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Skeletal muscle dysfunction is a major problem in critically ill patients suffering from sepsis. This condition is associated with mitochondrial dysfunction and increased autophagy in skeletal muscles. Autophagy is a proteolytic mechanism involved in eliminating dysfunctional cellular components, including mitochondria. The latter process, referred to as mitophagy, is essential for maintaining mitochondrial quality and skeletal muscle health. Recently, a fluorescent reporter system called mito-QC (i.e. mitochondrial quality control) was developed to specifically quantify mitophagy levels. In the present study, we used mito-QC transgenic mice and confocal microscopy to morphologically monitor mitophagy levels during sepsis. To induce sepsis, Mito-QC mice received Escherichia coli lipopolysaccharide (10 mg kg -1 i.p.) or phosphate-buffered saline and skeletal muscles (hindlimb and diaphragm) were excised 48 h later. In control groups, there was a negative correlation between the basal mitophagy level and overall muscle mitochondrial content. Sepsis increased general autophagy in both limb muscles and diaphragm but had no effect on mitophagy levels. Sepsis was associated with a downregulation of certain mitophagy receptors (Fundc1, Bcl2L13, Fkbp8 and Phbb2). The present study suggests that general autophagy and mitophagy can be dissociated from one another, and that the characteristic accumulation of damaged mitochondria in skeletal muscles under the condition of sepsis may reflect a failure of adequate compensatory mitophagy. KEY POINTS: There was a negative correlation between the basal level of skeletal muscle mitophagy and the mitochondrial content of individual muscles. Mitophagy levels in limb muscles and the diaphragm were unaffected by lipopolysaccharide (LPS)-induced sepsis. With the exception of BNIP3 in sepsis, LPS administration induced either no change or a downregulation of mitophagy receptors in skeletal muscles., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Out of the context of haematological patients, Candida sp. is rarely retrieved from pyogenic liver abscesses (PLA)., Objectives: Our objective was to assess the risk factors for occurrence, and clinical, microbiological characteristics, management and outcome of Candida pyogenic liver abscesses (C-PLA)., Patients/methods: We retrospectively analysed C-PLA cases and compared them to pyogenic liver abscesses exclusively due to bacteria (B-PLA) included in our monocentric database on liver abscesses. Unfavourable course was defined as the occurrence of a primary treatment failure (PTF), recurrence after an initial cure, or death within 3 months after diagnosis., Results: Between 2010 and 2018, 15 C-PLA and 292 B-PLA were included. All C-PLA had a biliary origin and were polymicrobial. All patients with C-PLA had at least one comorbidity at risk for Candida infection and 7 (53.3%) presented with sepsis requiring an admission in intensive care unit. Median duration of antifungal treatment was 42 days [24-55]. In multivariate analysis, compared with B-PLA, a medical history of malignancy (OR 4.16; 95%CI 1.15-18.72) or liver abscess (OR 7.39; 95%CI 2.10-26.62), and sepsis with severity criteria (OR 3.52; 95%CI 1.07-11.90) were independently associated with the occurrence of C-PLA. In multivariate analysis, C-PLA was associated with a higher risk of recurrence (HR 3.08; 95%CI 1.38-11.22)., Conclusion: Candida liver abscesses in non-neutropenic is a rare and severe disease. The high rate of recurrence should lead to discuss a more intensive treatment., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Background & Aims: Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy., Methods: Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis., Results: Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14±3 vs. 8±1, respectively p<0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin., Conclusions: Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Abstract: Introduction: Sepsis is a dysregulated host response to infection that can lead to life-threatening organ dysfunction. Clinical and animal studies consistently demonstrate that female subjects are less susceptible to the adverse effects of sepsis, demonstrating the importance of understanding how sex influences sepsis outcomes. The signal transducer and activator of transcription 3 (STAT3) pathway are a major signaling pathway that facilitates inflammation during sepsis. STAT3 is abundantly expressed in white adipose tissue; however, little is known about the contribution of white adipose tissue STAT3 activation during sepsis. We hypothesize that adipocyte STAT3 inhibition during severe sepsis will exaggerate the inflammatory response and impact organ injury, in a sex-dependent manner. Methods: We generated STAT3 flox/flox (wild-type [WT]) and adipocyte STAT3 knock out (A-STAT3 KO) mice using Cre-lox technology. Studies were done in 12- to 16-week-old male and female mice. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Control nonseptic mice did not undergo CLP (0 h CLP). Tissues were harvested 18 h after CLP. Body composition was determined by echo magnetic resonance imaging. Energy metabolism was determined by indirect calorimetry. White adipose tissue morphology was determined by hematoxylin and eosin staining, while STAT3 activation in the white adipose tissue was determined by western blot analysis and immunohistochemistry staining of STAT3 activation/phosphorylation at tyrosine 705. Plasma cytokines (TNF-α, IL-6, and leptin) were determined by luminex assay. Neutrophil infiltration of the lung and liver was assessed by myeloperoxidase activity assay. Histological signs of organ injury on lung and liver tissue were assessed by hematoxylin and eosin staining. Liver injury was further assessed by measuring plasma alanine and aspartate aminotransferase. In a separate cohort of mice, sepsis was induced by CLP and mice were monitored every 6-12 h over a 7-day period to assess survival rate. Results: We demonstrate that neither body composition nor energy metabolism is altered with adipocyte STAT3 inhibition in male or female mice, under nonseptic conditions. Sepsis was associated with reduced adipocyte size in female WT and A-STAT3 KO mice, suggesting that this event is STAT3 independent. Sepsis did not alter adipocyte size in male WT and A-STAT3 KO mice, suggesting that this event is also sex dependent. Although STAT3 phosphorylation at tyrosine 705 expression is negligible in male and female A-STAT3 KO mice, septic female WT and A-STAT3 KO mice have higher white adipose tissue STAT3 activation than male WT and A-STAT3 KO mice. Adipocyte STAT3 inhibition did not alter the proinflammatory cytokine response during sepsis in male or female mice, as measured by plasma TNF-α, IL-6, and leptin levels. Adipocyte STAT3 inhibition reduced lung neutrophil infiltration and histological signs of lung injury during sepsis in male mice. On the contrary, adipocyte STAT3 inhibition had no effect on lung neutrophil infiltration or lung injury in female mice. We further demonstrate that neither liver neutrophil infiltration nor histological signs of liver injury are altered by adipocyte STAT3 inhibition during sepsis, in male or female mice. Lastly, adipocyte STAT3 inhibition did not affect survival rate of male or female mice during sepsis. Conclusions: Our study demonstrates that sex influences white adipose tissue STAT3 activation and morphology during sepsis, which is not dependent on the presence of functional STAT3 in mature adipocytes. Furthermore, genetic inhibition of adipocyte STAT3 activation in male, but not female mice, results in reduced lung neutrophil infiltration and lung injury during sepsis. The results from our study demonstrate the importance of considering biological sex and the white adipose tissue as potential sources and targets of inflammation during sepsis., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 by the Shock Society.)

Background: Sepsis is an important cause of mortality and morbidity in the intensive care unit (ICU). We performed a study to describe the epidemiology of sepsis syndromes in patients admitted to ICUs of the Piedmont region., Methods: In this prospective, multicentre, observational study, all 3902 patients admitted to a network of 24 ICUs from 17 hospitals during a 180 day period (April 3-September 29, 2006) were included. Patients were followed from the first day of admission until death or ICU discharge., Results: The incidence of sepsis during the ICU stay was 11.4% (N.=446), corresponding to an incidence of 25 cases/100,000 inhabitants/year; 141 (31.6%) patients had only sepsis, 160 patients had severe sepsis (35.9%) and 145 patients (32.5%) had septic shock In 227 patients (50.9%), sepsis was observed within 48 hours after admission to the ICU, and 219 patients (49.1%) developed ICU-acquired sepsis. The main sources of infection were the lungs, abdomen, and urinary tract. ICU mortality was higher (41.3 vs. 17.3%, P<0.0001) and the median ICU length of stay longer (15 vs. 2 days, P<0.0001) in patients with sepsis than in those without sepsis. The mortality rate increased with the severity of sepsis. ICU-acquired sepsis was associated with higher ICU mortality rates than sepsis occurring within 48 hours of ICU admission (49.8 vs. 33.0%, P<0.0001)., Conclusion: Sepsis is a common occurrence in critically ill patients. Our data underscore the regional variability in the epidemiology and outcome of sepsis syndromes and may be useful to guide appropriate resource allocation.

