Chronic Critical Limb Ischemia Research Articles

A comparative retrospective analysis of the results of hybrid interventions and femoral-tibial bypass in extended multi-level infrainguinal arterial segment lesions in patients with chronic critical limb ischemia

A comparative retrospective analysis of the results of hybrid interventions and femoral-tibial bypass in extended multi-level infrainguinal arterial segment lesions in patients with chronic critical limb ischemia

Trends in outcomes associated with the use of Auryon atherectomy system in a real-world setting

BackgroundWhile endovascular approaches are considered first line treatment for stenosis or occlusion of the lower limb arteries, major dissections and embolic events remain procedural risks. Newer technologies are needed which limit these complications while achieving desired clinical outcomes. MethodsThe Auryon atherectomy system (AngioDynamics) consists of a 355-nm wavelength solid-state Nd:YAG short pulse laser combined with dedicated optical catheters. This single-center, retrospective chart review assessed the safety and efficacy of this device in patients with PAD treated at our center between March and December 2020. ResultsA total of 55 patients were included. Mean age was 73.7 ± 9.3 years with 63.6 % of patients being males. Lesions were above the knee only for 16.4 % of patients, below the knee only for 3.6 %, and both above and below the knee for 80.0 % of patients. One patient had in-stent restenosis. Chronic total occlusions and critical limb ischemia were present for 43.6 % of patients respectively. Procedural success, defined as <30 % residual stenosis without any complications, was achieved in 85.5 % of patients. Stenosis/re-occlusion occurred in 25.5 % of patients at a mean of 168.9 ± 73.4 days with resultant target lesion revascularization (TLR) at 218.3 ± 92.4 days. Four patients underwent minor amputations. No patients experienced procedure-related complications. One patient died unrelated to the procedure. ConclusionThe Auryon laser system was shown to be safe and effective in this real-world patient population with no procedural adverse events or deaths and improvements in patient outcomes.

A Modified Run-Off Resistance Score from Cross-Sectional Imaging Discriminates Chronic Critical Limb Ischemia from Intermittent Claudication in Peripheral Arterial Disease.

Atherosclerotic peripheral arterial disease (PAD) leads to intermittent claudication (IC) and may progress into chronic limb-threatening ischemia (CLTI). Scoring systems to determine the atherosclerotic burden of a diseased extremity have been developed. This study aimed to evaluate a modification of the run-off resistance (mROR) score for its usability in cross-sectional imaging. The mROR was determined from preoperative imaging of patients undergoing revascularization for PAD. A total of 20 patients with IC and 20 patients with CLTI were consecutively included. A subgroup analysis for diabetic patients was conducted. The mROR was evaluated for its correlation with disease severity and clinical covariates. Patients with CLTI were older; cardiovascular risk factors, diabetes, and ASA 4 were more frequent. The mROR scores were higher in CLTI than in IC. In diabetic patients, no difference was detected between CLTI and IC. In CLTI, non-diabetic patients had a higher mROR. The mROR score is positively correlated with the severity of PAD and can discriminate CLTI from IC. In diabetic patients with CLTI, the mROR is lower than in non-diabetic patients. The mROR score can be determined from cross-sectional imaging angiographies. It may be useful for clinicians helping with vascular case planning, as well as for scientific purposes.

Effectiveness and safety of anticoagulant versus antiplatelet therapy in patients after endovascular revascularisation of the lower limb

