Cytokine storm in Chikungunya: Can we call it multisystem inflammatory syndrome associated with Chikungunya?

Paraguay is currently facing a new outbreak of Chikungunya virus. This report summarizes two severe cases of Chikungunya (CHIKV) infection, confirmed by real-time reverse transcription polymerase chain reaction. We present the cases of patients with acute CHIKV infection and multisystem involvement, with fever, rash, abdominal pain, vomiting, myocarditis, and coronary artery anomalies, very similar to the cases described in MIS-C related to SARS-CoV-2 during the COVID-19 Pandemic. Both patients received IVIG and methylprednisolone, with good clinical response. In this setting of cytokine storm in Chikungunya, can we call it "Multisystem inflammatory syndrome associated with Chikungunya"?.

Multisystem Inflammatory Syndrome in Children and Cardiac Involvement: A Quaternary Center Experience.

We prospectively analyzed clinical and laboratory characteristics associated with cardiac involvement and severe presentation in multisystem inflammatory syndrome in children. Of 146 patients, 66 (45.2%) had cardiac dysfunction and 26 (17.8%) had coronary artery abnormalities. Lower serum albumin levels, absolute lymphocyte and platelet counts, and elevated ferritin, fibrinogen, d-dimer and interleukin-6 levels were associated with cardiac dysfunction. Possible treatment complications were identified.

Treatment of multisystem inflammatory syndrome in children.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a relatively uncommon but severe pediatric complication, is associated with coronavirus disease 2019 (COVID-19). A variety of treatment approaches, including intravenous immunoglobulins (IVIGs), glucocorticoids (GCs) and biologic agents, such as anakinra and infliximab, have been described for the management of COVID-19-related MIS-C. Anticoagulant therapy is also important. However, a well-developed treatment system has not been established, and many issues remain controversial. Several recently published articles related to the treatment of MIS-C have been released. Hence, in this review, we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically. DATA SOURCES: We reviewed the literature on the treatment of MIS-C through 20 September 2023. The PubMed/Medline, Web of Science, EMBASE, and Cochrane Library databases were searched with the combination of the terms "multisystem inflammatory syndrome", "MIS-C", "PIMS-TS", "therapy", "treatment", "drug", "IVIG", "GCs", "intravenous immunoglobulin", "corticosteroids", "biological agent", and "aspirin". RESULTS: The severity of MIS-C varies, and different treatment schemes should be used according to the specific condition. Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C. CONCLUSIONS: MIS-C is a disease involving multiple systems and has great heterogeneity. With the accumulation of additional experience, we have garnered fresh insights into its treatment strategies. However, there remains a critical need for greater standardization in treatment protocols, alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols. Supplementary file1 (MP4 208044 kb).

Continuous monitoring of physiological data using the patient vital status fusion score in septic critical care patients.

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

Evaluating Clinical Prediction Rules for Bacteremia Detection in the Emergency Department: A Retrospective Review.

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

Clinical presentation and management of multisystem inflammatory syndrome in children associated with covid-19: a retrospective observational descriptive study in a pediatric hospital in Syria.

OBJECTIVE: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is a rare and serious medical condition. This study aims to review the clinical presentation, laboratory parameters, outcomes, and management of MIS-C cases in a pediatric hospital in Syria. METHODS: This retrospective observational study aimed to investigate MIS-C between May 2020 and October 2021. Data collection involved extracting information from medical records, and patients were identified based on the case definition established by the World Health Organization (WHO). Various laboratory investigations, diagnostic evaluations, clinical presentations, and treatments were performed to assess patients. Descriptive statistical analysis was conducted using Microsoft Excel. RESULTS: A total of 232 COVID-19 cases were reported with COVID-19 Infection. Among these cases, 25 (10.77%) were identified as MIS-C. The median age of the patients was 5.5 years, with the majority being male patients (72%). Patients experienced fever (100%), bilateral conjunctivitis (88%), rash (84%), gastrointestinal symptoms (76%), and cardiac dysfunction (72%). Other notable findings included oral cavity changes (64%), edema (36%), cervical lymphadenopathy (36%), and neurological manifestations (28%). Respiratory symptoms were uncommon (16%). All patients recovered, with no recorded deaths. CONCLUSION: The predominant presence of positive SARS-CoV-2 IgG in the majority of patients in this study supports the post-infectious nature of MIS-C. Respiratory symptoms were less prevalent in both pediatric COVID-19 and MIS-C patients. Early supportive care is crucial in management, although additional research is needed to establish definitive guidelines. Larger studies are necessary to overcome the limitations of this study and to enhance our understanding of MIS-C in pediatric COVID-19 patients.

