A recent meta-analysis suggested percutaneous transluminal angioplasty (PTA) for below the knee (BTK) lesions has inferior procedural and short-term outcomes relative to other endovascular modalities (Razavi MK et al, J Vasc Interv Radiol 2014;25:1489-96). The authors felt there is a general paucity of modern data reflective of the current status of endovascular interventions for treatment of atherosclerotic infrapopliteal disease and therefore conducted a systematic review and meta-analysis of contemporary series on the use and outcomes of PTA for this population, while also attempting to comprehensively characterize sources of data heterogeneity. MEDLINE and EMBASE databases were searched for contemporary studies (2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015) of PTA for treatment of infrapopliteal lesions. A random effects meta-analysis model was used to analyze procedural outcomes (technical success, flow-limiting dissections, provisional stent placement) and long-term outcomes (primary patency, repeat revascularization, major amputation, all-cause mortality). There were 52 studies encompassing 6769 patients with 9399 BTK lesions ultimately included in the analysis. Technical success was 91.1% (95% confidence interval [CI], 88.8-93.0). The incidence of flow-limiting dissections and bailout stenting was 5.6% (95% CI, 3.2-9.8) and 9.1% (95% CI, 6.3-12.9), respectively. Outcomes at 1-year were primary patency, 63.1% (95% CI, 57.3-68.6); repeat revascularization, 18.2% (95% CI, 14.5-22.6); major amputation, 14.9% (95% CI, 12.3-18.0); and all-cause mortality, 15.1% (95% CI, 12.8-17.7). There was significant heterogeneity and publication bias observed for most PTA outcomes.Comment: Contemporary studies of PTA for infrapopliteal arteries suggest suboptimal short-term and 1-year clinical outcomes. Also significant heterogeneity of the data limits interpretation and generalized ability of the studies. Clearly, procedural failures and loss of primary patency are therapeutic challenges that need to be addressed in this population of patients. The field is ripe for large scale multi-center prospective studies to evaluate existing infrapopliteal treatment modalities and to provide advanced contemporary evidence based treatment standards for BTK arterial disease.
A nitric oxide synthase (NOS) inhibitor, NG-nitro-L -arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to determine whether it prevents the intestinal damage usually observed under these conditions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg), whereas control rats including pair-fed (PF) and ad libitum consumption (AL) groups were given a zinc-supplemented (50.8 mg zinc/kg) diet for 4 wk. Half of the ZD rats received L-NAME (0.3 g/L in drinking water) for 3 wk starting at the wk 2 of the deficient period. Plasma zinc concentration in ZD rats was significantly lower (P < 0.05) than that of AL and PF rats. Administration of L-NAME did not alter this concentration. Intestinal zinc concentration did not differ among groups. However, metallothionein-1 (MT-1) mRNA level was significantly lower in the intestine of ZD rats than in AL or PF rats. Treatment of ZD rats with L-NAME did not affect this level. Intestinal microvascular permeability evaluated by Evans blue showed significantly higher extravasation in ZD rats than in AL rats, whereas L-NAME administration inhibited the extravasation. Expression of inducible NOS mRNA was observed in intestine of ZD but not of AL or PF rats, and there was no significant difference between ZD rats, regardless of L-NAME treatment. The activity ratio of inducible NOS to total NOS in ZD rats not receiving L-NAME was significantly higher than that in AL rats or ZD rats treated with L-NAME (P < 0.05). The number of apoptotic-positive and goblet cells in intestinal villi was significantly higher in ZD rats compared with AL or PF rats. L-NAME administration in ZD rats reversed this effect. These results indicate that inhibition of NOS ameliorates zinc deficiency-induced intestinal damage in rats.
These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine.
These data suggest that the mucus gel layer located in front of Peyer's patches is one of the important factors for the uptake of noxious macromolecules, and this in turn plays a major role on small intestinal permeability and subsequent translocation to MLNs.
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