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Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in human sepsis. ApoA-IV (analyzed in 156 patients with systemic inflammatory response syndrome (SIRS)/sepsis) and cholesteryl ester (CE) (analyzed in 121 of these patients) were lower in patients compared to 43 healthy controls. In contrast, triglyceride (TG) levels were elevated in patients. ApoA-IV levels in plasma of the patients did not correlate with these lipids. Patients with SIRS, sepsis or septic shock had comparable apoA-IV, TG, CE and free cholesterol (FC) levels. Patients on dialysis had significantly lower CE levels, whereas apoA-IV levels did not change much. CE levels were elevated in patients with viral sepsis due to SARS-CoV-2 infection in comparison to SIRS/sepsis patients not infected by this virus. CE levels correlated negatively with procalcitonin, interleukin-6 and bilirubin, while TGs were positively associated with bilirubin and C-reactive protein. ApoA-IV, TG, CE and FC levels were not associated with bacterial infection or survival. In conclusion, this analysis suggests that CE levels decline in sepsis-related renal failure and also shows that plasma apoA-IV and CE levels are early biomarkers of sepsis. [ABSTRACT FROM AUTHOR]

Background: Surgery often leads to bleeding associated with hypofibrinogenemia. Supplementation with fibrinogen concentrate appears to be effective and safe, although findings from studies are inconsistent. The primary aim of this study was to assess the safety of fibrinogen concentrate during the perioperative period. Methods: This single-centre, prospective, observational study included adult patients undergoing scheduled or emergency surgery related to bleeding coagulopathy and the administration of fibrinogen concentrate. Patients were followed until their discharge from the institution. Comprehensive data were collected, including age, sex, type of surgery, associated comorbidities, anticoagulant and/or anti-aggregating therapy, and the number of blood transfusions. Laboratory data on plasma fibrinogen concentration, haemoglobin, and platelet count before and after surgery were also collected. The primary outcomes were the mortality rate at discharge and any reported thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, and myocardial infarction. Results: The study included 91 adult patients who had undergone surgery, with 29 surgeries (32%) conducted in an emergency setting. The mean age was 59.2 years, and 53.8% were male. Major bleeding occurred in 29 cases, mainly in older males and those on anticoagulant therapy. The pre-operative fibrinogen level averaged 161 mg/dL, and the average dosage of fibrinogen concentrate administered was 2.7 g. Eight patients died (8.8%), mostly due to septic or cardiogenic shock, with deaths being more frequent in emergency settings. Thromboembolic events occurred in eight patients, none of whom died. No additional adverse events directly related to the administration of fibrinogen concentrate were reported. Conclusions: Our findings suggest a favourable safety profile for fibrinogen concentrate in surgical patients, as evidenced by a low incidence of deaths and thromboembolic events, which were primarily attributed to other factors. Future research should strive to increase statistical robustness to further illuminate clinically significant patient safety measures. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with Non-Alcoholic Fatty Liver Disease (NAFLD) are reported to have an increased risk of developing severe infections, leading to hospitalizations with sepsis. However, data regarding the impact of comorbid NAFLD on in-hospital outcomes of patients with sepsis is scarce. Methods: This nationwide retrospective observational study using discharge data from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), and Agency for Healthcare Research and Quality included 21,057,911 adult patients who were admitted to hospitals in the United States between 2000 and 2019 with a primary discharge diagnosis of sepsis. These patients were categorized according to the presence or absence of comorbid NAFLD. The twenty-year trend of nationwide NAFLD prevalence among sepsis inpatients was elucidated. Multivariable logistic regression analysis was used to analyze NAFLD's impact on sepsis outcomes. Results: In the twenty-year study period, the prevalence of NALFD among sepsis inpatients trended up from 1.2% in 2000 to 4.2% in 2019. Similar trends were observed in regional analysis. While overall sepsis mortality decreased, comorbid NAFLD in sepsis patients was consistently associated with a higher adjusted in-hospital all-cause mortality rate (adjusted odds ratio (OR), 1.19; 95% confidence interval (CI), 1.07–1.32), higher odds of developing septic shock, and higher likelihood of development of multi–organ dysfunction. Conclusions: Comorbid NAFLD in the stage of NASH or cirrhosis is associated with higher in-hospital all-cause mortality and worse clinical outcomes in sepsis inpatients. Addressing this rising epidemic will be of paramount importance to improve sepsis in-hospital outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Sepsis and septic shock remain significant contributors to high early mortality rates among patients admitted to the emergency department (ED). The objective of this study was to identify among newer biomarkers those with the highest sensitivity in early mortality prediction. Methods: This prospective, unicentric, observational study enrolled 47 adult patients admitted to the ED between November 2020 and December 2022. This study monitored the kinetics of the older and newer biomarkers, including azurocidin (AZU1), soluble triggering receptor expressed on myeloid cells (sTREM), soluble urokinase-type plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), and interleukin-6 (IL-6), and their capacity in predicting mortality. Results: SuPAR showed the most significant predictive utility for early prognosis of mortality in the ED, with an area under the curve (AUC) of 0.813 (95% CI: 0.672 to 0.912), a cutoff value > 8168 ng/mL, sensitivity of 75%, and specificity of 81.48% (p < 0.001). IL-6 and PCT showed comparable prognostic accuracy, whereas hsCRP and AZU1 demonstrated lower predictive performance. Conclusions: In our study, suPAR, IL-6, and PCT showed good predictive value for short-term mortality in sepsis and septic shock patients. [ABSTRACT FROM AUTHOR]

Sepsis poses a significant challenge due its lethality, involving multiple organ dysfunction and impaired immune responses. Among several factors affecting sepsis, monocytes play a crucial role; however, their phenotype, proteomic profile, and function in septic shock remain unclear. Our aim was to fully characterize the subpopulations and proteomic profiles of monocytes seen in septic shock cases and discuss their possible impact on the disease. Peripheral blood monocyte subpopulations were phenotype based on CD14/CD16 expression by flow cytometry, and proteins were extracted from the monocytes of individuals with septic shock and healthy controls to identify changes in the global protein expression in these cells. Analysis using 2D-nanoUPLC-UDMSE identified 67 differentially expressed proteins in shock patients compared to controls, in which 44 were upregulated and 23 downregulated. These proteins are involved in monocyte reprogramming, immune dysfunction, severe hypotension, hypo-responsiveness to vasoconstrictors, vasodilation, endothelial dysfunction, vascular injury, and blood clotting, elucidating the disease severity and therapeutic challenges of septic shock. This study identified critical biological targets in monocytes that could serve as potential biomarkers for the diagnosis, prognosis, and treatment of septic shock, providing new insights into the pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis, a leading global health challenge, accounts for around 20% of deaths worldwide. The complexity of sepsis, especially the difference between bacterial and viral etiologies, requires an effective assessment of microcirculation during resuscitation. This study aimed to evaluate the impact of infusion therapy on microcirculation in patients with sepsis, focusing on bacterial- and COVID-19-associated sepsis using remote photoplethysmography (rPPG) and the automated capillary refill time (aCRT). Materials and Methods: This single-center prospective study was conducted in the ICU of Pauls Stradins Clinical University Hospital, including 20 patients with sepsis/septic shock. The patients were selected based on hemodynamic instability and divided into COVID-19 and Bacterial Septic Shock groups. Fluid responsiveness was assessed using the Passive Leg Raising Test (PLRT). Systemic hemodynamics and microcirculation were monitored through MAP CRT, rPPG, and serum lactate levels. Statistical analyses compared responses within and between the groups across different stages of the protocol. Results: The Bacterial group exhibited higher initial serum lactate levels and more pronounced microcirculatory dysfunction than the COVID-19 group. rPPG was more sensitive in detecting perfusion changes, showing significant differences between the groups. The automated CRT demonstrated greater sensitivity compared to the manual CRT, revealing significant differences during PLRT stages between bacterial- and COVID-19-associated sepsis. Both groups had a transient hemodynamic response to PLRT, with subsequent stabilization upon fluid infusion. Conclusions: When managing patients with sepsis in intensive care, monitoring microcirculation is of paramount importance in infusion therapy. Our study highlights the potential of rPPG and aCRT as tools for this purpose. These techniques can be used in conjunction with routine parameters, such as lactate levels and systemic hemodynamic parameters, to provide a comprehensive assessment of a patient's condition. [ABSTRACT FROM AUTHOR]

