Efficacy and safety of various oral regimens (three oral doses) and schedules (daily v. monthly) of cholecalciferol in North Indian adults with low vitamin D status: evidence from a randomised controlled trial.

Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 µg/d (Group A), 1000 µg/d (Group B), 2000 µg/d (Group C) and 60 000 µg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration (P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks (P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks (P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) (P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 µg or monthly 60 000 µg of oral cholecalciferol among adults seems optimal and safe.

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Haematological profile of patients with mixed-phenotype acute leukaemia from a tertiary care centre of north India.

BACKGROUND & OBJECTIVES: Mixed-phenotype acute leukaemia (MPAL) is a rare neoplasm with no definite treatment protocols and a distinctly poor outcome. Advancement in polychromatic flow cytometry has made its identification easier. This prospective study was designed to identify cases of MPAL and study their clinical presentation and haematological profile in a tertiary care hospital in north India. METHODS: Ethylenediaminetetraacetic acid (EDTA)-anticoagulated bone marrow aspirate samples of patients diagnosed as acute leukaemia (AL) on the basis of morphology were utilized for immunophenotyping. A comprehensive panel of fluorochrome-labelled monoclonal antibodies targeting myeloid, B-cell, T-cell and immaturity markers was utilized. The patients diagnosed to have MPAL, on the basis of the World Health Organization 2008 classification, were selected for further analyses. RESULTS: There were 15 (2.99%) patients with MPAL of the total 501 cases of AL. Seven were children, all males and mean age of 5.08±3.88 yr. Eight were adults, male:female=6:2 and mean age of 21.43±5.74 yr. Eight were diagnosed as B/myeloid and seven were T/myeloid. No association was observed between age and immunophenotype of MPAL. On morphology, 11 were diagnosed as AML and four as ALL, and no specific morphology of blasts was predictive of a MPAL. INTERPRETATION & CONCLUSIONS: MPAL appeared to be a rare neoplasm (2.99% of AL cases). A comprehensive primary panel of monoclonal antibodies should be used to identify this neoplasm known to have a poor outcome.

Regional and seasonal variations in ultraviolet B irradiation and vitamin D synthesis in India.

UNLABELLED: Evaluation of ultraviolet B index (UVBI) and its impact on vitamin D synthesis is important. We observed the maximum UVBI between 11 am and 1 pm. There was no increase in serum 25(OH)D levels following sun exposure during winter as the UVBI was significantly low, emphasizing the need for vitamin D supplementation during these months. INTRODUCTION: The amount of vitamin D3 synthesizing UVB irradiation (290-320 nm) reaching the earth's surface at different altitudes and seasons in different parts of India and it's impact on vitamin D synthesis has not been well studied. METHODS: The hourly UVB index (UVBI) from 10 am to 3 pm everyday for 12 months was measured by a solar meter in 4 different zones (North, Northeast, West and South) of the country. To study the impact of sun light exposure on vitamin D synthesis during winter, healthy school children aged 10-15 years were exposed to sunlight for a period of 30 min per day, between 11 am to 12 noon with 10 % body surface area, for 4 weeks. The main outcome measures were serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase levels before and after sun exposure. RESULTS: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. The highest UVBI was recorded from the North zone (4.5 ± 2.7 µW/Cm(2)), while the least was recorded in the Northeast zone (2.1 ± 1.2 µW/Cm(2)). UVBI readings in the Northeast zone were consistently low throughout the year, while all the other three zones showed significant seasonal fluctuations. Surprisingly, we observed a significant decrease in serum 25(OH)D levels from baseline (6.3 ± 4.6 to 5.1 ± 2.7 ng/mL; p < 0.001) despite sun exposure. CONCLUSION: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. No increase in the serum 25(OH)D levels was observed following sun exposure in winter, emphasizing the need for vitamin D supplementation during these months.

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.

Cellular proteolytic modification of tumor-suppressor CYLD is critical for the initiation of human T-cell acute lymphoblastic leukemia.

