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.

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.

Inherited Bleeding Disorders in North Indian Children: 14 years' Experience from a Tertiary Care Center.

Inherited bleeding disorders are not uncommon in pediatric practice: most of them being chronic, require lifelong replacement therapy. To frame a management policy, it is essential to assess the load and pattern of bleeding disorders in the local population. However, there is paucity of data reporting the clinical spectrum of coagulation and platelet function disorders in Indian children. Hence to find out the exact burden and clinico-investigational profile of these patients we conducted this study. In this retrospective case review, detailed clinical information was extracted from case records in 426 children with a suspected diagnosis of hereditary bleeding disorder registered in the Pediatric Hematology clinic of a tertiary referral centre over a period of 14 years (1998-2011) and pooled for analysis. In our cohort prevalence of hemophilia A, hemophilia B, platelet function disorders, von Willebrand disease and other rare factor deficiencies were 72%, 11%, 7%, 4% and 4% respectively. Common clinical spectrum included skin bleeds, arthropathy, mucosal bleeds. 10% had deeper tissue bleeding and 16% received replacement therapy at the first visit. Nearly 3/4th of cases were lost for follow up after the initial visit. Hemophilia A was the commonest inherited bleeding disorder in our population. Skin bleeds and arthropathy were common clinical presentations. Factor replacement therapy was restricted to a minority. There is an urgent need for establishing centres of excellence with administrative commitment for factor replacement therapy for comprehensive management of such children in resource-limited countries.

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.

Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population.

Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. AIM: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. RESULTS: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. CONCLUSIONS: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.

Characterization of immunophenotypic aberrancies in adult and childhood acute lymphoblastic leukemia: A study from Northern India.

BACKGROUND: Identification of aberrant antigen expression is important in characterizing neoplastic population among non.neoplastic bone marrow counterparts and further in the detection of minimal residual disease. (MRD). Flow cytometry (FCM) is an important tool in identifying aberrant phenotypes. Incidence of aberrant phenotypes varies considerably in independent studies and its association with prognostic factors is still debatable. AIM: To identify the prevalence of aberrant phenotypes on immunophenotyping in a large series of de novo acute lymphoblastic leukemia (ALL) and to evaluate any association with initial clinical and hematological features. MATERIALS AND METHODS: In the current study, 303 patients of de novo ALL were included from the Department of Hematology, PGIMER, Chandigarh during the time period (July 2010 to June 2012). The immunophenotype of all cases of ALL was studied using FCM. RESULTS: Aberrant myeloid antigen expression was seen in 42.5% cases. Most frequent aberrant myeloid antigen was CD13 (32.2% cases), followed by CD33 (27.2% cases) and CD117 (18.5% cases). The expression of CD117 was relatively frequent in comparison to earlier reports which describe its rare expression. Adult T- ALL showed higher expression of CD33 and CD117 than pediatric T-ALL (P = 0.032 and 0.043, respectively). Myeloid antigen expression in ALL was associated with lower WBC count (P < 0.05) and lower number of peripheral blasts (P < 0.05). Expression of CD34 was higher in My + ALL group (P < 0.05) than My- ALL group. CONCLUSION: In summary, CD117 is a relatively frequently expressed myeloid marker contrary to earlier reports which describes its rare expression. Pediatric and adult ALL cases with low blast count and CD34 positivity are more likely to express aberrant myeloid markers. Current study also supports that myeloid antigen expression in both adult and pediatric ALL is not associated with adverse presenting clinical and biological features.

Age of Onset of Puberty in Apparently Healthy School Girls from Northern India.

OBJECTIVE: To determine the age of pubertal onset and menarche in school-going girls, and to assess the impact of obesity on pubertal timing. DESIGN: Cross-sectional. SETTING: Seven schools across Delhi, India. PARTICIPANTS: 2010 school girls, aged 6-17 years. METHODS: Anthropometric measurement and pubertal staging was performed for all subjects. Menarche was recorded by status quo method. Body mass index was used to define overweight/obesity. Serum gonadotropins and serum estradiol were measured in every sixth participant. MAIN OUTCOME MEASURES: Age at thelarche and menarche analyzed for entire cohort and stratified based on body mass index. RESULTS: Median (95% CI) ages of thelarche, pubarche and menarche were 10.8 (10.7-10.9) y, 11.0. y (10.8-11.2) y and 12.4 y (12.2-12.5) y. Overweight/obese girls showed six months earlier onset of thelarche and menarche than those with normal BMI (P<0.05). Serum gonadotropins did not vary significantly in overweight/obese subjects. CONCLUSION: The study provides the normative data for pubertal growth in Indian girls. Pubertal onset occurs earlier in overweight and obese girls.

