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OBJECTIVE: To describe the clinical profile and determine the factors affecting mortality of children admitted with adenovirus infection in a tertiary care centre in South India. METHODS: In this observational study, respiratory specimens (nasopharyngeal swab / endotracheal aspirate) were collected from all hospitalized pediatric patients presenting with fever, cough, breathlessness, gastrointestinal symptoms, unexplained encephalopathy or multisystem involvement, between February 2023 and August 2023. Infection with adenovirus was determined by viral pathogen panel based on polymerase chain reaction (PCR) technique. Those referred from elsewhere with positive adenovirus report but non-availability of treatment details and children with coinfections were excluded. The clinical and laboratory profile of children with adenovirus infection were collected and predictors for in-hospital mortality were determined by logistic regression analysis. RESULTS: Out of 527 children who were screened, 130 children with a median (IQR) age of 18 (10, 48) months, had adenovirus infection. 84.5% were aged below 5 years. 62 (41.33%) children required intensive care admission. Abnormal chest radiograph, multisystem involvement and non-respiratory illness were present in 90 (69.2%), 97 (74.62%) and 26 (20%) children. Complications included acute respiratory distress syndrome (n = 8), hemophagocytic lymphohistiocytosis (n = 7), left ventricular dysfunction (n = 11), acute liver cell failure (n = 7), acute kidney injury (n = 13), and multiorgan dysfunction (n = 16). Overall mortality was 13%. Acute kidney injury, left ventricular dysfunction and pancytopenia were identified as factors that may be significantly associated with death. CONCLUSION: Multisystem involvement was observed in majority of children presenting with adenovirus infection. Non respiratory presentation is seen in a fifth of children with adenovirus infection.

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BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. METHODS: The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. RESULTS: MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1ß, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. CONCLUSIONS: This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.

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OBJECTIVES: To describe the clinical presentation, phenotype and outcome of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (Covid-19) from a tertiary care center in southern India. METHODS: 257 children fulfilling the inclusion criteria of MIS-C were prospectively enrolled from June, 2020 to March, 2022. RESULTS: Median (range) age at presentation was 6 year (35 day to 12 years). Presenting features were fever (98%), vomiting (75.8%), red eyes (63%), rashes (49%), pain abdomen (49%), shock (45.9%), lymphopenia (73%, thrombocytopenia (58.3%) and anemia (45%). 103 (39.7%) children required intensive care admission. Shock phenotype, Kawasaki-like phenotype and no specific phenotype were diagnosed in 45.9%, 44.4%, and 36.6% children, respectively. Left ventricular dysfunction (30.3%), acute kidney injury (13%), acute liver failure (17.4%), and hemophagolymphohistiocytosis (HLH) (13.6%) were the major system involvement in MIS-C. Mitral regurgitation (P=0.029), hyperechogenic coronaries (P=0.006), Left ventricular dysfunction (P=0.001) and low ejection fraction (P=0.007) were significantly associated with shock. Overall mortality was 11.7%. CONCLUSION: Kawasaki-like and shock-like presentation were common in MIS-C. Coronary abnormalities were seen in 118 (45.9%) children. Children with acute kidney injury, HLH, need for mechanical ventilation, and echocardiogram evidence of mitral regurgitation in MIS-C have a poor outcome.

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BACKGROUND: Severe dengue is associated with a considerable risk of mortality, and there is currently a lack of appropriate prognostic biomarkers to predict its severity. Pathogenesis of severe dengue is characterized by overt inflammation, endothelial activation, and increased vascular permeability. The current study investigates the utility of endothelial, inflammatory, and vascular permeability factors as biomarkers to identify dengue severity, which could improve disease prognosis and management. METHODS: The dengue-positive subjects were classified based on seropositivity for NS1, IgM, and IgG. The samples in each group were quantified for basic clinical investigations. The levels of Interleukin-6 (IL-6), Tumor necrosis factor receptor 1 (TNFR1), EOTAXIN, Monocyte chemoattractant protein-1 (MCP-1), Monokine induced by interferon-gamma (MIG), Intercellular adhesion molecule-1 (ICAM-1), Vascular cell adhesion molecule-1 (VCAM-1), Thrombomodulin, and Angiopoietin-2 were estimated in all serum samples using the multiplex bead-based assay. RESULTS: IgG seropositive dengue patients showed abnormal laboratory characteristics and severe dengue symptoms. Among the studied markers, only IL-6, TNFR1, ICAM-1, VCAM-1, Thrombomodulin, and Angiopoietin-2 were significantly elevated in IgG seropositive patients compared to healthy controls. Increased IL-6 and TNFR1 levels were associated with decreased platelet count and elevated Hematocrit levels in IgG seropositive patients. Furthermore, ROC curve analysis indicated that IL-6, TNFR1, Thrombomodulin, and Angiopoietin-2 showed good potential for predicting dengue severity. CONCLUSION: Inflammatory markers IL-6 and TNFR1, and endothelial factors Angiopoietin-2 and Thrombomodulin, could serve as prognostic markers for severe dengue. These findings also encourage the future study of these biomarkers in the pathogenesis of severe dengue infection.

