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Background: Soluble lectin-like oxidised low-density lipoprotein receptor 1 (sLOX-1) is overproduced during inflammation, with its expression and release triggered by C-reactive protein (CRP). As CRP levels are typically elevated in sepsis, this study aimed to investigate whether sLOX-1 levels increase in parallel., Methods: Plasma sLOX-1 levels of 52 patients with systemic inflammatory response syndrome (SIRS), 45 patients with sepsis, 88 patients with septic shock and 37 controls were measured by ELISA. Associations with CRP, underlying diseases, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and bacterial infections were analysed., Results: Plasma sLOX-1 levels were similarly elevated in patients with SIRS, sepsis, or septic shock compared to controls. Plasma sLOX-1 levels did not differ between male and female controls or patients. Plasma sLOX-1 levels were comparable in patients infected with SARS-CoV-2, Gram-negative bacteria, or Gram-positive bacteria. No association was observed between sLOX-1 levels and underlying liver cirrhosis or pancreatitis. Notably, plasma sLOX-1 levels correlated positively with leukocyte and basophil counts but showed no correlation with CRP or procalcitonin. Of clinical relevance, positive correlations were also found with aspartate aminotransferase (AST) and bilirubin levels. Among the 41 patients who did not survive, sLOX-1, AST, and bilirubin levels were significantly higher compared to those of survivors., Conclusions: Plasma levels of sLOX-1 are elevated in patients with SIRS or sepsis and are significantly higher in non-survivors. Of note, they do not correlate with classical inflammatory markers, suggesting that sLOX-1 may function as an independent prognostic biomarker for predicting poor outcomes in patients with SIRS or sepsis., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the ethical committee of the University Hospital of Regensburg (18-1029-101) and was performed according to the updated guidelines of good clinical practice and the updated Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

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).)

Multisystemic inflammatory syndrome (MIS-C) is a severe postinfectious condition. This study aims to detail long-term follow-up. Forty-five patients were followed up for 24 months, inflammatory markers were normalized at 3 months and echocardiographic alterations were resolved in all patients at 6 months, remaining normal. MIS-C, despite being a serious disease, presents a fast resolution of clinical, laboratory and echocardiographic alterations., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: An elevated defensive reaction of the body to a harmful stressor like infection, trauma, surgery, acute inflammation, ischemia, reperfusion, or malignancy to localize and eliminate the endogenous or exogenous source of the injury is known as systemic inflammatory response syndrome (SIRS). Sepsis is a term used for SIRS with suspected or documented sources of infection. It is characterized by the fulfillment of any two of the following conditions: white blood cell (WBC) count ≥4000/µL or >10% immature forms or bands; body temperature over 38°C or below 36°C; pulse rate above 90 beats per minute; tachypnea (respiratory rate greater than 20 breaths per minute); or partial pressure of CO 2 below 32 mm Hg. Procalcitonin (PCT) is one of the more complex and expensive lab indicators used to diagnose and prognosticate this disorder. Less expensive tests include total leukocyte count (TLC), neutrophil count, and neutrophil/lymphocyte ratio (NLR)., Objectives: To ascertain the correlation between procalcitonin and TLC, neutrophil count, and NLR in patients with SIRS without documented infection and SIRS with infection (sepsis), and to evaluate TLC, neutrophil count, and NLR ratios between SIRS without infection and sepsis., Materials and Methods: Acutely ill patients aged 18 years or older who fulfilled the criteria for SIRS were included in this study. The serum PCT value, TLC, and blood culture were done within 12 hours of admission. All other relevant investigations at the time of admission were also noted., Results: Out of 282 patients with SIRS, 194 patients had no documented infection (group I), whereas 88 patients had a documented infection (sepsis group II). The difference in age and sex between both groups ( p < 0.05) was found to be statistically significant. All four markers-PCT, TLC, neutrophils, and NLR-were significantly higher in the sepsis group., Conclusion: PCT is the best biomarker to predict sepsis, and it correlated significantly with TLC, neutrophil count, and NLR in SIRS without infection, and with neutrophil count and NLR in sepsis in our study. Secondly, TLC and NLR are also good predictors of sepsis and can diagnose sepsis in resource-poor settings., (© Journal of The Association of Physicians of India 2025.)

Background: Early recognition of cardiac involvement and prediction of disease prognosis are essential for the management of inflammatory diseases such as multisystem inflammatory syndrome. This study aimed to investigate the role of Pentraxin-3 levels in identifying cardiac involvement and evaluating disease severity in patients with multisystem inflammatory syndrome., Methods: The study included 56 multisystem inflammatory syndrome patients and 26 healthy children as a control group. The multisystem inflammatory syndrome group was divided into those with cardiac involvement ( n = 34) and those without ( n = 22), as well as those with clinically mild-moderate ( n = 30) and severe ( n = 26) multisystem inflammatory syndrome. Blood samples for measurement of Pentraxin-3 levels were obtained from all patients before treatment and from the healthy controls., Results: In the patient group, the mean age was 8.2 ± 4 years (range: 2-17 years), and the male-to-female ratio was 1.8. In the control group, these values were 9.5 ± 3.7 years (range: 2-16 years) and 1.9, respectively ( p > 0.05). Plasma Pentraxin-3 levels were significantly higher in multisystem inflammatory syndrome patients compared to controls (7.1 ± 5 ng/mL vs. 2.9 ± 2.1 ng/mL, p = 0.001). Patients with cardiac involvement had a significantly higher median Pentraxin-3 level than those without (5.8 ng/mL vs. 4.1 ng/mL, p = 0.004). Severe disease was also associated with a higher median Pentraxin-3 level compared to mild-moderate disease (6.1 ng/mL vs. 4.4 ng/mL, p = 0.001). Pentraxin-3 level was negatively correlated with left ventricular ejection fraction and positively correlated with B-type natriuretic peptide, troponin., Conclusion: Elevated Pentraxin-3 levels in multisystem inflammatory syndrome patients may help predict the clinical course of the disease and cardiac involvement. However, larger-scale prospective studies are needed to further elucidate this.

