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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: 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.)

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.

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.)

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).)

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.)

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.)

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).)

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare complication, which develops within 3-6 weeks after SARS-CoV2 infection. The coronavirus disease 2019 (COVID-19) vaccine was firstly introduced in adults and adolescents and later in patients aged 5-11 years old. Although a reduced incidence of MIS-C and with less severe symptoms has been reported in vaccinated adolescents, there is little knowledge in children younger than 12 years of age. In addition, it is not understood whether MIS-C in vaccinated patients can be triggered by Covid19 vaccination or be secondary to a recent asymptomatic Sars-Cov2 infection., Case Presentation: We describe the case of a Caucasian 6-year-old girl, one month after double COVID-19 vaccination, who presented fever, acute abdominal pain, rash, pharyngotonsillitis, cheilitis, cervical lymphadenopathy without a prior detected Sars-Cov2 infection. She also had lymphopenia, increase in inflammatory markers, cardiac and pulmonary involvement. Therefore, we dosed both anti Sars-Cov2 Spike and Nucleocapsid antibodies, which were positive and allowed us to confirm the diagnosis of MIS-C. We promptly administered intravenous immunoglobulins and methylprednisone, resulting in the initial regression of fever. During the hospitalization, the child also developed pancreatitis and severe neurological involvement, including irritability, drowsiness, distal tremor, dyskinesia and buccal asymmetry with complete resolution after 2 months. After 3 months from the onset of the symptoms, she reported a transient loss of hair compatible with telogen effluvium. After 12 months of follow-up, she did not show any symptomatic sequelae., Conclusions: This case raises the question of whether COVID-19 vaccination may be involved in the pathogenesis of MIS-C in children between the ages of 5 and 11 years old., (© 2024. The Author(s).)

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes., Competing Interests: Competing interests statement:C.J.L and I.D.V are inventors on submitted patents pertaining to cell-free nucleic acids (US patent applications 63/237,367 and 63/429,733). I.D.V. is listed as an inventor on submitted patents pertaining to cell-free nucleic acids (US patent applications 63/237,367, 63/056,249, 63/015,095, 16/500,929, 41614P-10551-01-US) and receives consulting fees from Eurofins Viracor. C.A.R. has received institutional support from ModernaTX, Inc., Pfizer Inc., BioFire Inc., GSK plc, MedImmune, Micron Technology Inc., Janssen Pharmaceuticals, Merck & Co., Inc., Novavax, PaxVax, Regeneron, and Sanofi Pasteur. She is co-inventor of patented RSV vaccine technology which has been licensed to Meissa Vaccines, Inc. C.Y.C. receives grant funding for research unrelated to this work from the Bay Area Lyme Disease Foundation, the Chan-Zuckerberg Biohub, and Abbott Laboratories, Inc.

