轻度脓毒症对机体的影响

An early identification of sepsis patients likely to progress towards multiple organ failure is crucial in order to initiate targeted therapeutic strategies to decrease mortality. Our recent publication highlighted the greater accuracy of mid-regional proadrenomedullin (MR-proADM) compared with conventional biomarkers and clinical scores in predicting 28-day mortality in patients with initially low (≤7 points; N = 240) or moderate (8–13 points; N = 653) Sepsis-related Organ Failure Assessment (SOFA) scores [1], thus confirming results from smaller investigations [2, 3]. This additional post hoc analysis aimed to further describe the non-surviving patient population of both subgroups and identify those likely to progress towards sepsis-related multiple organ failure. In our study, patients with low SOFA scores had a lower 28-day mortality rate (N = 35; 14.6% vs. N = 181; 27.7%) and incidence of septic shock [4] (N = 87; 36.7% vs. N = 399; 61.5%) compared to those with moderate values. Nevertheless, multiple organ failure was the most common cause of death irrespective of initial SOFA classification (low vs. moderate SOFA: N = 16; 45.7% vs. N = 79; 43.6%). Patients with low SOFA scores tended to take longer to progress towards multiple organ failure (10 [6–18] vs. 7 [3–11] days) and had an increasing number of dysfunctional organs (identified by organ-specific SOFA scores ≥2) and an increasing overall SOFA score (e.g. diagnosis to day 7: 2 [1–2] vs. 4 [3–5] dysfunctional organs; P < 0.01; 6.3 ± 1.3 vs. 10.2 ± 4.7 points; P < 0.01). Area under the receiver operating characteristic curve (AUROC) and Cox regression analysis indicated that MR-proADM had the highest accuracy in predicting progression towards sepsis-related multiple organ failure mortality in both groups (Fig. 1). High initial concentrations in non-surviving patients with low or moderate SOFA scores resulted in a high progression rate towards multiple organ failure (N = 6; 100.0% and N = 25; 52.1%), with similar results found in patients with increasing concentrations over the first 24 h (e.g. moderate SOFA population: N = 15; 57.8%). Conversely, mortality in patients with low MR-proADM concentrations was predominantly due to non-sepsis-related causes (N = 14; 60.9%), with a low subsequent progression rate towards sepsis-related multiple organ failure in the total patient population with continuously low concentrations over the first 24 h (N = 3; 1.4%). Results suggest that initially high or increasing MR-proADM concentrations may help to identify patients with a high risk of progression towards sepsis-related multiple organ failure. Elevated microcirculation dysfunction and endothelial permeability may therefore play a significant role in driving the development of further organ dysfunction, as described previously [5]. Further studies in larger patient populations are essential to confirm these hypotheses.

Key Points Question Does the Sepsis Prediction Model (SPM) outperform other sepsis prediction scores with respect to validity and timeliness? Findings This cohort study of 60 507 adult admissions found that although balanced accuracy of the SPM at a predicting sepsis score (PSS) threshold of 8 or greater was better than that of the quick Sepsis-Related Organ Failure Assessment (qSOFA), Sequential Organ Failure Assessment (SOFA), and Systemic Inflammatory Response Syndrome (SIRS), there was longer time to score positivity from time zero for the SPM vs SIRS and SOFA. Meaning While the balanced accuracy of the SPM was better than qSOFA, SOFA, and SIRS at higher-threshold PSS, it had poor timeliness for sepsis prediction.

Objective Sepsis has been defined as a life-threatening organ dysfunction that develops as a result of impaired host response to infection. This study aimed to investigate sequential organ failure assessment (SOFA) score, systemic inflammatory response syndrome (SIRS), quick SOFA (qSOFA), and qSOFA + lactate criteria (qSOFA+L) in the diagnosis and prognosis of sepsis. Materials and Methods A retrospective study was performed that included all patients diagnosed with sepsis between January 1, 2013 and December 31, 2017 in Izmir Tepecik Training and Research Hospital Infectious Diseases and Clinical Microbiology Clinic. Results A total of 976 patients diagnosed with sepsis (mean age 72.5±13.7 years, 52.7% women) over five years were included in this study. Of all patients admitted to the emergency department and diagnosed with sepsis, 37.4% (n=365) were hospitalized and 52.3% (n=191) of these patients died. Emergency department mortality was 12.5% (n=122). The mortality rate was higher in patients with qSOFA and qSOFA+L criteria ≥2 in the emergency department. There was no statistically significant difference in terms of SIRS, qSOFA, or qSOFA+L criteria among patients who died in the hospital. The SOFA score (area under receiver operator characteristic curve, AUC=0.89) was highly discriminative in predicting sepsis. When the SOFA score was>11, its sensitivity and negative predictive values were both 100%. The SOFA score (AUC=0.75 and 0.72, respectively) was also highly discriminative in predicting emergency and in-hospital mortality. When the SOFA score was>11, the sensitivity and specificity of predicting emergency department mortality were 63.5% and 78.8%, respectively. The sensitivity was 65.8% and the specificity was 75.5% when describing in-hospital mortality for SOFA scores>9. Conclusion The SOFA score was highly sensitive and predictive in the diagnosis of sepsis. The SOFA score had a high discriminative ability to predict emergency and in-hospital mortality.

Introduction Patients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections. Methods 259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients). Results Sepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p&lt;0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3. Conclusions Sepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a useful bedside tool to assess risk for worse outcomes in these patients. Patients with Sepsis-3 and positive qSOFA deserve more intensive management and strict surveillance.

