Occurrence of Existing BCR-ABL Baseline Mutations and Associated Haplotype (NmR) Among CML Patients with Diverse IM Response: A Hospital-based Study from North-East India.

Highly polymorphic BCR-ABL kinase domains have been reported to harbor more than a hundred mutations, and among these, 40-60% have been identified as influencers of imatinib mesylate (IM) resistance. The emergence of IM resistance poses a significant challenge in the management of Chronic Myeloid Leukemia (CML). M351T (rs121913457), E255K (rs387906517), and Y253H (rs121913461) are of particular clinical significance due to their association with high-level imatinib resistance. This study was conducted to investigate the potential role of three significant SNPs in CML progression due to IM resistance. During the study period from 2018 to 2022 (48 months), the blood samples from 219 Reverse transcriptase-PCR-confirmed CML patients following RNA extraction and cDNA preparation were subjected to M351T, E255K, and Y253H mutation analysis by PCR-RFLP. After agarose gel visualization, the samples were subjected to Sanger sequencing to confirm the nucleotide change at the polymorphic loci. The wild-type genotype of all three ABL1 SNPs under investigation exhibits a significant reduction in frequency among IM non-responders compared to the responder group. The CGT haplotype frequency exhibits a significant difference between IM responder (4.2%) and non-responder (11.8%) (p = 0.002 < 0.05). Further, CGC haplotype was observed solely among the imatinib non-responder patients with a frequency percentage of 3.3% (p = 0.004), whereas the said genotype was absent among the responder group. A reduced overall survival rate was observed with deviation from wild-type genotype (M351T loci (T > C) with 1.217 times, E255K (G > A) with 1.485 and Y253H (T > C) with 1.399 times increase in hazard ratio) thereby enhancing mortality risk due to disease progression. The significant increase in the frequency of M351T, E255K, and Y253H loci among the IM non-responder group indicated their probable association with the development of IM resistance among CML patients. A haplotype frequency distribution pattern analysis of ABL1 loci further identified the CGC haplotype as an independent predictor for IM resistance. As such the study highlights the importance of patient characteristics, genotype distribution, and haplotype frequency distribution in predicting the response to IM treatment and clinical outcomes of CML patients.

Epigenetic Modulation of DDIT3 and MGMT Expression Acts Synergistically with Resistance to Imatinib towards CML Disease Progression: A Hospital based Study.

INTRODUCTION: Imatinib Mesylate is an authenticated drug that aids in the treatment of Chronic Myeloid Leukaemia and Philadelphia patients which is recognized as a BCR-ABL tyrosine kinase inhibitor. Indeed, DNA Methylation occupies a key role in the stability of chromosomes. OBJECTIVE: Changes in the methylation status of genes may impart to the advancement of Chronic Myeloid Leukaemia. The present investigation aims to assess the role of expression analysis and methylation status of DDIT3 and MGMT genes in imatinib-resistant and nonresistant cases. METHODS: The Imatinib resistance was screened through RFLP. In this case maximum number of patients were recorded in the chronic phase belonging to the age group 40-59 and the accelerated and blast phase is more common in elderly patients showing the progressive nature of the disease with age. Hemoglobin and platelet count are found to be higher in cases where WBC count was minimal. A history of long-term alcohol consumption is found to be associated with the progression of the disease. RESULTS: The maximum level of expression of the DDIT3 gene was recorded in the chronic phase regardless of upstream (67.8%) and downstream (57.9%) regulation. The highest MGMT expression regulation was also observed in the case of chronic phase in both upstream (78.9%) and downstream (44%) regulation. Further, the MGMT gene showed the highest methylation of 6.6% and DDIT3 showed 3.3% in CML cases. CONCLUSION: In the present study notable depletion of survivality was established in the Imatinib resistance patients manifesting genetic malfunction of BCR-ABL transcripts among the North East Indian inhabitants and advocating for the expansion of the disease.

A hospital-based study of socioeconomic status and clinical spectrum of rheumatic heart disease patients of Assam, North-East India.

