Publications by authors named "Devi Dayal"

112 Publications

Indian Research in Gestational Diabetes Mellitus during the Past Three Decades: A Scientometric Analysis.

J Obstet Gynaecol India 2021 Jun 16;71(3):254-261. Epub 2021 Feb 16.

Endocrinology and Diabetes Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: India plays an important role in global research on gestational diabetes mellitus (GDM), but a bibliometric assessment of this research is lacking.

Objective: To provide a comprehensive analysis of Indian GDM research during the last 30 years using select bibliometric indicators.

Methods: The Scopus international database was used to retrieve publication data, using a defined search strategy. The analysis focused on research output of Indian authors and organizations and their collaborations. The qualitative performance was assessed in terms of relative citation index and citations per paper (CPP).

Results: Overall, 100 countries participated in GDM research producing 13,193 publications during 1990-2019. India ranked ninth in global output (1182 publications, 3.1% share) and CPP of 18.6. Only 21.3% of publications had international collaboration and 9.4% were funded. Of the 235 organizations and 544 authors that participated in India's research on GDM, the top 50 organizations and authors contributed 53.8 and 36.4% to national publication share, respectively. The leading productive organizations were AIIMS, New Delhi, KEMH, Pune and PGIMER, Chandigarh, whereas the most productive authors were S. Kalra, V. Seshiah and C.S. Yajnik. Indian Journal of Endocrinology and Metabolism, Journal of Clinical and Diagnostic Research, Journal of Obstetrics and Gynecology of India and Diabetes Research and Clinical Practice were the most productive journals.

Conclusions: Indian research on GDM is lagging behind other countries which have a similar disease burden. Increasing national and international collaborations, and active support of national and international funding agencies is urgently required to produce quality research on GDM.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13224-021-01444-7.
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http://dx.doi.org/10.1007/s13224-021-01444-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310827PMC
June 2021

"Puddles on the Road": Hurdles in the Pathway from Symptoms to Diagnosis and Treatment in Children with Type 1 Diabetes.

Indian J Endocrinol Metab 2021 Jan-Feb;25(1):23-30. Epub 2021 Jul 21.

Endocrinology and Diabetes Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: This study was conducted to investigate the pathway from first symptoms to initiation of insulin regimen in children with new-onset Type 1 Diabetes Mellitus (T1DM) and explore the reasons behind diabetes ketoacidosis (DKA) at onset among children with T1DM.

Materials And Methods: An exploratory study was conducted using a pretested questionnaire, among parents of children diagnosed with T1DM within preceding 3 months.

Results: Out of the total 105 children, 56.1% were males. The median age was 7 years. The commonest reported symptoms were polydipsia (97.8%), polyuria (75.2%), and nocturia (75.2%). The mean time taken by parents from onset of symptoms to decide to visit the physician (appraisal gap) was 7.85 ± 7.95 days. The help-seeking gap (from decision-making to visiting a physician) was 3.01 ± 8.31 days, diagnostic gap (from first visit to diagnosis) was 4.19 ± 6.72 days, and the treatment gap (from diagnosis to the start of insulin) was 2.12 ± 6.87 days. The DKA at onset (was present in 39 out of 105 children 37.1%) and was higher among children with lower per-capita income (-0.017), lack of previous experience among parents (-0.017), longer appraisal (-0.023), and treatment gap (-0.009).

Conclusion: Increasing awareness about the diabetes among children among the public and primary healthcare workers can help prevent DKA at onset.
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http://dx.doi.org/10.4103/ijem.IJEM_519_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323632PMC
July 2021

Diabetes Self-Management Education and Support to Improve Outcomes for Children and Young Adults With Type 1 Diabetes: An Umbrella Review of Systematic Reviews.

Sci Diabetes Self Manag Care 2021 Aug 1:26350106211031809. Epub 2021 Aug 1.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Purpose: The objectives of this umbrella review were to describe various aspects of diabetes self-management education and support (DSMES)-related interventions and their effect on clinical, behavioral, and psychosocial outcomes among children and young adults with type 1 diabetes (T1DM) and identify gaps in current DSMES-related research.

Methods: An umbrella review of systematic reviews on DSMES interventions was conducted in accordance with the PRISMA 2009 statement. Four international medical databases were searched for eligible review articles published in English in the last 10 years that dealt with children and youths with T1DM and were conducted in accordance with a priori protocol.

Results: Out of the 234 citations screened, only 8 systematic reviews representing 166 studies were considered eligible for further analysis. Glycemic management (A1C) is the most common outcome variable (108 studies). Common behavioral and psychosocial outcome variables examined are episodes of hypoglycemia (27 studies) and diabetic ketoacidosis (21 studies) and self-care behavior and generic quality of life (20 studies each). Several gaps in DSMES-related research studies are identified, including uneven geographical distribution of study population, methodological weaknesses in study designs, missing important outcome variables, use of nonstandardized assessment tools, and lack of assessment of the sustainability of effects.

Conclusion: The effects of DSMES interventions on clinical, behavioral, and psychosocial outcomes are varied. The heterogeneity of implementation and evaluation makes it difficult to draw clear conclusions about elements of DSMES that are most effective. There is a need for long-term assessment of the psychosocial and behavioral outcomes using validated and generalizable instruments.
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http://dx.doi.org/10.1177/26350106211031809DOI Listing
August 2021

Effect of an Oral Health Preventive Protocol on Salivary Parameters and Gingival Health of Children with Type 1 Diabetes.