The study aims to evaluate the long-term outcomes - functional, pulmonary and non-pulmonary (other organs) - in children hospitalized with COVID-19 infection or with Multisystem inflammatory syndrome (MIS-C) after 1-2 y of discharge. All children with moderate or severe COVID-19 or MIS-C were enrolled. Out of 45 enrolled subjects, 19.8% had COVID-19 infection and 82% had MIS-C. Four children (8.9%) had abnormal baseline echocardiography; two each with cardiac dysfunction and coronary dilatation. At baseline, 44% had moderate disability and 24% had mild disability as per Pediatric Cerebral Performance Category (PCPC). On follow-up, only 8.9% (n = 4) had mild and 2.2% (n = 1) had moderate disability as per the PCPC score. One child developed new onset tuberculosis of the bone. None had any pulmonary morbidities. Follow-up echocardiogram was also within normal limits for children with abnormal findings. Further studies in different populations (settings) are required to draw meaningful conclusions about long-term effects of COVID-19 on children., Competing Interests: Declarations. Conflict of Interest: None., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Purpose: To summarize the latest research on the epidemiology, pathogenesis, diagnosis, and treatment of multisystem inflammatory syndrome in children (MIS-C)., Recent Findings: The epidemiology of MIS-C has been dynamic since its initial description. The pathogenesis remains poorly understood. Case definitions of MIS-C have evolved over time, and practice patterns for treating MIS-C are variable with generally positive long-term outcomes yet persistent changes noted. MIS-C has become less prevalent and less severe over time, yet racial and ethnic disparities persist, and vaccination against COVID-19 is highly effective in preventing this disease. The link between acute infection and subsequent inflammation is not well understood, with growing evidence describing its immunologic signature. Newer case definitions require excluding other inflammatory conditions, including Kawasaki Disease (KD), before diagnosing MIS-C. Corticosteroid monotherapy may be non-inferior to IVIg alone or combination IVIg plus corticosteroids for initial treatment, distinguishing the approaches to MIS-C and KD. A wide range of biologic therapies have been employed for rescue therapy with general success and no clear benefit of one over another. Despite reports of a high rate of coronary artery abnormality regression and resolution of heart failure, long-term studies suggest persistent changes to cardiac function. The long-term effects of MIS-C continue to be active areas of research., Competing Interests: Declarations. Conflict of Interest: The authors declare no competing interests. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe post-COVID-19 complication with multiple phenotypes., Objectives: The aim of this study is to study inflammatory biomarkers (cytokines and oxidative stress) in critical MIS-C patients and to observe if there is association between these biomarkers and mortality., Methods: A single-center prospective study enrolled patients with MIS-C (with positive molecular test), aged between 1 month and 18 years of age. Data was collected from 20 pediatric intensive care unit (PICU)'s bed. Inflammatory biomarkers (cytokines and oxidative stress markers) were performed on day 1 and 3 after hospitalization. Survival rate was calculated, and Kaplan-Meier curves were plotted. Univariate and multivariate Cox regression analyses were conducted. The ROC (Receiver Operating Characteristic) curve analysis was performed., Results and Conclusions: A total of 41 patients out of 109 patients admitted at PICU with suspected MIS-C during the study period were included, of which 33 (80.5%) were male, 9 (22%) were under one year old, and 30 (73.2%) presented comorbidities. Among them, 16 (39%) did not survive. The mean survival time was shorter in patients with higher levels of IL-17A (≥ 19.71 pg/mL) on day 1 (115 vs 323 days, p = 0.004). Higher levels of IL-17A on day 1 were associated with mortality in both the crude model (HR 1.03, CI95% 1.004-1.057, p = 0.022) and the adjusted model (HR 1.043, CI95% 1.013-1.075, p = 0.012). ROC analysis revealed a cut-off value for the IL-17A of 14.32 pg/ml. The other immunological and inflammatory markers did not demonstrate an association with survival (p>0.05). Our findings suggest that patients with high levels of IL-17A are at greater risk for death., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 de Farias, Nascimento, Pavão Junior, Pavão, Pinheiro, Pinheiro, Alves, Ferraro, Aires, Dias, Machado, Serrão, Gomes, de Moraes, Pontes, Carvalho, Silva, Neves, Santos, de Sousa, da Silva, de Mello, Carvalho, Braga, Harada, Justino, Costa, Brasil-Costa, Monteiro, Clemente and Terreri.)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-COVID condition due to a delayed hyperimmune response to SARS-CoV-2. High-density lipoproteins (HDL) are pivotal players in inflammatory and immune modulation through the remodeling of their subfractions., Methods: This study aimed to evaluate serum levels of cholesterol, HDL, and HDL subfractions (HDL-SUB) to define their role in the pathogenesis of MIS-C and their potential use as biomarkers of this condition. We analyzed serum cholesterol, HDL and HDL-SUB (by capillary electrophoresis) in relation to serum values of biomarkers of inflammation and endothelial damage (by microfluidic immunoassays) in 48 patients with MIS-C at hospital admission and in 48 age- and sex-matched healthy controls., Results: Serum cholesterol, as well as HDL, were significantly lower in MIS-C patients than controls. Serum cholesterol was inversely correlated with all biomarkers of inflammation, confirming the impact of cytokines on reverse cholesterol transport, whereas HDL values were inversely correlated with serum biomarkers of endothelial damage, suggesting a role of HDL in endothelial damage in MIS-C patients. Furthermore, we found a remodeling of HDL-SUB with a more pronounced decrease in small HDL that have anti-inflammatory activity., Conclusions: These data confirm the severe impairment of reverse cholesterol transport in MIS-C and indicate serum HDL and HDL-SUB as potential useful diagnostic biomarkers of MIS-C., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the University Federico II of Naples. Written informed consent to participate in this study was provided by the legal guardian/next relative of the participants. Competing interests: The authors declare that they have 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).)

