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Pediatric Inflammatory Multisystem Syndrome (PIMS-TS), associated with SARS-CoV-2 infection, is a severe complication after COVID-19 in children. It is caused by the immune reaction to SARS-CoV-2, and usually appears three to six weeks after the infection. Unfortunately, PIMS causes non-specific symptoms, which makes its diagnosis and treatment difficult. In this paper, we propose Fourier Transform InfraRed spectrometry (FTIR) to identify chemical changes in blood serum of children induced by PIMS and caused by subsequent treatment of the syndrome. The results suggest that although the Principal Component Analysis (PCA) of FTIR data did not allow for differentiation of healthy children and children with PIMS before and after the treatment, the implementation of Support Vector Machine (SVM) showed that the accuracy of the FTIR region between 800 cm - 1 and 1800 cm - 1 in PIMS detection is as high as 92% with a sensitivity of 100%. The difference in the chemical compositions of sera from the control group and the children after the treatment was detected in 54%, indicating that the treatment was effective. Indeed, the obtained medical data clearly showed a decrease of C-reactive protein (CRP) and Procalcitonin (PCT) concentration in serum after the treatment. The decision tree showed that peak 1455 cm - 1 could be used as a potential FTIR PIMS marker. Importantly, FTIR data correlates well with medical parameters, however the correlation differs with respect to the groups before and after the treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethic declaration: This research was conducted according to the norm and standard in of the Declaration of Helsinki. This study was approved by the local Bioethics Committee of the Jagiellonian University (nr 1072.6120.360.2020). Moreover, written informed consent was obtained from the parents of the children from whom serum was collected. The consent was approved by the Bioethics Committee of the Jagiellonian University, (© 2025. The Author(s).)

This study aims to develop a machine learning model utilizing Computed Tomography (CT) values to predict systemic inflammatory response syndrome (SIRS) after endoscopic surgery for kidney stones. The goal is to identify high-risk patients early and provide valuable guidance for urologists in the early diagnosis and intervention of post-operative urosepsis. This study included 833 patients who underwent retrograde intrarenal surgery (RIRS) or percutaneous nephrolithotomy (PCNL) for kidney stones. Five machine learning algorithms and ten preoperative or intraoperative variables were used to develop a predictive model for SIRS. The SHapley Additive exPlanations (SHAP) method was used to explain the distribution of feature importance in the model's predictions. Among the 833 patients, 126 (15.1%) developed SIRS postoperatively. All five machine learning models demonstrated strong discrimination on the validation set (AUC: 0.690-0.858). The eXtreme Gradient Boosting (XGBoost) model was the best performer [AUC: 0.858; sensitivity: 0.877; specificity: 0.981; accuracy: 0.841; positive predictive value: 0.629; negative predictive value: 0.851]. The characteristic importance of the Machine Learning model (ML model) and SHAP results indicated Hounsfield Unit (HU), Urinary protein, Stone burden, and Serum uric acid as important predictors for the model. A machine learning model utilizing CT values was developed to predict postoperative SIRS in endoscopic kidney stone surgery. The model demonstrates strong predictive performance and can assist in assessing the risk of urosepsis in postoperative patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Sepsis is a severe infectious disease with high mortality. However, the indicators used to evaluate its severity and prognosis are relatively complicated. The systemic inflammatory response index (SIRI), a new inflammatory indicator, has shown good predictive value in chronic infection, stroke, and cancer. The purpose of this study was to investigate the connection between sepsis and SIRI and evaluate its predictive usefulness. A total of 401 patients with sepsis were included in this study. Multiple linear regression and logistic regression analyses were performed to evaluate the relationship between SIRI and sepsis. The restricted cubic spline (RCS) method was employed to illustrate the dose-response relationship. The area under the curve (AUC) and decision curve analysis (DCA) were used to evaluate the prognostic value of SIRI. Multiple linear regression analysis revealed a significant positive correlation between SIRI and both blood cell count and Sequential Organ Failure Assessment (SOFA) score. Additionally, higher SIRI levels were significantly linked to a higher risk of sepsis worsening, according to logistic regression analysis. The RCS curve demonstrated that the risk of poor prognosis rose with increasing SIRI, particularly when SIRI exceeded 6.1. Furthermore, AUC and DCA results showed that SIRI had superior predictive value compared to traditional indicators. A higher SIRI is linked to a worse prognosis and more severe sepsis. SIRI may serve as a novel prognostic indicator in sepsis, though further clinical studies are necessary to confirm these findings., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The association of anosmia/ageusia with a positive severe respiratory syndrome coronavirus 2 (SARS-CoV-2) test is well-established, suggesting these symptoms are reliable indicators of coronavirus disease 2019 (COVID-19) infection. This study investigates the clinical characteristics and systemic inflammatory markers in hospitalized COVID-19 patients in Taiwan, focusing on those with anosmia/ageusia. We conducted a retrospective observational study on 231 hospitalized COVID-19 patients (alpha variant) from April to July 2021. Clinical symptoms, dyspnea grading, and laboratory investigations, including neutrophil-lymphocyte ratios (NLRs), platelet-lymphocyte ratios (PLRs), and ANDC scores (an early warning score), were analyzed. Cough (64.1%), fever (58.9%), and dyspnea (56.3%) were the most common symptoms, while anosmia/ageusia affected 9% of patients. Those with anosmia/ageusia were younger, had lower BMI, lower systemic inflammatory markers, and better ANDC scores than those without these symptoms. Female patients exhibited lower NLR values and ANDC scores compared to male patients (all p < 0.05). Multivariable regression analysis demonstrated significant associations between NLR and CRP and ferritin levels (all p < 0.01), and between PLR and ESR and ferritin levels (p < 0.01). Categorized ANDC scores significantly correlated with the total hospital length of stay (all p < 0.05). Despite ethnic differences in the prevalence of anosmia/ageusia, our study highlights similar clinical presentations and inflammatory profiles to those observed in Western countries. The ANDC score effectively predicted hospital stay duration. These findings suggest that anosmia/ageusia may be associated with less severe disease and a lower inflammatory response, particularly in younger and female patients. The ANDC score can serve as a valuable prognostic tool in assessing the severity and expected hospital stay of COVID-19 patients., (© 2024. The Author(s).)

