Chromosomal microarray provides enhanced targetable gene aberration detection when paired with next generation sequencing panel in profiling lung and colorectal tumors.

The development of targeted therapies based on specific genomic alterations has altered the treatment and management of lung and colorectal cancers. Chromosomal microarray (CMA) has allowed identification of copy number variations (CNVs) in lung and colorectal cancers in great detail, and next-generation sequencing (NGS) is used extensively to analyze the genome of cancers for molecular subtyping and use of molecularly guided therapies. The main objective of this study was to evaluate the utility of combining CMA and NGS for a comprehensive genomic assessment of lung and colorectal adenocarcinomas, especially for detecting drug targets. We compared the results from NGS and CMA data from 60 lung and 51 colorectal tumors. From CMA analysis, 33% were amplified, 89% showed gains, 75% showed losses and 41% demonstrated loss of heterozygosity; pathogenic variants were identified in 81% of colon and 67% lung specimens through NGS. KRAS mutations commonly occurred with loss in TP53 and there was significant loss of BRCA1 and NF1 among male patients with lung cancer. For clinically actionable targets, 23% had targetable CNVs when no pathogenic variants were detected by NGS. The data thus indicate that combining the two approaches provides significant benefit in a routine clinical setting not available by NGS alone.

Occult HBV infection among anti-HBc positive HIV-infected patients in apex referral centre, Eastern India.

BACKGROUND: The prevalence of occult HBV, defined by the presence of HBV DNA in individuals with antibodies to HBV core antigen and with absence of HBV surface antigen, but its clinical significance and virological features in HIV-infected patients is still unclear. AIM: To investigate the prevalence, clinical significance and molecular characterization of occult hepatitis B virus infection in ART-Naive HIV-positive individuals. MATERIAL AND METHODS: Among the 1077 HIV-infected patients with different risk factors for HIV infection, 297 were HBsAg-ve ART-naive, of them 112 was randomly selected for the study. HBV DNA was tested by in-house PCR and quantified by qPCR. Molecular characterization was performed by sequencing the envelope and overlapping polymerase genes. RESULTS: We found the prevalence of occult HBV to be 10.7% among a randomly selected group of HBsAg-ve/antiHBc+ve HIV-infected patients. Overall 33.9% (38 of 112) of the patients were antiHBc positive indicating exposure to HBV infection. HBV DNA was detected in 12/38 (31.5%) antiHBc positive samples and 50% of them had CD4 T cell count < 200 cells/mm(3). HCV coinfection was low (2.7%). No surrogate marker for OBI could be identified. Presence of antiHBs antibodies did not rule out OBI. Liver biopsy in six cases showed varying stages of chronic hepatitis. Several mutations were detected but not the common immune escape mutant G145R. CONCLUSION: In conclusion the prevalence of OBI was significantly high among HIV coinfected patients, which highlights the importance of HBV DNA testing in these patients and indicates need for further prospective studies in larger cohorts to assess its clinical significance.

Neurofibromatosis, pathological fracture and hypervitaminosis-D.

Pathologic fractures in children may be due to various causes. Rarely, it may be the presenting symptom of neurofibromatosis. A misdiagnosis of Rickets and Vitamin D supplementation in such a case may wreak havoc in the form of iatrogenic hypervitaminosis D. We report one such case.

Subgenotypes of hepatitis B virus genotype D (D1, D2, D3 and D5) in India: differential pattern of mutations, liver injury and occult HBV infection.

Hepatitis B genotype D (HBV/D) is the most widespread genotype and exists as at least five subgenotypes (HBV/D1-D5). However, little is known about the association of virological characteristics with clinical differences among HBV/D subgenotypes. To investigate the virological characteristics of these subgenotypes and their clinical implications, we selected a cohort of 109 genotype D infected individuals from the state of West Bengal, India, including 68 HBsAg positive patients and 41 with occult HBV infection. Among the HBsAg positive subjects 28 had chronic hepatitis B virus infection, 40 were asymptomatic carriers based on clinical examination, liver function test and ultrasonograph results. Overall, HBV/D1 was found in 17%, HBV/D2 in 29%, HBV/D3 in 34% and HBV/D5 in 20% of the cases. HBV/D1 was significantly associated with chronic liver disease (P = 0.01), and in this subgenotype A1896 (PreC mutations) were most common. Although BCP mutations (A/C1753 and T1762/A1764) were found to be frequently associated with HBV/D2 (33% and 33%) and D5 (47% and 59%), no apparent clinical correlation was observed. On the other hand, occult HBV infection was significantly associated with HBV/D3 infection, along with low level of BCP and PreC mutations and several non-synonymous substitutions in the catalytic reverse transcriptase (RT) domain of polymerase gene. Similar nucleotide substitutions in the surface (S) gene region were observed from both northern and eastern Indian HBV/D3 isolates. In conclusion, HBV/D subgenotypes differ in their mutational patterns in the S, polymerase and the BCP/PreC regions that may influence their clinical outcomes.