Background: To assess the value of combined Monocyte Distribution Width (MDW) and Procalcitonin (PCT) detection in diagnosing and predicting neonatal sepsis outcomes., Methods: This retrospective study, conducted from January 2022 to December 2023.A retrospective analysis of 39 neonatal sepsis and 30 non-infectious systemic inflammatory response syndrome (SIRS) cases was conducted. MDW, PCT, and CRP levels were compared. Relationships between variables were analyzed with Pearson correlation and Cox regression models; diagnostic performance was assessed using ROC curves., Results: MDW, PCT, and CRP were significantly elevated in sepsis cases (p < 0.001). In non-survivors, MDW was higher and correlated with CRP, PCT, and SNAP scores. MDW was identified as an independent predictor of 28-day mortality. Optimal MDW, PCT, and CRP cut-offs (21.3, 1.23 ng/ml, 32.8 mg/L) achieved AUCs of 0.80, 0.84, and 0.60, respectively. Combined MDW/PCT detection achieved an AUC of 0.90 with 88.2% sensitivity and 88.7% specificity., Conclusion: MDW, especially when combined with PCT, improves diagnostic accuracy for neonatal sepsis management., Competing Interests: Declarations. Ethics approval and consent to participate: This study follows the ethical principles of the Declaration of Helsinki and has been approved by the Ethics Committee of Donghai Hospital Affiliated to Kangda College of Nanjing Medical University (Approval No.: LJYY2022-01).All participants provided signed informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This study aimed to evaluate pathological findings on abdominal ultrasonography upon admission of children diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C) that were associated with a more severe disease course and the need for intensive care unit (ICU) admission. This retrospective and observational study was conducted between March 2020 and May 2022. Abdominal ultrasonography findings were evaluated in children diagnosed with MIS-C associated with SARS-CoV-2. Ultrasound examinations were conducted within the first 24 h following hospital admission. Clinical severity was categorized as mild-moderate or severe based on the highest clinical severity score observed at any point during hospitalization, using the criteria of dehydration, oxygen or inotropic requirements, cardiac involvement, and respiratory support. The indications of ICU admission were decreased ejection fraction, pulmonary involvement, and any signs of shock. We compared the presence of any individual ultrasonography findings with clinical severity and the need for ICU admission. Multivariable logistic regression analysis was performed to identify independent sonographic predictors of clinical severity and ICU admission. A total of 70 children were included in the study, 16 of whom (23%) were categorized as having severe diseases. ICU admission was required for 14 children (20%), 13 of whom had severe disease. Notably, three children with severe clinical scores did not require ICU admission. The most common ultrasonography findings were intra-abdominal free fluid (41%), hepatomegaly (36%), splenomegaly (33%), mesenteric inflammation (21%) and mesenteric lymphadenopathy (%19). Intra-abdominal free fluid (p < 0.001; OR = 18.20; 95% CI, 3.69-89.86), mesenteric inflammation (p < 0.001; OR = 10.29; 95% CI, 2.80-37.83), mesenteric lymphadenopathy (p = 0.007; OR = 6.22; 95% CI; 1.69-22.88), and hepatosplenomegaly (p = 0.039; OR = 3.89; 95% CI, 1.15-13.17) were substantially associated with severe clinical outcomes. Intra-abdominal free fluid (p < 0.001; OR = 13.76; 95% CI, 2.77-68.29) and hepatosplenomegaly (p = 0.002; OR = 8.00; 95% CI, 2.19-29.25) were significantly more common in children who required ICU admission. Multivariable logistic regression analysis revealed that intra-abdominal free fluid was an independent predictor of severe disease (p = 0.026; OR = 7.41; 95% CI, 1.28-43.00) and ICU admission (p = 0.007; OR = 9.80; 95% CI, 1.88-51.04)., Conclusion: Abdominal ultrasonography findings may indicate clinical severity in children with MIS-C. Intra-abdominal free fluid strongly correlates with severe clinical outcomes and the need for intensive care., What Is Known: • Abdominal ultrasonography findings in children with MIS-C are non-specific and include intra-abdominal free fluid, mesenteric lymphadenopathy, and hepatosplenomegaly. • MIS-C is associated with significant systemic inflammation and can present with a variety of extracardiac symptoms, often overlapping with acute abdominal conditions., What Is New: • Intra-abdominal free fluid on ultrasonography is strongly associated with severe clinical outcomes and the need for ICU admission in MIS-C patients • This study identifies intra-abdominal free fluid as an independent sonographic predictor of disease severity and intensive care needs, emphasizing the importance of early abdominal ultrasonography in MIS-C management., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Multisystem inflammatory syndrome in children (MIS-C) is an uncommon but severe hyperinflammatory illness that occurs 2 to 6 weeks after SARS-CoV-2 infection. Presentation overlaps with other conditions, and risk factors for severity differ by patient. Characterizing patterns of MIS-C presentation can guide efforts to reduce misclassification, categorize phenotypes, and identify patients at risk for severe outcomes., Objective: To characterize phenotypic clusters of MIS-C and identify clusters with increased clinical severity., Design, Setting, and Participants: In this cohort study, MIS-C phenotypic clusters were inferred using latent class analysis applied to the largest cohort to date of cases from US national surveillance data from 55 US public health jurisdictions. Cases reported to the Centers for Disease Control and Prevention MIS-C national surveillance program as of April 4, 2023, with symptom onset on or before December 31, 2022, were retrospectively analyzed. Twenty-nine clinical signs and symptoms were selected for clustering after excluding variables with 20% or more missingness and 10% or less or 90% or more prevalence. A total of 389 cases missing 10 or more variables were excluded, and multiple imputation was conducted on the remaining cases., Main Outcomes and Measures: Differences by cluster in prevalence of each clinical sign and symptom, percentage of patients admitted to the intensive care unit (ICU), length of hospital and ICU stay, mortality, and relative frequency over time., Results: Among 8944 included MIS-C cases (median [IQR] patient age, 8.7 [5.0-12.5] years; 5407 [60.5%] male), latent class analysis identified 3 clusters characterized by (1) frequent respiratory findings primarily affecting older children (respiratory cluster; 713 cases [8.0%]; median [IQR] age, 12.7 [6.3-16.5] years), (2) frequent shock and/or cardiac complications (shock and cardiac cluster; 3359 cases [37.6%]; median [IQR] age, 10.8 [7.7-14.0] years), and (3) remaining cases (undifferentiated cluster; 4872 cases [54.5%]; median [IQR] age, 6.8 [3.6-10.3] years). The percentage of patients with MIS-C admitted to the ICU was highest for the shock and cardiac cluster (82.3% [2765/3359]) followed by the respiratory (49.5% [353/713]) and undifferentiated clusters (33.0% [1609/4872]). Among patients with data on length of stay available, 129 of 632 hospitalizations (20.4%) and 54 of 281 ICU stays (19.2%) in the respiratory cluster lasted 10 or more days compared with 708 of 3085 (22.9%) and 157 of 2052 (7.7%), respectively, in the shock and cardiac cluster and 293 of 4467 (6.6%) and 19 of 1220 (1.6%), respectively, in the undifferentiated cluster. The proportion of cases in both the respiratory cluster and the shock and cardiac cluster decreased after emergence of the Omicron variant in the US., Conclusions and Relevance: In this cohort study, MIS-C cases clustered into 3 subgroups with distinct clinical phenotypes, severity, and distribution over time. Use of clusters in future studies may support efforts to evaluate surveillance case definitions and identify groups at highest risk for severe outcomes.