Systemic inflammatory response index (SIRI) has been proven to be associated with the prognosis of coronary artery disease and many other diseases. However, the relationship between SIRI and acute traumatic spinal cord injury (tSCI) has rarely been evaluated. The study aims to assess the prognostic value of SIRI for clinical outcomes in individuals with acute tSCI. A total of 190 patients admitted within eight hours after tSCI between January 2021 and April 2023 were enrolled in our study. Logistic regression analysis was used to analyze the association between SIRI and American Spinal Injury Association Impairment Scale (AIS) grade at admission and discharge, as well as neurological improvement in tSCI patients, and receiver operating characteristic (ROC) analysis was performed to assess the discriminative ability of SIRI in predicting AIS grade at discharge. After adjusting for confounding factors, SIRI positively correlated with the AIS grade (A to C) at admission and discharge, and negatively correlated with neurological improvement. The area under the curve values in ROC analysis was 0.725 (95% CI 0.647, 0.803). The study suggests that SIRI is significantly associated with an increased risk of poor clinical outcome at discharge in tSCI patients and has a certain discriminative value., (© 2024. The Author(s).)

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 10 9 /L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 10 9 /L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes., (© 2024. The Author(s).)

To utilize metabolomics in conjunction with RNA sequencing to identify biomarkers in the blood of sepsis patients and discover novel targets for diagnosing and treating sepsis. In January 2019 and December 2020, blood samples were collected from a cohort of 16 patients diagnosed with sepsis and 11 patients diagnosed with systemic inflammatory response syndrome (SIRS). Non-targeted metabolomics analysis was conducted using liquid chromatography coupled with mass spectrometry (LC-MS/MS technology), while gene sequencing was performed using RNA sequencing. Afterward, the metabolite data and sequencing data underwent quality control and difference analysis, with a fold change (FC) greater than or equal to 2 and a false discovery rate (FDR) less than 0.05.Co-analysis was then performed to identify differential factors with consistent expression trends based on the metabolic pathway context; KEGG enrichment analysis was performed on the crossover factors, and Meta-analysis of the targets was performed at the transcriptome level using the public dataset. In the end, a total of five samples of single nucleated cells from peripheral blood (two normal controls, one with systemic inflammatory response syndrome, and two with sepsis) were collected and examined to determine the cellular location of the essential genes using 10× single cell RNA sequencing (scRNA-seq). A total of 485 genes and 1083 metabolites were found to be differentially expressed in the sepsis group compared to the SIRS group. Among these, 40 genes were found to be differentially expressed in both the metabolome and transcriptome. Functional enrichment analysis revealed that these genes were primarily involved in biological processes related to inflammatory response, immune regulation, and amino acid metabolism. Furthermore, a meta-analysis identified four genes, namely ITGAM, CD44, C3AR1, and IL2RG, which were highly expressed in the sepsis group compared to the normal group (P < 0.05). Additionally, scRNA-seq analysis revealed that the core genes ITGAM and C3AR1 were predominantly localized within the macrophage lineage. The primary genes ITGAM and C3AR1 exhibit predominant expression in macrophages, which play a significant role in inflammatory and immune responses. Moreover, these genes show elevated expression levels in the plasma of individuals with sepsis, indicating their potential as valuable subjects for further research in sepsis., (© 2024. The Author(s).)

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, η 2  = 0.54; Suspected Sepsis/No Suspected Sepsis: p = 0.00047, η 2  = 0.43; Proven Sepsis/No Proven Sepsis: p = 0.0055, η 2  = 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, η 2  = 0.8; Suspected Sepsis: p < 0.0001, η 2  = 0.8; Proven Sepsis: p = 0.002, η 2  = 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., (© 2024. The Author(s).)

The occurrence of systemic inflammatory response after percutaneous transhepatic gallbladder drainage brings great risks to patients and is one of the challenges faced by clinicians. Therefore, it is of great significance to find a suitable prediction method for clinicians to intervene early and reduce the transformation of serious complications. Easy-to-obtain and objectively measured clinical features were screened, and logistic regression was used to construct a prediction model. The predictive ability of the model was evaluated by using the receiver operating characteristic curve and the decision curve in the validation set and the training set, respectively. Nine clinical features (CRP, Fever, DBIL, Obstruction, Bile properties, PCT, Length, Width, and Volume factor) were used to construct the prediction model, and the validation results showed that the prediction model had good performance in the training set (AUC = 0.83) and the validation set (AUC = 0.81). The decision curve also showed that the predictive ability of the model incorporating nine clinical features is better than that of a single clinical feature. The model we constructed can accurately predict the occurrence of SIRS, which can guide clinicians to take treatment measures and avoid the deterioration of complications., (© 2023. The Author(s).)

Multi-system inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection in children, and there is a critical need to unfold its highly heterogeneous disease patterns. Our objective was to characterize the illness spectrum of MIS-C for improved recognition and management. We conducted a retrospective cohort study using data from March 1, 2020-September 30, 2022, in 8 pediatric medical centers from PEDSnet. We included 1139 children hospitalized with MIS-C and used their demographics, symptoms, conditions, laboratory values, and medications for analyses. We applied heterogeneity-adaptive latent class analyses and identified three latent classes. We further characterized the sociodemographic and clinical characteristics of the latent classes and evaluated their temporal patterns. Class 1 (47.9%) represented children with the most severe presentation, with more admission to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 (23.3%) represented a moderate presentation, with 4-6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 (28.8%) represented a mild presentation. Our results indicated that MIS-C has a spectrum of clinical severity ranging from mild to severe and the proportion of severe or critical MIS-C decreased over time., (© 2023. The Author(s).)