There exists a general recognition of the fact that post translational modification of CYLD protein through proteolytic cleavage by MALT-1 results in sustained cellular NF-kB activity which is conspicuously found to be associated with cancer in general and hematological malignancies in particular. The present study was directed to understand the contribution of MALT-1 and deubiquitinase CYLD to the initiation of T-cell acute lymphoblastic leukemia (T-ALL). Such a study revealed for the first time that the 35kDa CYLD cleaved factor generated by MALT-1 mediated proteolytic cleavage was conspicuously present in human T- ALL subjects of pediatric age group. Further, over-expression of this 35kDa CYLD factor within normal human peripheral blood mononuclear cells had the inherent capacity to program the genome of these cells resulting in T-cell lineage ALL. Based upon these results, we propose that MALT1 inhibitors may be of crucial importance in the treatment of T-ALL subjects of pediatric age group.

Threshold levels of 25-hydroxyvitamin D and parathyroid hormone for impaired bone health in children with congenital ichthyosis and type IV and V skin.

BACKGROUND: Patients with congenital ichthyosis, especially those with darker skin types, are at increased risk of developing vitamin D deficiency and rickets. The relationships between 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH) and bone health have not been studied previously, in ichthyosis. OBJECTIVES: To determine the threshold levels of 25(OH)D and PTH for impaired bone health in children with congenital ichthyosis. METHODS: In this cross-sectional study, 119 children with ichthyosis and 168 controls were recruited. Serum 25(OH)D, PTH, calcium, phosphate and alkaline phosphatase (ALP) were measured. Radiological screening for rickets was carried out only in children with ichthyosis. RESULTS: Forty-seven children with ichthyosis had either clinical or radiological evidence of rickets. The correlation between serum 25(OH)D and PTH showed that a serum level of 25(OH)D 8 ng mL(-1) was associated with a significant increase in PTH. The correlation between PTH and ALP showed that a serum PTH level of 75 pg mL(-1) was associated with a significant increase in ALP levels. Of the different clinical phenotypes of ichthyosis, both autosomal recessive congenital ichthyosis (ARCI) and epidermolytic ichthyosis (EI) were found to have significantly increased PTH, ALP and radiological rickets scores compared with common ichthyosis. CONCLUSIONS: Serum levels of 25(OH)D ≤ 8 ng mL(-1) and PTH ≥ 75 pg mL(-1) significantly increases the risk for development of rickets [odds ratio (OR) 2·8; 95% confidence interval (CI) 1·05-7·40; P = 0·04] in ichthyosis. Among the different types, patients with ARCI (OR 4·83; 95% CI 1·74-13·45; P < 0·01) and EI (OR 5·71; 95% CI 1·74-18·79; P < 0·01) are at an increased risk of developing rickets.

The deferiprone and deferasirox combination is efficacious in iron overloaded patients with ß-thalassemia major: A prospective, single center, open-label study.

BACKGROUND: The high cost, coupled with the need for continuous infusion, renders Desferrioxamine (DFO), a non-feasible option for iron-chelation in a large majority of patients with ß-thalassemia major in developing countries. Monotherapy with deferiprone (DFP) or deferasirox (DFX) may not always attain optimal control, particularly in heavily iron-loaded patients. Combination of DFP and DFX is a potential alternative. PROCEDURE: A prospective, single-center, open-label, uncontrolled study was conducted to evaluate the safety and efficacy of the combination in patients with ß-thalassemia major. Patients who had received either DFP or DFX for >1 year and a serum ferritin >2,000 µg/L were enrolled. Blood counts, liver/renal functions, and serum ferritin were monitored during the 1-year study period. Facilities for cardiac T2*-MRI were unavailable. RESULTS: Thirty-six patients with a mean age of 13 ± 6.9 years (range: 4-29) and a ferritin of 6,768 ± 4,145 µg/L formed the study cohort. Eight (22%) patients had transient gastrointestinal adverse effects. DFX was discontinued in one patient for persistent abdominal pain/diarrhea. Eight (22%) had joint symptoms; DFP was discontinued in two. Four (11%) patients had elevation in AST/ALT levels, managed with temporary interruption of DFX. Nine (25%) had an inconsistent elevation of creatinine to >33% of baseline; no intervention was done. One had transient proteinuria. None had neutropenia. At the end of 1 year, the serum ferritin reduced by a mean value of 3,275.3 ± 618.2 µg/L (P < 0.001). CONCLUSIONS: The oral combination was found to be safe, efficacious, and a feasible option in patients with suboptimal response to monotherapy.

The relationship between serum 25-hydroxy vitamin D, parathormone and bone mineral density in Indian population.