Background. Patients with peripheral arterial disease (PAD) are routinely prescribed antiplatelet treatment (APT) after revascularisation. An exception are patients who receive anticoagulant treatment (ACT) due to comorbidity. We set out to determine possible differences in the effectiveness and safety between ACT and APT in patients who underwent endovascular revascularisation of the lower limb arteries.&#x0D; &#x0D; Methods. In a single-centre retrospective study, we analysed the data of 1,587 consecutive patients with PAD who underwent successful endovascular revascularisation of the lower limb arteries due to disabling intermittent claudication or chronic critical limb ischemia in a 5-year period. Patients were divided in the ACT and APT group based on their prescribed treatment. After balancing both groups' baseline characteristics and cardiovascular risk factors with propensity score matching (PSM), we compared the effectiveness and safety of both treatment regimens in the first year afterrevascularisation.&#x0D; &#x0D; Results. Compared to patients with APT, patients with ACT were older, more often reported arterial hypertension, diabetes, chronic kidney disease, congestive heart failure, ischaemic heart disease, and a history of stroke or transient ischaemic attack. After PSM, the odds ratio (OR) for an effective outcome with ACT versus APT was 0.78 (95% CI 0.39–1.59; p=0.502), while the OR for a safe outcome with ACT versus APT was 4.12 (95% CI 0.82–20.73; p=0.085).&#x0D; &#x0D; Conclusions. Patients who required ACT were older, had more cardiovascular risk factors, and more advanced PAD than patients with APT. After matching, we found no statistically significant difference in the effectiveness and safety of both treatment regimens.&#x0D; &#x0D;

Bailout stenting in femoropopliteal arterial segment.

Background: Disabling peripheral arterial disease (PAD) of femoropopliteal segment is usually treated with percutaneous balloon dilatation, and when this is not successful, stent is placed. Long-term patency of stent is often compromised due to in-stent restenosis (ISR). We aimed to identify factors associated with bailout stenting, and to recognise risk factors for ISR in procedures without paclitaxel application. Patients and methods: We analysed 592 consecutive successful femoropopliteal interventions performed in patients with either disabling intermittent claudication or chronic critical limb ischemia (CLI). In patients with stent implantation, clinical and ultrasound (US) examination were performed one year after the intervention to establish the presence of ISR, defined as>50% stenosis on US imaging. Results: Bailout stenting was required in 133 (22.5%) procedures. Patients with stent placement were younger (70±10 vs 72±11years, p=0.007) and less often presented with CLI (29.3% vs 40.5%, p=0.019). They more often reported smoking (63.2% vs 49.2%, p=0.005), less often had diabetes mellitus (35.3% vs 47.5%, p=0.013) and arterial hypertension (82.0% vs 90.8%; p=0.004). Stenting was also dependent on lesion complexity (TASCII C>B>A; p<0.001). Subgroup analysis of 110 procedures with bare metal stent (BMS) placement performed in 107 patients revealed ISR in 46.4% of stents, in half of cases it was symptomatic. Neither clinical nor lesion characteristics proved to differ between the group of procedures with ISR and group of procedures without ISR. Conclusions: Factors associated with bailout stenting were age, diabetes mellitus, arterial hypertension, smoking, clinical picture of PAD and complexity of treated lesions. We did not find any risk factors influencing development of ISR in BMS.

Comparative assessment of the quality of life in patients with chronic critical lower limb ischemia after surgical treatment (literature review)

Today, there are several approaches to the treatment of critical lower limb ischemia (KINK). However, despite the high clinical effectiveness achieved, it is not always possible to achieve a high quality of life for the patient after surgery. This article presents modern aspects of surgical treatment of KINK and assesses the quality of life of patients depending on the type of intervention (literature review).

Корекція ендотеліальної дисфункції та порушень мікроциркуляції в пацієнтів із критичною ішемією нижніх кінцівок та високим ризиком розвитку реперфузійно-реоксигенаційних ускладнень