The injury severity score (ISS) is used in daily practice to evaluate the severity of trauma patients; however, the score is not always consistent with the prognosis. After injury, systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) are related to the prognosis of trauma patients. We aimed to evaluate the associations between the immune response and prognosis in trauma patients. Patients who admitted to the Trauma Intensive Care Unit (ICU) were eligible. Whole blood samples were collected at admission, and then 6, 12, 24, 48 and 72 h after admission. Natural killer (NK) cells, lymphocyte subset population and cytokines release were identified using flow cytometry. We grouped patients by their ISS (≤ 25 and > 25 as very severe injury) and ICU stay (≤ 10 days as a short ICU stay and > 10 days as a long ICU stay) for evaluation. Fifty-three patients were enrolled. ICU stay but not ISS was close correlated with activity daily living (ADL) at discharge. Patients with a long ICU stay had an immediate increase in NK cells followed by lymphopenia which persisted for 48 h. Immediate activation of CD8 + T cells and then exhaustion with a higher programmed cell death-1 (PD-1) expression and suppression of CD4 + T cells with a shift to an anti-inflammatory Th2 phenotype were also observed in the patients with a long ICU stay. When the patients were grouped by ISS, the dynamics of immune responses were inconsistent to those when the patients were grouped by ICU stay. Immune responses are associated with the prognosis of trauma patients, however the currently used clinical parameters may not accurately reflect immune responses. Further investigations are needed to identify accurate predictors of prognosis in trauma patients., (© 2023. The Author(s).)

This study examined whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with stage II/III gastric cancer. 444 consecutive patients who underwent radical gastrectomy for stage II/III gastric cancer were retrospectively reviewed. We evaluated maximum serum C-reactive protein (CRP max ) and white blood cell count (WBC max ), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers. In univariate analyses, CRP max , WBC max and infectious complications were significantly associated with both overall survival (OS) (p < 0.001, p < 0.001 and p = 0.011, respectively) and relapse-free survival (RFS) (p < 0.001, p = 0.001 and p < 0.001, respectively). Multivariate analysis revealed that high-CRP max (> 9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.19-2.36, p = 0.003) and RFS (HR 1.56, 95% CI 1.12-2.18, p = 0.009), while WBC max and infectious complications were not. CRP max , which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection., (© 2022. The Author(s).)

Glucocorticoids play a central role in the inflammatory response and alleviate the symptoms in critically ill patients. The glucocorticoid action relies on the glucocorticoid receptor (GR) which translocates into the nucleus upon ligand-binding and regulates transcription of a battery of genes. Although the GR is encoded by a single gene, dozens of its splice variants have been described in diverse species. The GRα isoform encodes the full, functionally active protein that is composed of a transactivation, a DNA-binding, and a C-terminal ligand-binding domain. The second most highly expressed receptor variant, the GR-P, is formed by an intron retention that introduces an early stop codon and results in a probably dysfunctional protein with truncated ligand-binding domain. We described the canine ortholog of GR-P and showed that this splice variant is highly abundant in the peripheral blood of dogs. The level of cGRα and cGR-P transcripts are elevated in patients of SIRS and the survival rate is increased with elevated cGRα and cGR-P expression. The ratio of cGRα and cGR-P mRNA did not differ between the survivor and non-survivor patients; thus, the total GR expression is more pertinent than the relative expression of GR isoforms in assessment of the disease outcome., (© 2021. The Author(s).)

During the winter months of 2020/2021 a wave of multisystem inflammatory syndrome in children (MIS-C) emerged in Poland. We present the results of a nationwide register aiming to capture and characterise MIS-C with a focus on severity determinants. The first MIS-C wave in Poland was notably high, hence our analysis involved 274 children. The group was 62.8% boys, with a median age of 8.8 years. Besides one Asian, all were White. Overall, the disease course was not as severe as in previous reports, however. Pediatric intensive care treatment was required for merely 23 (8.4%) of children, who were older and exhibited a distinguished clinical picture at hospital admission. We have also identified sex-dependent differences; teenage boys more often had cardiac involvement (decreased ejection fraction in 25.9% vs. 14.7%) and fulfilled macrophage activation syndrome definition (31.0% vs. 15.2%). Among all boys, those hospitalized in pediatric intensive care unit were significantly older (median 11.2 vs. 9.1 years). Henceforth, while ethnicity and sex may affect MIS-C phenotype, management protocols might be not universally applicable, and should rather be adjusted to the specific population., (© 2021. The Author(s).)