Multisystem inflammatory syndrome in children (MIS-C) post-COVID-19 in Iran: clinical profile, cardiac features, and outcomes.

BACKGROUND: In April 2020, an association between multisystem inflammatory syndromes (MIS-C) was observed in children with severe acute respiratory syndrome coronavirus infection (SARS-CoV-2). Most patients had heart involvement alone, and most patients had pericardial effusion. This study aimed to express and emphasize cardiac involvement in pediatric patients with respiratory symptoms who were diagnosed with COVID-19. METHODS: This study was conducted in July 2021 in Kerman province, Southeastern Iran, during a notable surge in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. The study included 904 pediatric patients diagnosed with COVID-19. Data collection involved a comprehensive assessment of clinical symptoms and manifestations. Patients with fever lasting more than five days were admitted to the hospital. Echocardiography was utilized for cardiac involvement diagnosis, with 47 patients undergoing this diagnostic procedure. RESULTS: Of the 904 patients, most of them had high fevers (74%). Fifty-five patients had a fever for more than five days and were hospitalized. Of the 47 patients who underwent echocardiography, 45 (81%) had heart involvement. In 75% of patients, pericardial effusion was the only cardiac involvement. Patients with pericardial effusion were treated with dexamethasone up to 3 mg every 8 h for 72 h. CONCLUSIONS: MIS-C has a wide range of clinical symptoms. In cases where the fever is prolonged and there are gastrointestinal symptoms, physicians have clinical suspicion to diagnose this syndrome. Most cases of pericardial effusion are alone and improve with treatment with glucocorticosteroids.

[Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China].

Objective: To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China. Methods: This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis. Results: Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) (Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS (Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion: Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Plasma Protein Biomarkers Distinguish Multisystem Inflammatory Syndrome in Children From Other Pediatric Infectious and Inflammatory Diseases.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious hyperinflammatory complication following infection with severe acute respiratory syndrome coronavirus 2. The mechanisms underpinning the pathophysiology of MIS-C are poorly understood. Moreover, clinically distinguishing MIS-C from other childhood infectious and inflammatory conditions, such as Kawasaki disease or severe bacterial and viral infections, is challenging due to overlapping clinical and laboratory features. We aimed to determine a set of plasma protein biomarkers that could discriminate MIS-C from those other diseases. METHODS: Seven candidate protein biomarkers for MIS-C were selected based on literature and from whole blood RNA sequencing data from patients with MIS-C and other diseases. Plasma concentrations of ARG1, CCL20, CD163, CORIN, CXCL9, PCSK9 and ADAMTS2 were quantified in MIS-C (n = 22), Kawasaki disease (n = 23), definite bacterial (n = 28) and viral (n = 27) disease and healthy controls (n = 8). Logistic regression models were used to determine the discriminatory ability of individual proteins and protein combinations to identify MIS-C and association with severity of illness. RESULTS: Plasma levels of CD163, CXCL9 and PCSK9 were significantly elevated in MIS-C with a combined area under the receiver operating characteristic curve of 85.7% (95% confidence interval: 76.6%-94.8%) for discriminating MIS-C from other childhood diseases. Lower ARG1 and CORIN plasma levels were significantly associated with severe MIS-C cases requiring inotropes, pediatric intensive care unit admission or with shock. CONCLUSION: Our findings demonstrate the feasibility of a host protein biomarker signature for MIS-C and may provide new insight into its pathophysiology.

Assessing pattern of the Pediatric Multisystem Inflammatory Syndrome (PMIS) in children during the COVID-19 pandemic: experience from the emergency department of tertiary care center of a low-middle-income country.

