Expanding the clinical and immunological phenotype of prolidase deficiency: A case report.

Prolidase deficiency (PD) is a rare autosomal recessive disorder associated with recurrent infections, immune dysregulation, and autoimmunity. PD is characterized by persistent dermatitis, skin fragility, and non-healing ulcerations on the lower limbs as its main dermatologic characteristics. Herein, we report a boy with PD due to a novel variant in PEPD who had abnormal facies, cognitive impairment, corneal opacity, recurrent infections, and persistent non-healing leg ulcers. Th17 lymphocyte counts and phosphorylated-STAT5 expression following IL-2 stimulation were reduced in our patient as compared to healthy control.

Novel device for automating exchange transfusions through umbilical venous route in neonates.

Manually performed double-volume exchange transfusion (DVET) is tedious, error-prone, and may incur the risk of embolism. We aimed to develop a device that automates the DVET procedure performed through the umbilical venous route. We evaluated changes in blood passing through the device during DVET. We developed an electro-mechanical device with accessories (tubing and valve assembly) to perform a complete DVET. It comprises two syringes driven by a common pump that moves back and forth to withdraw aliquots of the patient's blood and infuse equal volumes of donor blood. In tandem, it draws donor blood from a blood bank bag and pushes the patient blood drawn from the previous cycle into a waste bag, respectively. One-way duckbill valves and a two-way pinch valve ensure the separation of the donor and patient blood. A sensor detects bubbles and clots. A dashboard displays set and measured parameters. We tested the accuracy of the delivered flow rate and volume, electrical safety, embolus detection, and changes in hematological and biochemical values. The delivered flow and volume were within 5% of the set parameters. All electrical safety parameters were within normal limits. The sensor consistently detected microbubbles and clots. There were no clinically significant differences in laboratory parameters between samples drawn directly from the blood bank bag and drawn from the exit port at 80, 100, 120, and 160 s with a fixed aliquot volume. CONCLUSIONS: Our prototype of a novel device can safely automate a DVET. Further trials of this device are warranted. WHAT IS KNOWN: • Double volume exchange transfusion is often performed manually, but this is time-consuming and error-prone. • Previous attempts at automation were not widely adopted because they involved inserting two catheters and did not have mechanisms to prevent embolism. WHAT IS NEW: • This novel device fully automates double volume exchange transfusions through a single-lumen umbilical venous catheter. • It prevents air and clot embolism and has a screen for input and output parameters and alarms.

Knowledge and experiences of healthcare workers in managing children with neurometabolic disorders in a developing country: a cross-sectional study.

OBJECTIVE: To evaluate the knowledge and experiences of healthcare workers in the management of neurometabolic disorders. METHODS: A cross-sectional study was carried out among the 132 participants of a continued medical education program conducted in the Department of Pediatrics at a tertiary-care teaching hospital. A questionnaire-based feedback form was circulated among the participants, and their responses were analyzed. RESULTS: Ninety-three responses were analyzed. The most common pediatric illnesses identified were infections (91%), nutritional (91%), birth-related injuries (44.4%) and metabolic disorders (44.4%). Consanguinity (81.5%) and genetic heterogeneity (42.4%) were recognized as most important causes of neurometabolic disorders. Important steps identified for prevention were prenatal testing (65.6%) and newborn screening at birth (61%); while for improving the diagnosis were routine availability of metabolic investigations (65.3%) and screening at birth (46.6%). Most respondents (58.7%) expressed discomfort in managing a case with inherited metabolic defect due to a lack of knowledge (46.8%) and diagnostic facilities (44.6%). Despite access to testing in the majority, a high cost of testing was noticed for biochemical and genetic investigations. The majority of participants (73%) considered some of the inherited metabolic disorders as treatable. Dietary substitution (89.3%), enzyme replacement (69%), cofactor replacement (53.6%), gene therapy (35.7%) and regular dialysis (16.7%) were considered the treatment options. CONCLUSION: In spite of growing awareness of inherited metabolic disorders, there are still gaps in knowledge among healthcare workers. It is challenging to diagnose and manage these disorders. Cost-reduction of diagnostic tests, routine newborn screening and increased educational activities are key challenges to be addressed.

