Rare mediastinal masses - imaging review.

Mediastinal masses span a wide histopathological and radiological spectrum. Apart from primary thymic/thyroid masses and lymphomas, all other mediastinal masses can be considered rare tumors. Chest radiography and Computed tomography (CT) are helpful to characterize the mass and can reach a diagnosis or a close differential diagnosis. MRI in special situations can depict the pericardial/vascular invasion better, and diffusion studies can recognize benign from the malignant mass. The imaging details of 15 histopathologically proven cases of rare mediastinal tumors are described. Neuroblastoma (NB) (n = 3) was the most common among the rare masses. Three were sarcomas, one liposarcoma, one synovial sarcoma, one spindle-cell tumor and one Hemangiopericytoma (HPC). Lymphoma presenting as a single mass, neuroendocrine tumor (NET) of the anterior mediastinum, paraganglioma of the posterior mediastinum (one each) were seen.The imaging features of these rare mediastinal masses have to be kept in mind for appropriate diagnosis.

Primary Ewing's sarcoma of the lung: a rare case report.

The current case study had described the clinical presentation, evaluation, management, and outcome of a case of primary Ewing's Sarcoma of the lung. It was presented with cough, chest pain, and hemoptysis for 3 months in a 36-year-old male. Immunostaining of the sections prepared from the blocks using CD99 antibody revealed strong continuous cell membrane staining. Tumor cells showed negative staining for leukocyte common antigen (LCA), thyroid transcription factor 1 (TTF1), and pan-cytokeratin (AE1/AE3) consistent with extraskeletal Ewing's sarcoma (EES). Neoadjuvant chemotherapy of 6 cycles followed left lower lobectomy had led to good recovery and the patients are disease free at 18-month follow-up. Primary EES of the lung should be considered in the differential diagnosis when a young patient is presented with large mass without evidence of primary extrathoracic disease.

Association of CnB 5I/5D promoter gene polymorphism and serum calcineurin levels in early onset of coronary artery disease of south Indian cohort.

Calcineurin, a serine/threonine phosphatase is a calcium dependent protein which on activation triggers transcriptional up regulation of inflammatory genes associated with inflammation in the arteries and progressive formation of plaques in CAD. The present investigation is aimed to study the possible association of Calcineurin encoding gene PPP3R1 (CnB 5I/5D) polymorphism in correlation with serum levels of calcineurin in coronary artery disease (CAD). A total of 300 angiographically documented CAD patients and 300 age, gender ethnicity matched healthy controls were recruited for the study. Serum Calcineurin levels were estimated by enzyme-linked immunosorbent assay (ELISA) and genotypes were determined based on PCR-RFLP. The CnB 5I/5D variation was found to be significantly associated with CAD (p<0.03), correlated to elevated serum calcineurin levels encoded by (<0.01) 5I/5D allele authenticated by Insilco analysis. Multiple logistic regression analysis also confirmed these findings [adjusted OR for DD genotype was 3.19 (95% CI 1.40-7.24) and p=0.001]. The results suggest that 5-base pair deletion results in increased serum calcineurin levels and may trigger up regulation of calcineurin which mediates vascular inflammation and atherosclerosis in CAD.

Development of neuro-fuzzy model to explore gene-nutrient interactions modulating warfarin dose requirement.

AIM: To investigate the influence of alterations in vitamin K (K1, K2 and K3) in modulating warfarin dose requirement. PATIENTS & METHODS: Reverse phase HPLC to determine the plasma vitamin K; PCR-RFLP to detect polymorphisms; and the neuro-fuzzy model to predict warfarin dose were used. RESULTS: The developed neuro-fuzzy model showed a mean absolute error of 0.000024 mg/week. CYP2C9*2 and CYP2C9*3 mediated warfarin sensitivity was observed when vitamin K is in high and low tertiles, respectively. VKORC1-1639G>A exhibited warfarin sensitivity in all combinations. Higher vitamin K1 was observed in CYP4F2 V433M polymorphism. The requirement of warfarin is low in GGCX 8016 GG genotype compared with GA and AA genotypes. CONCLUSION: Vitamin K profile along with genetic testing ensures precision in warfarin dose optimization.