BACKGROUND: Pediatric Multisystem Inflammatory Syndrome (PMIS) is a hyperinflammatory condition affecting multiple organs in children, often resembling incomplete Kawasaki Disease during later phases of COVID-19 infection. Data on PMIS in low-middle-income countries, particularly in emergency department settings, is limited. OBJECTIVES: This prospective observational study at Aga Khan University Hospital, Karachi, aimed to determine the frequency, clinical presentation patterns, and laboratory parameters of children with PMIS visiting the emergency department during the COVID-19 pandemic. Secondary objectives included assessing factors associated with in-hospital mortality. METHODS: From March 2020 to September 2021, patients meeting World Health Organization PMIS criteria were enrolled. COVID-19 testing included PCR and antibody testing. Data was collected through a questionnaire and analyzed statistically. RESULTS: Among 56 PMIS patients (85.7% male, mean age 7.67 ± 4.8 years), respiratory symptoms (70%), neurological symptoms (57%), and gastrointestinal symptoms (54%) were common presentations. Signs included delayed capillary refill time (93%), low-volume pulses (89%), and hypotension (68%). COVID-19 antibodies were positive in the majority (78.6%) while PCR was positive in 18%. Risk factors for mortality included prolonged emergency department stay, and high Ferritin and Lactate Dehydrogenase levels. CONCLUSION: PMIS affects children of all ages. Respiratory and gastrointestinal symptoms are the most frequent presentations. Elevated inflammatory markers, including LDH, Ferritin, D-dimer, and Pro-BNP, correlate with higher mortality risk.

Early warning scores for sepsis identification and prediction of in-hospital mortality in adults with sepsis: A systematic review and meta-analysis.

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

Usefulness of combining inflammatory biomarkers and clinical scales in an emergency department to stratify risk in patients with infections. / Utilidad de la combinación de biomarcadores de respuesta inflamatoria y escalas clínicas para la estratificación del riesgo en pacientes atendidos en urgencias por sospecha de infección.

OBJECTIVES: To determine whether combining biomarkers of inflammatory response and clinical scales can improve risk stratification of patients with suspected infection in a hospital emergency department (ED). MATERIAL AND METHODS: Prospective observational study of ED patients treated for infections. We collected the following information on arrival: demographic and baseline clinical data, comorbidities, the focus of infection, and values for the following inflammatory biomarkers: leukocyte counts, and C-reactive protein, procalcitonin, and midregional proadrenomedullin (MR-proADM) concentrations. Scores on the following clinical scales were recorded based on the variables gathered: the SIRS (Systemic Inflammatory Response Syndrome) criteria, the qSOFA (Quick Sequential Organ Failure Assessment), and the NEWS (National Early Warning Score). The main outcome was a composite measure that included 30-day death or need for intensive care unit (ICU) admission. RESULTS: A total of 473 patients with a mean (SD) age of 70.3 (19.2) years were included. The majority were men (257, 54.3%). Thirty-one (6.6%) died within 30 days and 16 (3.4%) were admitted to the ICU. The composite outcome (death or ICU admission) occurred in 45 patients (9.5%). The MR-proADM concentration, with an area under the receiver operating characteristic curve of 0.739 (95% CI, 0671-0.809) was a better predictor than the other biomarkers or clinical scales, although the differences between MR-proADM and either lactate concentration or the NEWS were not significant in the comparisons (P = .064). Combining the MR-proADM concentration with any of the scales did not significantly improve risk prediction. CONCLUSION: Risk stratification of patients with infection is a key part of ED decision-making. MR-proADM concentration is superior to other biomarkers and clinical prediction scales for predicting short-term prognosis in the ED. Combining MR-proADM measurement with other scales or measures does not improve the yield.