Introduction: Determining which patients who meet systemic inflammatory response syndrome (SIRS) criteria have bacterial sepsis is a difficult challenge for emergency physicians. We sought to determine whether the neutrophil-to-lymphocyte ratio (NLR) could be used to exclude bacterial sepsis in adult patients who meet ≥2 SIRS criteria and are being evaluated for sepsis., Methods: Consenting adult patients meeting ≥2 SIRS criteria and undergoing evaluation for sepsis were enrolled. We recorded patient age, gender, vital signs, and laboratory results. We then later reviewed health records for culture results, end organ dysfunction, survival to discharge, and final diagnoses. Patients were classified as having sepsis if they met ≥2 SIRS criteria and were ultimately diagnosed with a bacterial source. We analyzed data using descriptive statistics and sensitivity and specificity analyses. A receiver operating characteristic curve (ROC) was created to determine test characteristics., Results: A total of 231 patients had complete datasets. Patients' median age was 69 (interquartile range [IQR] 54-81), and 49.6% were male. There were 154 patients (66.7%) ultimately diagnosed with sepsis with an identified bacterial source, while 77 patients with ≥2 SIRS criteria had non-infectious reasons for their presentations (33.3%). Septic patients had a median NLR 12.36 (IQR [interquartile range] 7.29-21.69), compared to those without sepsis (median NLR 5.62, IQR 3.89-9.11, P  < 0.001). The NLR value of 3 applied as a cutoff for sepsis had a sensitivity of 96.8 (95% confidence interval [CI] 92.2-98.8), and a specificity of 18.2 (95% CI 10.6-29.0). The ROC for NLR had an area under the curve of 0.74., Conclusion: The neutrophil-to-lymphocyte ratio is a sensitive tool to help determine which patients with abnormal SIRS screens have bacterial sepsis., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Background: Periprosthetic joint infection (PJI) is an extremely damaging complication that can occur after total knee arthroplasty (TKA). There is no study in the literature investigating the relationship between systemic inflammatory response index (SIRI) and systemic inflammation immune index (SII) values and prognosis and infection in patients who have undergone TKA. The aim of the study was to determine the relationship between the inflammatory index values and the rate of PJI in patients who had previously had TKA., Methods: A total of 187 patients who underwent TKA between 2015 and 2023 years were retrospectively analyzed., Results: The median value of the postoperative SII index was 1862.3 (1146.6-2630.4) in the infected group, while it was 1058.2 (605.0-1762.8) in the non-infected group (p < 0.001). In the infected group, the median value of preoperative SIRI was observed as 2.3 (1.7-3.5), while in the non-infected group it was 0.9 (0.7-1.5) (p < 0.001). The cutoff value for postoperative SIRI was observed to be 2.19, with a sensitivity value of 95%, a specificity value of 46%, the AUC value observed was 65%. The cutoff value for the postoperative SII index was observed to be 1058.96, with a sensitivity value of 100%, a specificity value of 50%., Conclusions: Our study has associated the inflammatory markers SIRI, SII, neutrophil lymphocyte ratio, and platelet lymphocyte ratio with PJI, which are easy and inexpensive to obtain. There is no widely recognized serum biomarker that can be used alone with good sensitivity and specificity. This study contributes to finding the gold standard inflammatory marker for diagnosing PJI., (© 2024. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Background and Objective: To evaluate long-term posterior segment findings in children recovering from multisystemic inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2., Patients and Methods: Our study included 22 patients who were admitted to an intensive care unit with a diagnosis of MIS-C between November 2021 and March 2022, and 25 healthy controls. The study included pediatric patients who had an eye examination an average of 12.35 ± 2.18 months after recovery from MIS-C. Detailed eye examinations and measurements of all participants were obtained retrospectively from patient files. Posterior segment parameters were measured using swept-source optical coherence tomography (OCT) and OCT-angiography (OCT-A); these parameters included peripapillary retinal nerve fiber layer (pRNFL) thickness, central macular thickness (CMT), subfoveal choroidal thickness (SCT), macular vascular densities (VD), and foveal avascular zone (FAZ) area., Results: Mean age was 9.7 ± 3.6 years in the MIS-C group and 10.6 ± 2.8 years in the healthy control group ( P = 0.316). There were no statistically significant differences between the MIS-C group and the healthy control group in terms of pRNFL thickness, CMT, and SCT. However, in the MIS-C group, the macular superficial vascular plexus and deep vascular plexus showed significantly lower VD in the superior, inferior, nasal, and temporal quadrants compared to the healthy controls ( P < 0.05 for all). A comparison of the superficial and deep FAZ area parameters of both groups showed no statistically significant difference ( P > 0.05)., Conclusions: We showed that patients who had recovered from MIS-C had retinal vascular damage at the long-term follow-up. Following up with these patients after recovery with OCT and OCT-A, which are noninvasive methods commonly used in the detailed evaluation of the posterior segment of the eye, could be beneficial for understanding the long-term effects of MIS-C on retinal microvasculature. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:518-526.] .

Aim: To comprehensively review the literature on multisystem inflammatory syndrome in children (MIS-C)., Methods: Narrative review of relevant studies published between April 2020 and January 2024., Results: MIS-C is a SARS-CoV-2-related hyperinflammatory syndrome developing 2-6 weeks after COVID-19 in genetically susceptible individuals. Persisting fever, mucocutaneous manifestations, GI and cardiac involvement, together with lymphopenia and elevated inflammatory and cardiac markers are the main clinical features. It is believed to recognise some pathogenetic and clinical overlap with Kawasaki disease. New case definitions have been proposed after an assessment of the diagnostic performance of existing criteria; epidemiological criterion is however progressively losing its usefulness as the pandemic turns into an endemic and in the areas with the highest rates of COVID-19 vaccination. Current guidelines recommend both intravenous immunoglobulin and glucocorticoids in the first-line immunomodulatory treatment, mainly based on comparative retrospective cohorts; the actual role of biologics remains to be adequately established. Strict follow-up is mandatory, especially for those with severe cardiac involvement, as longitudinal studies evaluate the long-term evolution of cardiac damage., Conclusion: In this paper, we review the epidemiological, pathogenetic, clinical and prognostic features of MIS-C, and outline the main questions which still remain unanswered after more than 3 years of research., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