Introduction: The impact of gender on outcome in critically ill patients is unclear. We investigated the influence of gender on the epidemiology of severe sepsis and associated morbidity and mortality in a large cohort of ICU patients in the region of Piedmont in Italy., Methods: This was a post-hoc analysis of data from a prospective, multicenter, observational study in which all patients admitted to one of 24 participating medical and/or surgical ICUs between 3 April 2006 and 29 September 2006 were included., Results: Of the 3,902 patients included in the study, 63.5% were male. Female patients were significantly older than male patients (66±16 years vs. 63±16 years, P<0.001). Female patients were less likely to have severe sepsis and septic shock on admission to the ICU and to develop these syndromes during the ICU stay. ICU mortality was similar in men and women in the whole cohort (20.1% vs. 19.8%, P=0.834), but in patients with severe sepsis was significantly greater in women than in men (63.5% vs. 46.4%, P=0.007). In multivariate logistic regression analysis with ICU outcome as the dependent variable, female gender was independently associated with a higher risk of ICU death in patients with severe sepsis (odds ratio=2.33, 95% confidence interval=1.23 to 4.39, P=0.009) but not in the whole cohort (odds ratio=1.07, 95% confidence interval=0.87 to 1.34)., Conclusion: In this large regional Italian cohort of ICU patients, there were more male than female admissions. The prevalence of severe sepsis was lower in women than in men, but female gender was independently associated with a higher risk of death in the ICU for patients with severe sepsis.

Purpose: To describe the epidemiology of obesity in a large cohort of intensive care unit (ICU) patients and study its impact on outcomes., Methods: All 3902 patients admitted to one of 24 ICUs in the Piedmont region of Italy from April 3 to September 29, 2006, were included in this retrospective analysis of data from a prospective, multicenter study., Results: Mean body mass index (BMI) was 26.0 ± 5.4 kg/m(2): 32.8% of patients had a normal BMI, 2.6% were underweight, 45.1% overweight, 16.5% obese, and 2.9% morbidly obese. ICU mortality was significantly (P < .05) lower in overweight (18.8%) and obese (17.5%) patients than in those of normal BMI (22%). In multivariate logistic regression analysis, being overweight (OR = 0.73; 95%CI: 0.58-0.91, P = .007) or obese (OR = 0.62; 95%CI: 50.45-0.85, P = .003) was associated with a reduced risk of ICU death. Being morbidly obese was independently associated with an increased risk of death in elective surgery patients whereas being underweight was independently associated with an increased risk of death in patients admitted for short-term monitoring and after elective surgery., Conclusions: In this cohort, overweight and obese patients had a reduced risk of ICU death. Being underweight or morbidly obese was associated with an increased risk of death in some subgroups of patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Abstract: An 85-year-old woman with a history of breast carcinoma presented to hospital after gradual onset of abdominal pain with hypotension, jaundice, and massive intravascular hemolysis. This was caused by Clostridium perfringens septicemia originating from a liver abscess. Clostridium perfringens septicemia is a rare infection that has a high mortality rate, given that it is frequently unable to be diagnosed until postmortem examination. The source of the pathogen is usually intra-abdominal. Hepatic abscesses, although an uncommon source of primary clostridial infection, should be considered in such cases., Competing Interests: The authors report no conflict of interest and have not received funding for this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Sepsis and septic shock are common causes of hospitalization and mortality in patients with cirrhosis. There is no data on the choice of fluid and resuscitation protocols in sepsis-induced hypotension in cirrhosis., Methods: In this open-label trial conducted at a single center, we enrolled 308 cirrhotics with sepsis-induced hypotension and randomized them to receive either 5% albumin or normal saline. The primary endpoint was a reversal of hypotension [mean arterial pressure, MAP, ≥ 65 mmHg] at 3 h. Secondary endpoints included serial effects on heart rate, arterial lactate and urine output., Results: 154 patients each received 5% albumin (males, 79.8%, mean MAP 52.9 ± 7.0 mm Hg) or 0.9% saline (85.1%, 53.4 ± 6.3 mm Hg) with comparable baseline parameters and liver disease severity. Reversal of hypotension was higher in patients receiving 5% albumin than saline at the end of one hour [25.3% and 11.7%, p = 0.03, Odds ratio (95% CI)-1.9 (1.08-3.42)] and at the end of three hours [11.7% and 3.2%, p = 0.008, 3.9 (1.42-10.9)]. Sustained reduction in heart rate and hyperlactatemia (p < 0.001) was better in the albumin group. At one week, the proportion of patients surviving was higher in the albumin group than those receiving saline (43.5% vs 38.3%, p = 0.03). Female gender and SOFA ≥ 11 were predictors of non-response to fluid., Conclusions: 5% human albumin is safe and beneficial in reversing sepsis-induced hypotension compared to normal saline in patients with cirrhosis improving clinically assessable parameters of systemic hemodynamics, tissue perfusion and in-hospital short-term survival of cirrhosis patients with sepsis., (© 2021. Asian Pacific Association for the Study of the Liver.)

Introduction: Severe sepsis is one of the leading causes of mortality among children. Studies in adults have suggested a protective effect of obesity on mortality among patients hospitalized with sepsis. Paediatric studies evaluating similar relationship is lacking., Methods: We analysed non-overlapping years of the Kids Inpatient Database (KID) and National Inpatient Sample (NIS) database between 2003 and 2014 of all paediatric patients with severe sepsis (PSS) up to 20 years of age. PSS was defined using specific International Classification of Diseases (ICD) codes and modified Angus criteria. Using ICD-9 diagnosis codes, patients were divided into three mutually exclusive groups (obesity, morbid obesity and control groups), and these groups were compared for outcomes measures including in-hospital mortality and healthcare resource utilization using the length of stay and inflation-adjusted hospitalization charges., Results: We analysed 109 026 hospitalizations due to PSS. The prevalence rate of obesity was 1.5% (n = 1643), and morbid obesity was 1.05% (n = 1147). Multivariate regression models showed obesity was associated with 63% (OR 0.37, CI: 0.29-0.47, p < 0.001) and 54% reduction in mortality among PSS patients and patients with septic shock respectively. Contrastingly, morbid obesity was not associated with mortality among PSS patients and but was associated with 1.37 times (CI: 1.06-1.78, p = 0.01) increased risk of mortality among paediatric patients with septic shock., Conclusions: Paediatric obesity is associated with reduced mortality among patients with PSS, with the exception of morbid obesity. Further prospective studies are needed to better understand the relationship between obesity and outcomes in PSS., (© 2021 World Obesity Federation.)