OBJETIVO: Investigar si la combinación de biomarcadores de respuesta inflamatoria (BMRI) y escalas clínicas mejora la estratificación pronóstica de pacientes atendidos en servicios de urgencias hospitalarios (SUH) por sospecha de infección. METODO: Estudio analítico, observacional y prospectivo que incluyó pacientes con sospecha de infección atendidos en un SUH. Se recogieron variables demográficas, comorbilidades, datos clínicos a la llegada al SUH, foco de infección y los siguientes BMRI: leucocitos, proteína C reactiva, procalcitonina, lactato y región medial de la proadrenomodulina (MR-proADM). Se calcularon los valores de las escalas SIRS (síndrome de respuesta inflamatoria sistémica), qSOFA (quick Sequential Organ Failure Assessment) y NEWS (National Early Warning Score). La variable de resultado principal fue una compuesta que incluía mortalidad a 30 días o necesidad de ingreso en la unidad de cuidados intensivos (UCI). RESULTADOS: Se incluyeron 473 pacientes, con una edad media de 70 (DE 19) años y el 54,3% (257). Hubo 31 fallecimientos (6,6%) y 16 (3,4%) ingresos en UCI. La variable de resultado se produjo en 45 (9,5%) pacientes. La MR-proADM mostró la mejor área bajo la curva de la característica operativa del receptor (ABC-COR) en comparación con el resto de biomarcadores y escalas clínicas [0,739 (IC 95% 0,671-0,809)], aunque sin diferencias respecto a lactato (p = 0,144) ni a la escala NEWS (p = 0,064). Al combinar MR-proADM con los diferentes biomarcadores y escalas clínicas, no se obtuvo ninguna combinación que mejore significativamente la precisión pronóstica individual del MR-proADM. CONCLUSIONES: La estratificación del riesgo de los pacientes con infección es una cuestión clave para la toma de decisiones en los SUH. La determinación de MR-proADM supera a otros BMRI y escalas clínicas para la estratificación pronóstica de los pacientes a corto plazo en los SUH. La combinación con otros biomarcadores o escalas clínicas no mejora su capacidad pronóstica.

Infection, Inflammation, and Poststroke Cognitive Impairment.

BACKGROUND: Infection and inflammation are dementia risk factors in population-based cohorts; however, studies in stroke are scarce. We determined the prevalence of infection after stroke and routinely measured inflammatory biomarkers during hospitalization and their associations with acute and 6-month cognitive impairment. METHODS AND RESULTS: A prospective stroke cohort completed the Oxford Cognitive Screen at ≤2 weeks and 6 months after stroke. Infection, inflammatory markers (C-reactive protein, white cell count, and neutrophil/lymphocyte ratio), and systemic inflammatory response syndrome were ascertained throughout admission with electronic patient records supplemented by hand searches. Associations with acute and 6-month global and domain-specific cognitive impairment were analyzed using multivariable regression, adjusting for demographic/vascular factors and stroke severity. Among 255 patients (mean age, 73.9 [SD, 12.6] years; 46.3% women; mean education, 12.6 [SD, 3.7] years; median National Institutes of Health Stroke Scale score 5 [range, minimum-maximum, 0-30]), infection was present in 90 patients (35.3%) at mean 4.4 (SD, 6.9) days after stroke, consisting predominantly of pneumonia (47/90; 52%) and urinary tract infection (39/90; 43%). Admission white cell count was elevated in 25.1% (n=64; mean, 9.5×109/L [SD, 3.2×109/L]), C-reactive protein in 41.2% (n=105; mean, 27.5 [SD, 50.9 mg/L]), neutrophil/lymphocyte ratio in 55.7% (n=97; mean, 5.5 [SD, 4.5]), and systemic inflammatory response syndrome in 26.6% (n=53 [45.2%] positive during hospitalization). Infection was associated with acute and 6-month poststroke cognitive impairment (P<0.05adj) with stronger associations acutely for severe infection (infection+systemic inflammatory response syndrome; P=0.03adj). Acute language, executive function and attention domain impairments, and 6-month number processing impairment were associated with infection (P<0.05adj). No significant relationships were found for any biomarker and cognitive impairment. CONCLUSIONS: Infection and elevations in routinely measured inflammatory biomarkers are common following stroke; however, only infection is associated with poststroke cognitive impairment, suggesting that increases in these biomarkers may be nonspecific. Infection may present a tractable target for reducing poststroke cognitive impairment.

Prolonged Systemic Inflammatory Response Syndrome After Cardiac Surgery.

