ITPA polymorphisms do not predict additional risk beyond TPMT and NUDT15 for thiopurine-induced cytopenia in inflammatory bowel disease.

INTRODUCTION AND AIM: Thiopurine-related leukopenia is associated with polymorphisms in the thiopurine methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X type motif 15 (NUDT15) genes. However, those polymorphisms explain only a fraction of thiopurine-related leukopenia. Our aim was to study the role of an inosine triphosphate pyrophosphatase (ITPA) polymorphism in patients with inflammatory bowel disease (IBD) and thiopurine-related leukopenia that was unexplained by the TPMT and NUDT15 polymorphisms. MATERIAL AND METHODS: We enrolled consecutive IBD patients on thiopurines (azathioprine or 6-mercaptopurine) from January 2019-March 2020, at a tertiary care center in North India. The presence of the ITPA (C.94C > A) polymorphism was evaluated in all patients, along with its association with thiopurine-related leukopenia. RESULTS: Of the 33 patients (from a total of 119 patients) that developed leukopenia, 8 had the TPMT (n = 1) or NUDT15 (n = 7) polymorphism. Of the remaining 111 patients, their mean age was 36.36 ±â€¯13.54 years and 57 (51.3%) were males. Twenty-five (21.01%) had unexplained leukopenia. The ITPA polymorphism was detected in 4 (16%) patients in the unexplained leukopenia group and 24 (27.9%) patients in the non-leukopenia group (p = 0.228). The odds ratio for predicting leukopenia with the ITPA polymorphism was 0.4921 (95% CI 0.1520-1.5830, p = 0.234). CONCLUSION: The ITPA (C.94C > A) polymorphism was frequently detected in the study population but was not predictive for leukopenia in patients with IBD on thiopurine therapy.

Functional and Speech Outcome of Unilaterally Cochlear Implanted Children after 1 year of Implantation in NIENT: A Retrospective Study.

Hearing loss can be congenital or acquired. Most of the time congenital hearing loss means profound sensorineural hearing loss. The invention of cochlear implantation has already an established role in improving the hearing capability in congenital sensorineural hearing loss. To speak properly after cochlear implant, one needs to go for speech therapy or audio-verbal therapy. Speech therapy has become an integral part of the cochlear implantation program. In Bangladesh cochlear implantation (CI) programs started around 15 years ago, which was limited to Bangabandhu Sheikh Mujib Medical University (BSMMU) and Combined Military Hospital (CMH). Our government takes initiative to provide this service to poor and lower income people. National Institute of ENT (NIENT) was the first government hospital where CI started in 2018 and the project is now ongoing. After CI auditory, verbal therapy (AVT) was given at the same institute. No study has not been done to find out the outcome of AVT. NIENT has taken steps to find out the functional and speech outcome of cochlear implanted children considering the two standard criteria: CAP and SIR score. This retrospective study was done to find out the auditory verbal outcome of unilaterally CI children in different ages and conducted at department of Audiology, National Institute of ENT, Tejgaon, Dhaka, Bangladesh from January 2021 to June 2021. The children who underwent cochlear implants and took the auditory verbal therapy were included in this study. Though it is a retrospective study, a written informed consent has been taken from the patient's parents as the cases are minor in age. From the record review, CAP and SIR scores were recorded four times: before implantation 1 time, after cochlear implantation 3 times (At the end of 3, 6 and 12 months after starting of AVT of Cochlear implantees). From the study it has been observed that out of 50 implantees, 48.0% of children's age range was in between >3 to ≤5 years. Most of the implantees were from rural areas and also from lower income group. The study showed significant association with CAP and SIR score at the end of one year of AVT. No significant association was found in different age groups with scores of CAP and SIR. But the parent's education showed significant association with CAP score at the end one year of AVT. Though the age of the recipient is not significantly associated with the AVT outcome but maternal education plays an important role in improving CAP and SIR score. So, maternal education or understanding along with professional speech therapy is vital for better AVT outcome.

A pilot randomized trial to study the success rate of early precut fistulotomy and its effect on radiation dose in patients with difficult biliary cannulation.