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.

Growth in Children Treated for Acute Lymphoblastic Leukemia: Single Institution Report from North India.

Survivors of childhood leukemia are at risk of impaired growth and short stature as adults due to intensive combination chemotherapy and radiation injury. This study was undertaken to evaluate anthropometry in children treated for acute lymphoblastic leukemia (ALL). Children treated for ALL and off treatment for a minimum period of 2 years were evaluated for height, weight and BMI. Z scores were calculated for height, weight and BMI: at induction, 6 months after starting treatment, at end of treatment and at 2 years after completion of therapy. Change in z scores were calculated and compared with CDC criteria and Agarwal standards for Indian children. Fifty two boys and 21 girls were analyzed. Height and weight z scores were seen to show a steep decrease during the initial intensive phase of therapy. The gain in height and weight continued to be slow during therapy and catch up occurred after cessation of therapy. On completion of therapy, patients were shorter, but not significantly so. Girls <9 years were significantly shorter. Weight remained on the lower side of normal. Change of z scores was statistically significant for weight at end of treatment (p = 0.032) and 2 years after completion of treatment (p = 0.00). BMI z score increased throughout the study period. Peak growth velocities were also late in the study subjects Anthropometric variables of height, weight and BMI are affected by ALL during therapy. Growth deceleration is maximum during the intensive phase of therapy. Catch up growth occurs but children remain smaller than their peers.

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.

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.

Bone marrow infiltration in Langerhan's cell histiocytosis - An unusual but important determinant for staging and treatment.

BACKGROUND: Langerhans' cell histiocytosis (LCH) is a reactive proliferative disease of unknown pathogenesis characterized by proliferation of Langerhans cells. Involvement of bone marrow (BM), liver and lung are related to high risk factors and poor survival. The aim of this report is to highlight the clinical and haematological findings of 5 cases of LCH with BM infiltration which may help to predict involvement of BM. CASE SERIES: Five cases of Langerhan's cell histiocytosis with bone marrow infiltration were retrieved from archives of Department of Hematology, PGIMER and Chandigarh for review and further analysis. Male to female ratio was 3:2 with mean age of 9.4 months. Two out of 5 patients had obvious skull swelling; however, radiography of the skull revealed lytic lesion of skull in 4 cases and 2 had skin rashes. Hepatomegaly was present in 4 cases and 2 of whom also had lymphadenopathy and splenomegaly. All patients had anaemia at the time of presentation. Bone marrow aspiration and trephine biopsy in all 5 cases revealed infiltration by large histiocytes with abundant cytoplasm and coffee bean shaped nucleus. Nodules of these Langerhans cells with admixture of eosinophils were seen on trephine biopsy. Immunohistochemistry showed positivity for CD1a stain. CONCLUSION: BM evaluation is important in LCH patients to categorize disease which further determines the type of therapy to be given. Clinical details may help to predict the BM involvement; however, demonstration of CD1a positive cells in marrow is most important tool to diagnose marrow infiltration by LCH.

Clinicoinvestigational and demographic profile of children with thalassemia major.

There are an estimated 200 million carriers of the ß-thalassemia gene worldwide, 20 million being in India. The mean prevalence in India is 3.3 %. Objective To evaluate the clinico-investigational profile and the demographic characteristics of patients with thalassemia major (TM). Methods This was a retrospective analysis of the clinico-demographic profile at presentation of patients of TM diagnosed in the Paediatric Hematology Clinic of our hospital. Results The clinical profile of 964 patients of TM was analyzed. The mean age at presentation of untransfused children was 13.2 ± 9.7 months. Nearly 2/3(rd) children presented before 1 year of age. Almost 40 % had symptoms for 3 months prior to presentation. The manifestations at presentation included pallor and failure to thrive. About 40 % presented with severe anemia, with a hemoglobin of <5.0 gm/dl. A large number received blood transfusions prior to establishment of the diagnosis. Half of the families had ancestors who hailed originally from Pakistan. Approximately 50 % belonged to the Khatri/Arora castes. The parental literacy rate was about 90 %. Conclusions Thalassemia needs greater public awareness and prevention strategies in our country. Some communities are at high risk as compared to others. Education programs and compulsory antenatal screening appear to be the order of the day.