Актуальність. Епідеміологічні дослідження свідчать, що критична ішемія нижніх кінцівок трапляється в 500–1000 пацієнтів на один мільйон населення на рік. В Україні щорічно проводиться близько 10 000 реконструктивних операцій із приводу оклюзійних уражень артерій нижніх кінцівок. Одночасно щорічно виконується близько 8–10 тис. ампутацій нижніх кінцівок на ґрунті атеросклерозу. Метою дослідження було вивчення можливості корекції ендотеліальної дисфункції та порушень мікроциркуляції в пацієнтів із хронічною критичною ішемією нижніх кінцівок та високим ризиком розвитку реперфузійно-реоксигенаційних ускладнень після реконструктивних операцій. Матеріали та методи. В основу роботи покладено аналіз комплексного обстеження та хірургічного лікування 220 хворих на облітеручий атеросклероз аорти та магістральних артерій нижніх кінцівок. Ендотеліальну дисфункцію оцінювали шляхом визначення рівня маркерів: Р-селектину, Е-селектину, тканинного активатора плазміногену, ендотеліну-1, молекули адгезії судинного ендотелію 1-го типу, циркулюючих ендотеліальних клітин. Результати. Порівнюючи рівень ендотеліальної дисфунції та стан мікроциркуляції в ранньому післяопераційному періоді в пацієнтів із спеціальною доопераційною підготовкою й без такої, можна говорити про потребу та ефективність перед­операційного застосування бета-блокатора небівололу, інгібітора АПФ периндоприлу аргініну та L-аргініну. Висновки. Застосування в передопераційному періоді бета-блокатора небівололу, інгібітора АПФ периндоприлу аргініну, L-аргініну та сольового гіперосмотичного гіпертонічного розчину декстрану в пацієнтів із високим ризиком реперфузійно-реоксигенаційних ускладнень дає можливість запобігти значним порушенням при розвитку ендотеліальної дисфункції та погіршенню функціонування мікроциркуляторного русла й забезпечити оксигенацію тканин на рівні 5,04 ± ,37 мм рт.ст. після реваскуляризації нижніх кінцівок.

Состояние антиоксидантной, прооксидантной и эндотелиальной систем у пациентов с хронической критической ишемией нижних конечностей и высоким риском развития реперфузионно-реоксигенационных осложнений

Актуальность. Облитерирующий атеросклероз магистральных периферических сосудов составляет более 20 % случаев всей сердечно­сосудистой патологии, то есть свыше 3 % общей численности населения. Несмотря на большой опыт выполнения оперативных вмешательств на артериях, 3­летняя способность бедренно­подколенных шунтов не превышает 80 %. Частота реокклюзии сосудов аорто­подвздошного сегмента составляет от 6 до 42 %. Целью исследования было изучение особенностей оксидантной, прооксидантной и эндотелиальной систем у пациентов с хронической критической ишемией нижних конечностей. Материалы и методы. В основу работы положен анализ комплексного обследования и хирургического лечения 220 больных облитерирующим атеросклерозом аорты и магистральных артерий нижних конечностей. Больные были распределены на две группы по объему операционной реваскуляризации аорто­бедренно­подколенного сегмента. Операционное вмешательство в первой группе пациентов включало одномоментную реконструкцию аорто­бедренного и бедренно­подколенного сегментов, у пациентов второй группы реконструкция указанных сегментов выполнена в два этапа. Активность составляющих прооксидантно­антиоксидантной системы определяли с помощью спектрофотометрического метода. Результаты. Исследование активности процессов свободного радикального окисления указывает на то, что процессы, происходящие в тканях нижних конечностей, из­за влияния на них свободных радикалов кислорода не только активируют свободнорадикальные процессы, но и могут усиливать процессы повреждающего воздействия на клетки тканей и прежде всего на эндотелиальную систему. Выводы. Риск развития реперфузионных осложнений в послеоперационном периоде у пациентов подтверждается высоким уровнем воспалительного ответа. При реваскуляризации происходит разрушение, отслоение эндотелиальных клеток, расширение эндотелиальных параклеточных контактов, что способствует гиперпроницаемости эндотелиального слоя.

Contemporary Medical Management of Peripheral Artery Disease.

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis. Modifiable risk factors including cigarette smoking, dyslipidemia, diabetes, poor diet quality, obesity, and physical inactivity, along with underlying genetic factors contribute to lower extremity atherosclerosis. Patients with PAD often have coexistent coronary or cerebrovascular disease, and increased likelihood of major adverse cardiovascular events, including myocardial infarction, stroke and cardiovascular death. Patients with PAD often have reduced walking capacity and are at risk of acute and chronic critical limb ischemia leading to major adverse limb events, such as peripheral revascularization or amputation. The presence of polyvascular disease identifies the highest risk patient group for major adverse cardiovascular events, and patients with prior critical limb ischemia, prior lower extremity revascularization, or amputation have a heightened risk of major adverse limb events. Medical therapies have demonstrated efficacy in reducing the risk of major adverse cardiovascular events and major adverse limb events, and improving function in patients with PAD by modulating key disease determining pathways including inflammation, vascular dysfunction, and metabolic disturbances. Treatment with guideline-recommended therapies, including smoking cessation, lipid lowering drugs, optimal glucose control, and antithrombotic medications lowers the incidence of major adverse cardiovascular events and major adverse limb events. Exercise training and cilostazol improve walking capacity. The heterogeneity of risk profile in patients with PAD supports a personalized approach, with consideration of treatment intensification in those at high risk of adverse events. This review highlights the medical therapies currently available to improve outcomes in patients with PAD.