The genetic basis of neonatal COVID-19 infection, which exhibits a range of severity, has not been investigated. We identified both shared and unique genetic variants involved in antiviral immune responses through whole exome sequencing of an infant who developed severe COVID-19 pneumonia and multisystem inflammatory syndrome and the twin brother also positive for severe acute respiratory syndrome-coronavirus-2, but with only moderate respiratory symptoms., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19), which is now known to be caused by severe acute respiratory syndrome coronavirus 2, has been a public health threat since early 2020 and has affected millions of people worldwide. Many studies have now shown that this virus exhibits a milder infection in children compared to adults. Acute COVID-19 infection, multisystem inflammatory syndrome in children (MIS-C), and long COVID have been recently well-established in the pediatric population with a myriad of systemic manifestations. This section of the review will focus on the following systems-neurology, psychiatry, endocrinology, hematology, and oncology-under three broad lenses, such as acute COVID-19, MIS-C, and long COVID. [ Pediatr Ann . 2025;54(1):e40-e44.] ., Competing Interests: Disclosure: The authors have disclosed no potential conflicts of interest, financial or otherwise.

Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Disclosures: Dr. Truong is an MPI on an NHLBI Pediatric Heart Network-Pfizer Partnership to Study COVID-19 Vaccine-Associated Myocarditis. Dr. Harahsheh serves as a scientific advisory board member of OP2 DRUGS (“OP2”) but this advisory position has no relevant disclosures for this manuscript., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Every hospital admission is associated with healthcare costs and a risk of adverse events. The need to identify patients who do not require hospitalization has emerged with the profound increase in hospitalization rates due to infectious diseases during the last decades, especially during the COVID-19 pandemic. This study aimed to identify predictors of safe early discharge (SED) in patients presenting to the emergency department (ED) with a suspected infection meeting the Systemic Inflammatory Response Syndrome (SIRS) criteria., Methods: We conducted a prospective cohort study on adult non-trauma patients with a suspected infection and at least two SIRS criteria. We defined SED as hospital discharge within 24 h (e.g. direct ED discharge or rapid ward discharge) without disease-related readmission to our hospital or death during the first seven days. A prediction model for SED was developed using multivariate logistic regression analysis and tested with k-fold cross-validation., Results: We included 1381 patients, of whom 1027 (74.4 %) were hospitalized for longer than 24 h or re-admitted within seven days and 354 (25.6 %) met SED criteria. Parameters associated with SED were relatively young age, absence of comorbidities, living independently, yellow or green triage urgency, lack of ambulance transport or general practitioner referral, normal clinical impression scores, and risk scores (i.e., qSOFA, PIRO, MEDS, NEWS, and SIRS), normal vital sign measurements and absence of kidney and respiratory failure. The model performance metrics showed an area under the curve of 0.824. The validation showed a minimal drop in performance and indicated a good fit., Conclusion: We developed and validated a model to identify patients with an infection at the ED who can be safely discharged early., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The systemic inflammatory response index (SIRI) is a recently developed composite index that assesses the entire extent of inflammation in the body, closely linked to heart failure (HF). This study aimed to evaluate the potential association between SIRI and HF., Methods: The cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) database from 2001 to 2018. SIRI is calculated based on the counts of monocytes, neutrophils, and lymphocytes. A weighted multiple-variable linear regression model examined the correlation between SIRI and HF. Using restrained cubic splines explored the nonlinear relationship between the two, and the robustness of the results was verified by subgroup analysis and interaction tests., Results: Our study included 30,294 participants, 814 of whom were diagnosed with HF and 29,480 with non-HF. The multiple linear regression analysis showed that SIRI was positively correlated with HF (OR = 1.66; 95 % CI, 1.21, 2.29) and that there was no nonlinear relationship between the two. This relationship persisted in subgroup analyses., Conclusions: The results indicate a linear positive correlation between SIRI and HF. Further extensive prospective studies are needed to validate these findings., (Copyright © 2024 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Studies on the severity in multisystem inflammatory syndrome in children (MIS-C) show heterogeneous results and may not reflect a global perspective. This systematic review aims to estimate the frequency of in-hospital unfavorable outcomes in patients with MIS-C over the 3 years since the onset of the SARS-CoV-2 pandemic. A systematic search was conducted in Medline, Scopus, Embase, Cochrane, Web of Science, Scielo, and preprint repositories until December 15, 2022. Study selection and data extraction were evaluated independently. The primary outcomes were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death. Additionally, we evaluated cardiovascular-related outcomes. We performed a random-effects model meta-analysis and assessed the certainty of the evidence. Fifty-seven studies (n = 13 254) were included. The frequency of ICU admission was 44.7% (95% CI 38.8-50.7), 11.9% for IMV (95% CI 9.6-14.4), and 2.0% for death (95% CI 1.3-3.0). The requirement of vasoactive/inotropic drugs was 40.1% (95% CI 35.9-44.4), 7.9% for coronary aneurysm (95% CI 4.1-12.7), 30.7% for decreased left ventricle ejection fraction (LVEF) (95% CI 26.3-35.4), and 29.7% for myocarditis (95% CI 18.4-42.4). We assess the included evidence as being of very low certainty. Finally, excess COVID-19 mortality by country and the diagnostic criteria for MIS-C (CDC compared to WHO) were associated with a higher frequency of ICU admissions. The year of study conduction (2022 compared to 2020) was associated with a lower frequency of IMV., Conclusion: The frequency of in-hospital unfavorable outcomes in patients with MIS-C was high. Well-designed studies are needed to explore other heterogeneity sources., Protocol Registration: CRD42021284878., What Is Known: • Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious condition linked to SARS-CoV-2. Studies on the severity of MIS-C show heterogeneous results. These findings may not be representative of the reality in other regions, making it challenging to draw generalizable conclusions., What Is New: • Over the 3 years since the onset of the SARS-CoV-2 pandemic, our systematic review has shown that the frequency of in-hospital unfavorable outcomes in patients with MIS-C is high, with a very low certainty of the evidence. Our results reflect the reality from a global perspective, across different countries with varying income levels. • The main sources of heterogeneity in the frequency of severe outcomes could be explained by the excess mortality due to COVID-19 in each country, the type of diagnostic criteria for MIS-C, and the year the study was conducted., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The performance of host immune responses biomarkers and clinical scores was compared to identify infection patient populations at risk of progression to sepsis, ICU admission and mortality., Methods: Immune response biomarkers were measured and NEWS, SIRS, and MEWS. Logistic and Cox regression models were employed to evaluate the strength of association., Results: IL-10 and NEWS had the strongest association with sepsis development, whereas IL-6 and CRP had the strongest association with ICU admission and in-hospital mortality. IL-6 [HR (95%CI) = 2.68 (1.61-4.46)] was associated with 28-day mortality. Patient subgroups with high IL-10 (≥ 5.03 pg/ml) and high NEWS (> 5 points) values had significantly higher rates of sepsis development (88.3% vs 61.1%; p  < 0.001), in-hospital mortality (35.0% vs. 16.7%; p  < 0.001), 28-day mortality (25.0% vs. 5.6%; p  < 0.001), and ICU admission (66.7% vs. 38.9%; p  < 0.001)., Conclusions: Patients exhibiting low severity signs of infection but high IL-10 levels showed an elevated probability of developing sepsis. Combining IL-10 with the NEWS score provides a reliable tool for predicting the progression from infection to sepsis at an early stage. Utilizing IL-6 in the emergency room can help identify patients with low NEWS or SIRS scores.

Background: Multisystem inflammatory syndrome (MIS-C) represents a diagnostic challenge because of its overlap with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome. Macrophage activation syndrome (MAS) is a frequently fatal complication of various pediatric inflammatory disorders and has been reported in MIS-C. Early diagnosis and prompt initiation by immune modulating therapies are essential for effectively managing MAS., Methods: We conducted a retrospective study to determine the frequency, natural history, diagnostic metrics, treatment, and outcome of MAS in MIS-C within a large cohort of patients across 84 Latin American centers in 16 countries. We compared the clinical and laboratory characteristics between patients with and without MAS., Results: Among 1238 patients with MIS-C, 212 (17.1%) fulfilled MAS criteria. Gastrointestinal and neurologic manifestations were more frequent in cases where MIS-C was complicated by MAS. Patients presenting with MIS-C complicated by MAS had a mortality rate of 12%, which was higher than those without it. Mortality was associated with MAS, seizures, arthritis, and shock. A ferritin or erythrocyte sedimentation rate ratio of >18.7 exhibited a sensitivity of 88.2% and a specificity of 75% in diagnosing MAS in MIS-C., Conclusions: MAS in MIS-C patients is associated with increased morbidity and mortality rates in the largest MIS-C Latin American cohort. Early recognition and appropriate management are crucial in improving patient outcomes and reducing mortality rates., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: To determine the short- and medium-term cardiac outcomes in children admitted with multisystem inflammatory syndrome in children at a tertiary care centre in Pakistan., Methods: Children fulfilling the criteria for multisystem inflammatory syndrome and admitted to the hospital between April 2020 and March 2022 were enrolled in this prospective longitudinal cohort study. From admission to discharge, laboratory and cardiac parameters were recorded for all patients, who were subsequently followed up in clinics at various intervals. Data analysis was conducted using STATA version 15.0., Results: A total of 51 children were included, with viral myocarditis (41.2%) and toxic shock syndrome (33.3%) being the most common phenotypes. The cardiovascular system was most commonly affected in 27 children (53%) with laboratory evidence of inflammation and myocardial injury with median and interquartile levels of ferritin 1169 (534-1704), C-reactive protein 83 (24-175), lactate dehydrogenase 468 (365-1270), N-terminal pro-B-type natriuretic peptide 8,656 (2,538-31,166), and troponin 0.16 (0.02-2.0).On admission, decreased left ventricular ejection fraction was observed in 58.8% of patients and impaired global longitudinal strain in 33.3%. At discharge, left ventricular ejection fraction had normalised in 83% of patients. Pericardial effusion resolved in all patients, and valvulitis resolved in 86% by 12 months. Paediatric ICU admission was required in 42 (82%) of patients with an overall mortality of 12% ( n = 6)., Conclusion: Our study finds high hospital mortality for multisystem inflammatory syndrome in children compared to 1-2% from previous studies. Yet, in Pakistan, surviving children with multisystem inflammatory syndrome show favourable short- to medium-term cardiac outcomes.

The coronavirus disease 2019 (COVID-19) originated in Wuhan, China, in late 2019. Within a span of a few months, it was deemed a global pandemic by the World Health Organization. It was first thought to affect the adult population, but soon after, cases of COVID-19 in children started emerging. As more and more pediatric cases started unveiling, an entity called multisystem inflammatory syndrome in children (MIS-C) that replicated Kawasaki disease was established. More recently, it has been noted that children have persistent symptoms for weeks or months after acute COVID-19 infection, and the term coined for these symptoms is "long COVID." This section of the review will summarize the respiratory, cardiovascular, dermatological, and gastroenterological manifestations noted in infants in three broad categories: acute COVID, MIS-C, and long COVID. [ Pediatr Ann . 2024;53(12):e473-e477.] .

