Search

The objective of this prospective observational study was to assess the clinical significance of neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and lymphocyte–monocyte ratio (LMR) as potential biomarkers to identify post-PNL SIRS or sepsis. Demographic data and laboratory data including hemoglobin (Hb), total leucocyte count (TLC), serum creatinine, urine microscopy and culture were collected. The NLR, LMR and PLR were calculated by the mathematical division of their absolute values derived from routine complete blood counts from peripheral blood samples. Stone factors were assessed by non-contrast computerized tomography of kidneys, ureter and bladder (NCCT KUB) and included stone burden (Volume = L × W × D × π × 0.167), location and Hounsfield value and laterality. Intraoperative factors assessed were puncture site, tract size, tract number, operative time, the need for blood transfusion and stone clearance. Of 517 patients evaluated, 56 (10.8%) developed SIRS and 8 (1.5%) developed sepsis. Patients developing SIRS had significantly higher TLC (10.4 ± 3.5 vs 8.6 ± 2.6, OR 1.19, 95% CI 1.09–1.3,p = 0.000002), higher NLR (3.6 ± 2.4 vs 2.5 ± 1.04, OR 1.3, 95% CI = 1.09–1.5,p = 0.0000001), higher PLR (129.3 ± 53.8 vs 115.4 ± 68.9, OR 1.005, 95% CI 1.001–1.008,p = 0.005) and lower LMR (2.5 ± 1.7 vs 3.2 ± 1.8, OR 1.18, 95% CI 1.04–1.34,p = 0.006). Staghorn stones (12.8 vs 3.24%, OR 4.361, 95% CI 1.605–11.846,p = 0.008) and long operative times (59.6 ± 14.01 vs 55.2 ± 16.02, OR 1.01, 95% CI 1.00–1.03,p = 0.05) had significant association with postoperative SIRS. In conclusion, NLR, PLR and LMR can be useful independent, easily accessible and cost-effective predictors for early identification of post-PNL SIRS/sepsis.

Systemic inflammatory response syndrome (SIRS) is a life-threatening condition with nonspecific symptoms. Because of that, defining a targeted therapy against SIRS in children and adults remains a challenge. The identification of diagnostic patterns from individualized immuneprofiling can lead to development of a personalized therapy. The aim of this study was to identify and analyze ethical issues associated with personalized research and therapy for SIRS in pediatric populations. We conducted an ethical analysis based on a principled approach according to Beauchamp and Childress’ four bioethical principles. Relevant information for the research objectives was extracted from a systematic literature review conducted in the scientific databases PubMed, Embase and Web of Science. We searched for pertinent themes dealing with at least one of the four bioethical principles: “autonomy”, “non-maleficence”, “beneficence” and “justice”. 48 publications that met the research objectives were included in the thorough analysis, structured and discussed in a narrative synthesis. From the analysis of the results, it has emerged that traditional paradigms of patient’s autonomy and physician paternalism need to be reexamined in pediatric research. Standard information procedures and models of informed consent should be reconsidered as they do not accommodate the complexities of pediatric omics research.

Purpose Surgery initiates pro-inflammatory mediator cascades leading to a variably pronounced sterile inflammation (SIRS). SIRS is associated with intestinal paralysis and breakdown of intestinal barrier and might result in abdominal sepsis. Technological progress led to the development of a neurostimulator for transcutaneous auricular vagal nerve stimulation (taVNS), which is associated with a decline in inflammatory parameters and peristalsis improvement in rodents and healthy subjects via activation of the cholinergic anti-inflammatory pathway. Therefore, taVNS might be a strategy for SIRS prophylaxis. Methods The NeuroSIRS-Study is a prospective, randomized two-armed, sham-controlled, double-blind clinical trial. The study is registered at DRKS00016892 (09.07.2020). A controlled endotoxemia is used as a SIRS-mimicking model. 2 ng/kg bodyweight lipopolysaccharide (LPS) will be administered after taVNS or sham stimulation. The primary objective is a reduction of clinical symptoms of SIRS after taVNS compared to sham stimulation. Effects of taVNS on release of inflammatory cytokines, intestinal function, and vital parameters will be analyzed. Discussion TaVNS is well-tolerated, with little to no side effects. Despite not fully mimicking postoperative inflammation, LPS challenge is the most used experimental tool to imitate SIRS and offers standardization and reproducibility. The restriction to healthy male volunteers exerts a certain bias limiting generalizability to the surgical population. Still, this pilot study aims to give first insights into taVNS as a prophylactic treatment in postoperative inflammation to pave the way for further clinical trials in patients at risk for SIRS. This would have major implications for future therapeutic approaches.

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

Systemic inflammatory response syndrome (SIRS) is a very common finding in critically ill patients. To accurately identify patients with SIRS and those who need intensive care, several markers have been evaluated, including cortisol, WBC or lactate. It is widely known that a stress leukogram includes eosinopenia as one of its main markers (neutrophilia, eosinopenia, lymphopenia and mild monocytes). It is known that cortisol concentration in plasma is the main stress biomarker and is strongly correlated with the severity of disease in horses. However, it is not possible to measure this parameter routinely in clinical conditions. Hence, in this study it was hypothesized that the eosinophil count could be a reliable parameter to identify critically ill horses. Horses included in this study were divided into three groups: Group A (sick horses received at the Emergency Unit which did not fulfil the criteria for SIRS), Group B (horses that meet two or more criteria for inclusion in the definition of SIRS) and a control group of healthy horses. In this study, horses with SIRS showed lower eosinophil counts than healthy horses. Moreover, non-surviving horses exhibited lower eosinophil counts than survivors. Eosinopenia could be used to identify horses with SIRS and can be useful as a prognostic marker.

Asmaa Nasr El-Din,1 Abdelhady Ragab Abdel-Gawad,2 Wesam Abdelgalil,3 Nahed F Fahmy1 1Department of Microbiology and Immunology, Faculty of Medicine, Sohag University, Sohag, Egypt; 2Department of Clinical and Chemical Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt; 3Departments of Anesthesia and Intensive Care, Faculty of Medicine, Sohag University, Sohag, EgyptCorrespondence: Asmaa Nasr El-Din Tel +20 10-2809-0703Email asmaanasredin81@gmail.comBackground: The purpose of this study was to explore the diagnostic role of sTREM1 in the diagnosis of sepsis and in differentiating between sepsis and systemic inflammatory response syndrome (SIRS). We also aimed to assess the prognostic value of suPAR in comparison to sequential organ-failure assessment (SOFA), acute physiology and chronic health evaluation (APACHE) II scores, and 28-day mortality.Methods: This was a cross-sectional study conducted in the Medical Microbiology and Immunology Department and Central Research Laboratory, Faculty of Medicine, Sohag University from June 2019 to January 2021. The study population was classified into two groups: SIRS (no evidence of infection) and sepsis (with SIRS and evidence of infection). Patients were rated on the SOFA and APACHE II scoring systems at admission and after 7 days. Serum levels of sTREM1 and suPAR were measured by ELISA at the same time points.Results: CRP and sTREM1 values were significantly higher in the sepsis group than the SIRS group on both days (P< 0.0001). The area under the curve (AUC) for CRP was 0.87 on the first day and 0.97 on the seventh, while the AUC for sTREM1 was 1.00 and 0.93 on the first and seventh days, respectively. The sensitivity of sTREM1 was 100% and specificity 84% at a cutoff of 49 pg/mL. There was a significantly positive correlation between CRP and sTREM1 values (P< 0.0001). On the seventh day, nonsurvivors had significantly higher serum levels of suPAR (median 4.9 ng/mL) than survivors (median 2.9 ng/mL; P< 0.0001). Nonsurvivors also had significantly higher SOFA and APACHE II scores than survivors (P< 0.0001 and P< 0.0001, respectively).Conclusion: sTREM1 can be used as a good indicator for diagnosing sepsis in intensive care–unit patients. suPAR can also be used as a predictor of bad prognosis and poor survival at 7 days following admission.Keywords: SIRS, sTREM, suPAR, sepsis

Background: This prospective study aimed to explore the correlation between circulating mitochondrial DNA (mtDNA), intestinal barrier function impairment, and postoperative SIRS in patients undergoing gastrointestinal surgery. Methods: Patients were recruited into this study after signing an informed consent form. Circulating mitochondrial DNA and serum DAO concentrations were measured preoperatively and on day 1 and day 7 postoperatively. Postoperative vitals, routine tests, and biochemical indicators were recorded in detail. Results: Forty patients undergoing gastrointestinal surgery were recruited for and completed this study. Patients were divided into non-fever, fever, and SIRS groups according to their postoperative temperature and other corresponding indexes. The mtDNA was expressed as the number of PCR cycles using three specific sequences. Circulating mtDNA tended to increase in patients after gastrointestinal surgery, but the difference was not significant. Nevertheless, mtDNA in the SIRS group was significantly higher than in patients in the fever and non-fever groups (p < 0.05). Serum DAO showed a trend of increase on the first day after surgery compared with that before surgery, but the difference was not significant (p > 0.05). However, patients in the SIRS group showed a significant increase (p < 0.05) compared with the others. Both circulating mtDNA and DAO showed a downward trend on the seventh day after surgery. Conclusions: Circulating mtDNA presented a trend of increase after gastrointestinal surgery, and the degree of the increased fold was related to the extent of the inflammation response. In general, the intestinal barrier damage indicator DAO was the same as mtDNA and tended to increase after gastrointestinal surgery and then gradually decrease, which may play a synergistic role in inducing postoperative fever and SIRS.