Sepsis can be caused by malaria infection, but little is known about the utility of the quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) and SOFA score in malaria. We conducted a prospective observational study from March 2013 to February 2017 to examine adults admitted with community-acquired infection in a tertiary-care hospital in Ubon Ratchathani, Northeast Thailand (Ubon-sepsis). Subjects were classified as having sepsis if they had a modified SOFA score ≥2 within 24 hours of admission. Serum was stored and later tested for malaria parasites using a nested PCR assay. Presence of severe malaria was defined using modified World Health Organization criteria. Of 4,989 patients enrolled, 153 patients (3%) were PCR positive for either Plasmodium falciparum (74 [48%]), P. vivax (69 [45%]), or both organisms (10 [7%]). Of 153 malaria patients, 80 were severe malaria patients presenting with sepsis, 70 were non-severe malaria patients presenting with sepsis, and three were non-severe malaria patients presenting without sepsis. The modified SOFA score (median 5; IQR 4–6; range 1–18) was strongly correlated with malaria severity determined by the number of World Health Organization severity criteria satisfied by the patient (Spearman’s rho = 0.61, p<0.001). Of 80 severe malaria patients, 2 (2.5%), 11 (14%), 62 (77.5%) and 5 (6%), presented with qSOFA scores of 0, 1, 2 and 3, respectively. Twenty eight-day mortality was 1.3% (2/153). In conclusion, qSOFA and SOFA can serve as markers of disease severity in adults with malarial sepsis. Patients presenting with a qSOFA score of 1 may also require careful evaluation for sepsis; including diagnosis of cause of infection, initiation of medical intervention, and consideration for referral as appropriate.

Objective To investigate the prognostic value for predicting mortality of partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), the Sequential Organ Failure Assessment (SOFA) score and D-dimer in elderly patients with sepsis. Methods This retrospective cohort study enrolled elderly patients with sepsis admitted to the intensive care unit (ICU) between January 2019 and October 2020. Patients were divided into a survival group and a non-survival group. Biomarkers, SOFA, Acute Physiology and Chronic Health Evaluation II and Glasgow Coma Scale scores were recorded within 24 h after admission to the ICU. Results A total of 135 elderly patients with sepsis were enrolled in the study: 89 were in the survival group and 46 were in the non-survival group at 28 days. Univariate and multivariate regression analyses demonstrated that PaO2/FiO2, SOFA and D-dimer were independently associated with 28-day mortality. The predictive performance for mortality of the combination of PaO2/FiO2, SOFA score and D-dimer (area under the receiver operating characteristic curve of 0.926) was higher than the values for the individual factors (0.761, 0.745 and 0.878, respectively). Conclusion The combination of PaO2/FiO2, SOFA score and D-dimer represents a promising tool and biomarker for predicting 28-day mortality of the elderly patients with sepsis.

Background and Objectives: Procalcitonin (PCT), presepsin (PSEP), interferon-λ3 (IFN-λ3), and bioactive adrenomedullin (bio-ADM) are promising sepsis biomarkers. We explored the clinical utility of a multi-marker approach using these four biomarkers in patients with suspected sepsis. Materials and Methods: In a total of 248 patients, the biomarkers were evaluated with the sequential organ failure assessment (SOFA) score. Receiver operating characteristic curves with area under the curve (AUC) were analyzed to diagnose sepsis and predict in-hospital mortality. Survival and reclassification analyses were also used to predict in-hospital mortality. Results: The four biomarkers showed comparable diagnostic performance (AUC = 0.61–0.95, p < 0.001–0.003), and sepsis proportion increased significantly as the number of biomarkers used in the multi-marker approach increased (7.7–91.7%, p < 0.001). The proportion of biomarker quartiles (Q1–Q4) differed significantly according to SOFA score (p < 0.001). The four biomarkers predicted in-hospital mortality (AUC = 0.63–0.84, p < 0.001–0.004). The multi-marker approach performed better than the SOFA score (mortality rate, 58.3% vs. 31.3%; adjusted hazard ratio [HR], 14.7 vs. 4.6), and the addition of biomarkers to the SOFA score increased the performance. The multi-marker approach resulted in a higher HR in patients aged ≥75 years than in the overall population (9.2 vs. 4.2). Conclusions: Each biomarker showed clinical utility in patients with suspected sepsis. The multi-marker approach showed complementary clinical utility in addition to the SOFA score and better prognostic performance in patients aged ≥75 years. The use of biomarkers, alone or in combination, would be a valuable tool in combination with the SOFA score.

… underlying organ dysfunction and recovery relating to sepsis. The … Because early correction of hypotension and tissue … role of the circulation in causing organ dysfunction is vital, at least …

Sepsis is an ancient syndrome, as the term “sipo” (‘‘I rot’’ in Greek) was first used in a medical sense in the poems of Homer (1). Two thousand and seven hundred years later, sepsis remains a serious human disease with significant morbidity and mortality. Moreover, sepsis is increasingly common due to an aging population with multiple co-morbid illnesses that are being more aggressively treated with surgery and multiple complex therapies, including biologic and immunosuppressive therapies such as cancer chemotherapy (2-5).

Sepsis is a highly lethal disorder. Organ dysfunction in sepsis is not defined as a clinicopathological entity but rather by changes in clinical, physiological, or biochemical parameters. Pathogenesis and specific treatment of organ dysfunction in sepsis are unknown. The study of the histopathological correlate of organ dysfunction in sepsis will help understand its pathogenesis. We searched in PubMed, EMBASE, and Scielo for original articles on kidney, brain, and liver dysfunction in human sepsis. A defined search strategy was designed, and pertinent articles that addressed the histopathological changes in sepsis were retrieved for review. Only studies considered relevant in the field were discussed. Studies on acute kidney injury (AKI) in sepsis reveal that acute tubular necrosis is less prevalent than other changes, indicating that kidney hypoperfusion is not the predominant pathogenetic mechanism of sepsis-induced AKI. Other more predominant histopathological changes are apoptosis, interstitial inflammation, and, to a lesser extent, thrombosis. Brain pathological findings include white matter hemorrhage and hypercoagulability, microabscess formation, central pontine myelinolysis, multifocal necrotizing leukoencephalopathy, metabolic changes, ischemic changes, and apoptosis. Liver pathology in sepsis includes steatosis, cholangiolitis and intrahepatic cholestasis, periportal inflammation, and apoptosis. There is no information on physiological or biochemical biomarkers of the histopathological findings. Histopathological studies may provide important information for a better understanding of the pathogenesis of organ dysfunction in sepsis and for the design of potentially effective therapies. There is a lack of clinically available biomarkers for the identification of organ dysfunction as defined by the histological analysis.