Estimation of iron overload with T2*MRI in children treated for hematological malignancies.

Iron overload may contribute to long-term complications in childhood cancer survivors. There are limited reports of assessment of tissue iron overload in childhood leukemia by magnetic resonance imaging (MRI). A cross-sectional, observational study in children treated for hematological malignancy was undertaken. Patients ≥6 months from the end of therapy who had received ≥5 red-cell transfusions were included. Iron overload was estimated by serum ferritin (SF) and T2*MRI. Forty-five survivors were enrolled among 431 treated for hematological malignancies. The median age at diagnosis was 7-years. A median of 8 red-cell units was transfused. The median duration from the end of treatment was 15 months. An elevated SF (>1,000 ng/ml), elevated liver iron concentration (LIC) and myocardial iron concentration (MIC) were observed in 5 (11.1%), 20 (45.4%), and 2 (4.5%) patients, respectively. All survivors with SF >1,000 ng/ml had elevated LIC. The LIC correlated with SF (p < 0.001). MIC lacked correlation with SF or LIC. Factors including the number of red-cell units transfused and duration from the last transfusion were associated with elevated SF (p = 0.001, 0.002) and elevated LIC (p = 0.012, 0.005) in multiple linear regression. SF >595 ng/ml predicted elevated LIC with a sensitivity of 85% and specificity of 91.6% (AUC 91.2%). A cutoff >9 units of red cell transfusions had poor sensitivity and specificity of 70% and 75% (AUC 76.6%) to predict abnormal LIC. SF >600 ng/ml is a robust tool to predict iron overload, and T2*MRI should be considered in childhood cancer survivors with SF exceeding 600 ng/ml.

Otolith microchemistry of freshwater indigenous minor carp (Bangana dero) as a biomonitoring tool to trace heavy metals in River Sutlej, Ropar Wetland (Ramsar site), Punjab, India.

The elemental composition of the fish otolith may represent a permanent record of the environmental condition the fish inhabited. Fish otolith grows incrementally from the core to a marginal region that acts as a repository of trace metal signatures. The present study explores the potential application of otolith microchemistry of the benthopelagic indigenous minor carp Bangana dero sampled from the Ropar wetland on River Sutlej, Punjab. The concentration of sixteen metals was evaluated in the otolith (n = 42) and water (n = 48) for the post-monsoon and pre-monsoon season from 2020 to 2022 using inductively coupled plasma mass spectrometry (ICP-MS) followed by element detection in the core and marginal region of whole otolith, using energy-dispersive mass spectroscopy (EDS). All the heavy metals exhibited an increase in metal concentrations in fish otolith than water during the post-monsoon season. By indices approach, the otolith was found to have a high bioaccumulation factor for Se in the post-monsoon and Hg in the pre-monsoon. Certain trace metals like As and Hg exhibited fluctuations in their core and marginal region. Thus, trace metal patterns in the otolith could act as a potential tool for monitoring the seasonal changes of metals in water bodies. The EFHg, EFSe and EFAs in the fish otolith predicted its anthropogenic source, while the remaining studied elements showed ambient water origin. Thus, using the otoliths of Bangana dero as a long-term monitoring tool in the future may be helpful for environmental assessments and the reconstruction of historical exposure for safeguarding of water bodies.

Association of Micronutrients with Tuberculosis Development in HIV Infected Patients.

