HBP has a sensitivity of 0.71 (95% CI: 0.60; 0.79) and a specificity of 0.68 (95% CI: 0.51; 0.81) in diagnosing sepsis, respectively. HBP demonstrated moderate prognostic accuracy for mortality at a cutoff value of 161.415 ng/mL, with a sensitivity and specificity of 72%, and for severe sepsis outcomes at a cutoff value of 58.907 ng/mL, with a sensitivity and specificity of 71%. Our findings indicate a relatively moderate diagnostic and prognostic accuracy of HBP for sepsis. Future studies are required to verify the accuracy of HBP as a biomarker for sepsis.

Loss-of-function/gain-of-function polymorphisms of the ATP sensitive P2X7R influence sepsis, septic shock, pneumonia, and survival outcomes.

Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.

Epidemiology and Outcomes of Neonatal Sepsis: Experience from a Tertiary Australian NICU

Introduction: Neonatal sepsis is associated with significant mortality and morbidity. Low-middle-income countries are disproportionately affected, but late-onset sepsis (LOS) still occurs in up to 20% of infants <28 weeks in high-income countries. Understanding site-specific data is vital to guide management. Methods: A retrospective cohort study was conducted at King Edward Memorial Hospital (KEMH), Perth. Infants admitted between January 2012 and June 2022 were included. Data were extracted from routine electronic databases. Incidence and aetiology of sepsis were determined and the association of sepsis with neonatal outcomes analysed. Results: During the study period, 23,395 newborns were admitted with a median gestation of 37 weeks and birth weight of 2,800 g. There were 370 sepsis episodes in 350 infants; 102 were early-onset sepsis (EOS) (1.6 per 1,000 live births), predominantly Streptococcus agalactiae (35, 34.3%) and Escherichia coli (27, 26.5%); 268 were LOS (0.9 per 1,000 inpatient days), predominantly coagulase-negative staphylococci (CONS) (156, 57.6%) and E. coli (30, 11.1%). The incidence of LOS declined from 2012 to 2022 (p = 0.002). Infants with EOS had increased brain injury (25.7% vs. 4.1%; p = 0.002) and mortality (18.8% vs. 1.6%; p < 0.001). Those with LOS had increased hospital stay (median 95 vs. 15 days; p < 0.001), mortality (15.3% vs. 1.6%; p = 0.018), necrotising enterocolitis (NEC) (7.4% vs. 0.5%; p < 0.001), and chronic lung disease (CLD) (58.1% vs. 5.9%; p = 0.005). Infants <28 weeks with sepsis were at increased risk of neurodevelopmental impairment compared to those without infection (43.2% vs. 30.9%, p = 0.027). Conclusions: While we observed a reduction in LOS incidence, sepsis remains associated with higher mortality, and in survivors with longer hospital stay and increased risk of brain injury, NEC, CLD, and neurodevelopmental impairment.

Predictors of thirty-day mortality among patients with blood stream infection with WHO priority pathogens: single centre exploratory study from a referral teaching hospital in central India.

Bloodstream infection (BSI) is defined by the presence of viable microorganisms in the bloodstream. BSI is one of the major causes of sepsis and subsequent adverse clinical outcomes all across the globe. The present study was undertaken to identify clinico-epidemio-microbiological variables associated with 30-day mortality in patients having BSI with WHO priority pathogens. The study was conducted at a public sector tertiary care institute in central India from April 2019 to March 2021. Blood samples collected from patients with clinical suspicion of sepsis, were processed by automated bacterial culture system and interpreted as per CLSI guidelines. Calculated sample size was 150. Data was analyzed by R software. Respiratory tract infection was the most common source (43.3%) of BSI, followed by the gastrointestinal (20%) and urinary tract (18.7%). Among the patients, 33% required invasive mechanical ventilation, and 31% required inotropes. Diabetes mellitus (DM) was the most common co-morbidity (34%). The incidence of multi-drug resistant organisms (MDRO) was 59.3%. Escherichia coli was the most commonly (24%) isolated organism, followed by Klebsiella pneumoniae (17.3%) and Acinetobacter baumannii (16%). Higher age, higher qSOFA score / SIRS score / mean SOFA score at presentation had higher mortality. Use of mechanical ventilation and inotropes during treatment and isolation of critical category organisms of WPP and multi drug resistant organisms were independent 30-day mortality predictors.

MicroRNA as Sepsis Biomarkers: A Comprehensive Review.