Background/Aims The quick Sepsis-related Organ Failure Assessment (qSOFA) is a newly developed risk stratification tool, which has been presented along with a new sepsis definition, to classify infected patients outside of the intensive care unit (ICU). We evaluated the clinical usefulness of qSOFA for predicting adverse outcomes in sepsis patients with liver cirrhosis. Methods We performed a retrospective cohort study to assess the utility of qSOFA in sepsis patients with liver cirrhosis for whom medical emergency teams (METs) were activated in general wards at an academic tertiary care hospital between March 2008 and December 2015. qSOFA, Systemic inflammatory response syndrome (SIRS), modified early warning score (MEWS), and sequential (sepsis- related) organ failure assessment (SOFA) scores were calculated according to data at MET activation. Results Of 188 patients, 69 (36.7%) had a qSOFA score of 0 or 1 point and 119 (63.3%) had ≥ 2 points. The areas under the receiver operating characteristic curve (AUROC) for ICU transfer on the SOFA (AUROC, 0.691; 95% confidence interval [CI], 0.615 to 0.767) or MEWS (AUROC, 0.663; 95% CI, 0.586 to 0.739) were significantly higher compared to those for qSOFA (AUROC, 0.589; 95% CI, 0.507 to 0.671) or SIRS (AUROC, 0.533; 95% CI, 0.451 to 0.616). Conclusions Our findings suggest that qSOFA score may have limited utility in predicting adverse outcomes in sepsis patients with liver cirrhosis at MET activation. Either MEWS or another screening tool is needed for detecting early sepsis in these patients.

Aims: To investigate initial Sequential Organ Failure Assessment (SOFA) score of patients in Intensive Care Unit (ICU), who were diagnosed with infectious disease, as an indicator of multiple organ dysfunction and to examine if initial SOFA score is a better mortality predictor compared to Simplified Acute Physiology Score (SAPS). Materials and Methods: Hospital-based study done in medical ICU, from June to September 2014 with a sample size of 48. Patients aged 18 years and above, diagnosed with infectious disease were included. Patients with history of chronic illness (renal/hepatic/pulmonary/  cardiovascular), diabetes, hypertension, chronic obstructive pulmonary disease, heart disease, those on immunosuppressive therapy/chemoradiotherapy for malignancy and patients in immunocompromised state were excluded. Blood investigations were obtained. Six organ dysfunctions were assessed using initial SOFA score and graded from 0 to 4. SAPS was calculated as the sum of points assigned to each of the 17 variables (12 physiological, age, type of admission, and three underlying diseases). The outcome measure was survival status at ICU discharge. Results: We categorized infectious diseases into dengue fever, leptospirosis, malaria, respiratory tract infections, and others which included undiagnosed febrile illness, meningitis, urinary tract infection and gastroenteritis. Initial SOFA score was both sensitive and specific; SAPS lacked sensitivity. We found no significant association between age and survival status. Both SAPS and initial SOFA score were found to be statistically significant as mortality predictors. There is significant association of initial SOFA score in analyzing organ dysfunction in infectious diseases (P < 0.001). SAPS showed no statistical significance. There was statistically significant (P = 0.015) percentage of nonsurvivors with moderate and severe dysfunction, based on SOFA score. Nonsurvivors had higher SAPS but was not statistically significant (P = 0.094). Conclusions: Initial SOFA score is a superior mortality predictor. It easily measures degree of organ dysfunction in infectious diseases and complements other scoring systems.

Development of organ dysfunction discriminates sepsis from uncomplicated infection. The paradigm shift implicated by the new sepsis-3 definition holds that initial impairment of any organ can pave the way for multiple organ dysfunction and death. Moreover, the role of the systemic inflammatory response, central element in previous sepsis definitions, has been questioned. Most strikingly, a so far largely underestimated defense mechanism of the host, i.e., “disease tolerance,” which aims at maintaining host vitality without reducing pathogen load, has gained increasing attention. Here, we summarize evidence that a dysregulation of critical cellular signaling events, also in non-immune cells, might provide a conceptual framework for sepsis-induced dysfunction of parenchymal organs in the absence of significant cell death. We suggest that key signaling mediators, such as phosphoinositide 3-kinase, mechanistic target of rapamycin, and AMP-activated protein kinase, control the balance of damage and repair processes and thus determine the fate of affected organs and ultimately the host. Therapeutic targeting of these multifunctional signaling mediators requires cell-, tissue-, or organ-specific approaches. These novel strategies might allow stopping the domino-like damage to further organ systems and offer alternatives beyond the currently available strictly supportive therapeutic options.