Background and Objectives: The predictive value of changes in C-reactive protein (CRP), procalcitonin, and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. The aim of this study was to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of 230 patients admitted to the intensive care unit (ICU) with the diagnosis of sepsis and pneumonia-related septic shock between 1 April 2022 and 31 December 2023, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Materials and Methods: This single-center, retrospective, cross-sectional observational study included patients who developed sepsis and septic shock due to community-acquired pneumonia and were admitted to the ICU. Demographic data, 1-month and 90-day mortality rates, length of stay in the ICU, discharge to the ward or an outside facility, need for dialysis after sepsis, need for invasive or noninvasive mechanical ventilation during the ICU stay and the duration of this support, whether patients admitted with sepsis or septic shock required inotropic agent support during their stay in the ICU and whether they received monotherapy or combination therapy with antibiotics during their admission to the ICU, the Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score were analyzed. Additionally, CRP, procalcitonin, and leukocyte levels were recorded, and univariate and multivariate logistic regression analyses were performed to evaluate their effects on 1- and 3-month mortality outcomes. In all statistical analyses, a p-value of <0.05 was accepted as a significant level. Results: According to multivariate logistic regression analysis, low BMI, male gender, and high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p < 0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both the 1-month and 3-month mortality cases (p < 0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared with those who survived (p = 0.004). Conclusions: In patients with pneumoseptic or pneumonia-related septic shock, the persistent elevation and concurrent increase in PCT, CRP, and leukocyte values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality. [ABSTRACT FROM AUTHOR]

The lactate to albumin ratio (LAR) has been associated with the severity and outcome of critical illness and sepsis. However, there are no studies on the kinetics of the LAR during the early phase of sepsis. Therefore, we aimed to investigate the LAR and its kinetics in critically ill patients with new onset sepsis regarding the severity and outcome of sepsis. We prospectively enrolled 102 patients with sepsis or septic shock within 48 h from diagnosis. LARs were recorded at inclusion in the study and one week later. Patients were followed for 28 days. LAR was significantly lower one week after enrollment compared to baseline in all patients (p < 0.001). LARs were significantly higher in patients with septic shock and in nonsurvivors compared to patients with sepsis and survivors, respectively, both at inclusion (p < 0.001, p < 0.001) and at one week later (p < 0.001, p < 0.001). LARs at baseline were positively associated with the severity of sepsis (APACHE II: r = 0.29, p = 0.003; SOFA: r = 0.33, p < 0.001) and inflammatory biomarkers, such as C-reactive protein (r = 0.29, p < 0.1), procalcitonin (r = 0.47, p < 0.001), interleukin 6 (r = 0.28, p = 0.005) interleukin 10 (r = 0.3, p = 0.002) and suPAR (r = 0.28, p = 0.004). In addition, a higher LAR, but not its kinetics, was an independent predictor of 28-day mortality (at inclusion: HR 2.27, 95% C.I. 1.01–5.09, p = 0.04; one week later: HR: 4.29, 95% C.I. 1.71–10.78, p = 0.002). In conclusion, the LAR may be a valuable prognostic indicator in critically ill patients with sepsis at admission and one week later. [ABSTRACT FROM AUTHOR]

Amyloidosis is defined as a rare group of 30 protein-folding diseases characterized by the extracellular deposition of a specific soluble precursor protein that aggregates in the form of insoluble fibrils. The gastrointestinal tract (GI) is a common site for amyloid deposits: Among patients with systemic amyloidosis, at least 70% present with gastrointestinal deposition. Rarely, the deposition is exclusively localized in this area, leading to various gastrointestinal symptoms (bleeding, weight loss, etc.). In this case report, we present a rare and unusual form of localized gastrointestinal amyloidosis, diagnosed after a post-mortem examination of an 83-year-old woman who died due to septic shock resulting from post-colonoscopy iatrogenic perforation of the sigma, in a suspected medical liability case. Morphological examination revealed AL amyloid deposits within the muscular wall of the submucosal vessels of the rectum, which caused increased friability of the vessels and ischemic changes in the intestinal mucosa. A renal cell carcinoma (RCC) was found, which might be related to amyloid deposits, as reported by the literature. Amyloid deposits are an unknown and unpredictable pathological substrate that increase the risk of iatrogenic perforation. Analysis of the medical documentation did not reveal any censurable conduct in terms of prescribing the procedure, technical execution, or subsequent management of the patient following the perforation. GI amyloidosis should be part of the risk stratification of patients with rectal bleeding and gastrointestinal symptoms, and awareness is essential to guide subsequent diagnostic and therapeutic approaches and investigate underlying causes. [ABSTRACT FROM AUTHOR]

Despite enormous developments in medicine, infective endocarditis (IE) remains an ongoing issue for physicians due to increased morbidity and persistently high mortality. Our goal was to assess clinical outcomes in patients with IE and identify determinants of in-hospital mortality. Material and methods: The analysis was retrospective, single-centered, and comprised 270 patients diagnosed with IE from 2005 to 2021 (median age 65 (51–74), male 177 (65.6%). Native IE (NVIE) was observed in 180 (66.7%), prosthetic IE (PVIE) in 88 (33.6%), and cardiac device-related IE (CDRIE) in 2 (0.7%), with non-survivors having much higher rates. Healthcare-associated IE (HAIE) was 72 (26.7%), Staphylococci were the most prevalent pathogen, and the proportion of Gram-negative bacteria (GNB) non-HACEK was significantly greater in non-survivors than survivors (11 (15%) vs. 9 (4.5%), p = 0.004). Overall, 54 (20%) patients underwent early surgery, with a significant difference between dead and alive patients (3 (4.5%) vs. 51 (25.1%, p = 0.000). The overall in-hospital mortality rate was 24.8% (67). Logistic regression was conducted on the total sample (n = 270) for the period 2005–2021, as well as the sub-periods 2005–2015 (n = 119) and 2016–2021 (n = 151), to identify any differences in the trend of IE. For the overall group, the presence of septic shock (OR-83.1; 95% CI (17.0–405.2), p = 0.000) and acute heart failure (OR—24.6; 95% CI (9.2–65.0), p = 0.000) increased the risk of mortality. Early surgery (OR-0.03, 95% CI (0.01–0.16), p = 0.000) and a low Charlson comorbidity index (OR-0.85, 95% CI (0.74–0.98, p = 0.026) also lower this risk. Between 2005 and 2015, the presence of septic shock (OR 76.5, 95% CI 7.11–823.4, p = 0.000), acute heart failure (OR-11.5, 95% CI 2.9–46.3, p = 0.001), and chronic heart failure (OR-1.3, 95% CI 1.1–1.8, p = 0.022) enhanced the likelihood of a fatal outcome. Low Charlson index comorbidity (CCI) lowered the risk (OR-0.7, 95% CI 0.5–0.95, p = 0.026). For the period 2016–2021, the variable with the major influence for the model is the failure to perform early surgery in indicated patients (OR-240, 95% CI 23.2—2483, p = 0.000) followed by a complication of acute heart failure (OR-72.2, 95% CI 7.5–693.6. p = 0.000), septic shock (OR-17.4, 95% CI 2.0–150.8, p = 0.010), previous stroke (OR-9.2, 95% CI 1.4–59.4, p = 0.020) and low ejection fraction (OR-1.1, 95% CI 1.0–1.2, p = 0.004). Conclusions: Knowing the predictors of mortality would change the therapeutic approach to be more aggressive, improving the short- and long-term prognosis of IE patients. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) and sepsis are a major cause of morbidity and mortality. Appropriate early antibiotic therapy is crucial for improving the survival of patients with sepsis and septic shock. T2 magnetic resonance (T2MR®) technology may enable fast and sensitive detection of ESKAPEc pathogens directly from whole-blood samples. We aimed to evaluate concordance between the T2Bacteria® Panel and standard blood culture and its impact on antibiotic therapy decisions. We conducted a single-centre retrospective study on patients with sepsis-induced hypotension or septic shock admitted to general, post-operative/neurosurgical, and cardiothoracic Intensive Care Units who were tested with the T2Bacteria® Panel from January 2021 to December 2022. Eighty-five consecutively admitted patients were included, for a total of 85 paired tests. A total of 48 ESKAPEc pathogens were identified by the T2Bacteria® Panel. The concordance rate between the T2Bacteria® Panel and blood cultures was 81% (69/85), with 20 concordant-positive and 49 concordant-negative cases. For the 25 microorganisms grown from accompanying blood cultures, blood pathogen coverage by the T2Bacteria® Panel was 88%. In this cohort of severely ill septic patients, the T2Bacteria® Panel was highly concordant and was able to detect more ESKAPEc pathogens, with a significantly shorter turn-around time compared to conventional blood cultures. The T2Bacteria® Panel also significantly impacted decisions on antibiotic therapy. [ABSTRACT FROM AUTHOR]