BACKGROUND: Role of precut fistulotomy in reducing fluoroscopy time and the radiation dose in difficult selective biliary cannulation is unknown. METHODS: We performed a randomized trial where patients with difficult biliary cannulation were randomized into 2 groups: early precut fistulotomy (precut five minutes after failed standard biliary cannulation) or late precut fistulotomy (precut fifteen minutes after failed standard biliary cannulation). We compared the success rates of selective biliary cannulation, fluoroscopy time, radiation dose, complication rates, need for repeat endoscopic retrograde cholangiography (ERC) and need for other interventions. RESULTS: Of the 130 eligible patients screened, 40 patients were randomized. The technical success was comparable between early and late group. The fluoroscopy time and radiation dose were significantly less in the early group [4 minutes (3, 6) vs 15 minutes (8, 28), p=0.001] and [1.35 mGy (0.90, 1.63) vs 2.40 mGy (1.58, 3.25), p=0.010] respectively. In the late group, 60% required need for rescue precut fistulotomy. One patient from late group developed post ERC pancreatitis while 1 from early group developed perforation. Three needed other interventions due to failed second attempt. CONCLUSION: Early precut fistulotomy has comparable technical success and reduces the radiation dose as compared to late precut fistulotomy for difficult biliary cannulation.

Endovascular and percutaneous transabdominal embolisation of pseudoaneurysms in pancreatitis: an experience from a tertiary-care referral centre.

AIM: To analyse the technical challenges, clinical success, and associated complications of endovascular and percutaneous embolisation of pancreatitis-related pseudoaneurysms. MATERIALS AND METHODS: A retrospective study of patients referred for embolisation of pancreatitis-related pseudoaneurysms between January 2014 and March 2019 was conducted. Computed tomography angiography (CTA) was performed to assess the morphology of the aneurysms prior to any intervention. Percutaneous or endovascular embolisation was performed. Details of CTA and methods of embolisation were recorded. Technical success, clinical success, and complications were reported. RESULTS: A total of 80 patients (mean age, 40.69 ± 13.41 years, 73 male) underwent embolisation during the study period. Pseudoaneurysms were related to chronic pancreatitis (CP) in 44 (55%) patients and acute pancreatitis (AP) in 36 (45%) patients. Pseudoaneurysms were detected in 65 (81.2%) patients on CTA. The most common site of pseudoaneurysms was gastroduodenal artery (GDA) followed by splenic artery. Seven patients were treated with percutaneous thrombin injection and five were treated with percutaneous glue injection under ultrasound/fluoroscopy guidance. The remaining patients (n=68) underwent catheter angiography with endovascular embolisation. Technical success was achieved in 4/7 (57%) percutaneous thrombin cases and in all the cases (5/5, 100%) with percutaneous glue or endovascular (68/68,100%) embolisation. CONCLUSION: Endovascular or percutaneous embolisation of pseudoaneurysms has high technical success with an excellent safety profile.

Variability of contrast enhancement of pancreas on computed tomography in patients with acute pancreatitis and isolated extrapancreatic necrosis.

BACKGROUND AND STUDY AIM: To evaluate the variability in the enhancement of pancreas on computed tomography (CT) in patients with acute pancreatitis (AP) and isolated extrapancreatic necrosis (EPN) and to investigate whether it affects the extrapancreatic findings and patient outcomes. PATIENTS AND METHODS: This retrospective study comprised of consecutive patients with isolated EPN evaluated between April 2017 and April 2019. A radiologist measured the pancreatic attenuation values (PAV) of head, body, and tail on a contrast enhanced CT. Using a cut-off PAV of 100HU, patients were divided into two groups. The extrapancreatic CT findings and outcome parameters were compared between the two groups. RESULTS: Thirty patients (mean age, 42.13 years, 17 males) with isolated EPN were evaluated. The mean PAV in the head, body, and tail was 83.13 HU (range, 59-161), 84.17 HU (range, 60-160), and 82.23 HU (range, 53-137). The overall mean PAV was 83.12 HU (range, 58-152). There were six patients with overall mean PAV≥100 HU. The group with PAV≥100 HU had a higher number of patients with infected necrosis (66.6% vs. 14.2%, P=0.018). PAV had a significant association with length of hospitalization (P=0.045). CONCLUSION: There is significant variability in the pancreatic enhancement on CT among patients with AP and isolated EPN. Patients with PAV≥100 HU had a significantly longer hospital stay. This, however, may be related to a greater number of patients with infected necrosis in this group.