… (MODS) which is associated with a mortality rate of 50% [30]. The mechanisms leading to MODS in septic … relation between whole blood viscosity and the SOFA score (low shear: r2 = 0.…

Objective To evaluate the prognosis significance of a newly simplified immune-dysregulation index, interleukin-6-to-lymphocyte ratio (IL-6/LY), in individuals diagnosed with sepsis. Methods This was a retrospective cohort study enrolling consecutive patients diagnosed with sepsis who qualified the inclusion criteria and were admitted to the intensive care unit of the First Affiliated Hospital of Soochow University between March 2017 and January 2023. Multivariate COX and logistic regression models were used to estimate the association between IL-6/LY and 28-day in-hospital mortality or multiple organ dysfunction syndrome (MODS). Restricted cubic splines and survival analysis were used to show a nonlinear correlation between IL-6/LY and mortality. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognostic value of IL-6/LY. was performed using the Kaplan‒Meier method. Results The study encompassed 301 participants, categorized into two groups—those with low IL-6/LY and high IL-6/LY—determined by the cutoff value of 326.04. On multivariate analyses, a high IL-6/LY was independently associated with 28-day in-hospital mortality (hazard ratio [HR]: 8.01, 95% confidence interval [CI] 4.67–13.74, P < 0.001) and MODS (odds ratio [OR] 3.44, 95% CI 1.85‒6.38, P < 0.001). The area under the curve of IL-6/LY for predicting death and MODS were 0.893 (95% CI, 0.855–0.931) and 0.743 (95% CI, 0.688–0.798), respectively. The Kaplan‒Meier analysis showed a significantly higher risk of mortality in the high IL-6/LY group (≥ 326.04) (log-rank P < 0.001). Conclusion The IL-6/LY is significantly associated with the risk of 28-day in-hospital mortality and MODS in patients with sepsis, making it a potential prognostic marker for risk stratification, which enables early identification of high-risk patients, timely interventions, and personalized treatment strategies to optimize patient outcomes.

… or develop organ failure despite showing a qSOFA <2, probably because they could have other forms of organ dysfunction not assessed by qSOFA, such as hypoxemia, renal failure, …

OBJECTIVES: Consensus regarding biomarkers for detection of infection-related organ dysfunction in the emergency department is lacking. We aimed to identify and validate biomarkers that could improve risk prediction for overt or incipient organ dysfunction when added to quick Sepsis-related Organ Failure Assessment (qSOFA) as a screening tool. DESIGN: In a large prospective multicenter cohort of adult patients presenting to the emergency department with a qSOFA score greater than or equal to 1, admission plasma levels of C-reactive protein, procalcitonin, adrenomedullin (either bioavailable adrenomedullin or midregional fragment of proadrenomedullin), proenkephalin, and dipeptidyl peptidase 3 were assessed. Least absolute shrinkage and selection operator regression was applied to assess the impact of these biomarkers alone or in combination to detect the primary endpoint of prediction of sepsis within 96 hours of admission. SETTING: Three tertiary emergency departments at German University Hospitals (Jena University Hospital and two sites of the Charité University Hospital, Berlin). PATIENTS: One thousand four hundred seventy-seven adult patients presenting with suspected organ dysfunction based on qSOFA score greater than or equal to 1. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was of moderate severity with 81% presenting with qSOFA = 1; 29.2% of these patients developed sepsis. Procalcitonin outperformed all other biomarkers regarding the primary endpoint (area under the curve for receiver operating characteristic [AUC-ROC], 0.86 [0.79–0.93]). Adding other biomarkers failed to further improve the AUC-ROC for the primary endpoint; however, they improved the model regarding several secondary endpoints, such as mortality, need for vasopressors, or dialysis. Addition of procalcitonin with a cutoff level of 0.25 ng/mL improved net (re)classification by 35.2% compared with qSOFA alone, with positive and negative predictive values of 60.7% and 88.7%, respectively. CONCLUSIONS: Biomarkers of infection and organ dysfunction, most notably procalcitonin, substantially improve early prediction of sepsis with added value to qSOFA alone as a simple screening tool on emergency department admission.

BackgroundWe aimed to evaluate the clinical usefulness of qSOFA as a risk stratification tool for patients admitted with infection compared to traditional SIRS criteria or our triage system; the Rapid Emergency Triage and Treatment System (RETTS).MethodsThe study was an observational cohort study performed at one Emergency Department (ED) in an urban university teaching hospital in Norway, with approximately 20,000 visits per year. All patients >16 years presenting with symptoms or clinical signs suggesting an infection (n = 1535) were prospectively included in the study from January 1 to December 31, 2012. At arrival in the ED, vital signs were recorded and all patients were triaged according to RETTS vital signs, presenting infection, and sepsis symptoms. These admission data were also used to calculate qSOFA and SIRS. Treatment outcome was later retrieved from the patients’ electronic records (EPR) and mortality data from the Norwegian population registry.ResultsOf the 1535 admitted patients, 108 (7.0%) fulfilled the Sepsis2 criteria for severe sepsis. The qSOFA score ≥2 identified only 33 (sensitivity 0.32, specificity 0.98) of the patients with severe sepsis, whilst the RETTS-alert ≥ orange identified 92 patients (sensitivity 0.85, specificity 0.55). Twenty-six patients died within 7 days of admission; four (15.4%) of them had a qSOFA ≥2, and 16 (61.5%) had RETTS ≥ orange alert. Of the 68 patients that died within 30 days, only eight (11.9%) scored ≥2 on the qSOFA, and 45 (66.1%) had a RETTS ≥ orange alert.DiscussionIn order to achieve timely treatment for sepsis, a sensitive screening tool is more important than a specific one. Our study is the fourth study were qSOFA finds few of the sepsis cases in prehospital or at arrival to the ED. We add information on the RETTS triage system, the two highest acuity levels together had a high sensitivity (85%) for identifying sepsis at arrival to the ED - and thus, RETTS should not be replaced by qSOFA as a screening and trigger tool for sepsis at arrival.ConclusionIn this observational cohort study, qSOFA failed to identify two thirds of the patients admitted to an ED with severe sepsis. Further, qSOFA failed to be a risk stratification tool as the sensitivity to predict 7-day and 30-day mortality was low. The sensitivity was poorer than the other warning scores already in use at the study site, RETTS-triage and the SIRS criteria.