OBJECTIVES: Vitamin D deficiency (VDD) is a global problem. Not all patients with VDD have clinical manifestations or secondary hyperparathyroidism. We studied the interaction between serum 25-hydroxy vitamin D (25OHD), parathormone (PTH) and bone mineral density (BMD) in Indian adolescents and adults. DESIGN: Population survey. PATIENTS: A total of 1829 adolescents and 1346 adults aged 50 years and above were analysed in this study. MEASUREMENTS: Serum biochemistry, 25OHD, PTH and BMD were estimated. Subjects were grouped according to quartiles of serum PTH. VDD was defined as severe (25OHD ≤ 5 ng/ml), moderate (25OHD ≤ 10 ng/ml) and mild (25OHD ≤ 20 ng/ml) and secondary hyperparathyroidism (SHPT) when serum PTH levels >65 pg/ml. RESULTS: Only 30-40% of subjects with moderate and severe VDD, respectively, had SHPT. BMD decreased from Quartile 1 to Quartile 4 of PTH at all sites among adolescents and adults, with only a marginal decline in serum 25OHD levels between these quartiles. Further, within each PTH quartile, there was no difference in BMD according to categories of VDD. Analysing BMD in the different PTH quartiles, the PTH cut-offs beyond which BMD showed a significant decline, was 35 pg/ml in adolescents and 53 pg/ml in adults. CONCLUSIONS: Less than half of the subjects with VDD have SHPT. BMD levels start to decline at PTH values currently considered to be normal. These data suggest the need to redefine SHPT in different age groups keeping in mind the relationship between PTH and BMD. This may also influence the decision to supplement subjects with VDD.

HSV-1 as well as HSV-2 is frequent in oral mucosal lesions of children on chemotherapy.

PURPOSE: Prevalence data of herpes simplex virus (HSV) in oral mucositis in children on treatment for cancer is limited. Quantitative polymerase chain reaction (PCR) has been seldom utilized for detection of HSV-1/2 in oral mucosa. METHODS: Children on treatment for cancer with oral mucositis were enrolled as cases and healthy children as controls. An oral swab from the lesion in cases and mucosal scraping in controls were obtained. Both qualitative and real-time quantitative PCR for HSV-1/2 were performed. Serum ELISA-IgG/IgM for HSV-1/2 antibodies (NovaLisa™-Dietzenbach-Germany) were measured. RESULTS: Thirty-two cases (Age, 6.3±3.4 years) and 30 controls were enrolled. Majority (69%) of cases had ALL. All patients had febrile neutropenia, except two. ELISA-IgM-HSV-1/2 was not positive in any case or control. ELISA-IgG-HSV-1/2 was positive in 11 (34%) cases and nine (30%) controls (p=1.0). Qualitative PCR for HSV-1 detected the virus in eight (25%) cases and nil controls (p=0.009). HSV-2 was not detected in any case/control by qualitative PCR. Quantitative PCR detected HSV-1 in 21 (66%) and HSV-2 in 22 (69%) cases. In controls, quantitative PCR detected HSV-1 in three (10%) and HSV-2 in none. In patients, the mean viral load of HSV-1 (5,500±15,987×10(4) copies/nanogram DNA) was more than HSV-2 (4.03±8.5×10(4)) (p=0.11). There was no correlation of HSV-1/2 with grading of mucositis. CONCLUSIONS: Both HSV-1/2 are commonly shed from oral mucosal lesions in children receiving chemotherapy. In a novel finding, real-time PCR detected copies of HSV-2 in 69% cases, all missed by conventional PCR. Implication for morbidity, if any, or treatment needs to be determined.

Impact of vitamin D fortified milk supplementation on vitamin D status of healthy school children aged 10-14 years.

