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Background: Extracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC). Methods: Patients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1β, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection. Results: Patients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2–4.5 vs. CECC 4.6 pg/mL; CI 3.4–5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes. Conclusions: Lower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study. Clinical registration number: NCT03216720. [ABSTRACT FROM AUTHOR]

As the mortality of severe acute pancreatitis (SAP) is significantly higher than those with mild or moderate severity, it is of clinical significance to identify patients most likely to develop SAP at the time of emergency department (ED) presentation. The aim of this study was to compare the performance of the Bedside Index for Severity in Acute Pancreatitis (BISAP) and the Emergency Department SpO 2 , Age and SIRS (ED-SAS) scoring systems as early risk assessment tools for identifying patients at high-risk of developing SAP. We retrospectively reviewed adult patients with AP presented to ED between January 2019–September 2022. We calculated the scores of each patient with the parameters of the initial data. The primary outcome was SAP. The secondary outcomes were 30-day mortality, intensive care admission, and identifying low-risk patients without complications. Of 415 patients, 34 (8.2%) developed SAP and 15 (3.6%) died. With regard to predicting SAP, BISAP and ED-SAS scores had similar discriminative ability with area under the curves (AUCs) of 0.84 (95% confidence interval [CI]:0.80–0.88) and 0.83 (95% CI:0.79–0.86), respectively (p = 0.642). At a cut-off score of ≥2 for SAP, sensitivity/specificity values were 73.5%/82.4% for BISAP, 76.5%/83.2% for ED-SAS. BISAP and ED-SAS scores of ≥3, yielded sensitivity/specificity values of 50%/95.8% and 35.3%/95.5%, respectively. BISAP and ED-SAS were also similar in predicting mortality (AUCs of 0.92 vs. 0.90, respectively) and intensive care unit admission (AUCs 0.91 vs. 0.91). The BISAP and ED-SAS scores performed similarly in predicting SAP, mortality, and intensive care unit admission. As an easily calculated tool early in the ED, ED-SAS may be helpful in disposition decisions for emergency physicians. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationships of serum monocyte chemotactic protein-1 (MCP-1) level and T helper cells 17 (Th17）/T regulatory cells (Treg) cellular balance with chronic obstructive pulmonary disease (COPD) complicated with systemic inflammatory response syndrome (SIRS) in the elderly. Methods Eighty-two elderly patients with COPD combined with SIRS (SIRS group) were selected, and elderly patients with COPD alone (non-SIRS group) were selected at the case-control ratio of 1∶1. Serum MCP-1 levels and the ratio of Th17 and Treg were measured by enzyme-linked immunosorbent assay and flow cytometry. Logistic regression was used to analyze the factors for COPD com‑ plicated with SIRS in the elderly, and ROC curves were used to analyze the predictive value of serum MCP-1 and peripheral blood Th17/Treg for COPD complicated with SIRS in the elderly. Results Compared with the non-SIRS group, serum MCP-1 and peripheral blood Th17 and Th17/Treg increased, and the peripheral blood Treg ratio decreased in the SIRS group (all P<0. 05）. Th17 (OR=3. 640，95% CI：1. 929 to 6. 867）, MCP-1 (OR=1. 035，95% CI：1. 016 to 1. 054）, elevated Th17/Treg (OR=3. 612，95% CI：1. 835 to 7. 107) were independent risk factors for COPD complicated with SIRS in the elderly, and elevated Treg (OR=0. 651，95% CI：0. 467 to 0. 907) was an independent protective factor (P< 0. 05）. The area under the curve of serum MCP-1 combined with peripheral blood Th17/Treg in predicting COPD complicated with SIRS in the elderly was 0. 890 (95% CI：0. 832 to 0. 934）, which was greater than that of serum MCP-1［0. 786 (95% CI：0. 715 to 0. 846）］ and peripheral blood Th17/Treg ［0. 815 (95% CI：0. 747 to 0. 871）］ alone, respectively (both P<0. 05）. Conclusion The elevated serum MCP-1 level and Th17/Treg cellular imbalance were independently associated with COPD complicated with SIRS in the elderly, and serum MCP-1 combined with peripheral blood Th17/Treg had a high predictive value for COPD complicated with SIRS in the elderly [ABSTRACT FROM AUTHOR]

The systemic inflammatory response syndrome can occur due to an inflammatory reaction to the release of cytokines, and it has been linked to the circulation of pro- and anti-inflammatory cytokines. The cardiopulmonary bypass (CPB) system is known to activate numerous inflammatory pathways. Applying CPB in large animals for an extended period may be useful as a controlled experimental model for systemic inflammatory responses. The authors hypothesized that 0.2 mg/kg NuSepin® would inhibit CBP-induced proinflammatory cytokine release, and attenuate CPB-induced vasoplegia. CPB was maintained for 2 h in 8 male Yorkshire pigs. Ten ml of saline was administered intravenously to the control group, while the study group received 10 ml of NuSepin® (0.2 mg/kg), before start of CPB. Blood samples were collected at four different time points to evaluating the level of cytokine (TNF-α, IL-1β, IL-6, IL-8) release during and after CBP. All vital signals were recorded as continuous waveforms using the vital recorder®. Our study demonstrated that IL-6 increased in both groups during CPB remained unchanged. However, in the Nusepin group, IL-6 levels rapidly decreased when CPB was stopped and the proinflammatory reaction subsided. Furthermore, the dose of norepinephrine required to maintain a mean pressure of 60 mmHg was also lower in the Nusepin group. [ABSTRACT FROM AUTHOR]

Background: Premature newborns are at a significant risk for Systemic Inflammatory Response Syndrome SIRS, a condition associated with high morbidity and mortality. This study aimed to evaluate the predictive and diagnostic capability of laboratory markers like Neutrophil to Lymphocyte Ratio (NLR), derived Neutrophil to Lymphocyte Ratio (dNLR), Platelet-to-Lymphocyte Ratio (PLR), and Neutrophil-to-Lymphocyte-to-Platelet Ratio (NLPR) in diagnosing SIRS in premature newborns. Methods: Premature newborns with and without SIRS were evaluated in a prospective design during a one-year period. Among 136 newborns, early and 72 h post-birth analyses were performed. Results: At 24 h, NLR's cutoff value was 8.69, yielding sensitivity and specificity rates of 52.77% and 83.47% (p = 0.0429), respectively. The dNLR showed a cutoff of 5.61, with corresponding rates of 63.27% and 84.15% (p = 0.0011), PLR had a cutoff of 408.75, with rates of 51.89% and 80.22% (p = 0.1026), and NLPR displayed a cutoff of 0.24, with rates of 75.85% and 86.70% (p = 0.0002). At 72 h, notable sensitivity and specificity improvements were observed, particularly with NLPR having a cutoff of 0.17, showing sensitivity of 77.74% and specificity of 95.18% (p < 0.0001). NLR above the cutoff indicated a 33% increase in SIRS risk, with a hazard ratio (HR)of 1.33. The dNLR was associated with a twofold increase in risk (HR 2.04). NLPR demonstrated a significant, over threefold increase in SIRS risk (HR 3.56), underscoring its strong predictive and diagnostic value for SIRS development. Conclusion: Integrating these findings into clinical practice could enhance neonatal care by facilitating the early identification and management of SIRS, potentially improving outcomes for this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Paroxysmal sympathetic hyperactivity (PSH) occurs in a subset of patients with traumatic brain injury (TBI) and is associated with worse outcomes. Sepsis is also associated with worse outcomes after TBI and shares several physiologic features with PSH, potentially creating diagnostic confusion and suboptimal management of each. This is the first study to directly investigate the interaction between PSH and infection using robust diagnostic criteria. Methods: We performed a retrospective cohort study of patients with TBI admitted to a level I trauma center intensive care unit with hospital length of stay of at least 2 weeks. From January 2016 to July 2018, 77 patients diagnosed with PSH were 1:1 matched by age and Glasgow Coma Scale to 77 patients without PSH. Trauma infectious diseases subspecialists prospectively documented assessments corroborating diagnoses of infection. Extracted data including incidence, timing, classification, and anatomical source of infections were compared according to PSH diagnosis. We also evaluated daily PSH clinical feature severity scores and systemic inflammatory response syndrome (SIRS) criteria and compared values for patients with and without confirmed infection, stratified by PSH diagnosis. Results: During the first 2 weeks of hospitalization, there were no differences in rates of suspected (62%) nor confirmed (48%) infection between patients with PSH and controls. Specific treatments for PSH were initiated on median hospital day 7 and for confirmed infections on median hospital day 8. SIRS criteria could identify infection only in patients who were not diagnosed with PSH. Conclusions: In the presence of brain injury-induced autonomic nervous system dysregulation, the initiation and continuation of antimicrobial therapy is a challenging clinical decision, as standard physiologic markers of sepsis do not distinguish infected from noninfected patients with PSH, and these entities often present around the same time. Clinicians should be aware that PSH is a potential driver of SIRS, and familiarity with its diagnostic criteria as proposed by the PSH assessment measure is important. Management by a multidisciplinary team attentive to these issues may reduce rates of inappropriate antibiotic usage and misdiagnoses. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome caused by trauma or infection, which can lead to multiple organ dysfunction. In severe cases, sepsis can also progress to septic shock and even death. Effective treatments for sepsis are still under development. This study aimed to determine if targeting the PI3K/Akt signaling with CAL-101, a PI3K p110δ inhibitor, could alleviate lipopolysaccharide (LPS)-induced sepsis and contribute to immune tolerance. Our findings indicated that CAL-101 treatment improved survival rates and alleviated the progression of LPS-induced sepsis. Compared to antibiotics, CAL-101 not only restored the Th17/regulatory T cells (Treg) balance but also enhanced Treg cell function. Additionally, CAL-101 promoted type 2 macrophage (M2) polarization, inhibited TNF-α secretion, and increased IL-10 secretion. Moreover, CAL-101 treatment reduced pyroptosis in peritoneal macrophages by inhibiting caspase-1/gasdermin D (GSDMD) activation. This study provides a mechanistic basis for future clinical exploration of targeted therapeutics and immunomodulatory strategies in the treatment of sepsis. • CAL-101 improved the survival rate and alleviated the progression in LPS-induced sepsis compared to antibiotic therapy. • CAL-101 not only rebalanced proportion of Th17/Treg, but also restored the function of Treg cells in LPS-induced sepsis. • CAL-101 promoted the M2 macrophages polarization and reduced pyroptosis by inhibiting the activation of Caspase 1/GSDMD. [ABSTRACT FROM AUTHOR]

