A Prospective, Randomized, Interventional Study of Oral Iron Supplementation Comparing Daily Dose with Alternate Day Regimen Using Hepcidin as a Biomarker in Iron Deficiency Anemia.

AIM: To assess effect of daily vis-a-vis alternate day oral iron therapy in terms of hemoglobin, reticulocyte hemoglobin equivalent (RET-He) and GI side effects using hepcidin as a biomarker. METHODS: A hospital based randomized interventional two-arm analytical study was done among patients of IDA (20 in each group). The study population was divided into two groups by randomisation. Group 1 received oral iron supplements on alternate day and Group 2 received iron supplements daily. Hemoglobin, RET-He, Serum ferritin and Hepcidin level were assessed. RESULTS: On day 2nd, the rise in Hepcidin was not significant from base line in alternate day therapy group but was significantly increased in daily therapy group. On day 3, the rise in hepcidin was significant from base line in both the groups but the mean change in hepcidin was more in daily therapy group. RET-He began increasing on day 2nd in both the groups. In alternate day therapy group, the rise in RET-He was significant from base line from the day 2nd onwards while the rise in RET-He in daily therapy group was not significant even on day 3. In alternate day iron therapy group, the mean increase in hemoglobin on day 21th (1.58 ±0.53 gm/dl) was significantly more than mean increase among daily therapy (0.41 ± 0.25 gm/dl, P <0.05). CONCLUSION: Alternate day single tablet dosing schedule of oral iron therapy (60mg of elemental iron, ferrous sulfate) was more effective and better tolerated (gastrointestinal side effects) compared to daily supplementation in IDA.

Hemophagocytic Lymphohistiocytosis in a Patient of Scrub Typhus.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but aggressive and potentially fatal condition characterized by excessive immune activation. It can occur as primary/ familial and secondary/sporadic/ acquired form. Infections can play a role as triggers in the secondary form of HLH. A case of Hemophagocytic lymphohistiocytosis (HLH) in a patient of Scrub typhus is being reported here. Such association of scrub typhus and HLH is rare.

Assessment of Pituitary Gonadal Axis and Sperm Parameters in Anemic Eugonadal Males Before and After Correction of Iron Deficiency Anemia.

ABSTRACT: :Iron deficiency anemia (IDA) is one of the most common nutritional anemia worldwide. Anemia imposes a significant hypoxic environment in different organs and tissues including the testes. This study evaluated the effect of treatment of IDA on the pituitary gonadal axis (Serum FSH, LH, Testosterone) and sperm parameters in adult eugonadal males. METHODOLOGY: A hospital based interventional, analytic study was conducted at a tertiary care center among 25 eugonadal males (fully sexually developed, fertile) with newly diagnosed and untreated IDA, admitted in medicine wards and not suffering from any inflammatory disorders (excluded by C-reactive protein) after exclusion of patients having other forms of anemia/ hemoglobinopathies/ any malignancy/having MCV >80 fL, aplastic anemia and primary hypogonadism. Sexual maturation was assessed according to maturity stages 5. Investigations were performed before and 6 weeks after treatment of IDA with intravenous iron sucrose included CBC, peripheral blood smear, serum ferritin, serum iron, TIBC, serum FSH, serum LH, serum Testosterone and semen analysis (Semen volume, Sperm count, Sperm motility and Sperm morphology). RESULTS: The change in mean Hb level before (5.66 ± 1.97gm/dl) and after treatment (11.96 ± 0.87 gm/dl) was statistically significant. (P<0.001) Patients who had subnormal and normal serum level of FSH, LH, Testosterone and sperm parameters before treatment were divided into group A and group B respectively. Serum levels of FSH, LH and testosterone along with sperm parameters significantly improved after correction of anemia (p<0.01). The mean change in these parameters was significantly higher in patients having subnormal value of these parameters before treatment (Group A) than in patients having normal pre-treatment level (Group B) (p<0.01). The level of anemia (hemoglobin) had significant positive correlation with serum FSH, serum LH, serum testosterone levels and sperm parameters (semen volume, sperm count, sperm morphology, RPM and sperm motility) (p<0.001). CONCLUSION: IDA had significant negative association with the pituitary gonadal axis (Serum FSH, LH, Testosterone) and sperm parameters in adult eugonadal males. The serum levels of FSH, LH and testosterone along with sperm parameters significantly improved after correction of anemia, especially in patients having subnormal value of these parameters.

Reticulocyte Hemoglobin Vis-À-Vis Immature Reticulocyte Fraction, as the earliest Indicator of Response to Therapy in Iron Deficiency Anemia.