Sepsis, a life-threatening condition caused by the body's dysregulated response to infection, presents a significant challenge in clinical management. Timely and accurate diagnosis is paramount for initiating appropriate interventions and improving patient outcomes. In recent years, there has been growing interest in identifying biomarkers that can aid in the early detection and prognostication of sepsis. MicroRNAs (miRNAs) have emerged as potential biomarkers for sepsis due to their involvement in the regulation of gene expression and their stability in various biological fluids, including blood. MiRNAs are small non-coding RNA molecules that play crucial roles in post-transcriptional gene regulation by binding to target messenger RNAs (mRNAs), leading to mRNA degradation or translational repression. The diagnostic and prognostic potential of miRNAs in sepsis stems from their ability to serve as sensitive and specific biomarkers reflective of the underlying pathophysiological processes. Compared to traditional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT), miRNAs offer several advantages, including their early and sustained elevation during sepsis, as well as their stability in stored samples, making them attractive candidates for clinical use. However, despite their promise, the clinical translation of miRNAs as sepsis biomarkers faces several challenges. These include the need for standardized sample collection and processing methods, the identification of optimal miRNA panels or signatures for differentiating sepsis from other inflammatory conditions, and the validation of findings across diverse patient populations and clinical settings. In conclusion, miRNAs hold great promise as diagnostic and prognostic biomarkers for sepsis, offering insights into the underlying molecular mechanisms and potential therapeutic targets. However, further research is needed to overcome existing challenges and realize the full clinical utility of miRNAs in improving sepsis outcomes.

Sepsis phenotypes, subphenotypes, and endotypes: are they ready for bedside care?

Sepsis remains a leading global cause of morbidity and mortality, and despite decades of research, no effective therapies have emerged. The lack of progress in sepsis outcomes is related in part to the significant heterogeneity of sepsis populations. This review seeks to highlight recent literature regarding sepsis phenotypes and the potential for further research and therapeutic intervention. Numerous recent studies have elucidated various phenotypes, subphenotypes, and endotypes in sepsis. Clinical parameters including vital sign trajectories and microbial factors, biomarker investigation, and genomic, transcriptomic, proteomic, and metabolomic studies have illustrated numerous differences in sepsis populations with implications for prediction, diagnosis, treatment, and prognosis of sepsis. Sepsis therapies including care bundles, fluid resuscitation, and source control procedures may be better guided by validated phenotypes than universal application. Novel biomarkers may improve upon the sensitivity and specificity of existing markers and identify complications and sequelae of sepsis. Multiomics have demonstrated significant differences in sepsis populations, most notably expanding our understanding of immunosuppressed sepsis phenotypes. Despite progress, these findings may be limited by modest reproducibility and logistical barriers to clinical implementation. Further studies may translate recent findings into bedside care.

Outcomes of interventions in neonatal sepsis: A systematic review of qualitative research.

While a systematic review exists detailing neonatal sepsis outcomes from clinical trials, there remains an absence of a qualitative systematic review capturing the perspectives of key stakeholders. Our aim is to identify outcomes from qualitative research on any intervention to prevent or improve the outcomes of neonatal sepsis that are important to parents, other family members, healthcare providers, policymakers, and researchers as a part of the development of a core outcome set (COS) for neonatal sepsis. A literature search was carried out using MEDLINE, EMBASE, CINAHL, and PsycInfo databases. Publications describing qualitative data relating to neonatal sepsis outcomes were included. Drawing on the concepts of thematic synthesis, texts related to outcomes were coded and grouped. These outcomes were then mapped to the domain headings of an existing model. Out of 6777 records screened, six studies were included. Overall, 19 outcomes were extracted from the included studies. The most frequently reported outcomes were those in the domains related to parents, healthcare workers and individual organ systemas such as gastrointestinal system. The remaining outcomes were classified under the headings of general outcomes, miscellaneous outcomes, survival, and infection. The outcomes identified in this review are different from those reported in neonatal sepsis clinical trials, thus highlighting the importance of incorporating qualitative studies into COS development to encapsulate all relevant stakeholders' perspectives.

High-throughput mass spectrometry maps the sepsis plasma proteome and differences in patient response.

Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis and comparator groups (noninfected critical illness, postoperative inflammation, and healthy volunteers) involving 2612 samples (from 1611 patients) and 4553 liquid chromatography-mass spectrometry analyses acquired through a single batch of continuous measurements, with a throughput of 100 samples per day. We show how this scale of data can delineate proteins, pathways, and coexpression modules in sepsis and be integrated with paired leukocyte transcriptomic data (837 samples from n = 649 patients). We mapped the plasma proteomic landscape of the host response in sepsis, including changes over time, and identified features relating to etiology, clinical phenotypes (including organ failures), and severity. This work reveals subphenotypes informative for sepsis response state, disease processes, and outcome; identifies potential biomarkers; and advances opportunities for a precision medicine approach to sepsis.