According to the 2020 CDC criteria, multisystem inflammatory syndrome in children (MIS-C) due to Coronavirus disease-19 (COVID-19) is diagnosed when all of the following criteria are met: fever for+≥+24 hours, laboratory evidence of inflammation, multisystem (+≥+2) organ involvement, evidence of SARS-CoV-2 infection or exposure, and no alternative plausible diagnoses (CDC, 2020). Alternative diagnosis need to be excluded before coming upon an MIS-C diagnosis since there are plenty of infectious diseases that may mimic MIS-C (Dworsky et al., Pediatr Infect Dis J 2021; 40; e159-e161; Yalçinkaya et al., Pediatr Infect Dis J 2021; 40; e524-e525; Kaneta et al., Pediatr Infect Dis J 2023; 42; 590-593; Stanzelova et al., Pediatr Infect Dis J 2023; 42; e201-e203; Kolsi et al., Arch Pediatr 2023; 30; 521-523). Herein, we present a 6-year-old girl who was preliminarily diagnosed with MIS-C and received intravenous immunoglobulin (IVIG) treatment before referral to our center. She was diagnosed with acute pneumococcal meningitis due to serotype 19 F and ultimately suffered from sensorineural hearing loss (SNHL) as a sequela. We present this case to remind physicians that MIS-C should not be diagnosed unless other infectious causes are excluded., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The effects of SARS-CoV-2 infection on children continue to evolve following the onset of the COVID-19 pandemic. Although life-threatening multisystem inflammatory syndrome in children (MIS-C) has become rare, long-standing symptoms stemming from persistent immune activation beyond the resolution of acute SARS-CoV-2 infection contribute to major health sequelae and continue to pose an economic burden. Shared pathophysiologic mechanisms place MIS-C and long COVID within a vast spectrum of postinfectious conditions characterized by intestinal dysbiosis, increased gut permeability, and varying degrees of immune dysregulation. Insights obtained from MIS-C will help shape our understanding of the more indolent and prevalent postacute sequelae of COVID and ultimately guide efforts to improve diagnosis and management of postinfectious complications of SARS-CoV-2 infection in children.

