A novel mutation in the KCNJ11 gene (p.Val36Glu), predisposes to congenital hyperinsulinemia.

The hypoglycemia induced by insulin hypersecretion in congenital hyperinsulinemia (CHI), a rare life-threatening condition can lead to irreversible brain damage in neonates. Inactivating mutations in the genes encoding KATP channel (ABCC8 and KCNJ11) as well as HNF4A, HNF1A, HADH, UCP2, and activating mutations in GLUD1, GCK, and SLC16A1 have been identified as causal. A 3-month-old male infant presenting tonic-clonic seizures and hyperinsulinemia was clinically assessed and subjected to genetic analysis. Besides the index patient, his parents were clinically investigated, and a detailed family history was also recorded. The laboratory investigations and the genetic test results of the parents were compared with the index patient. The biochemical and hormonal profile of the patient confirmed his suffering from CHI and did not respond to diazoxide treatment. The genetic testing revealed that the subject harbored a novel homozygous missense mutation in the KCNJ11 gene, (c.107T>A, p.Val36Glu.). The bioinformatic analysis revealed that valine is highly conserved and predicted that the variant allele (p.Val36Glu) is likely pathogenic and causal for CHI. Parents were heterozygous carriers and did not report any abnormal metabolic profile. Identification of such mutations is critical and likely to change the therapeutic interventions for such patients in the future.

Enhancing respiratory disease diagnosis by bronchoalveolar lavage in Kashmir: an audit of findings.

OBJECTIVE: To study bronchoalveolar lavage (BAL) findings in various respiratory diseases in children in Kashmir India. DESIGN: Prospective observational study. SETTING: Paediatric department of the tertiary care hospital. PATIENTS: Children of both genders from 1 month to 17 years of age INTERVENTION: All studied patients underwent flexible bronchoscopy and BAL. OUTCOME MEASURE: To observe the BAL findings in various respiratory diseases in the studied population. RESULTS: A total of 283 patients underwent BAL procedure. The positive BAL report was received in 131 (46%) patients. Out of these, 55 (42%) patients had positive BAL culture/ microscopy for different bacterial (50) and fungal species (Candida spp (3), Mucormycosis (1) and Aspergillus (1)). MTB was isolated in 25 (19%) patients. Twenty-three (17.5%) patients had bronchoalveolar lavage fluid (BALF) positive for pulmonary hydatidosis. Foamy macrophages were seen in 13 patients, significant eosinophilia in nine patients and hemosiderin-laden macrophages were seen in three patients. CONCLUSION: We found BALF a very useful sample for the evaluation of many infective and non-infective respiratory diseases in our region, which otherwise lacks high end diagnostics. 46% of our patients had some abnormalities in the BAL specimen. It provided us with valuable information regarding organism profile and drug sensitivity in case of lung infection. BALF analysis was also found useful in the diagnosis of some non-infective pulmonary disorders like acute eosinophilic pneumonia, aspiration syndromes and bronchial asthma.

Role of procalcitonin in diagnosis of community acquired pneumonia in Children.

BACKGROUND: The role of serum Procalcitonin (PCT) in adults in diagnosis of Community acquired pneumonia (CAP) is well established, however, role in pediatric CAP remains controversial. OBJECTIVES: The objective of this study was to investigate the utility of serum procalcitonin in differentiating bacterial community-acquired lower respiratory tract infection from non-bacterial respiratory infection in children; radiologically confirmed pneumonia was used as the reference. In addition, we assessed the utility of adding the PCT assay to the clinical criteria for diagnosis of pneumonia. STUDY DESIGN: Subanalysis of a larger prospective,multicentriccohort study. PARTICIPANTS: Children, 2 months to 59 months of age, attending paediatric OPD of 5 urban tertiary care hospitals, suffering from acute respiratory infection (ARI). INTERVENTION: Detailed clinical history and examination findings of enrolled children were recorded on predesigned case record form. Samples for PCT were obtained at admission and were measured centrally at the end of the study except for one site using VIDAS® B.R.A.H.M.S PCT kit (Biomerieux SA, France). OUTCOMES: Sensitivity and specificity of procalcitonin for diagnosis of radiologically confirmed pneumonia. RESULTS: Serum Procalcitonin was measured in 370 patients; median (IQR) age of these children being 12 (7, 22) months, 235 (63.5%) were boys. The median (IQR) serum procalcitonin concentration was 0.1(0.05, 0.4) ng/mL.Sensitivity and specificity of raised PCT (> 0.5 ng/mL) for pneumonia as per any CXR abnormalities were 29.7% and87.5%,(P < 0.001) respectively. Raised PCT was also significantly associated with consolidation (34.5%,79.2%,P < 0.02)and pleural effusion(54.6%,79%,P < 001). Adding PCT to the existing clinical criteria of WHO did not improve the sensitivity for diagnosis of pneumonia. PCT was significantly higher in children with severe pneumonia. CONCLUSION: Positive PCT (> 0.5 ng/mL) is significantly associated with radiographic pneumonia but not with pneumonia based on WHO criteria.However, it can act as a surrogate marker for severe pneumonia.