Human immunodeficiency virus (HIV) infection associated with weakened immune system due to decreased CD4 T cell count favors development of tuberculosis. Effector immune responses are also associated with micronutrient status due to their prominent role in maintaining immune functions. Micronutrient deficiencies are quite common among HIV patients that further result into compromised immunity thus making the conditions even more favorable for mycobacteria to establish disease. So, current study was designed to assess association of different micronutrients with development of TB in HIV patients. Micronutrient levels were measured in asymptomatic HIV patients who were monitored for the development of TB during follow up period (incident TB) within one month to one year and also in symptomatic microbiologically confirmed HIV-TB patients. Among various micronutrients assessed, levels of ferritin were found to be significantly increased (p < 0.05) with significant decreased zinc (p < 0.05) and selenium (p < 0.05) levels in incident TB group as well as in HIV-TB subjects compared to asymptomatic HIV patients who did not develop TB in the follow up period. Importantly, increased levels of ferritin and decreased levels of selenium were significantly associated with development of tuberculosis in HIV patients.

Procalcitonin and C-reactive protein for diagnosing post-operative sepsis in neonates.

AIM: To determine whether serum procalcitonin (PCT) or C-reactive protein (CRP) can diagnose post-operative sepsis among neonates undergoing major non-cardiac surgery. METHODS: In this diagnostic study, we included neonates who underwent major non-cardiac surgery and were monitored for post-operative sepsis. We excluded pre-existing septic, inflammatory or life-threatening conditions. Subjects either had 'definite' (culture-positive, n = 14), 'probable' (clinical sepsis, culture-negative, n = 25) or no sepsis (n = 31). We measured serum CRP and PCT at 48 ± 6 h, 72 ± 6 h and 96 ± 6 h post-operatively and compared 'definite or probable sepsis' with 'no sepsis'. RESULTS: Median (Q1, Q3) CRP (mg/L) in 'definite or probable' sepsis group was higher than 'no sepsis' at 72 h (91.48 (57.87, 143.50) vs. 51.32 (33.0, 80.1); P = 0.009) and 96 h (87.51 (45.19, 128.22) vs. 31.00 (25.3, 45.2); P < 0.001). Median (Q1, Q3) PCT (ng/mL) in 'definite or probable' sepsis was higher than 'no sepsis' at 72 h (4.22 (2.04, 12.73) vs. 1.78 (0.9, 6.4); P = 0.01) and 96 h (3.54 (1.96, 9.65) vs. 0.97 (0.4, 3.0); P < 0.001). Ninety-six-hour CRP and PCT cut-offs (based on Youden's index) were 74.16 mg/L and 1.65 ng/mL, respectively. If both CRP and PCT were positive, specificity was 100% (95% confidence interval: 88.78-100). If either one was positive, sensitivity was 88.89% (95% confidence interval: 73.94-96.89). CONCLUSIONS: Septic neonates have significantly higher serum CRP and PCT compared to non-septic neonates at 72 and 96 h post-operatively. If both CRP and PCT are positive at 96 h after surgery, it has 100% specificity, and if either one is positive, 89% sensitivity.

A case series highlighting structured hematological, biochemical and molecular approach to clinical oral iron refractoriness in children: A pressing need for a 3-tier system for classification of variants in TMPRSS6 gene.

In current study, we discuss clinical oral iron refractoriness cases and highlight need for a classification system to define TMPRSS6 gene variants. Out of 231 cases of microcytic hypochromic anemia screened (Sept 2019-Dec 2020), 17 cases (7.35%) with unexplained iron refractoriness (URIDA) phenotype were enrolled after ruling out secondary causes and compliance related issues. 11 (65%) had absent/negligible response (0-0.4 g/dl Hb rise) while 6 (35%) partial (0.5-0.9 g/dl Hb rise) response to initial iron trial at 4-8 weeks. Of these 17 cases, inappropriate hepcidin levels (normal-high) were noted in 11/15 (73%) tested. TSAT/Hepcidin ratio was low in 13/15 (87%). Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. 10/15 cases with variations harbored a common splice site INDEL that was noted to be pathogenic SNP (MAF-0.19) on case-control association study in combination with other known missense SNPs with an odds ratio of 6.38 and relative risk 2.66 (p- < 0.01).