Failure to Rescue as a Quality Measure in Sepsis

This Viewpoint discusses the limitations of current tools to improve sepsis outcomes and proposes that these tools be supplemented with “failure to rescue,” a systems-level approach for recognizing and addressing complications and managing sepsis throughout the hospitalization period.

Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis

Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. The number of minutes from emergency department arrival to antibiotic administration. The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Legume-supplemented feed for children hospitalised with severe malnutrition: a phase II trial.

Children hospitalised with severe malnutrition have high mortality and readmission rates post-discharge. Current milk-based formulations target restoring ponderal growth but not the modification of gut barrier integrity or microbiome which increases the risk of gram-negative sepsis and poor outcomes. We propose that legume-based feeds rich in fermentable carbohydrates will promote better gut health and improve overall outcomes. We conducted an open-label phase II trial at Mbale and Soroti Regional Referral Hospitals, Uganda, involving 160 children aged 6 months to 5 years with severe malnutrition (mid-upper arm circumference (MUAC) < 11·5 cm and/or nutritional oedema). Children were randomised to a lactose-free, chickpea-enriched legume paste feed (LF) (n 80) v. WHO standard F75/F100 feeds (n 80). Co-primary outcomes were change in MUAC and mortality to day 90. Secondary outcomes included weight gain (> 5 g/kg/d), de novo development of diarrhoea, time to diarrhoea and oedema resolution. Day 90 MUAC increase was marginally lower in LF v. WHO arm (1·1 cm (interquartile range (IQR) 1·1) v. 1·4 cm (IQR 1·40), P = 0·09); day 90 mortality was similar (11/80 (13·8 %) v. 12/80 (15 %), respectively, OR 0·91 (95 % CI 0·40, 2·07), P = 0·83). There were no differences in any of the other secondary outcomes. Owing to initial poor palatability of the LF, ten children switched to WHO feeds. Per-protocol analysis indicated a trend to lower day 90 mortality and readmission rates in the LF (6/60 (10 %) and 2/60(3 %)) v. WHO feeds (12/71(17·5 %) and 4/71(6 %)). Further refinement of LF and clinical trials are warranted, given the poor outcomes in children with severe malnutrition.

Neutrophil-to-lymphocyte Ratio as a Marker for Diagnosis and Prognostication of Sepsis.

Exploring the ideal marker for early diagnosis and prognosis of sepsis is crucial due to limitations of available sepsis indicators. Hence, we aimed to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a diagnostic and prognostic marker of sepsis. This prospective case-control study was conducted at a tertiary care teaching public hospital. NLR values among cases and controls were compared for diagnosis. Among cases, serial trends in NLR values, outcome (survival or death), and various parameters [such as Sequential Organ Failure Assessment (SOFA) score, duration of intensive care unit (ICU) stay, etc.] were compared between survivors and nonsurvivors for prognosis. Analysis was performed using MS Excel and PSPP version 1.0.1. A total of 120 patients (60 cases and 60 controls) were analyzed. The NLR among cases was significantly higher (p = 1.31 × 10-16) than in controls. Using binary logistic regression, a high NLR was found to be a statistically significant predictor of sepsis category (p = 2.25 × 10-5). The association of various variables among survivors and nonsurvivors of cases showed statistically significant differences: NLR (p = 5.29 × 10-5), mean = 13.27, interquartile range (IQR) = 5.90, z-value = -4.042), C-reactive protein (CRP) (p = 4.80 × 10-7), mean = 74.40, IQR = 21.30, z-value = -5.034), D-dimer (p = 4.32 × 10-8), mean = 7.09, IQR = 0.88, z-value = -5.477), SOFA score (p = 0.00118, mean = 8.50, IQR = 3.00, z-value = -3.244), and duration of hospital stay (p = 0.03578, mean = 13.45, IQR = 8.00, z-value = -2.099). The NLR emerges as a valuable marker for both diagnosis and prognosis in sepsis. Elevated NLR levels aid in diagnosing sepsis at very early stages, and the trend of NLR demonstrates a dynamic course throughout the disease process. Persistently elevated NLR and high NLR values correlate with poor outcomes in sepsis. Additionally, NLR can be correlated with other prognostic markers of sepsis and mortality. Therefore, we recommend the utilization of NLR as a quick, easy, and cost-effective marker for both early diagnosis and regular prognostication of sepsis.

Malnutrition and Its Influence on Sepsis Outcomes in Elderly Patients.