This article explores the principles of dialysis and how it can affect antibiotic therapy in critically ill patients. It specifically focuses on the challenges of dosing antibiotics during dialysis and the variability in how drugs are processed in the body. The authors use the example of colistin, an antibiotic used for multidrug-resistant infections, to highlight the importance of understanding how antibiotics are metabolized in patients undergoing dialysis. They also discuss the potential risks and challenges associated with antibiotic dosing in critically ill patients on continuous kidney replacement therapy. The article emphasizes the need for careful monitoring and appropriate drug levels to ensure effective treatment and minimize the risk of therapeutic failure. [Extracted from the article]

Hypervirulent carbapenem-resistant Acinetobacter baumannii (hv-CRAB) has emerged in bloodstream infections (BSI). Cases of BSI caused by hv-CRAB (hv-CRAB-BSI) had posed a significant threat to hospitalized patients. In this study, 31 CRAB strains isolated from Chinese BSI patients were analyzed, of which 24 were identified as hv-CRAB-BSI and 7 as non-hv-CRAB-BSI, using the Galleria mellonella infection model. Patients with hv-CRAB-BSI had higher rates of septic shock (79.2% vs. 14.3%, p = 0.004) and mortality (66.7% vs. 14.3%, p = 0.028). All strains were resistant to most antibiotics but sensitive to colistin. Hv-CRAB-BSI showed lower resistance to minocycline than non-hv-CRAB-BSI (54.2% vs. 100%, p = 0.03). Whole-genome sequencing revealed that the detection rates of immune modulation genes ptk and epsA in hv-CRAB-BSI were significantly higher than in non-hv-CRAB-BSI (91.7% vs. 28.6%, p = 0.002). Additionally, all ST457 hv-CRAB-BSI lacked abaR, and all ST1486 non-hv-CRAB-BSI lacked adeG. The checkerboard dilution method assessed the efficacies of various antibiotic combinations, revealing that although synergism was rarely observed, the combination of colistin and minocycline showed the best efficacy for treating CRAB-BSI, regardless of whether the infections were hv-CRAB-BSI or non-hv-CRAB-BSI. These findings highlight the importance of analyzing molecular characteristics and exploring effective treatment strategies for hv-CRAB-BSI. [ABSTRACT FROM AUTHOR]

Background and Objective: New-onset atrial fibrillation (NOAF) is a common cardiac condition often observed in intensive care units. When amiodarone is used to treat this condition, either to maintain sinus rhythm after electrical cardioversion or to control heart rate, complications can arise when a systemic pathology is present. Systemic pathology can result in a decrease in cardiac output and blood pressure, making the management of NOAF and septic shock challenging. Limited international research exists on the coexistence of NOAF and septic shock, making it difficult to determine the optimal course of treatment. While amiodarone is not the primary choice of antiarrhythmic drug for patients in septic shock, it may be considered for those with underlying cardiac issues. This paper aims to investigate the safety of administering amiodarone to patients with septic shock and explore whether another antiarrhythmic drug may be more effective, especially considering the cardiac conditions that patients may have. Materials and Methods: To write this article, we searched electronic databases for studies where authors used amiodarone and other medications for heart rate control or sinus rhythm restoration. Results: The studies reviewed in this work have shown that for the patients with septic shock and NOAF along with a pre-existing cardiac condition like a dilated left atrium, the use of amiodarone may provide greater benefits compared to other antiarrhythmic drugs. For patients with NOAF and septic shock without underlying heart disease, the initial use of propafenone has been found to be advantageous. However, a challenge arises when deciding between rhythm or heart rate control using various drug classes. Unfortunately, there is limited literature available on this specific scenario. Conclusions: NOAF is a frequent and potentially life-threatening complication occurring in one out of seven patients with sepsis, and its incidence is rising among patients with septic shock. [ABSTRACT FROM AUTHOR]

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]

Septic abortion can lead to severe maternal morbidity and mortality. The management of septic abortion can be complicated by a history of radical trachelectomy and transabdominal cerclage placement. A 33-year-old G1P0 at 17 weeks and 6 days gestation presented in severe septic shock after being diagnosed 6 days prior with previable rupture of membranes at an outside hospital and managed expectantly. History was notable for cervical adenocarcinoma status post radical trachelectomy and transabdominal cerclage placement. Due to uterine occlusion from the cerclage, the patient underwent emergent uterine evacuation via an abdominal approach. The risks and benefits of expectant management of pre-viable rupture of membranes in patients with abdominal cerclage should be weighed very cautiously. Among women with abdominal cerclage for whom uterine evacuation is indicated, a transabdominal approach may be necessary. [ABSTRACT FROM AUTHOR]

As bloodstream infections and associated septic shock are common causes of mortality in hospitals, rapid antibiotic susceptibility testing (AST) performed directly on positive blood cultures is needed to implement an efficient therapy in clinical settings. We evaluated the Reveal® rapid AST system on a collection of 197 fully characterized carbapenem-resistant Enterobacterales, including 177 carbapenemase producers (CPE) spiked in blood culture bottles. The clinical categorization based on the Minimal Inhibitory Concentration (MIC) determination of eighteen antimicrobial molecules was compared to the clinical categorization based on the disk diffusion assay as a reference. The Reveal AST system provided results within a mean time to result of 5 h. Overall, the categorical agreement (CA) between the two techniques was 94.1%. The rates of very major errors (VMEs), major errors (MEs) and minor errors (mEs) were 3.8%, 3.7% and 5.6%, respectively. Imipenem was the antimicrobial with the lowest CA rate (78.7%), with rates of 15% VMEs and 10.7% MEs, but the performances were better when considering only the non-CPE category (CA of 89%). On this resistant collection of Enterobacterales with numerous acquired β-lactamases, the Specific Reveal assay proved to be useful for a rapid determination of AST compatible with a quick adaptation of the patient's antimicrobial treatment. [ABSTRACT FROM AUTHOR]

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19. Phytochemicals of functional foods and nutraceutical importance have an incredible impact on the healthcare system, which includes the prevention and/or treatment of chronic diseases. Hence, in the present review, we aim to explore the pathogenesis of sepsis associated with COVID-19 that disrupts the physiological homeostasis of the body, resulting in severe organ damage. Furthermore, we have summarized the diverse pharmacological properties of some potent phytochemicals, which can be used as functional foods as well as nutraceuticals against sepsis-associated complications of SARS-CoV-2 infection. The phytochemicals explored in this article include quercetin, curcumin, luteolin, apigenin, resveratrol, and naringenin, which are the major phytoconstituents of our daily food intake. We have compiled the findings from various studies, including clinical trials in humans, to explore more into the therapeutic potential of each phytochemical against sepsis and COVID-19, which highlights their possible importance in sepsis-associated COVID-19 pathogenesis. We conclude that our review will open a new research avenue for exploring phytochemical-derived therapeutic agents for preventing or treating the life-threatening complications of sepsis associated with COVID-19. [ABSTRACT FROM AUTHOR]