Aim: The early warning scores (EWS), quick Sequential Organ Failure Assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria have been proposed as sepsis screening tools. This review aims to summarise and compare the performance of EWS with the qSOFA and SIRS criteria for predicting sepsis diagnosis and in‐hospital mortality in patients with sepsis. Design: A systematic review with meta‐analysis. Review Methods: Seven databases were searched from January 1, 2016 until March 10, 2022. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, likelihood ratios and diagnostic odd ratios were pooled by using the bivariate random effects model. Overall performance was summarised by using the hierarchical summary receiver–operating characteristics curve. This paper adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses of Diagnostic Test Accuracy Studies (PRISMA‐DTA) guidelines. Results: Ten studies involving 52,474 subjects were included in the review. For predicting sepsis diagnosis, the pooled sensitivity of EWS (65%, 95% CI: 55, 75) was similar to SIRS ≥2 (70%, 95% CI: 49, 85) and higher than qSOFA ≥2 (37%, 95% CI: 20, 59). The pooled specificity of EWS (77%, 95% CI: 64, 86) was higher than SIRS ≥2 (62%, 95% CI: 41, 80) but lower than qSOFA ≥2 (94%, 95% CI: 86, 98). Results were similar for the secondary outcome of in‐hospital mortality. Conclusions: Although no one scoring system had both high sensitivity and specificity, the EWS had at least equivalent values in most measures of diagnostic accuracy compared with SIRS or qSOFA. Implications for the profession: Healthcare systems in which EWS is already in place should consider whether there is any clinical benefit in adopting qSOFA or SIRS. No patient or public contribution: This systematic review did not directly involve patient or public contribution to the manuscript. [ABSTRACT FROM AUTHOR]

Canine parvovirus 2 (CPV-2) is a highly contagious enteric virus that causes high morbidity and mortality, especially in dogs under six months of age. Recovery from this illness is dependent on several factors, including the patient's prognosis for adequate therapy. The aim of this study was to evaluate the risk factors associated with the death outcome in CPV-2 positive dogs in a case-control study conducted at the Veterinary Hospital of the Universidade Federal de Lavras (HV-UFLA) in Lavras, Minas Gerais, Brazil. Twenty-six dogs with CPV-2 symptoms that arrived at the HV-UFLA between 2017 and 2018 were evaluated for inclusion in the study. Data on medical history, clinical signs, blood count and rapid test of parvovirus and faecal test for polymerase chain reaction (PCR) were collected for all the animals. All the dogs received treatment at the HV-UFLA, and the overall fatality rate due to canine parvovirus was 30.77%. Descriptive analysis and univariate and multivariate statistical analyses (logistic regression) were performed to assess the variables that were possibly associated with an unfavourable prognosis (death). In the univariate and multivariate analyses, Systemic Inflammatory Response Syndrome (SIRS) was observed to be a significant risk factor for an unfavourable prognosis in canine parvovirus, as it increased the risk of death by 12.96 times (95% CI 1.85-133.70; P < 0.01) compared with patients who did not exhibit SIRS. Thus, SIRS was strongly associated with an unfavourable prognosis, suggesting that it can be used as a prognostic indicator for canine parvovirus in veterinary practice. [ABSTRACT FROM AUTHOR]

Sepsis-Associated Liver Injury (SALI) is an independent risk factor for death from sepsis. The aim of this study was to develop an interpretable machine learning model for early prediction of 28-day mortality in patients with SALI. Data from the Medical Information Mart for Intensive Care (MIMIC-IV, v2.2, MIMIC-III, v1.4) were used in this study. The study cohort from MIMIC-IV was randomized to the training set (0.7) and the internal validation set (0.3), with MIMIC-III (2001 to 2008) as external validation. The features with more than 20% missing values were deleted and the remaining features were multiple interpolated. Lasso-CV that lasso linear model with iterative fitting along a regularization path in which the best model is selected by cross-validation was used to select important features for model development. Eight machine learning models including Random Forest (RF), Logistic Regression, Decision Tree, Extreme Gradient Boost (XGBoost), K Nearest Neighbor, Support Vector Machine, Generalized Linear Models in which the best model is selected by cross-validation (CV_glmnet), and Linear Discriminant Analysis (LDA) were developed. Shapley additive interpretation (SHAP) was used to improve the interpretability of the optimal model. At last, a total of 1043 patients were included, of whom 710 were from MIMIC-IV and 333 from MIMIC-III. Twenty-four clinically relevant parameters were selected for model construction. For the prediction of 28-day mortality of SALI in the internal validation set, the area under the curve (AUC (95% CI)) of RF was 0.79 (95% CI: 0.73–0.86), and which performed the best. Compared with the traditional disease severity scores including Oxford Acute Severity of Illness Score (OASIS), Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Systemic Inflammatory Response Syndrome (SIRS), and Acute Physiology Score III (APS III), RF also had the best performance. SHAP analysis found that Urine output, Charlson Comorbidity Index (CCI), minimal Glasgow Coma Scale (GCS_min), blood urea nitrogen (BUN) and admission_age were the five most important features affecting RF model. Therefore, RF has good predictive ability for 28-day mortality prediction in SALI. Urine output, CCI, GCS_min, BUN and age at admission(admission_age) within 24 h after intensive care unit(ICU) admission contribute significantly to model prediction. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to identify and analyze the mitochondrial genes associated with sepsis patients in order to elucidate the underlying mechanism of sepsis immunity and provide new ideas for the clinical treatment of sepsis. Methods: The hospitalized cases of sepsis (n = 20) and systemic inflammatory response syndrome (SIRS) (n = 12) admitted to the Emergency Intensive Care Unit (EICU) of the Affiliated Hospital of Southwest Medical University from January 2019 to December 2019 were collected consecutively. RNA-seq was used to sequence the RNA (mRNA) of peripheral blood cells. Bioinformatics techniques were used to screen and identify differentially expressed RNAs, with an absolute value of fold change (FC) greater than or equal to 1.2 and a false discovery rate (FDR) less than 0.05. At the same time, mitochondrial genes were obtained from the MitoCarta 3.0 database. Differential genes were then intersected with mitochondrial genes. The resulting crossover genes were subjected to GO, KEGG, and PPI analysis. Subsequently, the GSE65682 dataset was downloaded from the GEO database for survival analysis to assess the prognostic value of core genes, and GSE67652 was downloaded for ROC curve analysis to validate the diagnostic value of core genes. Finally, the localization of core genes was clarified through 10X single-cell sequencing. Results: The crossing of 314 sepsis differential genes and 1136 mitochondrial genes yielded 28 genes. GO and KEGG analysis showed that the crossover genes were mainly involved in the mitochondrion, mitochondrial matrix, and mitochondrial inner membrane. Survival analysis screened four genes that were significantly negatively associated with the prognosis of sepsis, namely FIS1, FKBP8, GLRX5, and GUK1. A comparison of peripheral blood RNA-seq results between the sepsis group and the SIRS group showed that the expression levels of these four genes were significantly decreased in the sepsis group compared to the SIRS group. ROC curve analysis based on GSE67652 indicates these four genes' high sensitivity and specificity for sepsis detection. Additionally, single-cell RNA sequencing found that the core genes were mainly expressed in macrophages, T cells, and B cells. Conclusions: Mitochondria-related genes (FIS1, FKBP8, GLRX5, GUK1) were underexpressed in the sepsis group, negatively correlated with survival, and mainly distributed in immune cells. This finding may guide studying the immune-related mechanisms of sepsis. This study protocol was reviewed by the Ethics Committee of the Affiliated Hospital of Southwest Medical University (ethics number: KY2018029), the clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019. [ABSTRACT FROM AUTHOR]