Int J Clin Pediatr Dent 2021 Jan-Feb;14(1):109-114

Department of Microbial Type Culture Collection and Gene Bank, Institute of Microbial Technology, Chandigarh, India.

Context: Type 1 diabetic children exhibit poorer oral health than general population. However, no oral health preventive protocol exists for attending to the oral health needs of such children.

Aim: To evaluate the effect of an oral health preventive protocol on salivary parameters and gingival health of children with type 1 diabetes mellitus over a period of 6 months.

Materials And Methods: Fifty diabetic children, aged 6-12 years were selected and divided into two groups. Children in group I received a comprehensive oral health preventive protocol. The parameters recorded were oral hygiene practices, salivary flow rate, pH, buffer capacity, viscosity, electrolytes, and plaque and gingival indices. These were compared at baseline, 3-, and 6-month intervals.

Statistical Analysis: Statistical analysis was done using IBM SPSS STATISTICS (version 22.0). Tests were based on the type of data.

Results: The intervention group (group I) showed favorable improvements in the parameters assessed. A greater number of participants adopted the correct oral hygiene methods. Unstimulated salivary flow rate increased from 0.36 ± 0.21 to 0.82 ± 0.16 mL/minute in group I and from 0.32 ± 0.24 to 0.58 ± 0.16 mL/minute in group II after 6 months ( = 0.001). Salivary buffer capacity increased from 3.07 ± 2.64 to 10.40 ± 0.82 in group I while in group II, it improved from 3.20 ± 1.47 to 9.33 ± 1.44 ( = 0.02). Salivary viscosity decreased in group I from 1.97 ± 0.42 to 1.15 ± 0.06 and from 1.97 ± 0.35 to 1.23 ± 0.11 in group II after 6 months ( = 0.02). Gingival scores changed from 1.07 ± 0.35 to 0.20 ± 0.23 in group I and from 1.04 ± 0.28 to 0.85 ± 0.25 in group II ( = 0.001).

Conclusion: The preventive protocol used in the present study showed a significant ( < 0.05) improvement in the parameters assessed.

How To Cite This Article: Singh V, Gauba K, Goyal A, . Effect of an Oral Health Preventive Protocol on Salivary Parameters and Gingival Health of Children with Type 1 Diabetes. Int J Clin Pediatr Dent 2021;14(1):109-114.
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http://dx.doi.org/10.5005/jp-journals-10005-1871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311772PMC
July 2021

Metabolic complications of childhood obesity.

J Family Med Prim Care 2021 Jun 2;10(6):2325-2330. Epub 2021 Jul 2.

Department of Pediatrics, PGIMER, Chandigarh, India.

Context: Childhood obesity is a global health problem. A percentage of 2.3 of Indian boys and 2.5 of Indian girls are obese. Childhood obesity is associated with many morbidities like diabetes mellitus, coronary artery disease, musculoskeletal problems, and increased mortality.

Aims: The aim of this study is to estimate burden of metabolic complications of obesity in child and parents of obese children and compare it with normal-weight children.

Settings And Design: The study was done at a tertiary health center in northern India. It was a cross-sectional study.

Methods And Material: We enrolled 60 obese children and age- and sex-matched 26 controls, based on Indian Academy of Pediatrics (IAP)2015 body mass index (BMI) charts. Anthropometric parameters and metabolic complications in family were compared between cases and controls. Clinical markers of metabolic derangements and laboratory metabolic profile were assessed for obese children.

Statistical Analysis Used: Descriptive statistics was used to describe frequencies. Chi-square test and Mann-Whitney test and Spearman correlation were used for comparison.

Results: The prevalence of obesity and obesity-related complications was high in families of obese children. Ten percent of obese children had impaired fasting glucose and 30% had Haemoglobin A1c (HbA1c) in prediabetes category. Forty percent of obese children had dyslipidemia, 45% had transaminitis, and 46.7 were vitamin D deficient. A percentage of 41.7 of obese children had fatty liver on ultrasound.

Conclusions: The family health and child weight are linked through home environment and genetics. The metabolic complications of obesity prediabetes, dyslipidemia, fatty liver, and lower vitamin D level are common in childhood obesity. Regular screening and interventions of metabolic complications are essential for saving child's future health.
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http://dx.doi.org/10.4103/jfmpc.jfmpc_975_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284196PMC
June 2021

FSH-stimulated Inhibin B (FSH-iB): A Novel Marker for the Accurate Prediction of Pubertal Outcome in Delayed Puberty.

J Clin Endocrinol Metab 2021 Aug;106(9):e3495-e3505

Department of Endocrinology, PGIMER Chandigarh, India.

Background: Clinicians have long been struggling to find an effective tool to predict onset of puberty.

Objective: To explore stimulability of inhibin B after exogenous FSH and its potential role for prediction of onset of puberty.

Design And Participants: Study subjects were enrolled into "exploratory cohort" (n = 42) and "validation cohort" (n = 19). The exploratory cohort was further divided into group 1 (healthy children with spontaneous puberty [SP], n = 26) and group 2 (patients with hypogonadotropic hypogonadism [HH], n = 16). The validation cohort included children who presented with complaints of delayed puberty.

Intervention And Outcome: Participants were subjected to FSH stimulation test and GnRH analogue stimulation test. Cutoffs derived from the exploratory cohort for basal and FSH stimulated inhibin B (FSH-iB) were applied on the validation cohort. Basal LH, GnRH analogue-stimulated LH, basal inhibin B, and FSH-iB were compared with clinical outcomes on a prospective follow-up for prediction of onset of puberty.

