Transaortic transcatheter aortic valve implantation with the Edwards SAPIEN valve: feasibility, technical considerations, and clinical advantages

The randomized Partner study [1] has recently shown superiority of transfemoral transcatheter aortic valve implantation, in patients who are not candidates for surgical aortic valve replacement, when compared with conventional nonsurgical therapies. In patients who are not candidates for the transfemoral approach because of peripheral vascular disease or other contraindications, deployment of the SAPIEN valve (Edwards Lifesciences, Irvine, CA) in an antegrade fashion can be achieved through the apex of the left ventricle. However this valuable technique carries specific risks inherent to the access route. Transaortic implantation, through an upper ministernotomy, offers a new alternative that could avoid complications related to the transapical approach.     

A cohort study of enfuvirtide immunological and virological efficacy in clinical practice

The aim of the study was to evaluate, under routine circumstances, the immunological and virological efficacy of antiretroviral regimens containing enfuvirtide in multi-class experienced HIV-1 infected patients. This retrospective monocentric study analyzed the clinical, immunological, and virological data of 18 HIV-1 infected patients who started enfuvirtide and completed at least 3 months of therapy. Following 3 months of enfuvirtide therapy, 11 (61%) patients had HIV-1 RNA below 400 copies/ml, among whom 8 (44%) patients below 50 copies/ml. In the ten patients still receiving enfuvirtide after 12 months, the median increase in CD4 cell count was 159 cells/microl (range, -25 to +301) and the mean decrease in HIV-1 RNA was 2.5 +/- 1.4 log(10) copies/ml; in six of these patients, viral load remained below 50 copies/ml. Five patients discontinued enfuvirtide for virological failure but none as a consequence of adverse event. Mutations located within the 36-45 amino acid domain of HR1 region of gp41 and associated to enfuvirtide resistance were found in all seven patients with persistent viral replication. In addition, a new mutation, A50V, emerged in one patient with late viral rebound. Its disappearance after treatment discontinuation suggests that it could play a role in resistance to enfuvirtide. In conclusion, enfuvirtide may be a good therapeutic option as rescue therapy in treatment-experienced patients. However, the mutations conferring resistance to enfuvirtide develop rapidly when viral load is not controlled confirming that enfuvirtide should be prescribed in association with an active background regimen.     

GCH1 expression in human cerebellum from healthy individuals is not gender dependant

Dopa-responsive dystonia (DRD) is a familial childhood-onset disease characterized by fluctuating dystonia, associated with tremor and parkinsonism in some patients. In most families the disease displays autosomal dominant inheritance due to mutations in the GTP cyclohydrolase 1 gene (GCH1). Penetrance and symptom severity display strong female predominance for which gender-specific GCH1 expression has been hypothesized. In this study, GCH1 mRNA expression was measured in cerebellar tissue from 66 healthy human subjects (30 women), and in cerebellar and nigral tissue from eight individuals. No significant difference was found between men and women with small effect sizes observed. Although the correlation between cerebellar and nigral GCH1 expression remains to be further examined, this exploratory study does not support gender-specific GCH1 expression being the basis for the skewed gender distribution observed in DRD patients.     

Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation

A randomized, controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy (PIPN). Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy were randomly assigned to receive either chemotherapy with vitamin E (300 mg twice a day, Group I) or chemotherapy without vitamin E supplementation (Group II). A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy. The severity of PIPN was summarized by means of a modified Peripheral Neuropathy (PNP) score. The incidence of neurotoxicity differed significantly between groups, occurring in 3/16 (18.7%) patients assigned to the vitamin E supplementation group and in 10/16 (62.5%) controls (P=0.03). The relative risk (RR) of developing PIPN was significantly higher in controls than in vitamin E group patients (RR=0.3, 95% confidence interval (CI)=0.1-0.9). Mean PNP scores were 2.25+/-5.1 (range 0-15) for patients in Group I and 11+/-11.63 (range 0-32) for those in Group II (P=0.01). Vitamin E supplementation was well tolerated and showed an excellent safety profile. This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage. A double-blind, placebo-controlled trial is needed to confirm these results.