Aim of the study In this pilot study lipopolysaccharide-binding protein (LBP) levels were assessed as a possible risk factor for development of systemic inflammatory response syndrome (SIRS) and infectious and inflammatory complications in colorectal cancer (CRC) patients after surgery. Material and methods For LBP determination venous blood was taken 1 hour before the surgery and 72 hours after it. All patients were stratified by the presence or absence of acute bowel obstruction (ABO), SIRS and complications. Results 36 patients with CRC participated in the study. The LBP level before surgery was 879.8 ± 221.8 ng/ml (interquartile range (IQR) 749.3–1028.8); on the 3rd day it was 766.5 ± 159.4 ng/ml (IQR 669.5–847.6), which was a statistically significant decrease (p = 0.004). A decrease in LBP level by more than 280 ng/ml increases the probability of SIRS and complications in operated CRC patients (OR 6.6, 95% CI: 1.1–40.9 and OR 12.0, 95% CI: 1.8–80.4, respectively). In patients with ABO in the presence of SIRS, the LBP value decreased more than in those without SIRS (p = 0.046). Conclusions This study demonstrated that the LBP level in the operated CRC patients tends to decrease on the 3rd day after surgery. A bigger decrease in LBP level increases the probability of SIRS and postoperative infectious and inflammatory complications. Therefore, further studies with larger numbers of patients are required.

Networks constituting virtual cellular manufacturing system (VCMS) cells are partially interconnected while the interlinks are directional and the interlink numbers between cells are unequal, which was not considered in previous studies. In this study, a model based on susceptible–infectious–removed–susceptible was developed to analyze error spreading over an interconnected network, and theoretical analysis was performed. Based on simulations, we found the following: (i) random interlinks between subnetworks insignificantly affected the interconnected network; (ii) a large interlinking propagation efficiency raised the infection probability of the interconnected network of VCMS; (iii) the topological structures of scale-free subnetworks shaped by cells could inhibit infection propagation. Using two real cases, we verified the conclusions drawn from the error spreading model. This study provides sound foundations to optimize the structural constitution of a VCMS during its cell formation and arrangement periods.

Introduction Ischemia-Reperfusion Injury (IRI) is a complication following the reperfusion of ischemic tissues; it requires immediate treatment, as it can lead to severe infection and tissue death. The purpose of this study was to demonstrate the ability of Hyperbaric Oxygen Therapy (HBOT) to treat SIRS (Systemic Inflammatory Response Syndrome) caused by IRI and to provide long-term functional assessment for a period of up to 5 years. Case presentation Two cases of avulsions of the hand at the levels of the wrist joint and the medial third forearm, severed by machetes. Both patients were male and in their twenties. Hand replantation was carried out after 30 minutes (medial third forearm case) and 11 hours (wrist joint case) of ischemic time. A couple of days after surgery, both patients experienced SIRS as a result of IRI. The patients were brought to the hyperbaric chamber and received 3 consecutive 90-min sessions of HBOT at 2.4 ATA 3 days in a row. The outcomes were compared in a table with each patient's vital signs and laboratory results, both before and after HBOT. A significant improvement was seen at the follow-ups in vital signs and laboratory results for both patients after HBOT administration. Long-term follow-up also showed satisfying results for hand function, proven by low DASH (Disabilities of the Arm, Shoulder, and Hand) scores. Conclusion HBOT was able to treat SIRS in both patients. Favorable long-term hand function results signify successful extremity replantation., Highlights • Ischemia-Reperfusion Injury (IRI) is a complication following the reperfusion of ischemic tissues. • Two cases of avulsions of the hand that had underwent hand replantation had experienced systemic inflammatory response syndrome (SIRS) due to IRI. • Administration of HBOT has been proven to be an effective treatment for post-hand replantation SIRS.

Supplemental Digital Content is available in the text, Background: A declining selenium (Se) status constitutes a characteristic of critical illness and may affect disease course and survival. The dynamics of trauma-induced changes in biomarkers of Se status are poorly characterized, and an association with multiple organ failure (MOF) and mortality can be hypothesized. It was the aim of this study to investigate Se and selenoprotein P (SELENOP) concentrations in major trauma patients during the early posttraumatic period. Patients and Methods: Twenty-four patients after major trauma (ISS ≥16) were included at our level one trauma center. Se supplementation ever during the 90-day observation period was defined as an exclusion criterion. Serum samples were drawn within less than 60 min after trauma, and after 6 h, 12 h, 24 h, 48 h, and 72 h. Serum Se was analyzed by X-ray fluorescence and SELENOP concentrations by ELISA. The data were correlated to clinical parameters, occurrence of MOF defined by MOF and APACHE II score, lung injury defined by Horowitz index and clinical outcome (90-days survival). Results: Serum Se and SELENOP concentrations of the trauma patients were significantly below the average of healthy European subjects (mean ±SD; Se, 41.2±8.1 vs. 84.7±23.3 μg/L, P

Patients with MetS or SIRS experience higher rates of mortality and morbidity, across both cardiac and noncardiac surgery. Frailty assessment has acquired increasing importance in recent years as it predisposes elderly patients to a worse outcome. The aim of our study was to investigate the influence of MetS, SIRS, and with or without frailty on elderly patients undergoing emergency surgical procedures.We analyzed data of all patients with nonmalignant diseases requiring an emergency surgical procedure from January 2017 to December 2020. The occurrence of MetS was identified using modified definition criteria used by the NCEP-ATP III Expert Panel: obesity, hypertension, diabetes, or if medication for high triglycerides or for low HDL cholesterol was taken. Systemic inflammatory response syndrome (SIRS) was evaluated according to the original consensus study (Sepsis-1). The frailty profile was investigated by the 5-modified Frailty Index (5-mFI) and the Emergency Surgery Frailty Index (EmSFI). Postoperative complications have been reported and categorized according to the Clavien-Dindo (C-D) classification system. Morbidity and mortality have been mainly considered as the 30-day standard period definition.Of the 2,318 patients included in this study, 1,010 (43.6%) fulfilled the criteria for MetS (MetsG group). Both 5-Items score and EmsFI showed greater fragility in patients with MetS. All patients with MetS showed more frequently a CACI index greater than 6. The occurrence of SIRS was higher in MetSG. LOS was longer in patients with MetS (MetSG 11.4 ± 12 days vs.Impact of MetS and SIRS on elderly surgical patient outcomes has yet to be fully elucidated. The present study showed a 43.6% incidence of MetS in the elderly population. In conclusion, age per se should be not considered anymore as the main variable to estimate patient outcomes, while MetS and Frailty should have always a pivotal role.

Background Sepsis is the leading cause of death in the intensive care unit (ICU). Expediting its diagnosis, largely determined by clinical assessment, improves survival. Predictive and explanatory modelling of sepsis in the critically ill commonly bases both outcome definition and predictions on clinical criteria for consensus definitions of sepsis, leading to circularity. As a remedy, we collected ground truth labels for sepsis. Methods In the Ground Truth for Sepsis Questionnaire (GTSQ), senior attending physicians in the ICU documented daily their opinion on each patient’s condition regarding sepsis as a five-category working diagnosis and nine related items. Working diagnosis groups were described and compared and their SOFA-scores analyzed with a generalized linear mixed model. Agreement and discriminatory performance measures for clinical criteria of sepsis and GTSQ labels as reference class were derived. Results We analyzed 7291 questionnaires and 761 complete encounters from the first survey year. Editing rates for all items were > 90%, and responses were consistent with current understanding of critical illness pathophysiology, including sepsis pathogenesis. Interrater agreement for presence and absence of sepsis was almost perfect but only slight for suspected infection. ICU mortality was 19.5% in encounters with SIRS as the “worst” working diagnosis compared to 5.9% with sepsis and 5.9% with severe sepsis without differences in admission and maximum SOFA. Compared to sepsis, proportions of GTSQs with SIRS plus acute organ dysfunction were equal and macrocirculatory abnormalities higher (p SIRS proportionally ranked above sepsis in daily assessment of illness severity (p . Separate analyses of neurosurgical referrals revealed similar differences. Discriminatory performance of Sepsis-1/2 and Sepsis-3 compared to GTSQ labels was similar with sensitivities around 70% and specificities 92%. Essentially no difference between the prevalence of SIRS and SOFA ≥ 2 yielded sensitivities and specificities for detecting sepsis onset close to 55% and 83%, respectively. Conclusions GTSQ labels are a valid measure of sepsis in the ICU. They reveal suspicion of infection as an unclear clinical concept and refute an illness severity hierarchy in the SIRS-sepsis-severe sepsis spectrum. Ground truth challenges the accuracy of Sepsis-1/2 and Sepsis-3 in detecting sepsis onset. It is an indispensable intermediate step towards advancing diagnosis and therapy in the ICU and, potentially, other health care settings.