Endothelial-cell-specific molecule-1 (ESM-1) also called endocan is a well-known biomarker for detecting inflammation, endothelial dysfunction (ED), and cardiovascular (CV) risk in COVID-19 patients. Upon SARS-CoV-2 infection, a small percentage of children develop Multisystem Inflammatory Syndrome in children (MIS-C). Whether endocan can be used as a biomarker of MIS-C is unknown. In this study, we assessed ESM-1 levels in MIS-C (n = 19) and healthy controls (HC; n = 17). We observed a significant increase in serum ESM-1 levels in MIS-C vs HC (p = 0.0074). In addition, ROC curve analysis demonstrated that this factor has a reasonable discriminatory power between MIS-C patients and HC (AUC of 0.7585). Notably, after one week of hospitalization and care, ESM-1 levels decreased, and this reduction was observed also for other inflammatory and pro-thrombotic markers like C-reactive protein, procalcitonin, fibrinogen, D-dimer, and ferritin, suggesting a general recovery trend in MIS-C patients. In fact, we observed that serum ESM-1 levels positively correlated with procalcitonin (PCT) (r = 0.468; p = 0.043). Finally, logistic regression analysis demonstrated an association between endocan levels and cardiac complications like myocarditis. Therefore, this study suggests that ESM-1 is a valuable diagnostic and prognostic biomarker in patients with MIS-C that may help identify those MIS-C patients at higher risk for cardiovascular complications and guide treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Multisystemic inflammatory syndrome (Mis-C) has emerged in May 2020 as a serious complication of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). A total of 6 children presented to tertiary care hospitals with Mis-C, of which 5 (83%) have died during hospitalization. All included patients presented with respiratory symptoms (ranged from mild to severe acute respiratory distress syndrome) and gastrointestinal symptoms. Most of the patients are known to have medical illnesses. Pediatric Risk of Mortality (PRISM) IV score ranged from 3 to 87. All patients developed acidosis and varying stages of acute kidney injury and electrolyte disturbances. All were treated for coagulopathy, thrombocytopenia, bacterial infections as well as antiviral medications (either ritonavir or lopinavir). Most patients had chest X-ray changes either unilateral or bilateral lung changes. Multisystemic inflammatory syndrome is a rare, yet serious complication of SARS-CoV2 infection in children. Multisystem involvement should be anticipated and promptly treated., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Organ failure (OF) is a sinister development in the clinical course of acute pancreatitis, and its prediction is crucial for triaging the patient. Persistent systemic inflammatory response syndrome and raised interleukin-6 levels have a good predictive accuracy. Pathophysiology involves the release of damage-associated molecular patterns as a consequence of pancreatic injury, recruitment of inflammatory cells, and the release of proinflammatory cytokines and chemokines causing cytokine storm. Respiratory system is the most common and earliest to fail. Although a few therapeutic options are in the pipeline, renewed efforts are required to develop targeted therapies to mitigate systemic inflammation and OF., Competing Interests: Disclosure None of the authors declare any conflict of interest. Financial support: Pramod Garg is supported by JC Bose Fellowship by Science and Engineering Research Board, Govt. of India., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study aimed to explore the relationship between the Systemic Inflammatory Response Index (SIRI) and Cerebral Small Vessel Disease (CSVD), focusing on its key imaging markers., Methods: We enrolled 344 patients admitted to the neurology department between January 2022 and September 2024, comprising 223 patients diagnosed with CSVD and 121 without CSVD. Baseline characteristics were compared between groups, and multivariate logistic regression was performed to assess the impact of SIRI on CSVD risk. Further, univariate and multivariate logistic regression analyses were conducted to examine the relationship between SIRI and CSVD imaging markers, including White Matter Hyperintensity (WMH), lacunes, Perivascular Space (PVS), and Recent Small Subcortical Infarct (RSSI)., Results: Significant differences were observed between the CSVD and non-CSVD groups in terms of age, sex, history of hypertension, diabetes, white blood cell count, neutrophil count, lymphocyte count, homocysteine levels, and SIRI values. Multivariate analysis confirmed that elevated SIRI is independently associated with an increased risk of CSVD. Additionally, higher SIRI values were linked with more severe CSVD imaging features, including moderate-to-severe WMH, the presence of lacunes, and RSSI., Conclusion: These findings demonstrate that elevated SIRI is independently associated with both the occurrence of CSVD and the severity of key imaging markers such as WMH, lacunes, and RSSI. This suggests that SIRI could serve as a useful inflammatory marker for assessing CSVD risk and progression., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest in relation to this study., (Copyright © 2025. Published by Elsevier Inc.)