Results: There was statistically significant increment in inhibin B after exogenous FSH in group 1 (SP) in both male (188.8 pg/mL; P = 0.002) and female (1065 pg/mL; P = 0.023) subjects. The increment was not statistically significant in group 2 (HH) in both sexes. FSH-iB at a cutoff of 116.14 pg/mL in males and 116.50 pg/mL in females had 100% sensitivity and specificity for labelling entry into puberty. On application of these cutoffs on the validation cohort, FSH-iB had 100% positive predictive value, negative predictive value, and diagnostic accuracy for prediction of pubertal onset.

Conclusion: Inhibin B was stimulable in both male and female subjects. FSH-iB can be considered a novel and promising investigation for prediction of onset of puberty. Future studies are required for further validation.
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http://dx.doi.org/10.1210/clinem/dgab357DOI Listing
August 2021

Comparative efficacy of early morning versus bedtime administration of levothyroxine in children with hypothyroidism: a prospective, open label, randomized, case-control study.

Pediatr Endocrinol Diabetes Metab 2021 May 19. Epub 2021 May 19.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Introduction: Studies in adults with hypothyroidism suggest an equal efficacy of bedtime versus early morning intake of levothyroxine. There is limited data on timing of levothyroxine administration in children.

Material And Methods: Children with hypothyroidism on early morning levothyroxine, and clinically and biochemically euthyroid, were assigned to receive levothyroxine at bedtime (group A) or were continued on early morning levothyroxine intake (group B). Clinical, anthropometric and laboratory evaluation (thyroid and lipid profiles, liver enzymes and creatinine) was done at baseline, and at 3 and 6 months.

Results: Eighty-four children, 42 in each group, completed the study. The clinical and anthropometric parameters remained similar in the two groups at baseline and at 3- and 6-month follow-up visits. There was no difference in the mean serum concentrations of triiodothyronine, thyroxine and thyrotropin at the 3 time-points in the study. In addition, mean serum aspartate transaminase, alanine transaminase, creatinine and parameters of lipid profiles remained similar in the two groups. The requirement of levothyroxine was similar at baseline (48.6 ±16.9 µg vs. 49.6 ±19.5 µg, p-value 0.80) and at the endpoint (48.3 ±17.2 µg vs. 51.9 ±18.0 µg, p-value 0.46) in both groups. At the study end, 25 (60%) patients in group A and 17 (40%) in group B preferred bedtime dosing of levothyroxine.

Conclusions: We found an equal efficacy of bedtime intake compared to early morning intake of levothyroxine in maintaining an euthyroid state in children with hypothyroidism. Further studies are required to see if bedtime levothyroxine administration improves the quality of life of patients.
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http://dx.doi.org/10.5114/pedm.2021.105635DOI Listing
May 2021

Bone density and bone health alteration in boys with Duchenne Muscular Dystrophy: a prospective observational study.

J Pediatr Endocrinol Metab 2021 May 12;34(5):573-581. Epub 2021 Apr 12.

Pediatric Neurology Unit, Department of Pediatrics, APC, PGIMER, Chandigarh, India.

Objectives: Boys with Duchenne Muscular Dystrophy (DMD) are at increased risk for compromised bone health, manifesting as low-impact trauma long bone fractures and vertebral compression fractures.

Methods: In a prospective observational study, we studied bone health parameters in North Indian boys with DMD. We consecutively enrolled ambulatory boys with DMD on glucocorticoid therapy. Bone health was evaluated with X-ray spine, Dual-energy X-ray absorptiometry (DXA), serum calcium, vitamin D3 (25[OH]D), 1,25-dihyroxyvitamin D3 (1,25[OH]D), serum osteocalcin, osteopontin, and N terminal telopeptide of type 1 collagen (Ntx) levels.

Results: A total of 76 boys with DMD were enrolled. The median age was 8.5 (interquartile range [IQR] 7.04-10.77) years. Among these, seven (9.2%) boys had long bone fractures, and four (5.3%) had vertebral compression fractures. Fifty-four (71%) boys underwent DXA scan, and among these 31 (57%) had low bone mineral density (BMD, ≤-2 z-score) at the lumbar spine. The mean BMD z-score at the lumbar spine was -2.3 (95% confidence interval [CI] = -1.8, -2.8), and at the femoral neck was -2.5 (95% CI = -2, -2.9). 25(OH)D levels were deficient in 68 (89.5%, n=76) boys, and 1,25(OH)D levels were deficient in all. Mean serum osteocalcin levels were 0.68 ± 0.38 ng/mL (n=54), serum osteopontin levels were 8.6 ± 4.6 pg/mL (n=54) and serum Ntx levels were 891 ± 476 nmol/L (n=54). Boys with low BMD received glucocorticoids for longer duration, in comparison to those with normal BMD (median, IQR [16.9 (6-34) months vs. 7.8 (4.8-13.4) months]; p=0.04).

Conclusions: Bone health is compromised in North Indian boys with DMD. BMD at the lumbar spine is reduced in more than half of boys with DMD and nearly all had vitamin D deficiency on regular vitamin D supplements. Longer duration of glucocorticoid therapy is a risk factor for low BMD in our cohort.
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http://dx.doi.org/10.1515/jpem-2020-0680DOI Listing
May 2021

Mauriac syndrome: A failure of parent or physician.