Complex treatment of patients with chronic critical lower limb ischemia in multifocal arterial lesions complicated by trophic defects

Complex treatment of patients with chronic critical lower limb ischemia in multifocal arterial lesions complicated by trophic defects

БЛИЖАЙШИЕ И ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫРЕНТГЕНОЭНДОВАСКУЛЯРНЫХ ВМЕШАТЕЛЬСТВ ПРИ ЛЕЧЕНИИХРОНИЧЕСКОЙ КРИТИЧЕСКОЙ АТЕРОДИАБЕТИЧЕСКОЙИШЕМИИ НИЖНИХ КОНЕЧНОСТЕЙ

Background. The treatment of chronic critical ischemia of the lower extremities with their combined atherodiabetic lesion is one of the far from the resolved problems of modern surgery. Aim of the study. Analysis of the results of X-ray endovascular interventions in patients with critical lower limb ischemia due to atherodiabetic lesions of the femoral-popliteal-tibial segment. Material and methods. We analyzed the results of REVS in 60 patients with diabetes mellitus with critical ischemia of the lower extremities due to infra-anginal atherosclerotic occlusions with a follow-up period of up to 5 years from the moment of the manipulation. Results. The total shelf life of the lower limb after REVV was 492.4 ± 10.1 days. Out of 26 amputations performed, balloon angioplasty was performed in 18 cases and stenting in 8 cases. In individuals with type I diabetes, the duration of painless period was 415.4 ± 5.1 days, and the total shelf life of the leg was 465.4 ± 4.3 days. In type II diabetes, these indicators were, respectively, 181.4 ± 4.4 days and 317.8 ± 6.7 days. In the group of patients with type I diabetes, the lower limb was saved in 55.6% of cases (in 20 out of 36 patients), and in type II diabetes - in 58.3% (in 14 out of 24 people). Conclusions. The presence of simultaneously obliterating atherosclerosis and diabetes mellitus in patients leads to a combined atherodiabetic lesion of the arterial bed, including infra-anginal arteries. X-ray endovascular interventions (balloon angioplasty and stenting) on the arterial femoral-popliteal-tibial segment are a rather effective method of eliminating chronic critical lower limb ischemia, which allows preserving the lower limb in 56.7% patients with a follow-up period of up to 5 years from the date of surgery. Improving the results of X-ray endovascular interventions in case of chronic critical atherodiabetic lower limb ischemia requires a comprehensive study of the possible causes of occlusions of reconstructed arterial segments (blood coagulation potential, non-optimal processes in the intervention zone).

Percutaneous Deep Foot Vein Arterialization IVUS-Guided in No-Option Critical Limb Ischemia Diabetic Patients.

To report our clinical experience with IVUS-guided percutaneous deep vein arterialization (pDVA) to treat chronic critical limb ischemia (cCLI) patients with no-endovascular or surgical options approach due to creation of an arteriovenous fistula (AVF). In a 2 years period, 14 no-option cCLI patients were treated with percutaneous deep vein arterialization (pDVA) by creating an AVF with a IVUS-guided system between posterior tibial artery and its satellite deep vein. Technical success was defined as successful AVF creation and venous perfusion of the wound site. Patients' characteristics, procedure details, mortality and wound outcomes were assessed prospectively. Successful pDVA was successfully performed in all patients (mean age 82 years) without any procedural complications. Clinical improvement was achieved in all patients with resolution of rest pain, tissue formation of granulation tissue or both; only 3 major amputations were performed within the study period with a limb salvage rate of 78%. Median wound healing time was 4.8 months. pDVA is a safe and feasible revascularization technique alternative in no-option cCLI patients.