The human physiological response "to stress" includes all metabolic and hormonal changes produced by a traumatic event at the micro or macro cellular levels. The main goal of the body's first response to trauma is to keep physiological homeostasis. The perioperative non-specific adaptation response can sometimes be detrimental and can produce systemic inflammatory response syndrome (SIRS), characterized by hypermetabolism and hyper catabolism. We performed a narrative review consisting of a description of the surgical stress response's categories of changes (neurohormonal and immunological response) followed by reviewing methods found in published studies to modulate the surgical stress response perioperatively. We described various preoperative measures cited in the literature as lowering the burden of surgical trauma. This article revises the anesthetic drugs and techniques that have an impact on the surgical stress response and proven immune-modulatory effects. We also tried to name present knowledge gaps requiring future research. Our review concludes that proper preoperative measures, adequate general anesthetics, multimodal analgesia, early postoperative mobilization, and early enteral nutrition can decrease the stress response to surgery and ease patient recovery. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system and inflammatory system, with a consecutive impact on cancer recurrence and long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. Methods: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. Results: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322). Conclusion: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis. [ABSTRACT FROM AUTHOR]

Background: Sepsis ranks among the most formidable clinical challenges, characterized by exorbitant treatment costs and substantial demands on healthcare resources. Mitochondrial dysfunction emerges as a pivotal risk factor in the pathogenesis of sepsis, underscoring the imperative to identify mitochondrial-related biomarkers. Such biomarkers are crucial for enhancing the accuracy of sepsis diagnostics and prognostication. Methods: In this study, adhering to the SEPSIS 3.0 criteria, we collected peripheral blood within 24 h of admission from 20 sepsis patients at the ICU of the Southwest Medical University Affiliated Hospital and 10 healthy volunteers as a control group for RNA-seq. The RNA-seq data were utilized to identify differentially expressed RNAs. Concurrently, mitochondrial-associated genes (MiAGs) were retrieved from the MitoCarta3.0 database. The differentially expressed genes were intersected with MiAGs. The intersected genes were then subjected to GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and core genes were filtered using the PPI (Protein-Protein Interaction) network. Subsequently, relevant sepsis datasets (GSE65682, GSE28750, GSE54514, GSE67652, GSE69528, GSE95233) were downloaded from the GEO (Gene Expression Omnibus) database to perform bioinformatic validation of these core genes. Survival analysis was conducted to assess the prognostic value of the core genes, while ROC (Receiver Operating Characteristic) curves determined their diagnostic value, and a meta-analysis confirmed the accuracy of the RNA-seq data. Finally, we collected 5 blood samples (2 normal controls (NC); 2 sepsis; 1 SIRS (Systemic Inflammatory Response Syndrome), and used single-cell sequencing to assess the expression levels of the core genes in the different blood cell types. Results: Integrating high-throughput sequencing with bioinformatics, this study identified two mitochondrial genes (COX7B, NDUFA4) closely linked with sepsis prognosis. Survival analysis demonstrated that patients with lower expression levels of COX7B and NDUFA4 exhibited a higher day survival rate over 28 days, inversely correlating with sepsis mortality. ROC curves highlighted the significant sensitivity and specificity of both genes, with AUC values of 0.985 for COX7B and 0.988 for NDUFA4, respectively. Meta-analysis indicated significant overexpression of COX7B and NDUFA4 in the sepsis group in contrast to the normal group (P < 0.01). Additionally, single-cell RNA sequencing revealed predominant expression of these core genes in monocytes-macrophages, T cells, and B cells. Conclusion: The mitochondrial-associated genes (MiAGs) COX7B and NDUFA4 are intimately linked with the prognosis of sepsis, offering potential guidance for research into the mechanisms underlying sepsis. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation (SI) is linked to chronic kidney disease (CKD) progression and multiple complications. Data regarding SI biomarkers in pediatric patients are scarce. This case–control and cross-sectional study investigates the correlation of neutrophil–lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin to serum interleukin-6 (IL-6). Methods: NLR and PLR were measured in 53 patients (median age: 12.9 years), including 17 on dialysis and 36 with a median glomerular filtration rate of 39 ml/min/1.73m2, and in 25 age and sex-matched healthy controls. Iron profile, serum albumin and IL-6 were measured in the patient group. IL-6 levels > 3rd quartile were classified as high. Results: Patients presented higher NLR and PLR and particularly those on dialysis (p < 0.001 and p = 0.001). We observed a significant correlation between natural logarithm (ln) of IL-6 (lnIL-6) and NLR (rs = 0.344, p = 0.014), serum albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Combination of NLR, serum albumin and TIBC predicted high IL-6 (13 patients) with an AUC of 0.771 (95% CI 0.608–0.943). Pairing of NLR ≥ 1.7 and TIBC ≤ 300 μg/dL exhibited the highest sensitivity (76.9%), while incorporating serum albumin ≤ 3.8 g/dL along with them achieved the highest specificity (95%) for detecting high IL-6 levels. Conclusion: Both NLR and PLR levels increase in CKD, especially in patients on chronic dialysis. NLR, rather than PLR, along with TIBC and serum albumin, are associated with IL-6 in pediatric CKD. [ABSTRACT FROM AUTHOR]

Burn wound conversion is the observed process where superficial partial thickness burns convert into deep partial or full thickness burn injuries. This conversion process often involves surgical excision to achieve timely wound healing. Unfortunately, the pathophysiology of this phenomenon is multifactorial and poorly understood. Thus, a therapeutic intervention that may prevent secondary progression and cell death in burn-injured tissue is desirable. Recent work by our group and others has established that tranexamic acid (TXA) has significant anti-inflammatory properties in addition to its well-known anti-fibrinolytic effects. This study investigates TXA as a novel therapeutic treatment to mitigate burn wound conversion and reduce systemic inflammation. Sprague-Dawley rats were subjected to a hot comb burn contact injury. A subset of animals underwent a similar comb burn with an adjacent 30%TBSA contact injury. The interspaces represent the ischemic zones simulating the zone of stasis. The treatment group received injections of TXA (100 mg/kg) immediately after injury and once daily until euthanasia. Animals were harvested for analyses at 6 h and 7 days after injury. Full-thickness biopsies from the ischemic zones and lung tissue were assessed with established histological techniques. Plasma was collected for measurement of damage associated molecular patterns (DAMPs), and liver samples were used to study inflammatory cytokines expression. Treatment with TXA was associated with reduced burn wound conversion and decreased burn-induced systemic inflammatory response syndrome (SIRS). Lung inflammation and capillary leak were also significantly reduced in TXA treated animals. Future research will elucidate the underlying anti-inflammatory properties of TXA responsible for these findings. • Burn wound conversion is the observed process where partial thickness burns convert into full thickness burn injuries. • Burn wound conversion has been attributed to a combination of prolonged inflammation, ischemia, ROS, and autophagy. • Animals treated with systemic tranexamic acid had reduced burn wound conversion and decreased burn-induced SIRS. • Future research will elucidate the underlying anti-inflammatory properties of TXA responsible for these findings. [ABSTRACT FROM AUTHOR]

Introduction: Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. Methods: A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. Results: The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31–4.55, p = 0.005). Conclusion: Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL. Plain Language Summary: Systemic inflammatory response syndrome (SIRS) is a frequent and severe complication in patients underwent percutaneous nephrolithotomy (PCNL), which can be challenging to diagnose early, potentially leading to delayed treatment. Identifying SIRS risk factors and promptly treating high-risk patients is crucial. Glucocorticoids are commonly used to prevent SIRS in clinical practice, and this study aims to investigate whether preoperative glucocorticoid administration is associated with SIRS after PCNL. In total, 1259 patients underwent PCNL and were enrolled in the study. The study utilized both propensity score matching (PSM) analysis and regression analysis to identify risk factors for post-PCNL SIRS. The incidence of SIRS after PCNL was 9.6 % in the study and patients with postoperative SIRS had longer hospital stays and higher hospital costs. After minimizing the potential influence of confounding factors through the use of PSM, we found a significant association between the preoperative use of glucocorticoids and the occurrence of SIRS in patients undergoing PCNL. Based on our analysis, we can conclude that the preoperative administration of glucocorticoids represents an independent risk factor for the development of SIRS in these patients. [ABSTRACT FROM AUTHOR]

Data on systemic inflammatory response syndrome (SIRS) after transcatheter aortic valve implantation (TAVI) are scarce and limited to small cohorts. We aimed to investigate its incidence and mid-term impact in a large cohort of TAVI patients. From January 2018 to December 2020, 717 patients with severe aortic valve stenosis undergoing TAVI were included. SIRS was defined as fulfilling at least two of the following criteria within 48 h from the procedure: leucocyte count >12.0 or <4.0 × 109/l, respiratory rate > 20 breaths per minute or PaCO 2 ≤ 4.3 kPa/32 mmHg, heart rate > 90 beats per minute and temperature > 38.0 °C or <36.0 °C. Clinical endpoints were 1-year rehospitalization for chronic heart failure (CHF) and 2-years all-cause mortality. Event rates during follow-up were calculated as Kaplan-Meier estimates. SIRS developed in 56.3 % (404/717) of patients after TAVI. SIRS occurred more frequently in patients with post-dilatation (SIRS 34.7 % (140/404) vs. no SIRS 23.3 % (73/313); p < 0.001) and major vascular complications (SIRS 16.1 % (65/404) vs. no SIRS 8.6 % (27/313); p = 0.004). Further, ICU days were more in patients who developed SIRS (SIRS 1.56 ± 1.50 days vs. no SIRS 1.22 ± 1.02 days; p = 0.001). At 2-years, all-cause mortality in the entire population was 23.9 %. However, there was no difference in CHF at 1-year (5.9 % vs. 4.1 %; log-rank = 0.347) nor in all-cause mortality at 2-years (22.0 % vs. 26.2 %; log-rank = 0.690) between the groups. SIRS is a common finding after TAVI, which may prolong hospital stay but is without effect on mortality during 2-years follow-up. • SIRS is a common finding after TAVI, occurring in more than half of patients. • SIRS occurs more often in patients with post-dilatation and major vascular complications. • Inflammatory markers after TAVI increase, irrespective of SIRS development. • The occurrence of SIRS after TAVI is without effect on 2-years mortality. [ABSTRACT FROM AUTHOR]