Trop Doct 2021 Jul 4;51(3):437-440. Epub 2021 Apr 4.

Professor, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Mauriac syndrome is rare; we share our experience of nine patients who presented at a young age with malnutrition, short stature, abdominal distention and deranged liver function.
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http://dx.doi.org/10.1177/00494755211005205DOI Listing
July 2021

Juvenile granulosa cell tumor of the ovary: A comprehensive clinicopathologic analysis of 15 cases.

Ann Diagn Pathol 2021 Jun 10;52:151721. Epub 2021 Feb 10.

Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

Objective: Juvenile granulosa cell tumor(JGCT) is an uncommon ovarian sex-cord stromal tumor, with diverse clinical, radiological and histopathologic features. The present study describes the clinicopathological and histomorphological spectrum of JGCTs, and highlights the key differentiating features from its mimics.

Methods: A retrospective analysis of all cases reported as JGCTs during 2011-19 (8 years) was performed with detailed evaluation of clinical, histopathologic data and follow-up details.

Results: Of a total 115 GCTs reported during the study period, 15(13%) were reported as JGCTs. The mean age at presentation was 17 years. Abdominal pain and distension were the most common clinical presentations. Five patients were pre-menarchal with 3 exhibiting precocious puberty. Majority of tumors were unilateral(left>right), solid-cystic, ranging in size from 4 to 20 cm. Microscopically, macrofollicular architecture was most frequent (n = 12;80%). The tumor cells depicted variable nuclear pleomorphism, small distinct nucleoli and moderate-abundant pale eosinophilic-clear/vacuolated cytoplasm. Mitotic activity ranged from 1 to 10/10HPFs. Uncommon histopathologic features included microcystic and tubulo-cystic architecture, myxoid degeneration, bizarre tumor giant cells, hob-nailing of the tumor cells, intracytoplasmic hyaline globules, multifocal calcification and thick hyalinized blood vessels. Majority(n = 12;80%) presented in stage I. Surgical treatment included unilateral salpingo-oophorectomy without any adjuvant chemotherapy, bilateral salpingo-oophorectomy (BSO) and total abdominal hysterectomy with BSO with adjuvant BEP chemotherapy (Bleomycin, etoposide, cisplatin).

Conclusions: JGCT is a rare ovarian tumor affecting young women and children with diverse histopathologic features. Despite an aggressive histopathology, these tumors have a good outcome, when diagnosed at an early stage.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151721DOI Listing
June 2021

A novel homozygous variant in exon 10 of the gene causing hyperphosphatemic familial tumoral calcinosis in a family from North India.

Intractable Rare Dis Res 2021 Feb;10(1):55-57

Institute of Human Genetics, Technische Universität München, Munich, Germany.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is an extremely rare autosomal recessive disorder caused by variants in the (N-acetylgalactosaminyltransferase 3), (Fibroblast Growth Factor-23) and (α-Klotho) genes, which results in progressive calcification of soft tissues. We describe the case of a 9-year-old girl who presented with recurrent hard nodular swellings on her feet and knees which intermittently discharged chalky white material. Her younger brother also had a similar condition. Both siblings showed hyperphosphatemia, but the parentsbiochemical parameters were normal. The histological features of the material aspirated from a skin lesion were consistent with tumoral calcinosis. Sanger sequencing identified a novel homozygous non-synonymous sequence variant in exon 10 of the gene (NM_004482.3:c.[1681T>A];[1681T>A], NP_004473.2:p. [Cys561Ser];[Cys561Ser] in the proband and her affected brother. The parents were heterozygous carriers for the same sequence variant. In conclusion, we report a new variant in the gene that caused HFTC in a North Indian family.
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http://dx.doi.org/10.5582/irdr.2020.03084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882081PMC
February 2021

Characterisation of LDL receptor gene mutations in a North Indian cohort of children with homozygous familial hypercholesterolaemia.

Pediatr Endocrinol Diabetes Metab 2021 ;27(1):32-36

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, India.

Introduction: Homozygous familial hypercholesterolaemia (HoFH) carries a grave prognosis but is often underdiagnosed and undertreated. Confirmation of molecular diagnosis helps in planning effective management and determining prognosis accurately. Aim of the study: To determine the spectrum of mutations in the LDLR gene in a cohort of children with a clinical diagnosis of HoFH.

Material And Methods: Genomic DNA was extracted from peripheral blood samples of 8 patients, who were children of either sex, aged under 16 years, and diagnosed clinically with HoFH using the Simon Broome criteria. The potential variants in the LDLR gene were analysed by Sanger sequencing.

Results: Fifty variations were found in the 8 patients; 39 (78%) were single nucleotide variations while 8 (16%) and 3 (6%) were deletions and insertions, respectively. The pathogenic variants in the LDLR gene were detected in four patients; three showed duplication in exon 17 (c.2416dupG) creating an amino acid change at position 806 (p.Val806GlyfsTer11) while one had a missense variant in the exon 9 at position c.1285G>A resulting in a change in amino acid at position 429 (p.Val429Met). The variants were found in heterozygous state in the parents or siblings of probands who showed pathogenic variants.

Conclusions: The frequency of disease-causing variants in the LDLR gene in our patients with HoFH was 50%. Further studies to characterise mutations in genes for apolipoprotein B, proprotein convertase subtilisin/kexin type 9, or LDL adaptor protein are suggested in all children with a clinical diagnosis of HoFH.
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http://dx.doi.org/10.5114/pedm.2020.103056DOI Listing
August 2021

Environmental exposure to urinary Bisphenol-A in North Indian children aged between 6 and 16 years and its association with body mass index.