Role of computed tomography in prediction of gastrointestinal fistula in patients with acute pancreatitis.

AIM: To identify computed tomography (CT) features that predict gastrointestinal fistula (GIF) in patients with acute pancreatitis (AP). METHODS: This retrospective study comprised consecutive patients with AP and GIF from June 2017 to June 2018. The diagnosis of GIF was based on upper gastrointestinal endoscopy, colonoscopy or surgery. A cohort of 19 matched patients from a prospective database of AP served as control group. Measures of severity, and clinical outcome were evaluated. CT parameters were compared between the groups to assess the features that could predict the development of GIF. RESULTS: There was no difference between the two groups in terms of disease etiology, severity, drainage, and mortality. On univariate analysis, the CT features that were found to be significantly different between the two groups were the presence of bowel wall thickening (P=0.005), maximum thickness of the bowel wall (P=0.007), presence of air foci in extra pancreatic necrosis/ collection (P=0.013), discontinuity of the bowel wall (P=0.046) and the displacement/ compression of bowel by fluid collection (P=0.014). On multivariate analysis, all the above-mentioned CT findings except discontinuity of bowel wall were found to be statistically significant. CONCLUSION: CT is helpful in predicting GIF in patients with AP.

Partial proximal trisomy 14: identification and molecular characterization in a girl with global developmental delay.

Chromosomal rearrangements associated with a disease play a significant role in the phenotypic manifestation. Here we report a 9-month-old girl with de novo partial proximal trisomy 14 with seizures and global developmental delay. Cytogenetic investigations revealed a karyotype of 47,XX+marker. The marker was approximately the size of G-group chromosomes and almost mistaken as chromosome 22 due to its banding pattern but the trisomy 22 was ruled out considering its lethality. To find out the origin of the marker chromosome, Spectral karyotyping (SKY) was performed which showed the marker to be of chromosome 14 origin. Further Molecular cytogenetic analysis with whole chromosome 14 confirmed the marker as a derivative 14. Fluorescence in situ hybridization (FISH) with centromeric probe 14 also showed 3 signals. Further fine mapping with three Bacterial Artificial Chromosome clones helped us to tentatively find the extent of the break point regions. The use of SKY and FISH permitted the characterization of this cytogenetic abnormality. The clinical data of the present case are compared with other published cases in the literature. This helps in better genetic counseling and also in the genotype/phenotype correlation. The impact of the extra chromosomal part in relation with the phenotype of the patient is also discussed.

Parathyroid failure following thyroid surgery.

This cross-sectional study was done to see the association of post thyroidectomy parathyroid failure with thyroid disease and type of surgery. It was carried out in the Department of Otolaryngology-Head and Neck Surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka during the period of July 2008 to June 2010. Total 50 cases of thyroid malignancy and multinodular goiter who had undergone total or near total thyroidectomy with or without neck dissection were studied. In this study highest number of cases were found in 3rd decade of age (28%) and there was female predominance (M:F=1:3.54). Overall frequency of post operative hypocalcaemia was 30% (26% was temporary hypocalcaemia and 4% was permanent). Hypocalcaemia revealed clinically in 20% cases and remained subclinical in 10% cases. Hypocalcaemia developed in 42.30% cases of malignant thyroid disease and 16.66% cases of benign thyroid disease (p<0.05). It was found in 54.54% cases with neck dissection and 23.07% cases without neck dissection (p<0.05). Hypocalcaemia developed in 62.5% cases where parathyroid gland were not identified and 23.8% cases where parathyroid gland was identified. Hypocalcaemia developed most commonly on the 2nd post operative day (73.33%). There is a significance difference with development of parathyroid failure after thyroid surgery between benign and malignant thyroid disease and also between thyroid surgery with or without neck dissection.

High prevalence of human papillomavirus in esophageal squamous cell carcinoma: a study in paired samples.