A high frequency and geographical distribution of MMACHC R132* mutation in children with cobalamin C defect.

Cobalamin C defect is caused by pathogenic variants in the MMACHC gene leading to impaired conversion of dietary vitamin B12 into methylcobalamin and adenosylcobalamin. Variants in the MMACHC gene cause accumulation of methylmalonic acid and homocysteine along with decreased methionine synthesis. The spectrum of MMACHC gene variants differs in various populations. A total of 19 North Indian children (age 0-18 years) with elevated methylmalonic acid and homocysteine were included in the study, and their DNA samples were subjected to Sanger sequencing of coding exons with flanking intronic regions of MMACHC gene. The genetic analysis resulted in the identification of a common pathogenic nonsense mutation, c.394C > T (R132*) in 85.7% of the unrelated cases with suspected cobalamin C defect. Two other known mutations c.347T > C (7%) and c.316G > A were also detected. Plasma homocysteine was significantly elevated (> 100 µmol/L) in 75% of the cases and methionine was decreased in 81% of the cases. Propionyl (C3)-carnitine, the primary marker for cobalamin C defect, was found to be elevated in only 43.75% of cases. However, the secondary markers such as C3/C2 and C3/C16 ratios were elevated in 87.5% and 100% of the cases, respectively. Neurological manifestations were the most common in our cohort. Our findings of the high frequency of a single MMACHC R132* mutation in cases with combined homocystinuria and methylmalonic aciduria may be proven helpful in designing a cost-effective and time-saving diagnostic strategy for resource-constraint settings. Since the R132* mutation is located near the last exon-exon junction, this is a potential target for the read-through therapeutics.

Metabolic epilepsy in hyperprolinemia type II due to a novel nonsense ALDH4A1 gene variant.

Hyperprolinemia type II (HPII) is a rare autosomal recessive disorder of proline degradation pathway due to deficiency of delta-1-pyrroline-5-carboxylate dehydrogenase. Pathogenic variants in the ALDH4A1 gene are responsible for this disorder. We here describe an 11-month-old infant with recurrent seizures refractory to multiple antiepileptic drugs. She was hospitalized in view of acute-onset encephalopathy, exacerbation of generalized seizures following an upper respiratory infection. Laboratory investigation revealed significantly elevated proline levels in dried blood spots. DNA sample of the child was subjected to a targeted next-generation sequencing gene panel for hyperprolinemias. We detected a novel nonsense homozygous variant in the ALDH4A1 gene in the child and the heterozygous variant of the same in both the parents. Based on the location of the variant i.e. in the last exon, truncated protein is expected to be expressed by skipping nonsense-mediated decay and such point-nonsense variants could be an ideal target for readthrough drugs to correct genetic defects.

Thiamine Status in Children with Septic Shock from a Developing Country: A Prospective Case-Control Study.

