A Pilot Study of Femoropopliteal Artery Revascularisation with a Low Dose Paclitaxel Coated Balloon: Is Predilatation Necessary?

OBJECTIVE/BACKGROUND: The objective was to compare 2 year outcomes in patients treated with or without predilatation prior to drug coated balloon (DCB) angioplasty for symptomatic femoropopliteal lesions. METHODS: This prospective multicentre pilot study was conducted at three sites in Germany. It compared claudicants undergoing predilatation with a bare percutaneous transluminal angioplasty (PTA) balloon before DCB (predilatation group) with patients undergoing direct DCB (direct DCB group). Patients were followed for 2 years. Outcomes included late lumen loss at 6 months, and ankle brachial index (ABI), major adverse events, and primary patency at 2 years. A Clinical Events Committee and core laboratories analysed adverse events and angiographic/duplex images, respectively. RESULTS: Between December 2011 and November 2012, 50 patients were enrolled to the predilatation group (12% total occlusions) and 28 to the direct DCB group (5% total occlusions). Follow-up compliance at the 2 year visit was 88% (n = 44) and 86% (n = 24), respectively. Late lumen loss at 6 months was lower in the direct DCB group (0.03 ± 0.68 mm vs. 0.54 ± 0.97 mm; p = .01). Major adverse events over 2 years occurred in seven (15%) patients who underwent predilatation and in five (19%) after direct DCB. Mean ABI at 2 years was 0.94 ± 0.15 after predilatation and 1.0 ± 0.12 after direct DCB. Over 2 years, primary patency (80.3% vs. 78.2%; p = .55) was not statistically different between the groups. After propensity score adjustments, 2 year findings remained unchanged. CONCLUSION: Paclitaxel coated PTA, with or without bare predilatation, is effective over 2 years in symptomatic patients with femoropopliteal stenotic lesions. Adequately powered randomised controlled comparisons are required to confirm these preliminary results.

Safety assessment of DHA-rich microalgae from Schizochytrium sp.

The purpose of this study was to determine the potential toxicity of docosahexaenoic acid-rich microalgae from Schizochytrium sp. (DRM), administered in the diet to rats for at least 13 weeks. DRM was administered in the diet to groups of 20 male and 20 female Sprague-Dawley derived rats (Crl:CD(SD)BR) to provide dosages of 0, 400, 1500, and 4000 mg/kg/day for at least 13 weeks. DRM contained high levels of fat (approximately 41% w/w) of which long-chain highly unsaturated fatty acids (PUFAs) were a major component. Vitamin E acetate was added to DRM at manufacture to provide supplementary dietary antioxidant given the highly unsaturated fat content of DRM. Untreated controls received the basal diet only. An additional group of 20 males and 20 females received basal diet mixed with fish oil (Arista) to provide a target dosage of 1628 mg/kg/day, an amount of fat comparable to that received by rats administered the highest dose of DRM. Vitamin E acetate was also added to the fish oil to provide a comparable level of dietary antioxidant provided to high-dose DRM rats. There were no treatment-related effects in clinical observations, body weights or weight gains, food consumption, hematologic or urinalysis values, gross necropsy findings, or organ weights and there were no deaths. The only treatment-related changes in clinical chemistry parameters were decreases in high-density lipoproteins and cholesterol in the DRM and fish oil groups when compared to the untreated controls. These changes were expected based on the high PUFA content of DRM and fish oil. There were no microscopic findings suggestive of toxicity. Periportal hepatocellular fat vacuolation (accumulation of fat) was observed only in the livers of female rats in both the DRM (all dosages) and fish oil groups. This finding was expected given the higher fat content of both the DRM and the fish oil diets compared to the basal diet fed to the untreated controls. A slight increase in the incidence, but not severity, of cardiomyopathy was observed only in the 4000 mg/kg/day DRM males. This finding was not considered adverse because cardiomyopathy occurs spontaneously in rats and especially male rats of the Sprague-Dawley strain when fed high levels of fat. Since cardiomyopathy does not develop in other species including primates fed high-fat diets, its occurrence in rats is considered to have little relevance to human health. This study demonstrates that administration of DRM did not produce any treatment-related adverse effects in Sprague-Dawley rats of relevance to humans at dosages up to 4000 mg/kg/day for 13 weeks.

Morphology and pathogenesis of tumors of the thymus and stomach in Sprague-Dawley rats following intragastric administration of methyl nitrosourea (MNU).

Intragastric intubation of MNU (20 mg/kg twice weekly for 9 weeks) into young Srague-Dawley rats resulted in a 100% incidence of thymic lymphomas and gastric carcinomas in animals surviving more than 14 weeks. Progressive thymic atrophy followed the successive MNU administration culminating in marked lymphoid depletion by the 5th week of MNU treatment. At 6 weeks, repopulation of the thymus with lymphoblastic cells was observed, which progressed to thymic neoplasia. The first thymic lymphoma appeared at the 6th week. By the 15th week all rats were either moribund or had succumbed to anoxia caused by pleural effusions associated with thymic neoplasia. Twenty-six of 31 thymic tumors were classified as lymphocytic lymphomas, 2 as histiocytic, 1 as mixed lymphocytic-histiocytic, 1 as bimorphic and 1 as an epithelial thymoma. All but 2 lymphomas were restricted to the thymus. Of these 2 (both histiocytic lymphomas), 1 involved the spleen, liver and abdominal lymph nodes and the other infiltrated locally into cervical and thoracic regions. Significant thymic enlargement occurred only after MNU treatment was stopped (MNU acting as an anti-cancer drug). The gastric carcinomas were restricted to the non-glandular portion of the stomach and developed as a final step following ulceration, hyperplasia and neoplastic transformation. The short latency period and the high incidence of thymic neoplasms represent valuable criteria for future use of this model for pathomorphogenetic as well as immuno- and chemotherapeutic investigations.