Clinical Profile, Intensive Care Needs and Predictors of Outcome Among Children Admitted with Non-COVID Severe Acute Respiratory Illness (SARI) During the Pandemic.

OBJECTIVES: To study the epidemiology of non-coronavirus disease-2019 (non-COVID-19) respiratory viral infections with respect to their clinical profile, intensive care needs and predictors of outcome once the non-pharmacological interventions (NPI) during the coronavirus disease-2019 (COVID-19) pandemic were relaxed. METHODS: Retrospective analysis of children with Severe Acute Respiratory Illness (SARI) who were SARS-CoV-2 negative, admitted to the Pediatric Emergency/Intensive Care Unit (PICU) from July 2021 through October 2021 was conducted. RESULTS: One hundred and thirty nine children with median age of 11 (4-28.5) mo were included. Besides respiratory symptoms in all, diarrhea was reported in 90 (64.7%) children. Nearly half (n = 66; 47%) presented in hypoxemic respiratory failure (SpO2 <88%). Fifty-two (37.4%) children had co-morbidities, commonest being congenital heart disease in 12 (23.1%). Baseline parameters revealed leukopenia (specifically lymphopenia) 39 (28%), elevated aspartate transaminase [Serum glutamic-oxaloacetic transaminase (SGOT)] in 108 (77.6%), elevated N-acetyl-cysteine-activated creatinine kinase (CK-NAC) 23 (79%) and lactate dehydrogenase (LDH) 15 (88%). Intensive care needs included mechanical ventilation 51 (36.6%), vasoactive support 34 (24.5%), and renal replacement therapy 10 (7.1%). Forty-two (30.2%) children developed multi-organ dysfunction syndrome (MODS). One hundred and three (74.1%) children were discharged, 31 (22.3%) died, and 5 (3.6%) left against medical advice. On multivariate regression analysis, elevated liver enzymes (>5 times normal), hypoxemic respiratory failure at admission, hypotensive shock and MODS predicted mortality. CONCLUSIONS: A surge in non-COVID SARI was observed once lockdown measures were relaxed. Nearly 1/3rd progressed to multi-organ failure and died. Elevated liver enzymes, hypoxemic respiratory failure at admission, hypotensive shock and MODS predicted death.

Clinico-Laboratory Profile, Intensive Care Needs and Short-Term Outcome of Multisystem Inflammatory Syndrome in Children (MIS-C): Experience during First and Second Waves from North India.

OBJECTIVES: To describe the clinico-laboratory profile, intensive care needs and outcome of multisystem inflammatory syndrome in children (MIS-C) during the first and second waves. METHODOLOGY: This retrospective study was conducted in the paediatric emergency and paediatric intensive care unit (PICU) of a tertiary care teaching hospital in North India involving 122 children with MIS-C admitted during the first wave (September 2020-January 2021, n = 40) and second wave (February 2021-September 2021, n = 82) of coronavirus disease 2019 (COVID-19). RESULTS: The median (interquartile range) age was 7 (4-10) years and 67% were boys. Common manifestations included fever (99%), abdominal symptoms (81%), rash (66%) and conjunctival injection (65%). Elevated C-reactive protein (97%), D-dimer (89%), procalcitonin (80%), IL-6 (78%), ferritin (56%), N-terminal pro B-type natriuretic peptide (84%) and positive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody (81%) were common laboratory abnormalities. Cardiovascular manifestations included myocardial dysfunction (55%), shock (48%) and coronary artery changes (10%). The treatment included intensive care support (57%), non-invasive (33%) and invasive (18%) ventilation, vasoactive drugs (47%), intravenous immunoglobulin (IVIG) (83%), steroids (85%) and aspirin (87%). The mortality was 5% (n = 6). During the second wave, a significantly higher proportion had positive SARS-CoV-2 antibody, contact with COVID-19 and oral mucosal changes; lower markers of inflammation; lower proportion had lymphopenia, elevated IL-6 and ferritin; lower rates of shock, myocardial dysfunction and coronary artery changes; lesser need of PICU admission, fluid boluses, vasoactive drugs and IVIG; and shorter hospital stay. CONCLUSION: MIS-C is a febrile multisystemic disease characterized by hyperinflammation, cardiovascular involvement, temporal relationship to SARS-CoV-2 and good outcome with immunomodulation and intensive care. During the second wave, the severity of illness, degree of inflammation, intensive care needs, and requirement of immunomodulation were less as compared to the first wave.

Cerebral Phaeohyphomycosis: Subacute Meningoencephalitic Presentation in a Child.

Cerebral phaeohyphomycosis is a rare but serious fungal infection of the central nervous system caused by dematiaceous septate fungi characterized by the presence of melanin-like pigment within the cell wall that is a pale brown to black. It is associated with poor prognosis despite aggressive treatment. We report a previously well 3-year boy with cerebral phaeohyphomycosis who had subacute meningoencephalitic presentation with refractory raised intracranial pressure and had fatal outcomes. The diagnosis was confirmed by histopathological examination of brain tissue obtained by brain biopsy.