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: We proposed a link between the first systemic inflammatory response index (SIRI) and acute kidney injury (AKI), as well as the prognosis of pediatric patients in intensive care units (PICU)., Methods: This study comprised 5114 children from the pediatric-specific intensive care (PIC) database. SIRI was estimated as a neutrophil monocyte lymphocyte ratio. All patients were arbitrarily allocated to the training set (n = 3593) and the validation cohort (n = 1521) and divided into two groups depending on their SIRI levels. The diagnostic value of SIRI for pediatric ICU patients was subsequently determined using LASSO regression models., Results: After controlling for additional confounding variables in the training set, the higher SIRI value (≥ 0.59) had a greater risk of AKI (adjusted odds ratio, OR, 3.95, 95% confidence interval, 95%CI, 2.91-5.36, P<0.001) and in-hospital mortality (hazard ratio, HR, 5.01, 95%CI 2.09-12.03, P<0.001). Similar findings were discovered in the validation set. Furthermore, the suggested nomogram derived from SIRI and other clinical metrics showed outstanding calibration capability as well as therapeutic usefulness in both groups., Conclusions: SIRI is a reliable and useful factor for AKI and fatality in pediatric ICU patients, and the proposed nomogram based on SIRI yields an appropriate prediction value for critically sick pediatric patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu 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: Fetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients' hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts., Case Presentation: We performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies' alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal., Conclusions: . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions., (© 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).)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition caused by recent infection with severe acute respiratory syndrome coronavirus 2, but the underlying immunological mechanisms driving this distinct syndrome are unknown., Methods: We utilized high-dimensional flow cytometry, cell-free (cf) DNA, and cytokine and chemokine profiling to identify mechanisms of critical illness distinguishing MIS-C from severe acute coronavirus disease 2019 (SAC)., Results: Compared to SAC, MIS-C patients demonstrated profound innate immune cell death and features of emergency myelopoiesis (EM), an understudied phenomenon observed in severe inflammation. EM signatures were characterized by fewer mature myeloid cells in the periphery and decreased expression of HLA-DR and CD86 on antigen-presenting cells. Interleukin 27 (IL-27), a cytokine known to drive hematopoietic stem cells toward EM, was increased in MIS-C, and correlated with immature cell signatures in MIS-C. Upon recovery, EM signatures decreased and IL-27 plasma levels returned to normal levels. Despite profound lymphopenia, we report a lack of cfDNA released by adaptive immune cells and increased CCR7 expression on T cells indicative of egress out of peripheral blood., Conclusions: Immune cell signatures of EM combined with elevated innate immune cell-derived cfDNA levels distinguish MIS-C from SAC in children and provide mechanistic insight into dysregulated immunity contributing toward MIS-C, offering potential diagnostic and therapeutic targets., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The predictive value of systemic inflammatory response index (SIRI) for stroke-associated pneumonia (SAP) risk in patients with acute ischemic stroke (AIS) treated by thrombectomy remains unclear. This study aimed to investigate the predictive value of SIRI for SAP in patients with AIS treated by thrombectomy., Methods: We included AIS patients treated by thrombectomy between August 2018 and August 2022 at our institute. We used multivariate logistic regression to construct the prediction model and performed a receiver operating characteristic curve analysis to evaluate the ability of SIRI to predict SAP and constructed a calibration curve to evaluate the prediction accuracy of the model. We evaluated the clinical application value of the nomogram using decision curve analysis., Results: We included 84 eligible patients with AIS in the analysis, among which 56 (66.7%) had SAP. In the univariate analysis, there were significant differences in sex (p = 0.035), National Institute of Health Stroke Scale score at admission ≥ 20 (p = 0.019) and SIRI (p < 0.001). The results of multivariable logistic analysis showed that the risk of SAP increased with the SIRI value (OR = 1.169, 95% CI = 1.049-1.344, p = 0.014). Age ≥ 60 (OR = 4.076, 95% CI = 1.251-14.841, p = 0.024) was also statistically significant. A nomogram with SIRI showed good prediction accuracy for SAP in AIS patients treated by thrombectomy (C-index value = 0.774)., Conclusions: SIRI is an independent predictor for SAP in patients with AIS treated by thrombectomy. A high SIRI value may allow for the early identification of patients with AIS treated by thrombectomy at high risk for SAP., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest JA is an investigator for AiCuris, Biogen, Pfizer and Astra Zeneca.

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions.

Background: Sepsis, a deadly infection causing organ failure and Systemic Inflammatory Response Syndrome (SIRS), is detected early in hospitalization using the SIRS criteria, while sequential organ failure (SOFA) assesses organ failure severity. A systematic review and meta-analysis was evaluated to investigate the predictive value of the SIRS criteria and the SOFA system for mortality in early hospitalization of sepsis patients., Methods: Inclusion criteria were full reports in peer-reviewed journals with data on sepsis assessment using SOFA and SIRS, and their relationship with outcomes. For quality assessment, we considered study population, sepsis diagnosis criteria, and outcomes. The area under the curve (AUC) of these criteria was extracted for separate meta-analysis and forest plots., Results: Twelve studies met the inclusion criteria. The studies included an average of 56.1% males and a mean age of 61.9 (±6.1) among 32,979 patients. The pooled AUC was 0.67 (95% CI: 0.60-0.73) for SIRS and 0.79 (95% CI: 0.73-0.84) for SOFA. Significant heterogeneity between studies was indicated by an I2 above 50%, leading to a meta-regression analysis. This analysis, with age and patient number as moderators, revealed age as the major cause of heterogeneity in comparing the predictive value of the SOFA score with SIRS regarding the in-hospital mortality of sepsis patients ( P <0.05)., Conclusion: The SOFA score outperformed the SIRS criteria in predicting mortality, emphasizing the need for a holistic approach that combines clinical judgment and other diagnostic tools for better patient management and outcomes., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