Environ Sci Pollut Res Int 2021 Jun 6;28(23):29085-29095. Epub 2021 Feb 6.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

This study investigates the effect of environmental risk factors among North Indian children aged between 6 and 16 years associated with body mass index by comparing fasting and non-fasting urine Bisphenol-A, urine creatinine, and serum thyroid levels with other potential confounding factors. A total of 301 children were enrolled, and term fasting and non-fasting were used based on the sample collection, either first morning or random. Children were grouped into obese, non-obese, and underweight categories based on age- and gender-specific Centre for Disease Control (CDC) 2000 growth chart and grouped according to their body mass index. The overall mean ± SD (standard deviation) of age (years) was 10.45±2.39 (boys age 10.38±2.38 and girls age 10.45±2.40). Urinary Bisphenol-A concentration (ng/mL ± SD) was higher among obese (2.40±4.70) than non-obese (1.30±1.67) and underweight (1.84±3.46) category children. Higher levels of fasting urinary Bisphenol-A (≥2 ng/mL) and thyroid-stimulating hormone (TSH) (≥12.7 μg/dL) were associated with obesity than those of non-fasting children. Being non-fasting among girls at quartile 4 (obese, >2.1800 ng/mL; underweight, >2.1325 ng/mL) had higher odds (obese adjusted odds ratio (aOR) 7.72 (95% CI 0.08-1368.52), underweight adjusted odds ratio (aOR) 12.45 (95% CI 1.55-171.24)] than fasting children. We recommend awareness programs and policy guidelines by engaging teachers and parents for the physical assessment of the presence of Bisphenol-A in food packaging materials to reduce the potential exposure to other chemical migrations sources. Graphical abstract.
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http://dx.doi.org/10.1007/s11356-021-12555-zDOI Listing
June 2021

Central obesity and dyslipidemia in pediatric patients with psoriasis: An observational study from India.

J Am Acad Dermatol 2021 Jan 9. Epub 2021 Jan 9.

Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.12.072DOI Listing
January 2021

Ten-year use of recombinant parathyroid hormone for the treatment of hypoparathyroidism in a boy with partial Jacobsen syndrome.

Pediatr Endocrinol Diabetes Metab 2021 ;27(1):57-61

Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Pediatric hypoparathyroidism (HPT) is caused by inherited or acquired defects involving the synthesis or secretion of PTH, resistance to PTH action, or inappropriate regulation of PTH. Several syndromes such as DiGeorge syndrome, HDR (hypoparathyroidism, sensorineural deafness and renal dysplasia) syndrome, HRD (hypoparathyroidism, retardation, and dysmorphism) syndrome, Kenny-Caffey syndrome etc. may have associated HPT. In the present communication, we describe, the hitherto unreported, occurrence of HPT in a child with partial Jacobsen syndrome. Chromosomal Microarray analysis showed a heterozygous deletion of 4.7 Mb at cytoband 11q24.3q25 encompassing approximately 20 genes including JAM3 and NTM genes. The child was treated with recombinant human parathyroid hormone (rhPTH1-34) for 10 years. Throughout follow up, he required several adjustments in dosages of rhPTH1-34 and oral calcium to maintain serum calcium concentrations in low normal ranges. The bone turnover markers remained normal and oral calcium supplements were completely taken off after 8 years. In conclusion, our single-case experience indicates that long-term therapy of chronic HPT with rhPTH1-34 is safe and reduces the need for additional therapies.
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http://dx.doi.org/10.5114/pedm.2020.100402DOI Listing
August 2021

Can BCG vaccine protect against COVID-19 via trained immunity and tolerogenesis?

Bioessays 2021 03 9;43(3):e2000200. Epub 2020 Nov 9.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

As the number of infections and mortalities from the SARS-CoV-2 pandemic continues to rise, the development of an effective therapy against COVID-19 becomes ever more urgent. A few reports showing a positive correlation between BCG vaccination and reduced COVID-19 mortality have ushered in some hope. BCG has been suggested to confer a broad level of nonspecific protection against several pathogens, mainly via eliciting "trained immunity" in innate immune cells. Secondly, BCG has also been proven to provide benefits in autoimmune diseases by inducing tolerogenicity. Being an acute inflammatory disease, COVID-19 requires a therapy that induces early priming of anti-viral immune responses and regulates aberrant hyperactivity of innate-immune cells. Here, we hypothesize that BCG can offer reliable spatiotemporal protection from COVID-19 by triggering trained immunity and tolerogenesis, through multiple cellular pathways. We propose further research on BCG-mediated immunoprotection, especially in vulnerable individuals, as a strategy to halt the progress of the SARS-CoV-2 pandemic. Also see the video abstract here https://youtu.be/P2D2RXfq6Vg.
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http://dx.doi.org/10.1002/bies.202000200DOI Listing
March 2021

Clinical application of a novel next generation sequencing assay for CYP21A2 gene in 310 cases of 21- hydroxylase congenital adrenal hyperplasia from India.

Endocrine 2021 01 18;71(1):189-198. Epub 2020 Sep 18.

Consultant Pediatrician and Deputy Director, Hirabai Cowasji Jehangir medical research Institute, Jehangir Hospital, Pune, Maharashtra, India.

