Vascularized tissue‐engineered chambers promote survival and function of transplanted islets and improve glycemic control

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154402/1/fsb2fj054879fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154402/2/fsb2fj054879fje-sup-0001.pd

Angioplasty versus stenting for infrapopliteal arterial lesions in chronic limb-threatening ischaemia

Background: Chronic limb-threatening ischaemia (CLTI) is a manifestation of peripheral arterial disease (PAD) that includes chronic ischaemic rest pain or ischaemic skin lesions, ulcers, or gangrene for longer than two weeks. The severity of the disease depends on the extent of arterial stenosis and the availability of collateral circulation. Treatment for CLTI aims to relieve ischaemic pain, heal ischaemic ulcers, prevent limb loss, improve quality of life, and prolong survival. CLTI due to occlusive disease in the infrapopliteal arterial circulation (below-knee circulation) can be treated via an endovascular technique by a balloon opening the narrowed vessel, so called angioplasty, with or without the additional deployment of a scaffold made of metal alloy or other material, so called stenting. Endovascular interventions in the infrapopliteal vasculature may improve symptoms in patients with CLTI by re-establishing in-line blood flow to the foot. Controversy remains as to whether a balloon should be used alone to open the vessel, or whether a stent should also be deployed. Objectives: To determine the efficacy and safety of percutaneous transluminal angioplasty (PTA) alone versus PTA with stenting of infrapopliteal arterial lesions (anterior tibial artery, posterior tibial artery, fibular artery (formerly known as peroneal artery), and common tibioperoneal trunk) for patients with chronic limb-threatening ischaemia (CLTI). Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, as well as World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 25 June 2018. We applied no language restrictions. Selection criteria: We planned to include randomised or quasi-randomised controlled trials comparing PTA versus PTA with a stent and including patients aged 18 years or over with CLTI. We defined CLTI as Fontaine stage III (ischaemic rest pain) and IV (ischaemic ulcers or gangrene) or consistent with Rutherford category 4 (ischaemic rest pain), 5 (minor tissue loss), and 6 (major tissue loss), with stenotic (> 50% luminal loss) or occluded infrapopliteal artery, including tibiofibular trunk, anterior tibial artery, posterior tibial artery, and fibular artery. We included all types of stents irrespective of design (e.g. bare-metal, drug-eluting, bio-absorbable). Data collection and analysis: Two review authors (CC-TH and GNCK) independently selected suitable trials, assessed trial quality, and extracted data. An additional third review author (MLvD) assessed trial quality and, when necessary, acted as arbiter for study selection and data extraction. Outcomes included technical success of the procedure, procedural complications, patency, major amputation, and mortality. We assessed the quality of evidence using the GRADE approach. Main results: We included in the review seven trials with 542 participants. One trial randomised limbs to undergo PTA alone or PTA with stent placement, and the remaining studies randomised participants. Five trials with 476 participants show that the technical success rate was greater in the stent group than in the angioplasty group (odds ratio (OR) 3.00, 95% confidence interval (CI) 1.14 to 7.93; 476 lesions; 5 studies; I2 = 23%). Meta-analysis of three eligible trials with 456 participants did not show a clear difference in short-term (within six months) patency between infrapopliteal arterial lesions treated with PTA and those treated with PTA and stenting (OR 0.88, 95% CI 0.37 to 2.11; 456 lesions; 3 studies; I2 = 77%). Results also did not show clear differences between treatment groups in procedure complication rate (OR 0.87, 95% CI 0.01 to 53.60; 360 participants; 5 studies; I2 = 85%), rate of major amputations at 12 months (OR 1.34, 95% CI 0.56 to 3.22; 306 participants; 4 studies; I2 = 0%), and rate of mortality at 12 months (OR 0.71, 95% CI 0.43 to 1.17; 497 participants; 6 studies; I2 = 0%). Heterogeneity between studies was high for the outcomes procedure complications and primary patency. The overall methodological quality of the trials included in this review was moderate due to selection and performance bias. Studies used different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication. We downgraded the certainty of the overall evidence for all outcomes by one level to moderate due to inconsistency of results across studies and large confidence intervals (small numbers of trials and participants). Authors' conclusions: Trials show that the immediate technical success rate of restoring luminal patency is higher in the stent group but reveal no clear differences in short-term patency at six months between infrapopliteal arterial lesions treated with PTA with stenting versus those treated with PTA without stenting. We ascertained no clear differences between groups in periprocedural complications, major amputation, and mortality. However, use of different regimens for pretreatment and post-treatment antiplatelet/anticoagulant medication and the duration of its use within and between trials may have influenced the outcomes. Limited currently available data suggest that high-quality evidence is insufficient to show that PTA with stent insertion is superior to use of standard PTA alone without stenting for treatment of infrapopliteal arterial lesions. Further studies should standardise the use of antiplatelets/anticoagulants before and after the intervention to improve the comparability of the two treatments

Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

Background: Autologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice. Methodology/Principal Findings: Human fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPOtreated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts. Conclusions/Significance: Our data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fa