BACKGROUND The concept of sepsis has recently been redefined by an International Task Force. The task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of Systemic Inflammatory Response Syndrome (SIRS) criteria to identify patients at high risk of mortality from sepsis outside of the intensive care unit, including in emergency departments (EDs). However, the primary outcome for qSOFA is prediction of risk for mortality, which is not the principal outcome measure considered in the ED. From the ED perspective, the priorities are the identification (diagnosis) of the septic patient and then the initiation of time-sensitive, life-saving interventions. METHOD We performed a structured review of PubMed from January 2012 to December 2018, limited to reports involving human subjects and written in English language and containing relevant keywords. The highest-quality studies were then reviewed in a structured format. We utilized these studies to estimate the sensitivity and specificity of SIRS and qSOFA for diagnosis of sepsis. RESULTS Thirteen unique articles were identified for further review, and the 11 highest-grade articles (C and D) were determined to be appropriate for inclusion in this review, and the two low-grade articles were excluded (E). CONCLUSIONS Based on multiple retrospective and few prospective studies, it appears that qSOFA performs poorly in comparison with SIRS as a diagnostic tool for ED patients who may have sepsis or septic shock. However, qSOFA does have a strong prognostic accuracy for mortality in those ED patients already diagnosed with sepsis or septic shock.

BackgroundThe usefulness of the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) score in providing bedside criteria for early prediction of poor outcomes in patients with suspected infection remains controversial. We investigated the prognostic performance of a positive qSOFA score outside the intensive care unit (ICU) compared with positive systemic inflammatory response syndrome (SIRS) criteria.MethodsA systematic literature search was performed using MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Data were pooled on the basis of sensitivity, specificity, and diagnostic OR. Overall test performance was summarized using a hierarchical summary ROC and the AUC. Meta-regression analysis was used to identify potential sources of bias.ResultsWe identified 23 studies with a total of 146,551 patients. When predicting in-hospital mortality in our meta-analysis, we identified pooled sensitivities of 0.51 for a positive qSOFA score and 0.86 for positive SIRS criteria, as well as pooled specificities of 0.83 for a positive qSOFA score and 0.29 for positive SIRS criteria. Discrimination for in-hospital mortality had similar AUCs between the two tools (0.74 vs. 0.71; P = 0.816). Using meta-regression analysis, an overall mortality rate ≥ 10% and timing of qSOFA score measurement could be significant sources of heterogeneity. For predicting acute organ dysfunction, although the AUC for a positive qSOFA score was higher than that for positive SIRS criteria (0.87 vs. 0.76; P < 0.001), the pooled sensitivity of positive qSOFA score was very low (0.47). In addition, a positive qSOFA score tended to be inferior to positive SIRS criteria in predicting ICU admission (0.63 vs. 0.78; P = 0.121).ConclusionsA positive qSOFA score had high specificity outside the ICU in early detection of in-hospital mortality, acute organ dysfunction, and ICU admission, but low sensitivity may have limitations as a predictive tool for adverse outcomes. Because between-study heterogeneity was highly represented among the studies, our results should be interpreted with caution.

Early administration of antibiotics is associated with better survival in sepsis, thus screening and early detection for sepsis is of clinical importance. Current risk stratification scores used for bedside detection of sepsis, for example Quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2), are primarily validated for death and intensive care. The primary aim of this study was to compare the diagnostic accuracy of qSOFA and NEWS2 for a composite outcome of sepsis with organ dysfunction, infection-related mortality within <72 h, or intensive care due to an infection. Retrospective analysis of data from two prospective, observational, multicentre, convenience trials of sepsis biomarkers at emergency departments were performed. Cohort A consisted of 526 patients with a diagnosed infection, 288 with the composite outcome. Cohort B consisted of 645 patients, of whom 269 had a diagnosed infection and 191 experienced the composite outcome. In Cohort A and B, NEWS2 had significantly higher area under receiver operating characteristic curve (AUC), 0.80 (95% CI 0.75–0.83) and 0.70 (95% CI 0.65–0.74), than qSOFA, AUC 0.70 (95% CI 0.66–0.75) and 0.62 (95% CI 0.57–0.67) p < 0.01 and, p = 0.02, respectively for the composite outcome. NEWS2 was superior to qSOFA for screening for sepsis with organ dysfunction, infection-related mortality or intensive care due to an infection both among infected patients and among undifferentiated patients at emergency departments.

… the quick Sepsis-related Organ Failure Assessment (qSOFA) … in patients with clinically diagnosed infection and to compare … evidence of infection and at least 2 of the following signs or …

OBJECTIVE Studies have suggested that qSOFA can be used for early detection of sepsis immediately upon arrival at the emergency department (ED). Despite this, little is known about the risk factors associated with the subsequent diagnosis of sepsis among patients with qSOFA<2 in the ED. METHODS This is a retrospective cohort study using ED data from a large tertiary medical center in Japan, 2018-2020. We included adult patients (aged ≥18 years) presenting to the ED with suspected infection (e.g., having a fever) and qSOFA<2. We identified patients who developed sepsis based on the Sepsis-3 criteria, and compared patient characteristics (e.g., demographics, vital signs upon the initial triage, chief complaint, and comorbidities) between patients who developed sepsis or not. Additionally, we identified the potential risk factors of sepsis among patients with qSOFA<2 using a multivariable logistic regression model. RESULTS We identified 151 (7%) patients who developed sepsis among 2025 adult patients with suspected infection and qSOFA<2. Compared with patients who did not develop sepsis, patients who developed sepsis were likely to be older and have vital signs suggestive of imminent sepsis (e.g., high respiratory rate). In the multivariable logistic regression model, the potential risk factors of sepsis among patients with qSOFA<2 were older age (adjusted OR, 1.92 [95%CI 1.19-3.19]), vital signs suggestive of imminent sepsis (e.g., adjusted OR of altered mental status, 3.50 [95%CI 2.25-5.50]), receipt of oxygen therapy upon arrival at the ED (adjusted OR, 1.91 [95%CI 1.38-2.26]), chief complaint of sore throat (adjusted OR, 2.15 [95%CI 1.08-4.13]), and the presence of comorbid diabetes mellitus, ischemic heart disease, and chronic kidney disease (e.g., adjusted OR of diabetes mellitus, 1.47 [95%CI 1.10-1.96]). On the contrary, chief complaint of abdominal and chest pain were associated with a lower risk of sepsis (e.g., adjusted OR of abdominal pain, 0.26 [95%CI 0.14-0.45]). CONCLUSIONS We found that older age, vital signs prognosticating sepsis, and the presence of some comorbidities were the potential risk factors of sepsis in patients with qSOFA<2. These potential risk factors could be useful to efficiently recognize patients who might develop sepsis in the ED.