OBJECTIVE: Mitochondrial dysfunction is central to sepsis-induced multi-organ dysfunction. Thiamine deficiency may contribute to mitochondrial dysfunction and thus high mortality. Study was planned to assess thiamine status in children with septic shock in comparison to healthy controls from a developing country and to study the effect of thiamine levels on its outcome. METHODS: A prospective case-control study (April 2017 to May 2018) enrolling consecutive children with septic shock as 'cases' (n = 76), their healthy siblings (n = 51) and apparently healthy children from immunization clinic (n = 35) as 'controls'. Whole blood total thiamine (WBTT) level was measured on days 1, 10 and 1-month post-discharge. Outcome parameters were acute care area free days on days 14 and 28, and mortality. RESULTS: WBTT [nMol/l; median (interquartile range, IQR)] was significantly lower on day 1 in cases compared with sibling controls [23.1 (21.8-26.3) vs. 36.9 (33.6-40.5); p < 0.001]. It fell further on day 10 [20.8 (18.1-21.1); p < 0.02]. Levels rose significantly 1-month post-discharge [35.5 (31.2-36.6)] and became comparable to sibling controls (p = 0.4). Immunization clinic controls also had lower WBTT [42.3 (40.1-45.9)], but was significantly higher than sibling controls and cases at 1-month post-discharge (p < 0.001). Survivors and non-survivors of septic shock were similar. WBTT levels did not correlate with any of the severity indicators of septic shock or its outcomes. CONCLUSIONS: WBTT was significantly low in all children, and fell further during septic shock. Observed severe deficiency might have precluded any further association of thiamine levels with severity of septic shock and its outcome. Data obtained may inform trials on metabolic resuscitation in paediatric septic shock in developing countries. Lay summaryThiamine deficiency may contribute to high mortality in paediatric septic shock as thiamine is an essential factor for functioning of mitochondria, the powerhouse of the cells. This prospective case-control study was conducted to assess thiamine status in children with septic shock in comparison with healthy controls in a developing country. Consecutive children with fluid-refractory septic shock were enrolled as 'cases'. Their apparently healthy siblings, and apparently healthy children from immunization clinic, were enrolled as 'controls'. The whole blood total thiamine (WBTT) level was measured on days 1, 10 and 1 month after hospital discharge. Seventy-six children were enrolled as cases, 51 children as sibling controls and 35 children as immunization clinic controls. WBTT was significantly lower on day 1 in cases as compared with their sibling controls. It fell further on day 10. The level rose significantly after a month of discharge and became comparable to sibling controls. Immunization clinic controls also had lower WBTT but was significantly higher compared with sibling controls and cases at 1-month post-discharge. Survivors and non-survivors of septic shock had similar WBTT levels. Observed severe deficiency might have precluded any further association of thiamine levels with septic shock outcome.

Plasma and Urinary Amino Acid Profile in Children with Infantile Tremor Syndrome.

BACKGROUND: Infantile Tremor Syndrome (ITS) is a disorder of infancy, and characterized by developmental delay and/or regression, pallor, skin hyperpigmentation and hypopigmented hair. It is commonly seen in infants in whom exclusive breastfeeding is given inappropriately for longer durations than recommended. ITS is predominantly reported from the Indian subcontinent and in children from a lower socioeconomic background. It is a clinical diagnosis and vitamin B12 deficiency is the most commonly accepted etiology of this entity. OBJECTIVES: The primary objectives of study were to compare the plasma and urine amino acid levels among children with ITS spectrum with those of healthy children. The secondary objectives were to compare the plasma and urine amino acid levels among children with ITS and Pre-ITS. STUDY DESIGN: This cross-sectional, observational study was carried out at a tertiary care hospital in North India. PARTICIPANTS: A total of 50 children aged < 36 months with ITS/Pre-ITS were enrolled. Children with Pre-ITS and ITS were compared with healthy age-matched study subjects. RESULTS: Thirty-nine (78%) cases and twelve (24%) healthy children had low serum vitamin B12 levels. Folate levels were normal in all the controls, while only one case had folate deficiency. There were significant differences (p < 0.05) in the values of 32 amino acids in plasma. Among 44 urinary amino acids, levels of 30 amino acids were significantly different in the cases compared with the controls (p < 0.05). CONCLUSIONS: Several changes in amino acids in the children suffering from ITS were observed. These changes may be a reflection of the metabolic derangements in ITS.

Intramuscular Followed by Oral Vitamin A Supplementation in Neonates with Birth Weight from 750 to 1250 g: A Randomized Controlled Trial.