UNLABELLED: Vitamin D deficiency is a major public health problem, needing immediate attention. We studied the effect of vitamin D fortification of milk in school children. Our results show that fortification of milk is safe and effective strategy to deal with widespread vitamin D deficiency. INTRODUCTION: Vitamin D deficiency among school children and adolescents is a well-documented major public health problem, needing immediate attention. To assess the effect of vitamin D fortified milk on serum 25 hydroxy vitamin D [S.25(OH)D] levels, we carried out a prospective double-blind randomized control trial in apparently healthy school children, aged 10-14 years. METHODS: Of 776 subjects recruited out of 796 who consented, 713 (boys-300; girls-413) completed the study. Subjects were randomized into three groups. Group A (n = 237) received 200 ml of unfortified milk per day while group B (n = 243) and group C (n = 233) received 200 ml of milk fortified with 600 IU (15 µg) and 1,000 IU (25 µg) of vitamin D per day for 12 weeks. Serum calcium, phosphate, alkaline phosphatase, S.25(OH)D, and urinary calcium/creatinine ratio were estimated at baseline and after supplementation. RESULTS: Hypovitaminosis D [25(OH)D < 20 ng/ml] was observed in 92.3 % subjects with mean S.25(OH)D level of 11.69 ± 5.36 ng/ml. There was no significant difference in S.25(OH)D levels among the three groups at baseline. The mean percentage change in S.25(OH)D level in groups B (137.97 %) and C (177.29 %.) were significantly greater than group A (-5.25 %). The percentage of subjects having S.25(OH)D levels >20 ng/ml following supplementation were 5.9 % in group A, 69.95 % in group B, and 81.11 % in group C in comparison to 6.32 %, 4.9 % and 12 %, respectively, at baseline. CONCLUSION: Fortification of milk with vitamin D is an effective and safe strategy in improving S.25(OH)D levels in children aged 10-14 years.

Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF-1 axis.

BACKGROUND: The frontline treatment for chronic myeloid leukemia (CML) is tyrosine kinase inhibitor therapy. There is increasing evidence that imatinib results in growth failure in children; etiology is unclear. PROCEDURE: The cross-sectional study was conducted from January 2011 to June 2012 in a pediatric oncology unit. Patients with chronic-phase CML, receiving imatinib for more than 6 months were enrolled. Growth hormone (GH): Insulin like growth factor-1 (IGF-1) axis was evaluated by GH stimulation test by insulin tolerance and clonidine stimulation test, among other hormonal assays. RESULTS: Eighteen patients with a median age of 12.9 years (range 6.5-17) completed the study. The mean duration of imatinib therapy was 43.7 ± 32.8 months. The height-for-age z-scores at the start of imatinib and at enrollment were -1.07 ± 0.88 and -1.8 ± 0.98, respectively (P < 0.001). Seven (39%) patients were GH deficient and lacked a sufficient response to either of the two stimulation tests. Majority, 16 (89%) patients had IGF-1 z-scores less than the mean. IGFBP-3 levels were below the mean in all patients. Every patient had deficiency of either GH, or IGF-1, or both. Bone age was delayed in 7 (39%). CONCLUSIONS: This study demonstrates that imatinib results in growth failure in children with CML by disturbing the GH:IGF-1 axis. GH stimulation test and serum IGF-1 levels should be performed in children on treatment with imatinib who have growth retardation. Future studies should evaluate the role of recombinant GH therapy for ameliorating the adverse effect on growth.

Symptom to door interval in febrile neutropenia: perspective in India.

PURPOSE: Febrile neutropenia (FN) is an oncological emergency to be treated within an hour. In a developing country, patients are often unable to reach hospital speedily. Our aim was to determine the symptom to door interval (SDI) in febrile neutropenic children with acute lymphoblastic leukaemia [ALL] and to identify factors resulting in delay. METHODS: All consecutive children of ALL (< 14 years) presenting with FN over a period of 1 year were evaluated. Data for demographics, clinical details, phase of therapy, profile of caregivers, travelling time, SDI, reasons for delay, modes of transport, complications, invasive bacterial infections (IBI), length of hospital stay and outcome were recorded. RESULTS: Among 320 FN episodes, median SDI (in hours) was 24 (IQR 8, 36). SDI during intensive phases was significantly less as compared to nonintensive phases 12 (IQR 6, 24) and 24 (IQR 24, 48) (p < 0.001). Children on induction phase reported to hospital at earliest [median 8 (IQR 4, 12)], while those on maintenance phase came late [median 36 (24, 48)]. Median travelling time was 15 min (IQR 15, 25) for patients on intensive phase and was 180 min (IQR 60, 285) for those on nonintensive phase (p< 0.001). Ingestion of acetaminophen at home (30 %), inability to realise the gravity of the situation (27 %), unawareness of parents (9 %) and nonavailability of transport (12 %) were the most common reasons for delay. No significant association of SDI was seen with complications, IBI, duration of hospital stay and mortality (p > 0.05). CONCLUSIONS: Considerable time lag was seen between onset of symptoms and reaching hospital. Health education and establishment of shared care are urgent needs in countries where tertiary care facilities are limited.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

BACKGROUND & OBJECTIVES: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. METHODS: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. RESULTS: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. INTERPRETATION & CONCLUSIONS: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Tropical pyomyositis in children: 10 years experience of a tertiary care hospital in northern India.

