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Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Cell therapy has had satisfactory safety and efficacy outcomes for no-option critical limb ischaemia (NO-CLI) patients. In the current study, we aimed to compare the image quality of ischaemic lower limb blood vessels shown on volumetric CT-based time maximum intensity projection CT perfusion (t-MIP CTP) versus single-phase CTA (sCTA). We also tried to quantify the blood flow of the ischaemic lower extremity based on the t-MIP technique, not only to precisely show the dynamic change in blood flow from before to after cell therapy but also to detect any relationship between this change and patient prognosis., Methods: A total of 31 patients with thromboangiitis obliterans (TAO)-induced NO-CLI who had been referred from the department of vascular surgery to undergo autologous stem cell transplantation into a single limb from January 2020 to March 2021 were prospectively enrolled in this study. Preoperative sCTA or t-MIP CTP and postoperative 1-month t-MIP CTP were performed in all patients. Clinical outcomes, including the 1-month ankle-brachial index (ABI) and 3-month CLI status, were also analysed. Image quality, including objective scores (attenuation, signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]), subjective scores and collateral scores, was compared between preoperative sCTA and t-MIP CTP. Vascular volume was calculated as the total volume (mL) of lower limb arteries within the scanning range. All images and calculations were performed by 2 separate radiologists. Receiver operating characteristic curves were drawn to reveal the sensitivity and specificity of vascular volume and ABI in predicting prognosis., Results: Both sCTA and t-MIP CTP images exhibited good quality for diagnosis. t-MIP CTP images showed significantly higher attenuation, SNR and CNR in all arterial segments (popliteal artery, anterior tibial artery, posterior tibial artery and peroneal artery). In subjective and collateral score evaluations, t-MIP CTP images were also significantly better than sCTA images (both p < .05). At 1 month after transplantation, both vascular volume and ABI showed significant improvement (both p < .01). At 3 months after transplantation, 38.71% of patients (12/31) achieved CLI relief (Rutherford class < 4). Through the receiver operating characteristic (ROC) curve, the 1-month vascular volume increase ratio showed better ability to predict the 3-month prognosis (radiologist 1: AUC, 0.757; sensitivity, 0.750; specificity, 0.840; radiologist 2: AUC, 0.803; sensitivity, 0.500; specificity, 1.000) than the 1-month ABI increase ratio (AUC, 0.607; sensitivity, 0.230; specificity, 0.820) or 1-month ABI (AUC, 0.410; sensitivity, 0.080; specificity, 0.580)., Conclusion: t-MIP CTP showed significantly higher-quality images of ischaemic limb vascularity than sCTA. t-MIP CTP can reveal the anatomical information of collaterals more accurately, which is of great importance for NO-CLI patients undergoing cell transplantation. The 1-month vascular volume increase ratio can predict the 3-month prognosis more precisely on this basis., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Here we report the effects of low-intensity pulsed ultrasound (LIPUS) on symptoms in peripheral arterial disease patients with Buerger disease. A double-blinded and randomized study with active and inactive LIPUS was conducted. We assessed symptoms in leg circulation during a 24-week period of LIPUS irradiation in 12 patients with Buerger disease. Twelve patients without LIPUS irradiation served as controls. The pain intensity on visual analog score was significantly decreased after 24-week LIPUS treatment. Skin perfusion pressure was significantly increased in patients who received LIPUS treatment. There was no significant difference in symptoms and perfusion parameters in the control group. No severe adverse effects were observed in any of the patients who underwent LIPUS treatment. LIPUS is noninvasive, safe and effective option for improving symptoms in patients with Buerger disease., (© 2024. The Author(s).)