Introduction: There is growing evidence that the use of robotic-assisted surgery (RAS) in colorectal cancer resections is associated with improved short-term outcomes when compared to laparoscopic surgery (LS) or open surgery (OS), possibly through a reduced systemic inflammatory response (SIR). Serum C-reactive protein (CRP) is a sensitive SIR biomarker and its utility in the early identification of post-operative complications has been validated in a variety of surgical procedures. There remains a paucity of studies characterising post-operative SIR in RAS. Methods: Retrospective study of a prospectively collected database of consecutive patients undergoing OS, LS and RAS for left-sided and rectal cancer in a single high-volume unit. Patient and disease characteristics, post-operative CRP levels, and clinical outcomes were reviewed, and their relationships explored within binary logistic regression and propensity scores matched models. Results: A total of 1031 patients were included (483 OS, 376 LS, and 172 RAS). RAS and LS were associated with lower CRP levels across the first 4 post-operative days (p < 0.001) as well as reduced complications and length of stay compared to OS in unadjusted analyses. In binary logistic regression models, RAS was independently associated with lower CRP levels at Day 3 post-operatively (OR 0.35, 95% CI 0.21–0.59, p < 0.001) and a reduction in the rate of all complications (OR 0.39, 95% CI 0.26–0.56, p < 0.001) and major complications (OR 0.5, 95% CI 0.26–0.95, p = 0.036). Within a propensity scores matched model comparing LS versus RAS specifically, RAS was associated with lower post-operative CRP levels in the first two post-operative days, a lower proportion of patients with a CRP ≥ 150 mg/L at Day 3 (20.9% versus 30.5%, p = 0.036) and a lower rate of all complications (34.7% versus 46.7%, p = 0.033). Conclusions: The present observational study shows that an RAS approach was associated with lower postoperative SIR, and a better postoperative complications profile. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro , revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings. [Display omitted] • Atorvastatin regulates the formation of neutrophil extracellular traps (NETs). • Atorvastatin inhibits NETs through the ERK/NOX2 signaling pathway. • Atorvastatin combined with imipenem alleviates sepsis-induced lung injury by inhibiting NETs. [ABSTRACT FROM AUTHOR]

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process. [ABSTRACT FROM AUTHOR]

This meta-data exploration aimed to determine the impact of exertional-heat stress (EHS) on gastrointestinal status of masters age and young adult endurance athletes. Sixteen MASTERS (mean: 44y) and twenty-one YOUNG (26y) recreational endurance athletes completed 2 h of running at 60% ˙V O2max in 35˚C ambient conditions. Blood samples were collected pre-, immediately and 1 h post-EHS, and analyzed for markers of exercise-induced gastrointestinal syndrome (EIGS). Thermo-physiological measures and gastrointestinal symptoms (GIS) were recorded every 10–20 min during EHS. Peak Δ pre- to post-EHS did not substantially differ (p>0.05) between MASTERS and YOUNG for intestinal epithelial injury [I-FABP: 1652pg/ml vs. 1524pg/ml, respectively], bacterial endotoxic translocation [sCD14: -0.09µg/mL vs. 0.84µg/mL, respectively], lipopolysaccharide-binding protein [LBP: 0.26µg/mL vs. 1.76µg/mL, respectively], and systemic inflammatory response profile (SIR-Profile: 92.0arb.unit vs. 154arb.unit, respectively). A significantly higher peak Δ pre- to post-EHS in endogenous endotoxin anti-body IgM (p=0.042), and pro-inflammatory cytokine IL-1β (p=0.038), was observed in YOUNG compared to MASTERS. No difference was observed between incidence (81% and 80%, respectively) and severity (summative accumulation: 21 and 30, respectively) of reported GIS during EHS between MASTERS and YOUNG. Pathophysiology of EIGS in response to EHS does not substantially differ with age progression, since masters and younger adult endurance athletes responded comparably. [ABSTRACT FROM AUTHOR]

Background Identification of bloodstream infection (BSI) in transplant recipients may be difficult due to immunosuppression. Accordingly, we aimed to compare responses to BSI in critically ill transplant and non-transplant recipients and to modify systemic inflammatory response syndrome (SIRS) criteria for transplant recipients. Methods We analyzed univariate risks and developed multivariable models of BSI with 27 clinical variables from adult intensive care unit (ICU) patients at the University of Virginia (UVA) and at the University of Pittsburgh (Pitt). We used Bayesian inference to adjust SIRS criteria for transplant recipients. Results We analyzed 38.7 million hourly measurements from 41 725 patients at UVA, including 1897 transplant recipients with 193 episodes of BSI and 53 608 patients at Pitt, including 1614 transplant recipients with 768 episodes of BSI. The univariate responses to BSI were comparable in transplant and non-transplant recipients. The area under the receiver operating characteristic curve (AUC) was 0.82 (95% confidence interval [CI],.80–.83) for the model using all UVA patient data and 0.80 (95% CI,.76–.83) when using only transplant recipient data. The UVA all-patient model had an AUC of 0.77 (95% CI,.76–.79) in non-transplant recipients and 0.75 (95% CI,.71–.79) in transplant recipients at Pitt. The relative importance of the 27 predictors was similar in transplant and non-transplant models. An upper temperature of 37.5°C in SIRS criteria improved reclassification performance in transplant recipients. Conclusions Critically ill transplant and non-transplant recipients had similar responses to BSI. An upper temperature of 37.5°C in SIRS criteria improved BSI screening in transplant recipients. [ABSTRACT FROM AUTHOR]

Preoperative inspiratory muscle training reduces the incidence of postoperative pulmonary complications after cardiac surgery, but training protocols vary widely in terms of intensity. Currently, the mechanisms underlying the effectiveness of this practice are not known. The purpose of the present study is to determine whether preoperative high-intensity inspiratory muscle training (HI-IMT) modulates the perioperative systemic inflammatory response in cardiac surgery patients. Participants awaiting surgical aortic valve replacement were randomized to 3 to 6 weeks preoperative home-based HI-IMT or same duration low-intensity inspiratory muscle training (LI-IMT). The primary outcome was the preoperative value of the soluble tumor necrosis factor receptor 1 (sTNFR1). Secondary outcomes assessed perioperative evolution of the cytokines: sTNFR1, Tumor necrosis factor-α, Interleukin (IL)-6, IL-8, IL10, IL1β, and their combined z-score; reflecting post-training and postoperative inflammatory response. Perioperative pulmonary function and postoperative clinical outcomes were collected. Between February 2018 and March 30, 2019 patients were randomized, to HI-IMT or LI-IMT. There were no differences between the groups in terms of baseline characteristics. The median (IQR) training duration was 34 (28–44) days. After training, the median (IQR) predicted maximal inspiratory pressure was higher in the HI-IMT vs LI-IMT group (119 (96–142%) vs 97 (81–107%); p =.04) Levels of the sTNFR1 cytokine increased during training in the HI-IMT group, pre vs post training (Median (IQR) 1073 (920; 1219) vs 1172 (965; 1368) ng/L; p =.03). The 24-h postoperative global inflammatory score was lower in the HI-IMT than in the LI-IMT group (Median (IQR), −0.37 (−0.62, 0.03) vs −0.10 (−0.17, 0.49), p =.04). Global inflammatory scores were not different at other time points. There were no significant differences between the groups in post-operative pulmonary function and postoperative clinical outcome. High intensity inspiratory muscle training shows immunomodulatory properties. These properties could explain why preoperative inspiratory muscle training can lead to lung protection after cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: Intestinal barrier dysfunction in acute pancreatitis (AP) may progress to systemic inflammatory response syndrome (SIRS) and multi-organ failures by causing bacterial translocation. Larazotide acetate (LA) is a molecule that acts as a tight junction (TJ) regulator by blocking zonulin (Zo) receptors in the intestine. Aims: In our study, we aimed to investigate the effects of LA on intestinal barrier dysfunction and bacterial translocation in the AP model in rats. Methods: Thirty-two male Sprague-Dawley rats were divided into 4 groups; control, larazotide (LAR), AP, and AP + LAR. The AP model was created by administering 250 mg/100 g bm l-Arginine intraperitoneally 2 times with an hour interval. AP + LAR group received prophylactic 0.01 mg/mL LA orally for 7 days before the first dose of l-Arginine. For intestinal permeability analysis, fluorescein isothiocyanate-dextran (FITC-Dextran) was applied to rats by gavage. The positivity of any of the liver, small intestine mesentery, and spleen cultures were defined as bacterial translocation. Histopathologically damage and zonulin immunoreactivity in the intestine were investigated. Results: Compared to the control group, the intestinal damage scores, anti-Zo-1 immunoreactivity H-Score, serum FITC-Dextran levels and bacterial translocation frequency (100% versus 0%) in the AP group were significantly higher (all p < 0.01). Intestinal damage scores, anti-Zo-1 immunoreactivity H-score, serum FITC-Dextran levels, and bacterial translocation frequency (50% versus 100%) were significantly lower in the AP + LAR group compared to the AP group (all p < 0.01). Conclusions: Our findings show that LA reduces the increased intestinal permeability and intestinal damage by its effect on Zo in the AP model in rats, and decreases the frequency of bacterial translocation as a result of these positive effects. [ABSTRACT FROM AUTHOR]

