Risk of critical limb ischemia in long-term uterine cancer survivors:A population-based study

BACKGROUND The risk of critical limb ischemia(CLI)which causes ischemic pain or ischemic loss in the arteries of the lower extremities in long-term uterine cancer(UC)survivors remains unclear,especially in Asian patients,who are younger at the diagnosis of UC than their Western counterparts.AIM To conduct a nationwide population-based study to assess the risk of CLI in UC long-term survivors.METHODS UC survivors,defined as those who survived for longer than 5 years after the diagnosis,were identified and matched at a 1:4 ratio with normal controls.Stratified Cox models were used to assess the risk of CLI.RESULTS From 2000 to 2005,1889 UC survivors who received surgery alone or surgery combined with radiotherapy(RT)were classified into younger(onset age<50 years,n=894)and older(onset age≥50 years,n=995)groups.While compared with normal controls,the younger patients with diabetes,hypertension,and receiving hormone replacement therapy(HRT)were more likely to develop CLI.In contrast,the risk of CLI was associated with adjuvant RT,obesity,hypertension,and HRT in the older group.Among the UC survivors,those who were diagnosed at an advanced age(>65 years,aHR=2.48,P=0.011),had hypertension(aHR=2.18,P=0.008)or received HRT(aHR=3.52,P=0.020)were at a higher risk of CLI.CONCLUSION In this nationwide study,we found that the risk factors associated with CLI were similar in both cohorts except for adjuvant RT that was negligible in the younger group,but positive in the older group.Among the survivors,hypertension,advanced age,and HRT were more hazardous than RT.Secondary prevention should include CLI as a late complication in UC survivorship programs.

Autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia

Objective： To study the efficacy and safety of autologous transplantation of bone marrow mesenchymal stem cells on diabetic patients with lower limb ischemia. Methods： Fifty Type 2 diabetic patients with lower limb ischemia were enrolled and randomized to either transplanted group or control group. Patients in both group received the same conventional treatment. Meanwhile, 20 ml bone marrow from each transplanted patient were collected, and the mesenchymal stem cells were separated by density gradient centrifugation and cultured in the medium with autologous serum. After three-weeks adherent culture in vitro, 7.32×10^8-5.61×10^9 mesenchymal stem cells were harvested and transplanted by multiple intramuscular and hypodermic injections into the impaired lower limbs. Results： At the end of 12-week follow-up, 5 patients were excluded from this study because of clinical worsening or failure of cell culture. Main ischemic symptoms, including rest pain and intermittent claudication, were improved significantly in transplanted patients. The ulcer healing rate of the transplanted group （1 5 of 18, 83.33%） was significantly higher than that of the control group （9 of 20, 45.00%, P=0.012）.The mean of resting ankle-brachial index （ABI） in transplanted group significantly was increased from 0.61±0.09 to 0.74±0.11 （P〈0.001）. Magnetic resonance angiography （MRA） demonstrated that there were more patients whose score of new vessels exceeded or equaled to 2 in the transplant patients （11 of 15） than in control patients （2 of 14, P=0.001）. Lower limb amputation rate was significantly lower in transplanted group than in the control group （P=0.040）. No adverse effects was observed in transplanted group. Conclusion： These results indicate that the autologous transplantation of bone marrow mesenchymal stem cells relieves critical lower limb ischemia and promotes ulcers healing in Type 2 diabetic patients.

Overcoming ischemia in the diabetic foot:Minimally invasive treatment options

As the global burden of diabetes is rapidly increasing,the incidence of diabetic foot ulcers is continuously increasing as the mean age of the world population increases and the obesity epidemic advances.A significant percentage of diabetic foot ulcers are caused by mixed micro and macro-vascular dysfunction leading to impaired perfusion of foot tissue.Left untreated,chronic limb-threatening ischemia has a poor prognosis and is correlated with limb loss and increased mortality;prompt treatment is required.In this review,the diagnostic challenges in diabetic foot disease are discussed and available data on minimally invasive treatment options such as endovascular revascularization,stem cells,and gene therapy are examined.

Autologous bone marrow stem cell transplantation in critical limb ischemia： a meta-analysis of randomized controlled trials

Background Amputation-free survival （AFS） has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia （NO-CLI） therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells （BMCs） transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear. Methods We conducted a meta-analysis using data from randomized controlled trials （RCTs） by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials （to approximately July 25, 2012） were searched. Results Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI （odds ratio （OR）, 0.37; 95% confidence interval （CI）, 0.22 to 0.62; P=-0.0002）, and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95% CI, 0.16 to 0.70; P=0.004 within 6 months and OR, 0.30; 95% CI, 0.11 to 0.79; P=0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI （OR 3.28; 95% CI, 1.12 to 9.65; P=0.03）, while there was no significant improvement in patients with Rutherford class 4 （OR 0.35; 95% CI, 0.05 to 2.33; P=0.28） compared with controls. The BMCs therapy also improved ulcer healing （OR, 5.83; 95% CI, 2.37 to 14.29; P=-0.0001）. Conclusions Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.