OBJECTIVES: Cardiac surgery induces systemic inflammatory response syndrome (SIRS), leading to higher morbidity and mortality. There are no individualized predictors for worse outcomes or biomarkers for the multifactorial, excessive inflammatory response. The interest of this study was to evaluate whether a systematic use of the SIRS criteria could be used to predict postoperative outcomes beyond infection and sepsis, and if the development of an exaggerated inflammation response could be observed preoperatively. DESIGN: The study was observational, with prospectively enrolled patients. SETTING: This was a single institution study in a hospital setting combined with laboratory findings. PARTICIPANTS: The study included a cohort of 261 volunteer patients. INTERVENTIONS: Patients underwent cardiac surgery with cardiopulmonary bypass, and were followed up to 90 days. Biomarker profiling was run preoperatively. MEASUREMENTS AND MAIN RESULTS: Altogether, 17 of 261 (6.4%) patients had prolonged SIRS, defined as fulfilling at least 2 criteria on 4 consecutive postoperative days. During hospitalization, postoperative atrial fibrillation (POAF) was found in 42.2% of patients, and stroke and transient ischemic attack in 3.8% of patients. Prolonged SIRS was a significant predictor of POAF (odds ratio [OR] 4.5, 95% CI 1.2-17.3), 90-day stroke (OR 4.5, 95% CI 1.1-18.0), and mortality (OR 10.7, 95% CI 1.7-68.8). Biomarker assays showed that preoperative nerve growth factor and interleukin 5 levels were associated with prolonged SIRS (OR 5.6, 95%, CI 1.4-23.2 and OR 0.7, 95%, CI 0.4-1.0, respectively). CONCLUSIONS: Nerve growth factor and interleukin 5 can be used to predict prolonged systemic inflammatory response, which is associated with POAF, stroke, and mortality.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

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

Evolution of Cardiovascular Findings in Multisystem Inflammatory Syndrome in Children (MIS-C) Across COVID-19 Variants: Common Trends and Unusual Presentations.

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following COVID-19 infection. Cardiac involvement is common and includes left ventricular systolic dysfunction, cardiac marker elevation, electrocardiogram (ECG) changes, and coronary artery dilation. This single-center retrospective cohort study compares cardiovascular disease between three major SARS-CoV-2 variants and describes the evolution of findings in medium-term follow-up. Of 69 total children (mean age 9.2 years, 58% male), 60 (87%) had cardiovascular involvement with the most common features being troponin elevation in 33 (47%) and left ventricular dysfunction in 22 (32%). Based on presumed infection timing, 61 patients were sorted into variant cohorts of Alpha, Delta, and Omicron. Hospitalization was longer for the Delta group (7.7 days) vs Alpha (5.1 days, p = 0.0065) and Omicron (4.9 days, p = 0.012). Troponin elevation was more common in Delta compared to Alpha (13/20 vs 7/25, p = 0.18), and cumulative evidence of cardiac injury (echocardiographic abnormality and/or troponin elevation) was more common in Delta (17/20) compared with Alpha (12/25, p = 0.013) or Omicron (8/16, p = 0.034). Forty-nine (77%) of the original cohort (n = 69) had no cardiac symptoms or findings beyond 3 months post-hospitalization. Cardiac MRI was performed in 28 patients (between 3 and 6 months post-hospitalization) and was normal in 25 patients (89%). The differences in the variant cohorts may be due to alteration of the immune landscape with higher severity of COVID-19 infection. Despite overall reassuring cardiac outcomes, it is important to note the variability of presentation and remain vigilant with future variants.

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Multisystem inflammatory syndrome in children (MIS-C) is a complex syndrome characterized by multi-organ involvement that has emerged in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. The clinical presentation of MIS-C is similar to Kawasaki disease but predominantly presents with fever and gastrointestinal symptoms, and severe cases can involve toxic shock and cardiac dysfunction. Epidemiological findings indicate that the majority of MIS-C patients test positive for SARS-CoV-2 antibodies. The pathogenesis and pathophysiology of MIS-C remain unclear, though immune dysregulation following SARS-CoV-2 infection is considered a major contributing factor. Current treatment approaches for MIS-C primarily involve intravenous immunoglobulin therapy and symptomatic supportive care. This review article provides a comprehensive overview of the definition, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of MIS-C.