Multiple intramuscular (IM) injections of vitamin A have been shown to decrease bronchopulmonary dysplasia in very low birth weight (VLBW) neonates. However, this regime is neither practical nor popular. Oral vitamin A has failed to achieve adequate plasma levels. We aimed to investigate if a schedule of initial IM followed by oral supplementation can reduce vitamin A deficiency. This was a blinded, randomized controlled trial, conducted in a level III neonatal unit. Neonates with birth weight from 750 to 1250 g, were enrolled at the age of 24-96 h of life. They were randomly allocated to vitamin A supplementation (VAS) (n = 61) or placebo group (n = 59). VAS group received vitamin A 5000 IU IM on alternate days till establishment of adequate enteral feeds, followed by oral 10,000 IU daily for 28 days. The primary outcome was incidence of vitamin A deficiency (plasma retinol < 200 µg/L) on day 28. A total of 120 neonates with mean (SD) gestation age and birth weight of 31 (2.4) weeks and 1065 (141) g, respectively were enrolled. More than 90% of cases were vitamin A deficient at the baseline. The proportion of vitamin A deficient infants on day 28 of study was significantly lower in VAS group compared to placebo group (4% vs. 61%, p < 0.001). The median (1st-3rd quartile) plasma retinol levels (µg/L) were significantly higher in VAS group compared to placebo [489 (295,627) vs. 184 (156,240), p < 0.001]. We conclude that the IM followed by oral VAS significantly reduced the incidence of vitamin A deficiency in VLBW infants.

Energy Balance in Critically Ill Children With Severe Sepsis Using Indirect Calorimetry: A Prospective Cohort Study.

OBJECTIVES: Energy needs in critically ill children are dynamic and variable. Data on energy balance in children with severe sepsis using indirect calorimetry (IC) is lacking. Thus, we planned to study the energy needs and balance of this cohort. METHODS: Prospective observational study conducted in ventilated children aged 5 to 12 years, admitted in pediatric intensive care unit with severe sepsis from May 2016 to June 2017. Measured resting energy expenditure (mREE) was measured with IC (Quark RMR, COSMED) till 7 days or pediatric intensive care unit discharge. Predicted energy expenditure (pREE) was estimated using Schofield, Harris and Benedict, and FAO/WHO/UNU equations. Primary outcome was to study the daily energy balance. Secondary outcome was to determine nitrogen balance and agreement of mREE with pREE. RESULTS: Forty children (24 boys) with median age of 7 (5.2, 10) years were enrolled. All received enteral nutrition; 35 (87.5%) received inotropic support. Median ventilation-free days were 19 days and 4 children died (10%). A total of 176 IC measurements were obtained with an average of 4 per patient. The mean mREE was 51 ±â€Š17 kcal/kg and mean respiratory quotient was 0.77 ±â€Š0.07. There was persistent negative energy balance from days 1 to 7 and negative nitrogen balance from days 1 to 5. There was poor agreement of pREE with mREE using Bland Altman plots. None of severity of illness scores (PRISM III, daily Sequential Organ Function Assessment, daily Vasoactive Inotropic Score) showed correlation with mREE. CONCLUSIONS: Persistent negative energy and nitrogen balance exist during acute phase of severe sepsis. Predictive equations are inaccurate compared with IC as the criterion standard.

Serum C-Reactive Protein Levels in Healthy Neonates in Different Gestational and Postnatal Ages.

There is paucity of normative data on serum C-reactive protein (CRP) in neonates. In Part I of study, we compared CRP in healthy neonates (from 28°/7 weeks to 416/7 weeks of gestation) between various gestational and postnatal age groups in first week. We planned recruitment of 50 participants each in 'term', 'late preterm' and 'moderate-to-very preterm' groups, equally divided in '24-95 h' and '96-168 h' postnatal age sub-groups. In Part II of study, we assayed CRP weekly in moderate-to-very preterm neonates until day 28 to evaluate its trend. Among 154 subjects, term neonates had higher CRP, with highest values among term infants aged 24-95 h. Barring postnatal age, maternal/perinatal factors did not affect CRP levels. CRP did not change significantly over 28 days in moderate-to-very preterm neonates. In conclusion, serum CRP in healthy neonates is highest among term infants aged 24-95 h and does not vary significantly in the first month of life among moderate-to-very preterm infants.

Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin.