Cardiac surgery on cardiopulmonary bypass (CPB) is associated with postoperative renal dysfunction, one of the most common complications of this surgical cohort. Acute kidney injury (AKI) is associated with increased short-term morbidity and mortality and has been the focus of much research. There is increasing recognition of the role of AKI as the key pathophysiological state leading to the disease entities acute and chronic kidney disease (AKD and CKD). In this narrative review, we will consider the epidemiology of renal dysfunction after cardiac surgery on CPB and the clinical manifestations across the spectrum of disease. We will discuss the transition between different states of injury and dysfunction, and, importantly, the relevance to clinicians. The specific facets of kidney injury on extracorporeal circulation will be described and the current evidence evaluated for the use of perfusion-based techniques to reduce the incidence and mitigate the complications of renal dysfunction after cardiac surgery. [ABSTRACT FROM AUTHOR]

The strict application of vital signs has substantial risk of over-triage. Therefore, this study assessed the predictive value of Korean Triage and Acuity Scale (KTAS) level calculated using strict Systemic Inflammatory Response Syndrome (SIRS) criteria versus that evaluatedby a verified triage nurse (TN). The study is based on a retrospective observational cohort of a single-center emergency department (ED) from 01 May 2018 to 30 April 2019. Study subjects were patients aged ≥18 years with fever. Intensive care unit admission rate or death in ED (IADE) and general ward admission rate according to two differently defined KTAS levels were compared by receiver operating characteristic curve and logistic regression. A total of 2322 patients were included. In comparing the area under the curves (AUCs) of TN- and SIRS-KTAS, TN-KTAS' predictive power for IADE (0.802) was higher than that of SIRS-KTAS (0.7440, p = 0.0489). The odds ratio of level 3 for IADE (1.35) was not significantly different from that of level 4 in SIRS-KTAS (p = 0.5429). In KTAS, the severity of illness in patients was more accurately predicted by the triage nurse's decision based on clinical experience than the strict application of SIRS criteria with only vital signs. [ABSTRACT FROM AUTHOR]

Objective: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are blood markers of systemic inflammatory response (SIR). The purpose of this study was to investigate the clinical utility of SIR markers for severe anaphylaxis in children. Materials and Methods: The medical records of 103 children aged 0-18 years experiencing a total of 204 anaphylactic episodes between 2013 and 2020 were analyzed. The children were categorized into mild, moderate, and severe anaphylaxis groups. The SIR markers were measured during anaphylaxis. Results: Anaphylaxis was mild in 47 (45.6%), moderate in 28 (27.2%), and severe in 28 (27.2%) children. NLR was higher in children with severe anaphylaxis (p=0.001). The ROC curve demonstrated by the increase in NLR yielded an area under the curve (AUC) of 0.666 (CI: 0.5-0.79), with a cut-off value of ≥2.1 in discriminating severe anaphylaxis from mild and moderate anaphylaxis, with sensitivity of 73.6% and specificity of 76.9%. The risk of severe anaphylaxis increased in drug- and venom-induced reactions (OR: 11.83, 95%CI: 2.89-48.38, p=0.001, and OR: 13.03, 95%CI: 2.82-60.22, p=0.001, respectively), and in case of NLR ≥ 2.1 (OR: 3.92, 95%CI: 1.53-10.04, p=0.004), particularly in children aged <6 years (OR: 9.33, 95%CI: 1.27- 68.59, p=0.028). Conclusion: NLR was higher in severe anaphylaxis than mild and moderate, whereas MLR and PLR were not. NLR could be used as a quick and easily accessible marker to predict the severity of anaphylaxis in children. [ABSTRACT FROM AUTHOR]

Simple Summary: Myelofibrosis is a rare bone marrow disorder, leading to an increasing failure to generate healthy blood cells. Defining clinical prognosis scores for rare diseases is difficult, as sufficient numbers of patients for score validation are difficult to obtain. The current study investigates the utility of the TriNetX database, containing electronic medical records for over 140 million patients, to identify risk factors and establish clinical scores. TriNetX includes more than 64,000 myelofibrosis patients, and the present study explores factors influencing survival and common complications. Age over 65, anemia, an increased number of leukocytes, a low platelet count and an increased number of monocytes are associated with increased risks, while high numbers of eosinophiles and basophiles show positive associations. We demonstrate that the TriNetX database offers insights to refine predictive models, crucial for tailoring treatments to individual patient risks in the complex landscape of rare diseases like myelofibrosis. Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 103/µL) and thrombocytopenia (<150 × 103/µL) reduced survival and increased risks across all assessed events. Monocytosis is associated with decreased survival, whereas eosinophilia and basophilia were linked to improved survival. Further, as proof of concept for the applicability of TriNetX for clinical scores, we devised a simplified IPSS, and confirmed its value in predicting outcomes. This comprehensive study underscores the importance of age, anemia, leukocytosis and thrombocytopenia in predicting disease trajectory and contributes to refining prognostic models, addressing the challenges posed by the disease's heterogeneity. [ABSTRACT FROM AUTHOR]

Bacteremia is a major cause of morbidity. Blood cultures are the gold standard for diagnosing bacteremia. To compare previously published clinical decision rules for predicting a true positive blood culture (bacteremia) in the emergency department. Retrospective analysis of medical records of patients who had a blood culture performed in a tertiary hospital emergency department in 2020 (12 months). Positive blood cultures were compared with randomly selected negative blood cultures (1:4 ratio). Blood cultures were analyzed per patient presentation. Clinical data from patient presentations were extracted and appraised against the modified-Shapiro (mShapiro) rule and systemic inflammatory response syndrome (SIRS) criteria to calculate diagnostic accuracy to detect bacteremia. During the study period, 3870 blood cultures were taken from 2921 patients: 476 (12.3%) cultures were positive for bacterial growth, from 421 individual patient presentations (10 excluded as incomplete data). Of included patients, 338 were true positives and 73 contaminates, these were compared with 1446 patients with negative blood culture presentations. Evaluating mShapiro's rule and SIRS criteria to detect bacteremia vs. no bacteremia (negative + contaminated cultures) had a sensitivity of 94.4% (95% confidence interval [CI] 91.4–96.4%) and 84.9% (95% CI 80.7–88.3%), respectively, and a specificity of 37.9% (95% CI 35.5–40.1%) and 33.8% (95% CI 31.5–36.3%), respectively. Both had a high negative predictive value for bacteremia of 96.8% (95% CI 95.1–98.0) and 91.0% (95% CI 88.3–93.1) for mShapiro's rule and SIRS criteria, respectively. In this cohort, mShapiro's rule performed better than the SIRS criteria at predicting bacteremia. [ABSTRACT FROM AUTHOR]