Objective The aim of this study was to assess the impact of socioeconomic factors in increased prevalence of rheumatic heart disease and its clinical spectrum in Assam, North-East India. Method A case-control questionnaire-based study of 100 echocardiography confirmed rheumatic heart disease cases with age- and sex-matched healthy controls from Assam medical college and hospital in Dibrugarh, Assam was conducted. Results There was a trend toward increased risk of rheumatic heart disease and its clinical spectrum with respect to low socioeconomic status. Three parameters were found to be statistically significant in posing increased risk towards rheumatic heart disease: rural dwelling location ( p < 0.0001, odds ratio (OR) 4.1, 95% confidence interval (CI = 2.29-7.45), low monthly income ( p < 0.001, OR=9.5, 95% CI = 4.99-18.1) and education status ( p < 0.05, OR=9.5, 95% CI = 1.866). Out of the severe cases of mitral stenosis, mitral regurgitation and aortic regurgitation, 69.6%, 58.3% and 34% patients were of low socioeconomic status. Conclusion Socioeconomic factors can be of significant importance in increased prevalence of rheumatic heart disease and might also influence the clinical spectrum of the disease. Increased awareness and up-gradation of socioeconomic status might ameliorate the prevalence of rheumatic heart disease.

Morphological Variations of the Thyroid Gland among the People of Upper Assam Region of Northeast India: A Cadaveric Study.

INTRODUCTION: The morphological variations of the thyroid gland have been reported from different parts of the world. The variations are due to remnant or non-specific development of the parts of the thyroid gland. Surgical operation of the thyroid gland has been the treatment of choice in various thyroid pathologies. Prior knowledge of the morphological variation is important to ensure better results from these surgical operations. AIM: To study the prevalence of morphological variations seen in the thyroid glands in the upper Assam region of Northeast India. MATERIALS AND METHODS: This was a hospital based cadaveric study. Total number of Thyroid glands dissected were 80. The thyroid gland was examined properly for the presence of pyramidal lobe, levator glandulae thyroideae and complete absence of isthmus. Statistical analysis was done by SPSS 21.0. RESULTS: It was found that 17 (21.25%) cadavers did not show an isthmus. The pyramidal lobe was present in 31(38.75%) cases and frequently arising from the left side (74.2%) of the isthmus. Levator glandulae thyroideae was found in 15 (18.75%) of the thyroid specimens. In all cases, it was extended from the apex of the pyramidal lobe to the hyoid bone. CONCLUSION: Morphological variation of the thyroid gland is very common hence requires detection prior to any surgery on the thyroid gland.

Agnathia Holoprosencephaly and Situs Inversus in A Neonate Born to an Alcoholic Mother.

Agnathia, holoprosencephaly and situs inversus complex is an extremely rare form of congenital malformation. Though a few cases have been reported from other parts of the world, to the best of our knowledge none has been reported from India so far. Maternal alcoholism is regarded as an important factor causing holoprosencephaly. Disruption of the Shh gene signaling pathway is also said to be a factor for the occurrence of holoprosencephaly as well as left right asymmetry. Though several factors are suspected as a cause of this deformity, the precise aetiopathogenesis is still under debate. Lack of knowledge might be due to paucity of data from cases due to its rarity. Hereby, we are presenting a case of agnathia, holoprosencephaly and situs inversus born at 32 wk of gestation by an alcoholic mother. Externally the child had agnathia and cyclopia. There was no mandible or any oral cavity. It was accompanied by noticeable limb deformity. Internally there was holoprosencephaly, situs inversus totalis with several visceral abnormalities. To the best of our knowledge this is the first case of agnathia, holoprosencephaly and situs inversus complex to be reported in an indexed literature from India. This report also strengthens the association of maternal alcoholism with occurrence of holoprosencephaly.

Robertsonian translocation T (21; 21) in a female born to normal parents: a case report.