Retrograde ankle tibial artery approach for endovascular treatment of below-knee chronic critical limb ischemia: appraisal of early outcome and complications

Background Infragenicular arterial total occlusion is a major cause of critical ischemia of the lower limbs (CLTI) treated by endovascular intervention. Retrograde pedal artery access is an alternative method to cross total occlusion from below when antegrade passage fails. The aim of this study was to evaluate the short-term outcome in terms of patency, limb salvage, redoangioplasty rate, and complications. Patients and methods From June 2018 to July 2019, adult patients who had critical lower limb ischemia (Rutherford 4 and 5) were admitted to the vascular surgery unit of Alexandria main university hospital and department of CLTI clinical and experimental surgery at Alexandria medical research institute. They all were planned to be treated by infragenicular angioplasty. After failure of antegrade lesion crossing, angioplasty was done via retrograde access. Patients were followed for outcome and complications for 6 months. Results A total of 20 patients were included, comprising 14 (70%) males and six (30%) females. Mean age±SD was 71±13.5 years. Overall, 85% were diabetic, 75% hypertensive, 30% coronary heart disease, and 80% were smokers. CLTI clinical presentation was ischemic rest pain (20%) and tissue loss and gangrene (80%). Technical success was 85%. There were no procedural mortalities or complications except one case of limited leg hematoma (5%). The 6-month mortality was 5.8%, and major amputation was 5.8%. The 6-month primary and secondary patency rates were 62.5 and 87.5%, respectively, whereas the 6-month limb salvage rate was 93.75%. Conclusions Retrograde pedal access angioplasty to treat below-knee CLTI is a safe and feasible alternative to antegrade tibial angioplasty when it fails, with similar limb salvage and acceptable complications, but with possible higher reintervention rate, which needs to be studied further on a larger scale.

Distal embolization during percutaneous revascularization of the lower extremity arteries.

Background: Percutaneous endovascular therapy is nowadays the leading treatment option for patients with symptomatic peripheral arterial disease, but it can be complicated with distal embolization (DE). Patients and methods: We retrospectively analyzed 2054 endovascular revascularization interventions performed in patients with disabling claudication or chronic critical limb ischemia in the Catheterisation Laboratory of the Department of Vascular Diseases, University Medical Centre Ljubljana between January 2014 and December 2018. Lesions were treated by balloon angioplasty and/or stent implantation, without atherectomy. Results: The overall incidence of DE was 0.9%. DE was more frequent in females than males (1.6% vs 0.5%, p=0.011), in the absence of antiplatelet treatment prior to intervention compared to previous antiplatelet treatment (2.1% vs 0.6%, p=0.005) and in femoropopliteal stenting compared to angioplasty without stenting (2.2% vs 0.8%, p=0.037). DE was successfully managed with percutaneous aspiration, in combination with angioplasty when necessary, in 84% of cases. In remaining 16% of patients, DE was managed with surgical thromboembolectomy. Conclusions: The incidence of DE during endovascular revascularization of chronic atherosclerotic lesions in lower limb arteries without use of atherectomy was low. DE was more frequent in women, in patients without prior antiplatelet treatment and in femoropopliteal stenting. The majority of DE was successfully managed percutaneously.

The Effects of Spinal Cord Stimulators on End Organ Perfusion: A Literature Review.

Spinal cord stimulators (SCS) have been gaining momentum in the last decade as their role in the management of chronic pain has become more apparent. Our intention was to search, analyze and highlight the effects of spinal cord stimulators on end-organ perfusion. We also looked at vascular diseases of atherosclerotic and nonatherosclerotic nature by examining objective evidence of improved circulation, pain control, limb salvage, and quality of life. We paid specific attention to disease processes such as cerebral hypoperfusion, Chronic-Critical Limb Ischemia, Intractable Angina Pectoris (IAP), Raynaud’s syndrome and Thromboangiitis Obliterans.We performed a Medline database search for medical literature relevant to Spinal cord stimulators encompassing the years 1950 to 2019. Search terms included “Spinal cord stimulator,” plus one of the following search terms: vasculopathy, stroke, cerebral blood flow, angina pectoris, diabetic ulcers, chronic critical leg ischemia, thromboangiitis obliterans and peripheral vascular disease. We included both clinical and experimental human studies that investigated the effect of SCS’s on end-organ perfusion. We also investigated the pathophysiological mechanism of action of SCS’s on the vasculature. We found 497 articles of which 43 more relevant and impactful articles investigating the hemodynamic effects of SCS and its possible mechanism were selected. Animal studies were excluded from the literature review as they provided heterogeneity. In addition to reporting literature supporting the use of stimulators for currently FDA approved uses, we also actively looked for potential future uses. Spinal Cord stimulators showed improvement in cerebral blood flow, increased capillary recruitment, and better quality of life in many studies. Patients also had increased exercise capacity and a significant reduction in the use of narcotic drug use and daily anginal attacks in patients suffering from IAP.