Clinical Profile and Risk Factors for Severe Disease in 402 Children Hospitalized with SARS-CoV-2 from India: Collaborative Indian Pediatric COVID Study Group.

INTRODUCTION: There is a lack of large multicentric studies in children with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in children hospitalized with COVID-19 from India. METHODS: In this multicentric retrospective study, we retrieved data related to demographic details, clinical features, including the severity of disease, laboratory investigations and outcome. RESULTS: We included 402 children with a median (IQR) age of 7 (2-11) years. Fever was the most common symptom, present in 38.2% of children. About 44% had underlying comorbidity. The majority were asymptomatic (144, 35.8%) or mildly symptomatic (219, 54.5%). There were 39 (9.7%) moderate-severe cases and 13 (3.2%) deaths. The laboratory abnormalities included lymphopenia 25.4%, thrombocytopenia 22.1%, transaminitis 26.4%, low total serum protein 34.7%, low serum albumin 37.9% and low alkaline phosphatase 40%. Out of those who were tested, raised inflammatory markers were ferritin 58.9% (56/95), c-reactive protein 33.3% (41/123), procalcitonin 53.5% (46/86) and interleukin-6 (IL-6) 76%. The presence of fever, rash, vomiting, underlying comorbidity, increased total leucocyte count, thrombocytopenia, high urea, low total serum protein and raised c-reactive protein was factors associated with moderate to severe disease. CONCLUSION: Fever was the commonest symptom. We identified additional laboratory abnormalities, namely lymphopenia, low total serum protein and albumin and low alkaline phosphatase. The majority of the children were asymptomatic or mildly symptomatic. We found high urea and low total serum protein as risk factors for moderate to severe disease for the first time.

Intussusception in children aged under two years in India: Retrospective surveillance at nineteen tertiary care hospitals.

OBJECTIVE: Intussusception has been linked with rotavirus vaccine (RVV) as a rare adverse reaction. In view of limited background data on intussusception in India and in preparation for RVV introduction, a surveillance network was established to document the epidemiology of intussusception cases in Indian children. METHODS: Intussusception in children 2-23 months were documented at 19 nationally representative sentinel hospitals through a retrospective surveillance for 69 months (July 2010 to March 2016). For each case clinical, hospital course, treatment and outcome data were collected. RESULTS: Among the 1588 intussusception cases, 54.5% were from South India and 66.3% were boys. The median age was 8 months (IQR 6, 12) with 34.6% aged 2-6 months. Seasonal variation with higher cases were documented during March-June period. The most common symptoms and signs were vomiting (63.4%), bloody stool (49.1%), abdominal pain (46.9%) and excessive crying (42.8%). The classical triad (vomiting, abdominal pain, and blood in stools) was observed in 25.6% cases. 96.4% cases were diagnosed by ultrasound with ileocolic location as the commonest (85.3%). Management was done by reduction (50.8%) and surgery (41.1%) and only 1% of the patients' died. 91.1% cases met Brighton criteria level 1 and 3.3% Level 2. Between 2010 and 2015, the case load and case ratio increased across all regions. CONCLUSION: Intussusception cases have occurred in children across all parts of the country, with low case fatality in the settings studied. The progressive rise cases could indicate an increasing awareness and availability of diagnostic facilities.