Purpose: Accurate diagnosis is required for management of Congenital adrenal hyperplasia (CAH). The conventional method for detection of mutations in the CYP21A2 gene is targeted capillary sequencing which is labor intensive and has limited multiplexing capability. Next generation sequencing (NGS) provides data with high sequence coverage and depth. Our objective was to develop an accurate NGS-based assay to characterize the mutation spectrum in CYP21A2 gene in Indian patients suspected to have 21-OH CAH.

Methods: Cases with 21-OH CAH from 12 endocrine units across India were studied. DNA was extracted from proband's and parent's(subset) blood. Locus-specific long-range PCR and gel electrophoresis of amplicons was followed by NGS where no visible 30 kb homozygous/whole gene deletion was observed. Orthogonal confirmation was performed by capillary sequencing (ABI 3500) and Multiplex Ligation-dependent Probe Amplification (MLPA, MRC-Holland). PCR products were purified and individual libraries were pooled and sequenced (Illumina).

Results: Of the 310 CAH cases, biallelic mutations (pathogenic/ likely pathogenic variants involving both CYP21A2 gene copies) were detected in 256 (82.6%), heterozygous mutations in 13 (4.2 %), and none in 41 (13.2%). Most common mutation was c.293-13A/C>G (29.03%), followed by 30 kb deletion (18.24%). Thirty samples tested orthogonally (by capillary sequencing or MLPA) showed 100% concordance with NGS assay. Nine novel variants were identified.

Conclusions: We have developed and validated a comprehensive NGS-based assay for detection of variants in CYP21A2 gene in patients with 21-OH CAH. We describe CYP21A2 mutation spectrum and novel variants in a large cohort of Indian patients with CAH.
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http://dx.doi.org/10.1007/s12020-020-02494-zDOI Listing
January 2021

Photographic Journey of Cushing Syndrome.

Indian J Pediatr 2021 Sep 15;88(9):935-936. Epub 2020 Sep 15.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s12098-020-03490-xDOI Listing
September 2021

Pediatric type 1 diabetes research in the 21st century: a scientometric review.

Pediatr Endocrinol Diabetes Metab 2020 ;26(3):132-139

Endocrinology and Diabetes Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, India.

Introduction: Scientometric studies help scientists to identify research gaps and plan future research. There is no scientometric assessment of research on childhood onset type 1 diabetes (T1D), despite an intensive research in this field over the past 2 decades.

Aim Of The Study: To provide a scientometric assessment of global research output in pediatric T1D.

Material And Methods: Publications on pediatric T1D indexed in Scopus database over the 20-year period from 2000 to 2019 were examined. The most productive and impactful countries, organizations and authors, trends in research, the media of publications and characteristics of high cited publications were identified using appropriate bibliographic tools.

Results: Pediatric T1D research registered 7.84% and 79.99% annual and 10-year cumulative growth and averaged 19.35 citations per paper (CPP). The field witnessed an uneven participation of 141 countries, wherein 82.67% of the global research output share came from top 10 countries. USA leads the ranking with 29.76% share, followed by UK (10.56%), Germany, Italy, Sweden and Australia (5.15% to 7.88%), and Poland, Finland, Canada and Denmark (3.04% to 4.24%). Five countries which registered relative citation index (RCI) higher than their group average of 1.63 were Finland (2.30), UK (1.82), Canada (1.77), Denmark and USA (1.74 each). The number of participating organizations and authors was 3627 and 5596 respectively.

Conclusions: The USA and Finland are the most productive and the most impactful countries respectively in global pediatric T1D research. The contribution from developing countries especially from Southeast Asia is meager despite a large disease burden.
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http://dx.doi.org/10.5114/pedm.2020.98165DOI Listing
January 2020

Cross-cultural adaptation and psychometric evaluation of Hindi version of Diabetes Self-Management Profile-Self Report in Indian type 1 diabetes patients.

Pediatr Diabetes 2021 02 23;22(1):101-111. Epub 2020 Jul 23.

Department of Paediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: No validated measures exist for evaluating diabetes self-management in Indian type 1 diabetes (T1D) patients.

Objective: To cross culturally adapt and evaluate the psychometric properties of Hindi version of Diabetes Self-Management Profile-Self Report (DSMP-SR-Hindi) in Indian T1D patients.

Methods: Total 160 T1D patients and their parents participated in the study. The mean age of patients was 13.5 ± 2.5 years and HbA1c was 8.6 ± 2.2%.

Results: Exploratory factor analysis employing principle axis factoring with promax rotation was conducted. Monte Carlo parallel analysis identified three sub-scales instead of five sub-scales proposed in original version. Because of underlying ceiling and floor effects and insufficient loadings, five items were eliminated. Consequently, final Hindi version of DSMP-SR contained 19 items from DSMP-SR-24. Internal consistencies were adequate for overall scale (Cronbach's α = 0.835), identified sub-scales (Cronbach's α = 0.702-0.802) and comparable between genders. DSMP-19 total scores (r = -0.74) and three subscales correlated significantly with HbA1c (SMBG and Corrective Adjustments [r = -0.58], Exercise [r = -0.48], and Conformity to Diet and Insulin Routine [r = -0.64]). For every one SD improvement (11.2 marks) in DSMP-SR-Hindi score, odds of falling into poor glycaemic group (HbA1c > 7.5%) dropped to 0.242 times (95% CI 0.144-0.405; P < .001).