Abstract: In this mini-review we provide an overview of sex- and gender-dependent issues in both clinical and preclinical sepsis. The increasing recognition for the need to account for sex and gender in biomedical research brings a unique set of challenges and requires researchers to adopt best practices when conducting and communicating sex- and gender-based research. This may be of particular importance in sepsis, given the potential contribution of sex bias in the failures of translational sepsis research in adults and neonates. Clinical evidence of sex-dependent differences in sepsis is equivocal. Since clinical studies are limited to observational data and confounded by a multitude of factors, preclinical studies provide a unique opportunity to investigate sex differences in a controlled, experimental environment. Numerous preclinical studies have suggested that females may experience favorable outcomes in comparison with males. The underlying mechanistic evidence for sex-dependent differences in sepsis and other models of shock (e.g., trauma-hemorrhage) largely centers around the beneficial effects of estrogen. Other mechanisms such as the immunosuppressive role of testosterone and X-linked mosaicism are also thought to contribute to observed sex- and gender-dependent differences in sepsis. Significant knowledge gaps still exist in this field. Future investigations can address these gaps through careful consideration of sex and gender in clinical studies, and the use of clinically accurate preclinical models that reflect sex differences. A better understanding of sex-and gender-dependent differences may serve to increase translational research success., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Objectives: Sepsis is a life-threatening condition and is one of the leading causes of death in the United States. The burden of sepsis-related mortality in the United States in recent years is not well characterized. We sought to describe sepsis-related mortality rates and mortality trends in the United States from 2005 to 2018., Design: Retrospective population-based study., Setting: We used the Multiple Cause of Death Database available through the Centers for Disease Control and Prevention website., Patients: Decedents with sepsis-related deaths were identified using previously validated International Classification of Diseases codes., Interventions: None., Measurements and Main Results: From 2005 to 2018, 6.7% of decedents had a diagnosis of sepsis. The overall sepsis-related mortality rates remained stable in both males (57 deaths per 100,000) and females (45.1 deaths per 100,000) during this period. Compared with Whites, the sepsis-related mortality rates were higher in Blacks (rate ratio = 1.78), Native Americans (rate ratio = 1.43), and Hispanics (rate ratio = 1.04) and were lower in Asians (rate ratio = 0.73). Sepsis-related mortality rates declined in Blacks, Hispanics, and Asians but increased in Whites and Native Americans. The majority of sepsis-related deaths occurred in the hospital. The percentage of deaths in the nursing home decreased, whereas deaths occurring at home and hospice increased., Conclusions: From 2005 to 2018, the overall sepsis-related mortality rates were stable, but there were significant racial and gender disparities in mortality trends. Further research is needed to evaluate the genetic and environmental contributors to these differences., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Bacterial infections are more frequent and severe in patients with advanced liver disease and, therefore, in liver transplant candidates. The increased risk of infection in these patients parallels the severity of the immune dysfunction associated with cirrhosis, which is related to systemic inflammation and progressive immunodeficiency. Other factors contribute to this risk, such as genetic polymorphisms, proton pump inhibitor overuse, the numerous invasive procedures and hospitalizations these patients go through, or the immunosuppressive effects of malnutrition or alcohol abuse. Bacterial infections have a great impact on disease progression and significantly increase mortality rates before and after liver transplantation. Mechanisms leading to organ failure in sepsis are associated not only with the hemodynamic derangement but also with an excessive inflammatory response triggered by infection. Furthermore, prophylactic and empirical antibiotic treatment strategies in patients with cirrhosis are being modified according to the growing prevalence of multidrug-resistant bacteria in the past decade. Also, new criteria have been introduced for the diagnosis of sepsis and septic shock. These new definitions have been validated in patients with cirrhosis and show a better accuracy to predict in-hospital mortality than previous criteria based on systemic inflammatory response syndrome. Accurate prophylaxis and early identification and treatment of bacterial infections are key to reducing the burden of sepsis in patients with cirrhosis awaiting liver transplantation., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

A dysregulated host response to infection causes organ dysfunction in sepsis and septic shock, two potentially fatal diseases. They continue to be major worldwide health burdens with high rates of morbidity and mortality despite advancements in medical care. The goal of this thorough review was to present a thorough summary of the current body of knowledge about the prevalence of sepsis and septic shock worldwide. Using widely used computerized databases, a comprehensive search of the literature was carried out, and relevant studies were chosen in accordance with predetermined inclusion and exclusion criteria. A narrative technique was used to synthesize the data that were retrieved. The review's conclusions show how widely different locations and nations differ in terms of sepsis and septic shock's incidence, prevalence, and fatality rates. Compared to high-income countries (HICs), low- and middle-income countries (LMICs) are disproportionately burdened more heavily. We talk about risk factors, comorbidities, and difficulties in clinical management and diagnosis in a range of healthcare settings. The review highlights the need for more research, enhanced awareness, and context-specific interventions in order to successfully address the global burden of sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Here we review the epidemiology of sepsis, focusing on its definition, incidence, and mortality, as well as the demographic insights and risk factors that influence its occurrence and outcomes. We address how age, sex, and racial/ethnic disparities impact upon incidence and mortality rates. Sepsis is more frequent and severe among the elderly, males, and certain racial and ethnic groups. Poor socioeconomic status, geographic location, and pre-existing comorbidities also elevate the risk of developing and dying from sepsis. Seasonal variations, with an increased incidence during winter months, is also apparent. We delve into the predictive value of disease severity scores such as the Sequential Organ Failure Assessment score. We also highlight issues relating to coding and administrative data that can generate erroneous and misleading information, and the need for greater consistency. The Sepsis-3 definitions, offering more precise clinical criteria, are a step in the right direction. This overview will, we hope, facilitate understanding of the multi-faceted epidemiological characteristics of sepsis and current challenges. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a frequent cause of admission to intensive care units (ICUs). High mortality rates are estimated globally, and in our country, few studies have reported one-year survival. The objective of this study is to determine one-year survival in patients with sepsis admitted to the ICU in Colombia, compared with the survival of patients admitted for other conditions. Methods: Retrospective cohort study using administrative databases from the Ministry of Health of Colombia. One-year survival and the adjusted hazard ratio for survival, adjusted for comorbidities included in the Charlson Index, were determined using a Cox proportional hazards model for patients admitted for other causes as well as for those admitted for sepsis. This was then compared with an inverse propensity score weighting model. Results: A total of 116.407 patients were initially admitted to the ICUs, with 12.056 (10.36%) diagnosed with sepsis. Within the first year, 4.428 (36.73%) patients died due to sepsis. Age and male gender were associated with an increased risk of death from sepsis, and the covariates associated with one-year mortality were as follows: age over 80 years with HR 9.91 (95% CI: 9.22–10.65), renal disease with HR 3.16 (95% CI: 3.03–3.29), primary tumoral disease with HR 2.07 (95% CI: 1.92–2.23), liver disease with HR 2.27 (95% CI: 2.07–2.50), and metastatic solid tumor with HR 2.03 (95% CI: 1.92–2.15). Conclusion: This study revealed a high one-year sepsis mortality rate in the population, associated with variables such as age over 80 years, the presence of renal disease, liver disease, connective tissue diseases, and cancer. Men exhibited higher mortality compared to women. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition mainly caused by gram-negative and gram-positive bacteria. Understanding the type of causative agent in the early stages is essential for precise antibiotic therapy. This study sought to identify a host gene set capable of distinguishing between sepsis induced by gram-negative bacteria; Escherichia coli and gram-positive bacteria; Staphylococcus aureus in community-onset adult patients. In the present study, microarray expression information was used to apply the Least Absolute Shrinkage and Selection Operator (Lasso) technique to select the predictive gene set for classifying sepsis induced by E. coli or S. aureus pathogens. We identified 25 predictive genes, including LILRA5 and TNFAIP6, which had previously been associated with sepsis in other research. Using these genes, we trained a logistic regression classifier to distinguish whether a sample contains an E. coli or S. aureus infection or belongs to a healthy control group, and subsequently assessed its performance. The classifier achieved an Area Under the Curve (AUC) of 0.96 for E. coli and 0.98 for S. aureus-induced sepsis, and perfect discrimination (AUC of 1) for healthy controls from the other conditions in a 10-fold cross-validation. The genes demonstrated an AUC of 0.75 in distinguishing between sepsis patients with E. coli and S. aureus pathogens. These findings were further confirmed in two distinct independent validation datasets which gave high prediction AUC ranging from 0.72–0.87 and 0.62 in distinguishing three groups of participants and two groups of patients respectively. These genes were significantly enriched in the immune system, cytokine signaling in immune system, innate immune system, and interferon signaling. Transcriptional patterns in blood can differentiate patients with E. coli-induced sepsis from those with S. aureus-induced sepsis. These diagnostic markers, upon validation in larger trials, may serve as a foundation for a reliable differential diagnostics assay. [ABSTRACT FROM AUTHOR]