BACKGROUND: A lack of access to methotrexate levels is common in low- and middle-income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high-dose methotrexate (HD-MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH. METHODS: The prospective study was conducted at a single centre in Chandigarh, India in 2015. Patients with B-cell acute lymphoblastic leukemia (ALL) or with T-cell ALL or non-Hodgkin lymphoma (T-NHL) were administered 3 and 5 gm/m2 of MTX (24 hr infusion), respectively. Six doses of leucovorin (15 mg/m2 /dose), instead of recommended three (for optimally reduced levels) at standard timing (42 hr from start of HD-MTX) were administered. Hydration (125 ml/m2 /hr) was continued for 72 hr, instead of the recommended 30 hr. Hydration fluid consisted of 0.45% sodium chloride, 5% dextrose, 7.5% sodium bicarbonate (50 mmol/l) and potassium chloride (20 mmol/l). Serum creatinine and urine pH were measured at baseline, 24 and 48 hr. The volume of hydration was increased (200 ml/m2 /hr) for a serum creatinine > 1.25 times the baseline. RESULTS: The study included 100 cycles of HD-MTX in 53 patients: B-ALL 25 patients (51 cycles), T-ALL 16 patients (28 cycles), T-NHL 10 patients (18 cycles), and relapsed ALL 2 patients (3 cycles). The mean age was 6.8 ± 3.2 years. Patients were underweight in 15 (15%) cycles. Patients in 23% of cycles had a rise in creatinine to >1.25 times the baseline. Toxicities (NCI CTCAE v4.0) included mucositis (32%), diarrhoea (10%), and febrile neutropenia (9%). One patient died from dengue shock syndrome. CONCLUSIONS: It is safe to administer 3 or 5 gm/m2 of MTX (24 hr infusion) without measuring MTX levels, with extended hydration, additional doses of leucovorin, and monitoring of serum creatinine and urine pH.

Randomised controlled trial of diazoxide for small for gestational age neonates with hyperinsulinaemic hypoglycaemia provided early hypoglycaemic control without adverse effects.

AIM: Hyperinsulinaemic hypoglycaemia (HH) is a very common cause of hypoglycaemia in small for gestational age (SGA) neonates. We compared using early oral diazoxide or a placebo for this patient group. METHODS: This was a randomised, double-blind, placebo-controlled trial that focused on SGA neonates born at at least 32 weeks of gestation with HH during the first five days of life. Neonates with severe perinatal asphyxia, sepsis or contraindications for oral feeds were excluded. The primary outcome was the hours taken to achieve hypoglycaemic control, with a glucose infusion rate of ≤4 mg/kg/min. The secondary outcomes were the duration of intravenous fluids, sepsis episodes, time to achieve full feeds and mortality. RESULTS: We screened 490 neonates and 30 neonates were eligible for randomisation and completed the trial. Half received diazoxide and half received a placebo. The median time to achieve hypoglycaemia control (40 vs 71.5 hours, p = 0.015), the total duration of intravenous fluids (114 vs 164 hours, p = 0.04) and time to achieve full feeds (74 vs 124 hours, p = 0.02) were significantly lower in the diazoxide group, with no adverse effects attributed to the drug. CONCLUSION: Using oral diazoxide for SGA neonates with HH provided early hypoglycaemic control with no apparent adverse effects.

A mechanistic approach to explore the neuroprotective potential of zonisamide in seizures.