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients. [ABSTRACT FROM AUTHOR]

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06–1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome. [ABSTRACT FROM AUTHOR]

This study explores whether Escherichia coli Nissle 1917 (EcN) can preserve the integrity of the intestinal barrier by modulating the metabolism pathway of short-chain fatty acids (SCFAs) in a C57BL/6J mouse model of lipopolysaccharide (LPS)-induced acute enteritis and a model of a Caco-2 monolayer. The study involved establishing a septic shock model in mice through lipopolysaccharide (LPS) injection. Clinical scores and intestinal permeability were meticulously documented. Immunofluorescence was utilized to localize the tight junction proteins. A quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the expression of G protein-coupled receptors (GPRs) signaling. Additionally, the supplement of acetate and butyrate with Caco-2 monolayers to elucidate the potential of EcN in augmenting the intestinal barrier primarily via the modulation of SCFAs and qRT-PCR was performed to detect the expression of tight junction proteins and the activation of the GPRs protein signaling pathway. EcN mitigated the clinical symptoms and reduced intestinal permeability in the colon of LPS-induced mice. It also enhanced the production of SCFAs in the gut and upregulated the expression of SCFA receptor proteins GPR41 and GPR43 in the colon tissue. Our findings reveal that EcN activates the SCFA/GPRs pathway, thereby preserving intestinal barrier function and alleviating inflammation in a mouse sepsis model. [ABSTRACT FROM AUTHOR]

Background: Coagulation abnormalities are common in sepsis patients and are associated with increased mortality. This study aimed to assess the hemostatic profile of sepsis patients using rotational thromboelastometry (ROTEM) and to find the ROTEM parameters best predicting short-term mortality. Methods: We conducted a prospective analysis of consecutive sepsis patients hospitalized in the intensive care unit. The inclusion criteria were diagnosis of sepsis or septic shock and pro-calcitonin concentration >0.5 ng mL−1. Clinical, standard laboratory, and ROTEM analyses were performed. Results: The study group comprised 38 (49%) males and 40 (51%) females. Median Sequential Organ Failure Assessment (SOFA) score was 8 (interquartile range IQR 5–11) points. The most common primary sites of infection were pneumonia (n = 27/35%), intra-abdominal (n = 27/35%), urinary tract infection (n=20/26%), and others (n = 4/6%). The following parameters evaluating fibrinogen function were outside the reference range: clotting time (CT), clot amplitude (A) at 10 and 20 min, and maximal clot firmness (MCF). Out of 78 patients, 28 (36%) died in the intensive care unit. Significant differences between survivors and non-survivors of sepsis were present for the ROTEM parameters assessing fibrinolytic activity. Conclusions: ROTEM in the early phase of sepsis reveals increased coagulation mediated through the function of fibrinogen. Non-survivors showed slightly lower fibrinolytic activity than survivors; however, it was still within test reference values. The highest predicting value was obtained by a model incorporating, among others, extrinsic coagulation pathway fibrinolytic parameters. [ABSTRACT FROM AUTHOR]

Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis represents a global health challenge and requires advanced diagnostic and prognostic approaches due to its elevated rate of morbidity and fatality. Our study aimed to assess the value of a novel set of six biomarkers combined with severity scores in predicting 28 day mortality among patients presenting with sepsis in the Emergency Department (ED). Materials and Methods: This single-center, observational, prospective cohort included sixty-seven consecutive patients with septic shock and sepsis enrolled from November 2020 to December 2022, categorized into survival and non-survival groups based on outcomes. The following were assessed: procalcitonin (PCT), soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1), the soluble form of the urokinase plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and azurocidin 1 (AZU1), alongside clinical scores such as the Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II and III (SAPS II/III), the National Early Warning Score (NEWS), Mortality in Emergency Department Sepsis (MEDS), the Charlson Comorbidity Index (CCI), and the Glasgow Coma Scale (GCS). The ability of each biomarker and clinical score and their combinations to predict 28 day mortality were evaluated. Results: The overall mortality was 49.25%. Mechanical ventilation was associated with a higher mortality rate. The levels of IL-6 were significantly higher in the non-survival group and had higher AUC values compared to the other biomarkers. The GCS, SOFA, APACHEII, and SAPS II/III showed superior predictive ability. Combining IL-6 with suPAR, AZU1, and clinical scores SOFA, APACHE II, and SAPS II enhanced prediction accuracy compared with individual biomarkers. Conclusion: In our study, IL-6 and SAPS II/III were the most accurate predictors of 28 day mortality for sepsis patients in the ED. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with infective endocarditis (IE) are more susceptible to acute kidney injury (AKI). The presence of AKI increases in-hospital complications in these patients. Methods: The 2016–2020 National Inpatient Sample (NIS) database consisting of adult admissions with IE and AKI was utilized. The primary outcome was all-cause inpatient mortality. Secondary outcomes included fluid and electrolyte disorders, stroke, septic arterial embolism, septic shock, cardiogenic shock, valve surgery, vasopressor support, mechanical ventilation, length of stay (LOS), and total hospital charges. Results: Out of a total of 63,725 adult admissions with IE, 16,295 (25.5%) admissions had AKI. Patients with AKI were more likely to be males (63% vs. 57.6%, p < 0.001) and older (55.8 vs. 50.4, p < 0.001). A higher proportion of these patients were admitted to large hospitals (60.6 vs. 55.3%, p < 0.001) and urban teaching hospitals (81.9 vs. 75%, p < 0.001). Patients with AKI had higher LOS (17 ± 16.1 vs. 11.32 ± 11.7, p < 0.001) and hospital charges (USD 239,046.8 ± 303,977.3 vs. USD 124,857.6 ± 192,883.5, p < 0.001). Multivariable analysis showed higher odds of all-cause inpatient mortality (aOR: 2.22, 95% CI: 1.81–2.73, p < 0.001). They also had higher risk for fluid and electrolyte disorder (aOR: 2.31, 95% CI: 2.10–2.53, p < 0.001), septic arterial embolism (aOR: 1.61, 95% CI: 1.42–1.84, p < 0.001), septic shock (aOR: 3.78, 95% CI: 2.97–4.82, p < 0.001), cardiogenic shock (OR: 3.37, 95% CI: 2.65–4.28, p < 0.001), valve surgery (aOR: 1.52, 95% CI: 1.35–1.71, p < 0.001), vasopressor requirement (aOR: 1.99, 95% CI: 1.52–2.60, p < 0.001), and mechanical ventilation (aOR: 2.75, 95% CI: 2.33–3.24, p < 0.001). The association with stroke was elevated but not statistically significant. Conclusions: This large retrospective analysis demonstrated that patients with AKI and infective endocarditis had increased mortality, adverse hospital outcomes, increased LOS, and hospital costs. [ABSTRACT FROM AUTHOR]