Lactate clearance prognosticates outcome in pediatric septic shock during first 24 h of intensive care unit admission.

This study was undertaken to examine the clinical utility of lactate clearance as an indicator of mortality in pediatric septic shock, and to compare the performance of lactate clearance at 6, 12, and 24 h for predicting in-hospital and 60-day mortality. Pediatric patients with septic shock were prospectively studied. Vital signs, laboratory values, Pediatric Risk of Mortality Score, and pediatric logistic organ dysfunction score were obtained at presentation (hour 0), hour 6, hour 24 and over the first 72 h of hospitalization. Lactate clearance was obtained at 6, 12, and 24 h of hospital admission. Therapy received, outcome parameters of mortality, and duration of hospitalization were recorded. The primary outcome variable of 60-day mortality rate was 31.25%. Only lactate clearance at 6 and 24 h was significantly associated with mortality, with odds of 0.97 (95% CI, 0.951-981; p < 0.001) and 0.975 (95% CI, 0.964-0.986; p < 0.001), respectively. Approximately there was a 24% decrease in likelihood of mortality for each 10% increase in lactate clearance at 24 h. At a threshold value of 10% 6-h lactate clearance had a sensitivity of 0.948 and specificity of 0.571, while at a threshold of 20% 24-h lactate clearance had a sensitivity of 0.922 and specificity of 0.629. The comparison of clearance at 6 and 24 h using receiver operating characteristic showed that former was "fair" (area under the curve = 0.753) and later was "good" (area under the curve = 0.81) in predicting mortality in pediatric septic shock. CONCLUSION: We concluded that optimal lactate clearance in pediatric septic shock both during the early presentation and after the initial "golden hours" is associated with lower in-hospital and 60-day mortality. Further, 24-h lactate clearance appears superior to 6 h lactate clearance in predicting mortality in such patients.

Infantile Thiamine Deficiency: New Insights into an Old Disease.

CONTEXT: The wide spectrum of clinical presentation in infantile thiamine deficiency is difficult to recognize, and the diagnosis is frequently missed due to the lack of widespread awareness, and non-availability of costly and technically demanding investigations. EVIDENCE ACQUISITION: The topic was searched by two independent researchers using online databases of Google scholar and PubMed. We considered the related studies published in the last 20 years. The terms used for the search were 'thiamine', 'thiamine deficiency', 'beri-beri', 'B-vitamins','micronutrients', 'malnutrition', 'infant mortality'. 'Wernicke's syndrome','Wernicke's encephalopathy', and 'lactic acidosis'. RESULTS: In the absence of specific diagnostic tests, a low threshold for a therapeutic thiamine challenge is currently the best approach to diagnose infantile thiamine deficiency in severe acute conditions. The practical approach is to consider thiamine injection as a complementary resuscitation tool in infants with severe acute conditions; more so in presence of underlying risk factors, clinically evident malnutrition or where a dextrose-based fluid is used for resuscitation. Further, as persistent subclinical thiamine deficiency during infancy can have long-term neuro-developmental effects, reasonable strategy is to treat pregnant women suspected of having the deficiency, and to supplement thiamine in both mother and the baby during breastfeeding. CONCLUSIONS: Health care professionals in the country need to be sensitized to adopt a high level of clinical suspicion for thiamine deficiency and a low threshold for the administration of thiamine, particularly when infantile thiamine deficiency is suspected.

Vitamin D status correlates with the markers of cystic fibrosis-related pulmonary disease.