The release of extracellular vesicles (EVs) is increased under cellular stress and cardiomyocyte damaging conditions. However, whether the cardiomyocyte-derived EVs eventually reach the systemic circulation and whether their number in the bloodstream reflects cardiac injury, remains unknown. Wild type C57B/6 and conditional transgenic mice expressing green fluorescent protein (GFP) by cardiomyocytes were studied in lipopolysaccharide (LPS)-induced systemic inflammatory response syndrome (SIRS). EVs were separated both from platelet-free plasma and from the conditioned medium of isolated cardiomyocytes of the left ventricular wall. Size distribution and concentration of the released particles were determined by Nanoparticle Tracking Analysis. The presence of GFP + cardiomyocyte-derived circulating EVs was monitored by flow cytometry and cardiac function was assessed by echocardiography. In LPS-treated mice, systemic inflammation and the consequent cardiomyopathy were verified by elevated plasma levels of TNFα, GDF-15, and cardiac troponin I, and by a decrease in the ejection fraction. Furthermore, we demonstrated elevated levels of circulating small- and medium-sized EVs in the LPS-injected mice. Importantly, we detected GFP+ cardiomyocyte-derived EVs in the circulation of control mice, and the number of these circulating GFP+ vesicles increased significantly upon intraperitoneal LPS administration (P = 0.029). The cardiomyocyte-derived GFP+ EVs were also positive for intravesicular troponin I (cTnI) and muscle-associated glycogen phosphorylase (PYGM). This is the first direct demonstration that cardiomyocyte-derived EVs are present in the circulation and that the increased number of cardiac-derived EVs in the blood reflects cardiac injury in LPS-induced systemic inflammation (SIRS).

Objective: Analyze the diagnostic precision of the qSOFA scale against the SIRS criteria in emergency triage to identify patients with suspected sepsis. Method: Ambispective cohort study in the emergency room of the Costa del Sol Hospital. The study subjects were older than 14 years who attended with suspected or confirmed infection in the years 2017 and 2019. Sociodemographic variables were evaluated, the physiological variables of qSOFA and SIRS, level of triage, attention circuit, activation of sepsis code. Descriptive analysis was performed in a segmented manner according to the year of study. The statistics of the diagnostic tests were described to know the prognostic capacity of qSOFA. Results: 42 patients were recruited in 2017 and 41 in 2019.The mean age of the patients exceeded 75 years on average in both periods. When analyzing the diagnostic effort for activating the sepsis code, 2 patients (4.8%) had completed all the parameters contemplated by SIRS and 1 (2.4%) with qSOFA (p = 1) for each year of study. Conclusions: The lack of records of physiological parameters that contemplate the study scales has made it difficult to determine the diagnostic validity of qSOFA in hospital emergencies. However, the experience and clinical judgment of the triage nurse has contributed to the fact that all the patients studied were correctly classified according to the level of priority and care circuit, guaranteeing early care in sepsis. Objetivo: Analizar la precisión diagnóstica de la escala qSOFA frente a los criterios SIRS en el triaje de urgencias para identificar pacientes con sospecha de sepsis. Método: Estudio de cohorte ambispectivo en urgencias del Hospital Costa del Sol. Los sujetos de estudio fueron mayores de 14 años que acudieron con sospecha o confirmación de infección en los años 2017 y 2019. Se evaluaron variables sociodemográficas, las fisiológicas del qSOFA y SIRS, nivel de triaje, circuito de atención, activación de código sepsis. Se realizó análisis descriptivo de forma segmentada según el año de estudio. Se describieron los estadísticos de pruebas diagnósticas para conocer la capacidad pronóstica de qSOFA. Resultados: Se reclutaron 42 pacientes en 2017 y 41 en 2019.La edad media de los pacientes superó los 75 años de media en ambos períodos. Al analizar el esfuerzo diagnóstico para la activación del código sepsis, 2 pacientes (4,8%) tuvieron cumplimentado todos los parámetros que contempla SIRS y 1 (2,4%) con qSOFA (p=1) por cada año de estudio. Conclusiones: La falta de registros de parámetros fisiológicos que contemplan las escalas del estudio ha obstaculizado determinar la validez diagnóstica de qSOFA en urgencias hospitalarias. Sin embargo, la experiencia y el juicio clínico de la enfermera de triaje han contribuido a que todos los pacientes estudiados fueron correctamente clasificados según el nivel de prioridad y circuito de atención, garantizando una atención precoz en la sepsis.

Background SIRS and qSOFA are two ancillary scoring tools that have been used globally, inside and outside of ICU to predict adverse outcomes of infections such as secondary peritonitis. A tertiary teaching hospital in Uganda uses SIRS outside the ICU to identify patients with secondary peritonitis, who are at risk of adverse outcomes. However, there are associated delays in decision making given SIRS partial reliance on laboratory parameters which are often not quickly available in a resource limited emergency setting. In response to the practical limitations of SIRS, the sepsis-3 task force recommends qSOFA as a better tool. However, its performance in patients with secondary peritonitis in comparison to that of SIRS has not been evaluated in a resource limited setting of a tertiary teaching hospital in a low and middle income country like Uganda. Objective To compare the performance of qSOFA and SIRS scores in predicting adverse outcomes of secondary peritonitis among patients on the adult surgical wards in a tertiary teaching hospital in Uganda. Methods This was a prospective cohort study of patients with clinically confirmed secondary peritonitis, from March 2018 to January 2019 at the Accident and Emergency unit and the adult surgical wards of a tertiary teaching hospital in Uganda. QSOFA and SIRS scores were generated for each patient, with a score of ≥2 recorded as high risk, while a score of Results A total of 153 patients were enrolled. Of these, 151(M: F, 2.4:1) completed follow up and were analysed, 2 were excluded. Mortality rate was 11.9%. Fourty (26.5%) patients had a prolonged hospital stay. QSOFA predicted in-hospital mortality with AUROC of 0.52 versus 0.62, for SIRS. Similarly, qSOFA predicted prolonged hospital stay with AUROC of 0.54 versus 0.57, for SIRS. Conclusion SIRS is superior to qSOFA in predicting both mortality and prolonged hospital stay among patients with secondary peritonitis. However, overall, both scores showed a poor discrimination for both adverse outcomes and therefore not ideal tools.

IntroductionSphingosine-1-phosphate (S1P) is a signaling lipid and crucial in vascular protection and immune response. S1P mediated processes involve regulation of the endothelial barrier, blood pressure and S1P is the only known inducer of lymphocyte migration. Low levels of circulatory S1P correlate with severe systemic inflammatory syndromes such as sepsis and shock states, which are associated with endothelial barrier breakdown and immunosuppression. We investigated whether S1P levels are affected by sterile inflammation induced by cardiac surgery.Materials and MethodsIn this prospective observational study we included 46 cardiac surgery patients, with cardiopulmonary bypass (CPB, n=31) and without CPB (off-pump, n=15). Serum-S1P, S1P-sources and carriers, von-Willebrand factor (vWF), C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) were measured at baseline, post-surgery and at day 1 (POD 1) and day 4 (POD 4) after surgical stimulus.ResultsMedian S1P levels at baseline were 0.77 nmol/mL (IQR 0.61-0.99) and dropped significantly post-surgery. S1P was lowest post-surgery with median levels of 0.37 nmol/mL (IQR 0.31-0.47) after CPB and 0.46 nmol/mL (IQR 0.36-0.51) after off-pump procedures (PDiscussionIn summary, serum-S1P levels are disrupted by major cardiac surgery. Low S1P levels post-surgery may play a role as a new marker for severity of cardiac surgery induced inflammation. Due to well-known protective effects of S1P, low S1P levels may further contribute to the observed prolonged ICU stay and worse clinical status. Moreover, we cannot exclude a potential inhibitory effect on circulating S1P levels by heparin anticoagulation during surgery, which would be a new pro-inflammatory pleiotropic effect of high dose heparin in patients undergoing cardiac surgery.