Tropical pyomyositis (TP) is characterized by suppuration within skeletal muscles, manifesting as single or multiple abscesses. It has been reported frequently from Africa and Latin America. However, there are only a few cases reported in children from India. Between January 2002 and December 2011, 40 children with TP were admitted to our hospital, and their retrospective review formed the study material. TP is not an uncommon disease in children in Northern India, especially during rainy seasons. Most of the patients were admitted with short history of fever, pain and localized swelling. Pus drainage was done in 87.5% cases, with the amount of pus varying from 5 to 2000 ml. The pus grew methicillin-sensitive Staphylococcus aureus (MSSA) in 42.5% cases, whereas initial blood cultures were sterile. All received antibiotics along with surgical drainage, and recovered. It is important for health professionals to have a high index of suspicion and familiarity with this imminently treatable disease entity.

Imatinib has adverse effect on growth in children with chronic myeloid leukemia.

BACKGROUND: Long-term adverse effects of Imatinib in children with chronic myeloid leukemia (CML) are uncertain. The aim was to study the effect of imatinib on growth in children with CML. PROCEDURE: Children ≤13 years of age at diagnosis were enrolled retrospectively, from 2004 to 2011, from a single center in India. Patients who received imatinib for >1 year were included for growth assessment. Height standard deviation scores (SDS) were derived from WHO-AnthroPlus, a global growth monitoring tool. RESULTS: Thirty-four children received imatinib. Twenty children fulfilled the criteria for assessment of growth. Median age was 10 years (range: 2-13). Of 20 children, 13 were prepubertal at commencement of imatinib. The mean duration of imatinib in 20 children was 61.3 ± 16.2 months (range: 31-83). No patient was treated with a second-generation tyrosine kinase inhibitor or a stem cell transplant. Highly significant reduction in height SDS's was observed (P = 0.002 at 5th year). Children who started imatinib therapy after the onset of puberty were immune to this adverse effect (P = 0.448 and 0.003 at 5th year of treatment for pubertal and prepubertal children, respectively). The 5-year survival probability of 33 children who received imatinib in chronic phase was 80% with a median survival time of 60 months (mean: 70.2; 95% CI: 60-80.5). CONCLUSIONS: Growth retardation is a significant adverse effect of imatinib in children with CML. The failure to gain appropriate height was most discernible when imatinib was initiated in the prepubertal period. Etiology and remedial measures need to be investigated.

Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

BACKGROUND: Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. AIM/OBJECTIVE: In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. SUBJECTS AND METHODS: Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. RESULTS: We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. CONCLUSIONS: 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

Iron deficiency anemia in children presenting with lymphoreticular malignancies and the effect of induction therapy.

There is scant information regarding iron deficiency in children with malignant disorders. Serum iron status of children with lymphoreticular malignancies (LRMs) at onset and at the end of induction therapy, compared to the normal population, was evaluated. Prospective cohort study conducted between July 2002 and March 2004. Previously untreated children recently diagnosed with LRM were studied. Age-matched controls were enrolled from follow-up and growth monitoring clinics. Hematological (complete blood counts and red cell indices) parameters and markers of iron status (serum iron, serum ferritin, total iron binding capacity) were estimated at presentation and at the end of remission induction therapy, that is, 5 weeks after initial evaluation. Bone marrow iron store were only assessed in cases. Thirty-five children (31 with acute lymphoid leukemia, 2 with acute myeloid leukemia, and 2 with non-Hodgkin lymphoma; 27 boys and 8 girls; 2 to 12 years of age) were evaluated in the study cohort. Anemia was documented in 80% of children with LRM. Iron deficiency was an important etiological factor. In the majority of cases therapy resulted in significant improvement towards normalization of deranged hematological parameters. This phenomenon could be attributed to enhanced quantity and quality of erythropoietic activity and red cell transfusions. The observation suggests that therapeutic iron supplements are not indicated in the majority of children on therapy for malignant disorders. Various hematological and body iron status parameters should be assessed on a case-by-case basis.

