Plasmablastic lymphoma of bone marrow: Report of a rare case and immunohistochemistry based approach to the diagnosis

Plasmablastic lymphoma (PBL) is a distinctly rare neoplasm believed to arise from post-germinal center, terminally differentiated, activated B cells before transformation to plasma cells; and predominantly affecting human immunodeficiency virus (HIV) infected or immunodeficient males. Here, we report a rare case of primary PBL of bone marrow in an immunocompetent male, the diagnosis of which is complicated by the overlapping morphology and immunophenotype with several large cell lymphomas and plasma cell neoplasms; and showing dramatic response to anti-CD30 monoclonal antibody based therapy. We discuss the immunohistochemistry based approach and the possible diagnostic pitfalls in such cases. The inclusion of markers of plasmablastic differentiation in the diagnostic panel of large cell lymphomas is essential to avoid misclassification of these rare lymphomas.

A Retrospective Study Of Kras And Nras Mutations In Metastatic Colo-Rectal Cancer Patients And Treatment Outcomes With Cetuximab- Or Bevacizumab-Containing Regimens In Central India

Background: The presence of a Kristen-Rat Sarcoma (KRAS) and NRAS activating mutations in metastatic CRC (mCRC) were significantly associated with absence of response to agents targeting epidermal growth factor receptor(EGFR). Our study aims to describe the pattern of KRAS and NRAS mutations and effectiveness of Cetuximab- and Bevacizumab-containing regimens in mCRC patients. Methodology: In this retrospective observational study, a total of 156 mCRC patients data were evaluated, out of which 124 patient’s KRAS and NRAS mutation status was known. We evaluated demographic and clinical characteristics and progression-free survial(PFS) of mCRC patients treated with cetuximab-or bevacizumab-containing regimens. Results: Median age was 56 yrs(18-78yrs). Total 124 patient’s mutation status was known,out of which 34 (27%) were positive for KRAS and 4 (3%) for NRAS. Overall, there were 83 (67%) males and 41 (33%) females. In KRAS positive group, 26 (76%) were males and 08 (24%) females. Bevacizumab treated patients(69.2%) mostly received oxaliplatin-based backbone, whereas, cetuximab treated pateints(56.8%) mostly received irinotecan-based chemotherapy. There was no significant difference in PFS between cetuximab-and bevacizumab-based treated patients. Conclusion: Efforts to obtain tissue samples should be encouraged for KRAS and NRAS mutation testing in mCRC patients to provide a molecular basis to treat with available anti-EGFR monoclonal antibodies in mutation wild-type patients.

Maternal and Foetal Outcomes of Gestational Diabetes Mothers Treated with Human Insulin

Background: The most common adverse event that is associated with GDM is that it has led to higher incidence of maternal diabetes mellitus later in life and the major morbidities among the infants born to the diabetic mothers include respiratory distress, macrosomia, polycythaemia, hypoglycaemia, hypocalcaemia, hypomagnesemia, and congenital malformations. As most of the oral hypoglycaemic agents is prone to cause teratogenic effects the most preferred was the insulin therapy and the subcutaneous insulin therapy has been considered as the standard therapy in the management of GDM. Aim: To assess the factors associated in the incidence of diabetes among the gestational diabetes mothers and to assess the effect of insulin on them in terms of maternal and foetal outcome. Methodology: A prospective study was undertaken among the gestational mothers with diabetes for a period of one year during Jan 2015 – Dec 2015 at the Government Medical College Hospital, Salem. A total of 150 maternal mothers with more than 24 weeks of gestation were included in the study and who had been diagnosed as gestational diabetes mellitus. The insulin used for majority of the patients was novo rapid and it was used four times a day. The outcome parameters which were used for antenatal mothers were their weight gain and the type of complications at the time of delivery whereas for the neonates their birth weight and the necessity for NICU admission were considered as the outcome parameters. Results: the risk factors found to be associated with the gestational diabetes among the study population were age more than 30 years, BMI of more than 25, family history both father and mother being diabetic, having a bad obstetric history, primigravida and the mothers who had gained more than 7 kgs in the first two trimesters. majority of the mothers delivered macrosomia babies (29.3%), hypoglycaemia and hypothyroidism was found only in 6% and 5.3% of the new-born babies and 4 were still births and 15 babies were got admitted to NICU for respiratory distress. The pearson’s correlation had shown a strong positive correlation between the dose of the insulin given to the antenatal mother and their increase in the weight (r=0.819) and a strong negative correlation with the weight of the neonate (r= -0.532). Conclusions: Gestational diabetes mellitus being associated with maternal and neonatal adverse outcomes, so maintaining adequate blood glucose levels in GDM helps in reducing the morbidity for both the mother and baby. Insulin would be a right choice for treating GDM and when initiated early it prevents most of the complications due to GDM both in the mother and the neonate.