Introduction The differentiation between systemic inflammatory response syndrome and sepsis is very important as it determines essential treatment decisions, such as selection, initiation, and duration of antibiotic therapy. Objectives We aimed to investigate the diagnostic value of Procalcitonin, Monocyte Chemoattractant Protein-1, soluble Mannose Receptor, Presepsin as early biomarkers of pediatric sepsis in comparison to systemic inflammatory response syndrome in severely ill children. Patients and methods This study included 58 children diagnosed as sepsis (group 1), 24 children with systemic inflammatory response syndrome without infection (group 2), and 50 healthy children as controls (group 3). All the plasma levels of the studied biomarkers were measured and ROC curves were created for all the tested parameters to discriminate between sepsis and SIRS. Results The area under the curve for Monocyte Chemoattractant Protein-1 was 0.926 (0.846-0.927) with sensitivity 100% and specificity 62.5%. The soluble Mannose Receptor had the highest sensitivity (100%), with AUC equals 1(.0.956-1.0) and specificity of 100%. The cut-off values for Procalcitonin, Presepsin, soluble Mannose Receptor, and Monocyte Chemoattractant Protein-1 and were: 0.62 ng/ml, 100 pg/ml, 13 ng/ml and 90 pg/ml, respectively. In septic cases, both soluble Mannose Receptor and Procalcitonin have positive correlations with the severity of sepsis, low Glasgow Coma Scale, ventilatory support, use of inotropic drugs and mortality rate (r = 0.950, 0.812, 0.795, 0.732 and 0.861respectively) for soluble Mannose Receptor and (0.536, 0.473, 0.422, 0.305 and 0.474 respectively) for Procalcitonin. Conclusion Soluble Mannose Receptor, Presepsin, and Monocyte Chemoattractant Protein-1 can be used to differentiate between sepsis and SIRS in critically ill children.

Introduction: The discrimination and calibration accuracy of prediction models tends to become poor over time. The performance of predictive models should be reevaluated periodically. The aim of this study was to reassess the discrimination of the six commonly used models for predicting 28-day mortality in patients with sepsis based on the Sepsis 3.0 criteria. Methods: Patient data were extracted from the fourth edition of the Medical Information Mart for Critical Care (MIMIC IV) database. The systemic inflammatory response syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Logistic Organ Dysfunction System (LODS), and Simplified Acute Physiology Score II (SAPS II) and III (SAPS III) scores were calculated and collected. The area under the receiver operating characteristic curve (AUROC) was used to compare the discrimination abilities of the models using non-parametric Wilcoxon statistics. The Delong method was used to perform pairwise comparisons of the AUROCs of the models. Multiple subgroup analyses for age, body mass index, and sex were performed with regard to the 28-day mortality prediction of the models. Results: A total of 12 691 patients were included. The mean age of the patients was 65.97 ± 15.77 years; 7673 patients (60.50%) were male. The mean SIRS, SOFA, OASIS, SAPS II, LODS, and SAPS III scores were higher in the non-survivor group than in the survivor group. The discrimination for 28-day mortality with the SAPS III (AUROC 0.812, 95% confidence interval (CI) 0.802–0.822) and LODS (AUROC 0.804, 95% CI 0.743–0.765) models was superior to that of the SIRS (AUROC 0.575, 95% CI 0.562–0.589), SOFA (AUROC 0.612, 95% CI 0.598–0.626), OASIS (AUROC 0.753, 95% CI 0.742–0.764), and SAPS II (AUROC 0.754, 95% CI 0.743–0.765) models. The Youden index of the SAPS III model was 0.484, which was the highest among the models. Subgroup analyses showed similar results to the overall results. Conclusions: The discrimination for 28-day mortality with the SAPS III and LODS models was superior to that of the SIRS, SOFA, OASIS, and SAPS II models. The SAPS III model showed the best discrimination capacity for 28-day mortality compared with the other models.

Severe lung inflammation is common in life-threatening coronavirus disease 2019 (COVID-19). This study tested the hypothesis that polymorphonuclear (PMN, neutrophil) phenotype early in the course of disease progression would predict peak lung disease severity in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is increasingly evident that PMN activation contributes to tissue injury resulting from extracellular reactive oxygen species generation, granule exocytosis with release of proteases, neutrophil extracellular trap (NET) formation, and release of cytokines. The current study focuses on PMN activation in response to SARS-CoV-2 infection, specifically, the association between NETs and lung disease. This is a prospective cohort study at an academic medical center with patients enrolled within 4 days of admission at 3 tertiary hospitals: Clements University Hospital, Parkland Memorial Hospital, and Children’s Health in Dallas, TX. Patients were categorized as having minimal or moderate to severe lung disease based on peak respiratory support. Healthy donor controls matched for age, sex, race, and ethnicity were also enrolled. Neutrophils from COVID-19 patients displayed greater IL-8 expression, elastase release, and NET formation as compared with neutrophils from healthy donors. Importantly, neutrophils from COVID-19 patients had enhanced NET formation in the absence of any additional stimulus, not seen in PMN from healthy donors. Moreover, PMA-elicited NET formation by circulating PMN correlated with severity of lung disease. We speculate that neutrophil immuno-phenotyping can be used to predict lung disease severity in COVID-19 patients. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s10753-021-01585-x.

Introduction Insufficient attention has been directed towards urosepsis. Notably, no protocols or clinical decision rules currently exist outlining the appropriate use of imaging in uroseptic patients. The primary objective of our study was to retrospectively evaluate uroseptic emergency department (ED) patients who underwent abdominal imaging, to report the proportion of patients with imaging findings necessitating emergent surgical consultation. Methods We retrospectively identified 1142 patients ≥ 18 years of age that presented to the ED from January 2009 to December 2012 with ICD9 code indicative of urosepsis. All included patients underwent ED-ordered abdominal computerized tomography (CT) or retroperitoneal ultrasound (US). Imaging and urinalysis (UA) results were categorized. We report proportions with odds ratios and 95% confidence intervals. Results Of 1142 patients, we excluded 80 for neg UA, 167 for < 2 SIRS (systemic inflammatory response syndrome), 320 for positive blood cultures, and 37 for incomplete data. This yielded 538 patients which the authors reviewed the results of the CT or US to determine the proportion who required emergent surgical consultation and who underwent surgical or interventional procedure. There were 243 (45%) that had CT or US results that necessitated emergency surgical consultation, of those 180 (33%) underwent surgical or interventional procedure. Similar rates of emergency surgical consultation occurred when sub-divided by positive versus equivocal UA, with 43% and 47%, respectively. Conclusions Forty-five percent of our abdominally imaged urosepsis cohort had imaging findings that necessitated emergent surgical consultation, with a similar proportion in the subset with positive versus equivocal UA. The utility of abdominal imaging in this population should be studied prospectively.

To measure plasma N-terminal fragments of pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) concentration in hospitalized dogs and relate these markers to underlying conditions and evaluate their potential as prognostic markers in dogs with systemic inflammatory response syndrome (SIRS)., info:eu-repo/semantics/published

The report illustrates a case with innumerable disseminated cerebral microbleeds (CMBs) and posterior reversible encephalopathy syndrome (PRES) in a patient with hypertension and sepsis. Both sepsis and uncontrolled hypertension, if severe enough, might lead to PRES and CMBs via multiple mechanisms including endothelial dysfunction, vasoconstriction and coagulopathy. This case highlights their effect might be additive in milder cases.

Objective. To determine the effect of the tinctorial properties of microorganism on the nutritional status and the early outcome in patients with systemic inflammatory response syndrome (SIRS) of bacterial origin. Materials and Methods. A retrospective statistical analysis of case histories of 137 patients with signs and symptoms of SIRS and bacterial infections (caused by a single pathogen) was performed. The following clinical and laboratory parameters of protein-energy undernutrition (PEU) were determined and assessed: body mass index, body weight deficit, total protein, serum albumin, absolute peripheral blood lymphocyte count. Basic metabolic rate indicators (daily energy demand, macronutrient demand) were calculated by indirect calorimetry. The severity of patients at hospital admission is assessed using the SOFA. Results. The statistically significant effect of the tinctorial properties of microorganism on the nutritional status and the early outcome in patients with SIRS of bacterial origin was confirmed. Conclusions. The type of microorganism determined by tinctorial properties has a different effect on patient’s metabolic status. Patients with Gram-negative infections have an increased protein and protein caloric intake. Patients with Gram-positive infections have an increased energy requirements and macronutrient intake. The indicators of the baseline PEU in patients with SIRS of bacterial origin have a significant effect on the disease outcome. The study results stress the importance of nutritional therapy directed to adjustment of daily caloric intake and the percentage of protein calories in patients with systemic bacterial inflammation.

Objective. To compare the Quick Sequential (Sepsis-Related Organ Failure Assessment (qSOFA), National Early Warning Score (NEWS) and Systemic Inflammatory Response Syndrome (SIRS) scores value in predicting poor outcomes in emergency department patients with/without infection in Russia. Materials and Methods. This prospective observational study included data from 270 patients, of whom 132 (48.8%) patients had an infection and 138 (51.2%) did not have an infection. Comparison of areas under the ROC-curves (Receiver Operating Characteristic Curve) for the qSOFA, NEWS and SIRS scores in predicting the composite outcome (death and/or length of intensive care unit stay >1 day) was performed. Results. A total of 24 (8.8%) patients had the composite outcome. For prediction of the composite outcome in patients without infection, the area under the ROC-curve of the NEWS score (0.908 [95% CI 0.847–0.951]) was not significantly different to the area under the ROC-curve of the qSOFA score (0.839 [95% CI 0.767–0.896]), p = 0.255, and was significantly superior to the area under the ROCcurve of the SIRS score (0.776 [95% CI 0.698–0.843]), p = 0.011. The difference between the areas under the ROC-curves of the qSOFA and SIRS scores was not significant (p = 0.379). In the group of patients with infection the area under the ROC-curve of the NEWS score (0.808 [95% CI 0.731–0.872]) was significantly superior to the areas under the ROC-curves of the qSOFA score (0.715 [95% CI 0.630– 0.790]), p = 0.004, and the SIRS score (0.641 [95% CI 0.553–0.722]), p = 0.015. The difference between the areas under the ROC-curves of the qSOFA and SIRS scores was not significant (p = 0.286). Conclusions. The NEWS score has better prognostic value than the qSOFA and SIRS scores in predicting poor outcome in emergency department patients, irrespective of their infection status. The advantage of the NEWS score over the qSOFA score is more significant in patients with infection. Prognostic values of the qSOFA and SIRS scores are comparable in the both patient groups.