Background: The Sequential Organ Failure Assessment (SOFA) score is an important tool in diagnosing sepsis and quantifying organ dysfunction. However, despite emerging evidence of differences in sepsis pathophysiology between women and men, sex is currently not being considered in the SOFA score. We aimed to investigate potential sex-specific differences in organ dysfunction, as measured by the SOFA score, in patients with sepsis or septic shock and explore outcome associations. Methods: Retrospective analysis of sex-specific differences in the SOFA score of prospectively enrolled ICU patients with sepsis or septic shock admitted to one of 85 certified Swiss ICUs between 01/2021 and 12/2022. Results: Of 125,782 patients, 5947 (5%) were admitted with a clinical diagnosis of sepsis (2244, 38%) or septic shock (3703, 62%). Of these, 5078 (37% women) were eligible for analysis. A statistically significant difference of the total SOFA score on admission was found between women (mean 7.5 ± SD 3.6 points) and men (7.8 ± 3.6 points, Wilcoxon rank-sum p < 0.001). This was driven by differences in the coagulation (p = 0.008), liver (p < 0.001) and renal (p < 0.001) SOFA components. Differences between sexes were more prominent in younger patients < 52 years of age (women 7.1 ± 4.0 points vs men 8.1 ± 4.2 points, p = 0.004). No sex-specific differences were found in ICU length of stay (women median 2.6 days (IQR 1.3–5.3) vs men 2.7 days (IQR 1.2–6.0), p = 0.13) and ICU mortality (women 14% vs men 15%, p = 0.17). Conclusion: Sex-specific differences exist in the SOFA score of patients admitted to a Swiss ICU with sepsis or septic shock, particularly in laboratory-based components. Although the clinical meaningfulness of these differences is unclear, a reevaluation of sex-specific thresholds for SOFA score components is warranted in an attempt to make more accurate and individualised classifications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data regarding the incidence and mortality of sepsis are scarcely available. The present study aimed to delineate the epidemiology of sepsis and related mortality among patients hospitalized in Sicily, Italy. Methods: Data on the discharge forms of all patients with sepsis in all Sicilian hospitals from January 2016 to December 2020 were retrospectively collected. Results: In Sicily, 15,373 hospitalizations associated with sepsis occurred from 2016 to 2020, with an overall in-hospital mortality rate of 36.3%. The percentage of hospitalizations associated with sepsis represented 0.65% of all admissions, with an increase over the years. Most patients were admitted to non-surgical and non-infectious disease units, accounting for 50.3% of total admissions. Stratification of patients according to age, intensive care unit (ICU) admission, and presence of septic shock revealed variations in in-hospital mortality rates. Among adult ICU-admitted patients with septic shock, mortality was highest at 81.0%, followed by non-ICU adult patients with septic shock (63.5%), ICU pediatric patients with septic shock (56.7%), ICU adult patients without septic shock (43.9%), non-ICU pediatric patients with septic shock (37.9%), non-ICU adult patients without septic shock (17.9%), ICU pediatric patients without septic shock (10.4%), and non-ICU pediatric patients without septic shock (1%). [ABSTRACT FROM AUTHOR]

Sex differences in the in-hospital management of sepsis exist. Previous studies either included patients with sepsis that was defined using previous definitions of sepsis or evaluated the 3-h bundle therapy. Therefore, this study sought to assess sex differences in 1-h bundle therapy and in-hospital management among patients with sepsis and septic shock, defined according to the Sepsis-3 definitions. This observational study used data from Korean Shock Society (KoSS) registry, a prospective multicenter sepsis registry. Adult patients with sepsis between June 2018 and December 2021 were included in this study. The primary outcome was adherence to 1-h bundle therapy. Propensity score matching (PSM) and multivariable logistic regression analyses were performed. Among 3264 patients with sepsis, 3129 were analyzed. PSM yielded 2380 matched patients (1190 men and 1190 women). After PSM, 1-h bundle therapy was performed less frequently in women than in men (13.0% vs. 19.2%; p < 0.001). Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently in women than in men (25.4% vs. 31.6%, p < 0.001), whereas adequate fluid resuscitation was performed more frequently in women than in men (96.8% vs. 95.0%, p = 0.029). In multivariable logistic regression analysis, 1-h bundle therapy was performed less frequently in women than in men [adjusted odds ratio (aOR) 1.559; 95% confidence interval (CI) 1.245–1.951; p < 0.001] after adjustment. Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently to women than men (aOR 1.339, 95% CI 1.118–1.605; p = 0.002), whereas adequate fluid resuscitation was performed more frequently for women than for men (aOR 0.629, 95% CI 0.413–0.959; p = 0.031). Invasive arterial blood pressure monitoring was performed less frequently in women than in men. Resuscitation fluid, vasopressor, steroid, central-line insertion, ICU admission, length of stay in the emergency department, mechanical ventilator use, and renal replacement therapy use were comparable for both the sexes. Among patients with sepsis and septic shock, 1-h bundle therapy was performed less frequently in women than in men. Continuous efforts are required to increase adherence to the 1-h bundle therapy and to decrease sex differences in the in-hospital management of patients with sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether the age at menarche (AAM) and the age at menopause (ANM) are causally related to the development of sepsis. Methods: We performed a two-sample Mendelian randomization (MR) analysis by utilizing summary statistics from genome-wide association study (GWAS) datasets for both the exposure and outcome variables. Single nucleotide polymorphisms (SNPs) that exhibited significant associations with AAM and ANM were chosen as instrumental variables to estimate the causal effects on sepsis. Our study employed a variety of methods, including MR-Egger regression, weighted median estimation, inverse variance weighting, a simple model, and a weighted model. Odds ratios (ORs) along with their corresponding 95% confidence intervals (CIs) were used as the primary indicators for assessing causality. Furthermore, we conducted sensitivity analyses to explore the presence of genetic heterogeneity and validate the robustness of the tools employed. Result: Our analysis revealed a significant negative causal relationship between AAM and the risk of sepsis (IVW: OR = 0.870, 95% CI = 0.793–0.955, P = 0.003). However, our Mendelian randomization (MR) analysis did not yield sufficient evidence to support a causal link between ANM and sepsis (IVW: OR = 0.987, 95% CI = 0.971–1.004, P = 0.129). Conclusions: Our findings suggest that an earlier AAM may be associated with an increased risk of sepsis. However, we did not find sufficient evidence to support a causal relationship between ANM and sepsis. [ABSTRACT FROM AUTHOR]