Epidemiology of male seminomatous and nonseminomatous germ cell tumors and response to first‑line chemotherapy from a tertiary cancer center in India.

INTRODUCTION: Unlike the developed countries, there is a lack of good epidemiologic data for testicular germ cell tumors (GCTs) in India with majority presenting in advanced stage. This study aims to elaborate on the epidemiology of testicular GCTs and response to standard first‑line chemotherapy (CT). METHODS: GCTs treated at our center from January 2013 to June 2014 were retrospectively analyzed. Patients underwent orchidectomy either outside or at our hospital. Based on stage and risk group, standard CT (bleomycin, etoposide, and cisplatin/etoposide and cisplatin/carboplatin AUC7) and radiotherapy were given as appropriate. Response was calculated based on the Response Evaluation Criteria in Solid Tumors. Statistical analysis was performed using SPSS 18 software. RESULTS: Fifty nonseminomatous germ cell tumor (NSGCT) and 36 of SGCT cases were studied. 30%, 46%, and 64% of NSGCT and 11%, 28%, and 22% of SGCT had N2, N3, and M1 diseases, respectively. The mean nodal size was 7 cm (1.5–19) in NSGCT and 5.5 cm (1.3–11) in SGCT. As per the International Germ Cell Cancer Collaborative Group classification, in patients with metastatic disease, 9% of NSGCT were good, 53% were intermediate, and 38% were poor risk whereas 75% of SGCT were good and 25% were intermediate risk. Following CT among NSGCT, 5% and 71% had radiologic complete response (CR) and partial response (PR), respectively. Among SGCT, 46% and 38% had radiologic CR and PR, respectively. 22%, 53%, and 13% of NSGCT and 12%, 24%, and 20% of SGCT developed febrile neutropenia, Grade 3 or 4 hematological and nonhematological toxicities, respectively, after standard chemotherapy. CONCLUSIONS: GCTs in India present with high nodal and high‑risk diseases wherein the standard first‑line CT may not be adequate as curative therapy; however, significant chemotoxicity is also a hindrance.

A prospective study of drug utilization pattern in cardiac intensive care unit at a tertiary care teaching hospital.

Background: Cardiovascular diseases remain the most common cause of sudden death. Appropriate drug therapy in cardiac intensive care unit (CICU) is crucial in managing cardiovascular emergencies and to decrease morbidity and mortality. The present study was conducted to observe the emergency cardiac diseases which are most frequently being treated and to study the prescribing prevalence among inpatients in CICU. Methods: A prospective, observational study was carried out among 102 patients admitted in CICU at a tertiary care teaching hospital, Karnataka, for a period of 3 months. Demographic data, clinical history, and complete drug therapy received during their stay in CICU was noted. Results: In our study, males (64.7%) had a higher incidence of cardiovascular emergencies than females (35.3%). Hypertension (32.4%) and Type 2 diabetes mellitus (28.4%) were the frequently associated co-morbid conditions. Antiplatelet drugs 80 (78.4%) was most commonly prescribed, followed by hypolipidemic drugs 75 (73.5%) and anticoagulants 65 (63.7%). The mean duration of stay in the hospital was 4.79±1.9 days. The average number of drugs per prescription was 7.8±2.2. Percentage of drugs prescribed by generic names was 52.9%. The percentage of drugs prescribed from essential drug list was 75.1%. Conclusions: Antiplatelet drugs were the most frequently prescribed drug group. Mean number of drugs per prescription were high. The prescribing pattern could be improved by reducing the number of drugs per prescription and by prescribing generic drugs to reduce the economic burden of the patients.