Pyrexia is a protective physiologic response of the body against external and internal aggression. Temperature control is safe in and effective in septic shock but remain controversial in sepsis. Treating pyrexia to reduce oxygen consumption appears to have beneficial in cardiac arrest, low cardiac output and acute brain injury. Multiple therapeutic options are available for managing pyrexia, with precise targeted temperaturemanagement. Notably, the use of pharmacotherapy versus surface cooling has not been shown to be advantageous. When these two-therapy failed to control the extra-corporal method of cooling should be started. Renal replacement therapies are not typically indicated for temperature control but, in patients requiring renal support, they contribute to heat loss and participate in pyrexia control. Renal replacement therapies may represent a confounding factor in comparative trials on temperature control.

Kambô is a cleansing ritual involving the application of a toxin produced by the giant leaf frog ( Phyllomedusa bicolor). The Kambô ritual has increasingly been adopted among cancer patients in Europe. Accumulating data indicate various adverse effects. We report another severe adverse reaction to Kambô, a systemic inflammatory response syndrome mimicking disease progression in a patient with cholangiocarcinoma. We describe a systemic reaction to Kambô, manifested as tachycardia, tachypnea, impaired liver cholestatic enzymes, and enlargement of lymphadenopathy mimicking disease progression. The clinical features and onset of symptoms, the rapid reaction, and the lack of other identified causes make the diagnosis of Kambô-induced SIRS highly probable. This case report calls for future studies examining standard oncological care such as chemotherapy, radiotherapy, and immunotherapy in conjunction with alternative therapy. Additionally, greater awareness and physician education should be promoted, encouraging inquiry of oncology patients’ administration of alternative, complementary, and integrative medicine.

Purpose: This study was aimed to compare the quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), and National Early Warning Score (NEWS) scoring systems for diagnosing sepsis and predicting mortality and morbidity. Patients and methods: A prospective study was designed. qSOFA, SIRS, and NEWS scores were calculated at the admission. The diagnosis of sepsis was made with SOFA scoring initially. The morbidity and mortality of the patients were identified during follow-up. Also, the sensitivity, specificity, negative predictive value, and positive predictive value of three scoring systems were calculated. The scoring systems were compared with ROC analysis. Results: A total of 463 patients were evaluated. There were 287 (62.0%) patients diagnosed with sepsis, and septic shock occurred in 64 (13.8%) of patients. Seven-day mortality rate was 8.4% (n = 39), 30-day mortality rate was 18.1% (n = 84). The sensitivity for qSOFA, SIRS, and NEWS for diagnosis of sepsis was 23%, 77%, 58%, and specificity was 99%, 35%, 81% respectively. The sensitivity of the qSOFA, SIRS and NEWS scoring systems for mortality was 39%, 82%, 77% and specificity 91%, 29%, and 64%, respectively. AUROC values for mortality detected as NEWS = 0.772, qSOFA = 0.758, SIRS = 0.542. According to the ROC analysis, the SIRS system was significantly less useful than the qSOFA and NEWS system in the diagnosis of sepsis and mortality (p < 0.0001). Conclusion: NEWS and qSOFA scoring systems have similar prognosis in both diagnosing sepsis and predicting mortality and both are superior to SIRS. (c) 2021 Elsevier Inc. All rights reserved.

Background: The degree of systemic inflammation, reperfusion injury and endothelial activation are potentially important determinants of clinical outcomes in dogs with gastric dilatation volvulus (GDV).Objective: To evaluate plasma concentrations and kinetics of inflammatory markers in dogs with GDV over a time frame of 48 h, and to compare to healthy dogs.Design and Setting: Prospective, observational cohort study in client-owned dogs with GDV.Materials and Methods: Fifteen dogs with GDV and 9 healthy control dogs were enrolled. Plasma concentrations of interleukin (IL)-6, IL-7, IL-8, IL-10, IL-15, IL-18, interferon gamma (IFN-γ), keratinocyte chemotactic-like, monocyte chemotactic protein (MCP)-1, Angiopoietin (Ang)-2, and C-reactive protein (CRP) were measured at admission (prior any therapeutic intervention, (T0), immediately after surgery (T1), 24 ± 4 h (T24), and 48 ± 4 h (T48) post-surgery. Cytokines were measured using multiplex magnetic bead assay. Plasma Ang-2 was measured with a commercial human ELISA test kit validated for dogs.Results: Dogs with GDV had significantly higher plasma concentrations of IFN-γ and IL-10 compared to healthy control dogs at all time points. Concentrations of IL-6 were significantly higher at T1 and T24, concentrations of MCP-1 at T24, and concentrations of CRP at T24 and T48. A significant increase between T0 and T1 was found for IL-6, IL-10, and CRP, between T1 and T24 for IL-8, IFN-γ, MCP-1, and CRP, and between T24 and T48 for IL-15, Ang-2, and CRP. A significant decrease between T0 and T1 was found for IL-7, IL-8, IL-15, IL-18, and Ang-2; between T1 and T24 for IL-6 and KC-like; and between T24 and T48 for IL-6.Conclusion: In GDV dogs, a mild pro-inflammatory reaction was present at admission, which peaked immediately after and up to 24 h post-surgery, mainly represented by IL-6, IFN-γ, MCP-1, and CRP, and which decreased at T48. In addition, the anti-inflammatory IL-10 was increased in GDV dogs at all time points.

BackgroundMost of the maxillofacial infections are bacterial infections, and there is a possibility that systemic infections occur by maxillofacial infections. The aim of this study was to investigate the diagnostic value of procalcitonin in patients with odontogenic bacterial infections of the maxillofacial region.MethodsWe enrolled sixty patients, who were admitted with odontogenic maxillofacial infection from September 2018 to March 2020. White blood cell counts, C-reactive protein, and procalcitonin concentrations were evaluated. Sixty patients were classified into two groups, sepsis and non-sepsis groups, based on systemic inflammatory response syndrome. A Studentttest was performed to statistically analyze the difference in inflammatory markers between sepsis and non-sepsis groups.ResultsThe mean procalcitonin values on admission were 7.24 ng/mL (range, 0.09–37.15 ng/mL) and 0.40 ng/mL (range, 0.02–4.94 ng/mL) in the sepsis group and non-sepsis group, respectively. The procalcitonin values between the two groups showed a significant difference (P< 0.05). The area under the curve of procalcitonin was 0.927 (P< 0.001), and the cutoff value of procalcitonin that maximizes the area under the curve was calculated to be 0.87 ng/mL.ConclusionsAccording to our study, routine laboratory tests have insufficient accuracy in diagnosing sepsis syndrome. Therefore, it is strongly recommended to perform the procalcitonin test in patients with maxillofacial infection in addition to the conventional laboratory tests to diagnose the systemic inflammatory condition of the patients.

Background The diagnostic and prognostic utility of various sepsis scores varied among different cohorts and settings. Methods A prospective cohort study in adult patients with sepsis at Siriraj Hospital (Bangkok, Thailand) was conducted during January to July 2019. The performance of sepsis assessments, including systemic inflammatory response syndrome (SIRS) score, sequential organ failure assessment (SOFA) score, quick sepsis-related organ failure assessment (qSOFA) score, modified early warning score (MEWS), and national early warning score (NEWS), for sepsis detection and mortality prediction were compared with agreement between 2 infectious disease (ID) specialists to determine their sepsis and septic shock status as the reference standard. Results Among the 470 subjects included in this study, 206 patients (43.8%) were determined by 2 ID specialists to have sepsis. Systemic inflammatory response syndrome ≥2, qSOFA ≥2, and NEWS ≥5 yielded the highest sensitivity (93.2%), specificity (81.3%), and accuracy (72.6%), respectively, for detecting sepsis. The SIRS ≥2 had the highest sensitivity (97.8%), whereas qSOFA ≥2 had the highest specificity (61%) and accuracy (69.7%) for predicting mortality among sepsis patients. Receiver operating characteristic (ROC) curve showed MEWS to have the highest discriminatory power for sepsis detection (area under the ROC curve [AUROC], 0.79; 95% confidence interval [CI], 0.74–0.83), whereas SOFA had the highest discriminatory power for predicting hospital mortality (AUROC, 0.76; 95% CI, 0.69–0.79). Conclusions The NEWS ≥5 and qSOFA ≥2 were the most accurate scoring systems for sepsis detection and mortality prediction, respectively. Each scoring system is useful for different specific purposes relative to early detection and mortality prediction in sepsis patients., NEWS ≥5 and qSOFA ≥2 were the most accurate scoring systems for sepsis detection and mortality prediction, respectively. Each scoring system is useful for different specific purposes relative to early detection and mortality prediction in sepsis.