Malnutrition is common among the elderly and has significant implications for hospitalization outcomes. This is particularly true for severe illnesses such as sepsis, given age-related physiological changes and comorbidities. This study examined how malnutrition affected hospitalization outcomes in older adults admitted for sepsis. A prospective cohort study was conducted at Lady Reading Hospital in Peshawar, Pakistan, from January to December 2023, focusing on 390 sepsis patients aged 55 years and older. Data on clinical history, length of stay, mortality rates, comorbidities, and nutritional assessments were collected using standardized forms. After controlling for confounding variables, statistical analysis using SPSS version 23(IBM Corp., Armonk, NY) examined the relationship between hospitalization outcomes and nutritional status. The research included 390 elderly sepsis patients and showed significant variations in the demographics, comorbidities, and severity of disease between the well-nourished and malnourished groups. Malnourished patients had higher rates of ICU admission(52.82% vs. 29.23%), mechanical ventilation (45.13% vs. 16.41%), mortality (27.18% vs. 14.87%), and 30-day readmission (28.21% vs. 12.82%) as compared to the well-nourished group. They also had longer hospital stays (18.1 days vs. 12.6 days). Malnutrition significantly influenced outcomes, with multivariate analysis indicating it as a predictor of longer stays (β = 2.8, p < 0.001) and increased mortality risk (OR = 3.2, 95% CI: 1.9-5.4, p < 0.001). Malnutrition significantly worsens outcomes for elderly sepsis patients, increasing ICU admissions, ventilation needs, mortality rates, and readmissions, emphasizing the need for proactive nutritional interventions.

Bacterial pathogens and treatment outcomes in neonatal sepsis: A comparative observational study across various hospital settings

Bacterial pathogens and treatment outcomes in neonatal sepsis: A comparative observational study across various hospital settings

Association of chronic or acute systolic and diastolic heart failure with incidence rates of pneumonia, sepsis, and septic shock in patients with lung cancer.

e24005 Background: Systolic heart failure (SHF) and diastolic heart failure (DHF) can lead to volume overload and cause pulmonary venous congestion and pulmonary edema. While an association between lung cancer (LC) and increased infection rates is well established, we investigated whether chronic SHF or DHF, as well as acute SHF or DHF in concomitance with LC, influenced the incidence of pneumonia (PNA), sepsis, and septic shock. Methods: A retrospective study was conducted by obtaining patients with LC by applying specific ICD 10 codes (C34.0 - C34.9 including all sub-codes) from the National Inpatient Sample 2019-2020. Among this cohort, patients with acute and chronic SHF or DHF were further identified by applying specific ICD 10 codes ((I50.1 - I50.4 including all sub-codes). Pneumonia, sepsis, and septic shock outcomes were compared between LC patients with each of these types of heart failures versus those without using multivariate regression analysis (MVRA), adjusting for demographic factors, hospital-specific characteristics, common comorbidities and alcohol, smoking, or substance use. Results: 802,230 patients were identified with LC. 48.7% were female. 77.9% were Caucasian, 12.8% were African American, 4.6% were Hispanic, and 3.5% belonged to other ethnicities. Patients with LC and chronic SHF (n = 25880) had no significant difference in rates of PNA [Adjusted (Ad) odds ratio (OR): 0.9, p = 0.13] and sepsis (Ad OR: 0.9, p = 0.59) but had higher rates of septic shock (Ad OR: 1.4, p &lt; 0.001) compared to those LC patients without any heart failure (HF). Patients with LC who had acute SHF (n = 22295) showed higher rates of PNA (Ad OR: 1.4, p &lt; 0.001), sepsis (Ad OR: 1.5, p &lt; 0.001), as well as septic shock (Ad OR: 1.6, p &lt; 0.001) versus those without any HF. Patients with LC and concurrent chronic DHF (n = 31580) had similar rates of PNA (Ad OR: 1, p = 0.64), sepsis (Ad OR: 1.1, p = 0.62) and septic shock (Ad OR: 1, p = 0.77) compared to LC patients without any HF. However, acute DHF (n = 24080) led to a higher incidence of PNA (Ad OR: 1,4, p &lt; 0.001) and sepsis (Ad OR: 1.2, p = 0.05) in patients with LC, but no difference in the incidence of septic shock (Ad OR: 0.8, p = 0.072). Conclusions: Chronic SHF led to an increased incidence of septic shock, whereas acute SHF was associated with accentuated rates of PNA, sepsis, and septic shock in patients with LC. Chronic DHF did not predict an increased risk of infections; however, acute DHF was associated with enhanced rates of PNA and sepsis. Future investigations may focus on the effect of SHF or DHF on outcomes beyond hospitalization in patients with LC and the subtypes of LC and infection risk. Based on this signal-finding analysis, it may be postulated that early inter-disciplinary collaboration between oncology and cardiology may be crucial in managing patients with heart failure and LC and potentially lead to better patient outcomes.