Background: Sepsis and trauma are known to disrupt gut bacterial microbiome communities, but the impacts and perturbations in the fungal (mycobiome) community after severe infection or injury, particularly in patients experiencing chronic critical illness (CCI), remain unstudied. Methods: We assess persistence of the gut mycobiome perturbation (dysbiosis) in patients experiencing CCI following sepsis or trauma for up to two-to-three weeks after intensive care unit hospitalization. Results: We show that the dysbiotic mycobiome arrays shift toward a pathobiome state, which is more susceptible to infection, in CCI patients compared to age-matched healthy subjects. The fungal community in CCI patients is largely dominated by Candida spp; while, the commensal fungal species are depleted. Additionally, these myco-pathobiome arrays correlate with alterations in micro-ecological niche involving specific gut bacteria and gut-blood metabolites. Conclusions: The findings reveal the persistence of mycobiome dysbiosis in both sepsis and trauma settings, even up to two weeks post-sepsis and trauma, highlighting the need to assess and address the increased risk of fungal infections in CCI patients. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-lymphocyte ratio (NLR) is an easily computable parameter and is believed to accurately determine the disease-related organ dysfunction severity and prognosis in sepsis. Methods: This study aimed at identifying the role of NLR in predicting organ dysfunction severity and prognosis in patients with sepsis requiring admission to an intensive care unit (ICU). In this observational study, NLR and Sequential Organ Failure Assessment (SOFA) scores were calculated at the time of admission in patients with sepsis. Patients were followed until discharge or death. Results: Fifty five ICU patients with sepsis were enrolled. The mean NLR and SOFA scores for the total study cohort were 7.91 ± 3.01 and 8.76 ± 3.16, respectively. The corresponding values for those in septic shock were 8.96 ± 2.80 and 9.94 ± 3.78. A positive correlation was observed between SOFA score and NLR in all patients (r = 0.5584, P < 0.001); patients with sepsis only (r = 0.4821, P = 0.002); and patients with sepsis and shock (r = 0.6321, P = 0.004). In the total population, mean NLR was significantly higher among non-survivors, compared to survivors (9.17±3.1 vs. 7.09±2.7; P = 0.0054). Conclusions: NLR at admission shows a good correlation with the organ dysfunction severity in sepsis and may be used as a prognostic marker, thereby guiding the intensification of management. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis is more common in males than females, but whether outcomes differ by sex in various pediatric age groups is unclear. The Life After Pediatric Sepsis Evaluation (LAPSE) was a multicenter prospective cohort study that evaluated health-related quality of life (HRQL) in children after community-acquired septic shock. In this secondary analysis, we evaluated whether male children are at increased risk of mortality or long-term decline in HRQL than female children by age group. Methods: Children (1 month–18 years) with community-acquired septic shock were recruited from 12 pediatric intensive care units in the U.S. Data included sex, age group (<1 year, 1–<13 years, 13–18 years), acute illness severity (acute organ dysfunction and inflammation), and longitudinal assessments of HRQL and mortality. Persistent decline in HRQL was defined as a 10% decrease in HRQL comparing baseline to 3 months following admission. Male and female children were stratified by age group and compared to evaluate the difference in the composite outcome of death or persistent decline in HRQL using the Cochran–Mantel–Haenszel test. Results: Of 389 children, 54.2% (n = 211) were male. Overall, 10% (21/211) of males and 12% (22/178) of females died by 3 months (p = 0.454). Among children with follow-up data, 41% (57/138) of males and 44% (48/108) of females died or had persistent decline in HRQL at 3 months (p = 0.636), with no observed difference by sex when stratified by age group. There was no significant difference in acute illness severity between males and females overall or stratified by age group. Conclusions: In this secondary analysis of the LAPSE cohort, HRQL, and mortality were not different between male and female children when stratified by age group. There were no significant differences by sex across multiple measures of illness severity or treatment intensity. [ABSTRACT FROM AUTHOR]

There is growing awareness that sex differences are associated with different patient outcomes in a variety of diseases. Studies investigating the effect of patient sex on sepsis-related mortality remain inconclusive and mainly focus on patients with severe sepsis and septic shock in the intensive care unit. We therefore investigated the association between patient sex and both clinical presentation and 30-day mortality in patients with the whole spectrum of sepsis severity presenting to the emergency department (ED) who were admitted to the hospital. In our multi-centre cohort study, we retrospectively investigated adult medical patients with sepsis in the ED. Multivariable analysis was used to evaluate the association between patient sex and all-cause 30-day mortality. Of 2065 patients included, 47.6% were female. Female patients had significantly less comorbidities, lower Sequential Organ Failure Assessment score and abbreviated Mortality Emergency Department Sepsis score, and presented less frequently with thrombocytopenia and fever, compared to males. For both sexes, respiratory tract infections were predominant while female patients more often had urinary tract infections. Females showed lower 30-day mortality (10.1% vs. 13.6%; p =.016), and in-hospital mortality (8.0% vs. 11.1%; p =.02) compared to males. However, a multivariable logistic regression model showed that patient sex was not an independent predictor of 30-day mortality (OR 0.90; 95% CI 0.67–1.22; p =.51). Females with sepsis presenting to the ED had fewer comorbidities, lower disease severity, less often thrombocytopenia and fever and were more likely to have a urinary tract infection. Females had a lower in-hospital and 30-day mortality compared to males, but sex was not an independent predictor of 30-day mortality. The lower mortality in female patients may be explained by differences in comorbidity and clinical presentation compared to male patients. Only limited data exist on sex differences in sepsis patients presenting to the emergency department with the whole spectrum of sepsis severity. Female sepsis patients had a lower incidence of comorbidities, less disease severity and a different source of infection, which explains the lower 30-day mortality we found in female patients compared to male patients. We found that sex was not an independent predictor of 30-day mortality; however, the study was probably underpowered to evaluate this outcome definitively. [ABSTRACT FROM AUTHOR]

Immature/total neutrophils (I/T) ratio is a simple and inexpensive method used as an early sign of bacterial infection. Meanwhile, the S100B protein is found in glial cells and functions as a neuroprotection. Then, the interleukin-10 cytokine acts as an anti-inflammatory cytokine during infection. In addition, the NEWS2 score is used to see the early and fast changes in patients with sepsis. The purpose of the study was to prove the correlation between the I/T ratio, S100B, IL-10, and NEWS2 score in patients with sepsis. A crosssectional study was conducted on 34 patients with sepsis from September 2020 to February 2021. I/T ratio was calculated in 100 leukocytes from microscopic blood smear preparation. Levels of S100B and IL-10 serum were measured using the ELISA method. Pearson correlation test was used for normally distributed data, and the Spearman correlation test was utilized for abnormally distributed data. Correlation test between I/T ratio, S100B, and IL-10 with NEWS2 score respectively showed values of r=0.58; P=0.01, r=0.36; P=0.03, and r=0.39; P=0.02, in which P<0.05. There was a moderate positive correlation between I/T ratio and NEWS2 score, a weak positive correlation between S100B and NEWS2 score, and a weak positive correlation between IL-10 and NEWS2 score. [ABSTRACT FROM AUTHOR]

Sepsis is one of the primary causes of mortality in the world. When the sepsis develops into acute organ dysfunction it is considered severe. Severe sepsis increases the economic burden by means of potential treatment for inflammatory responses and multiple organ failure. Several factors, including age, inappropriate use of antibiotics, comorbidities, multiple organ dysfunction, and site of infection, are considered to increase mortality risk in severe septic patients. This systematic review analyses various factors influencing mortality in ICU-hospitalized patients with severe sepsis. A systematic search for relevant articles up to September 2022 was carried out on 6 electronic databases, including Scopus, MEDLINE, PubMed, ScienceDirect, Embase and Google Scholar. Of 1078 articles, only nine studies were reviewed after meeting the inclusion criteria. Meta-analysis of three studies reveal significantly more fatality in older patients than the younger (OR; 2.28: 1.65, 3.15: 95% CI: I² = 11%, P <0.00001). The number of organ failure also significantly influences the mortality with the mortality rate being higher for patients with =4 organ failures (OR; 0.19: 0.11, 0.30: 95% CI: I² = 93%: P <0.00001). The mortality rates for hospital-acquired, community-acquired and ICU-acquired infections were 0.41 (95% CI; 0.18, 0.69), 0.40 (95% CI; 0.20, 0.63), and 0.42 (95% CI; 0.44, 0.53), respectively. Gender shows no significant difference on mortality rates (OR; 1.05: 0.95, 1.16: 95% CI: I² = 27%: p = 0.35). Age, the number of organ failures, and the acquisition sites seem to significantly influence the mortality, while gender has an insignificant influence on the mortality of ICU-admitted severe septic patients. [ABSTRACT FROM AUTHOR]

