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India is the highest TB burden country in the world having an estimated incidence of 26.9 lakh cases in 2019. With a population of 1.32 billion, India has the highest burden of drug resistant TB (DR-TB) in the world. North zone of India is the second highest MDR-TB prevalent zone after the West zone of India. MDR TB treatment involves prolonged treatment with injectable second-line drugs, associated with more adverse effects, suboptimal treatment outcomes and higher risks of mortality compared to patients with drug-sensitive TB and those with lesser resistant forms of TB. Materials methods: This retrospective study was conducted in the department of Microbiology Government Medical College Anantnag, data was analyzed from March 2017 to February 2018. Non-sterile specimens were processed by Modified Petroff Method. Sterile specimens were concentrated by centrifugation and smear and cultures was inoculated from the sediment. CBNAAT assay was performed by Gene Xpert (Cepheid) 4 system according to the manufacturers’ recommendations. Results: Of the total 1497 clinically suspected tuberculosis specimens collected, 1370 (91.5%) were pulmonary and 127 (8.5%) were presumptive extra pulmonary tuberculosis received from different anatomical sites. Maximum clustering of cases was seen in 10-20 years age group. Out of the total 1497 samples 200 were CBNAAT confirmed Mycobacterium Tuberculosis positive samples. In which 155 were pulmonary and 45 were extra pulmonary. The average percentage positivity rate (i.e. percentage of MTB positive samples out of total samples tested) was 13.3% (200/1497). Rifampicin resistance (RR-TB) was seen in 5.5% (11/200) samples. Out of the samples detected positive (200): 155 were pulmonary samples and out of these 155 pulmonary samples 8 were found to be RR MTB 5.1% (8/155). Also out of the 200 positive samples 45 were extra pulmonary and out of these 45 extra pulmonary samples 3 were found to be RR MTB 6.6% (3/45). Conclusion: In this study we found that in our region 5.5% cases of TB were RR-TB, 3.2% were new cases and 13% RR-TB was seen in previously treated cases of MTB. The screening of drug resistance has to be expanded to offer universal DST including expanded DST .The second and most important activity is to strengthen drug resistance surveillance under the various national programs with inclusion of laboratories in the private sector as well. The state level regional studies also give us the opportunity to plan and execute intervention prioritization, based on the drug resistance trends observed.

INTRODUCTION Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML). We aimed to analyze relation of different GST gene sequence variants with susceptibility and response to Imatinib in CML. MATERIAL AND METHODS A total of 150 CML cases and equal number of age and gender matched healthy controls were genotyped for five GST polymorphisms by multiplex-PCR and PCR-RFLP techniques. BCR-ABL1 transcripts were quantified by quantitative Real Time PCR (qRT-PCR). RESULTS GSTT1, GSTO1, and GSTO2 SNPs revealed no association, while as GSTM1null genotype was observed to protect against the development of CML (OR = 0.53, P = .01). GSTP1 variant genotypes AG (OR = 2.1, P = .003) and GG (OR = 5.6, P

Inherited polymorphic sequence variations in drug transport genes like ABCB1 impact a portion of patients with hematologic malignancies that show intrinsic or acquire resistance to treatment. Keeping in view inter-individual sensitivities for such drugs, we through this case–control study tested whether ABCB1 C3435T and G2677T polymorphisms have any influence on the risk and treatment response in patients with chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Genotyping for ABCB1 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism in 100 CML and 80 B-ALL patients along with 100 age and gender matched healthy controls. ABCB1 C3435T and G2677T polymorphism showed no association with CML. Genotype distribution revealed significant higher frequency of TT genotype for both SNPs in B-ALL cases and associated with increased B-ALL risk (OR 2.5, p = 0.04 for 3435TT; OR 2.4, p = 0.04 for 2677TT). There was no significant difference in genotype frequency of 3435C > T and 2677G > T among resistant and responsive groups for the two leukemia types. Kaplan–Meier survival plots revealed significantly lower event free survival in CML and B-ALL patients that were carriers of 3435TT genotype (p

IntroductionGlutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to chemotherapy in acute lymphoblastic leukemia (ALL). This case–control study investigated the association of GST gene polymorphisms with the etiology and therapeutic outcome of B-ALL among Kashmiri population.MethodsA total of 300 individuals including 150 newly diagnosed B-ALL patients and an equal number of age and gender matched controls were genotyped for five GST gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism technique (PCR-RFLP) and multiplex PCR techniques.ResultsHigher frequency of GSTT1null, GSTO2-AG, and GSTO2-GG genotypes was observed in ALL cases compared to controls that associated significantly with ALL risk (GSTT1null: OR = 2.93, p = 0.0001; GSTO2-AG: OR = 2.58, p = 0.01; GSTO2-GG: OR = 3.13, p = 0.01). GSTM1, GSTP1, and GSTO1 SNPs showed no significant association (p > 0.05). Combined genotype analysis revealed significant association of GSTT1null/GSTM1null (OR = 4.11, p = 0.011) and GSTT1null/GSTP1-AG (OR = 4.93, p = 0.0003) with B-ALL susceptibility. Haplotype analysis of rs4925 and rs156697 revealed that carriers of CG haplotype had increased risk of B-ALL (p = 0.04). Kaplan–Meier plots revealed significantly inferior 3-year disease-free survival for GSTO2-GG carriers (p = 0.002). Multivariate analysis confirmed GSTO2-GG as an independent poor prognostic factor for DFS (HR = 4.5, p = 0.034). Among combined genotypes, only GSTT1null/GSTP1-AG associated significantly with poorer DFS rates (p = 0.032).ConclusionThis study demonstrated that GSTT1null individually or in combination with GSTM1null and GSTP1-AG genotypes associated with increased B-ALL risk. Also, rs156697 variant genotypes (AG and GG) associated with B-ALL, whereas the GG genotype of rs156697 influenced the treatment outcome.

Introduction: Acute myeloid leukemia (AML) is a clonal accumulation of myeloid precursors in body tissues, which ultimately leads to bone marrow failure. This is an 8-year prospective, observational study in which 254 patients were enrolled. Aim of the Study: To document the clinical profile of AML and differential outcome in M3 versus non-M3 phenotype and to see impact of different variables on its survival. Methods: Patients enrolled in the study were examined, evaluated, and given standard 3:7 induction protocol, and acute promyelocytic leukemia (APML) patients were given the ICAPL 2006 protocol. Results: In our study, males outnumbered females and most of our patients were in 20–60 years of age group. The better prognosis was in patients who were in the second decade of life. Total leukocyte count and platelet count had a significant impact on the survival of the a patient. Bone marrow morphology of M3 type has extremely good prognosis and was the most common FAB type seen in our study. Flow cytometric markers such as CD15, CD33, CD117, and myeloperoxidase had positivity among 90% of patients. Overall survival is around 40% in whole-study group, 87% in APML group, and 16.5% in non-M3 group. There are still unmet needs in managing the non-M3 patients in resource-constraint countries where allogenic transplant and newer drugs have the least access. For improving the outcome in M3 AML, further newer molecules such as Flt3 and PIK3 inhibitors are being used in trials. Conclusion: There are still unmet needs in managing the non-M3 patients in resource-constraint countries where allogenic transplant and newer drugs have the least access. For improving the outcome in M3 AML, further newer molecules such as Flt3 and PIK3 inhibitors are being used in trials.