Background Sepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis. Methods We created 72-h SOFA score trajectories in patients with sepsis from four diverse intensive care unit (ICU) cohorts. We then used dynamic time warping (DTW) to compute heterogeneous SOFA trajectory similarities and hierarchical agglomerative clustering (HAC) to identify trajectory-based subphenotypes. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership at 6 and 24 h after being admitted to the ICU. The model was tested on three validation cohorts. Sensitivity analyses were performed with alternative clustering methodologies. Results A total of 4678, 3665, 12,282, and 4804 unique sepsis patients were included in development and three validation cohorts, respectively. Four subphenotypes were identified in the development cohort: Rapidly Worsening ( n  = 612, 13.1%), Delayed Worsening ( n  = 960, 20.5%), Rapidly Improving ( n  = 1932, 41.3%), and Delayed Improving ( n  = 1174, 25.1%). Baseline characteristics, including the pattern of organ dysfunction, varied between subphenotypes. Rapidly Worsening was defined by a higher comorbidity burden, acidosis, and visceral organ dysfunction. Rapidly Improving was defined by vasopressor use without acidosis. Outcomes differed across the subphenotypes, Rapidly Worsening had the highest in-hospital mortality (28.3%, P -value < 0.001), despite a lower SOFA (mean: 4.5) at ICU admission compared to Rapidly Improving (mortality:5.5%, mean SOFA: 5.5). An overall prediction accuracy of 0.78 (95% CI, [0.77, 0.8]) was obtained at 6 h after ICU admission, which increased to 0.87 (95% CI, [0.86, 0.88]) at 24 h. Similar subphenotypes were replicated in three validation cohorts. The majority of patients with sepsis have an improving phenotype with a lower mortality risk; however, they make up over 20% of all deaths due to their larger numbers. Conclusions Four novel, clinically-defined, trajectory-based sepsis subphenotypes were identified and validated. Identifying trajectory-based subphenotypes has immediate implications for the powering and predictive enrichment of clinical trials. Understanding the pathophysiology of these differential trajectories may reveal unanticipated therapeutic targets and identify more precise populations and endpoints for clinical trials.

Background A greater understanding of disease heterogeneity may facilitate precision medicine for coronavirus disease 2019 (COVID-19). Previous work identified four distinct clinical phenotypes associated with outcome and treatment responses in non-COVID-19 sepsis patients, but it is unknown if and how these phenotypes are recapitulated in COVID-19 sepsis patients. Methods We applied the four non-COVID-19 sepsis phenotypes to a total of 52,274 critically ill patients, comprising two cohorts of COVID-19 sepsis patients (admitted before and after the introduction of dexamethasone as standard treatment) and three non-COVID-19 sepsis cohorts (non-COVID-19 viral pneumonia sepsis, bacterial pneumonia sepsis, and bacterial sepsis of non-pulmonary origin). Differences in proportions of phenotypes and their associated mortality were determined across these cohorts. Results Phenotype distribution was highly similar between COVID-19 and non-COVID-19 viral pneumonia sepsis cohorts, whereas the proportion of patients with the δ-phenotype was greater in both bacterial sepsis cohorts compared to the viral sepsis cohorts. The introduction of dexamethasone treatment was associated with an increased proportion of patients with the δ-phenotype (6% vs. 11% in the pre- and post-dexamethasone COVID-19 cohorts, respectively, p  < 0.001). Across the cohorts, the α-phenotype was associated with the most favorable outcome, while the δ-phenotype was associated with the highest mortality. Survival of the δ-phenotype was markedly higher following the introduction of dexamethasone (60% vs 41%, p  < 0.001), whereas no relevant differences in survival were observed for the other phenotypes among COVID-19 patients. Conclusions Classification of critically ill COVID-19 patients into clinical phenotypes may aid prognostication, prediction of treatment efficacy, and facilitation of personalized medicine.

… Sepsis is a major cause of morbidity and mortality worldwide, … sub-phenotypes within the sepsis population could help … may lead to minor differences in sub-phenotype assignment for …

RATIONALE Biological heterogeneity in critical illness syndromes, such as sepsis and acute kidney injury (AKI), has hindered development of effective therapies. In sepsis-associated AKI, two molecular sub-phenotypes (SP1 and SP2) have been identified with differing characteristics, outcomes and response to vasopressor treatment. It is unknown if these sub-phenotypes extend to all patients with sepsis, and whether they respond differently to fluid resuscitation strategy. METHODS Patients enrolled in the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) clinical trial with plasma collected at study enrollment were classified into two sub-phenotypes using a previously validated parsimonious prediction model that included angiopoietin-1 and 2, and soluble tumor necrosis factor receptor-1. Kaplan-Meier estimates were used to test differences in outcomes and sub-phenotype by treatment interaction. MEASUREMENTS AND MAIN RESULTS Among 1289 patients, we identified 1016 as SP1 and 273 as SP2. The risk of poor clinical outcomes was greater in SP2 relative to SP1 independent of demographics, comorbidities and illness severity scores. Patients with SP2, characterized by more severe endothelial injury and inflammation, had higher 28-day mortality with a liberal versus restrictive fluid strategy (41% vs 27%), while patients with SP1 had no difference (9% vs 9%) (p-value-for-interaction = 0.02). Furthermore, SP2 had fewer days free from ventilation, renal replacement therapy and vasopressors with a liberal compared to a restrictive resuscitation strategy. CONCLUSION Molecular sub-phenotypes previously identified in AKI are also identifiable in sepsis and respond differently to fluid resuscitation strategy. Future prospective identification of these sub-phenotypes could inform a precision-guided therapeutic approach in sepsis.