Background: Abscess, an infection with viable infecting organisms and polymorphonuclear cells, contained within a fibrous capsule, limiting the infection, and preventing its further spread. It may be monomicrobial or polymicrobial. Aims and Objectives: The aims of the study were to determine microbiological profile of abscesses of different body sites and associated complications. Materials and Methods: An observational study was conducted in our department with 35 pus samples from abscesses of different body sites between August 2022 and December 2022. Gram stain, Z-N stain, fungal stain, aerobic, anaerobic, and fungal culture were performed. Statistical analysis was done by statistical tool R. Results: Out of 35 sampleslimb, liver, paraspinal, psoas, appendicular, breast, perineal, ear, brain and lung abscesses were 11,4,2,3,1,7,2,2,2,1 respectively. Most common organisms from limb, ear, paraspinal and breast abscesses was MRSA (Methicillin resistant Staphylococcal aureus). Also most common organisms were - Escherichia coli from liver abscess, Enterobacteriaceae and Pseudomonas aeruginosa from psoas and appendicular abscess, Enterobacter aerogenes from perineal, Escherichia coli and Actinomyces species from brain and Candida auris from lung abcesses. No growth were also found in few samples. Their susceptibility testing showed-MRSA strains susceptible to both Vancomycin and Linezolid, gram negative bacteria were susceptible to Cephalosporins, Piperacillin-tazobactam, Carbapenems, polymixins, etc. C.auris was resistant to all antifungals. Their blood samples were also collected - ten patients showed fever with bacteremia and one with candidemia. They were treated with systemic antimicrobials along with drainage and/or surgical resection. Conclusion: Abscesses must be suspected in cases with non-resolving fever with/without septicemia and treated promptly with appropriate antimicrobials based on susceptibility report and with drainage and/or surgical resection. [ABSTRACT FROM AUTHOR]

Background: Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group. Methods: This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19–50 years, 50–80 years, and ≥ 80 years old individuals. Results: During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02–1.29). Interestingly, in the age 19–50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35–0.93)]. For female, the risk of death remained relatively stable until around age 80 (P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 (P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19–50 groups (adjusted OR = 0.29, 95% CI = 0.12–0.69). Conclusions: Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in the clinical management and understanding of sepsis and septic shock, these complex clinical syndromes continue to have high mortality rates. The effect of sex on these diseases' mortality, clinical presentation and morbidity remains controversial. This study aimed to investigate the association of sex with mortality and organ dysfunction in patients with sepsis and septic shock. Methods: Prospectively enrolled patients with clinically defined sepsis and septic shock in three intensive care units at University Medical Center Göttingen, Germany, were investigated. The primary outcomes were 28- and 90-day mortality, while the secondary endpoints included the evaluation of organ dysfunction as measured by clinical scores and laboratory parameters. Results: A total of 737 septic patients were enrolled, including 373 in septic shock, 484 males, and 253 females. No significant differences in 28- and 90-day mortality were observed in the cohort. However, men with sepsis had significantly higher SOFA scores, SOFA respiratory and renal subscores, bilirubin and creatinine values, and lower weight-adapted urine outputs, indicating higher organ dysfunction compared to women. Conclusions: Our findings revealed notable differences in organ dysfunction between male and female patients, with males exhibiting more pronounced dysfunction across multiple clinical indicators. These results highlight the potential influence of sex on sepsis disease severity and suggest the need for tailored approaches in sepsis management according to patient sex. [ABSTRACT FROM AUTHOR]

Most sepsis deaths are due to the development of multiple organ failure, in which heart failure is a recognized manifestation of sepsis. To date, the role of liver X receptors α (NR1H3) in sepsis is still uncertain. Here, we hypothesized that NR1H3 mediates multiple essential sepsis‐related signalings to attenuate septic heart failure. Adult male C57BL/6 or Balbc mice and HL‐1 myocardial cell line were performed for in vivo and in vitro experiments, respectively. NR1H3 knockout mice or NR1H3 agonist T0901317 was applied to evaluate the impact of NR1H3 on septic heart failure. We found decreased myocardial expression levels of NR1H3‐related molecules while increased NLRP3 level in septic mice. NR1H3 knockout worsensed cardiac dysfunction and injury in mice subjected to cecal ligation and puncture (CLP), in association with exacerbated NLRP3‐mediated inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis‐related markers. The administration of T0901317 reduced systemic infection and improve cardiac dysfunction in septic mice. Moreover, Co‐IP assays, luciferase reporter assays, and chromatin immunoprecipitation analysis, confirmed that NR1H3 directly repressed NLRP3 activity. Finally, RNA‐seq detection further clarified an overview of the roles of NR1H3 in sepsis. In general, our findings indicate that NR1H3 had a significant protective effect against sepsis and sepsis‐induced heart failure. [ABSTRACT FROM AUTHOR]

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Common causes include gram-negative and gram-positive bacteria as well as fungi. Neutrophils are among the first cells to arrive at an infection site where they function as important effector cells of the innate immune system and as regulators of the host immune response. The regulation of neutrophil migration is therefore important both for the infection-directed host response and for the development of organ dysfunctions in sepsis. Downregulation of CXCR4/CXCL12 stimulates neutrophil migration from the bone marrow. This is followed by transmigration/extravasation across the endothelial cell barrier at the infection site; this process is directed by adhesion molecules and various chemotactic gradients created by chemotactic cytokines, lipid mediators, bacterial peptides, and peptides from damaged cells. These mechanisms of neutrophil migration are modulated by sepsis, leading to reduced neutrophil migration and even reversed migration that contributes to distant organ failure. The sepsis-induced modulation seems to differ between neutrophil subsets. Furthermore, sepsis patients should be regarded as heterogeneous because neutrophil migration will possibly be further modulated by the infecting microorganisms, antimicrobial treatment, patient age/frailty/sex, other diseases (e.g., hematological malignancies and stem cell transplantation), and the metabolic status. The present review describes molecular mechanisms involved in the regulation of neutrophil migration; how these mechanisms are altered during sepsis; and how bacteria/fungi, antimicrobial treatment, and aging/frailty/comorbidity influence the regulation of neutrophil migration. [ABSTRACT FROM AUTHOR]

Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen–cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition with diverse clinical presentations. Understanding the clinical characteristics and outcomes of sepsis patients in the intensive care unit (ICU) is crucial for optimizing patient care. This prospective observational study included 58 sepsis patients admitted to the ICU. Demographic, clinical, and laboratory data were collected. The "Sequential Organ Failure Assessment (SOFA)" score was used to assess organ dysfunction. Microbiological cultures and biomarkers (Procalcitonin and C-reactive protein) were analyzed. Patients were followed up until discharge or death. The study included sepsis patients 58 in the ICU. Patients exhibited elevated heart rate, leukocyte count, and SOFA scores, reflecting the severity of sepsis. Procalcitonin and C-reactive protein levels were elevated, correlating with positive culture results. Gram-negative organisms were the most commonly isolated pathogens. No significant age or gender-based differences in sepsis outcomes were observed. These findings highlight the clinical characteristics of sepsis in the ICU and the significance of biomarkers in assessing disease severity. This study provides valuable insights into the clinical characteristics and outcomes of sepsis patients in the ICU. It aligns with existing literature, emphasizing the heterogeneity of sepsis and the importance of early diagnosis and appropriate management. Procalcitonin and C-reactive protein are useful biomarkers for assessing disease severity. Further research with larger cohorts is needed to validate these findings and improve sepsis care. [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a common complication in sepsis and is associated with higher mortality. Activated platelets express CD62P, which facilitates platelet-leukocyte aggregate (PLA) formation and contributes to thrombocytopenia in sepsis. We have reported that thrombocytopenia in murine sepsis is partly attributable to TLR7 signaling, but the underlying mechanism is unclear. In the current study, we tested the hypothesis that TLR7 mediates platelet activation and PLA formation during sepsis. In vitro, whole blood from WT mice treated with loxoribine, a TLR7 agonist, exhibited a dose-dependent increase in activated platelets compared to the control (PBS with 0.05% DMSO) or loxoribine-treated TLR7−/− whole blood. In a murine model of sepsis, there was a significant increase in platelet activation and PLA formation 24 hours after cecal ligation and puncture (CLP) as evidenced by double positive expression of CD41+/CD62P+ and CD45+/CD62P+, respectively. The sepsis-induced PLA formation was significantly attenuated in TLR7−/− mice. Finally, in ex-vivo experiments, plasma isolated from septic mice induced WT platelet activation, but such effect was significantly attenuated in platelets deficient of TLR7. These findings demonstrate a pivotal role of TLR7 signaling in platelet activation and PLA formation during bacterial sepsis. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 µg/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed. [ABSTRACT FROM AUTHOR]

The present study was aimed at elucidating the epidemiology of sepsis, with a special emphasis on identifying the common bacterial aetiology, proportion of infections caused by multi-drug resistant (MDR) bacteria, and risk factors associated with 28-day mortality at a university hospital in South India. A prospective study was undertaken from January 2017 to March 2018. Adult patients with the diagnosis of sepsis requiring intensive care unit (ICU) care were recruited. Baseline clinical, epidemiological, and laboratory data were recorded, and their association with 28-day mortality was assessed using logistic regression models. 400 subjects with a qSOFA score ≥2 at the time of ICU admission were included in the study. The mean age was 55.7 ± 16.6 years, and 69% were males. The mean SOFA score at the time of admission was 9.9 ± 2.7. Bacterial aetiology of sepsis was established in 53.5% of cases and 24% were caused by MDR pathogens. Carbapenem resistance was observed in 37% of the Gram-negative isolates. Escherichia coli (34.1%) was the leading pathogen. Overall, the 28-day mortality in ICU was 40%. 38% died within 48 h of ICU admission. Hypertension and SOFA > 9, male gender, and baseline-creatinine values >2.4 mg/dl were risk factors for mortality. Male gender, hypertension, SOFA > 9, and increased creatinine were identified as the predictors for mortality. Infectious aetiology remained undetected in nearly half of the cases using routine microbiology culture methods. Mortality within the first 48 h of admission to ICU is high and prompts the need for increasing awareness about early sepsis diagnosis in community health care settings. [ABSTRACT FROM AUTHOR]

First described by Bright in 1836, who reports two cases secondary to suppurative angiocolitis and pilephlebitis, intrahepatic suppurations were, until the era of the discovery of antibiotics, one of the most dreaded causes of mortality, reaching a rate of almost 100%. Today, both the incidence of liver abscesses and the mortality rate have been significantly reduced, as the introduction of antibiotics has dramatically reduced the number of septic piles due to peritoneal outbreaks. Their etiology is more recently, most frequently, a biliary or neoplastic disease. On the other hand, the improvement of germ isolation techniques has made it possible to identify anaerobic germs with maximum frequency, and diagnostic and treatment performance has increased so much with the advent of non-invasive or minimally-invasive procedures that the overall mortality rate of 70% in 1975 is now about 30–38%. We present the case of a 75-year-old male patient with no known history of ilnesses who is admitted for fever, chills, myalgia, arthralgia and visual disturbances with onset of approximately one week. Biologically he presents with leukocytosis with marked neutrophilia, mild thrombocytopenia and significant biological inflammatory syndrome. Suspicion is raised for a diagnosis of Sepsis with unspecified starting point with possible pyogenic cavernous sinus thrombosis, a complication suggested by the presence of visual disturbances. Neuro-imaging evaluation by CT and brain MRI is performed, with the diagnosis of thrombosis being refuted. Abdominal CT is performed which identifies a space replacement formation in the left hepatic lobe for which MRI evaluation is required. MRI detects an expansive hepatic formation with semiology suggestive of liver abscess. Treatment was instituted with a combination of broad-spectrum antibiotics and antifungal treatment, but the evolution was unfavourable with maintenance of leukocytosis with marked neutrophilia and progression of inflammatory samples. It was necessary to evaluate the case by a multidisciplinary team (infectious disease specialist, gastroenterologist, surgeon) to establish the appropriate therapeutic management, with surgical resolution of the case, with a favourable postoperative evolution. [ABSTRACT FROM AUTHOR]

Providing effective screening tools to nurses is necessary to improve patient outcomes and health care quality. This research examines if the modification of two electronic health record sepsis screening tools using a combined systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and national early warning score (NEWS) criteria improves the recognition of sepsis by nurses. Medical-surgical/telemetry units at a medical center in the Midwest were examined using a quasiexperimental design. Modifications of tool 1 captured 18% more correct classifications of sepsis (odds ratio [OR] =.82, 95% CI = [0.68, 0.98]), triggering for 10% fewer patients, t (1033) = 9.31, p <.001. 95% CI = [0.078, 0.119]. Modifications of tool 2 captured 3 times more correct alerts (OR =.29, 95% CI = [0.24, 0.35]), triggering for 46% fewer patients, t (1033) = 24.38, p <.001. 95% CI = [0.420, 0.493]. The updated criteria showed significant improvement toward correctly identifying sepsis and presents the opportunity to develop an effective tool that balances sensitivity with specificity. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that a variety of blood inflammatory markers can be used to assess the criticality of patients with sepsis. In this study, the blood inflammatory factors related to the sepsis survival group and the death group were compared and analyzed, which can be used by clinicians to adjust sepsis patient treatment.Methods: This study used retrospective methods to analyze the medical records of 428 patients with sepsis. The test of blood samples includes the patient's age, gender, hospital stays, the concentration of procalcitonin (PCT), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), D-dimer (DD), Fe3+, and hemoglobin (Hb) in the venous blood of patients with sepsis. The detection of PCT methods adopts the sandwich immunofluorescence (IF). ROC curve was used for the diagnosis and analysis of various factors of sepsis.Results: Among all the patients with sepsis, 133 patients died, with a mortality rate of 31.07%. Analysis of related inflammatory indicators and the patient's baseline parameters showed the patients age, the values of PCT, ANC, NLR, and DD in death group were statistically higher than those in survival group (all p values were <0.05). However, the concentration of Fe3+ and ALC show an opposite trend between the two groups. Regression analysis results showed the patient's gender, Fe3+, PCT, ANC, and DD are all independent prognostic factors for patients with sepsis. The results of the ROC curve of related diagnostic indicators show that DD has the best area under curve (AUC=0.700), the most sensitive index is ANC (74.44), and the most specific index is PCT (89.80). The results of the two-by-two combined diagnosis of the four indicators showed that the PCT+DD group had better AUC (0.748) and specificity (78.23), and the Fe3++DD group had the best sensitivity (75.89).Conclusion: In this study, the patient's gender and the inflammation-related markers of Fe3+, PCT, ANC, and DD can be used as independent risk factors affecting the prognosis of patients with sepsis. The combination of PCT+DD and Fe3++DD has high diagnostic value for patients with sepsis. [ABSTRACT FROM AUTHOR]