CYP2D6 is one of the most widely investigated CYPs in relation to gene polymorphism. This study analyzed the relationship between CYP2D6 rs35742686 and rs3892097 single-nucleotide polymorphisms (SNPs) and potential risk factors in the development of acute lymphoblastic leukemia (ALL) in Kashmiri children. We recruited 300 cases and 600 controls for genotyping and risk factors assessment. Genotypes of rs35742686 and rs3892097 were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. CYP2D6 expression analysis was done by quantitative reverse transcription polymerase chain reaction in ALL cases. Conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). High risk of ALL was observed in cases who carried the mutant genotypes of rs35742686 (OR = 18.15; 95% CI = 4.13–79.66, p

The well-established molecular pathogenesis of chronic myelogenous leukemia (CML) and its consequences for laboratory testing and clinical management illustrate a classic paradigm for the importance of molecular diagnostics in targeted drug therapy. The success of the tyrosine kinase inhibitor (TKI), Imatinib, as the currently recommended first-line treatment of early chronic phase CMLhas both fueled the need for timely and reproducible molecular testing of the BCR-ABL fusion transcript in diagnosis and monitoring. As ongoing research continues to refine guidelines for monitoring residual disease in patients undergoing TKI therapy, an understanding of molecular technologies and their interpretation is critical. In this regard, we at Cancer Diagnostic and Research Centre, Immunology and Molecular Medicine established a gold standard RT-PCR and RQ-PCR technique to diagnose and monitor residual disease in CMLpatients. JMS 2016; 19(2):82-84

Objective: The aim was to evaluate the efficacy and safety profile of dapsone as a cheap second-line treatment for chronic immune thrombocytopenia (ITP) in developing countries. Materials and Methods: A prospective study on 100 chronic ITP patients. These patients were put on dapsone after ruling out glucose 6 phosphate dehydrogenase deficiency and secondary causes of ITP. Results: The basic work up for secondary causes of ITP was negative. All these patients had been treated with steroids in the past. Anti-D had been given acutely in 20 patients, and intravenous immunoglobulin G had been given in 10 patients. Vincristine had been given to 20 of these patients. Dapsone was started in these patients, and 44% patients showed a response to treatment. The mean time to onset of response was 21 days. Out of these 44 patients, 21 (47.7%) went into remission and had platelet count >100,000/μl at 2 years post tapering of the treatment. Remaining 23 patients were kept on low dose dapsone and maintained their platelet counts. Adverse drug reactions included mild skin eruptions in 5% of patients, pruritus in 10% of patients, dose-related hemolysis in 1% of patients, methemoglobinemia in 1% of patients and Stevens Johnson syndrome in 1% of patients. 56 patients were nonresponders to the available, affordable conventional medical treatment and were referred to the surgical department for splenectomy, with a cure rate of 86% postsurgery. Conclusions: Dapsone is a safe, cheap and effective treatment option for patients with chronic ITP, who cannot afford the usual costlier second-line drugs.

Anemia and other hematological abnormalities are common in patients with Sheehan's syndrome. The response of these abnormalities to replacement of thyroxine and glucocorticoids is not clear. The aim of the present study was to document the profile of hematological abnormalities and response to treatment in patients with Sheehan's syndrome. Forty patients of Sheehan's syndrome and an equal number of age and parity matched healthy controls were studied for prevalence of hematological abnormalities. Hemoglobin concentration, hematocrit, red cell, white cell and platelet count were significantly decreased in patients with Sheehan's syndrome compared to controls. Frequency of anemia, leucopenia, thrombocytopenia and pancytopenia was significantly higher in these patients compared to controls. After achieving euthyroid and eucortisol state, there was a complete recovery of these hematological abnormalities. We conclude that anemia and other cytopenias are common in patients with Sheehan's syndrome and replacement with thyroxine and glucocorticoids results in complete recovery of these abnormalities.

Kangari, an earthenware brazier containing burning charcoal, is used for personal warming during the winter months by most of the people in Kashmir valley. Kangari is usually held close to the lower abdomen or in between the legs while squatting on the ground. The use of kangari is associated with development of skin cancer at the sites of prolonged exposure. In the present study 43 patients with Kangari cancer were analyzed prospectively with the objective of understanding their clinico-pathological profile and the response to various treatment modalities. Variables such as age, gender, grade, site of lesion etc., were evaluated for their prognostic significance.