Simple Summary: Post-pancreaticoduodenectomy complications are still a major concern nowadays, and we focused on one of the most catastrophic conditions observed from clinical practice, the postoperative biliary infection, which may cause postoperative intensive care unit admission or mortality. Evaluating the impact on postoperative biliary tract infection from endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography and drainage before surgery is important to clinical circumstances. Biliary pathogens identified with a positive yield of intra-operative bile culture in patients undergoing pancreaticoduodenectomy were also investigated. The result showed that performing endoscopic retrograde cholangiopancreatography enhances the likelihood of achieving a positive yield from intraoperative biliary culture. Thus, PTCD emerges as a potentially favorable option for patients with obstructive jaundice and is indicated for pancreaticoduodenectomy. Background: For patients with obstructive jaundice and who are indicated for pancreaticoduodenectomy (PD) or biliary intervention, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD) may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be a concern. We tried to evaluate the impact of ERCP and PTCD on postoperative BTI. Methods: Patients diagnosed from June 2013 to March 2022 with periampullary lesions and with PD indicated were enrolled in this cohort. Patients without intraoperative bile culture and non-neoplastic lesions were excluded. Clinical information, including demographic and laboratory data, pathologic diagnosis, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis. Results: One-hundred-and-sixty-four patients from the cohort (164/689) underwent preoperative biliary intervention, either ERCP (n = 125) or PTCD (n = 39). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than in PTCD (90.4% vs. 41.0%, p < 0.001). Although there was no significance, a trend of higher postoperative BTI (13.8% vs. 2.7%) and BTI-related septic shock (5 vs. 0, 4.0% vs. 0%) in the ERCP group was noticed. While the risk factors for postoperative BTI have not been confirmed, a trend suggesting a higher incidence of BTI associated with ERCP procedures was observed, with a borderline p-value (p = 0.05, regarding ERCP biopsy). Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary intervention is indicated. [ABSTRACT FROM AUTHOR]

Simple Summary: Autologous hematopoietic cell transplantation (auto-HCT) can be used to salvage at least a proportion of plasma cell myeloma patients who relapse after a previous auto-HCT. It may, however, occur that there is either no or an insufficient stem cell dose in storage to proceed to transplantation. Remobilization to procure new cells is then required. There are very limited data in the literature concerning the efficacy of stem cell remobilization after previous auto-HCT. In our previous report, we showed that remobilization with cytarabine was associated with a lower risk of remobilization failure in comparison to etoposide or cyclophosphamide. In the current study, we analyze the efficacy and safety of different doses of cytarabine (800, 1600, and 2400 mg/m2), showing that all doses are efficacious but that the dose of 2400 mg/m2 is associated with the most toxicity. Therefore, lower doses of cytarabine seem to be preferable, with plerixafor rescue when needed. Salvage autologous hematopoietic cell transplantation (auto-HCT) may be used to treat relapse of plasma cell myeloma occurring after previous auto-HCT. When an insufficient number of hematopoietic stem cells have been stored from the initial harvest, remobilization is necessary. Here, we aimed to analyze the efficacy and safety of different doses of cytarabine (total 800 vs. 1600 vs. 2400 mg/m2) for remobilization. Sixty-five patients, 55% male, with a median age at remobilization 63 years, were included. Remobilization was performed with cytarabine_800 in 7, cytarabine_1600 in 36, and cytarabine_2400 in 22 patients. Plerixafor rescue was used in 25% of patients receiving cytarabine_1600 and 27% of those receiving cytarabine_2400. Patients administered cytarabine_800 were not rescued with plerixafor. Remobilization was successful in 80% of patients (57% cytarabine_800; 86% cytarabine_1600; 77% cytarabine_2400; p = 0.199). The yield of collected CD34+ cells did not differ between the different cytarabine doses (p = 0.495). Patients receiving cytarabine_2400 were at the highest risk of developing severe cytopenias, requiring blood product support, or having blood-stream infections. One patient died of septic shock after cytarabine_2400. In summary, remobilization with cytarabine is feasible in most patients. All doses of cytarabine allow for successful remobilization. Cytarabine_2400 is associated with higher toxicity; therefore, lower doses (800 or 1600 mg/m2) seem to be preferable. [ABSTRACT FROM AUTHOR]

Background: Previous guidelines for endocarditis have suggested repeating blood cultures until they become negative, with limited evidence. Methods: Literature reviews were conducted (1) on the incidence of persistent bacteremia and association with outcome and (2) on timing of valve culture negativization to examine the claim for prolongation of antibiotic therapy starting from negative blood cultures. Results: Persistent bacteremia and fever may be present in the first 3 days of endocarditis, despite treatment, and are more common in Staphylococcus (especially MRSA) and Enterococcus species. Persistent bacteremia (48–72 h), persistent infection (day 7), and new onset septic shock are related and predict in-hospital mortality. It is, however, persistent infection at day 7 and septic shock that primarily determine the infectious course of endocarditis, and not persistent bacteremia. Valve cultures at surgery become negative in most cases (>85–90%) after 14–21 days of antibiotic therapy, with no calculated benefit for prolonging therapy after 21 days. Conclusions: Persistent infection at 7 days after appropriate antibiotic therapy is a better key event for prognosis then positive or negative blood cultures at 48–72 h. Therapy prolongation from the day of negative blood cultures is not reasonable. There is no need to survey blood cultures in endocarditis patients after starting therapy. [ABSTRACT FROM AUTHOR]

Systemic steroids are frequently used in critically ill patients for their anti-inflammatory properties. Potential benefits of these agents should be balanced against their known side effects. In this paper, we review trials assessing the use of systemic steroids in common conditions requiring admission to the intensive care unit. These include septic shock, the acute respiratory distress syndrome, severe pneumonia, COVID-19, and hypercapnic respiratory failure due to chronic obstructive pulmonary disease. We will mainly focus on well-conducted randomized controlled trials to determine whether steroids should be administered to critically ill patients presenting with these conditions. [ABSTRACT FROM AUTHOR]

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock. [ABSTRACT FROM AUTHOR]

Sepsis poses a significant threat to human health due to its high morbidity and mortality rates worldwide. Traditional diagnostic methods for identifying sepsis or its causative organisms are time-consuming and contribute to a high mortality rate. Biomarkers have been developed to overcome these limitations and are currently used for sepsis diagnosis, prognosis prediction, and treatment response assessment. Over the past few decades, more than 250 biomarkers have been identified, a few of which have been used in clinical decision-making. Consistent with the limitations of diagnosing sepsis, there is currently no specific treatment for sepsis. Currently, the general treatment for sepsis is conservative and includes timely antibiotic use and hemodynamic support. When planning sepsis-specific treatment, it is important to select the most suitable patient, considering the heterogeneous nature of sepsis. This comprehensive review summarizes current and evolving biomarkers and therapeutic approaches for sepsis. [ABSTRACT FROM AUTHOR]

Simple Summary: Joint infection, or septic arthritis, is an important disease in horses and requires aggressive treatment to eradicate the infection. Using current diagnostic methods, it is difficult to determine when the infection has been eliminated following treatment, leading to often prolonged antimicrobial therapy, which may be unnecessary and is associated with side effects and antimicrobial resistance. Thus, better markers of eradication of joint infection are needed. In this study, a class of molecules called messenger ribonucleic acid (mRNA) in synovial fluid was investigated for potential biomarkers of the eradication of infection in an experimental model of equine septic arthritis using transcriptomics methods. Transcriptomics data were also compared to our previously published data on putative protein biomarkers of the eradication of joint infection and to an mRNA biomarker panel used to differentiate septic from non-septic shock in humans. Eight mRNAs were identified that were at least three times increased in horses with active septic arthritis compared to horses post-eradication of infection after treatment and horses with non-septic synovitis. The presence of mRNAs corresponding to our previously reported protein markers of eradication of joint infection and to the validated mRNA biomarker panel detecting sepsis in humans was also confirmed. Further investigation of mRNAs as a source of potential markers of the eradication of joint infection in horses is needed. Septic arthritis (SA) in horses has long-term health implications. The success of its resolution hinges on the implementation of early, aggressive treatment, which is often sustained over a prolonged period. Common diagnostic methods do not allow for the reliable detection of the eradication of joint infection. A potential alternative is the discovery and characterization of mRNA biomarkers. The purpose of this study was to identify potential mRNA biomarkers for the eradication of joint infection in equine SA and to compare their expression with our previously published proteomics data. In addition, the transcriptomics data were compared to the mRNA biomarker panel, SeptiCyte Lab, used to distinguish sepsis from non-septic shock in humans. A comparative transcriptomics analysis of synovial fluid from the SA joints of five horses with active infection and subsequent post-treatment eradicated infection in the same joints and five horses with non-septic synovitis was performed. Eight novel mRNA transcripts were identified that were significantly upregulated (>3-fold) in horses with active SA compared to horses post-eradication of infection after treatment and horses with non-septic synovitis. Two proteins in our proteomics data corresponded to these mRNA transcripts, but were not statistically different. The transcripts used in the SeptiCyte test were not differentially expressed in our study. Our results suggest that mRNA may be a useful source of biomarkers for the eradication of joint infection in horses and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: The importance of perfusion-guided resuscitation in septic shock has recently emerged. We explored whether the use of hemoadsorption led to a potential beneficial role in microvascular alterations in this clinical setting. Methods: A pre-planned secondary analysis of a Phase-II interventional single-arm pilot study (NCT05658588) was carried out, where 17 consecutive septic shock children admitted into PICU were treated with continuous renal replacement therapy (CRRT) and CytoSorb. Thirteen patients were eligible to be investigated with sublingual microcirculation at baseline, 24, 48, 72 and 96 h from the onset of blood purification. Patients achieving a microvascular flow index (MFI) ≥ 2.5 and/or proportion of perfused vessels (PPV) exceeding 90% by 96 h were defined as responders. Results: In 10/13 (77%), there was a significant improvement in MFIs (p = 0.01) and PPVs% (p = 0.04) between baseline and 24 h from the end of treatment. Eight patients displayed a high heterogenicity index (HI > 0.5) during blood purification and among these, five showed an improvement by the end of treatment (HI < 0.5). Conclusions: In this pilot study, we have found a potential association between CytoSorb hemoadsorption and a microcirculation improvement in pediatric patients with septic shock, particularly when this observation has been associated with hemodynamic improvement. [ABSTRACT FROM AUTHOR]