Sepsis is a potentially fatal condition caused by infection. It is frequently difficult to distinguish sepsis from systemic inflammatory response syndrome (SIRS), often resulting in poor prognoses and the misuse of antibiotics. Hence, highly sensitive and specific biomarkers are needed to differentiate sepsis from SIRS. Urine samples were collected and segregated by group (a sepsis group, a SIRS group, and a healthy control group). iTRAQ was used to identify the differentially expressed proteins among the three groups. The identified proteins were measured by ELISA in urine samples. Finally, all the acquired data were analyzed in SPSS. C-reactive protein, leucine-rich alpha glycoprotein-1 and serum amyloid A (SAA) protein were differentially expressed among the three groups. The adjusted median concentrations of urinary C-reactive protein were 1337.6, 358.7, and 2.4 in the sepsis, SIRS, and healthy control groups, respectively. The urinary leucine-rich alpha glycoprotein-1 levels in these three groups were 1614.4, 644.5, and 13.6, respectively, and the levels of SAA were 6.3, 2.9, and 0.07, respectively. For all three of these measures, the sepsis group had higher levels than the SIRS group (P < 0.001), and the SIRS group had higher levels than the healthy control group. When combined, the three biomarkers had a sensitivity of 0.906 and a specificity of 0.896 in distinguishing sepsis from SIRS. Urinary C-reactive protein, urinary leucine-rich alpha glycoprotein-1 and urinary SAA have diagnostic value in cases of sepsis. This initial study suggests the possibility of improved differential diagnosis between sepsis and systemic inflammatory response syndrome; additional confirmation is necessary to corroborate the findings., (© 2021. The Author(s).)

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil-lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9-86.5) vs. 16% (12.6-23.1) vs. 7.05% (1.4-9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229-1828) vs. 853 (20-968) vs. 99.5 (54.7-140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area under curve (AUC) of 0.95. At a cut-off value of 0.261 ng/ml, the sensitivity and specificity of serum procalcitonin was 83% and 72%, respectively, with AUC of 0.86. Serum CRP, total leukocyte count, NLR had AUCs of 0.78, 0.63 and 0.64, respectively. Quantitative measurement of nCD64 can better distinguish systemic bacterial infection and inflammation in SAH as compared to traditional biomarkers., (© 2021. The Author(s).)

To characterize the new SARS-Co-V-2 related multisystem inflammatory syndrome in children (MIS-C) among Israeli children and to compare it with Kawasaki disease (KD). We compared, in two medical centers, the clinical and laboratory characteristics of MIS-C, KD and an intermediate group, which met the case definitions of both conditions. MIS-C patients were older, were more likely to be hypotensive, to have significant gastrointestinal symptoms, lymphopenia and thrombocytopenia and to have non-coronary abnormal findings in their echocardiogram. Lymphopenia was an independent predictor of MIS-C. Most of our MIS-C patients responded promptly to corticosteroid therapy. KD incidence in both centers was similar in 2019 and 2020. Although there is clinical overlap between KD and MIS-C, these are separate entities. Lymphopenia clearly differentiates between these entities. MIS-C patients may benefit from corticosteroids as first-line therapy.

Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014-June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.

Sepsis remains a critical problem with high mortality worldwide, but there is still a lack of reliable biomarkers. We aimed to evaluate the serum lysophosphatidylcholine (LPC) 16:0 as a biomarker of sepsis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Patients admitted to intensive care unit at Severance Hospital from March 2017 through June 2018 were prospectively enrolled. The inclusion criteria were the fulfillment of at least two criteria of systemic inflammatory response syndrome (SIRS) or the presence of sepsis. Of the 127 patients, 14 had non-infectious SIRS, 41 had sepsis, and 72 had septic shock. The mean serum LPC 16:0 concentration (µmol/L) in non-infectious SIRS was significantly higher than in patients with sepsis and septic shock (101.1 vs. 48.92, p < 0.05; 101.1 vs. 25.88, p < 0.001, respectively). The area under the curve (AUC) predicting 28-day mortality using ΔLPC16:0 (D1-D0) levels was 0.7, which was comparable with the APACHE II score (AUC 0.692) and SOFA score (AUC 0.67). Mechanical ventilation, CRRT, lactate, Δ LPC16:0 (D1-D0) less than the cut-off value were significantly associated with 28-day mortality in multivariable analysis. Our results suggest that LPC16:0 could be a useful biomarker for sepsis diagnosis and mortality prediction in ICU patients.