BACKGROUND: Epilepsy, a disease of the brain, is one of the most common serious neurological conditions. It is associated with a group of processes which alter energy metabolism, interrupt cellular ionic homeostasis, cause receptor dysfunction, activate inflammatory cascade, alter neurotransmitter uptake and result in neuronal damage. The increasing knowledge and understanding about the basis of neuronal changes in epilepsy lead to investigate the mechanistic pathway of neuroprotective agents in epilepsy. With this background, the present study is designed to reveal the molecular and biochemical mechanisms involved in the neuroprotective potential of zonisamide in epilepsy. METHODS: Seizure-induced neuronal damage was produced by maximal electroshock seizures in animals. The oxidative stress and neuroinflammatory and apoptotic markers were assessed in the brain tissue of animals. RESULTS AND DISCUSSION: The present findings revealed that zonisamide treatment prevented the development of seizures in animals. Seizures-induced free radicals production and neuroinflammation were markedly ameliorated by zonisamide administration. In conclusion, the present study demonstrated the mechanisms behind the strong neuroprotective potential of zonisamide against seizures by attenuating the oxidative stress, inflammatory cascade and neuronal death associated with progression of seizures. It can be further developed as a neuroprotective agent for epilepsy and other neurodegenerative disorders.

Carotid Intima-Media Thickness and Lipid Profile in Children With Kawasaki Disease: A Single-Center Follow-up Study After a Mean Duration of 6.9 Years.

BACKGROUND: Kawasaki disease (KD) has a predilection to involve coronary arteries, leading to several long-term cardiovascular sequelae. Apart from coronary artery abnormalities, children with KD are also prone to develop premature atherosclerosis, endothelial dysfunction, and lipid abnormalities. Some of these complications may occur even in children who have received appropriate treatment with intravenous immunoglobulin in the acute phase. METHODS: In 2009, we had studied carotid intima-media thickness (cIMT) and lipid profile in 27 children with KD at least 1 year after the acute episode. In the present study, we have followed up the same cohort of 27 children at least 5 years after the acute episode of KD. We measured the cIMT, a surrogate marker for premature atherosclerosis, and fasting lipid profile in the cohort and compared the results with values obtained in our previous study. RESULTS: There was significantly higher mean cIMT in children with KD as compared with control subjects. However, there was no significant difference in cIMT among children in the cohort at 1 and 5 years of follow-up. Abnormal lipid profile was seen in 7 of 27 children in the present study, 5 of whom also had had lipid abnormality at 1-year follow-up. This suggests that lipid abnormalities in KD may be long lasting. CONCLUSIONS: Children with KD need careful long-term follow-up even when they do not have overt and persistent coronary artery abnormalities. It is possible that consequences of KD in childhood may impact health status of young adults several years later.

Is there an increased risk of metabolic syndrome among childhood acute lymphoblastic leukemia survivors? A developing country experience.

Data on metabolic syndrome (MS) in survivors of childhood acute lymphoblastic leukemia (ALL) from developing countries are lacking. The purpose of this single-center, uncontrolled, observational study was to assess the frequency of MS in our survivors. The survivors of ALL ≤15 years at diagnosis, who had completed therapy ≥2 years earlier, were enrolled. Anthropometric measurements (weight, height, waist circumference), biochemistry (glucose, insulin, triglycerides, high-density lipoprotein [HDL], thyroid function tests, C-reactive protein [CRP], magnesium), measurement of blood pressure, and Tanner staging were performed. MS was defined by International Diabetes Federation (IDF) and the National Cholesterol Education Program Third Adult Treatment Panel guidelines (NCEP ATP III) criteria, modified by Cook et al. (Arch Pediatr Adolesc Med. 2003;157:821-827) and Ford et al. (Diabetes Care. 2005;28:878-881). The median age of 76 survivors was 11.9 years (interquartile range [IQR]: 9.6-13.5). Twenty-four (32%) survivors were obese or overweight. The prevalence of insulin resistance (17%), hypertension (7%), hypertriglyceridemia (20%), and low HDL (37%) was comparable to the prevalence in children/adolescents in historical population-based studies from India. The prevalence of MS ranged from 1.3% to 5.2%, as per different defining criteria. Cranial radiotherapy, age at diagnosis, sex, or socioeconomic status were not risk factors for MS. The prevalence of MS in survivors of childhood ALL, at a median duration of 3 years from completion of chemotherapy, was comparable to the reference population. The prevalence of being obese or overweight was, however, greater than historical controls.