Artificial neural network-based pharmacogenomic algorithm for warfarin dose optimization.

AIM: To develop more precise pharmacogenomic algorithm for prediction of safe and effective dose of warfarin. MATERIALS & METHODS: An artificial neural network (ANN) algorithm was developed by using age, gender, BMI, plasma vitamin K levels, thyroid status and ten genetic variables as the inputs and therapeutic warfarin dose as the output. Hyperbolic tangent function was used to build an ANN architecture. RESULTS: This model explained 93.5% variability in warfarin dosing and predicted warfarin dose accurately in 74.5% patients whose international normalized ratio (INR) was less than 2.0 and in 83.3% patients whose INR was more than 3.5. This algorithm reduced the out-of-range INRs (odds ratio [OR]: 0.49; 95% CI: 0.30-0.79; p = 0.003), the rate of adverse drug reactions (OR: 0.00; 95% CI: 0.00-1.21; p = 0.06) and time to reach first therapeutic INR (OR: 6.73; 95% CI: 2.17-22.31; p < 0.0001). This algorithm was found to be applicable in both euthyroid and hypothyroid status. S-warfarin/7-hydroxywarfarin ratio was found to increase in subjects with CYP2C9*2 and CYP2C9*3 justifying the warfarin sensitivity attributed to these variants. CONCLUSION: An application of ANN for warfarin dosing improves predictability and provides safe and effective dosing.

Pryce type I sequestration: no mosquito shooting.

We report a case of a 40-year-old woman with congenital dual arterial supply to an otherwise normal left lower lobe, causing hyperperfusion lung injury. In addition to near normal pulmonary arterial supply, the lower lobe of the left lung received a systemic arterial supply from the descending thoracic aorta. The patient was successfully managed by surgical ligation of the systemic arterial supply without lobectomy. We discuss when to defer lobectomy in Pryce type I sequestration.

Retrospective evidence for clinical validity of expanded genetic model in warfarin dose optimization in a South Indian population.

AIM: To optimize warfarin dose in patients at risk for thrombotic events, we have recently developed a pharmacogenomic algorithm, which explained 44.9% of the variability in warfarin dose requirements using age, gender, BMI, vitamin K intake, CYP2C9 (*2 and *3) and VKORC1 (*3, *4 and -1639 G>A) as predictors. The aim of the current study is to develop an expanded genetic model that can explain greater percentage of warfarin variability and that has clinical validity. PATIENTS & METHODS: CYP2C9*8, CYP4F2 V433M, GGCX G8016A and thyroid status were added to an expanded genetic model (n = 243). RESULTS: The expanded genetic model explained 61% of the variability in warfarin dose requirements, has a prediction accuracy of ±11 mg/week and can differentiate warfarin sensitive and warfarin resistant groups efficiently (areas under receiver operating characteristic curves: 0.93 and 0.998, respectively; p < 0.0001). Higher percentage of International Normalized Ratios in therapeutic range (52.68 ± 4.21 vs 43.80 ± 2.27; p = 0.04) and prolonged time in therapeutic range (61.74 ± 3.18 vs 47.75 ± 5.77; p = 0.03) were observed in subjects with a prediction accuracy of <1 mg/day compared with subjects with prediction accuracy >1 mg/day. In the warfarin-resistant group, primary hypothyroidism was found to induce more resistance while in the warfarin-sensitive group, hyperthyroidism was found to increase sensitivity. CONCLUSION: The expanded genetic model explains greater variability in warfarin dose requirements and it prolongs time in therapeutic range and minimizes out-of-range International Normalized Ratios. Thyroid status also influences warfarin dose adjustments.