Background: Multisystem inflammatory syndrome in children (MIS-C) presents some clinical overlap with Kawasaki disease (KD). Although KD is common in Japan, the clinical characteristics of MIS-C in Japan remain unknown. Therefore, we aimed to determine the epidemiological and clinical features of MIS-C in Japan., Methods: Using a case reporting form, a nationwide registry was created between November 2020 and March 2023, involving 2,080 facilities throughout Japan. We prospectively and retrospectively enrolled patients with MIS-C. The primary outcomes were the number and incidence rates of children with MIS-C. The secondary outcomes included clinical features, such as KD phenotype, organ involvement, shock, intensive care unit admission, and coronary artery lesions., Results: Among 398 patients registered, central review identified 129 MIS-C cases (mean age: 8·8 ± 3·7 years). The overall incidence rate was estimated to be 1·5 per 100,000 COVID-19 cases, exhibiting a decline as the COVID-19 pandemic progressed, from 12·3 cases (Pre-Delta) to 1·3 cases (Omicron); 80% of MIS-C cases occurred during the Omicron variant predominant period, and 72% of children with MIS-C met the KD criteria. Cardiovascular (88%) and gastrointestinal (90%) involvement were frequent. In Japan, MIS-C cases showed comparatively less severe clinical features, with shock in 29% and admission to the intensive care unit in 12% of cases. Coronary artery lesions were identified in 15 cases (11·6%), irrespective of the presence of shock. No fatalities were reported., Conclusion: The incidence of MIS-C was low in Japan. The clinical features distinctively exhibited a more KD-like phenotype, with less severe clinical features., Competing Interests: Declarations. Ethics Approval and Consents: This study was approved by the Institutional Review Board of Jichi Medical University (IRB: 23-026) and the respective multicenter institutes involved in this study. The participating sites obtained approval from their local IRB if needed. Written informed consent was not necessary as only deidentified data were used; instead, an opt-out opportunity was made available on the websites of the Department of Public Health at Jichi Medical University and at each participating facility. This study was performed in line with the principles of the Declaration of Helsinki. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Severe alcoholic hepatitis is a catastrophic disease with a mortality rate of up to 35-50% at 30 days. Bacterial infection is an important prognostic factor in patients with severe alcoholic hepatitis, but it is difficult to detect the presence of infection immediately. Procalcitonin (PCT) is a well-known inflammatory marker that can detect bacterial infections in various diseases early. Therefore, we aimed to evaluate the diagnostic accuracy of PCT for bacterial infection in severe alcoholic hepatitis., Methods: We prospectively enrolled patients with severe alcoholic hepatitis, defined as modified Maddrey's Discriminant Function ≥ 32, from 10 medical centers. At admission, we performed an initial evaluation including physical examination, laboratory test, radiology, blood and urine culture, PCT, and C-reactive protein (CRP). We compared the receiver operating characteristic (ROC) curves of PCT and CRP for bacterial infection, systemic inflammatory response syndrome (SIRS), and sepsis among total patients., Results: A total of 108 patients with severe alcoholic hepatitis were enrolled. The number of bacterial infections, SIRS, and sepsis were 31 (28.7%), 41 (38.0%), and 19 (17.6%), respectively. The patients with bacterial infection had significantly higher MELD scores (24.0 vs. 15.0), PCT levels (1.5 vs. 0.4 ng/mL), and CRP levels (4.9 vs. 2.5 mg/dL) compared to those without bacterial infection. The area under the ROC curve (AUROC) of PCT vs. CRP for bacterial infection was 0.752 and 0.655, respectively (P = 0.113). The AUROC of PCT vs. CRP for SIRS was 0.699 and 0.662, respectively (P = 0.490). The AUROC of PCT vs. CRP for sepsis was 0.780 and 0.630, respectively (P = 0.027)., Conclusions: Among patients with severe alcoholic hepatitis, PCT showed a trend of superior diagnostic performance in the early detection of bacterial infection and sepsis compared to CRP. Although PCT might have better potential to diagnose sepsis in the setting of severe alcoholic hepatitis, it is necessary to find more reliable diagnostic markers., Competing Interests: Declarations. Ethical approval and consent to participate: This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study protocol was approved by Institutional review boards of all ten participating medical centers; Inje University Haeundae Paik Hospital (Inje University Haeundae Paik Hospital Institutional Review Board), Inje University Busan Paik Hospital (Inje University Busan Paik Hospital Institutional Review Board), Dong-A University Hospital (Dong-A University Hospital Institutional Review Board), Pusan National University Yangsan Hospital (Pusan National University Yangsan Hospital Institutional Review Board), Kosin University Gospel Hospital (Kosin University Gospel Hospital Institutional Review Board), Gyeongsang National University Changwon Hospital (Gyeongsang National University Changwon Hospital Institutional Review Board), Daegu Catholic University Medical Center (Daegu Catholic University Medical Center Institutional Review Board), Kyungpook National University Hospital/Kyungpook National University Chilgok Hospital (Kyungpook National University Hospital Institutional Review Board), Keimyung University Dongsan Hospital (Keimyung University Dongsan Hosptial Institutional Review Board), Yeungnam University Medical Center (Yeungnam University Hospital Institutional Review Board). Consent for publication: Not applicable. Informed consent: was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Multisystem inflammatory syndrome in children (MIS-C) has been reported in patients with inborn errors of immunity (IEI), providing insights into disease pathogenesis. Here, we present the first case of MIS-C in a child affected by Wiskott-Aldrich syndrome (WAS) gene mutation, elucidating underlying predisposing factors and the involved inflammatory pathways. Genetic analysis revealed a frameshift truncating variant in the WAS gene, resulting in WAS protein expression between mild and severe forms, despite a clinical phenotype resembling X-linked thrombocytopenia (XLT). IL-1β secretion by LPS-stimulated peripheral blood mononuclear cells from patient during MIS-C was lower compared to healthy subjects but increased during follow-up. Conversely, the percentage of ASC (apoptosis-associated speck-like protein containing a CARD) specks in the patient's circulating monocytes during the acute phase was higher than in healthy subjects. The type I interferon (IFN) signature during MIS-C was normal, in contrast to the raised IFN signature measured far from the acute event. This case supports the association of IEI with MIS-C, potentially linked to delayed immune responses to SARS-CoV-2. The XLT phenotype underlies a subclinical immunodysregulation involving the NLRP3 inflammasome and the type-I IFN response., Competing Interests: Declarations. Ethical Approval: The study was approved by the Local Ethics Committee and conducted in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Patients or parents/legal guardians provided written informed consent. Consent to Participate: The authors confirm that a relevant local consent has been signed by the patient and/or the legally authorized representative. Consent for Publication: The authors confirm that a relevant local consent has been signed by the patient and/or the legally authorized representative. Competing Interests: MG reports grants and personal fees from Novartis, grants and personal fees from SOBI, outside the submitted work. FP, AB, IP, SV and RC report speaker fee from SOBI. The other authors declared that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to evaluate the range of clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C) with COVID-19 in a tertiary children's hospital in Northwest Iran during 2020-2022. According to the CDC guidelines, this cross-sectional study included 300 pediatric patients diagnosed with MIS-C. Data were collected retrospectively from medical records, focusing on symptoms, organ involvement, laboratory findings, and outcomes. Statistical analysis was performed using SPSS software, with significance set at p-values <0.05. The study population had a median age of 3 years, with a slight male predominance (57.3%). The most affected systems in MIS-C disease were hematological (87%), gastrointestinal (85%), and respiratory (67%). Laboratory analysis highlighted elevated inflammatory markers such as D-dimer (83.3%), ferritin (71.4%), and CRP (49.7%). Abnormal urinalysis was observed in 151 patients (50.3%), with glucosuria in 83 cases (27.7%) and proteinuria in 29 cases (9.7%). The study found a significant correlation between cardiovascular issues and elevated blood platelets, ESR, CRP, and troponin levels (P ≤ 0.01) but not with ferritin, albumin, or D-dimer levels. Also, the examination of disease outcomes in this study revealed that 81.7% of MIS-C patients were isolated during their hospital stay, 18.3% needed ICU care, and 1% died in hospital. We have presented an experience with distinct clinical and laboratory manifestations in MIS-C. Given the lower median age in this study compared to previous studies, reporting clinical and laboratory manifestations of MIS-C in pediatrics with a younger age is valuable for the diagnosis and treatment course. Some laboratory factors were risk factors for cardiovascular involvement, and consequently, echocardiography is recommended in MIS-C patients with these laboratory indications. Given the lack of a specific diagnostic test for this emerging disease, studies focusing on investigating clinical symptoms and findings are valuable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Farshidgohar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Systemic inflammatory response syndrome (SIRS) following cardiovascular interventions is associated with adverse events during hospitalization and follow-up. Mitral transcatheter edge-to-edge repair is increasingly utilized for treatment of mitral regurgitation (MR). We investigated whether SIRS following mitral transcatheter edge-to-edge repair may occur and be associated with adverse clinical outcomes., Methods and Results: A total of 158 consecutive patients with severe MR undergoing mitral transcatheter edge-to-edge repair were studied. SIRS was defined by leukocytosis (≥12 × 10 9 /L) and fever (≥38 °C) within 48 hours after intervention. Baseline inflammation was measured by absolute neutrophil and lymphocyte counts and neutrophil-lymphocyte ratio. The primary end point of major cardiovascular events was the composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. Recurrent MR at follow-up was also recorded. The mean patient age was 80.8±8.8 years. Forty-four (27.9%) developed SIRS. Neutrophil-lymphocyte ratio correlated with onset of leukocytosis and fever ( P =0.04). During a median follow-up of 12.5 (5.4-17.4) months, the primary end point occurred in 27 (17.1%) patients (6 myocardial infarction, 5 strokes, and 16 deaths). Patients with SIRS more often had severe MR (79.5% versus 62.7%, P =0.02) at follow-up. After adjustment for pertinent variables, SIRS (HR 2.73 [95% CI, 1.08-6.86]; P =0.03) was independently associated with major cardiovascular events., Conclusions: SIRS after mitral transcatheter edge-to-edge repair is a strong independent predictor of major cardiovascular events. Closer follow-up is warranted because patients with SIRS have more severe MR at follow-up.

In 2020, 20% of patients with COVID-19 developed severe complications, including life-threatening pneumonia with systemic inflammatory response syndrome (SIRS). We developed a preliminary SIRS monitor that does not require blood sampling, is noninvasive, and can collect data 24 h per day. The proposed monitor comprises a piezoelectric respiratory sensor located beneath the patient's mattress and a fingertip pulse sensor that determines ultra-high accuracy respiratory rate (mode of a 40-min frequency distribution of respiratory rates (M40FD-RR)). We assessed the clinical performance of the M40FD-RR preliminary SIRS monitor in 29 patients (12 female, 17 male, aged 15-90 years) hospitalized at Suwa Central Hospital with COVID-19, which was confirmed by a positive polymerase chain reaction test. SIRS was evaluated by logistic regression analysis using M40FD-RR, heart rate, age, and sex as explanatory variables. We compared the results of 109 examinations of 29 COVID-19 inpatients with SIRS against those determined by the proposed monitor. The proposed monitor achieved 75% sensitivity and 83% negative predictive value, making it a promising candidate for future 24 h noninvasive preliminary SIRS tests.