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BACKGROUND: Plasma leakage is a major pathogenic manifestation of severe dengue and is a precursor of life-threatening complications associated with dengue. Accumulating evidence indicates the role of Matrix Metalloproteinases (MMPs) in mediating vascular permeability and plasma leakage following induction by the dengue virus. This study aims to investigate the utility of MMP-2, MMP-3, and MMP-9 in predicting the severity of dengue infection and further explore the relationship of these markers with the pathogenic factors associated with plasma leakage. METHODS: The dengue-positive subjects were classified into mild and severe dengue groups based on the manifestation of warning signs. The samples in each group and healthy controls were quantified for basic laboratory characteristics. The levels of MMP-2, MMP-3, MMP-9, and Macrophage migration inhibitory factor (MIF) were estimated in all serum samples using a multiplex bead-based assay. RESULTS: MMP-2 and MMP-9 were markedly elevated in severe dengue patients compared to mild dengue patients and healthy controls. No alteration in the circulating levels of MMP-3 was observed between the study groups. ROC curve analysis indicated that MMP-2 and MMP-9 exhibited good potential for predicting severe dengue. Notably, an increase in MMP-9 was associated with increased MIF and Hematocrit levels in severe dengue patients. CONCLUSION: MMP-2 and MMP-9 could serve as prognostic biomarkers for severe dengue. These findings also identify the association of MMP-9 with markers of plasma leakage, thereby encouraging further studies to explore the therapeutic potential of targeting MMP-9 in managing plasma leakage in severe dengue.

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Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes (67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India.

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Fazio Londe Syndrome is a rare neurological disorder presenting with progressive bulbar palsy with respiratory failure. Initially considered to have an unrelenting course, is now found to be due to mutations in the SLC52A3 gene which encodes the intestinal (hRFT2) riboflavin transporter in some children. We report an 11-year-old child with features of Fazio Londe syndrome who presented to our Institute with respiratory failure.

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BACKGROUND AND AIMS: Pediatric index of mortality (PIM) 2 score is one of the severity scoring systems being used for predicting outcome of patients admitted to intensive care units (ICUs). The aim of the present study was to evaluate the usefulness of PIM2 score in predicting mortality in a tertiary care pediatric ICU (PICU) and to assess the associated factors in predicting mortality such as presence of shock, need for assisted ventilation and Glasgow coma scale <8. MATERIALS AND METHODS: This was a prospective observation study done at tertiary care PICU from May 2011 to July 2011. Consecutive 119 patients admitted to PICU (aged 1 month to 12 years) were enrolled in the study. PIM2 scoring was done for all patients. The outcome was recorded as death or discharge. The associated factors for mortality were analyzed with SPSS 17. RESULTS: PIM2 score discriminated between death and survival at a 99.8 cut-off, with area under receiver operating characteristic curve 0.843 with 95% confidence interval (CI) (0.765, 0.903). Most patients were referred late to this hospital, which explains higher death rate (46.2%), lesser length of hospital stay (mean 2.98 days) in the mortality group, and increased rate of mechanical ventilation (68.1%). Presence of shock was independently associated with mortality, as evidenced by binary logistic regression. CONCLUSION: PIM2 score discriminated well between survivors and death at PICU. Presence of shock was significantly associated with mortality.

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Studies have reported high adiponectin levels in children with type 1 diabetes mellitus (T1DM). Adiponectin has been found to have anti-atherogenic action and other protective functions. We wanted to estimate adiponectin level in south Indian T1DM children and compare it with that of non-diabetic children and study its correlation with anthropometry and glycemic status. Sixty children with T1DM and forty non-diabetic children of age less than 15 years were analysed. Mean adiponectin level was higher in T1DM group than in non diabetic group (p < 0.001) irrespective of the age group or sex. Negative correlation was observed between SFT- triceps and adiponectin in diabetic and control group. Multiple regression coefficient analysis of various parameters showed SFT- triceps as a statistically significant predictor of adiponectin level (p = 0.001). We conclude that, children with T1DM had higher adiponectin level than non-diabetic children. Low SFT- triceps measuremet may be a predictor of higher adiponectin level.

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OBJECTIVE: To study the etiology, clinical presentation and outcome of infantile onset diabetes mellitus (IODM). DESIGN: Descriptive cohort study. Retrospective study from 1999-2007 and prospective from 2008-2012. SETTING: The diabetic clinic at a Pediatric tertiary care referral institute in Chennai. METHODS: All infants diagnosed to have diabetes at less than one year of age were studied. Study variables were age at onset, gender, mode of presentation, birth weight, initial blood glucose, serum HbA1c, serum c peptide levels, outcome at initial presentation, insulin requirement, associated comorbid conditions, genetic analysis and outcome at the end of the study or until they were followed up. RESULTS: 40 infants with infantile onset diabetes were studied, constituting 8% of all children with onset of DM at less than 12 years of age. 67.5% of these children presented with diabetic keto acidosis (DKA), only 30% had a provisional diagnosis of DM or DKA at first physician contact. 63% of IODM with onset less than 6 months and 30% with onset more than 6 months were of low birth weight. Nearly 85% of the study group had low C-peptide levels. 84.5% of IODM with onset less than 6 months and 55% of those with onset more than 6 months were monogenic. Wolcott Rallison syndrome was the commonest type encountered. Genetic diagnosis aided switching over from insulin to oral sulphonylurea in 5 children with KCNJ11 and ABCC8 mutations. Missed diagnosis, recurrent admissions for metabolic instability and developmental delay were common problems in IODM. Mortality at 12.5 year follow up was 32.5%. CONCLUSIONS: IODM with onset at less than 6 months is predominantly monogenic and low birth weight is more common. 55% of IODM were misdiagnosed at onset. Developmental delay is the common co morbid condition in IODM. Genetic diagnosis aids change of therapy to oral sulphonylurea.

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