Impact of Iron Profile and Vitamin D Levels on Clinical Outcomes in Patients with Sepsis and Septic Shock: A Cross-sectional Analysis at a Tertiary Care Center.

Sepsis is a major global health affecting millions worldwide, hence understanding its contributing factors becomes paramount. This cross-sectional study at a tertiary care center explores the relationship between iron profile, vitamin D levels, and outcomes in sepsis and septic shock patients. The primary objective was to explore the prevalence of iron profile and vitamin D parameters during early intensive care unit (ICU) admission and their association with 28-day mortality. Spanning 18 months, the study enrolled adult patients meeting sepsis or septic shock criteria at the ICU. Data collection included demographic information, clinical characteristics, and blood samples for iron profile and vitamin D levels at admission. Disease severity was assessed using sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores, and treatment was administered as per surviving sepsis-3 guidelines. The research involved 142 participants, uncovering prevalent organisms such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Noteworthy connections to mortality were identified for factors including vasopressor support, ICU stay duration, SOFA score, and APACHE-II score. Interestingly, age, gender, and vitamin D levels showed no significant associations. However, the study did reveal a significant association between iron, ferritin, and transferrin saturation levels with increased 28-day mortality. Our study concluded that low Iron, elevated ferritin, and decreased transferrin saturation levels maintained associations with the outcome of interest. While no such relationship was established with vitamin D levels. These results suggest potential implications for patient management and prognosis, warranting further exploration in future research. Bairwa M, Jatteppanavar B, Kant R, Singh M, Choudhury A. Impact of Iron Profile and Vitamin D Levels on Clinical Outcomes in Patients with Sepsis and Septic Shock: A Cross-sectional Analysis at a Tertiary Care Center. Indian J Crit Care Med 2024;28(6):569-574.

Association between prehospital ROX index with 30-day mortality among septic shock

PurposeRespiratory dysfunction is one of the most frequent symptoms observed during sepsis reflecting hypoxemia and/or acidosis that may be assessed by the ROX index (ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate). This study aimed to describe the relationship between the prehospital ROX index and 30-day mortality rate among septic shock patients cared for in the prehospital setting by a mobile intensive care unit (MICU).MethodsFrom May 2016 to December 2021, 530 septic shock patients cared for by a prehospital MICU were retrospectively analysed. Initial ROX index value was calculated at the first contact with MICU. A Cox regression analysis after propensity score matching was performed to assess the relationship between 30-day mortality rate and a ROX index ≤ 10.ResultsPulmonary, digestive and urinary sepsis were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality reached 31%. Cox regression analysis showed a significant association between 30-day mortality and a ROX index ≤ 10: adjusted hazard ratio of 1.54 [1.08–2.31], p < 0.05.ConclusionsDuring the prehospital stage of septic shock patients cared for by a MICU, ROX index is significantly associated with 30-day mortality. A prehospital ROX ≤ 10 value is associated with a 1.5-fold 30-day mortality rate increase. Prospective studies are needed to confirm the ability of prehospital ROX to predict sepsis outcome since the prehospital setting.

Novel Active Proteins for Sepsis Prognosis Revealed through ScRNA-seq and Quantitative Proteomics.

To uncover critical active proteins influencing sepsis outcomes through multi-omics analysis. This study collected peripheral blood from sepsis patients (NS = 26, SV = 27) and controls (Con = 16). Cellular heterogeneity was assessed using scRNA-seq. Cellular populations were identified through clustering and annotation. GSVA was employed to detect pathway alterations in sepsis, while the Viper algorithm estimated protein activity at the single-cell level. Signaling networks were investigated via cell-cell communication analysis. Differentially expressed proteins were identified by DIA proteomics and confirmed through integrated analysis. Prognostic value was evaluated via meta and survival analyses. scRNA-seq of 22,673 features within 34,228 cells identified five cellular clusters and 253 active proteins via Viper, validated by DIA (FC > 2, P < 0.05). Four proteins (SPI1, MEF2A, CBX3, UBTF) with prognostic significance were discovered and mapped onto the cellular landscape. GSVA enrichment analysis revealed that the NS group exhibited significant alterations in pathways related to cellular apoptosis and inflammatory responses, while the SV group displayed increased activity in DNA repair and cellular survival pathways. The study's findings advance the understanding of sepsis pathophysiology by linking differentially active proteins to patient prognosis, paving the way for targeted therapeutic strategies.