Efficacy of treatment of lower-limb critical ischaemia by methods of indirect revascularization

The study was aimed at comparing the efficacy of implantation of autologous bone marrow cells with that of revascularizing osteotrephination in treatment of lower limb chronic critical ischaemia in patients with a poor distal vascular bed. We analysed the results of comprehensive examination and treatment of a total of 60 patients presenting with lower limb chronic critical ischaemia due to atherosclerotic lesions of the femoropopliteal-tibial segment. According to the technology of treatment, the patients were divided into two statistically homogenous groups of 30 people each. Group One patients underwent standard revascularizing osteotrephination and Group Two patients in accordance with the original technique received intramuscular implantation of 40 ml of autologous bone marrow cells, with this volume distributed in 2-ml injections to 20 points of the muscles of the crus and femur along the internal and external surface. The use of the original technique of treatment made it possible to achieve the clinical status in the form of moderate or minimal improvement 6 months after bone marrow cells implantation in 29 (96.7%) patients and after 12 months in 28 (93.3%) patients, whereas after revascularizing osteotrephination in 25 (83.3%) and 20 (66.7%) patients, respectively. In the remote period after 12 months, the limb was saved in 28 (93.3%) and 26 (86.7%) patients in Group Two and Group One, respectively. The patients of the second group as compared with those of the first group after 12 months demonstrated a statistically significant increase in the physical health component by 19.8% and the mental health component by 9.8%. Implantation of autologous bone-marrow cells in chronic critical limb ischaemia is pathogenetically substantiated and makes it possible to optimize the results of treatment of patients.

Adherence to guideline recommended medical therapies in type 2 diabetic patients with chronic critical limb ischemia

AimThe aim of this study was to evaluate the adherence to guideline recommended medical therapies in type 2 diabetic patients with chronic critical limb ischemia (CCLI). MethodsWe retrospectively analyzed the data of 1315 admissions performed in our Department, focusing on diabetic foot patients (842–64%) of which 603 consecutive type 2 diabetic patients with CCLI (M/F(%): 73/27; age: 70.3 ± 10.4 yrs; diabetes duration: 17.3 ± 13.7 yrs; BMI: 27.7 ± 5.3 Kg/m2; HbA1c 7.8 ± 1.8%) referred to a third-level Center from 2011 to 2015. We focused on medical therapy of diabetes, dyslipidemia, hypertension, peripheral vascular disease and smoke habits. ResultsIn total, at admission, 66.6% of patients had HbA1c levels higher than recommended; 65.9% of patients were on statins; 81.4% on anti-hypertensive treatment and 72.4% on antiplatelet drugs. Concerning smoke habits, 27% of patients were no-smokers; 41% former smokers and 32% active smokers. Among all patients, only 24% were prescribed all five guideline recommended therapies while 32% reached four out of five of these. As for patients treated with anti-hypertensive drugs, we observed higher levels of systolic pressure (138.0 ± 29.5 vs 107.7 ± 36.6 p < 0.02) while no differences were observed in diastolic pressure levels. ConclusionsIn conclusion, when it comes to diabetic patients with a severe limb and life threatening clinical condition, we noticed a lower-than-expected application of international guideline-recommended medical therapies. In fact, only one out of four patients was following all the recommended therapies. Nevertheless, these patients did not reach the standard targets requested to prevent cardiovascular disease.

Successful limb salvage by endovascular treatment for critical limb ischemia subsequent to acute limb ischemia.