Purpose: Although thrombolysis obliterans (TAO) has been recognized for more than a century, there is no optimal treatment for this disease. The aim of this report was to compare the short-term efficacies of catheter-directed thrombolysis (CDT), percutaneous transluminal angioplasty (PTA) and CDT+PTA in treating TAO disease., Method: Consecutive patients with TAO treated at Ganzhou People's Hospital between 2012 and 2022 were included in this retrospective study. According to the information provided in the medical records, endovascular procedures included CDT, PTA or CDT+PTA. One-year follow-up outcomes of the patients with TAO who underwent endovascular procedures were compared. The primary outcome was major adverse limb event (MALE) and the secondary outcomes were the technical success, complications, ABI at 1 week after surgery and minor amputation., Results: Sixty-nine patients with TAO were assessed for inclusion in our single-center study from 2012 to 2022 and received endovascular procedures. Among them, 22 patients underwent CDT, 21 patients underwent PTA, and 26 patients underwent PTA+CDT. The one-year follow-up revealed significant differences in the MALE-free survival rates among the three groups, particularly between the CDT group and the PTA+CDT group (the hazard ratio (HR) for MALE-free survival was 0.173, 95% CI [0.050-0.599], p  = 0.006). The technical success rates of the three groups were 63.6%, 90.5%, and 92.3%, respectively. There were differences in the ABI at one week after surgery among the three groups., Conclusions: Endovascular procedures are effective for TAO in the short term. The effectiveness of CDT alone is suboptimal; combining CDT with PTA achieves the most favorable endovascular treatment outcome; while the effectiveness of PTA falls in between these two procedures.

Buerger's disease (BD), also known as thromboangiitis obliterans, is a non-atherosclerotic inflammatory disorder of unknown aetiology that affects small-sized and medium-sized vessels of the extremities. It is usually observed in middle-aged adults, especially those who smoke or use tobacco products. This condition is more frequently observed in men, although recent findings indicate an increasing prevalence among women, potentially due to increased cigarette use. The association between pregnancy and BD is rare, with only a few published cases. Previous reports have indicated that BD may worsen during gestation due to the characteristic hypercoagulable state of pregnancy. In addition, it seems to be associated with intrauterine growth restriction secondary to infarction of placental vessels. Careful obstetric management of maternal and fetal status is mandatory in pregnancies complicated with BD. We report a successful case of a pregnancy in a patient with BD treated with low-molecular-weight heparin., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Thromboangiitis obliterans (TAO) is one of the most common types of peripheral arterial disease (PAD). This study aimed to explore the characteristics of the top 100 most cited articles in the TAO., Methods: A bibliometric analysis based on the Web of Science (WOS) database was performed. Literature was retrieved and ranked by the citations. Listed below are the top 100 citations, including original articles, reviews, full-length proceeding papers, and case reports that were included for analysis. The type of literature, research areas, and languages were recorded. The trends of citations including the total citations, an analysis of publication and citation numbers were conducted each year. We analyzed citations from highly cited countries, authors, institutions, and journals. Research hotspots were gathered by a visualized analysis of author keywords., Results: Most of the highly cited literature was original articles. A rising trend was observed in the number of citations per year. The peaks in the number of highly cited articles appeared in the year 1998 and 2006. The majority of the articles focused on the cardiovascular system and surgery. Journal of Vascular Surgery published most of the highly cited articles. The USA and Japan contributed nearly half the number of highly cited articles. Mayo Clinic and Nagoya University were highly cited institutions. Shionoya S and Olin JW were both the author with the largest number of citations and the most highly cited author in the reference. Articles that were highly cited most often addressed the following topics: "vasculitis", "autoimmune disease", and "critical limb ischemia". Keywords that were mostly used in recent years were "stem cell therapy", "progenitor therapy", and "immunoadsorption". The detection of bursts of author keywords showed the following: "permeability", "differentiation", and "critical limb ischemia" are recent keywords that have burst., Conclusions: In this study, the highly cited contributors in the field of TAO research were identified. Most cited articles in the top 100 focused on the cardiovascular system and surgery. Treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO., (© 2023. The Author(s).)