This study aims to evaluate the changes in helper T lymphocyte (Th)1/Th2 factor levels in peripheral blood of patients with severe multiple injuries and their prognostic value for nosocomial infection using bioinformatic analysis. The experimental group consisted of 180 patients with numerous injuries admitted to our hospital between January 2021 and June 2023, with 80 healthy volunteers serving as controls. Th1 cytokines (interleukin-2 and interferon-γ) and Th2 cytokines (IL-4 and IL-10) were evaluated 48 hours after admission using enzyme-linked immunosorbent assays. The experimental group was separated into two groups: those with systemic inflammatory response syndrome (SIRS) and those without SIRS, for cytokine analysis and SIRS incidence. Furthermore, the study examined Th1 and Th2 cytokine levels in trauma patients in various body locations within the experimental group. A receiver operating characteristic (ROC) curve analysis was performed to determine the predictive value of Th1/Th2 cytokines for SIRS incidence. The experimental group had lower IL-2 and IFN-γ levels compared to the control group, but greater levels of IL-4 and IL-10. There were no significant variations in Th1 and Th2 cytokine levels across the experimental groups. Patients with SIRS had lower levels of IL-2 and IFN-γ but greater levels of IL-4 and IL-10 compared to those without SIRS. Combined cytokine levels have a better predictive value for SIRS than individual cytokines alone. In conclusion, individuals with severe multiple injuries had a change from Th1 to Th2 cytokine profiles, which was most evident in those with SIRS. The combined cytokine levels had a substantial predictive value for SIRS incidence in this patient cohort., 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 Inc.)

Background: The main aim of this study is to analyze changes in the lipopolysaccharide-binding protein (LBP) level in blood serum over time and assess it as a potential risk factor for the development of SIRS, infectious and inflammatory complications, organ dysfunction and mortality in patients operated on colorectal cancer (CRC)., Methods: 90 CRC patients were divided into 2 groups: Group 1-50 patients operated on for CRC without acute bowel obstruction (ABO); Group 2-40 patients operated on for CRC with ABO. To determine LBP by ELISA method venous blood was taken 1 h before surgery and 72 h after it (3rd day)., Results: LBP level on the 3rd day after surgery was lower in CRC patients with SIRS, postoperative complications, organ dysfunction and in dead patients. With an LBP value on the 3rd day after surgery being at ≤821.95 ng/mL, the risk of SIRS occurrence is 3.5 times higher, that of the postoperative complications is 5.2 times higher and death is 12.9 times higher than with its higher level (OR 3.5, CI 1.46-8.4; OR 5.2, CI 1.80-15.12; OR 12.9, CI 1.54-108.21, respectively). If the LBP value on the 3rd day after surgery is ≤ 700.15 ng/mL, the risk of organ dysfunctions is 13.5 times higher than with its higher level (OR 13.5, CI 3.536-51.54)., Conclusions: This study demonstrated that in the patients with CRC, the LBP can be used as a predictive criterion for the development of SIRS, postoperative infectious and inflammatory complications, organ dysfunction, and mortality., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Multisystem inflammatory syndrome in children is an inflammatory syndrome related to severe acute respiratory syndrome coronavirus 2 with a high risk of cardiovascular complications (vasoplegia, cardiac shock). We investigated the cardiac outcomes in multisystem inflammatory syndrome in children, focusing on the identification of predictors for late cardiac function impairment., Methods: Clinical characteristics, conventional echocardiography (left ventricle ejection fraction, fractional shortening), 4-chamber left ventricular global longitudinal strain, and cardiac MRI of multisystem inflammatory syndrome in children patients (n = 48) were collected during admission, 6 weeks, 6 months, >12-≤18 months, and >18-≤24 months post-onset. Paired over-time patterns were assessed and multivariable regression analyses were performed to identify predictors for late global longitudinal strain impairment., Results: In total, 81.3% of patients had acute cardiac dysfunction (left ventricle ejection fraction <50% and/or fractional shortening <28%). The left ventricle ejection fraction and fractional shortening reached a plateau level ≤6 weeks, while the global longitudinal strain continued to decrease in the first 6 months post-onset (median -17.3%, P < 0.001 [versus acute]). At 6 months, 35.7% of the patients still had an abnormal global longitudinal strain, which persisted in 5/9 patients that underwent echocardiography >12-≤18 months post-onset and in 3/3 patients >18-≤24 months post-onset. In a multivariable analysis, soluble troponin T (>62.0 ng/L [median]) was associated with reduced global longitudinal strain at 6 months. Our cardiac MRI findings indicated acute myocardial involvement (increased T1/T2 value) in 77.8% (7/9), which recovered quickly without signs of fibrosis on convalescent cardiac MRIs., Conclusions: Late global longitudinal strain impairment is seen in some multisystem inflammatory syndrome in children patients up to one-year post-onset. Careful cardiac follow-up in patients with elevated troponin in the acute phase and patients with persistent abnormal global longitudinal strain is warranted until resolution of the global longitudinal strain since the long-term implications of such abnormalities are still unclear.