Objectives: To examine the trends in hospitalization rates, mortality, and costs for sepsis during the years 2005 to 2014. Methods: This was a retrospective serial cross-sectional analysis of patients ≥18 years admitted for sepsis in National Inpatient Sample. Trends in sepsis hospitalizations were estimated, and age- and sex-adjusted rates were calculated for the years 2005 to 2014. Results: There were 541 694 sepsis admissions in 2005 and increased to 1 338 905 in 2014. Sepsis rates increased significantly from 1.2% to 2.7% during the years 2005 to 2014 (relative increase: 123.8%; Ptrend < .001). However, the relative increase changed by 105.8% (Ptrend < .001) after adjusting for age and sex and maintained significance. Although total cost of hospitalization due to sepsis increased significantly from US$22.2 to US$38.1 billion (Ptrend < .001), the mean hospitalization cost decreased significantly from US$46,470 to US$29,290 (Ptrend < .001). Conclusions: Hospitalizations for sepsis increased during the years 2005 to 2014. Our study paradoxically found declining rates of in-hospital mortality, length of stay, and mean hospitalization cost for sepsis. These findings could be due to biases introduced by International Classification of Diseases, Ninth Revision, Clinical Modification coding rules and increased readmission rates or alternatively due to increased awareness and surveillance and changing disposition status. Standardized epidemiologic registries should be developed to overcome these biases. [ABSTRACT FROM AUTHOR]

Purpose: Sepsis is recognized as a global public health problem, but the proportion due to hospital-acquired infections remains unclear. We aimed to summarize the epidemiological evidence related to the burden of hospital-acquired (HA) and ICU-acquired (ICU-A) sepsis. Methods: We searched MEDLINE, Embase and the Global Index Medicus from 01/2000 to 03/2018. We included studies conducted hospital-wide or in intensive care units (ICUs), including neonatal units (NICUs), with data on the incidence/prevalence of HA and ICU-A sepsis and the proportion of community and hospital/ICU origin. We did random-effects meta-analyses to obtain pooled estimates; inter-study heterogeneity and risk of bias were assessed. Results: Of the 13,239 studies identified, 51 met the inclusion criteria; 22 were from low- and middle-income countries. Twenty-eight studies were conducted in ICUs, 13 in NICUs, and ten hospital-wide. The proportion of HA sepsis among all hospital-treated sepsis cases was 23.6% (95% CI 17–31.8%, range 16–36.4%). In the ICU, 24.4% (95% CI 16.7–34.2%, range 10.3–42.5%) of cases of sepsis with organ dysfunction were acquired during ICU stay and 48.7% (95% CI 38.3–59.3%, range 18.7–69.4%) had a hospital origin. The pooled hospital incidence of HA sepsis with organ dysfunction per 1000 patients was 9.3 (95% CI 7.3–11.9, range 2–20.6)). In the ICU, the pooled incidence of HA sepsis with organ dysfunction per 1000 patients was 56.5 (95% CI 35–90.2, range 9.2–254.4) and it was particularly high in NICUs. Mortality of ICU patients with HA sepsis with organ dysfunction was 52.3% (95% CI 43.4–61.1%, range 30.1–64.6%). There was a significant inter-study heterogeneity. Risk of bias was low to moderate in ICU-based studies and moderate to high in hospital-wide and NICU studies. Conclusion: HA sepsis is of major public health importance, and the burden is particularly high in ICUs. There is an urgent need to improve the implementation of global and local infection prevention and management strategies to reduce its high burden among hospitalized patients. [ABSTRACT FROM AUTHOR]

Background: Sepsis syndrome is an emerging healthcare problem, especially in critically ill patients, regardless whether it's community- or hospital-acquired sepsis. This study evaluates the characteristics of these patients, in addition to the type, source, and outcome of sepsis and septic shock, in a university tertiary hospital in Palestine. It also studies the most common organisms encountered in these patients. Materials and methods: This is retrospective observational chart review study of all adult admissions to the intensive care unit over a period of 2 years. The presence of sepsis and septic shock was assessed and documented based on the Third International Consensus Definitions (Sepsis-3). Data regarding demographics, severity, comorbidities, source of infection, microbiology, length of stay, and outcomes (dead/alive at discharge from ICU) were recorded. Results: A total number of 174 patients were included. The mean age was 57.4 years, with cardiovascular diseases and diabetes being the leading comorbidities encountered in them. Respiratory infections were the most common site of sepsis, found in around 71% of patients, followed by urinary tract infections. More than 70% of cases were due to hospital-acquired infections (HAIs). Acinetobacter species were the most common gram-negative organisms encountered, while Enterococcus was the most common gram-positive organisms. Around 54% of patients had multidrug-resistant organisms. The average length of stay in the ICU was 8 days. The average mortality rate was 39.7%, which is higher among septic shock patients. Conclusion: Both sepsis and septic shock carry high morbidity and mortality rates, and they are very frequent among critically ill patients. Special care and developing management bundles are crucial in controlling and preventing this threat. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening syndrome that occurs in response to a severe infection. In recent years, the understanding of the pathobiology of sepsis has been refined, with research describing an altered host response as the underlying cause. Survivors of sepsis often have long hospital stays and suffer from subsequent frailty and long-term health consequences. Predicting attributes of sepsis survivors remains challenging; however, an obesity paradox exists, wherein obese individuals survive sepsis at higher rates than their normal-weight counterparts. We present a model that describes the relationships between sepsis and obesity, focusing on inflammation as a shared pathway for dysregulation in obese and healthy-weight adults. Understanding the interaction of these complex variables is an important first step toward developing interventions and treatments to augment sepsis survival. [ABSTRACT FROM AUTHOR]

Alterations in the energy homeostasis contribute to sepsis-mediated multiple organ failure. The liver plays a central role in metabolism and participates to the innate immune and inflammatory responses of sepsis. Several clinical and experimental studies have suggested that females are less susceptible to the adverse outcome of sepsis. However, underlying mechanisms of organ damage in sepsis remain largely undefined. AMP-activated protein kinase (AMPK) is an important regulator of mitochondrial quality control. The AMPK catalytic α1 isoform is abundantly expressed in the liver. Here, we determined the role of hepatocyte AMPKα1 in sepsis by using hepatocyte-specific AMPKα1 knockout mice (H-AMPKα1 KO) generated with Cre-recombinase expression under the control of the albumin promoter. Using a clinically relevant model of polymicrobial sepsis by cecal ligation and puncture (CLP), we observed that male H-AMPKα1 KO mice had higher plasma levels of tumor necrosis factor-α and interleukin-6 and exhibited a more severe liver and lung injury than male H-AMPKα1 WT mice, as evaluated by histology and neutrophil infiltration at 18 h after CLP. Plasma levels of interleukin-10 and the keratinocyte-derived chemokine were similarly elevated in both KO and WT male mice. At transmission electron microscopy analysis, male H-AMPKα1 KO mice exhibited higher liver mitochondrial damage, which was associated with a significant decrease in liver ATP levels when compared to WT mice at 18 h after sepsis. Mortality rate was significantly higher in the male H-AMPKα1 KO group (91%) when compared to WT mice (60%) at 7 days after CLP. Female H-AMPKα1 WT mice exhibited a similar degree of histological liver and lung injury, but significantly milder liver mitochondrial damage and higher autophagy when compared to male WT mice after CLP. Interestingly, H-AMPKα1 KO female mice had lower organ neutrophil infiltration, lower liver mitochondrial damage and lower levels of cytokines than WT female mice. There was no significant difference in survival rate between WT and KO mice in the female group. In conclusion, our study demonstrates that AMPKα1 is a crucial hepatoprotective enzyme during sepsis. Furthermore, our results suggest that AMPK-dependent liver metabolic functions may influence the susceptibility to multiple organ injury in a sex-dependent manner. [ABSTRACT FROM AUTHOR]