Prevention of perinatal group B streptococcal infections: A review with an Indian perspective.

Group B Streptococcus (GBS) is an important cause of maternal and neonatal morbidity and mortality in many parts of the world. Asymptomatic colonisation of the vagina and rectum with Group B streptococci is common in pregnancy. Maternal colonisation of GBS can vary depending on ethnicity and geographical distribution. Vertical transmission of this organism from mother to foetus may lead to neonatal GBS disease. Intra-partum use of antibiotics in these women has led to a decrease in the rate of early onset but not late onset GBS disease. Identifi cation of women with GBS is the key factor in the prevention of perinatal GBS disease. There are different screening strategies available to identify women at risk of perinatal GBS disease. Clinicians continue to face the challenge of choosing between preventive strategies to reduce the impact of perinatal GBS disease. Controversy exists regarding the ideal preventive strategy. In India, the mortality and morbidity associated with the GBS disease remains largely a under-recognised problem. This comprehensive review summarises the salient features of GBS disease and discusses the epidemiology, risk factors, screening strategies, intra-partum antibiotic prophylaxis with an Indian perspective and how it compares with the Western nations.

Human leukocyte antigen alleles, genotypes and haplotypes frequencies in renal transplant donors and recipients from West Central India.

BACKGROUND: Human leukocyte antigen (HLA) is comprised of a highly polymorphic set of genes which determines the histocompatibility of organ transplantation. The present study was undertaken to identify HLA class I and class II allele, genotype and haplotype frequencies in renal transplant recipients and donors from West Central India. MATERIALS AND METHODS: HLA typing was carried out using Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and unrelated renal transplant recipients and donors. RESULTS: The most frequent HLA class I and class II alleles and their frequencies in recipients were HLA-AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1 (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two-locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors, respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144-DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and 0.0323, respectively in donors. Genotype frequency revealed a high prevalence of genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109) whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in donors (0.0797). The phylogenetic and principal component analysis of HLA allele and haplotype frequency distribution revealed genetic similarities of various ethnic groups. Further, case control analysis provides preliminary evidence of association of HLA-A genotype (P < 0.05) with renal failure. CONCLUSION: This study will be helpful in suitable donor search besides providing valuable information for population genetics and HLA disease association analysis.

Sildenafil improves survival in idiopathic pulmonary arterial hypertension.

AIMS AND OBJECTIVES: Idiopathic Pulmonary Arterial Hypertension (IPAH) is a serious disorder of unknown etiology with limited therapeutic options. Sildenafil has been shown to decrease symptoms, improve hemodynamics and quality of life. Its impact on survival is uncertain. We studied the efficacy of sildenafil in improving survival in patients with IPAH. METHODS AND RESULTS: Data on survival of patients with IPAH was collected from prospectively maintained registry at our hospital from January 1999 to December 2005. Thirty nine patients who were treated with conventional therapy including digoxin, diuretics, anticoagulants and calcium channel blockers prior to January 2001 served as historical controls (control group). One hundred and thirty nine patients received sildenafil additionally from January 2001 (sildenafil group). All patients in sildenafil group showed improvement in symptoms. Survival of patients in sildenafil group was significantly better compared to historical controls receiving only conventional therapy. It was 89%, 43% and 19% in the control group Vs 93%, 75% and 54% in the sildenafil group at the end of 1, 3 and 5 years respectively (P Value=0.0002). Sildenafil was well tolerated and none of the patients had to discontinue the treatment. CONCLUSION: Sildenafil when added to conventional therapy improves symptoms as well as survival significantly compared to conventional therapy alone. Further randomized controlled trials are needed to evaluate its impact on survival when used either alone or in combination with other drugs.

Cerebral salt wasting syndrome in a patient with tuberculous meningitis.

We report a case of a 65 year male with meningitis who had polyuria, severe hyponatremia, volume depletion and very high urinary sodium excretion. He was diagnosed to have cerebral salt wasting syndrome based on clinical and laboratory parameters.