Background Studies comparing the microbiological profiles among sepsis patients identified with either Sequential Organ Failure Assessment (SOFA) score or systemic inflammatory response syndrome (SIRS) criteria are limited. The aim was to examine if there are differences in the microbiological findings among septic patients identified by Sepsis-3 criteria compared to patients identified by the previous sepsis criteria, SIRS, and without organ failure. A secondary purpose was to examine if we could identify microbiological characteristics with increased risk of 28-day mortality. Methods Prospective cohort study of all adult (≥ 18 years) patients admitted with sepsis to the Emergency Department of Slagelse Hospital, Denmark from 1st October 2017 to 31st March 2018. Information regarding microbiological findings was obtained via linkage between a sepsis database and the local microbiological laboratory data system. Data regarding 28-day mortality were obtained from the Danish Civil Registration System. We used logistic regression to estimate the association between specific microbiological characteristics and 28-day mortality. Results A total of 1616 patients were included; 466 (28.8%; 95% CI 26.6%-31.1%) met SOFA criteria, 398 (24.6%; 95% CI 22.5–26.8%) met SIRS criteria. A total of 127 patients (14.7%; 95% CI 12.4–17.2%) had at least one positive blood culture. SOFA patients had more often positive blood cultures compared to SIRS (13.9% vs. 9.5%; 95 CI on difference 0.1–8.7%). Likewise, Gram-positive bacteria (8.6% vs. 2.8%; 95 CI on difference 2.8–8.8%), infections of respiratory origin (64.8% vs. 57.3%; 95 CI on difference 1.0–14%), Streptococcus pneumoniae (3.2% vs. 1.0%; 95% CI on difference 0.3–4.1) and polymicrobial infections (2.6% vs. 0.3% 95 CI on difference 0.8–3.8%) were more common among SOFA patients. Polymicrobial infections (OR 3.70; 95% CI 1.02–13.40), Staphylococcus aureus (OR 6.30; 95% CI 1.33–29.80) and a pool of “other” microorganisms (OR 3.88; 95% CI 1.34–9.79) in blood cultures were independently associated with mortality. Conclusion Patients identified with sepsis by SOFA score were more often blood culture-positive. Gram-positive pathogens, pulmonary tract infections, Streptococcus pneumoniae, and polymicrobial infections were also more common among SOFA patients. Polymicrobial infection, Staphylococcus aureus, and a group of other organisms were independently associated with an increased risk of death.

Accurate and fast diagnostic tests for sepsis are important to improve patient outcomes. This thesis discusses different diagnostic approaches for sepsis. There exists no perfect gold standard for sepsis, which complicates the development of an adequate and consistent definition. We discuss how different applications of the sepsis definitions result in the selection of different patient populations within research. Besides we validate the Septicyte LAB test, which is an RNA-signature that was developed to distinguish infectious from non-infectious inflammation. We validated the test in two patient cohorts and discuss the diagnostic performance of this test in an Intensive Care Setting. Furthermore, we evaluated if routine blood cultures upon ICU admission could improve the diagnosis of bloodstream infections, also when an infection is not immediately evident. At last we devote one chapter on the description of a cohort with E. Coli bacteremias and its serotypes. Currently, an O-polysaccharide vaccine is under development which targets the ten most common E. coli serotypes, and we describe the potential coverage of this vaccine in an ICU population. This thesis was written within the framework of the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project. This database contains detailed data and biorepository material and was set up to improve our understanding of sepsis.

Objectives The aim of this study was to systematically assess the accuracy of circulating microRNAs (miRNAs) as a promising biomarker for sepsis via a meta-analysis. Methods PubMed, Cochrane Library, Embase, Web of Science, Scopus, and Ovid databases were searched up to April 3, 2020. The Quality in Prognostic Studies (QUADAS-2) tool was used to assess methodological quality. The pooled sensitivity (Sen), specificity (Spe), positive or negative likelihood ratios (PLR or NLR), diagnostic odds ratio (DOR), curve, and area under the curve (AUC) were calculated with 95% confidence interval (95% CI). The overall accuracy (OA) of miRNAs, procalcitonin (PCT), and C-reactive protein (CRP) was analyzed by the chi-square test. Results A total of 22 records were eligible for systematic review, including 2210 sepsis, 426 systemic inflammatory response syndrome (SIRS), and 1076 healthy controls (HC). The pooled Sen, Spe, and DOR of miRNAs were 0.80 (95% CI 0.75–0.83), 0.85 (95% CI 0.80–0.89), and 22 (15–32), respectively. The DOR of PCT and CRP were 17 (95% CI 4–68) and 7 (95% CI 1–48), respectively. The OA value of miRNAs (79.02%) and PCT (76.95%) were higher than CRP (61.22%) (P < 0.000). The subgroup analysis indicated that miRNAs in adults, serum type, downregulation of miRNA expression, criteria of Sepsis-3, internal reference of non-U6, and dysregulation expression of miR-223 had superior diagnostic accuracy. In addition, there was no significant publication bias among the included studies. Fagan’s nomogram showed valuable clinical utility. Conclusions Our meta-analysis indicated that the level of circulating miRNAs, particularly the miR-223, could be used as an indicator for sepsis.

Aims: There is no gold standard to predict outcome in acute decompensated heart failure (ADHF). Several scores for mortality prediction of patients with ADHF have been developed and mostly consist of complex regression models. None of these models has been widely adopted by clinicians. The quick SOFA score (qSOFA) is a simple score including three parameters (systolic blood pressure ≤ 100 mmHg, respiratory rate ≥22 breathes/min, and GCS

Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS) of non-infectious origin. Sepsis presents with a range of pathophysiological and genetic features which make clinical differentiation from SIRS very challenging. This may reflect a poor understanding of the key gene inter-activities and/or pathway associations underlying these disease processes. Improved understanding is critical for early differential recognition of sepsis and SIRS and to improve patient management and clinical outcomes. Judicious selection of gene biomarkers suitable for development of diagnostic tests/testing could make differentiation of sepsis and SIRS feasible. Here we describe a methodologic framework for the identification and validation of biomarkers in SIRS, sepsis and septic shock patients, using a 2-tier gene screening, artificial neural network (ANN) data mining technique, using previously published gene expression datasets. Eight key hub markers have been identified which may delineate distinct, core disease processes and which show potential for informing underlying immunological and pathological processes and thus patient stratification and treatment. These do not show sufficient fold change differences between the different disease states to be useful as primary diagnostic biomarkers, but are instrumental in identifying candidate pathways and other associated biomarkers for further exploration.

The discovery of inflammasomes has enriched our knowledge in the pathogenesis of multiple inflammatory diseases. The NLR pyrin domain-containing protein 3 (NLRP3) has emerged as the most versatile and well-characterized inflammasome, consisting of an intracellular multi-protein complex that acts as a central driver of inflammation. Its activation depends on a tightly regulated two-step process, which includes a wide variety of unrelated stimuli. It is therefore not surprising that the specific regulatory mechanisms of NLRP3 inflammasome activation remain unclear. Inflammasome-mediated inflammation has become increasingly important in acute pancreatitis, an inflammatory disorder of the pancreas that is one of the fatal diseases of the gastrointestinal tract. This review presents an update on the progress of research into the contribution of the NLRP3 inflammasome to acute pancreatic injury, examining the mechanisms of NLRP3 activation by multiple signaling events, the downstream interleukin 1 family of cytokines involved and the current state of the literature on NLRP3 inflammasome-specific inhibitors., This study was supported by grant from Ministerio de Ciencia e Innovación, reference PID2019-104130RB-I00 awarded to E.F.-P.