Esophageal squamous cell carcinoma (ESCC) is one of the common cancers with a poor prognosis. Incidences of human papillomavirus (HPV) infection range from 0 to 67% in different parts of the world. It has been frequently associated with high-risk HPV genotypes 16 and 18. The present study analyzes the prevalence of HPV infection in ESCC tumor and adjoining mucosa. Fresh tissue samples were obtained from ESCC tumor (group I) and adjoining mucosa (group II). Aliquots of DNA extracts were used. There were 23 patients with paired samples, 19 (83%) were male. HPV was positive in 20/23 (87%). Mean age of HPV positive in group I was 56.63 ± 6.96 and in group II 54.31 ± 7.13 years (P > 0.05). Majority had more than one viral type. HPV52 was the most common observed in 14 (61%) males and two (9%) females. Other common viruses were HPV55, 39, and 59. Smoking had a significant association with viral positivity. p63 and p16 oncoproteins correlated with degree of tumor differentiation but not with viral status. We documented high prevalence of high-risk HPV in ESCC. Our observations support the concept of persistent infection by an oncogenic HPV in cancer development. Our study highlights importance of documenting viral genotype in a defined geographic area.

Phenotypic and molecular characterization of partial trisomy 2q resulting from insertion-duplication in chromosome 18q: a case report and review of literature.

Trisomy 2q is a well-documented chromosomal anomaly with considerable variation in the phenotype depending upon the breakpoints and the co-existing chromosomal aberrations. The case of a dysmorphic male infant found to have trisomy of the 2q31.1-q37.3 segment, resulting from insertion-duplication of this segment in chromosome 18q23 is reported here. The rearrangement was resolved in detail by cytogenetic microarray and whole chromosome paint-based fluorescence in situ hybridization studies. There is some overlap of the phenotypic features in the reported patient with those described in previously reported cases with partial trisomy 2q. A detailed review of the available literature on 2q trisomy has also been presented and delineation of the phenotypic characteristics common to all patients with 2q trisomy has been attempted.

The 9p24.3 breakpoint of a constitutional t(6;9)(p12;p24) in a patient with chronic lymphocytic leukemia maps close to the putative promoter region of the DMRT2 gene.

B-cell chronic lymphocytic leukemia (B-CLL) is a very common hematological malignancy. Although several alterations in different loci have been identified and established as prognostic factors the pathogenetic cascade remains obscure. Here we give an account on a 71-year-old man with B-CLL and a translocation t(6;9) in his diagnostic bone marrow. Subsequent chromosome analysis of his blood lymphocytes revealed a constitutional karyotype 46,XY,t(6;9) (p12;p24) that has not been previously reported. Seeking for gene disruption correlated with the B-CLL we precisely mapped both breakpoints by fluorescence in situ hybridization (FISH) analysis with chromosome-specific bacterial artificial chromosome (BAC) clones and their long-range polymerase chain reaction (LRPCR) subfragments. An 11-kb LRPCR subfragment derived from RP11-399A15 was found to span the breakpoint at 6p12.1. FISH analysis with a 12-kb LRPCR fragment derived from RP11-147I11 which overlaps with RP11-110M16 as well as with a cDNA for DMRT2 (doublesex and mab-3 related transcription factor 2) maps the 9p24.3 breakpoint maximum 10 kb upstream from DMRT2. In silico analysis of the transcripts within the vicinity of the breakpoints revealed that the translocation does not disrupt any known genes but could affect the putative DMRT2 promoter. Long range effects on gene expression cannot be excluded so far.

Wandering spleen presenting as bleeding gastric varices.

Ectopic spleen (splenoptosis) is an extremely rare condition in which the spleen is present in a nonanatomical position. Patients' symptomatology is variable and ranges from mere feeling of an abdominal lump to sudden abdominal pain due to infarction. Patient may have subacute to chronic abdominal or gastrointestinal complaints. Because of nonspecific symptoms, clinical diagnosis can be difficult; hence, imaging plays an important role. Presentation as a case of portal hypertension is extremely rare. We report a case of splenic torsion in a middle-aged woman who presented with hemetemesis from gastric varices secondary to chronic volvulus of an ectopic spleen. Preoperative diagnosis was made on the basis of ultrasonography, endoscopy, and computed tomography, which was later proved on surgery and treated successfully.