Background: The aim of this study was to investigate the prognostic value of systematic inflammatory response in patients with lymph node-negative colorectal cancer., Methods: We retrospectively investigated 245 patients with lymph node-negative colorectal cancer who underwent curative resection and evaluated the prognostic impact of systematic inflammatory response, which was represented by neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and C-reactive protein-to-albumin ratio (CAR). Then, the prognostic significance of the systematic inflammatory response on survival was analyzed using the Kaplan-Meier method in patients selected by propensity score matching (PSM) analysis., Results: In the multivariate analysis, CAR ≥ .081 ( P = .004) was independent predictors of disease-free survival, while American Society of Anesthesiologists physical status ≥3 ( P = .049) and CAR ≥ .081 ( P < .001) were independent predictors of overall survival. By PSM analysis, PSM-high-CAR was significantly associated with worse disease-free survival ( P = .043) and overall survival ( P = .041) in patients with lymph node-negative colorectal cancer., Conclusions: C-reactive protein-to-albumin ratio may be a significant indicator of poor long-term outcomes in patients with lymph node-negative colorectal cancer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Post implantation syndrome (PIS) is a well-defined entity with unclear etiology, complicating a number of patients with abdominal aortic aneurysms treated with endovascular aortic repair (EVAR). The aim of this study was to assess the platelets' role and the influence of aneurysmal sac thrombus volumes in the development of PIS. A retrospective analysis of prospectively collected data was performed, and 76 patients who were treated by EVAR (2011-2013) were studied. Aneurysms with endoleak were not included in the study. Based on the criteria for systemic inflammatory response syndrome (SIRS), 17 patients (22%) developed PIS (which is considered a SIRS analogue), while 59 (78%) did not., Methods: The 2 groups were compared in relation to the following parameters: baseline platelet count (PLT), decrease of platelet count (PLT drop), volume of the arterial flow before the procedure (V flow), volume of thrombus of the aneurysm (V thromb), ratio of thrombus volume to aneurysm sac volume (V ratio), and the volume of newly formed thrombus (V new). Volume flow measurements were calculated by Osirix software preoperatively and in the first month postoperatively. Parametric and nonparametric techniques (unpaired t-test, Mann-Whitney U test) were used accordingly., Results: Baseline platelets absolute count was greater in the PIS group (239,000 ± 17,000) versus the non-PIS group (194,000 ± 6,900, P = 0.004), and the PLT drop was larger in the PIS group (74,000 ± 15,600 versus 45,000 ± 5,300, P = 0.019). No difference was found regarding the aneurysm volumes (V flow, V thromb, V ratio, and V new) between the 2 groups., Conclusions: Platelets, in terms of their absolute baseline count and their decrease after the procedure, seem to be an important factor in developing PIS after EVAR. Further, more tailored studies are needed to elucidate the role of platelets and flow or thrombus volumes in the development of PIS., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In recent years, some studies classified patients with sepsis and predicted their mortality by using some evaluation scales. Several studies reported significant differences in the predictive values of several tools, and the non-uniformity of the cut-off value., Aim: To determine and compare the prognostic accuracy of Sequential Organ Failure Assessment (SOFA) score, Modified Early Warning Score (MEWS), and Systemic Inflammatory Response Syndrome (SIRS) criteria in predicting the mortality of patients with sepsis., Methods: This study comprised of systematic literature review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched PubMed, Embase, Web of Science and Cochrane Library databases from their establishment to July 31, 2022. The research articles published in the index journals provide sufficient data (true positive, false positive, true negative, and false negative results) for patients with sepsis. The combined sensitivity and specificity of the 95% confidence interval (CI) were calculated using the bivariate random effect model (BRM). The hierarchical overall subject working characteristics (HSROC) curve was drawn to evaluate the accuracy of the overall prognosis., Results: Data of 55 088 patients from 32 studies were included in this meta-analysis. SOFA had an intermediate sensitivity of 0.73 (95% CI: 0.67-0.78) and a specificity of 0.70 (0.63-0.76). SIRS criteria had the highest sensitivity of 0.75 (0.66-0.82) and the lowest specificity of 0.40 (0.29-0.52). MEWS had the lowest sensitivity of 0.49 (0.40-0.59) and the highest specificity of 0.82 (0.78-0.86)., Conclusions: Among SOFA, MEWS, and SIRS criteria, SOFA showed moderate sensitivity and specificity for predicting mortality in patients with sepsis, the highest sensitivity of SIRS and the strongest specificity of MEWS for predicting mortality in patients with sepsis. The future research direction is to combine the relevant indicators of MEWS and SIRS to develop a measurement tool with high reliability and validity., Relevance to Clinical Practice: The review provides useful insights into the prognostic accuracy of different assessment tools in predicting mortality in sepsis patients, which will help clinicians choose the most appropriate tool for early identification and treatment of sepsis. The findings may also contribute to the development of more accurate and reliable prognostic models for sepsis., (© 2023 British Association of Critical Care Nurses.)

Objectives: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C., Methods: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset., Results: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors., Conclusion: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001)., Conlusion: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial., What Is Known: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up., What Is New: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being., (© 2024. The Author(s).)

Sepsis is the leading cause of mortality in children worldwide. There is a paucity of data on the criteria used to define sepsis and septic shock and predict mortality. Schlapbach et al. published Phoenix criteria to define sepsis in JAMA in 2024. Previously, paediatricians have used systemic inflammatory response syndrome (SIRS) criteria, but these criteria lack sensitivity and specificity. This group 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. Though included in the 8-point criteria, important criteria like renal and liver are missing from the main criteria. We remain worried about the way these criteria got excluded from the main criteria. Therefore, in this brief report, whilst commending the authors for this stelar task, we highlight the main pitfalls in these criteria especially the renal, neurologic, and liver criteria. These criteria have been shown to be independently associated with outcomes, and we recommend that in the future iterations of the criteria, renal and liver criteria should be defined according to latest definitions and the task force consider utilizing latest criteria for each organ system involved within the formulated criteria., Conclusion:  In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed., What Is Known: • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset., What Is New: • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria., (© 2024. The Author(s).)

Background and Objectives : Due to its link with the SARS-CoV-2, Multisystem Inflammatory Syndrome in Children (MIS-C) gained global attention as a serious condition that requires hospital care. Our study aimed to present the clinical and laboratory characteristics of MIS-C patients by age group and intensive care unit (ICU) admission status and assess early echocardiographic changes. Materials and Methods : A single-center partly retrospective, partly prospective observational cohort study was performed from December 2020 to June 2024. The study included 42 patients aged between 1 month and 18 years who were diagnosed with MIS-C and gave informed consent. Results : The median age was 6.5 years (IQR 2.0-9.3). The predominant symptoms were cardiovascular (88.1%), mucocutaneous (85.7%) and gastrointestinal (76.2%). Five children (11.9%) developed shock. About two-thirds of patients (66.7%) were admitted to the ICU. Adolescents (≥12 years) were less likely to exhibit mucocutaneous or cardiovascular symptoms and thus less frequently having Kawasaki-like disease symptoms compared with other age groups (<5 years or 5-11 years). Lymphopenia was more common among patients aged 5 years and older. Adolescents had higher procalcitonin (PCT) and a lower estimated glomerular filtration rate. Troponin I and B-type natriuretic peptide (BNP) levels were higher in children aged 5-11 years, while ferritin levels were lower among the youngest (<5 years). Patients treated at the ICU were more likely to have cardiovascular and respiratory symptoms, as well as a history of symptomatic COVID-19, higher C-reactive protein (CRP), PCT, BNP and lower albumin levels. Echocardiographic abnormalities were found in 71.4% of cases. During hospitalization, left ventricular ejection fraction values increased significantly ( p < 0.001) over 12 (IQR 9.0-14.0) days. Conclusions : Symptoms and laboratory markers of MIS-C vary according to age. Higher CRP, PCT, BNP and hypoalbuminemia are predictors of MIS-C severity. Cardiovascular involvement is common and might be severe, but rapid resolution is encouraging.