Ischemia-modified albumin (IMA) is produced during ischemia and reactive oxygen species production. This study aimed to evaluate the association between IMA and mortality in a larger population and the prognostic value of the combination of IMA and lactate for predicting mortality in septic shock patients in the emergency department. This retrospective observational study included adult septic shock patients between October 2019 and December 2021. A multivariable Cox proportional hazards model was performed. IMA was significantly higher in the non-surviving group than in the surviving group (89.1 ± 7.2 vs. 83.8 ± 6.2 U/mL, p < 0.001). IMA was independently associated with 28-day mortality after adjustments (adjusted hazard ratio [aHR]: 1.075, 95% confidence interval [CI]: 1.016–1.138, p = 0.012). The area under the ROC curve (AUROC) of IMA was 0.712 (95% CI: 0.648–0.775, p < 0.001) and was comparable to that of lactate. The AUROC of the combination of IMA and lactate was 0.838 (95% CI: 0.786–0.889, p < 0.001). The group with both high lactate and high IMA levels showed an extremely high risk of mortality than other groups (86.1%; aHR 8.956, 95% CI 4.071–19.70, p < 0.001). The elevation of IMA was associated with mortality in septic shock patients. The combination of IMA and lactate can be a helpful tool for early risk stratification of septic shock patients. [ABSTRACT FROM AUTHOR]

Circulating nucleosome levels are commonly elevated in physiological and pathological conditions. Their potential as biomarkers for diagnosing and prognosticating sepsis remains uncertain due, in part, to technical limitations in existing detection methods. This scoping review explores the possible role of nucleosome concentrations in the diagnosis, prognosis, and therapeutic management of sepsis. A comprehensive literature search of the Cochrane and Medline libraries from 1996 to 1 February 2024 identified 110 potentially eligible studies, of which 19 met the inclusion criteria, encompassing a total of 39 SIRS patients, 893 sepsis patients, 280 septic shock patients, 117 other ICU control patients, and 345 healthy volunteers. The enzyme-linked immunosorbent assay [ELISA] was the primary method of nucleosome measurement. Studies consistently reported significant correlations between nucleosome levels and other NET biomarkers. Nucleosome levels were higher in patients with sepsis than in healthy volunteers and associated with disease severity, as indicated by SOFA and APACHE II scores. Non-survivors had higher nucleosome levels than survivors. Circulating nucleosome levels, therefore, show promise as early markers of NETosis in sepsis, with moderate diagnostic accuracy and strong correlations with disease severity and prognosis. However, the available evidence is drawn mainly from single-center, observational studies with small sample sizes and varied detection methods, warranting further investigation. [ABSTRACT FROM AUTHOR]

The most widely known pyrogen impurity in vaccines is the Gram-negative bacterial endotoxin lipopolysaccharide (LPS). When administered at toxic doses, endotoxin triggers inflammatory responses, which lead to endotoxic shock. The literature on endotoxic content (EC) for preclinical vaccines' formulations used in animal studies is very poor, and the recommended thresholds are solely based on commercial vaccine limits set for humans and are, therefore, not connected to the actual impact of EC on animal welfare for species used in preclinical research studies. An extensive study to evaluate the presence of a potential relationship between endotoxin content in formulations administered to mice (the most common species used in preclinical research studies) and their welfare was conducted to calculate an EC threshold for formulations of candidate vaccines. Three years of historical data, from more than 500 formulations of different antigen types (i.e., proteins, glycoconjugates, OMV/GMMA) injected into more than 5000 mice, was evaluated with two alternative statistical methodologies, both demonstrating that there is no significant relationship between actual endotoxin levels and mouse welfare. The calculation of thresholds was, therefore, performed by consistency versus formulations that demonstrated no impact on animal welfare. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis involves a dysregulated host response, characterized by simultaneous immunosuppression and hyperinflammation. Initially, there is the release of pro-inflammatory factors and immune system dysfunction, followed by persistent immune paralysis leading to apoptosis. This study investigates sepsis-induced apoptosis and its pathways, by assessing changes in PD-1 and PD-L1 serum levels, CD4+ and CD8+ T cells, and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) severity scores. Materials and Methods: This prospective, observational, single-centre study enrolled 87 sepsis patients admitted to the intensive care unit at the County Emergency Clinical Hospital in Târgu Mureș, Romania. We monitored the parameters on day 1 (the day sepsis or septic shock was diagnosed as per the Sepsis-3 Consensus) and day 5. Results: Our study found a statistically significant variation in the SOFA score for the entirety of the patients between the studied days (p = 0.001), as well as for the studied patient groups: sepsis, septic shock, survivors, and non-survivors (p = 0.001, p = 0.003, p = 0.01, p = 0.03). On day 1, we found statistically significant correlations between CD8+ cells and PD-1 (p = 0.02) and PD-L1 (p = 0.04), CD4+ and CD8+ cells (p < 0.0001), SOFA and APACHE II scores (p < 0.0001), and SOFA and APACHE II scores and PD-L1 (p = 0.001 and p = 0.01). On day 5, we found statistically significant correlations between CD4+ and CD8+ cells and PD-L1 (p = 0.03 and p = 0.0099), CD4+ and CD8+ cells (p < 0.0001), and SOFA and APACHE II scores (p < 0.0001). Conclusions: The reduction in Th CD4+ and Tc CD8+ lymphocyte subpopulations were evident from day 1, indicating that apoptosis is a crucial factor in the progression of sepsis and septic shock. The increased expression of the PD-1/PD-L1 axis impairs costimulatory signalling, leading to diminished T cell responses and lymphopenia, thereby increasing the susceptibility to nosocomial infections. [ABSTRACT FROM AUTHOR]