Multisystemic inflammatory syndrome in children (MIS-C) is a rare, severe, post-infectious hyperinflammatory condition that occurs after COVID-19 infection. In this study, we aimed to demonstrate the risk reduction of MIS-C and severe MIS-C after Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccination. This nationwide cohort study included 526,685 PCR-confirmed COVID-19 cases (age < 19 years), of whom 14,118 were fully vaccinated prior to COVID-19 infection. MIS-C cases were collected from all hospitals in Israel from April 2020 through November 2021. The MIS-C rates were calculated among two COVID-19 populations: positive PCR confirmed cases and estimated COVID-19 cases (PCR confirmed and presumed). Vaccination status was determined from Ministry of Health (MoH) records. The MIS-C risk difference (RD) and 95% confidence intervals (95%CI) between vaccinated and unvaccinated patients are presented. Overall, 233 MIS-C cases under the age of 19 years were diagnosed and hospitalized in Israel during the study period. Among the estimated COVID-19 cases, MIS-C RD realistically ranged between 2.1 [95%CI 0.7-3.4] and 1.0 [95%CI 0.4-1.7] per 10,000 COVID-19 cases. For severe MIS-C, RD realistically ranged between 1.6 [95%CI 1.3-1.9] and 0.8 [95%CI 0.7-1.0], per 10,000 COVID-19 cases. Sensitivity analysis was performed on a wide range of presumed COVID-19 rates, demonstrating significant RD for each of these rates., Conclusion: This research demonstrates that vaccinating children and adolescents against COVID-19 has reduced the risk of MIS-C during the study period., What Is Known: • Most of the published literature regarding vaccine effectiveness is based on case-control studies, which are limited due to small sample sizes and the inability to fully estimate the risk of MIS-C among vaccinated and unvaccinated children and adolescents. • The known underestimation of COVID-19 diagnosis among children and adolescents is challenging, as they often have few to no symptoms., What Is New: • Significant risk difference was found in favor of the vaccinated group, even after including extreme assumptions regarding the underdiagnosed COVID-19 rate. • During this nationwide study period, it was found that vaccinating children and adolescents reduced the risk of MIS-C and its complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory and immunosuppressed condition affecting children exposed to COVID-19. MIS-C has been associated with an over-exaggerated innate and adaptive immune response characterized by a 'selective' cytokine production and T cell suppression. As COVID-19 information has evolved, the knowledge and field surrounding MIS-C is ever evolving. Thus, a comprehensive clinical review that concisely presents current literature findings regarding common clinical presentations and comparisons with similar conditions, associations with the COVID-19 vaccine effects and relevant epigenetic markers and evaluates treatment and long-term outcomes to help guide future studies is needed and provided.

Purpose of Review: This review provides updates on postinfectious skin rashes in the pediatric population from recently published literature., Recent Findings: The COVID-19 pandemic and its sequelae remain a focus of research on pediatric infectious skin rashes. Multisystem inflammatory syndrome in children (MIS-C) and reactive infectious mucocutaneous eruption (RIME) are common complications of infection with SARS-COV-2 in the pediatric population. Most cases of MIS-C show low mortality and suggest mucocutaneous symptoms do not correlate with COVID-19 disease severity. Cases of papular acrodermatitis of childhood, also known as Gianotti-Crosti, have also been reported in association with SARS-COV-2, and can present similarly in reaction to other viral infection like molluscum contagiosum, known as a Gianotti-Crosti syndrome-like reaction (GCLR). Other relevant studies on postinfectious skin rashes include updates on the management of staphylococcal scalded skin syndrome (SSSS), with newer evidence advocating for beta-lactam monotherapy without clindamycin and reduced ancillary testing. Finally, the emergence of antifungal resistance due to Trichophyton indotinae is a growing global health concern emphasizing the need for improved antifungal stewardship., Summary: It is prudent for clinicians to be informed of both common and rare diagnoses that have emerged more recently in association with the COVID-19 pandemic, in addition to other diseases with newer evidence-based recommendations to guide management., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