Cytokine Levels in Critically Ill Children With Severe Sepsis and Their Relation With the Severity of Illness and Mortality.

OBJECTIVE: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. DESIGN: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Pediatric intensive care unit of a tertiary level teaching hospital in India. PATIENTS: Fifty children with severe sepsis aged 3 months to 12 years. MATERIAL AND METHODS: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor ß1 [TGF-ß1]) cytokines. PRIMARY OUTCOME: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). SECONDARY OUTCOMES: To compare cytokine levels among survivors and nonsurvivors. RESULTS: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-ß1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = -0.257, P = .09) and TGF-ß (ρ = -0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. CONCLUSION: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.

Hemophagocytic Lymphohistiocytosis in a PICU of a Developing Economy: Clinical Profile, Intensive Care Needs, Outcome, and Predictors of Mortality.

OBJECTIVES: To describe the clinical profile, intensive care needs, outcome, and predictors of mortality in critically ill children with hemophagocytic lymphohistiocytosis. DESIGN: Retrospective case series. SETTING: PICU of a tertiary care teaching hospital in North India. PATIENTS: Children 2 months to 12 years old with the diagnosis of hemophagocytic lymphohistiocytosis admitted to PICU from January 2012 to April 2019 (7» yr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-two children with hemophagocytic lymphohistiocytosis (60 secondary and two primary) were enrolled. The median (interquartile range) age of the study group was 82 months (50.5-124 mo). The median (interquartile range) Pediatric Risk of Mortality III score was 16 (10-23). Majority of hemophagocytic lymphohistiocytosis was infection-associated (n = 51; 82.3%). Among these, scrub typhus accounted for 29% of cases (n = 18), dengue 17.7% (n = 11), bacterial sepsis 14.5% (n = 9), enteric fever 6.5% (n = 4), and other infections 14.5% (n = 9). Systemic-onset juvenile idiopathic arthritis accounted for 9.7% of cases (n = 6) and malignancy for 4.8% patients (n = 3). Majority of cases were treated with steroids (77.4%) and IV immunoglobulin (25.8%). Various complications noted were shock (71%), acute kidney injury (66.1%), acute respiratory distress syndrome (41.9%), disseminated intravascular coagulation (54.8%), CNS dysfunction (54.8%), multiple organ dysfunction syndrome (82.3%), and healthcare-associated infections (14.5%). Intensive care needs for primary illness and/or hemophagocytic lymphohistiocytosis included mechanical ventilation (74.2%); packed RBC (72.3%), fresh frozen plasma (40.3%), and platelet (48.4%) transfusion; vasoactive drugs (71%); and renal replacement therapy (24.2%). The median duration of PICU stay was 5 days (2.5-9.5 d) and mortality was 59.7% (n = 37). On univariate analysis, nonsurvivors had higher Pediatric Risk of Mortality III score; higher proportion of shock, acute kidney injury, acute respiratory distress syndrome, disseminated intravascular coagulation, and multiple organ dysfunction syndrome; the need for blood and blood components, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged duration of mechanical ventilation compared with survivors. CONCLUSIONS: Hemophagocytic lymphohistiocytosis in PICU is commonly secondary to tropical infections and associated with high mortality. Higher severity of illness; shock and multiple organ dysfunction syndrome; need for blood and blood products, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged mechanical ventilation predicted death. Treatment of underlying infection and a less intense immunosuppressive therapy (steroids ± IV immunoglobulin) are suggested options. A high index of suspicion for complicating hemophagocytic lymphohistiocytosis is required in children with prolonged fever, cytopenias, organomegaly, and organ dysfunction not responding to conventional treatment.

Severe Dengue and Associated Hemophagocytic Lymphohistiocytosis in PICU.

OBJECTIVES: To study the clinico-laboratory profile and outcome of children with severe dengue and dengue-associated hemophagocytic lymphohistiocytosis (HLH). METHODS: In this retrospective study, 22 children with laboratory confirmed severe dengue admitted to pediatric intensive care unit (PICU) were enrolled. Clinical features, laboratory parameters, and outcome were noted and compared between cases fulfilling HLH-2004 criteria and those without HLH. RESULTS: Median (IQR) age was 8 (5-10.3) y. Fever was present for mean (SD) duration of 5.3 (2.1) d. Vomiting, respiratory distress, pain abdomen and hepatomegaly were other clinical features. Thrombocytopenia, anemia and elevated serum transaminases were noted in 91%, 41% and 30% respectively; coagulopathy and hypoalbuminemia were seen in 36% each. Half (n = 11, 50%) had dengue shock syndrome. Acute respiratory distress syndrome (ARDS) (n = 7, 32%) and acute kidney injury (AKI) (n = 6, 28%) were other major organ dysfunctions. Mean (SD) duration of PICU stay was 3.6 (1.5) d with 13.6% mortality. HLH was noted in 7 (32%) cases at a median (IQR) hospital stay of 5 (2-8) d. Children with HLH had significantly higher Pediatric Index of Mortality 2 (PIM 2) score at admission and higher frequency of pain abdomen, anemia, hypoalbuminemia, elevated alanine aminotransferase (ALT) and ARDS. Length of PICU stay (5.1 vs. 2.9 d) and mortality (28.6% vs. 6.7%) were higher in HLH group, however the difference was not statistically significant. Steroids were used in 4 cases with HLH and all survived, whereas among 3 who did not receive steroids, 2 died (p = 0.23). CONCLUSIONS: Severe dengue presents with life-threatening organ dysfunctions. HLH is increasingly recognized in dengue infection and maybe considered as a differential diagnosis in children with lower hemoglobin, hypoalbuminemia, elevated ALT and severe organ dysfunction.