Recently, there have been increasing opportunities to treat patients with peripheral arterial disease. Of those patients, both pathological conditions, such as acute limb ischemia (ALI) and chronic critical limb ischemia (CLI), are closely associated with high risks of major amputation, disability and death. We encountered a very rare case of CLI subsequent to ALI. An 83-year-old male showed the sudden onset of ALI, probably due to thromboembolism from an abdominal aortic aneurysm during an operation for gastric cancer. The patient was referred to another hospital for Fogarty thrombectomy. About 1 month after ALI onset, necrosis of the left first toe gradually progressed. On angiography of the left lower limb, we noted occlusions of both anterior and posterior tibial arteries. Then, we successfully conducted balloon angioplasty for the below-the-knee arteries. Thereby, favorable blood flow was achieved, which led to successful wound healing without amputations.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Relieve Hind Limb Ischemia by Promoting Angiogenesis in Mice.

Chronic critical limb ischemia (CLI) represents a clinical end stage of peripheral arterial disease. Many CLI patients are ineligible for conventional revascularization therapies; thus, it is urgent to explore an alternative strategy to rescue the ischemic limb. Recent stem cell studies have greatly developed the field of therapeutic angiogenesis, which aims to significantly improve the limb blood supply. In our study, bone marrow mesenchymal stem cells (BMMSCs) served as the control to evaluate the function of umbilical cord mesenchymal stem cells (UCMSCs) in enhancing angiogenesis. We compared gene expression between BMMSCs and UCMSCs, and a bioinformatics analysis indicated that both UCMSCs and BMMSCs could stimulate angiogenesis and angiogenesis-related factors were upregulated in UCMSCs. In vitro assays indicated that both BMMSCs and UCMSCs promoted human umbilical vein endothelial cell proliferation, migration, and tube formation, and the effects of UCMSCs were more obvious. Consistent with in vitro results, both UCMSCs and BMMSCs improved the limb blood supply in a mouse model of hind limb ischemia, in which UCMSCs promoted angiogenesis more significantly. Finally, we found that activation of ERK and PI3K-Akt pathways might be the mechanism by which UCMSCs promote angiogenesis. These results indicate that UCMSCs play an important role in therapeutic angiogenesis to improve limb blood perfusion.

Long-term results of complex therapy in patients with nonreconstructible chronic lower limb ischemia

The aim — to improve the results of surgical treatment of patients with chronic critical lower limb ischemia by developing methods of autologous transplantation of multipotent stem mesenchymal stromal cells, administration of endothelial cells growth factors and therapeutic and diagnostic measures to preserve the lower limb or reduce the level of its amputation, reduce ischemia and the frequency of disability of such patients, improve their quality of life.Materials and methods. The study included 110 patients with a clinical picture of pain at rest, ischemic edema, and trophic changes (IIIA, IIIB, and IV stage of lower limb ischemia according to the classification of the European Association of Angiologists and Vascular Surgeons) caused by nonreconstructible occlusive and obliterating diseases of lower limb arteries. The patients were divided into three groups according to the method of treatment: in the 1st group (n = 48), revascularization osteotrepanation was performed as an operation of indirect revascularization, in the 2nd group (n = 21) a drug of endothelial cells growth factor was administered to stimulate their own angiogenesis, in the 3rd group (n = 41) subcutaneous fat was collected, autologous mesenchymal cells were cultivated and transplanted according to the developed technique. The control group of patients (n = 50) was selected retrospectively according to the case histories in accordance with the criteria of involvement and the results of treatment which could be followed up in a 3‑year observation period.Results and discussion. The safety of the lower limb in the 3rd group was statistically more significant than in the 1st and 2nd groups and remained at the level of 82 % after three years of observation. The smallest number of large amputations was in the 3rd group (2.3 % — above knee‑joint and 7.3 % — below, knee‑joint whereas in the control group the number was 18 % and 24 %, respectively).Conclusions. The level of high amputations directly affects the life expectancy of patients. Only treatment in the 3rd group reduced the risk of large amputation compared with the control group (odds ratio 2.752 (95 % confidence interval — 1.12 — 6.733)). Only treatment in the 3rd group reduced the risk of amputation compared with other types of treatment (odds ratio 0.358 (95 % confidence interval 1.111 — 1.158).