Background/Objectives: Septic shock is a severe condition with high mortality necessitating precise prognostic tools for improved patient outcomes. This study aimed to evaluate the collective predictive value of the Simplified Acute Physiology Score 3 (SAPS-3) and lactate measurements (initial, peak, last, and clearance rates within the first 24 h) in patients with septic shock. Specifically, it sought to determine how these markers enhance predictive accuracy for 28-day mortality beyond SAPS-3 alone. Methods: This retrospective cohort study analyzed data from 66 septic shock patients at two ICUs of Vienna General Hospital (2017–2019). SAPS-3 and lactate levels (initial, peak, last measurement within 24 h, and 24 h clearance) were obtained from electronic health records. Logistic regression models were constructed to identify predictors of 28-day mortality, and receiver operating characteristic (ROC) curves assessed predictive accuracy. Results: Among 66 patients, 36 (55%) died within 28 days. SAPS-3 scores significantly differed between survivors and non-survivors (76 vs. 85 points; p = 0.016). First, last, and peak lactate were significantly higher in non-survivors compared to survivors (all p < 0.001). The combination of SAPS-3 and first lactate produced the highest predictive accuracy (AUC = 80.6%). However, 24 h lactate clearance was not predictive of mortality. Conclusions: Integrating SAPS-3 with lactate measurements, particularly first lactate, improves predictive accuracy for 28-day mortality in septic shock patients. First lactate serves as an early, robust prognostic marker, providing crucial information for clinical decision-making and care prioritization. Further large-scale studies are needed to refine these predictive tools and validate their efficacy in guiding treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Reptiles usually carry Salmonella without showing any signs of infection. In this case, an adult male corn snake died 48 h after eating a feeder mouse bought online. The snake and mouse livers tested positive for Salmonella, specifically Salmonella enterica subsp. enterica serovar Midway. A genome analysis revealed that the two samples were from the same bacterial strain, and both had genes responsible for the bacteria's virulence. This report is about a pet snake that acquired Salmonella from a feeder mouse and then died from septic shock. It shows how feeder mice can be a source of clinical salmonellosis in pet snakes, which can pose a risk to humans too. Reptiles are usually asymptomatic carriers of Salmonella, with the manifestation of typical clinical signs of acute forms in adult and non-immunocompromised animals being considered exceptions. In the present case, an adult male corn snake (Pantherophis guttatus) was found dead due to septic shock 48 h after consuming a feeder mouse purchased online. The snake's tissue samples and faeces were cultured for bacteria isolation. Microbiological examinations of the snake and mouse livers revealed the presence of Salmonella enterica subsp. enterica serovar Midway. A whole-genome analysis of these two isolates showed a high correlation between them: they belonged to the strain type ST-357 for the classic MLST scheme and to the strain type ST 171322 for the cgMLST scheme. Also, a virulence gene analysis revealed the presence of stdB and STM3026 genes. This report conveys a case of food-borne salmonellosis in a pet snake, transmitted from a feeder mouse, likely responsible for the snake's death due to septic shock. It highlights the relevance of feeder mice as a source of Salmonella infections in snakes and the associated risks to human health. [ABSTRACT FROM AUTHOR]

Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock. [ABSTRACT FROM AUTHOR]

Introduction: Lactate is a useful prognostic marker, as its level increases in hypoxic tissue and/or during accelerated aerobic glycolysis due to excessive beta-adrenergic stimulation and decreased lactate clearance. The Surviving Sepsis Campaign Bundle 2018 Update suggests premeasurement of lactate within 2–4 h so that physicians perform, assist, administer, and introduce lactate-guided resuscitation to reduce mortality due to sepsis. Methods: A total of 108 patients with septic shock who underwent continuous renal replacement therapy (CRRT) for acute kidney injury were enrolled in this observational study. Demographic, clinical, and laboratory data were collected, and patients were divided into two groups: survivors and non-survivors. Results: Multivariate analysis demonstrated that lactate levels at 24 h after initiation of CRRT treatment, but not lactate levels at intensive care unit (ICU) admission, were associated with mortality. Lactate clearance was associated with lower mortality among the survivors (OR = 0.140) at 6 h after ICU admission and late mortality (OR = 0.260) after 24 h. The area under the ROC curves for mortality was 0.682 for initial lactate; 0.797 for lactate at 24 h; and 0.816 for lactate clearance at 24 h. Conclusions: Our result reinforces that the determination of lactate dynamics represents a good predictor for mortality, and serial lactate measurements may be more useful prognostic markers than initial lactate in patients with septic shock. [ABSTRACT FROM AUTHOR]

Background: This investigation assesses the prognostic value of lactate levels and their clearance in septic shock patients, particularly emphasizing the comparative analysis between COVID-19 and non-COVID-19 patients in the emergency department. This study aims to elucidate the unique prognostic implications of lactate dynamics in these distinct patient groups, thereby enhancing the management of septic shock. Methods: An observational prospective study was conducted, enrolling 114 septic shock patients from the Emergency County Hospital Resita, Romania, categorizing them into COVID-19 and non-COVID-19 groups to examine their initial lactate levels, clearance rates, and their correlation with patient outcomes. Results: This study identified significant differences in the initial lactate levels and clearance rates between the two groups, indicating higher initial lactate levels and slower clearance rates in COVID-19 patients. Survivors demonstrated significantly lower initial lactate levels (1.5 ± 0.4 mmol/L) and higher lactate clearance rates (33 ± 15%) compared to non-survivors (2.5 ± 0.5 mmol/L and 24 ± 9%, respectively; lactate levels p = 0.001, clearance rates p = 0.002). Conclusions: Lactate monitoring, particularly clearance rates, is crucial in the prognostic assessment of septic shock patients. These findings highlight the need for targeted interventions in COVID-19 patients to improve outcomes, underscoring lactate dynamics as a vital component of septic shock management in differing patient populations. [ABSTRACT FROM AUTHOR]

Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings. [ABSTRACT FROM AUTHOR]

Clostridium perfringens (C. perfringens) is an anaerobic, spore-forming Gram-positive rod responsible for necrotizing gangrene, bacteremia in patients with cancer or gastrointestinal tract infection. C. perfringens virulence is due in large part to toxin production. In 2014, a new enterotoxin, BEC (binary enterotoxin of Clostridium perfringens) encoded by becA and becB genes, distinct from enterotoxin (CPE) encoded by the cpe gene, has been described. BEC-producing strains can be causative agents of acute gastroenteritis in humans. We present herein the case of a 64-year-old man who presented to the emergency department of Toulouse University Hospital with pneumonia and septic shock, without digestive symptoms. Blood cultures showed C. perfringens bacteremia and despite appropriate antibiotic treatment the patient passed away 7 h after admission. The characterization of the strain by whole genome sequencing revealed the presence of typical genes of C. perfringens: plc gene (alpha-toxin, phospholipase C) and pfoA (theta-toxin, perfringolysine). Surprisingly, this strain also harbored becA and becB genes encoding the recently described BEC toxin. Interestingly, alpha-toxin typing of our isolate and other published BEC isolates showed that they belonged to different PLC subtypes, confirming the high genetic diversity of these strains. To our knowledge, it is the first clinical case reporting bacteremia due to a BEC-producing C. perfringens isolate. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are tools for intercellular communication, mediating molecular transport processes. Emerging studies have revealed that EVs are significantly involved in immune processes, including sepsis. Sepsis, a dysregulated immune response to infection, triggers systemic inflammation and multi-organ dysfunction, posing a life-threatening condition. Although extensive research has been conducted on animals, the complex inflammatory mechanisms that cause sepsis-induced organ failure in humans are still not fully understood. Recent studies have focused on secreted exosomes, which are small extracellular vesicles from various body cells, and have shed light on their involvement in the pathophysiology of sepsis. During sepsis, exosomes undergo changes in content, concentration, and function, which significantly affect the metabolism of endothelia, cardiovascular functions, and coagulation. Investigating the role of exosome content in the pathogenesis of sepsis shows promise for understanding the molecular basis of human sepsis. This review explores the contributions of activated immune cells and diverse body cells' secreted exosomes to vital organ dysfunction in sepsis, providing insights into potential molecular biomarkers for predicting organ failure in septic shock. [ABSTRACT FROM AUTHOR]