Revisiting endovascular treatment in below-the-knee disease. Are drug-eluting stents the best option？

Patients with below-the-knee arterial disease are primarily individuals suffering from critical limb ischemia(CLI), while a large percentage of these patients are also suffering from diabetes or chronic renal failure or both. Available data from randomized controlled trials and their meta-analysis demonstrated that the use of infrapopliteal drug-eluting stents(DES), in short-to medium-length lesions, obtains significantly better results compared to plain balloon angioplasty and bare metal stenting with regards to vascular restenosis, target lesion revascularization, wound healing and amputations. Nonetheless, the use of this technology in every-day clinical practice remains limited mainly due to concerns regarding the deployment of a permanent metallic scaffold and the possibility of valid future therapeutic perspectives. However, in the majority of the cases, these concerns are not scientifically justified. Large-scale, multicenter randomized controlled trials, investigating a significantly larger number of patients than those already published, would provide more solid evidence and consolidate the use of infrapopliteal DES in CLI patients. Moreover, there is still little evidence on whether this technology can be as effective for longer below-the-knee lesions, where a considerable number of DES is required. The development and investigation of new, longer balloon-expanding or perhaps selfexpanding DES could be the answer to this problem.

Quantifying tissue perfusion after peripheral endovascular procedures:Novel tissue perfusion endpoints to improve outcomes

Peripheral artery disease(PAD)is a flow-limiting condition caused by narrowing of the peripheral arteries typically due to atherosclerosis.It affects almost 200 million people globally with patients either being asymptomatic or presenting with claudication or critical or acute limb ischemia.PAD-affected patients display increased mortality rates,rendering their management critical.Endovascular interventions have proven crucial in PAD treatment and decreasing mortality and have significantly increased over the past years.However,for the functional assessment of the outcomes of revascularization procedures for the treatment of PAD,the same tests that have been used over the past decades are still being employed.Those only allow an indirect evaluation,while an objective quantification of limb perfusion is not feasible.Standard intraarterial angiography only demonstrates post-intervention vessel patency,hence is unable to accurately estimate actual limb perfusion and is incapable of quantifying treatment outcome.Therefore,there is a significant necessity for real-time objectively measurable procedural outcomes of limb perfusion that will allow vascular experts to intraop eratively quantify and assess outcomes,thus optimizing treatment,obviating misinterpretation,and providing significantly improved clinical results.The purpose of this review is to familiarize readers with the currently available perfusion-assessment methods and to evaluate possible prospects.

Long-term results of extensive aortoiliac occlusive disease (EAIOD) treated by endovascular therapy and risk factors for loss of primary patency

Background::Although endovascular therapy has been widely used for focal aortoiliac occlusive disease(AIOD),its performance for extensive AIOD(EAIOD)is not fully evaluated.We aimed to demonstrate the long-term results of EAIOD treated by endovascular therapy and to identify the potential risk factors for the loss of primary patency.Methods::Between January 2008 and June 2018,patients with a clinical diagnosis of the 2007 TransAtlantic Inter-Society Consensus II(TASC II)C and D AIOD lesions who underwent endovascular treatment in our institution were enrolled.Demographic,diagnosis,procedure characteristics,and follow-up information were reviewed.Univariate analysis was used to identify the correlation between the variables and the primary patency.A multivariate logistic regression model was used to identify the independent risk factors associated with primary patency.Five-and 10-year primary and secondary patency,as well as survival rates,were calculated by Kaplan-Meier analysis.Results::A total of 148 patients underwent endovascular treatment in our center.Of these,39.2%were classified as having TASC II C lesions and 60.8%as having TASC II D lesions.The technical success rate was 88.5%.The mean follow-up time was 79.2±29.2 months.Primary and secondary patency was 82.1%and 89.4%at 5 years,and 74.8%and 83.1%at 10 years,respectively.The 5-year survival rate was 84.2%.Compared with patients without loss of primary patency,patients with this condition showed significant differences in age,TASC II classification,infrainguinal lesions,critical limb ischemia(CLI),and smoking.Multivariate logistic regression analysis showed age<61 years(adjusted odds ratio[aOR]:6.47;95%CI:1.47-28.36;P=0.01),CLI(aOR:7.81;95%CI:1.92-31.89;P=0.04),and smoking(aOR:10.15;95%CI:2.79-36.90;P<0.01)were independent risk factors for the loss of primary patency.Conclusions::Endovascular therapy was an effective treatment for EAIOD with encouraging patency and survival rate.Age<61 years,CLI,and smoking were independent risk factors for the loss of primary patency.