Objective: Postoperative delirium (POD) is a common complication following off-pump coronary artery bypass grafting (OPCABG) and is associated with significant morbidity. This study aims to evaluate the correlation of systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) with postoperative delirium (POD) in patients with cerebral infarction undergoing OPCABG., Methods: The perioperative cohort study included 321 patients who underwent OPCABG. Patients were divided into two groups based on the occurrence of POD: the delirium group (n = 113) and the non-delirium group (n = 208). Baseline characteristics, including gender, left ventricular ejection fraction (LVEF), surgery duration, hypertension, age, and smoking history were analyzed. SII and SIRI values were calculated preoperatively, and their association with POD was assessed using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of SII and SIRI., Results: Statistical differences between SII and SIRI in the two groups (P < 0.05) were observed. Multivariate analysis confirmed that SII and SIRI, age and preoperative smoking history were predictors of POD. ROC curve analysis demonstrated that SII and SIRI had considerable predictive power, with AUC values of 0.73 (0.67-0.79) for SII and 0.75 (0.69-0.81) for SIRI., Conclusion: SII and SIRI were found to be associated with an increased risk of POD in patients undergoing OPCABG, but further research is needed to confirm these findings and determine their independence as risk factors., (© 2024. The Author(s).)

Background/aim: Differentiating multisystem inflammatory syndrome in children (MIS-C) from adenovirus infection (AI) can be challenging due to similar clinical and laboratory findings. This study aimed to identify distinguishing characteristics and develop a scoring system to facilitate accurate diagnosis., Materials and Methods: A comprehensive review of medical records was undertaken for 108 MIS-C patients and 259 patients with confirmed AI. A comparison of laboratory data and clinical findings was conducted across the patient groups using appropriate statistical tests., Results: The MIS-C patients were significantly older than the AI patients (p < 0.001). Diarrhea, rash, abdominal pain, vomiting, nonexudative conjunctivitis, lymphadenopathy tachycardia, bradycardia, hypotension, hypoxia seizures, agitation, headache, and altered consciousness symptoms were more frequently associated with MIS-C (p < 0.001), while cough and runny nose were significantly more common in AI (p < 0.001). Lymphopenia and thrombocytopenia were more prevalent in the MIS-C patients (p < 0.001). AI and MIS-C were scored by giving one point each to the parameters that created the difference. For AI, being ≤60 months of age, the presence of cough, runny nose and absence of diarrhea, rash, abdominal pain, vomiting, nonexudative conjunctivitis, lymphadenopathy, tachycardia, bradycardia, hypotension, hypoxia seizures, agitation, headache, and altered consciousness, lymphopenia, thrombocytopenia, and C-reactive protein value <124.5 mg/L were determined as each parameter plus one point. A total score above 14 could predict AI with a high degree of accuracy, with sensitivity at around 97.5% and specificity at 92.6%., Conclusion: The proposed inpatient scoring system, when used in conjunction with polymerase chain reaction testing, may improve the early differentiation of AI and MIS-C. This approach could help reduce unnecessary testing and optimize resource allocation. Further research with larger samples should investigate this novel scoring system to establish its reliability and generalizability., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© TÜBİTAK.)

Background and Aims: Our aim was to investigate all children admitted to paediatric intensive care units (ICU) in the Republic of Ireland between January 2020 and August 2022 with an admitting diagnosis of acute COVID-19 infection or paediatric inflammatory multi-system syndrome, temporally associated with SARS-CoV-2 (PIMS-TS) or associated illness. The patients were identified to catalogue the severity of illness, analyse cardiovascular manifestations of their disease, and short-term outcomes., Methods: This is a retrospective multi-centre observational study., Results: 127 children were admitted to paediatric ICU in Ireland with a COVID-19- related illness between January 2020 and August 2022. 87 (68.5%) of patients had acute COVID-19 infection, 39 (30.7%) had PIMS-TS and 1 (0.8%) patient had post-COVID vaccine-related myocarditis. Ventilatory support was required for 47/87 (54%) in the COVID-19 group comparative to 9/39 (23%) of patients with PIMS-TS. Inotropic support was required for 13/87 (14.9%) children with COVID-19 and 29/39 (74.3%) with PIMS-TS. Evidence of any cardiac disease on ECHO was identified in 23/38 (60.5%) of the PIMS-TS cohort comparative to only 5/36 (13.9%) of patients with COVID-19. 38/39 (97.4%) of patients with PIMS-TS-related cardiac disease and 100% with COVID-19 had a normal echo at the time of discharge from hospital. Overall survival of patients was 100%., Conclusion: The burden of cardiac disease in children requiring paediatric ICU care for COVID-19-related disease was high in the acute phase; however, all children survived, and all cardiac investigations had normalised by short-term follow-up.

Objective: Biomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD., Methods: Consecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines., Results: 107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection., Conclusion: nCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Globally, sepsis is the primary cause of death for children. While research conducted on adults has a significant impact on the diagnosis and treatment of sepsis in newborns and young children, there are significant factors that are pertinent to pediatrics as well. This prospective case-control study was conducted during the period from August 2020 to October 2022 after approval by the institutional ethical committee. The study included 48 critically ill children admitted at the Pediatric intensive care unit and 30 apparently healthy children as a control group. Laboratory investigations including complete blood picture, C-reactive protein (CRP), blood culture and sensitivity and plasma level of cluster of differentiation 64 (CD64) and myeloperoxidase (MPO) were investigated for all participants. A daily follow up for the signs of systemic inflammatory response syndrome (SIRS) or sepsis was done, and the patients were divided into SIRS and non-SIRS subgroups then patients were divided into two groups according to the presence of severe sepsis. A follow up CD64 and MPO sample were withdrawn from them to assess their prognostic value. SIRS was reported in 39.58 % of patients while severe sepsis was reported in 20.8%. CD64 and MPO were significantly higher in cases than controls (p= 0.003, p < 0.001, respectively) and, in patients with SIRs and severe sepsis CD64 was 1559.00± 367.09 pg/ml and 1547.9 4± 436.14 pg/ml, respectively. Also, MPO was significantly higher in patients with SIRS (113.58± 25.19 mU/ml) and severe sepsis (111.70± 26.50 mU/ml). CD64 and MPO significantly increased after development of sepsis in admitted patients. ROC was significantly higher for CD64 and MPO at admission than that for CRP at admission (p=0.123, p=0.014, respectively). In conclusion, plasma level of CD64 and MPO in peripheral blood can be considered an early sensitive marker for the detection and follow up of pediatric sepsis., (Copyright© by the Egyptian Association of Immunologists.)

Background: Although 6-month follow-up of patients with multisystem inflammatory syndrome in children (MIS-C) was reassuring, there is scant data on long-term sequelae, including whether changing variants affect clinical severity and outcomes., Methods: Children (<18 years of age) admitted to Great Ormond Street Hospital between April 4, 2020, and January 2023, meeting diagnostic criteria for MIS-C were included. Admission and follow-up data were categorized by the predominant SARS-CoV-2 circulating variant in the United Kingdom., Results: One hundred and sixty children [median age, 10.1 (interquartile range, 7.9-12.6) years] were included. There was no difference in the time of symptom onset to diagnosis between waves ( P =0.23) or hospitalization days across all waves ( P =0.32). Inflammatory markers were normal for up to 2 years in all patients except one. Eleven patients (6.9%) remain in follow-up: cardiology (n=5), gastroenterology (n=5) and nephrology (n=1). The main self-reported symptoms at 2 years were abdominal pain (n=5) and myalgia (n=2). Fatigue was present in approximately a quarter of patients at admission; this reduced to 14 (9%), (2%) and 1 (2%) at 6-month, 1-year and 2-year follow-ups, respectively. Chronic fatigue or long-COVID symptomatology was rare (n=1) even with high rates of concurrent Epstein-Barr virus positivity (49/134). All patients had sustained neurological recovery with no new neurological pathology observed., Conclusions: Patients with MIS-C have a sustained recovery, which is reassuring for positive long-term outcomes. Across waves, time from symptom onset to diagnosis and treatment, symptomatology and length of stay were similar. Sustained recovery is reassuring for clinicians and parents alike. Differentiating long-COVID symptomatology from that of MIS-C is important in formulating an individualized treatment plan., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)