Comparative Outcomes of Interventions for Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From the Multicenter XLPAD Registry

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%

miR-210: fine-tuning the hypoxic response

Hypoxia is a central component of the tumor microenvironment and represents a major source of therapeutic failure in cancer therapy. Recent work has provided a wealth of evidence that noncoding RNAs and, in particular, microRNAs, are significant members of the adaptive response to low oxygen in tumors. All published studies agree that miR-210 specifically is a robust target of hypoxia-inducible factors, and the induction of miR-210 is a consistent characteristic of the hypoxic response in normal and transformed cells. Overexpression of miR-210 is detected in most solid tumors and has been linked to adverse prognosis in patients with soft-tissue sarcoma, breast, head and neck, and pancreatic cancer. A wide variety of miR-210 targets have been identified, pointing to roles in the cell cycle, mitochondrial oxidative metabolism, angiogenesis, DNA damage response, and cell survival. Additional microRNAs seem to be modulated by low oxygen in a more tissue-specific fashion, adding another layer of complexity to the vast array of protein-coding genes regulated by hypoxia

Choosing what works for whom: towards a better use of mechanistic knowledge in clinical practice

Abstract Background Clinicians commonly try to use mechanism-based knowledge to make sense of the complexity and uncertainty of chronic pain treatments to create a rationale for their clinical decision-making. Although this seems intuitive, there are some problems with this approach. Discussion The widespread use of mechanism-based knowledge in clinical practice can be a source of confusion for clinicians, especially when complex interventions with different proposed mechanisms of action are equally effective. Although the available mechanistic evidence is still of very poor quality, in choosing from various treatment options for people with chronic pain, an approach that correctly incorporates mechanistic reasoning might aid clinical thinking and practice. Conclusion By explaining that not all evidence of mechanism is the same and by making a proposal to start using mechanism-based knowledge in clinical practice properly, we hope to help clinicians to incorporate mechanistic reasoning to prioritize and start choosing what may best work for whom

Comparative Outcomes of Interventions for Femoropopliteal Chronic Total Occlusion Versus Non–Chronic Total Occlusion Lesions From the Multicenter XLPAD Registry

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non‐CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non‐CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1‐year major adverse limb events, a composite of all‐cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non‐CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non‐CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%, P<0.001) or drug‐coated balloon angioplasty (1.26% versus 2.93%, P<0.001) were more frequent in the non‐CTO group, whereas bare‐metal stents (28.09% versus 20.22%, P<0.001) or covered stents (4.08% versus 1.83%, P<0.001) were more frequent in the CTO group. Debulking procedures were more commonly performed in the non‐CTO group (41.44% versus 53.13%, P<0.001), despite a similar degree of calcification between the 2 groups. Procedural success was higher in the non‐CTO group (90.12% versus 96.79%, P<0.001). Procedural complications were higher in the CTO group (7.21% versus 4.66%, P=0.002), mainly due to excess distal embolization (1.5% versus 0.6%, P=0.015). Adjusted 1‐year major adverse limb events were higher in the CTO group (22.47% versus 18.77%, P=0.019), driven mainly by target limb revascularization (19.00% versus 15.34%, P=0.013). Conclusions Procedural success is lower for endovascular treatment of femoropopliteal CTO compared with non‐CTO lesions. CTO lesions are associated with higher rates of periprocedural complications and reinterventions after 1 year