Accurate and standardized methods for assessing the vital status of patients are crucial for patient care and scientific research. This study introduces the Patient Vital Status (PVS), which quantifies and contextualizes a patient's physical status based on continuous variables such as vital signs and deviations from age-dependent normative values. The vital signs, heart rate, oxygen saturation, respiratory rate, mean arterial blood pressure, and temperature were selected as input to the PVS pipeline. The method was applied to 70 pediatric patients in the intensive care unit (ICU), and its efficacy was evaluated by matching high values with septic events at different time points in patient care. Septic events included systemic inflammatory response syndrome (SIRS) and suspected or proven sepsis. The comparison of maximum PVS values between the presence and absence of a septic event showed significant differences (SIRS/No SIRS: p < 0.0001, η2 = 0.54; Suspected Sepsis/No Suspected Sepsis: p = 0.00047, η2 = 0.43; Proven Sepsis/No Proven Sepsis: p = 0.0055, η2 = 0.34). A further comparison between the most severe PVS in septic patients with the PVS at ICU discharge showed even higher effect sizes (SIRS: p < 0.0001, η2 = 0.8; Suspected Sepsis: p < 0.0001, η2 = 0.8; Proven Sepsis: p = 0.002, η2 = 0.84). The PVS is emerging as a data-driven tool with the potential to assess a patient's vital status in the ICU objectively. Despite real-world data challenges and potential annotation biases, it shows promise for monitoring disease progression and treatment responses. Its adaptability to different disease markers and reliance on age-dependent reference values further broaden its application possibilities. Real-time implementation of PVS in personalized patient monitoring may be a promising way to improve critical care. However, PVS requires further research and external validation to realize its true potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute hemorrhagic diarrhea syndrome (AHDS) is characterized by severe gastrointestinal fluid loss and necrotizing enteritis. This indicates an intestinal barrier dysfunction, altered intestinal permeability may indicate disease severity and might represent a risk factor for the development of chronic disorders. Serum iohexol measurement is utilized to assess intestinal permeability in dogs. Our study aimed to correlate intestinal permeability (measured by serum iohexol concentration (SIC)) with clinical severity in dogs with AHDS. We hypothesized increased intestinal permeability in dogs with AHDS, correlating with clinical severity. Fifty-three client-owned dogs, including those with AHDS and healthy controls, were enrolled. Clinical severity was assessed using the AHDS index and criteria for systemic inflammatory response syndrome (SIRS). Simultaneously, dogs were orally administered iohexol, and serum samples were collected for SIC measurement. The findings revealed significantly elevated SIC among dogs with AHDS compared to healthy controls, with a positive correlation between SIC and disease severity indices. These results highlight that dogs with a severe form of AHDS have an especially significant dysfunction of the intestinal barrier. Future studies are necessary to evaluate a potential association between an altered intestinal barrier at the phase of acute enteritis and the development of chronic intestinal disease later in life. Histopathologic examination of intestinal biopsies from dogs with acute hemorrhagic diarrhea syndrome (AHDS) reveals necrotizing enteritis and epithelial integrity loss. Serum iohexol measurement has been utilized to assess intestinal permeability. Our hypothesis is that dogs with AHDS have increased intestinal permeability, which is associated with the severity of clinical signs. In this prospective case–control study, 53 client-owned dogs (28 AHDS, 25 healthy controls) were evaluated. Clinical severity was assessed using the AHDS index and systemic inflammatory response syndrome (SIRS) criteria. Simultaneously, dogs received oral iohexol, and serum iohexol concentrations (SICs) were measured two hours later. Results indicated significantly higher (p = 0.002) SIC in AHDS dogs (median: 51 µg/mL; min–max: 9–246) than in healthy controls (30 µg/mL; 11–57). There was a significant positive correlation between AHDS index and SIC (rS = 0.4; p = 0.03) and a significant negative between SIC and serum albumin concentrations (Pearson r = −0.55; p = 0.01). Dogs with severe AHDS (mean 106 µg/mL; range: 17–246) demonstrated significantly higher (p = 0.002) SIC than those with mild to moderate disease (29 µg/mL; 9–54). These findings underscore the association between intestinal permeability and clinical severity in dogs with AHDS assessed by iohexol. [ABSTRACT FROM AUTHOR]

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0–15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1–5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4–15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86–0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission. [ABSTRACT FROM AUTHOR]

Infectious diseases are among the most common cause of morbidity and mortality among hospitalized patients while systemic inflammatory response syndrome is primarily attributed to the imbalance between pro‐inflammatory and anti‐inflammatory cytokines. Despite the improvements in the antibiotherapy alternatives and diagnostic modalities, the morbidity and mortality rates of sepsis and septic shock are relatively high among patients admitted to the intensive care units. Extracorporeal cytokine hemadsorption therapies are therapeutic approaches for such patient group with promising early results that especially have grown during COVID‐19 pandemic. In this narrative review, our aim is to evaluate the current pre‐clinical and clinical knowledge regarding the use of cytokine filtration systems among patients with septic shock. [ABSTRACT FROM AUTHOR]

Caffeic acid, a naturally occurring organic compound, possesses antioxidant and anti-inflammatory properties, along with its derivatives. This systematic review aimed to evaluate the effect of caffeic acid and its derivatives on oxidative stress and inflammatory response in cutaneous wound healing. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Searches were performed in PubMed, Scopus, and Ovid MEDLINE. Articles published between 2000 and June 2022, with seven articles meeting the inclusion criteria were retrieved. The articles constituted in-vivo studies that utilised caffeic acid phenethyl ester (CAPE) as the therapeutic agent in three types of cutaneous wound including full-thickness burn injury (n=4), two incisional wounds, and one pressure ulcer. CAPE scavenged reactive oxidative species and reduced lipid peroxidation, superoxide dismutase, nitrotyrosine, malondialdehyde, catalase, xanthine oxidase, and nitric oxide levels. The treated injured area revealed enhanced granulation tissue formation, vascularisation, and collagenisation as well as long-term effects of CAPE as evidenced by reduced myofibroblast amount, CD68-positive macrophages, and increased collagen deposition. The systematic review emphasised how antioxidant and anti-inflammatory effects of CAPE could improve the process of wound healing, suggesting its substantial potential for clinical applications in this domain. [ABSTRACT FROM AUTHOR]

Objective: The pathophysiology of uterine scar dehiscence is not yet clear. The aim of this study was to investigate whether preoperative hemogram parameters can be used as predictive markers of uterine scar dehiscence, thus improving prediction and contributing to management of repeat Cesarean section. Material and Methods: Between 2015 and 2020, 36670 (47.6%) cesarean sections were delivered in our hospital and 16943 of them had a previous Cesarean section. All cases of uterine scar rupture detected during Cesarean section were identified, and a total of 40 patients were included after excluding cases with impairment of the systemic inflammatory response (SIR). Controls consisted of 40 randomly selected, ageand body mass index (BMI)-matched patients, and the groups were compared. Results: Age, BMI, and gravidity were similar (p>0.05). Although the gestational week and Apgar scores were similar between the groups (p>0.05), the birth weight amongst controls was significantly higher than the uterine dehiscence group (p=0.028). Platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and other hemogram values were similar in both groups (p>0.05). Mean platelet volume (MPV) in the control group was significantly higher than in the uterine rupture group (p=0.049). Regression analysis found no significant result between hemogram parameters, birth weight, and dehiscence. Conclusion: In this study, which set out to identify predictors of the risk of uterine scar dehiscence with SIR parameters, only the MPV value was lower in the dehiscence group. [ABSTRACT FROM AUTHOR]

Systemic inflammatory response syndrome (SIRS) is a potentially fatal reaction to various forms of tissue damage and infections that cause damage to various organs. Furthermore, the brain is damaged earlier than other organs, resulting in diffuse brain dysfunction. The central clinical symptom of SIRS is delirium and emotional changes are involved in disease development. Although the amygdala is known to play a major role, the mechanisms underlying emotional changes in the early stages of SIRS have not been elucidated. Therefore, changes to dopamine levels in the amygdala were observed using an in vivo model of lipopolysaccharide (LPS)- induced SIRS to clarify the biochemical mechanisms activated in the early stages of SIRS. Extracellular dopamine was collected from the amygdala of free moving rats via microdialysis and then analyzed by high-performance liquid chromatography. In addition, emotional changes were assessed with the open field and sucrose preference tests. In the LPS group, dopamine release in the amygdala increased remarkably immediately after LPS administration, peaking at 120 min. Thereafter, dopamine release temporarily decreased, but then significantly increased again after 180 min. The present results suggest that diffuse brain dysfunction in the early stages of SIRS may involve altered dopamine levels in the amygdala. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory response syndrome caused by infection, which causes renal dysfunction known as sepsis-associated acute kidney injury (S-AKI). Ferroptosis is a form of lipid peroxidation dependent on iron and reactive oxygen species that differs from other forms of programmed cell death at the morphological and biochemical levels. Andrographolide (AG), a natural diterpenoid lactone compound extracted from Andrographis paniculata, has been shown to have therapeutic effects in kidney disease. In this study, we investigated the novel mechanism by which AG attenuates septic acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells (HK-2) through the Nrf2/FSP1 pathway. Cecum ligation and puncture (CLP)-induced septic rats and lipopolysaccharide (LPS)-induced HK-2 cells were used for in vivo and in vitro experiments. Firstly, in septic rats and HK-2 cells, AG effectively decreased the levels of kidney injury indicators, including blood creatinine, urea nitrogen, and markers of kidney injury such as neutrophil gelatinase-associated lipid transport protein and kidney injury molecule-1 (KIM-1). In addition, AG prevented ferroptotosis, by avoiding the accumulation of iron and lipid peroxidation, and an increase in SLC7A11 and GPX4 in AG-treated HK-2 cells. Furthermore, AG attenuated mitochondrial damage, including mitochondrial swelling, outer membrane rupture, and a reduction in mitochondrial cristae in LPS-treated HK-2 cells. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly inhibited LPS-induced ferroptosis in HK-2 cells. Importantly, our results confirm that Nrf2/FSP1 is an important pathway for ferroptosis resistance. Nrf2 siRNA hindered the effect of AG in attenuating acute kidney injury and inhibiting ferroptosis. These findings demonstrate that Nrf2/FSP1-mediated HK-2 ferroptosis is associated with AG, alleviates septic acute kidney injury, and indicates a novel avenue for therapeutic interventions in the treatment of acute kidney injury in sepsis. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammatory response syndrome (SIRS) is a complex condition that may be associated with sepsis or may progress with trauma, burns and major surgery. The aim of this study was to evaluate the systemic inflammatory response syndrome and survival rate in traumatized cats. Methods: The study material consisted of 34(22.66%) cats diagnosed with SIRS among 150 cats who were traumatized by falling from a height. Cats were monitored and vital signs such as pulse, respiration, arterial blood pressure, oxygen saturation and body temperature were recorded. In addition, laboratory whole blood and biochemical tests were performed. In the treatment of cats with SIRS, it was aimed to provide circulatory support and support measures to keep the animal alive. Result: 27(79.41%) cats with SIRS died due to lung failure or multi-organ failure and 7(20.58%) cats survived. The prognosis in SIRS patients with trauma depends on the patient's response to aggressive treatment and supportive care. SIRS has a high mortality rate. Common causes of death include cardiovascular collapse, multi-organ dysfunction and acute lung injury. [ABSTRACT FROM AUTHOR]