Background: Infective endocarditis (IE) continues to be a disease with high mortality despite medical advances. Objective: The objective of this study was to investigate the characteristics and prognosis of IE according to the affected valves. Materials and methods: This study was retrospective and single-centered, and it included 270 patients with a diagnosis of IE, for the period 2005–2021, who received treatment at the University Hospital "St. Georgi" in Plovdiv, Bulgaria. Results: Single-valve IE (SIE) was found in 82.6% (n-223), multivalvular IE (MIE) in 16.66% (n = 45) and device IE (CDRIE) in 0.74% (n = 2) of patients. The most commonly affected valve was the aortic valve, in 44.8% (n = 121). The predominant multivalvular involvement was aortic–mitral valves (AV-MV) (13.7%, n = 37). The patients with tricuspid valve (TV) IE were significantly younger, at 39 (30) years, and were more frequently male (80.8%). Mortality was higher in MIE than in SIE (31.1% vs. 23.8%) and was the highest in multivalve aortic–tricuspid (AV-TV) IE (75%). Early surgery was performed most in AV-MV IE, in 29.7% (n = 11). The Charlson comorbidity index (CCI) was significantly higher in MV 4 (4) and AV 3 (3) vs. TV IE 1 (5) (p = 0.048 and p = 0.011, respectively). Septic shock occurred most frequently in AV-TV involvement (75%; p = 0.0001). The most common causative agents were of the Staphylococcus group. Staphylococcus aureus more often affected TV alone (46.2%, n = 124) vs. AV (9.9%, n = 14; p = 0.0001) and vs. MV (22.6%, n = 17; p = 0.022); Staphylococcus coagulase-negative (CNG) was the prevalent cause of MV IE (22.7%, n = 17) vs. AV-MV (2.7%, n = 1; p = 0.007). Streptococci were represented in a low percentage and only in left-sided IE, more frequently in AV-MV (18.9%, n = 7) vs. AV (6.6%, n = 8; p = 0.025). Conclusions: The aortic valve is the most frequently affected valve, as single-valve IE or as multivalve AV-MV, with the predominant causative agents being of the Staphylococcus group. AV-TV IE has the worst prognosis, with the most common complication of septic shock and the highest in-hospital mortality. [ABSTRACT FROM AUTHOR]

(1) Background: Sepsis management in children is crucial, especially in emergency services. This study aims to evaluate Thai physicians' knowledge gaps in the emergency management of sepsis in children and to evaluate their adherence to the current sepsis clinical practice guidelines. (2) Methods: This is a cross-sectional survey of Thai physicians' management of septic shock in children. The survey was conducted through online questionnaires from March 2019–April 2019. (3) Results: Of the 366 responders, 362 (98.9%) were completed. Most of the responders were general practitioners (89.2%) and pediatricians (10.8%). The time from positive sepsis screening to being evaluated by physicians within 15 min was reported by 83.9%. The most common choice of fluid resuscitation was normal saline solution (77.3%). The practice of a fluid loading dose (20 mL/kg) consistent with the guidelines was 56.3%. The selection of the first vasoactive agent in warm shock (norepinephrine) and cold shock (epinephrine) according to recommendations in the guidelines was 74.3% and 36.2%, respectively. There was a significant difference between general practitioners and pediatricians in terms of knowledge about initial fluid resuscitation and the optimal vasoactive agent in cold shock (p-value < 0.001). In the multivariate model, factors associated with the guideline-based decision-making of vasoactive agent choice for cold shock were specialist training (pediatrician) and the completion of sepsis management training certification, with adjusted odds ratios (AORs) of 7.81 and 2.96, but working experience greater than ten years was inconsistent with the guideline-based decision-making (AOR 0.14). (4) Conclusions: Thai clinicians were unfamiliar with pediatric sepsis therapy standards, specifically the quantity of early fluid resuscitation and the appropriate vasoactive medications for cold shock. To encourage adherence to the guidelines, we propose a regularly required training course on pediatric sepsis management. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study is to investigate the prognostic utility of point-of-care (POC)-measured proenkephalin (PENK), a novel biomarker, in terms of predicting in-hospital mortality in patients presenting to the emergency department (ED) with septic shock. Methods: Bedside PENK was measured in consecutive patients presenting to the ED with septic shock according to the Sepsis-3 clinical criteria. The association of PENK with inflammatory and routine biomarkers, and its role as a predictor of in-hospital mortality, was examined. Results: Sixty-one patients with septic shock [53% females, median age 83 years (IQR 71–88)] were evaluated. Median (IQR) values of creatinine, plasma lactate, soluble urokinase plasminogen activator receptor (SuPAR), procalcitonin and PENK were 1.7 (1.0–2.9) mg/dL, 3.6 (2.1–6.8) mmol/L, 13.1 (10.0–21.4) ng/mL, 2.06 (0.84–3.49) ng/mL, and 205 (129–425) pmol/L, respectively. LogPENK significantly correlated with LogLactate (rho = 0.369, p = 0.004), LogCreatinine (rho = 0.537, p < 0.001), LogProcalcitonin (rho = 0.557, p < 0.001), and LogSuPAR (rho = 0.327, p = 0.011). During hospitalization, 39/61 (64%) patients died. In a multivariable logistic regression model, logPENK was an independent predictor of in-hospital mortality (OR 11.9, 95% CI: 1.7–84.6, p = 0.013). Conclusion: POC PENK levels measured upon presentation to the ED strongly correlated with metabolic, renal and inflammatory biomarkers, and may serve as a predictor of in-hospital mortality in patients with septic shock. [ABSTRACT FROM AUTHOR]

Sepsis, characterized by life-threatening organ dysfunction due to a maladaptive host response to infection, and its more severe form, septic shock, pose significant global health challenges. The incidence of these conditions is increasing, highlighting the need for effective treatment strategies. This review explores the complex pathophysiology of sepsis, emphasizing the role of the endothelium and the therapeutic potential of corticosteroids. The endothelial glycocalyx, critical in maintaining vascular integrity, is compromised in sepsis, leading to increased vascular permeability and organ dysfunction. Corticosteroids have been used for over fifty years to treat severe infections, despite ongoing debate about their efficacy. Their immunosuppressive effects and the risk of exacerbating infections are significant concerns. The rationale for corticosteroid use in sepsis is based on their ability to modulate the immune response, promote cardiovascular stability, and potentially facilitate organ restoration. However, the evidence is mixed, with some studies suggesting benefits in terms of microcirculation and shock reversal, while others report no significant impact on mortality or organ dysfunction. The Surviving Sepsis Campaign provides cautious recommendations for their use. Emerging research highlights the importance of genomic and transcriptomic analyses in identifying patient subgroups that may benefit from corticosteroid therapy, suggesting a move toward personalized medicine in sepsis management. Despite potential benefits, the use of corticosteroids in sepsis requires careful consideration of individual patient risk profiles, and further research is needed to optimize their use and integrate genomic insights into clinical practice. This review underscores the complexity of sepsis treatment and the ongoing need for evidence-based approaches to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Sepsis continues to be a significant public health challenge despite advances in understanding its pathophysiology and management strategies. Therefore, this study evaluated the value of cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) for assessing the severity and prognosis of sepsis. Ninety-four patients were divided into three groups: infection (n = 32), sepsis (n = 30), and septic shock (n = 32). Plasma samples were collected at the time of diagnosis, and cfDNA concentrations were determined by qPCR assay. The results showed that plasma cfDNA levels increased with the severity of the disease. To distinguish between patients with infection and those with sepsis, the biomarker L1PA290 achieved the highest AUC of 0.817 (95% CI: 0.725–0.909), demonstrating a sensitivity of 77.0% and a specificity of 79.3%. When cf-nDNA was combined with the SOFA score, there was a significant improvement in the AUC (0.916 (0.853–0.979)), sensitivity (88.1%), and specificity (80.0%). Moreover, patients admitted to the ICU after being diagnosed with sepsis had significantly higher cf-nDNA concentrations. In patients admitted to the ICU, combining cf-nDNA with the SOFA score yielded an AUC of 0.753 (0.622–0.857), with a sensitivity of 95.2% and a specificity of 50.0%. cfDNA can differentiate between patients with infection and those with sepsis. It can also identify patients who are likely to be admitted to the ICU by predicting those with indications for intensive care, suggesting its potential as a biomarker for sepsis. [ABSTRACT FROM AUTHOR]