Neutrophile Granulozyten (PMNs) bilden eine essentielle Komponente des angeborenen Immunsystems, sie wirken hauptsächlich proinflammatorisch. Granulozyten kommen nicht homogen in Funktionen und Eigenschaften vor, wodurch der Begriff „neutrophile Heterogenität“ geprägt wurde. Eine Subpopulation stellen Granulozyten geringer Dichte, sog. „Low-density-Granulocytes“ (LDGs), dar. Eine erhöhte Anzahl an LDGs konnten u.a. in Autoimmunerkrankungen und Sepsis nachgewiesen werden, ihnen wurden sowohl pro- als auch antiinflammatorische Eigenschaften zugeschrieben. Im systemischen Lupus erythematodes (SLE) korreliert der LDG-Anteil mit der Krankheitsaktivität und der Prävalenz von Vaskulitiden. Auch bei Sepsis konnten Zusammenhänge zwischen LDGs und Krankheitsschwere gezeigt werden. Die Zielsetzung dieser Arbeit ist es, die Zusammenhänge zwischen LDGs und systemischen Vaskulitiden sowie zwischen LDGs und systemischen Inflammationen näher zu beleuchten. Die genaue Charakterisierung und Quantifizierung von LDGs soll dabei auch Hinweise auf den bisher unklaren Ursprung von LDGs liefern. Es wurden Vollblutproben von Testpersonen mit systemischen Vaskulitiden und systemischer Inflammation gewonnen und mit denen einer gesunden Kontrollkohorte verglichen. Hierfür erfolgte die Trennung von PMNs und PBMCs, welche LDGs enthalten, mittels Dichtegradientenzentrifugation. Beide Ansätze wurden danach mit fluoreszenzgekoppelten Antikörpern gegen die Oberflächenantigene CD14, CD16, CD86, CD66b, CD177 und HLA-DR gefärbt. Abschließend erfolgte die durchflusszytometrische Messung der Rezeptorexpression und die statistische Auswertung der Daten. Es konnte demonstriert werden, dass LDGs in systemischen Vaskulitiden und Inflammationen vermehrt vorkommen. Gegenüber PMNs kommt es auf LDGs generell zu einer gesteigerten Expression von CD14, CD16 und HLA-DR. Das Vorliegen von systemischen Vaskulitiden und Inflammationen resultiert in einer verminderten Expression von CD16, zudem ist das Vorkommen CD14-positiver LDGs in systemischen Vaskulitiden erhöht. In systemischen Inflammationen liegt eine negative Korrelation zwischen LDG-Anteil und CRP, Krankheitsaktivität sowie Mortalität vor. In vitro Stimulationen von Vollblut gesunder Probanden führten zu einer Erhöhung des LDG-Anteils. 10 Ein erhöhter LDG-Anteil ist ein Merkmal systemischer Vaskulitiden und Inflammationen und daher Hinweis auf erhöhte Immunaktivität. Hohe LDG-Anteile stellen sich in systemischen Inflammationen als günstiger Marker für Krankheitsschwere und Mortalität dar, damit könnte der LDG-Anteil einen Wert als Prognosemarker haben. Die erhöhte Expression von CD14, CD16 und HLA-DR scheint ein inhärentes Merkmal von LDGs gegenüber PMNs zu sein, sie tritt in allen Testgruppen unabhängig auf. Dahingehend weisen LDGs Ähnlichkeit zu Monozyten auf. In systemischen Inflammationen und Vaskulitiden zeigt sich eine geringere Expression von CD16 auf LDGs, dies kann als Hinweis auf eine immunsuppressive Funktion gesehen werden. Durch in vitro-Stimulation von Vollblut lässt sich ein erhöhter LDG-Anteil provozieren. Dies spricht dafür, dass es sich bei LDGs nicht um Vorläuferzellen, sondern um ausgereifte, eventuell degranulierte Granulozyten handelt., Neutrophil granulocytes (PMNs) are an essential in innate immunity, they act primarily proinflammatory. Granulocytes are not homogeneous in functions and characteristics, therefore the term "neutrophilic heterogeneity" has been created. There is a distinct subpopulation of low-density granulocytes (LDGs). LDGs were isolated in autoimmune diseases and sepsis, they have been attributed both pro- and anti-inflammatory characteristics. In systemic lupus erythematosus (SLE), the proportion of LDG correlates with disease activity and the prevalence of vasculitis. In sepsis associations between LDGs and disease severity were found. The aim of this work is to analyse the relationships between LDGs and systemic vasculitis as well as between LDGs and systemic inflammations. The exact characterization and quantification of LDGs should also provide information on the unclear origin of LDGs. Whole blood samples of test persons with systemic vasculitis and systemic inflammation were taken and compared with those from healthy controls. Density gradient centrifugation has been used to separate PMNs from PBMCs, which contain LDGs. Both were stained with fluorescently labelled antibodies against surface antigens of CD14, CD16, CD86, CD66b, CD177 and HLA-DR. Then the receptor expression was measured by flow cytometry. The resulting data were statistically analysed. We found increased LDG levels in patients with systemic vasculitis and inflammation. Compared to PMNs, LDGs generally show increased expressions of CD14, CD16 and HLA-DR. The presence of systemic vasculitis and inflammation results in decreased expressions of CD16. The incidence of CD14-positive LDGs in systemic vasculitis is increased. In systemic inflammations, a negative correlation between LDG level and CRP, disease activity, and mortality was found. In vitro stimulation of whole blood from healthy individuals caused increased LDG levels. Increased LDG levels are a characteristic of systemic vasculitis and inflammation, so it could indicate increased immune activity. High LDG levels in systemic inflammations represent a more favourable prognosis regarding disease severity and mortality, therefore the LDG level could be a potential prognostic marker. The increased expression of CD14, CD16 and HLA-DR appears to be an inherent feature of LDGs over PMNs, 12 occurring independently in all test groups. In this regard, LDGs have similarities to monocytes. In systemic inflammations and vasculitis, lower expression of CD16 were shown on LDGs, which may be considered an indication of immunosuppressive functions. In vitro stimulation of whole blood can provoke higher LDG levels. This indicates that LDGs are not progenitor cells but mature, possibly degranulated granulocytes.

Systemic diseases characterized by elevated levels of C-reactive protein (CRP), such as sepsis or systemic inflammatory response syndrome, are usually associated with hardly controllable haemodynamic instability. We therefore investigated whether CRP itself influences blood pressure and heart rate. Immediately after intravenous injection of purified human CRP (3.5 mg CRP/kg body weight) into anesthetized rabbits, blood pressure dropped critically in all animals, while control animals injected with bovine serum albumin showed no response. Heart rate did not change in either group. Approaching this impact on a cellular level, we investigated the effect of CRP in cell lines expressing adrenoceptors (CHO-α1A and DU-145). CRP caused a Ca(2+)signaling being dependent on the CRP dose. After complete activation of the adrenoceptors by agonists, CRP caused additional intracellular Ca(2+)mobilization. We assume that CRP interacts with hitherto unknown structures on the surface of vital cells and thus interferes with the desensitization of adrenoceptors.

Contains fulltext : 225495.pdf (Publisher’s version ) (Open Access) BACKGROUND: The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, e.g., using inulin or iohexol, is laborious and not feasible in daily practice. Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the "true GFR" measured using a gold standard method: iohexol plasma clearance. METHODS: Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFRMDRD), Endogenous Creatinine Clearance (GFRECC), and iohexol plasma clearance (GFRiohexol) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay. RESULTS: The eGFRMDRD and GFRECC correlated with the GFRiohexol (R = 0.82, P

The purpose of the study was to assess the prognostic performances, in terms of in-hospital mortality, of the quick sequential organ failure assessment (qSOFA) score and the systemic inflammatory response syndrome (SIRS) criteria applied to patients with suspected infection outside the ICU, and to critically reappraise the results and the clinical impact of the SEPSIS-3 study and of the subsequent trials. We performed bivariate meta-analysis, evaluation of the Bayesian post-test probabilities of death, and computation of the unidentified deaths for every 1000 screened cases (UDS1000). The use of qSOFA for screening instead of the SIRS implies a relevant increase in the UDS1000. However, this difference appears far smaller in the SEPSIS-3 study, largely due to an underestimation of SIRS sensitivity. The increment in the pre-test probability of death implied by a positive qSOFA is higher than that implied by a positivity of the SIRS. However, the included studies use highly variable definitions of "suspected sepsis" and carry very high levels of heterogeneity. SIRS overperforms qSOFA as a rule-out tool for mortality, while qSOFA shows a higher rule-in power. However, the evident lack of consistency across the published studies undermines the significance of both the meta-analytic approach and the reproducibility of the outcomes, and demands for a standardized definition of the target population.

Alassan Kouamé Mahassadi,1 Justine Laure Konang Nguieguia,1 Henriette Ya Kissi,1 Anthony Afum-Adjei Awuah,2 Aboubacar Demba Bangoura,1 Stanislas Adjeka Doffou,1 Alain Koffi Attia1 1Medicine and Hepatogastroenterology Unit, Centre Hospitalier et Universitaire de Yopougon, Abidjan, Côte d’Ivoire; 2Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana Background: Systemic inflammatory response syndrome (SIRS) and model for end-stage liver disease (MELD) predict short-term mortality in patients with cirrhosis. Prediction of mortality at initial hospitalization is unknown in black African patients with decompensated cirrhosis.Aim: This study aimed to look at the role of MELD score and SIRS as the predictors of morbidity and mortality at initial hospitalization.Patients and methods: In this retrospective cohort study, we enrolled 159 patients with cirrhosis (median age: 49 years, 70.4% males). The role of Child–Pugh–Turcotte (CPT) score, MELD score, and SIRS on mortality was determined by the Kaplan–Meier method, and the prognosis factors were assessed with Cox regression model.Results: At initial hospitalization, 74.2%, 20.1%, and 37.7% of the patients with cirrhosis showed the presence of ascites, hepatorenal syndrome, and esophageal varices, respectively. During the in-hospital follow-up, 40 (25.2%) patients died. The overall incidence of mortality was found to be 3.1 [95% confidence interval (CI): 2.2–4.1] per 100 person-days. Survival probabilities were found to be high in case of patients who were SIRS negative (log-rank test= 4.51, p=0.03) and in case of patients with MELD score ≤16 (log-rank test=7.26, p=0.01) compared to the patients who were SIRS positive and those with MELD score >16. Only SIRS (hazard ratio (HR)=3.02, [95% CI: 1.4–7.4], p=0.01) and MELD score >16 (HR=2.2, [95% CI: 1.1–4.3], p=0.02) were independent predictors of mortality in multivariate analysis except CPT, which was not relevant in our study. Patients with MELD score >16 experienced hepatorenal syndrome (p=0.002) and encephalopathy (p=0.001) more frequently than that of patients with MELD score ≤16. SIRS was not useful in predicting complications.Conclusion: MELD score and SIRS can be used as tools for the prediction of mortality in black African patients with decompensated cirrhosis. Keywords: MELD, SIRS, cirrhosis, mortality, Africa