First described in 2020, multi-system inflammatory syndrome in children (MIS-C) is an, initially life-threatening, disease characterised by severe inflammation and following exposure to SARS-CoV-2. The immunopathology of MIS-C involves a hyperinflammation characterised by a cytokine storm and activation of both the innate and adaptive immune system, eventually leading to multi-organ failure. Several etiological theories are described in literature. Firstly, it is suggested that the gut plays an important role in the translocation of microbial products to the systemic circulation. Additionally, the production of autoantibodies that develop after the initial infection with SARS-CoV-2 might lead to many of its broad clinical symptoms. Finally, the superantigen theory where non-specific binding of the SARS-CoV-2 spike glycoprotein to the T-cell receptor leads to a subsequent activation of T cells, generating a powerful immune response. Despite the sudden outbreak of MIS-C and alarming messages, as of 2024, cases have declined drastically and subsequently show a less severe clinical spectrum. However, subacute cases not meeting current diagnostic criteria might be overlooked even though they represent a valuable research population. In the future, research should focus on adjusting these criteria to better understand the broad pathophysiology of MIS-C, aiding early detection, therapy, and prediction.

Introduction: Multisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings. In this study, the clinical findings, organ involvements, similarities, and differences in laboratory and imaging of the children with MIS-C and KD at the time of admission will be revealed in detail, and the treatment methods and follow-up results will be revealed., Material and Method: Our study was a single-center study and included pediatric patients who were treated with a diagnosis of MIS-C between March 2020 and July 2023 in the pediatric cardiology, pediatric emergency, pediatric infection, and pediatric intensive care clinics at Celal Bayar University and who were treated with a diagnosis of KD (complete/incomplete) between January 2015 and July 2023. MIS-C diagnosis was made according to the Turkish Ministry of Health COVID-19 guidelines. Sociodemographic characteristics, clinical, laboratory, and echocardiography findings, treatments given, and clinical course of all patients included in the study were evaluated., Results: The median age was 30 months (7-84) in KD and 96 months (6-204) in MIS-C, and it was significantly higher in the MIS-C group (p = 0.000). Symptom duration was significantly longer in the MIS-C group (p = 0.000). In terms of clinical features, gastrointestinal syndrome findings (nausea, vomiting, abdominal pain) and respiratory findings (dyspnea) were significantly higher in the MIS-C group (p = 0.007, p = 0.000, p = 0.002, respectively). Regarding cardiovascular system involvement, coronary involvement was significantly higher in the KD group. However, valvular involvement, left ventricular systolic dysfunction, and pericardial effusion were significantly higher in the MIS-C group (p = 0.000, p = 0.001, p = 0.003, p = 0.023, respectively). In terms of laboratory findings, white blood cell count was higher in KD (p = 0.000), absolute lymphocyte count, platelet level, blood sodium, and albumin levels were lower in MIS-C group (p = 0.000, p = 0.000, p = 0.000, p = 0.000, p = 0.003, respectively), ferritin and troponin levels were significantly higher in MIS-C group. These results were statistically significant (p = 0.000, p = 0.000, respectively). D-dimer and fibrinogen levels were high in both groups, and no significant statistical difference was detected between the two groups. There was no significant difference between the two groups regarding the length of hospitalization and mortality, but steroid use was significantly higher in the MIS-C group (p = 0.000)., Conclusion: In conclusion, this study has demonstrated the similarities and differences between MIS-C and KD regarding clinical findings, organ involvement, and laboratory and imaging results. The results of our study have important implications in terms of contributing to the data in the existing literature on these two diseases and for the correct diagnosis and better management of pediatric patients presenting with these disorders., What Is Known: Multisystemic inflammatory syndrome (MIS-C) is a newly described disease manifestation in children associated with the novel coronavirus SARS-CoV-2 infection and can be easily confused with Kawasaki disease with its clinical and laboratory findings., What Is New: Although MIS-C and KD have many similarities, their symptoms, disease processes, possible complications, and treatment regimens may differ., (© 2024. The Author(s).)

