Suresh Kumar Angurana

Vitamin D deficiency in critically ill children with sepsis.

Background: Data on the prevalence of vitamin D deficiency (VDD) in critically ill children with sepsis and its association with illness severity and outcome are limited. Aim: To investigate the prevalence of VDD in critically ill children with sepsis. Methods: One hundred and twenty-four critically ill children with sepsis aged 1–12 years were prospectively enrolled in a paediatric intensive care unit (PICU) in North India over a 1-year period. Demographic data, clinical signs and risk factors for VDD, Paediatric Index of Mortality III (PRISM III) score, and sequential organ failure assessment (SOFA) score were recorded. Plasma 25-hydroxy vitamin D [25(OH)D] levels were measured by ELISA within 24 hours of admission. The occurrence of septic shock, multiple organ dysfunction syndrome (MODS) and healthcare-associated infection (HCAI), need for mechanical ventilation and catecholamines, length of PICU stay and mortality were also recorded. Cases were compared with 338 apparently healthy children for baseline variables and vitamin D status. Results: Prevalence of VDD [25(OH)D level < 50 nmol/L] was higher among critically ill children with sepsis compared to healthy controls (50.8% vs 40.2%, P = 0.04). VDD was not associated with any significant difference in baseline demographic variables or risk factors for VDD. Although there was a trend toward increased PRISM III score, septic shock, MODS, HCAI, need for mechanical ventilation and catecholamines, length of PICU stay, and mortality, the difference was not statistically significant. Conclusion: A high prevalence of VDD in critically ill children with sepsis was found but it was not associated with greater severity of illness or other clinical outcomes.

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.

Defect of Cobalamin Intracellular Metabolism Presenting as Diabetic Ketoacidosis: A Rare Manifestation

Hypoglycemia is the usual feature of commonly occurring organic acidemias. Organic acidemias manifesting as hyperglycemia or diabetic ketoacidosis are rare and only a few cases have been reported. We report a 13-month-old boy who presented with vomiting, dehydration, coma, hyperglycemia, high anion gap metabolic acidosis and ketosis, mimicking diabetic ketoacidosis (DKA). Treatment with parenteral fluid, electrolytes, and insulin infusion resulted in an improvement in hyperglycemia, but persistence of metabolic acidosis and lack of improvement of neurologic status led us to suspect an organic acidemia. Urinary organic acid analysis revealed increased methylmalonic acid levels. In addition, hyperhomocysteinemia and homocystinuria were also noted in presence of normal vitamin B12 levels. This confirmed the diagnosis of cobalamin metabolism defect leading to combined methylmalonic aciduria and homocystinuria. There was some improvement in neurologic status and metabolic parameters after treatment with low-protein diet, vitamin B12, folic acid, and L-carnitine, but he ultimately succumbed to polymicrobial nosocomial sepsis. The entire MMACHC gene of the patient was sequenced and no mutations were identified. This is probably the first case report of cobalamin intracellular metabolism defect (CblC/CblD/CblF/CblJ or ABCD4) presenting as diabetic ketoacidosis.

Status Dystonicus in a Child with Familial Idiopathic Hypoparathyroidism

Hypoparathyroidism leading to status dystonicus is rarely reported in literature. The authors present an 8-y-old girl with idiopathic familial hypoparathyroidism who presented with status dystonicus. She was managed successfully with midazolam infusion, calcium and vitamin D supplementation, and oral anti-dystonia drugs.

Vitamin D deficiency among healthy children in developing countries: an epidemic being recognized.