Indian Academy of Pediatrics Revised (2021) Guidelines on Prevention and Treatment of Vitamin D Deficiency and Rickets.

JUSTIFICATION: The emerging literature on prevalence of vitamin D deficiency in India, prevention and treatment strategies of rickets, and extra-skeletal benefits of vitamin D suggest the need for revising the existing guidelines for prevention and treatment of vitamin D deficiency in India. OBJECTIVES: To review the emerging literature on vitamin D prevalence and need for universal vitamin D supplementation. To suggest optimum vitamin D therapy for treatment of asymptomatic and symptomatic vitamin D deficiency, and rickets. To evaluate the extra-skeletal health benefits of vitamin D in children. PROCESS: A National consultative committee was formed that comprised of clinicians, epidemiologists, endocrinologists, and nutritionists. The Committee conducted deliberations on different aspects of vitamin D deficiency and rickets through ten online meetings between March and September, 2021. A draft guideline was formulated, which was reviewed and approved by all Committee members. RECOMMENDATIONS: The group reiterates the serum 25-hydroxy vitamin D cutoffs proposed for vitamin D deficiency, insufficiency, and sufficiency as <12 ng/mL, 12-20 ng/mL and >20 ng/mL, respectively. Vitamin D toxicity is defined as serum 25OHD >100 ng/mL with hypercalcemia and/or hypercalciuria. Vitamin D supplementation in doses of 400 IU/day is recommended during infancy; however, the estimated average requirement in older children and adolescents (400-600 IU/day, respectively) should be met from diet and natural sources like sunlight. Rickets and vitamin D deficiency should be treated with oral cholecalciferol, preferably in a daily dosing schedule (2000 IU below 1 year of age and 3000 IU in older children) for 12 weeks. If compliance to daily dosing cannot be ensured, intermittent regimens may be prescribed for children above 6 months of age. Universal vitamin D supplementation is not recommended in childhood pneumonia, diarrhea, tuberculosis, HIV and non-infectious conditions like asthma, atopic dermatitis, and developmental disorders. Serum 25-hydroxy vitamin D level of >20 ng/mL should be maintained in children with conditions at high-risk for vitamin deficiency, like nephrotic syndrome, chronic liver disease, chronic renal failure, and intake of anticonvulsants or glucocorticoids.

Bone health in healthy Indian population aged 50 years and above.

UNLABELLED: One thousand six hundred healthy subjects aged more than 50 years, residing in Delhi, were evaluated for bone mineral metabolic parameters. High prevalence of osteoporosis (35.1% subjects) was observed in this population. Bone mineral density (BMD) correlated positively with body mass index (BMI) and negatively with PTH levels. No correlation was observed with serum 25(OH)D levels. INTRODUCTION: To assess the bone health status in elderly Indians and compare peripheral DXA (pDXA) with central DXA in evaluation of osteoporosis. METHODS: The study involved 1,600 healthy subjects more than 50 years of age residing in Delhi, India, who underwent anthropometric, biochemical, and hormonal evaluation. BMD was measured by DXA at lumbar spine, hip, and distal radius; and by pDXA at forearm and calcaneum. RESULTS: Seven hundred ninety-two males and 808 postmenopausal females, with a mean age of 57.67 ± 9.46 years were evaluated. Osteoporosis was present in 35.1% subjects (M-24.6%, F-42.5%) and osteopenia in 49.5% (M-54.3%, F-44.9%). Prevalence of osteoporosis increased with age in females, but not in males. BMD at all sites, except distal radius, was positively correlated with BMI (r=0.037, p=0.14). Total body BMD was negatively correlated with alkaline phosphatase (r= -0.184, p<0.00001) and PTH levels (r= -0.099, p<0.00001), respectively. No significant correlation was observed between serum 25(OH)D levels and BMD at any site. BMD at forearm and calcaneum, measured using pDXA, showed strong positive correlation with BMD measured by central DXA. pDXA had sensitivity of 88%, specificity of 55%, and negative and positive predictive values of 89% and 52%, respectively, at T-score -2.5 at peripheral sites compared to central DXA. CONCLUSIONS: A high prevalence of osteoporosis was observed in elderly Indian subjects. pDXA has high negative predictive value, making it a useful tool in population screening for osteoporosis.