Site specific integration of FLP recombinase in BHK-21 cell line.

A binary system for gene activation and site specific integration based on conditional recombination of transfected sequences mediated by FLP recombinase from yeast was implemented in mammalian cells. In several cell lines, FLP rapidly and precisely recombined copies of its specific target sequences to activate an otherwise silent beta-galactosidase reporter gene. Clones of marked cells were generated by excisional recombination within a chromosomally integrated copy of the silent reporters. These clones exhibited intense blue colour with X-Gal staining solution.

A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension.

BACKGROUND: Primary pulmonary hypertension is a disorder with limited treatment options and poor outcome. Sildenafil, a pulmonary vasodilator, is likely to be beneficial in primary pulmonary hypertension. We studied the clinical efficacy of sildenafil in patients with primary pulmonary hypertension. METHODS AND RESULTS: A registry of patients with primary pulmonary hypertension has been maintained in our hospital since January 1999. Of a total of 60 patients. 29 (M:16, F:13) consented to try sildenafiL. New York Heart Association functional class, six-minute walk test and Doppler echocardiographic evaluation of pulmonary artery pressure was done before and after treatment with sildenafil. Sildenafil was initiated at a dose of 25 mg thrice a day and increased up to 100 mg thrice a day as tolerated. There was a significant improvement in the functional class. The six-minute walked distance increased from 297.07+/-130.69 m at baseline to 427.68+/-85.35 m after 3 months of sildenafil therapy (p<0.0003). The mean of the pulmonary artery systolic pressure before starting sildenaffil was 109.26+/-24.15 mmHg (mean+/-SD) and it decreased to 95.15+/-24.64 mmHg (p<0.008). While 19 of the 31 historical controls in whom sildenafil was not given died during follow-up (11-44 months), only 1 of the 29 patients given sildenafil died (in an accident) during follow-up (5-20 months). CONCLUSIONS: Sildenafil, a pulmonary vasodilator, has a beneficial effect in patients with primary pulmonary hypertension in improving the functional class, six-minute walked distance and in decreasing the pulmonary artery pressures.

'O' set connector system in CAPD.

51 CAPD patients (age 55.5 +/- 14.5 yrs, 35 male, 16 female) on CAPD using 'O' set were studied retrospectively during the period January 1993 to April 1995. Etiology of ESRD was Diabetic nephropathy-25(49%) and the other causes-26(51%). The total duration of observation on 'O' set was 553 patient months, the mean duration was 10.8 +/- 6.1 months. 24 patients (47%) developed total of 30 episodes of peritonitis. The incidence of peritonitis was 18.4 patient months per episode of peritonitis. The organisms responsible for peritonitis were Gram positive-6(20%), Gram negative-3(10%), Fungal-1(3.3%), Mycobacterial-1(3.3%), Eosinophilic-1(3.3%), Sterile-12(40%) and unknown-6(20%) 2 patients of bacterial peritonitis and a patient with tuberculous peritonitis died while rest of the patients responded favourably to antibiotics. 13(52%) diabetic patients and 11(42%) non-diabetic patients had peritonitis (p-NS) and the peritonitis rates in diabetics and non diabetics were 18.3 and 18.6 patient months per episode respectively (p-NS). Exit site infection was seen in 5 patients (10%) (Staph aureus-4, Enterococci-1) and all responded to antibiotic therapy. 7 patients had total of 10 episodes of symptomatic accidental intraperitoneal sodium hypochlorite instillation, none had any long term adverse effects. The 'O' set procedure was done by self in 10(20%) and by others in 41(80%) cases. The peritonitis rates when performed by self and others were 18.5 and 18.4 patient months per episode respectively (p-NS). The cost of being on CAPD using 'O' set, Y-bag and twin bag were Rs. 1,50,000, 2,10,000 and 3,72,000 per annum respectively and cost of maintenance haemodialysis was 1,36,800 per annum. The cost of CAPD using 'O' set was comparable to that of maintenance haemodialysis. The 'O' set connector system in CAPD is found to be safe, cost effective and efficient.