Decreased risk of hepatocellular carcinoma recurrence with direct-acting antivirals compared with no treatment for hepatitis C: a meta-analysis.

BACKGROUND: Studies investigating the association between direct-acting antivirals (DAAs) and the recurrence of hepatocellular carcinoma (HCC) related to hepatitis C (HCV) have yielded conflicting results. The objective of this meta-analysis was to define the short- and long-term recurrence rates of HCC after DAA treatment. METHODS: A search of multiple databases was performed, including Scopus, Cochrane, MEDLINE/PubMed and abstracts from gastroenterology meetings. Only studies reporting the recurrence of HCC in patients receiving DAA treatment, compared to HCV controls without DAA treatment, were evaluated. A meta-analysis was completed using the Mantel-Haenszel model. RESULTS: A comprehensive literature search resulted in 32 abstracts and papers. Six papers met our inclusion criteria and were included in the analysis. Follow up ranged from 1.25-4 years. Analysis of these 6 studies found a >60% lower risk of HCC recurrence in patients exposed to DAA compared to controls (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.27-0.47; P<0.001; I 2=88%). A sensitivity analysis, which excluded studies showing the lowest recurrence rate to reduce heterogeneity, showed that patients receiving DAA still had a 60% lower risk of developing HCC (OR 0.4, 95%CI 0.26-0.61; P<0.0001; I 2=39%) and a 66% lower risk of developing HCC beyond 1 year (OR 0.34, 95%CI 0.22-0.54; P<0.00001; I 2=0%) compared to controls. CONCLUSIONS: The use of DAA is associated with a significantly lower risk of HCC development compared to DAA-untreated patients, both overall and beyond 1 year of treatment. Further studies are needed to assess the impact of DAAs on early recurrence.

Implementation of transcranial Doppler ultrasonography screening and primary stroke prevention in urban and rural sickle cell disease populations.

BACKGROUND: Transcranial Doppler (TCD) ultrasonography identifies children with sickle cell disease (SCD) at increased risk of stroke. Initiation of chronic transfusions as primary stroke prevention in children with abnormal TCD significantly reduces stroke risk. Here, we report the results describing the implementation of TCD screening and primary stroke prevention in both urban and rural clinical practices. PROCEDURE: Retrospective chart review identified children ages 2-16 years with Hgb SS or Sß0 -thalassemia and no history of stroke followed in either the local urban or rural SCD clinics at Georgia Regents University. We defined standard of care (SOC) as having one TCD performed annually between January 2010 and December 2012 starting at age 2 years. RESULTS: A total of 195 patients were included in the evaluation of SOC screening, overall 41% achieved SOC. There was no difference in SOC between the two clinics (35% urban and 47.4% rural). The majority of patients with abnormal TCDs are on chronic transfusions (83%), and none have experienced a stroke. Monitoring of effects of transfusion was difficult with 38% and 31% of rural patients lacking documentation of Hgb S% and ferritin levels, respectively, in the past year. CONCLUSIONS: We report here data describing primary stroke prophylaxis in rural patients. SOC rates are similar between the two clinical settings. While implementation of primary stroke prevention in rural patients was difficult, rural TCD screening is feasible and can achieve SOC equal to that in an urban setting. This suggests that barriers exist in provided primary stroke prevention to all patients. Pediatr Blood Cancer 2015;62:219-223. © 2014 Wiley Periodicals, Inc.

Elevated cyclic stretch and serotonin result in altered aortic valve remodeling via a mechanosensitive 5-HT(2A) receptor-dependent pathway.

INTRODUCTION: Serotonin/5-hydroxytryptamine (5-HT) has been implicated in valve disease and in the modulation of valve mechanical properties. Several 5-HT receptor subtypes are also known to be mechanosensitive in other cell types, but this has not been studied in the context of the valve. In this study, we sought to understand the effects of elevated 5-HT levels and stretch overload on aortic valve remodeling and the dominant 5-HT receptor subtype that regulates these processes. METHODS AND RESULTS: Collagen biosynthesis and tissue mechanical properties of porcine aortic valve cusps were evaluated after 10% (physiologic) and 15% (pathologic) dynamic stretch. These studies were performed in normal medium or medium supplemented with 5-HT (1, 10, 100 µM) in the absence and presence of 5-HT(2A) or 5-HT(2B) receptor antagonists. Fresh valves served as controls. Valve collagen content was maximal at the 10-µM 5-HT concentration for both 10% and 15% stretch. The 5-HT(2A) receptor antagonist reduced collagen synthesis, cell proliferation, and hsp47 expression under elevated and normal stretch, whereas the 5-HT(2B) receptor antagonist was effective only at normal stretch. The pretransition stiffness of the valve cusps was also increased in response to 5-HT via a stretch-sensitive 5-HT(2A) mechanism, with the post-transition stiffness unaltered. CONCLUSIONS: Combined elevated stretch and 5-HT resulted in increased valve collagen biosynthesis, cell proliferation, and tissue stiffness. These responses were inhibited by a 5-HT(2A) antagonist. This strongly suggests that the 5-HT(2A) receptor subtype is sensitive to elevated stretch.