Fetal ascites owing to congenital cytomegalovirus: response to ganciclovir.

A term newborn with severe congenital cytomegalovirus (CMV) infection is described. Fetal ascites was detected at 28 weeks gestation, and at birth there was tense ascites. There was intra-uterine growth retardation, microcephaly, chorioretinitis, jaundice, purpura and pneumonitis. Computed tomographic scan of the brain showed ventriculomegaly with periventricular calcifications. Serology was positive for cytomegalovirus-specific immunoglobulin M, and cytomegalovirus DNA was detected in the ascitic fluid and urine by nested polymerase chain reaction. He received 6 weeks of treatment with ganciclovir. Ascites resolved spontaneously and liver function tests became normal. Although there was a good clinical response to ganciclovir therapy without any side-effects, on follow-up the infant had global developmental delay and bilateral sensorineural deafness.

Clinical profile and outcome of abdominal tuberculosis in Indian children.

INTRODUCTION: Diagnosis of tuberculosis among children poses technical and operational challenges, more so in abdominal tuberculosis (ATB), where the protean clinical manifestations continue to challenge the physicians in its diagnosis and therapy. METHODS: Medical records of 115 patients who were diagnosed with ATB over a period of six years were studied retrospectively. Details of history, physical examination and investigations, treatment and outcome of therapy were evaluated. RESULTS: The mean age of the patients was 6.4 years. Commonest symptom at presentation was abdominal pain, followed by fever. Nine patients presented with acute abdomen. Mantoux test was positive in 33 percent and accelerated BCG reaction was found in 36.5 percent. Evidence of primary focus was found in 40 percent of chest radiographs. Commonest ultrasonography and computed tomography findings were mesenteric thickening, followed by intra-abdominal lymphadenopathy. Tuberculous infection could be confirmed in 38 patients. The classical plastic variety was the commonest type of ATB found. A complete cure with antituberculous drugs was documented in over 90 percent of the patients. CONCLUSION: In high prevalence zones, ATB should be considered as a differential diagnosis in children presenting with non-specific constitutional symptoms and abdominal pain. When confirmatory tests are negative or not available, supportive investigations and clinical suspicion should be considered strongly for diagnosis of ATB to avoid delay in treatment. Response to therapy in such conditions indirectly confirms diagnosis. Timely use of laparoscopy and laparotomy may be required for confirmation of diagnosis.

Ghosal type hemato-diaphyseal dysplasia: a rare variety of Engelmann's disease.

Ghosal type hemato-diaphyseal dysplasia is a recently described clinical entity. The authors describe such a case with severe anemia requiring transfusions and with clinical and radiological evidence of diaphyseal dysplasia. Very few such cases are reported in world literature.

Predominance of hepatitis B virus genotype C among Karens, the 'old settlers' of Andaman and Nicobar Islands, India.

The Karens, or 'old settlers', migrated from Myanmar to Andaman and Nicobar islands 80 years ago. A high HBV exposure rate among them has been reported. A study of 34 HBsAg carriers was done to investigate the origin of HBV infection among the Karens. RFLP-based genotyping was confirmed by sequencing and phylogenetic analysis. The predominance of HBV/C1/Cs suggests that they carried HBV during their migration, retained it, and in addition, acquired HBV/D2 from the people of mainland India. The reported association of HBV genotype C with disease severity thus warrants further epidemiological investigations among them and on possible spread among neighboring settlers.

Jervell-Lange Nielsen syndrome in a family with the long QT Syndrome (LQTS).

A child with Jervell-Lange Nielsen syndrome is presented from Kolkata. Family study showed that the other family members are suffering from long QT syndrome. The child had frequent syncopal attack and very prolonged QT interval requiring left cardiac sympathetic denervation and beta-blocker therapy as patient could not afford implantable defibrillator and cardiac pacing.

Assessment and predictability of ANB angle.

This cephalometric study consisting of thirty three orthodontic patients in the age group of 13 to 15 years was carried out to: 1. Evaluate the relationship between angle ANB and horizontal distance between jaws at the level of point A (r = 0.99); 2. Evaluate the relationship between angle ANB and Wits appraisal (r = 0.95 when mandibular plane angle is within normal limits of 32 +/- 5); 3. Predict angle ANB from Wits appraisal and vice versa (which was 90 percent correct in mesofacial type and obtained by the regression equation: angle ANB = 2.31 + 1.00 x Wits value; and 4. Evaluate the validity of angle ANB compared to other methods (angle ANB 78.5 percent in agreement with the standard followed by Wits 64.28 percent).