Sepsis is a clinically heterogeneous disease with high mortality. It is crucial to develop relevant therapeutic strategies for different sepsis phenotypes, but the impact of phenotypes on patients’ clinical outcomes is unclear. This study aimed to identify potential sepsis phenotypes using readily available clinical parameters and assess their predictive value for 28-day clinical outcomes by logistic regression analysis. In this retrospective analysis, researchers extracted clinical data from adult patients admitted to the First Affiliated Hospital of Anhui Medical University between April and August 2022 and from the 2014–2015 eICU Collaborative Study database. K-Means clustering was utilized to identify and refine sepsis phenotypes, and their predictive performance was subsequently evaluated. Logistic regression models were trained independently for each phenotype and five-fold cross-validation was used to predict clinical outcomes. Predictive accuracy was then compared to traditional non-clustered prediction methods using model assessment scores. The study cohort consisted of 250 patients from the First Affiliated Hospital of Anhui Medical University, allocated in a 7:3 ratio for training and testing, respectively, and an external validation cohort of 3100 patients from the eICU Cooperative Research Database. The results of the phenotype-based prediction model demonstrated an improvement in F1 score from 0.74 to 0.82 and AUC from 0.74(95%CI 0.71–0.80) to 0.84(95%CI 0.82–0.87), and these results also highlight the superiority of clinical outcome prediction with the help of sepsis phenotypes over traditional prediction methods. Phenotype-based prediction of 28-day clinical outcomes in sepsis demonstrated significant advantages over traditional models, highlighting the impact of phenotype-driven modeling on clinical outcomes in sepsis.

Background The role of site of infection in sepsis has been poorly characterized. Additionally, sepsis epidemiology has evolved. Early mortality has decreased, but many survivors now progress into chronic critical illness (CCI). This study sought to determine if there were significant differences in the host response and current epidemiology of surgical sepsis categorized by site of infection. Study design This is a longitudinal study of surgical sepsis patients characterized by baseline predisposition, insult characteristics, serial biomarkers, hospital outcomes, and long-term outcomes. Patients were categorized into five anatomic sites of infection. Results The 316 study patients were predominantly Caucasian; half were male, with a mean age of 62 years, high comorbidity burden, and low 30-day mortality (10%). The primary sites were abdominal (44%), pulmonary (19%), skin/soft tissue (S/ST, 17%), genitourinary (GU, 12%), and vascular (7%). Most abdominal infections were present on admission and required source control. Comparatively, they had more prolonged proinflammation, immunosuppression, and persistent organ dysfunction. Their long-term outcome was poor with 37% CCI (defined as >  14 in ICU with organ dysfunction), 49% poor discharge dispositions, and 30% 1-year mortality. Most pulmonary infections were hospital-acquired pneumonia. They had similar protracted proinflammation and organ dysfunction, but immunosuppression normalized. Long-term outcomes are similarly poor (54% CCI, 47% poor disposition, 32% 1-year mortality). S/ST and GU infections occurred in younger patients with fewer comorbidities, less perturbed immune responses, and faster resolution of organ dysfunction. Comparatively, S/ST had better long-term outcomes (23% CCI, 39% poor disposition, 13% 1-year mortality) and GU had the best (10% CCI, 20% poor disposition, 10% 1-year mortality). Vascular sepsis patients were older males, with more comorbidities. Proinflammation was blunted with baseline immunosuppression and organ dysfunction that persisted. They had the worst long-term outcomes (38% CCI, 67% poor disposition, 57% 1-year mortality). Conclusion There are notable differences in baseline predisposition, host responses, and clinical outcomes by site of infection in surgical sepsis. While previous studies have focused on differences in hospital mortality, this study provides unique insights into the host response and long-term outcomes associated with different sites of infection.

Objective: This study aimed to evaluate three phenotypic classifications based on their ability to predict mortality in critically ill adult patients with sepsis. Methods: This single-center cohort study involved 106 patients diagnosed with sepsis upon admission to the intensive care unit (ICU). The patient population was categorized according to three distinct clinical phenotypic models: the first based on age and thermal profiles, the second stratifying patients into four specific groups (multiple organ failure, respiratory dysfunction, neurological dysfunction, and miscellaneous), and the third assessing arterial blood pressure trajectories within the initial 10 hours of ICU stay. Multiple logistic regression models were fitted to evaluate the utility of these classifications in predicting in-hospital mortality. The performance of a model incorporating the three phenotypic classifications was compared with the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores. Results: It was observed that elderly patients presenting with hypothermia showed a significantly higher mortality risk compared to younger, normothermic, or febrile subjects (OR 17.32 [95% CI 1.95-153.14], p = 0.010). Furthermore, patients with multi-organ failure presented a significantly higher risk of death (OR 5.87 [95% CI 1.17-29.94], p = 0.031). Finally, persistent hypotensive individuals were not found to have a significantly elevated risk of death (p = 0.300). The final predictive model’s area under the ROC curve was 0.856, which was not inferior to that of APACHE II (0.776) or SOFA (0.764) in the sample studied. Conclusions: When used together, the phenotypically analyzed classifications demonstrated good accuracy in predicting mortality among critically ill patients with sepsis.