Objective: To discuss the definitions of sepsis in human and veterinary medicine. Design: International, multicenter position statement on the need for consensus definitions of sepsis in veterinary medicine. Setting: Veterinary private practice and university teaching hospitals. Animals: Dogs and cats. Interventions: None. Measurements and Main Results: Sepsis is a life‐threatening condition associated with the body's response to an infection. In human medicine, sepsis has been defined by consensus on 3 occasions, most recently in 2016. In veterinary medicine, there is little uniformity in how sepsis is defined and no consensus on how to identify it clinically. Most publications rely on modified criteria derived from the 1991 and 2001 human consensus definitions. There is a divergence between the human and veterinary descriptions of sepsis and no consensus on how to diagnose the syndrome. This impedes research, hampers the translation of pathophysiology insights to the clinic, and limits our abilities to optimize patient care. It may be time to formally define sepsis in veterinary medicine to help the field move forward. In this narrative review, we present a synopsis of prior attempts to define sepsis in human and veterinary medicine, discuss developments in our understanding, and highlight some criticisms and shortcomings of existing schemes. Conclusions: This review is intended to serve as the foundation of current efforts to establish a consensus definition for sepsis in small animals and ultimately generate evidence‐based criteria for its recognition in veterinary clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: We assessed the potential prognostic significance of the preoperative systemic inflammation index, platelet‐to‐lymphocyte ratio, and neutrophil‐to‐lymphocyte ratio in patients who underwent surgical resection. Subjects and Methods: This retrospective study included 224 patients with clinicopathologically confirmed squamous carcinoma of the tongue who underwent surgery between August 2009 and December 2017. The optimal cut‐off values for the indices were determined by receiver operating characteristic curves. Correlations between the indices and clinicopathological variables were determined by Pearson chi‐square or Fisher exact tests. The Kaplan–Meier test was used to compare overall survival between groups (high and low values); the log‐rank or Breslow test was used to assess differences in survival. Univariate and multivariate Cox regression models were used to analyze predictive values of the indices as independent indicators of overall survival. Bilateral p values of <0.05 were considered statistically significant. Results: Significant association was found between the indices and sex, tissue grade, tumor location, and lymph nodes metastases (p < 0.05). On Kaplan–Meier analysis, patients with lower values of the indices had longer overall survival (p < 0.05). Univariate and multivariate Cox regression models identified age, lymph node metastases, and neutrophil‐to‐lymphocyte ratio as independent predictors of overall survival. Conclusion: The studied indices have potential prognostic significance in patients with squamous tongue cancer. [ABSTRACT FROM AUTHOR]

This study aimed to assess the therapeutic effects of implementing the BioFire® Blood Culture Identification 2 (BCID2) Panel (bioMérieux, Marcy l'Etoile, France) in the clinical practice of children with sepsis. This retrospective cross-sectional study included children from 15 days of age to 18 years old with sepsis and of whom the BCID2 Panel was studied from the positive blood culture. If the antimicrobial treatment was changed according to the results of BCID2 Panel, it was recorded and re-grouped as targeted antimicrobial therapy, de-escalation of the antimicrobial treatment and shifting to another antimicrobial drug if any antimicrobial resistance was detected. Seven-days and thirty-days mortality rate was recorded. Thirty-two patients with 36 septic episodes with positive BCID2 Panel results were included. The median age was 10 months 15 days (ranging from 15 days to 16.5 years). The mean difference between having positive results by the BCID2 Panel and conventional culture methods was 82.2 ± 45.4 h (ranging from 12.3 to 207 h). Effect of the BCID2 Panel on the antimicrobial treatment was detected in 69.4% of the episodes (n = 25). Glycopeptides were ceased at 6 patients, piperacillin/tazobactam was ceased at 6 patients, and cefotaxime was ceased at one patient and de-escalation was achieved in 13 episodes which formed the 36.1% of the initial antimicrobial treatment. Conclusion: The BCID2 Panel had an important impact on the patients care and optimization according to the principles of antimicrobial stewardship. The BCID2 Panel may be one of the key items for rapid and accurate diagnosis in children with sepsis. Blood culture is still the mainstay for especially detection of antimicrobial drug resistance, while BCID2 tests had several advantages such as speed and diagnostic accuracy as good as blood culture. What is Known: • The BioFire® Blood Culture Identification 2 (BCID2) Panel (bioMérieux, Marcy l'Etoile, France) is a well-validated assay that allows for the simultaneous identification of 43 nucleic acid targets associated with bloodstream infections within about 1 h. What is New: • BCID2 Panel had a direct impact on the patient's treatment decision at the 69.4% of the sepsis episodes. • The clinicians received the microbiological results 82.2 h earlier with BCID2 panel compared to blood culture methods with antimicrobial resistance and de-escalation of the antimicrobial drugs was achieved at 13 episodes which formed the 36.1% of the initial treatment. [ABSTRACT FROM AUTHOR]

Background: Sepsis, a type of systemic disease, can impact nearly all organs, tissues and cells. Among them, endothelial cells are amongst the first to be affected and respond to the insult. In this study, we investigated the protective effects of microRNA-30a-5p (miR-30a-5p) on human pulmonary microvascular endothelial cells (HPMECs) treated with lipolysaccharide (LPS). Methods: An in vitro model of sepsis was established in HPMECs with the use of LPS. Transfecting with different tools (mimetic and inhibitor) to modify miR-30a-5p expression. Cell viability, proliferation and apoptosis were detected by the CCK-8 assay, the EdU kit and fluorescence staining, respectively. The autophagy-related protein and mRNA expression, the number of autophagosomes were separately examined through Western blot analysis, qPT-PCR and confocal microscopy. TargetScan and the luciferase reporter assays were used to probe target genes interacting with miR-30a-5p. Results: LPS caused a reduction in the viability and proliferation of HPMECs, as well as an elevation in the number of apoptotic cells. Subsequently, we observed that miR-30a-5p might play a role in preventing LPS-induced inhibition of cell damage and decreasing HPMEC apoptosis, suggesting the potential function of miR-30a-5p in this injury process. Finally, we confirmed that miR-30a-5p exerts its protective effect by regulating cell autophagy, possibly by targeting Beclin-1. Conclusion: Our study provided evidence that autophagy is a crucial aspect in the protective role of miR-30a-5p against LPS-induced HPMEC injury, identifying a promising target for sepsis-related endothelial cell injury. [ABSTRACT FROM AUTHOR]

Objective Acute bronchiolitis (AB) is one of the most common respiratory diseases in early childhood and is still an important health problem worldwide. The systemic immune-inflammatory index (SII) is thought to have potential to be a new-generation inflammatory biomarker. We sought to investigate the value of SII for severity assessment in children with AB. Methods A total of 74 AB patients were included in a prospective observational study. Patients were classified into 3 AB groups according to this classification: mild (1-5 points), moderate (6-10 points), and severe (11-12 points). Complete blood count, C-reactive protein, and procalcitonin tests were carried out. Modified Tal score was evaluated to determine severity. The performance of parameters to predict the severity of AB was assessed using the receiver operating characteristic (ROC). Results Whereas neutrophil count (P =.037), neutrophil-to-lymphocyte ratio (P =.030), and SII (P =.030) values increased significantly with disease severity, red cell distribution width (P =.048) values were higher in the moderate AB group. The SII was found to have the highest area under the curve in the comparison of the mild-moderate groups combination and the high group on ROC analysis (P =.009). Conclusion The SII values of pediatric patients hospitalized with the diagnosis of AB were significantly higher in the high-severity group. The SII may offer additional severity stratification in children with AB. [ABSTRACT FROM AUTHOR]