Background The original equine sepsis score provided a method of identifying foals with sepsis. New variables associated with sepsis have been evaluated, but the sepsis score has not been updated. Objectives To evaluate the sensitivity and specificity of 2 updated sepsis scores and the systemic inflammatory response syndrome (SIRS) criteria in regard to detecting sepsis in foals. Animals Two-hundred and seventy-three ill foals and 25 healthy control foals. Methods Historical, physical examination, and clinicopathologic findings were used to calculate the original sepsis score and 2 updated sepsis scores. SIRS criteria were also evaluated. Sepsis scores and positive SIRS scores were statistically compared to foals with sepsis. Results One-hundred and twenty-six foals were septic and 147 sick-nonseptic. The original and updated sepsis scores were significantly higher in septic foals as compared to sick-nonseptic and healthy foals. The sensitivity and specificity of the updated sepsis scores to predict sepsis were not significantly better than those of the original sepsis score. One-hundred and twenty-seven of 273 (46.5%) foals met the original SIRS criteria and 88/273 (32%) foals met the equine neonatal SIRS criteria. The original SIRS criteria had similar sensitivity and specificity for predicting sepsis as did the 3 sepsis scores in our study. Conclusions and clinical importance The updated sepsis scores did not provide improved ability in predicting sepsis. Fulfilling the original SIRS criteria provided similar sensitivity and specificity in predicting sepsis as the modified sepsis score and might serve as a diagnostic aid in identifying foals at risk for sepsis.

In this paper, a deep belief network (DBN) is proposed as an effective method to predict the mortality of patients within the first 72 h of visiting an emergency room (ER), i.e., 72-h mortality. Previously, physicians used the quick sequential organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) to determine the survival probability of patients. Although such prediction methods are convenient, there is room for improvement in their accuracy. To demonstrate the effectiveness of our proposed method, original data from a hospital was used. A single-center retrospective study was performed regarding adult ER patients who were admitted between January 2007 and December 2013 with an infection. The qSOFA and SIRS scores were calculated using primary vital signs and laboratory data. A DBN was then used to predict patients’ survival rates and to choose 65 clinical variables as an input. Utilizing the DBN, the joint probability distribution of the 65 clinical variables was calculated, and valid solutions of the decreased features were achieved. Results indicate that the DBN can predict the 72-h mortality of ER septic patients more accurately than the qSOFA or SIRS. This paper aims to design an effective prediction system to assist clinicians in their diagnosis using a DBN for early risk stratification and intervention.

Subjects and methods. The mult i-c enter, prospective, and observational trial was conducted. The following data were analyzed in the patients admitted to intensive care wards: number of q SOFA scores, the presence of SIRS criteria, levels of lactate, procalcitonin, C-r eactive protein in blood, the presence of sepsis according to Sepsi s-3 criteria. The value of q SOFA scores, SIRS criteria, and biomarkers for sepsis diagnostics was assessed by means of RO C -a nalysis. Results. The following areas under RO C -c urves were defined during diagnostics of sepsis in the patients in intensive care wards: q SOFA – 0.679 (95% CI 0.646–0.712); SIRS – 0.714 (95% CI 0.682–0.745), p = 0.099; when q SOFA exceeding 1 score: procalcitonin – 0.788 (95% CI 0.689–0.867), C-r eactive protein – 0.787 (95% CI 0.688–0.866), p = 0.970. Conclusion. q SOFA score is compatible with SIRS criteria for diagnostics of sepsis among the patients in intensive care wards. q SOFA score is highly sensitive, but it is of low specificity for sepsis diagnostics. Should there be at least 1 score of q SOFA , it is recommended to test levels of procalcitonin or C-r eactive protein in order to increase the specificity of this score for diagnostics of sepsis.

The objective of the study : to define the informative value of q SOFA score in the prediction of sepsis outcomes in the patients admitted to the intensive care wards of medical units in the Russian Federation. Subjects and methods. The mult i-c enter, prospective, and observational trial was conducted. The following data were analyzed in the patients admitted to intensive care wards: number of q SOFA and SOFA scores, the presence of SIRS criteria, levels of lactate, and the outcome of the admission to the intensive care wards. The informative value of different scores and lactate level was analyzed using RO C -a nalysis. Results. The following areas under RO C -c urves were defined for prediction of a lethal outcome in the patients with sepsis: q SOFA – 0.644 (95% CI 0.593–0.693); SOFA – 0.731 (95% CI 0.683–0.776); SIRS – 0.508 (95% CI 0.456–0.560); [q SOFA + lactate ≥ 4 mmo l/L ] – 0.713 (95% CI 0.646–0.774). Conclusion. To predict a lethal outcome in the patients with sepsis admitted to intensive care wards, q SOFA surpasses SIRS criteria, but it is not as good as SOFA score. The informative value of the prediction model [q SOFA +lactate ≥ 4 mmo l/L ] surpasses q SOFA score in the prediction of the outcome in sepsis patients, and it is as good as SOFA score.

We conducted a surveillance epidemiology and end results (SEER)‐based analysis to describe the incidence and characteristics of second primary acute lymphoblastic leukemia (sALL) among adults (≥18 years) with a history of primary malignancies (1M). Standardized incidence ratios (SIRs) of sALL cases were calculated by site and 1M stage. We also evaluated the differences in 5‐year sALL survival by age, site, and extent of 1M, latency of sALL after 1M, and evidence of underlying racial/ethnic disparity. We identified 10,956 patients with de‐novo/primary acute lymphoblastic leukemia (1ALL) and 772 with sALL. Women (49.1% vs. 42.9%), white patients (72.0% vs. 59.5%), older patients (58.8% vs. 25.2%; age ≥65 years), and patients diagnosed between 2003 and 2012 (66.8% vs. 53.9%) had a higher proportion of sALL compared with 1ALL. There was a significantly inferior median 5‐year survival for sALL patients compared to 1ALL (6 vs. 15 months; HR 1.20, 95% CI 1.10–1.31, P

Background: Since the first publication, of 2016, Sepsis-3 definitions have not been universally accepted, rather, they have become a source of controversy. Because clinical and laboratory parameters used had been derived mainly from patients hospitalized in United States’ Intensive Care Units (ICU). Purpose: the aim of this study was to evaluate the performance of the Sepsis‑3 definitions for the prediction of ICU-mortality in a Tunisian ICU population as compared to 2003 Consensus Definitions (Sepsis-2 definitions) Methods: It was a retrospective study conducted in an 18-bed medical surgical intensive care unit at the military hospital of Tunis (Tunisia). From January 2012 to January 2016, all patients admitted to the ICU for sepsis, severe sepsis or septic shock as defined according to 2003 Consensus Definitions (Sepsis-2 consensus) were eligible for this study. The new Sepsis-3 definition was secondly used to classify included patients. The primary area of interest was ICU mortality defined as death before ICU discharge Results: A total of 1080 patients were included during the recruitment period. . When the Sepsis-2 definitions were used there had been a difference in mortality only between septic shock and sepsis patients. While Sepsis-3 definitions show that mortality increased from 16 % among no-dysfunction-infected patients to 30 % among patients with qSOFA ≥ 2 and 44% or 46% for sepsis or septic shock patients, respectively. Conclusions: Sepsis-3 was better than sepsis-2 definitions at stratifying mortality among septic patients admitted to an ICU of a middle income country (Tunisia).

A compact spurious free, quad-band, band-pass filter (BPF) having independently controllable and widely spaced frequency bands is proposed. The design consists of a basic BPF to which the authors introduce transmission zeros (TZs) in the frequency response using T-shaped stubs loaded with a modified ring resonator (MRR) thereby creating the four passbands. This design results in very high band-to-band isolation. The TZs are obtained by transversal signal path cancellation and also due to the loaded T-shaped stubs. The BPF consists of a stepped impedance low-pass filter which provides spurious free out of band characteristics up to 20 GHz. By changing the tapping position of the MRR, the frequencies of the TZs can be adjusted to get the desired pass band characteristics. The proposed quad-band filter provides low-insertion loss (

Myocardial calcification is a rare and life-threatening condition that is a recognised complication of ischaemic heart disease, cardiac surgery, rheumatic fever and myocarditis. It is distinct from...