Phenotypic heterogeneity of kyphoscoliosis with vertebral and rib defects: a case series.

Disorders associated with multiple vertebral segmentation defects may have additional rib anomalies in form of absence or hypoplastic ribs, fanning of ribs, etc. Spondylocostal dysostosis is genetic disorder with abnormal vertebral segmentation and rib anomalies. Diagnosis is often delayed because of non-familiarity with the characteristic features. There are six genes identified for spondylocostal dysostosis, of which SCDO5 is responsible for autosomal dominant form of the disorder. Retrospective study was conducted in Genetic and Metabolic unit of a tertiary hospital in north India over a period of 9 years. Twenty patients with a clinical diagnosis of congenital scoliosis were identified, and reviewed. Three patients were discussed in an earlier report and 11 subsequent patients, are described in this case series here. The median age at presentation was 34 months. The patients showed hemivertebrae, vertebral fusion, fusion of ribs, fanning of ribs. Hydrocephalus/ventriculomegaly was found in three cases and diastematomyelia was identified in one case. Other associated anomalies included corpus callosal agenesis, club foot and capillary malformation. One parent showed rib/spinal defects in two cases. Further studies are needed to characterise the phenotype and genetic basis of scoliosis in Indian patients.

Principles of Management of Central Nervous System Infections.

CNS infections in children are medical emergency and are associated with high mortality and morbidity. For diagnosis, a high index of suspicion is required. Clinical assessment should be supplemented by laboratory investigations including CSF Gram stain and cultures, blood culture, PCR on CSF, serological tests, and imaging. Commonly associated life threatening complications include coma, seizure, raised intracranial pressure (ICP), focal deficits, shock, respiratory failure, and fluid and electrolyte abnormalities. Immediate management should first address control of airway, breathing and circulation; protocolized management of raised ICP and status epilepticus; maintaining adequate intravascular volume; and close monitoring for early detection of complications. Appropriate antimicrobial agents should be administered promptly according to the suspected pathogen. Clinical evaluation, laboratory workup, specific antimicrobial therapy, supportive treatment, and management of associated complications should go hand in hand in a protocolized way for better outcome.

Evaluation of micronutrient profile of North Indian children with cystic fibrosis: a case-control study.

BACKGROUND: Data on the micronutrient levels in children with cystic fibrosis (CF) are not available from developing countries, wherein the nutritional profile of children is quite different from that of Western countries. METHODS: Levels of fat-soluble vitamins (A, D, and E) and trace metals (iron, copper, and zinc) were measured in 27 CF cases and 27 controls. RESULTS: CF cases had significantly low levels of all studied micronutrients compared with controls, and the levels were even lower in cases with exacerbation than in stable CF cases. Prevalence of deficiency of vitamin D, vitamin E, iron, copper, and zinc was significantly higher in cases than in controls, whereas vitamin A deficiency was almost equal in both the groups. CONCLUSION: The prevalence of deficiency of vitamins A, D, and E and iron, copper, and zinc was high in CF cases, and their levels were significantly lower in cases than controls. CF cases should be regularly monitored for these micronutrients, and appropriate supplementation should be considered.

Proteus syndrome: Clinical profile of six patients and review of literature.

OBJECTIVE: Proteus syndrome (PS) is characterized by patchy or segmental overgrowth and hyperplasia of multiple tissues and organs, along with susceptibility to development of tumors. Very few cases are reported in literature from developing countries. Due to certain overlapping features with other overgrowth syndromes, diagnosis is usually delayed. Our aim was to describe clinical profile of this rare condition in six patients. MATERIALS AND METHODS: Retrospective case sheet review of patients followed in a Pediatric Genetic and Metabolic clinic at a tertiary care institute of North India with a diagnosis of hemihypertrophy/overgrowth syndrome. RESULTS: Six cases presented with asymmetric overgrowth and peculiar features suggestive of PS were included in this study. Age at presentation was 2 months to 10 years; two were males and four were females. Hemihypertrophy was noticed in only one case at birth, and focal overgrowths in rest of other patients were seen later during childhood. CONCLUSION: Due to certain overlapping features with other overgrowth syndromes, diagnosis of PS is usually delayed. Pediatricians are the first persons who come across such patients and they should be aware about this rare condition.