This study aimed to assess the significance of serum albumin levels within 24 h of patient admission in correlation with the incidence of outcomes and mortality in patients diagnosed with acute pancreatitis. A retrospective study was conducted over a 5-year period, from January 2018 to December 2023, at the Mohammed VI University Hospital in Oujda, Morocco. The study included 371 patients diagnosed with acute pancreatitis. Hypoalbuminemia (≤ 30 g/L) was observed in 124 patients (33.4% of cases), and these patients had a higher mean age compared to those with normal albumin levels (P = 0.003). Hypoalbuminemia was significantly associated with persistent Systemic Inflammatory Response Syndrome (SIRS) (70.8% vs. 29.2%, P = 0.000), a higher BISAP score (66.7% vs. 33.3%, P = 0.000), and a higher CTSI score (51.7% vs. 48.3%, P = 0.000). Hypoalbuminemia was also associated with the presence of pleural effusion (P = 0.000). The mortality in the sample was 4.6%, and it was significantly associated with hypoalbuminemia (76.5%, P = 0.000). In conclusion, serum albumin levels within 24 h of patient admission appear to be a significant prognostic biomarker in acute pancreatitis, particularly in anticipating persistent organ failure and mortality., (© 2024. The Author(s).)

Background: Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes., Methods and Results: Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity., Conclusions: We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes., Registration: https://www.clinicaltrials.gov Unique identifier: NCT01662895.

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).)

Objective: The objective of this study was to develop and evaluate the performance of machine learning models for predicting the possibility of systemic inflammatory response syndrome (SIRS) following percutaneous nephrolithotomy (PCNL)., Methods: We retrospectively reviewed the clinical data of 337 patients who received PCNL between May 2020 and June 2022. In our study, 80% of the data were used as the training set, and the remaining data were used as the testing set. Separate prediction models based on the six machine learning algorithms were created using the training set. The predictive performance of each machine learning model was determined by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity using the testing set. We used coefficients to interpret the contribution of each variable to the predictive performance., Results: Among the six machine learning algorithms, the support vector machine (SVM) delivered the best performance with accuracy of 0.868, AUC of 0.942 (95% CI 0.890-0.994) in the testing set. Further analysis using the SVM model showed that prealbumin contributed the most to the prediction of the outcome, followed by preoperative urine culture, systemic immune-inflammation (SII), neutrophil to lymphocyte ratio (NLR), staghorn stones, fibrinogen, operation time, preoperative urine white blood cell (WBC), preoperative urea nitrogen, hydronephrosis, stone burden, sex and preoperative lymphocyte count., Conclusion: Machine learning-based prediction models can accurately predict the possibility of SIRS after PCNL in advance by learning patient clinical data, and should be used to guide surgeons in clinical decision-making., (© 2024. The Author(s).)

Multisystem inflammatory syndrome in children (MIS-C) is a known complication of COVID-19. There is still limited knowledge about this condition. Here, we report the case of a previously healthy toddler boy, who presented with acute liver failure and duodenal lesions resulting in severe haematemesis and haemorrhagic shock, requiring intensive care unit care. The patient had persistent transaminitis, a deranged coagulation profile, inflammatory markers were elevated, and laboratory tests were negative for common infectious hepatitis aetiologies as well as COVID-19 Reverse transcription polymerase chain reaction. His COVID-19 antibody was reactive. Upper gastrointestinal endoscopy revealed a Forrest grade III duodenal ulcer. Looking into the constellation of symptoms and laboratory findings a confirmed diagnosis of acute viral hepatitis caused by MIS-C was made. Hence, he was given intravenous methylprednisolone along with intravenous immunoglobulins, after which he improved clinically and transaminitis resolved. The patient was discharged on clinical improvement and was doing fine on follow-up up to 6 months., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

COVID-19, the disease caused by SARS-CoV-2, has been disruptive worldwide. It was primarily a respiratory disease that affected many of the medically vulnerable, but the true impact of postacute sequelae of SARS-CoV-2 (PASC), which has been demonstrated to involve all organ systems, is now coming to light. In addition, a new disease entity emerged, multisystem inflammatory syndrome in children (MIS-C), which has had significant morbidity and mortality associated with it. This issue reviews the presentation, evaluation, and management of patients with COVID-19, MIS-C, and PASC. Additionally, the current literature supporting public health measures, as well as COVID-19 vaccinations and their complications are discussed.

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