BACKGROUND: The prevalence of Vitamin D deficiency remains high in cystic fibrosis despite daily supplementation. Vitamin D as an immunomodulator has been related to lower respiratory tract infections in children. The present study was undertaken to examine the association between vitamin D status and markers of cystic fibrosis-related pulmonary disease including exacerbations, bacterial colonization and pulmonary function. METHODS: The study includes review of records of 51 cystic fibrosis patients. Baseline patient variables and serum vitamin D levels were recorded. Based on vitamin D levels study patients were divided into three groups: vitamin-D sufficient (≥20 ng/mL), vitamin-D insufficient (12 to 20 ng/mL), and vitamin D-deficient (≤12 ng/ml). RESULTS: The proportion of children with deficient, insufficient and sufficient vitamin D levels were 47.1%, 15.7%, and 37.2%, respectively. Female sex, bacterial colonization and a greater number of exacerbations were associated with highest odds of developing vitamin D deficiency in patients with CF with 1.77 (0.22-4.61) (p = 0.002), 2.9(0.57-14.82) (p = 0.011), and 5.12 (1.28-20.50) (p = 0.021) respectively. The comparison of vitamin-D levels taken during exacerbations, colonization and during routine follow-up were significant [16.04 (7.42-27.91), 24.3 (15.5-32.4) and 48.54 (18.37-78.7) ng/ml, p < 0.001]. The FEV1 was determined in 24 patients; the comparison was significant between vitamin D-deficient and -sufficient groups [0.75 (0.717-0.777) vs. 0.82 (0.74-0.92) p < 0.05]. CONCLUSION: We concluded that vitamin D deficiency was highly prevalent in children with CF, despite daily supplementation of the vitamin in diet. Further, vitamin D deficiency was associated with a higher rate of pulmonary exacerbations and higher incidence of pulmonary bacterial colonization. In addition, in younger patients, low vitamin D levels were associated with reduced pulmonary function.

The Diagnostic Dilemma of Traumatic Lumbar Puncture: Current Standing of Cerebrospinal Fluid Leukocyte Corrections and Our Experience With Cerebrospinal Fluid Biomarkers.

OBJECTIVE: To assess the diagnostic efficiency of cerebrospinal fluid markers of procalcitonin, lactate, and cerebrospinal fluid/serum lactate ratio for detecting bacterial meningitis during traumatic lumbar puncture, and to compare these markers with routinely used uncorrected and corrected leukocyte measurements. METHODS: Infants aged ≤90 days with traumatic lumbar puncture were prospectively studied. The diagnostic characteristics of cerebrospinal fluid assays of uncorrected and corrected leukocyte count, procalcitonin, lactate, and lactate ratio were described and compared. RESULTS: Considering the area under the curve (95% CI) analysis and standard cutoff values, the lactate-ratio (0.985 [0.964-0.989] at cutoff 1.2) had the best test indexes for identifying meningitis, followed by lactate (0.964 [0.945-0.984] at cutoff 2.2 mmol/L) and procalcitonin (0.939 [0.891-0.986] at cutoff 0.33 ng/mL) measurement, whereas the corrected total leukocyte count assay (0.906 [0.850-0.962] at cutoff 350 cells/mm3) had diagnostic properties moderately superior to uncorrected total leukocyte count measurement (0.870 [0.798-0.943] at cutoff 430 cells/mm3). CONCLUSION: Cerebrospinal fluid levels of procalcitonin, lactate, and lactate-ratio are reliable markers to diagnose bacterial meningitis in blood-contaminated cerebrospinal fluid.

Flexible Bronchoscopy in Non-resolving Pneumonia.

OBJECTIVE: To study the utility of diagnostic flexible bronchoscopy and bronchoalveolar lavage (BAL) in children with non-resolving pneumonia. METHODS: This was a cross-sectional study conducted in a tertiary care hospital from July 2015 through June 2016. Fifty-two consecutive children of both genders from 1 mo to 14 y of age with a diagnosis of non-resolving pneumonia were included. Flexible bronchoscopy was done in all patients with or without bronchoalveolar lavage (BAL). BAL was sent for gram staining, culture, gene expert™ and lipid laden macrophages examination. Main outcome measures were to find any morphological abnormality in the tracheobronchial tree and organism profile of a positive BAL culture. RESULTS: During the period of 12 mo, 52 consecutive patients of non-resolving pneumonia were enrolled. Median (IQR) age of the study population was 12 (68.8) mo. Mean ± SD duration of illness was 22.7 ± 5.6 d. Flexible bronchoscopy was found to be very safe and effective tool that directly led to definitive diagnosis in 30.7% of cases. It was positive for different organisms in 22 (52.3%) children. Neglected foreign body was seen in five patients. CONCLUSIONS: Non-resolving pneumonia is often an area of clinical dilemma. Bacterial infections are the commonest etiology. Non-infectious causes like tracheobronchomalacia and foreign body aspiration are other important etiologies to be looked for. Early bronchoscopy and bronchoalveolar lavage analysis can play a crucial role in the evaluation of these patients and may provide an important clue or strongly support the specific diagnosis.