Background: Thromboangiitis obliterans (TAO) can lead to the development of critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients (<50 years) still require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has been tested and shown to have reasonable efficacy in CLTI. In this multicenter prospective clinical trial, we evaluated the safety and efficacy of BM-MNC implantation in CLTI patients with TAO., Methods and results: We enrolled 22 CLTI patients with skin perfusion pressure (SPP) <30 mmHg. The primary endpoint of this trial is the recovery of SPP in the treated limb after a 180-day follow-up period. Secondary endpoints include the pain scale score and transcutaneous oxygen pressure (TcPO 2 ). One patient dropped out during follow-up, leaving 21 patients (mean age 48 years, 90.5% male, Fontaine Class IV) for analysis. BM-MNC implantation caused no serious adverse events and increased SPP by 1.5-fold compared with baseline. Surprisingly, this effect was sustained over the longer term at 180 days. Secondary endpoints also supported the efficacy of this novel therapy in relieving pain and increasing TcPO 2 . Major amputation-free and overall survival probabilities at 3 years among all enrolled patients were high (95.5% and 89.5%, respectively)., Conclusions: BM-MNC implantation showed safety and significant efficacy in CLTI patients with TAO.

Purpose: To show that smoking cessation improves the technical success of lower extremity endovascular treatment in patients with thromboangiitis obliterans (TAO), or Buerger disease., Materials and Methods: One hundred two patients with TAO who underwent endovascular treatment for chronic limb-threatening ischemia or severe claudication of lower extremities in a tertiary hospital between 2015 and 2022 were included in this retrospective study. Data on serum cotinine levels were available for the last 45 patients, and 38 patients constituted the study population. Per the institution's protocol, patients were instructed to quit smoking 15 days before the intervention. However, cotinine levels showed that some of the patients continued smoking. Technical and recanalization successes were assessed as the primary end points. The secondary end point was the improvement in Rutherford scores at the 1-month follow-up. The McNemar test was used to compare the proportion of recanalized arteries after the intervention., Results: Thirty-seven men and 1 woman (mean age, 42.9 years ± 10.1) were evaluated. The overall technical success rate was 86.8% in the study group. The technical success rate was significantly higher in the nonsmoker group (n = 24 [96%]) than in the smoker group (n = 8 [61.5%]; P = .006). One-month clinical data were available for 100% of the patients. The Rutherford category of the nonsmoker group was significantly lower at the 1-month follow-up. In addition, the Wilcoxon signed-rank test revealed lower Rutherford scores after the intervention in the nonsmoker group. The adverse event rate was 8%. One (2.7%) patient in the smoker group underwent a minor amputation., Conclusions: Cessation of smoking before endovascular therapy improved technical success and recanalization rates in patients with TAO., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

Background: No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we aimed to summarize the results on endovascular treatment of such patients., Methods: We performed a meta-analysis using the following databases: PubMed, Scopus, and the Cochrane Library. The eligible studies had been reported up to December 2021 and had evaluated endovascular angioplasty to treat patients with TO and chronic limb ischemia. The early (mortality and technical success) and late (primary/secondary patency and limb salvage) outcomes were evaluated. StatsDirect (StatsDirect Ltd, Merseyside, UK) was used for the statistical analysis., Results: Overall, 15 eligible studies were included (only endovascular in 11 studies and both endovascular and open repair in 4 studies). Among 601 patients, 402 endovascular procedures (416 limbs) were recorded (angioplasty plus stenting for 7.2% and angioplasty plus thrombolysis for 3.7%). The clinical presentation was intermittent claudication (stage II-III) for 7.9% of the patients and critical ischemia (stage IV-VI) for 92.1% of the patients. Most of the patients had had lesions below the knee, and five had had upper extremity lesions. The pooled technical success rate was 86% (range, 81.1%-90.3%), with no in-hospital mortality. The other complications included perforations (1.9%), wound complications (2.2%), and distal embolism (0.2%). Primary patency was 65.7% (range, 52.7%-77.6%) at 12 months and 50.7% (range, 23.3%-77.9%) at 36 months. Secondary patency was 76.2% (range, 57.5%-90.8%) at 12 months and 64.5% (range, 32.3%-90.6%) at 36 months. The