Downs syndrome (DS) occurs due to an extra copy of chromosome 21. About 3% of cases of Downs syndrome occur due to Robertsonian translocation, most commonly t (14; 21), other types of translocations are very rare cause of the syndrome. A 10-year-old patient with mental retardation was admitted following road traffic accident. Patient had flabby muscles, had delayed mile stones, stunted growth for the age, slanting of eyes, flat nasal bridge, and ineligible speech. On cytogenetic analysis the patient had karyotype showing one normal chromosome 21 and one Robertsonian translocation t (21; 21). Parents and siblings of the patient were phenotypically normal. Robertsonian translocation t (21; 21), can occur by transmission from carrier parent, due to ovarian mosaicism for Robertsonian translocation or may appear de novo. In the present case as the parents had normal karyotype and siblings were phenotypically normal, Robertsonian translocation probably have arisen de novo. The present case was a case of Downs syndrome with Robertsonian translocation t (21;21) probably arising de novo.

Pattern of Gross Congenital Malformations in a Tertiary Referral Hospital in Northeast India.

OBJECTIVE: To explore the prevalence of structural congenital malformations among newborns and study some of the fetal and maternal characteristics of the malformed babies in North east India where such systematic study on congenital malformation has not been undertaken before. METHODS: A cross sectional study was undertaken from May 2010 through Feb 2013 for estimation of gross congenital malformations among live birth and stillbirth children born in Assam Medical College. All live births were clinically examined for detection of gross congenital malformations and autopsy was carried out on still births and neonates dying within 24 h of birth to detect gross congenital malformations in the internal organs. All malformations were classified as per ICD 10 classification. The mothers of the newborns with congenital malformations were interviewed in a predesigned, pretested proforma. The variables included maternal age, antenatal registration, antenatal history of drug intake, consanguinity and previous history of malformations. Statistical analysis was done using chi square test. RESULTS: A total 18,192 births including live births and still births were examined and 206 cases of structural malformations were observed. Prevalence of congenital malformations was 1.2 % of the total live births. Distribution of malformation was predominant among males than in females (60.67 vs. 37.37 %; p < 0.05). Musculoskeletal system was the most common system involved. Prevalence of malformation of the cardiovascular system was found to be very low. Malformations among stillbirths and newborns born to unregistered mothers were significantly more. Percentage of malformations in babies born to mothers of more than 30 y of age was higher than other age groups (2.2 %). Occurrence of malformations in low birth weight babies were significantly more (p < 0.001). CONCLUSIONS: Prevalence of malformations was 1.2 % of the total live births. Musculoskeletal system was the most common system involved. Congenital malformations were significantly associated with sex of the new born, registration of the mother and birth weight of the newborn.

The prune belly syndrome in a female foetus with urorectal septum malformation sequence: a case report on a rare entity with an unusual association.

The prune belly syndrome is a rare congenital anomaly which is characterized by the triad of an absent or a deficient development of the abdominal muscle, bilateral cryptorchidism and an anomalous urinary tract. In its full form, this condition occurs only in males. However, a similar condition occurs in females in the absence of cryptorchidism. On the other hand, the urorectal septum malformation sequence is a lethal congenital malformation which is characterized by the development of a phallus like structure, a smooth perineum and the absence of urethral, vaginal and anal openings. We are reporting a case of a female foetus with the prune belly syndrome, which was associated with a urorectal septum malformation sequence. A dead foetus with a protruded abdomen and ambiguous genitalia, was born at 32 weeks of pregnancy. On autopsy, it was found to have female internal genital organs. The left kidney, the urinary bladder and the rectum were absent. The sigmoid colon, the ureters and the fallopian tubes opened into a common cloacal sac. The histopathological examination of the ovary showed the presence of Leydig's cells. The occurrence of the female counterpart of the prune belly syndrome is extremely rare and only few of such cases were found to be discussed in the details in the indexed English literature so far. Hence, we hope that this case report will contribute to the existing knowledge on the prune belly syndrome.

Persistent left superior vena cava in a stillborn fetus - a case report

Persistent left superior vena cava is a rare congenital malformation. It represents some form of developmental arrest. It may coexist with right superior vena cava in different patterns and sizes. The knowledge of variations of central venous anatomy and its association with congenital malformation of the heart is important during central venous access device placement. Here we present a case of type A persistent left superior vena cava with hypertrophied right atrium, right ventricle and large ostium secundum defect in a stillborn fetus during routine fetal autopsy (AU)

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