Madam We read with interest the recently published article ‘Vitamin D status in pre-school children in rural Nepal’ by Avagyan et al. and would like to make few important comments. The authors noted a high prevalence (91·1 %) of vitamin D deficiency (VDD; defined as serum 25hydroxyvitamin D (25(OH)D) level <50 nmol/l) among pre-school children in rural Nepal. Their study contributed significantly to the limited literature on VDD in apparently healthy children in the South-East Asia region. Currently, both developed and developing countries are facing an unrecognized and untreated pandemic of VDD. Several studies from India also reported a high prevalence (in the range of 36–90%) of VDD in healthy children. Most of these studies defined VDD as 25(OH)D level <50 nmol/l. Among them, only a few studies also studied clinical signs suggestive of VDD (such as rachitic rosary, frontal bossing, Harrison’s sulcus, wrist widening, wide anterior fontanelle, double malleolus, craniotabes and bowing of the legs). Tiwari and Puliyel demonstrated that the prevalence of 25(OH)D level <35 nmol/l was 84% in slum children from three areas in Delhi. Marwaha et al. assessed the vitamin D status in 5137 healthy schoolchildren aged 10–18 years in northern India. They noticed that 10·8 % of children had clinical evidence of VDD. 25(OH)D level <50 nmol/l was found in 92·6 % of children in the lower socio-economic group and 84·9 % in the upper socioeconomic group. Puri et al. evaluated clinical and laboratory evidence of VDD among 3127 apparently healthy Delhi schoolgirls aged 6–18 years and demonstrated that 11·5 % of the girls had clinical evidence of VDD and 90·8 % of them had biochemical VDD. We assessed the prevalence of VDD in 338 apparently healthy children in the age group of 3 months–12 years (mean age 3·31 years) belonging to the upper socio-economic group in Chandigarh and found that 8·53% of them had clinical signs of VDD and 40·24% had biochemical VDD. We also noticed on univariate analysis that VDD was associated with relatively younger age group, female sex, failure to thrive, exclusive breast-feeding, inadequate sun exposure and no vitamin D supplements. A few of these findings were in contrast to those by Avagyan et al. who found that VDD was not related to gender, sun exposure or nutritional status. Recently, Reesukumal et al. found that VDD prevalence (25(OH)D <75 nmol/l) was 79·2 % among 159 healthy children aged 6–12 years in Bangkok, Thailand. Avagyan et al. enrolled children over a period of 3 months (i.e. from September to November, rainy and winter season). As we know that VDD is season dependent with lower 25(OH)D levels in winter, this might not be representative of the vitamin D status throughout the year and this may have overestimated the actual prevalence of VDD in rural Nepal. Also, the authors did not discuss the clinical features of VDD, children receiving vitamin D and Ca supplements, and the adequacy of sun exposure (definition). Serum Ca, P, alkaline phosphatase, parathyroid hormone and 1,25-dihydroxyvitamin D levels were not studied, which could have given more insight into VDD. It was not mentioned how deficient children were treated. Different studies have observed varied prevalence of VDD among healthy children. This could be due to differences in populations studied, sunlight exposure, latitude of residence, skin colour, sunscreen use, environmental pollution, weather, dietary intake, vitamin D supplementation, different methods used to measure 25(OH)D level and different cut-off values. The American Academy of Pediatrics recommends a daily vitamin D intake of 10 μg/d (400 IU/d) for all infants, children and adolescents, beginning in the first few days of life. In India and other South-East Asian countries, there are no such regulations regarding fortification of food products or routine supplementation with vitamin D. Now various studies demonstrating high prevalence of VDD from different countries in this region advocate for routine vitamin D supplementation throughout childhood.

Post-neonatal Tetanus in a PICU of a Developing Economy: Intensive Care Needs, Outcome and Predictors of Mortality

Objectives To evaluate pediatric intensive care unit (PICU) needs, outcome and predictors of mortality in post-neonatal tetanus. Materials and methods Review of 30 consecutive post-neonatal tetanus cases aged 1 months to 12 years admitted to a PICU in north India over a period of 10 years (January 2006 to December 2015). Results Chronic suppurative otitis media was the commonest portal of entry. All received tetanus toxoid, human tetanus immunoglobulin (HTIG) and appropriate antibiotics; 7 (23.3%) received intrathecal HTIG. Common complications were respiratory failure, rhabdomyolysis, autonomic dysfunction, acute kidney injury and healthcare-associated infections. PICU needs were as follows: ventilation; benzodiazepine, morphine and magnesium sulfate infusion; neuromuscular blockers, inotropes, tracheostomy and renal replacement therapy. Mortality rate was 40%; severity Grade IIIb, autonomic dysfunction, use of vasoactive drugs and those who did not receive intrathecal HTIG were significantly associated with mortality. Conclusion Post-neonatal tetanus is associated with high mortality, and PICU needs include management of spasms, autonomic dysfunction and complications and cardiorespiratory support.

Pediatric empyema thoracis: What has changed over a decade?