Pregnancy-adjusted sepsis screening criteria were most accurate in identifying sepsis for nondelivery admissions after 20 weeks of gestation and before 3 days postpartum. OBJECTIVE: To evaluate the performance characteristics of existing screening tools for the prediction of sepsis during antepartum and postpartum readmissions. METHODS: This was a case–control study using electronic health record data obtained between 2016 and 2021 from 67 hospitals for antepartum sepsis admissions and 71 hospitals for postpartum readmissions up to 42 days. Patients in the sepsis case group were matched in a 1:4 ratio to a comparison cohort of patients without sepsis admitted antepartum or postpartum. The following screening criteria were evaluated: the CMQCC (California Maternal Quality Care Collaborative) initial sepsis screen, the non–pregnancy-adjusted SIRS (Systemic Inflammatory Response Syndrome), the MEWC (Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System) obstetric SIRS, and the MEWT (Maternal Early Warning Trigger Tool). Time periods were divided into early pregnancy (less than 20 weeks of gestation), more than 20 weeks of gestation, early postpartum (less than 3 days postpartum), and late postpartum through 42 days. False-positive screening rates, C-statistics, sensitivity, and specificity were reported for each overall screening tool and each individual criterion. RESULTS: We identified 525 patients with sepsis during an antepartum hospitalization and 728 patients with sepsis during a postpartum readmission. For early pregnancy and more than 3 days postpartum, non–pregnancy-adjusted SIRS had the highest C-statistics (0.78 and 0.83, respectively). For more than 20 weeks of gestation and less than 3 days postpartum, the pregnancy-adjusted sepsis screening tools (CMQCC and UKOSS) had the highest C-statistics (0.87–0.94). The MEWC maintained the highest sensitivity rates during all time periods (81.9–94.4%) but also had the highest false-positive rates (30.4–63.9%). The pregnancy-adjusted sepsis screening tools (CMQCC, UKOSS) had the lowest false-positive rates in all time periods (3.9–10.1%). All tools had the lowest C-statistics in the periods of less than 20 weeks of gestation and more than 3 days postpartum. CONCLUSION: For admissions early in pregnancy and more than 3 days postpartum, non–pregnancy-adjusted sepsis screening tools performed better than pregnancy-adjusted tools. From 20 weeks of gestation through up to 3 days postpartum, using a pregnancy-adjusted sepsis screening tool increased sensitivity and minimized false-positive rates. The overall false-positive rate remained high. [ABSTRACT FROM AUTHOR]

During delivery admissions, the California Maternal Quality Care Collaborative and United Kingdom Obstetric Surveillance System pregnancy-adjusted sepsis screening tools have the lowest false-positive rates while maintaining greater than 90% sensitivity rates. OBJECTIVE: To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions. METHODS: This was a case–control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality Care Collaborative), SIRS (Systemic Inflammatory Response Syndrome), the MEWC (the Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System), and the MEWT (Maternal Early Warning Trigger Tool). Sensitivity, false-positive rates, and C-statistics were reported for each screening tool. Analyses were stratified into cohort 1, which excluded patients with chorioamnionitis–endometritis, and cohort 2, which included those patients. RESULTS: Delivery admissions at 59 hospitals were extracted for patients with sepsis. Cohort 1 comprised 647 patients with sepsis, including 228 with end-organ injury, matched with a control group of 2,588 patients without sepsis. Cohort 2 comprised 14,591 patients with chorioamnionitis–endometritis, of whom 1,049 had sepsis and 238 had end-organ injury. In cohort 1, the CMQCC and the UKOSS pregnancy-adjusted criteria had the lowest false-positive rates (6.9% and 9.6%, respectively) and the highest C-statistics (0.92 and 0.91, respectively). Although other screening criteria, such as SIRS and the MEWC, had similar sensitivities, it was at the cost of much higher false-positive rates (21.3% and 38.3%, respectively). In cohort 2, including all patients with chorioamnionitis–endometritis, the highest C-statistics were again for the CMQCC (0.67) and UKOSS (0.64). All screening tools had high false-positive rates, but the false-positive rates for the CMQCC and UKOSS were substantially lower than those for SIRS and the MEWC. CONCLUSION: During delivery admissions, the CMQCC and UKOSS pregnancy-adjusted screening criteria have the lowest false-positive results while maintaining greater than 90% sensitivity rates. Performance of all screening tools was degraded in the setting of chorioamnionitis–endometritis. [ABSTRACT FROM AUTHOR]

Key Points: Question: How should children with suspected infection at higher risk of mortality, indicative of sepsis, be identified? Findings: Using an international survey, systematic review, and analysis of more than 3 million pediatric health care encounters, and consensus process, new criteria for sepsis and septic shock in children were developed. Pediatric sepsis in children (<18 years) with suspected infection was identified by at least 2 points in the novel Phoenix Sepsis Score, including dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems; and septic shock as sepsis with at least 1 cardiovascular point in the Phoenix Sepsis Score. Meaning: The new criteria for pediatric sepsis and septic shock are globally applicable. Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4—respiratory, cardiovascular, coagulation, and/or neurological—organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world. This article revises criteria to identify sepsis in children after an exhaustive process that involved surveying clinicians, reviewing health record databases, conducting a systematic review and meta-analysis, and undergoing a Delphi consensus process. [ABSTRACT FROM AUTHOR]

Bacground: Off-pump coronary artery bypass graft (OPCABG) has a high incidence of postoperative systemic inflammation response syndrome (SIRS), and perioperative endothelial glycocalyx layer (EGL) disruption can be one of the predisposing factors. We hypothesized that EGL shedding happened earlier in OPCABG which can influence on postoperative SIRS, and sevoflurane might preserve EGL better than propofol. Methods: We randomly allocated 50 patients undergoing OPCABG to receive either sevoflurane-sufentanil or propofol-sufentanil anesthesia. Plasma syndecan-1, heparan sulfate (HS), atrial natriuretic peptide (ANP), IL-6, and cardiac troponin I (cTnI) were measured. Blood samples were collected at 6 timepoints: induction (T1), before grafting (T2), after grafting(T3), surgery done (T4), postoperative day1 (POD1,T5) and POD2 (T6). SIRS criteria and sequential organ failure assessment (SOFA) score were examined. Results: There were neither differences of syndecan-1, HS, IL-6 nor of SIRS criteria or SOFA score between the sevoflurane and propofol groups. All patients were pooled as a single group for further statistical analyses, plasma syndecan-1 (P < 0.001) and IL-6 (P < 0.001) increased significantly as a function of time; syndecan-1 increasing correlated significantly with the duration of coronary graft anastomosis (r = 0.329, P = 0.026). Syndecan-1(T3) correlated significantly with ANP(T3) (r = 0.0.354, P = 0.016) and IL-6 (T5) (r = 0.570, P < 0.001). The maximum value of IL-6 correlated significantly with SIRS (r = 0.378, P = 0.010), the maximum value of SOFA score (r = 0.399, P = 0.006) and ICU days (r = 0.306, P = 0.039). The maximum value of SOFA score correlated significantly with the occurrence of SIRS (r = 0.568, P < 0.001) and ICU days (r = 0.338, P = 0.022). Conclusions: OPCABG intraoperative early EGL shedding caused of grafts anastomosis greatly affected postoperative SIRS and SOFA score, sevoflurane did not clinically preserve EGL better. Trial registration: ChiCTR-IOR-17012535. Registered on 01/09/2017. [ABSTRACT FROM AUTHOR]

Background: Several factors are associated with increased postoperative complications after appendectomies. However, few studies combined these potential factors for comprehensive prediction of surgical outcomes. Whether high-risk patients benefit from a shorter waiting time for surgery remains unclear. This study aimed to explore the impact of surgical waiting time and potential risk factors on postoperative complications. Methods: A total of 1343 patients diagnosed with acute appendicitis requiring an emergent appendectomy were included from 2013 to 2018. The preoperative risk factors associated with postoperative complications were selected and the probability of postoperative complications was calculated by multivariate logistic regression model. Patients were divided into four groups based on the risk (high & low) and time to surgery (> 12 & ≤12 hours). The odds ratios for complications were evaluated between groups. Results: The selected risk factors included age, neutrophil-lymphocyte ratio, systemic inflammatory response syndrome and abdominal pain duration. Compared with low-risk patients with time to surgery ≤12 hours, high-risk patients with time to surgery > 12 hours had significant increased overall postoperative complication rate (16.85% vs. 8.16%, p = 0.002) and a trend toward increased surgical site infection rate (10.99% vs. 6.46%, p = 0.058). When operated within 12 hours, there was no difference in outcomes between high- and low-risk patients. On the other hand, time to surgery > 12 hours did not increase complication rate in low-risk patients. Conclusions: The surgical outcome may be affected by preoperative factors and time to surgery. It is suggested that high-risk patients receive appendectomy within 12 hours to avoid increased postoperative complications. [ABSTRACT FROM AUTHOR]

Purpose: Primary epiploic appendagitis (PEA) is not an uncommon cause of abdominal pain. The systemic inflammatory response syndrome (SIRS) criteria have high sensitivity for early detection of inflammation and infection. To date, there is limited data about the association between SIRS and PEA. The aims of this retrospective study were to evaluate the prevalence of SIRS response and its clinical relevance in patients diagnosed with PEA within a large tertiary hospital network. Methods: A retrospective study was performed on all consecutive adult patients who presented to four major emergency departments with CT-confirmed PEA from 01 January 2022 to 27 March 2023. The fulfilment of SIRS criteria, hospital admission rate and treatments provided were analysed for these patients. Results: Seventy-three patients had CT-confirmed PEA. Seventeen patients (23.2%) with PEA were SIRS positive. The hospital admission rate in the SIRS group trended higher than the non-SIRS group (odds ratio of 2.51, 95% CI (0.75, 8.39)). The odds of having an associated radiological comorbidity unrelated to PEA were 18.7 times higher in the SIRS positive group. Fifty-seven (78%) patients were discharged home, and 16 (22%) patients were admitted into hospital. Nearly all patients were treated conservatively (98.6%). Conclusion: PEA patients with SIRS response trend towards a higher hospital admission rate and are significantly more likely to have other radiological comorbidities than non-SIRS patients. It is important to look for other pathological conditions in a SIRS positive patient with a CT-diagnosis of PEA. [ABSTRACT FROM AUTHOR]