Exomic analysis of myxoid liposarcomas,synovial sarcomas,and osteosarcomas

Bone and soft tissue sarcomas are a group of histologically heterogeneous and relatively uncommon tumors. To explore their genetic origins, we sequenced the exomes of 13 osteosarcomas, eight myxoid liposarcomas (MLPS), and seven synovial sarcomas (SYN). These tumors had few genetic alterations (median of 10.8). Nevertheless, clear examples of driver gene mutations were observed, including canonical mutations in TP53, PIK3CA, SETD2, AKT1, and subclonal mutation in FBXW7. Of particular interest were mutations in H3F3A, encoding the variant histone H3.3. Mutations in this gene have only been previously observed in gliomas. Loss of heterozygosity of exomic regions was extensive in osteosarcomas but rare in SYN and MLPS. These results provide intriguing nucleotide‐level information on these relatively uncommon neoplasms and highlight pathways that help explain their pathogenesis. © 2013 Wiley Periodicals, Inc.     

Comparative effectiveness and survival of infliximab,adalimumab, and etanercept for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low rates of remission and 5-year drug survival

Objective

To compare effectiveness, drug survival, and safety between infliximab, adalimumab, and etanercept, in a nationwide cohort of rheumatoid arthritis (RA) patients.

Methods

This study is a prospective cohort study of 1208 active RA patients. Effectiveness, drug survival, and serious adverse events during entire follow-up (median 2.9 years) were monitored.

Results

EULAR and CDAI responses were comparable between the three agents (EULAR good/moderate responses at 12 months ranged 76–79%). At 12 months, 15–23% achieved remission. For adalimumab and etanercept, adjusted hazard rate (HR) for EULAR/ACR remission (reference: infliximab) was 2.7 and 2.1 (95% confidence interval was 1.7–4.1 and 1.3–3.4, respectively); males (HR 1.6; 1.1–2.4), use of glucocorticoids (HR 2.0; 1.3–3.0), and swollen joint count >7 (HR 0.36; 0.24–0.55) were independent predictors. Five-year drug survival was 31%, 43%, and 49% for infliximab, adalimumab, and etanercept, respectively (p = 0.010). Infliximab was associated with significantly more withdrawals due to adverse events. Disease activity, CRP, and use of glucocorticoids predicted efficacy-related drug survival; age, use of methotrexate, and prior DMARDs failures predicted safety-related survival. Risk for serious infections was lower with adalimumab (odds ratio [OR] 0.62; 0.38–1.00) or etanercept (OR 0.39; 0.21–0.72) than infliximab, independent of the effects of age (OR 1.65; 1.37–2.00 per 10 years), tender joint count >10 (OR 1.86; 1.21–2.86), and glucocorticoids >35 mg/week (OR 1.83; 1.12–2.99).

Conclusions

Response rates were comparable among anti-TNF agents. Overall, 5-year drug survival was below 50%, with infliximab demonstrating increased safety-related discontinuations. Remission rates are low in clinical practice. Strategies to increase effectiveness and long-term survival of anti-TNF agents in RA are needed.     

The Right Ventricle in Health and Disease: Insights into Physiology, Pathophysiology and Diagnostic Management

Until recently, the right ventricle (RV) received little attention in adult patients with congenital heart disease and even less attention in the setting of acquired heart failure. However, in the last two decades, our perspective towards the right side of the heart has begun to change. Advances in imaging modalities have permitted the accurate study of RV physiology and made it apparent that RV function is an important determinant of prognosis in heart failure irrespective of the underlying etiology. This article summarizes the existing data on the unique anatomical and physiological features of the RV. The hemodynamic conditions and cellular and biochemical pathways that lead to right heart failure are presented. Moreover, the imaging modalities that aid in the assessment of RV structure and function are described and the importance of the diagnostic and prognostic information they provide is discussed.