Impact of iron deficiency on hemoglobin A2% in obligate ß-thalassemia heterozygotes.

INTRODUCTION: The potential impact of concomitant iron deficiency on hemoglobin A2 (HbA2)-based identification of ß-thalassemia trait (ßTT) is a worrisome issue for screening laboratories. This is especially true for resource-constrained settings where iron deficiency is widespread and molecular confirmatory tests for borderline low HbA2 values may be unavailable. METHODS: Obligate ßTT carrier individuals (n = 752) were identified during screening studies on the parents of thalassemia major patients. HbA2%, complete blood counts and serum iron, ferritin and transferrin saturation were studied. Iron-deficient individuals (n = 135) with normal range HbA2% were taken as controls. RESULTS: Concomitant iron deficiency (defined as ferritin ≤15 ng/mL and/or transferrin saturation ≤15%) was present in 20.7% (156/752) ßTT cases, that is, 33.3% females (122/366) and 8.8% males with ßTT (34/386). Mean HbA2 in iron-replete ßTT was 5.4 ± 0.8 (range 3.1-7.9) and in iron-deficient ßTT was 5.4 ± 0.9 (range 3.3-7.6). HbA2 < 4.0% was found in 23/752 (3.1%) ßTT: 13/595 iron-replete (2.2%) and 10/157 (6.4%) iron-deficient ßTT individuals. However, five of the 10 iron-deficient ßTT cases carried the silent CAP+1 (A>C) ß-thalassemia allele accounting for the borderline HbA2%. On a separate analysis, all five severely anemic ßTT (Hb < 80 g/L) and 16/17 ßTT with severe hypoferritinemia (<5 ng/mL) had HbA2 > 4.5%. The single case with serum ferritin 4.8 ng/mL and HbA2 3.3% showed a CAP+1 (A>C) mutation. CONCLUSIONS: Iron deficiency was prevalent among north Indian ßTT individuals, especially women. After adjusting for other causes of low HbA2 in ßTT, iron deficiency, even when very severe, was very unlikely to interfere significantly with HbA2-based identification of ßTT.

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.

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.

Serum ferritin in thalassemia intermedia.

Serum ferritin is a useful monitoring tool for iron overload in thalassemia major. In resource poor settings access to modalities for assessment of iron overload are limited. This study was undertaken to assess the efficiency and usefulness of serum ferritin level in thalassemia intermedia (TI) patients. This was a cross sectional observational study. Seventy seven TI patients attending the pediatric hematology clinic were included. Fasting blood sample was taken from each patient in iron free vials for iron studies. Serum ferritin was estimated by immunometric enzyme immunoassay using Orgentec GmbH kits. Mean age of patients evaluated was 10.9 ± 5.03 (3-26) years. The mean age at diagnosis was 4.21 ± 2.3 (0.8-11) years. Mean serum ferritin was 486.54 ± 640.0 ng/ml (15-4,554). Thirty two (41.5 %) patients had a ferritin value of ≥500 ng/ml. Nine patients had a serum ferritin of ≥1,000 ng/ml. Three of the subjects with a ferritin >1,000 ng/ml had never received a blood transfusion (BT) and in the other six, the number of BTs ranged from 1 to 8. Serum ferritin did not correlate with age, total number of BTs splenectomy status or BT in last one year (p > 0.05). In 41.5 % of TI patients, serum ferritin was ≥500 ng/ml. Age, BT and splenectomized status did not affect ferritin level. We postulate interplay of other biological factors like HFE gene mutation, ferroportin, etc. to contribute to ferritin level and hence iron load in TI patients. Ferritin can possibly be used as screening and monitoring tool for iron load in TI patients when other modalities to assess iron overload are not easily available.