OBJECTIVES The purposes of this paper are to study clinicobacteriological profile, treatment modalities and outcome of pediatric empyema thoracis and to identify changes over a decade. DESIGN This is a retrospective study. SETTING Department of Pediatrics of a tertiary care hospital in North India. PATIENTS We enrolled 205 patients (1 month-12 years) of empyema thoracis admitted over 5 years (2007-11) and compared the profile with that of a previous study from our institute (1989-98). RESULTS Pleural fluid cultures were positive in 40% (n = 82) cases from whom 87 isolates were obtained. Staphylococcus aureus was the most common isolate (66.7%). Methicillin-sensitive S. aureus accounted for 56%, Methicillin-resistant S. aureus (MRSA) 10% and gram-negative organisms 18.3% of isolates. Intercostal drainage tube (ICDT) was inserted in 97.5%, intrapleural streptokinase was administered in 33.6%, and decortication performed in 27.8% cases. Duration of hospital stay was 17.2 (±6.3) days, duration of antibiotic (intravenous and oral) administration was 23.8 (±7.2) days and mortality rate was 4%. In the index study (compared with a previous study), higher proportion of cases received parenteral antibiotics (51.7% vs. 23.4%) and ICDT insertion (20.5% vs. 7%) before referral and had disseminated disease (20.5% vs. 14%) and septic shock (11.2% vs. 1.6%), less culture positivity (40% vs. 48%), more MRSA (10.3% vs. 2.5%) and gram-negative organisms (18.4% vs. 11.6%), increased use of intrapleural streptokinase and surgical interventions (27.8% vs. 19.7%), shorter hospital stay (17 vs. 25 days) and higher mortality (3.9% vs. 1.6%). CONCLUSIONS Over a decade, an increase in the incidence of empyema caused by MRSA has been noticed, with increased use of intrapleural streptokinase and higher number of surgical interventions.

Streptococcus pneumoniae-associated Hemolytic Uremic Syndrome

To the Editor: Hemolytic uremic syndrome (HUS) is a common cause of acute kidney injury (AKI) in young children and is characterized by triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and AKI. Diarrhea-associated/typical HUS is the commonest (80-90%) cause of HUS in children (caused by enterohemorrhagic Escherichia coli O157:H7) [1, 2]. Though rarely reported from India, Streptococcus pneumoniae-associated HUS is well described from different parts of the world [3–5]. An 11-mo-boy presented with fever, cough, and rapid breathing for 7 d; and decreased urine output for 1 d. He had tachycardia, tachypnea, well palpable pulses, blood pressure 80/50 mmHg, and severe pallor; subcostal and intercostal retractions, decreased chest movements on right side; and dull note, decreased air entry, bronchial breathing, and crepitations over right infraclavicular, mammary, and infraaxillary area. Investigations are shown in Fig. 1 and Tables 1 and 2. Diagnosis of Streptococcus pneumoniae-associated HUS was considered. He was treated with ceftriaxone, oxygen, drainage of right empyema by intercostal drainage tube, packed red blood cells for severe anemia; and 5 cycles of hemodialysis (on day 2, 3, 6, 9, and 11). Coagulopathy improved by day 2, anemia and thrombocytopenia by day 10, and AKI by day 16; and was discharged on day 21. He was followed up for 2 y and was doing fine. S. pneumoniae-associated HUS accounts for 5% of all HUS [1, 2]. Pathogenesis involves cleavage of neuraminic acid by neuraminidase produced by S. pneumoniae leading to exposure of Thomsen Friedenreich antigen (Tag) on cell surface of renal endothelium, erythrocytes, and platelets. Pre-formed antiTag IgM antibodies react with Tag and lead to activation of immune system, glomerular endothelial cell damage, AKI, MAHA, and platelet aggregation and consumption [1, 2]. Due to exposed Tag on red cells, direct Coombs test is positive in over 90% of patients, but this lacks specificity [2]. Management is supportive involving monitoring fluid, electrolytes, renal functions, and hemodynamic parameters; early dialysis; and aggressive antibiotic treatment [2]. Blood products should be avoided as they may worsen the condition by providing more anti-Tag IgM; and should only be used if unavoidable, RBCs should be washed with dextran (which removes 95% plasma), and FFP should only be used for severe bleeding [1].