AIM: To evaluate reticulocyte hemoglobin (RET-Hb) vis-à-vis immature reticulocyte fraction (IRF) as an earliest indicator of response to iron therapy in iron deficiency anemia (IDA), by assessing change in RET-He and IRF at 48 hours after initiation of intravenous iron therapy. MATERIAL AND METHODS: A hospital based interventional, analytic study was conducted among 144 patients (age group 15-65 years) with newly diagnosed and untreated IDA admitted in medicine ward and not suffering from any inflammatory disorders (excluded by C-reactive protein). Patient having other forms of anemia/hemoglobinopathies/ malignancy, MCV >80 fL and pregnant female were excluded. All patients were subjected to automated CBC, RET-He, iron studies and iron staining of bone marrow aspirates. Then intravenous iron sucrose was given along with oral antioxidants. After 48 hours, CBC, RET-He and IRF were repeated for each patient. RESULT: Total 144 patients were included. Of these, 42 patients were excluded due to aparticulate bone marrow aspirate. Remaining 102 patients were classified in to Group A (grade 0 and 1- depleted iron stores) and Group B (grade 2 and 3 - functional iron deficiency). RET-He and IRF increased significantly at 48 hours after initiation of intravenous iron therapy (post therapy) as compared to baseline (pre therapy) in both the two groups as well when all patients were considered together. Post therapy, the mean increase in RET-He was significantly smaller in magnitude in group B than in group A. The increase in IRF was not significantly different between the two groups. CONCLUSION: RET-Hb, a real time indicator of iron supply (hemoglobinization) to the developing RBC's, is the earliest marker of response to iron therapy as compared to IRF (representative of reticulocyte count).

Reticulocyte Hemoglobin vis-a-vis Serum Ferritin as a Marker of Bone Marrow Iron Store in Iron Deficiency Anemia.

AIM: To evaluate reticulocyte hemoglobin (RET-He) vis-a-vis serum ferritin as a marker of bone marrow iron store in iron deficiency anemia (IDA). MATERIAL AND METHODS: A hospital based analytic study was conducted among patients (age group 15-65 years) with newly diagnosed and untreated IDA admitted in medicine ward and not suffering from any inflammatory disorders (excluded by C-reactive protein). Patient having other forms of anemia/ hemoglobinopathies/ malignancy, MCV > 80 fL and pregnant female were excluded. All patients were subjected to automated CBC, RET-He, iron studies and iron staining of bone marrow aspirates. RESULTS: Total 142 patients were included. Of these, 42 patients were excluded due to aparticulate bone marrow aspirate. Remaining 102 patients were classified in to Group A (grade 0 and 1-depleted iron stores) and Group B (grade 2 and 3 - functional iron deficiency). There were significant difference in means of RET-He (Group A 17.84 ± 2.39 vs. Group B 25.08 ± 4.42; P< 0.0001) and serum ferritin (Group A 8.68 ± 2.80 vs. Group B 15.61 ± 4.68; P < 0.0001). We observed significant positive correlation of ferritin with RET-He in total patients (r = 0.7860, p 0.0000), Group A (r = 0.7089, p 0.00) and Group B (r = 0.4675, p < 0.05) patients. RET-He was the only significant predictor of bone marrow iron stores (at P < 0.05). On ROC curve analysis, the AUC for RET-He was found to be 0.894 (P value < 0.01) and best cut off value for predicting IDA was 22.4 pg (sensitivity 98.88%, specificity 84.21%). The AUC for serum ferritin was 0.891 (P value < 0.01) and best cut off value for predicting IDA was 11.6 ng/ml (sensitivity 86.75%, specificity 89.47 %). CONCLUSIONS: RET-He correlated significantly with serum ferritin and is also a better predictor of bone marrow iron stores than the latter.

Detection of mutations in TERT, the genes for telomerase reverse transcriptase, in Indian patients of aplastic anaemia: a pilot study.