… living compared to those without organ failure. A multiyear … hypoperfusion without shock, sepsis without shock, and shock … The major limitation is limited sensitivity in detecting milder …

Fever can be viewed as an adaptive response to infection. Temperature control in sepsis is aimed at preventing potential harms associated with high temperature (tachycardia, vasodilation, electrolyte and water loss) and therapeutic hypothermia may be aimed at slowing metabolic activities and protecting organs from inflammation. Although high fever (>39.5°C) control is usually performed in critically ill patients, available cohorts and randomized controlled trials do not support its use to improve sepsis prognosis. Finally, both spontaneous and therapeutic hypothermia are associated with poor outcomes in sepsis.

… median recovery time was 6 h; body temperature rarely fell below 34.0C. Bidirectional oscillations in body temperature … interfere with the body temperature (T b ) of septic patients? This …

Aims/Background Sepsis is a critical medical emergency with a significantly high mortality rate. This study aims to investigate the relationship between changes in early indicators and prognosis, exploring the link between early sepsis recognition and patient outcomes. Methods This retrospective analysis included clinical data from 183 sepsis patients admitted to the hospital between July 2021 and November 2024. Based on the recognition time, patients were divided into an early recognition group (within 6 hours after admission, n = 136) and a delayed recognition group (6 hours after admission, n = 47). The baseline characteristics, early recognition indicators, therapeutic measures, and prognostic outcomes were collected, and the relationship between these variables was analyzed using the logistic regression analysis. Results There were no significant differences between the early and delayed recognition groups regarding age, gender, immunity status, and the distribution of common underlying conditions (p > 0.05). However, the sequential organ failure assessment (SOFA) scores were significantly higher in the delayed recognition group compared to the early recognition group (p < 0.05). The two groups showed significant differences in key indicators such as body temperature, heart rate, respiratory rate, white blood cell count (WBC), C-reactive protein (CRP), neutrophil ratio, procalcitonin (PCT), lactate, platelet count, and D-dimer levels (p < 0.05). The early recognition group received anti-infective treatment timely, had reasonable fluid resuscitation, a lower proportion of vasoactive drug usage, and reduced mechanical ventilation use (p < 0.05). The early recognition group had a shorter duration of hospitalization, good recovery of organ function at discharge, and significantly lower mortality and complication rates than the delayed recognition group (p < 0.05). Logistic regression analysis revealed that heart rate, respiratory rate, CRP, PCT, neutrophil ratio, lactate, D-dimer, and SOFA score ≥8 points were independent risk factors affecting prognosis (p < 0.05). Conclusion Early sepsis recognition, followed by prompt therapeutic measures, significantly improves patient prognosis, and relevant indicators help early sepsis identification and prognosis assessment.

Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host’s immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host’s innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials.

In sepsis-3, in contrast with sepsis-1, the definition “systemic inflammatory response” has been replaced with “dysregulated host response”, and “systemic inflammatory response syndrome” (SIRS) has been replaced with “sequential organ failure assessment” (SOFA). Although the definition of sepsis has changed, the debate regarding its nature is ongoing. What are the fundamental processes controlling sepsis-induced inflammation, immunosuppression, or organ failure? In this review, we discuss the heterogeneity of sepsis-3 and address the central role of inflammation in the pathogenesis of sepsis. An unbalanced pro- and anti-inflammatory response, inflammatory resolution disorder, and persistent inflammation play important roles in the acute and/or chronic phases of sepsis. Moreover, powerful links exist between inflammation and other host responses (such as the neuroendocrine response, coagulation, and immunosuppression). We suggest that a comprehensive evaluation of the role of the inflammatory response will improve our understanding of the heterogeneity of sepsis.

Sepsis is characterized as a life-threatening organ dysfunction syndrome that is caused by a dysregulated host response to infection. The main etiological causes of sepsis are bacterial, fungal, and viral infections. Last decades clinical and preclinical research contributed to a better understanding of pathophysiology of sepsis. The dysregulated host response in sepsis is complex, with both pathogen-related factors contributing to disease, as well as immune-cell mediated inflammatory responses that can lead to adverse outcomes in early or advanced stages of disease. Due to its heterogenous nature, clinical diagnosis remains challenging and sepsis-specific treatment options are still lacking. Classification and early identification of patient subgroups may aid clinical decisions and improve outcome in sepsis patients. The initial clinical presentation is rather similar in sepsis of different etiologies, however, inflammatory profiles may be able to distinguish between different etiologies of infections. In this review, we summarize the role and the discriminating potency of host-derived inflammatory biomarkers in the context of the main etiological types of sepsis.

Sepsis is one of the leading causes of deaths world-wide and yet there are no therapies available other than ICU treatment. The patient outcome is determined by a complex interplay between the pro and anti-inflammatory responses of the body i.e., a homeostatic balance between these two competing events to be achieved for the patient’s recovery. The initial attempts on drug development mainly focused on controlling inflammation, however, without any tangible outcome. This was despite most deaths occurring during the immune paralysis stage of this biphasic disease. Recently, the focus has been shifting to understand immune paralysis (caused by apoptosis and by anti-inflammatory cytokines) to develop therapeutic drugs. In this review we put forth an argument for a proper understanding of the molecular basis of inflammation as well as apoptosis for developing an effective therapy.

… -threatening organ dysfunction that is caused by a dysregulated host response to infection. … is complex and involves an initial excessive host inflammatory response to infection that is …

… inflammatory pathways has also been demonstrated. For example, AT acts as a mediator of inflammation … hemostatic activation and inflammation in patients with sepsis and suspected …

… organ dysfunction that is caused by a dysregulated host response to infection. In … For many years, a disproportionate inflammatory response to invasive infection was considered to be …