Cerebral Phaeohyphomycosis: Fulminant Encephalitic Presentation

To the Editor: Cerebral phaeohyphomycosis is a rare but serious fungal infection of central nervous system caused by dematiaceous septate fungi and is characterized by presence of melanin-like pigment within the cells. Common causative organisms are Cladophialophora bantiana, Rhinocladiella mackenziei, Exophiala dermatitidis, Ochroconis gallopavum, and Exserohilum rostratum [1, 2]. Prolonged antifungal therapy and aggressive surgical resection of abscesses are mainstays of treatment. Despite aggressive treatment, mortality is high [1, 2]. There are limited reports of cerebral phaeohyphomycosis in children from India [3–5]. An 8-y-old boy presented with fever, headache, vomiting, and drowsiness since 4 d. He was febrile with heart rate 68/ min, respiratory rate 18/min, and blood pressure 134/ 62 mmHg; GCS 13; normal tone, exaggerated deep tendon reflexes, upgoing planters; and no cranial nerve palsy, signs of meningeal irritation, or papilledema. With provisional diagnosis of acute meningoencephalitis with raised intracranial pressure (ICP), intravenous ceftriaxone and acyclovir, and measures to control ICP were started. Investigations revealed hemoglobin 12.7 g/dl, total leucocyte count 19,200/cumm, platelet count 3,27,000/cumm; normal renal and liver functions, coagulation profile, and chest radiograph; and negative Herpes simplex and Japanese encephalitis serology, blood culture, and HIV ELISA. Neuroimaging are shown in Fig. 1. For progressive deterioration in neurological status he underwent ventilation, increase in sedo-analgesia, 3% saline infusion (1 ml/kg/h), ICP catheter (intraparenchymal) insertion (opening ICP 36 cmH2O), vasopressors to target cerebral perfusion pressure (CPP) >60 cmH2O; and a trial of mannitol, dexamethasone, and thiopentone. Decompressive hemicraniectomy was done and intra-operative findings revealed bulging duramater and brain matter with blackish discoloration of brain parenchyma at temporal area. Despite surgery he succumbed at 72 h of admission. Postmortem CSF examination revealed 200 cells (neutrophils 60%, lymphocytes 40%), glucose 65 mg/dl, proteins 840 mg/dl, and sterile culture. Brain biopsy was consistent with cerebral phaeohyphomycosis (Fig. 2). Cerebral phaeohyphomycosis commonly affect immunocompetent hosts. Spread to brain may occur through hematogenous dissemination, lymphatic vessels, and contiguous spread from adjacent organs (orbits/sinuses). Since mortality is high (100% in untreated cases and 65–70% with surgery and antifungal agents); high index of suspicion, histopathological examination and culture, prompt antifungal treatment (voriconazole), and aggressive surgical resection may improve the outcome [1]. * Karthi Nallasamy ny.karthi@gmail.com

Serum Vitamin D Status and Outcome among Critically Ill Children Admitted to the Pediatric Intensive Care Unit in South India: Correspondence.

To the Editor : Recently, many studies demonstrated that the prevalence of vitamin D deficiency (VDD) among critically ill children is 25–84 % at admission to pediatric intensive care unit (PICU) [1–5] (Table 1). Few of them also identified that VDD is associated with greater severity of illness and longer PICU stay [1, 2, 5] which suggests that VDD has an indirect impact on hospital burden in terms of increased duration and cost of hospital stay. I read with interest the recently published article ‘Serum vitamin D status and outcome among critically ill children admitted to the pediatric intensive care unit in South India’ by Ebenezer et al. [5] and would like tomake a few comments. Authors demonstrated that the prevalence of VDD among 52 critically ill children was 40.3 % and VDD was associated with higher PIM2 or SOFA score and requirement of mechanical ventilation but not with mortality. Authors enrolled small number of cases over a period of 20 d during winter season, which might had overestimated the prevalence of VDD in the study cohort. Even the number of patients calculated to be included in the study were not enrolled. It could have been better if authors had also included healthy controls to know about the baseline prevalence of VDD among apparently healthy children in the same population. Also, authors have not assessed socioeconomic status, serum phosphorus, alkaline phosphatase, parathyroidhormone, 1,25(OH)D levels, and radiographs for evidenceof VDD, which could give more insight into VDD. In this study, nearly 31 % cases had one or other underlying chronic disease condition which directly or indirectly affects vitamin D status. Recently, Ponnarmeni et al. [4] in a largest study from India involving 124 critically ill children with sepsis and 338 healthy controls demonstrated that the prevalence of VDD (level <20 ng/ml) was 50.81 and 40.24 %,