AIM: Detection of mutations in the genes for telomerase reverse transcriptase (TERT) in patients of apparently acquired aplastic anaemia. MATERIAL AND METHODS: Five patients with apparently acquired aplastic anaemia and six unrelated healthy individuals were recruited for this study. The genomic DNA was extracted from whole blood of subjects (patients and controls) and amplified by Polymerase chain reaction. The amplified products were sequenced and analysed in an automated genetic-sequence analyser to identify mutations in genes encoding telomerase complex - namely DKC1, NOP10, NHP2, and TERT. RESULT: In this study, mutations were observed in both coding and non-coding regions of TERTgene. Out of five patients, four patients had novel nonsynonymous mutation in TERT. Another substitution mutation was found in DKC1 gene in a healthy control. There was an important observation that two healthy controls had mutations in the coding region of TERTand DKC1 genes, but no symptoms or haematological abnormalities were expressed in both controls.There was no significant difference observed (Z = 0.666; P = 0.506) between two groups (controls and patients) with respect to no. of individuals having mutations. CONCLUSION: The present study was undertaken to evaluate the mutation spectrum in the genes implicated in aplastic anaemia, i.e. TERT, DKC1, NOP10, and NHP2 in small case-control group (5 + 6). We have been successful in finding mutations in TERTand DKC1 while no population specific mutations were found in NOP10 and NHP2. The statistical significance of these mutations is difficult to establish as the sample size was too low. None of the patients with TERT mutations had a response to immunosuppressive therapy.

Human Leukocyte Antigen-DQ Genotyping in Pediatric Celiac Disease.

Purpose: The purpose of this study was to determine the pattern of human leukocyte antigen (HLA)-DQ genotype in children diagnosed with celiac disease (CD) (biopsy proven), and to compare this with a control group; and secondarily, to correlate HLA genotypes with clinical profiles of CD. Methods: This cross-sectional comparative observational study included 26 controls and 52 patients diagnosed with CD who presented at Sir Padampat Mother and Child Health Institute, Jaipur, from May, 2017 to October, 2018. HLA DQ genotype was assessed for each patients and correlated with clinical profiles. Results: HLA DQ2/DQ8 genotypes were significantly more common in CD (present in 100.0% cases) than in controls (23.1%) in Northern India (Rajasthan). When HLA DQ2.5 and DQ8 were present together, individuals had significantly more atypical presentations and severe findings on duodenal biopsy. Similarly, patients with the HLA DQ 2.5 genotype were also predisposed to more severe endoscopic findings, while HLA DQ2.2 predisposed them to less severe biopsy findings. HLA DQ8 was significantly associated with later age at diagnosis (>5 years) and shorter stature. The highest HLA DQ relative risk (RR) for CD development was associated with HLA DQ2.5 and DQ2.2 in combination, followed by HLA DQ2.5 and DQ8 in combination, while HLA DQx.5 and HLA DQ2.2 together had the lowest risk. Conclusion: HLA DQ2/DQ8 genotypes are strongly associated with pediatric CD patients in northern India. These genotypes and their combinations may be associated with different clinical presentations of CD, and may help predict severity of CD.

Congenital B-cell Acute Lymphoblastic Leukemia with Congenital Rubella Infection.

BACKGROUND: Congenital B-cell Acute lymphoblastic leukemia (ALL) is a rare malignancy. CHARACTERISTICS: A newborn infant presented with purpuric spots and ecchymotic patches, blueberry muffin rash, depressed neonatal reflexes, respiratory distress and hepatosplenomegaly. Peripheral smear revealed atypical blast cells. Serum ELISA was positive for Rubella IgM and IgG antibodies. Flow cytometry suggested congenital B-cell ALL. OUTCOME: The baby died after 3 days due to suspected intracranial hemorrhage. MESSAGE: Congenital leukemia may be rarely associated with congenital rubella infection.

Mean platelet volume in patients with acute coronary syndromes: a supportive diagnostic predictor.

BACKGROUND: Platelets and their activity have a crucial role in acute coronary events. Larger platelets are enzymatically and metabolically more active and have a higher potential thrombotic ability as compared with smaller platelets. OBJECTIVES: The aim of this study is to investigate whether there is an association between mean platelet volume (MPV) measurement and cardiac Troponin I( cTn I ) in patients admitted with a suspected diagnosis of ACS and to assess the potential diagnostic efficiency of MPV in the diagnostic workup for ACS. MATERIALS AND METHODS: After thorough evaluation of 215 eligible patients, 3 ml. Venous blood collected using Becton, Dickinson and company vacutainer and MPV measured within 1-2 hr of sample collection. Sample for cTn I collected at 6 hr and at 12 hrs, if required and level measured using Biosite analyzer. RESULTS: Mean platelet volume (MPV) was found to be higher among ACS patients as compared to non ACS, 11.44±1.23 vs 9.91±1.27 fl (p-value<0.001). The NPV of MPV in the diagnostic workup of chest pain suggestive of ACS within 6 hours of presentation were found to be 82.53% . CONCLUSION: In this study the MPV is significantly higher in patients with ACS than in those with chest pain of non-cardiac origin and its negative predictive value of 82.53%, it might be useful as an assisting rule-out test in conjunction with other markers in the early prediction of the risk of ACS.