Conclusions: DSMP-SR-Hindi is a reliable and valid self-report measure of diabetes self-management behavior in Indian T1D patients. The revealed three subscales are reliable to use in isolation and across the genders. It will help in monitoring patient's progress in stepwise manner, ranging from their basic understanding of prescribed regimen to taking advance corrective actions in face of altered needs.
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http://dx.doi.org/10.1111/pedi.13071DOI Listing
February 2021

Missing during COVID-19 lockdown: Children with onset of type 1 diabetes.

Acta Paediatr 2020 Oct 12;109(10):2144-2146. Epub 2020 Jul 12.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1111/apa.15443DOI Listing
October 2020

Low serum copper and zinc concentrations in North Indian children with overweight and obesity

Pediatr Endocrinol Diabetes Metab 2020 ;26(2):79-83

Department of Paediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Introduction: There are limited data on the alterations of serum copper and zinc, which have been proposed to have associations among children with obesity.

Material And Methods: A total of 173 children were enrolled and grouped into overweight/obese (n = 69) and non-obese (n = 104) according to CDC 2000 growth charts. Serum and whole blood zinc and copper concentrations were measured by validated ICP-MS method, and copper/zinc ratios were calculated and correlated to various anthropometric parameters.

Results: Mean BMI in obese (24.78 ±3.93) was significantly higher as compared to non-obese (16.44 ±2.34; p < 0.0001, 95% CI: 15.9873-16.8998) children. Mean serum copper levels in obese children (1099.80 ±478.67 µg/l) were significantly lower than for non-obese children (2063.77 ±1006.81 µg/l; p = 0.0001, 95% CI: 1867.9755-2259.5755). Similarly, the mean serum zinc levels in obese children (851.53 ±406.33 µg/l) were also significantly lower as compared to non-obese children (1528.72 ±796.82 µg/l; p = 0.0001, 95% CI: 1373.76-1683.6879). Mean whole blood copper levels were significantly lower in obese (929.56 ±200.15 µg/l) as compared to non-obese (1393.22 ±861.92 µg/l; p = 0.0001, 95% CI: 1225.6023-1560.8481) children. Similarly, the mean whole blood zinc levels in obese (4384.11 ±881.87 µg/l) were also significantly lower as compared to non-obese (5380.14 ±2236.77 µg/l; p = 0.001, 95% CI: 4945.1491-5815.1416) children.

Conclusions: The serum and whole blood concentrations of zinc and copper were found to be significantly lower in children with exogenous obesity as compared to controls. Additional investigations are recommended to see the underlying aspect of these elements in the development of obesity along with their co-morbidities.
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http://dx.doi.org/10.5114/pedm.2020.95627DOI Listing
May 2021

Managing syndromic congenital ichthyosis at a tertiary care institute-Genotype-phenotype correlations, and novel treatments.

Dermatol Ther 2020 11 7;33(6):e13816. Epub 2020 Jul 7.

Department of Paediatric Genetics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Syndromic congenital ichthyoses (CI) are genetically determined disorders of cornification that are characterized by generalized scaling along with systemic symptoms. Data on congenital syndromic ichthyosis from developing countries are scarce. We aimed to assess the prevalence, phenotype-genotype correlation, and management of syndromic CI patients presenting to our outpatient during the specified period this was a retrospective study of congenital syndromic ichthyosis patients attending a dermatology clinic in a tertiary care center from 2105-2018. We reviewed epidemiological and comorbidities data, phenotype-genotype correlations, and treatments of syndromic congenital ichthyosis patients. Six patients of Syndromic CI were diagnosedamongst 86 patients of CI (8.1%). Amongst these, three patients of Sjogren-Larrson syndrome (SLS), two patients of Netherton syndrome (NS), and one of Chanarin-Dorfman disease (CDD) were reported. Next-generation sequencing (NGS) was performed with novel variants reported in one patient each of SLS, NS, and CDD. An atypical phenotype was observed in a patient with NS with associated growth hormone and adrenocorticotropic hormone deficiency but with favorable clinical response to intravenous immunoglobulin. Our reports point towards the unreported pool of genetic mutations in CI from India. Novel mutations were associated with variable cutaneous and systemic involvement.
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http://dx.doi.org/10.1111/dth.13816DOI Listing
November 2020

Neonatal Cushing Syndrome.

Indian J Pediatr 2021 01 4;88(1):74-75. Epub 2020 Jun 4.

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1007/s12098-020-03363-3DOI Listing
January 2021

Role of DNA-LL37 complexes in the activation of plasmacytoid dendritic cells and monocytes in subjects with type 1 diabetes.

Sci Rep 2020 06 1;10(1):8896. Epub 2020 Jun 1.

Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Initiation of type 1 diabetes (T1D) is marked by the infiltration of plasmacytoid dendritic cells (pDCs) and monocytes in pancreatic islets. Dying beta cells release self-DNA, which forms complexes with antimicrobial peptide, LL37, and its delayed clearance can activate pDCs and monocytes. Here, we studied the phenotypic effects of DNA-LL37 complexes on pDCs and monocytes in 55 recently diagnosed T1D and 25 healthy control (HC) subjects. Following in vitro stimulation with DNA-LL37 complexes, T1D group demonstrated higher frequency and mean fluorescence intensity (MFI) of pDCs expressing IFN-α. Similarly, the monocytes in T1D group showed an increase in MFI of IFN-α. Post-stimulation, an increase in the antigen presentation and co-stimulatory ability of pDCs and monocytes was observed in T1D group, as indicated by higher expression of HLA-DR, CD80 and CD86. Upon co-culture, the stimulated monocytes and pDCs, particularly in the T1D group were able to further activate autologous CD4 + T cells, with increase in expression of CD69 and CD71. Finally, in a transwell assay, the stimulated pDCs and monocytes induced an increase in apoptosis of 1.1B4 beta cells. Additionally, we observed reduced expression of indoleamine 2,3-dioxygenase 1 (IDO1) in pDCs and monocytes of T1D subjects. Our results suggest that DNA-LL37 complexes activate pDCs and monocytes towards a proinflammatory phenotype during pathogenesis of T1D.
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http://dx.doi.org/10.1038/s41598-020-65851-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264208PMC
June 2020

We urgently need guidelines for managing COVID-19 in children with comorbidities.