Prevalence, risk factors and consequences of overweight and obesity among schoolchildren: a cross-sectional study in Kashmir, India.

BACKGROUND: Obesity among children and adolescents is a growing public health problem. The objective of this study was to evaluate the prevalence, risk factors and metabolic consequences of obesity among schoolchildren from Kashmir, India. METHODS: The study subjects (n=2024) included 870 boys and 1154 girls, aged between 6 and 18 years. Data were collected by interviewer-administered questionnaires. Information was obtained about different lifestyles, anthropometric parameters and dietary habits. Obesity was defined as body mass index (BMI) percentile as per the guidelines of Centers for Disease Control, 2000. For the evaluation of different clinical parameters, blood samples were collected from the subjects in the fasting state at 8 to 9 am after an overnight (10-12 h) fast. RESULTS: The highest representation of subjects was from fee-paying private schools. Out of the total subjects, 6.69% were overweight and 4.64% were obese. The hip circumference, abdominal circumference, BMI, blood pressure (BP), use of ready-made foods as well as the clinical parameters like glucose, phosphorous, cholesterol and triglycerides were found significantly higher among girls than boys (p<0.05). Boys were taller and were physically more active than girls (p<0.01). Compared to the boys (3.33%), the girls were found to be more obese (5.63%). Rural dwelling subjects (4.22%) exhibited a lower percentage of obesity than urban population (5.00%). The difference in obesity among the different age groups was found statistically significant (p<0.05). Additionally, children with active lives in the form of vigorous (10.59%) or moderate (10.34%) exercise decreased their chances of gaining weight substantially. CONCLUSIONS: Results from the present study have shown that prevalence of obesity among children was high in our population.

Magnesium sulfate in severe perinatal asphyxia: a randomized, placebo-controlled trial.

OBJECTIVE: The goal was to study whether postnatal magnesium sulfate infusion could improve neurologic outcomes at discharge for term neonates with severe perinatal asphyxia. METHODS: Forty term (> or =37 weeks of gestation) neonates with severe perinatal asphyxia were studied in a prospective, longitudinal, placebo-controlled trial. Patients were assigned randomly to receive either 3 doses of magnesium sulfate infusion at 250 mg/kg per dose (1 mL/kg per dose) 24 hours apart (treatment group) or 3 doses of normal saline infusion (1 mL/kg per dose) 24 hours apart (placebo group). Both groups also received supportive care according to the unit protocol for perinatal asphyxia. RESULTS: In the treatment group, moderate encephalopathy was present in 35% (7 of 20) of the patients and severe encephalopathy in 65% (13 of 20) of patients at admission. In the placebo group, 40% (8 of 20) of patients had moderate encephalopathy and 60% (12 of 20) of patients had severe encephalopathy. The mean serum magnesium concentration in the treatment group remained at > or =1.2 mmol/L for 72 hours after the first infusion. At discharge, 22% (4 of 18) of infants in the treatment group had neurologic abnormalities, compared with 56% (10 of 18) of infants in the placebo group. Also, neuroimaging (head computed tomography) performed on day 14 yielded abnormal findings for fewer infants in the treatment group than in the placebo group (16% vs 44%). Infants in the treatment group were more likely to be receiving oral feedings (sucking) at discharge than were those in the placebo group (77% vs 37%). Good short-term outcomes at discharge occurred for 77% of the patients in the treatment group, compared with 37% of the patients in the placebo group. CONCLUSION: Postnatal magnesium sulfate treatment improves neurologic outcomes at discharge for term neonates with severe perinatal asphyxia.