Pentraxin 3 (PTX3) is an acute phase protein. Our goal was to assess PTX3 as a predictor of systemic inflammatory response syndrome (SIRS), death and disease severity in acute pancreatitis (AP) in comparison to C-reactive protein (CRP) and the APACHE II score. From April 2011 to January 2015, 142 patients with AP were included in this single center post hoc analysis of prospectively collected data at the University Hospital Basel, Switzerland. Disease severity was rated by the revised Atlanta criteria (rAC). Inflammatory response was measured by the SIRS criteria. PTX3, CRP and APACHE II score were measured. Patients median PTX3 plasma concentrations in AP were higher in moderate (3.311 ng/ml) and severe (3.091 ng/ml) than in mild disease (2.461 ng/ml). Overall, 59 occurrences of SIRS or death were observed. In the prediction of SIRS or death, PTX3 was inferior to CRP and APACHE II, with modest predictive discriminatory ability of all three markers and AUC of 0.54, 0.69 and 0.69, respectively. Upon combination of CRP with PTX3, AUC was 0.7. PTX3 seems to be inferior to CRP and APACHE II in the prediction of SIRS or death in AP and does not seem to improve the predictive value of CRP upon combination of both parameters.

The serum concentration of soluble urokinase-type plasminogen activator receptor (suPAR) reflects immune activation. We performed a meta-analysis to evaluate the usefulness of suPAR for the diagnosis and prognosis of bacterial infections. PubMed, Embase and Cochrane Library databases were searched for studies reporting the detection of suPAR in adult patients with bacterial infections. Seventeen studies were selected from 671 studies. The pooled sensitivity and specificity of suPAR for diagnosing infection were 0.73 and 0.79, respectively, and the area under the summary receiver operating characteristic curve (AUC) was 0.82. Subgroup analyses revealed suPAR showed similar AUC values for diagnosing sepsis and bacteremia, but the AUC for differentiating sepsis from systemic inflammatory response syndrome (SIRS) was only 0.68. Elevated suPAR levels were significantly associated with a high risk of death, with a pooled risk ratio of 3.37 (95% confidence interval, 2.60-4.38). The pooled sensitivity and specificity for predicting mortality were 0.70 and 0.72, respectivfely, with an AUC of 0.77. Serum suPAR could be a biomarker for the diagnosis and prognosis of bacterial infection, but it is relatively ineffective for differentiating sepsis from SIRS. Further investigation is required to evaluate whether using of suPAR in combination with other biomarkers can improve diagnostic efficacy.

Systemic inflammation in humans may be triggered by infection, termed sepsis, or non-infective processes, termed non-infective systemic inflammatory response syndrome (SIRS). MicroRNAs regulate cellular processes including inflammation and may be detected in blood. We aimed to establish definitive proof-of-principle that circulating microRNAs are differentially affected during sepsis and non-infective SIRS. Critically ill patients with severe (n = 21) or non-severe (n = 8) intra-abdominal sepsis; severe (n = 23) or non-severe (n = 21) non-infective SIRS; or no SIRS (n = 16) were studied. Next-generation sequencing and qRT-PCR were used to measure plasma microRNAs. Detectable blood miRNAs (n = 116) were generally up-regulated in SIRS compared to no-SIRS patients. Levels of these 'circulating inflammation-related microRNAs' (CIR-miRNAs) were 2.64 (IQR: 2.10-3.29) and 1.52 (IQR: 1.15-1.92) fold higher for non-infective SIRS and sepsis respectively (p < 0.0001), hence CIR-miRNAs appeared less abundant in sepsis than in SIRS. Six CIR-miRNAs (miR-30d-5p, miR-30a-5p, miR-192-5p, miR-26a-5p, miR-23a-5p, miR-191-5p) provided good-to-excellent discrimination of severe sepsis from severe SIRS (0.742-0.917 AUC of ROC curves). CIR-miRNA levels inversely correlated with pro-inflammatory cytokines (IL-1, IL-6 and others). Thus, among critically ill patients, sepsis and non-infective SIRS are associated with substantial, differential changes in CIR-miRNAs. CIR-miRNAs may be regulators of inflammation and warrant thorough evaluation as diagnostic and therapeutic targets.