Authors:
Devi Dayal

Acta Paediatr 2020 07 6;109(7):1497-1498. Epub 2020 May 6.

Department of Pediatrics, Endocrinology and Diabetes Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1111/apa.15304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262043PMC
July 2020

Simple virilising congenital adrenal hyperplasia in monozygotic twins: A rare report and review of previous cases.

Pediatr Endocrinol Diabetes Metab 2020 ;26(1):58-62

Endocrinology and Diabetes Unit, Department of Pediatrics, Postgraduate Institute of Medical Educa-tion and Research, India.

Congenital adrenal hyperplasia (CAH) occurring in twins is extremely rare. Most of these cases are of classic salt-wasting CAH due to 21-hydroxylase enzyme deficiency. Only two cases of the simple virilising form of CAH have been reported previously, with variable clinical presentations. In this report, we describe a pair of monozygotic twins with classic simple virilising form of CAH, who had a simultaneous onset and similar severity of clinical manifestations. Genetic analysis of the CYP21A2 gene in twin 1 showed the pres-ence of two heterozygous pathogenic sequence variants, c.518T>A and c.955C>T in the CYP21A2 gene, consistent with a diagnosis of CAH due to 21-hydroxylase deficiency. We also present a brief review of previous cases of twins with CAH.
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http://dx.doi.org/10.5114/pedm.2020.93248DOI Listing
March 2021

Allgrove Syndrome and a Novel Mutation of AAAS Gene in a Boy.

Indian Pediatr 2020 01;57(1):82

Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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January 2020

Etiological Spectrum of Precocious Puberty: Data from Northwest India.

Indian Pediatr 2020 01;57(1):63-64

Department of Pediatrics, PGIMER, Chandigarh, India.

We retrospectively analyzed clinic records of 55 children (36 girls) with precocious puberty. Majority (34, 62%) had central precocious puberty, out of which 19 were idiopathic. Peripheral precocious puberty was seen in 14 children. Congenital adrenal hyperplasia was the commonest cause of peripheral precocious puberty (6, 42.8%).
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January 2020

0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial.

Crit Care 2020 01 2;24(1). Epub 2020 Jan 2.

Division of Pediatric Allergy & Immunology, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India.

Background: Acute kidney injury (AKI) is an important complication encountered during the course of diabetic ketoacidosis (DKA). Plasma-Lyte with lower chloride concentration than saline has been shown to be associated with reduced incidence of AKI in adults with septic shock. No study has compared this in DKA.

Methods: This double-blind, parallel-arm, investigator-initiated, randomized controlled trial compared 0.9% saline with Plasma-Lyte-A as initial fluid in pediatric DKA. The study was done in a tertiary care, teaching, and referral hospital in India in children (> 1 month-12 years) with DKA as defined by ISPAD. Children with cerebral edema or known chronic kidney/liver disease or who had received pre-referral fluids and/or insulin were excluded. Sixty-six children were randomized to receive either Plasma-Lyte (n = 34) or 0.9% saline (n = 32).

Main Outcomes: Primary outcome was incidence of new or progressive AKI, defined as a composite outcome of change in creatinine (defined by KDIGO), estimated creatinine clearance (defined by p-RIFLE), and NGAL levels. The secondary outcomes were resolution of AKI, time to resolution of DKA (pH > 7.3, bicarbonate> 15 mEq/L & normal sensorium), change in chloride, pH and bicarbonate levels, proportion of in-hospital all-cause mortality, need for renal replacement therapy (RRT), and length of ICU and hospital stay.

Results: Baseline characteristics were similar in both groups. The incidence of new or progressive AKI was similar in both [Plasma-Lyte 13 (38.2%) versus 0.9% saline 15 (46.9%); adjusted OR 1.22; 95% CI 0.43-3.43, p = 0.70]. The median (IQR) time to resolution of DKA in Plasma-Lyte-A and 0.9% saline were 14.5 (12 to 20) and 16 (8 to 20) h respectively. Time to resolution of AKI was similar in both [Plasma-Lyte 22.1 versus 0.9% saline 18.8 h (adjusted HR 1.72; 95% CI 0.83-3.57; p = 0.14)]. Length of hospital stay was also similar in both [Plasma-Lyte 9 (8 to 12) versus 0.9% saline 10 (8.25 to 11) days; p = 0.39].

Conclusions: The incidence of new or progressive AKI and resolution of AKI were similar in both groups. Plasma-Lyte-A was similar to 0.9% Saline in time to resolution of DKA, need for RRT, mortality, and lengths of PICU and hospital stay.

Trial Registration: Clinical trial registry of India, CTRI/2018/05/014042 (ctri.nic.in) (Retrospectively registered).
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http://dx.doi.org/10.1186/s13054-019-2683-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6939333PMC
January 2020
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