limb salvage rate was 94.1% (range, 90.7%-96.7%) at 12 months and 89.1% (range, 80.6%-95.4%) at 36 months., Conclusions: Endovascular angioplasty for patients with TO and chronic limb ischemia was associated with optimal safety and low complication rates. The technical success and late outcomes were acceptable., (Copyright © 2023 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Buerger's disease or thromboangiitis obliterans is a type of obstructive vascular diseases categorized as vasculitis and usually present in 95% of young smoker men. The main pathogenetic mechanism is interplay between immune system and inflammation. Earlier our phase II study has shown that Stempeucel is safe when injected at 2 million cells/kg body weight by virtue of its anti-inflammatory, immunomodulatory, and angiogenetic properties. The present study was conducted to further assess the safety and efficacy of Stempeucel in critical limb ischemia due to Buerger's disease after obtaining approval from Indian FDA based on the data generated in the phase II study. This is an open label, multicenteric phase IV PMS study conducted across India with experienced vascular surgeons. Fifty patients of critical limb ischemia due to Buerger's disease with Rutherford III-5 or III-6 were included in the study and each individual received a dose of 2 million cells/kg body weight of Stempeucel in the calf muscles and around the ulcer. These patients were evaluated over 12 months from drug administration. The present study showed the continued long term efficacy over a period of 12 months follow up in these patients corroborating the result obtained in the previous phase II studies. There was significant improvement in rest pain, ankle systolic pressure, and ankle brachial pressure index with accelerated ulcer healing. In conclusion, the present study shows that the intramuscular administration of Stempeucel continues to be safe, tolerable, and effective alternative treatment in patients with Buerger's disease., (© 2021 Stempeutics Research Private Limited, Bangalore. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Even today thromboangiitis obliterans has disease features that remain misunderstood or underappreciated. The epidemiology, etiology and pathophysiology of the disease are still unclear. Biomarkers and disease activity markers are lacking, thus clinical assessment is difficult. We are still struggling to establish unique diagnostic, staging and treatment criteria. This is an academic-collaborative effort to describe the pathophysiology, the clinical manifestations, the diagnostic approach, and the challenges of management of patients with TAO. A systematic search for relevant studies dating from 1900 to the end of 2020 was performed on the PubMed, SCOPUS, and Science Direct databases. Given the intriguing nature of presentation of TAO, its management, to some extent is not only different in different regions of the world but also varies within the same region. Following this project, we discovered ambiguity, overlap and lack of clear-cut criteria for management of TAO. An international group of experts however came to one conclusion. They all agree that management of TAO needs a call for action for a renewed global look with multi-center studies, to update the geographical distribution of the disease and to establish a unique set of diagnostic criteria and a consensus-based guideline for best treatment based on current evidence.

Background: Thromboangiitis obliterans (TAO) is a nonatherosclerotic thromboticocclusive vasculitis that affects the vessels of the small and medium-sized extremities. No explicit etiology or pathogenesis of TAO has been proven, and more effective treatments are needed., Objective: The study aimed to summarize and present an overview of recent advances regarding the risk factors, mechanisms and treatments of TAO and to organize the related information in figures to provide a comparatively complete reference., Methods: We searched PubMed for English-language literature about TAO without article type limits, including articles about the risk factors, pathological mechanisms and treatments of TAO in the last 10 years with essential supplements (references over ranges and English abstracts of Russian literature)., Results: After screening content of works of literature, 99 references were evaluated. We found that risk factors of TAO include smoking, gene factors and periodontal diseases. The underlying mechanism of TAO involves oxidative stress, immunity, hemodynamic changes, inflammation and so on. Moreover, similarities in genetic factors and cigarette relevance existed between periodontal diseases and TAO, so further study of relationship was required. For TAO treatment, medicine, endovascular intervention and revascularization surgery, autologous cell therapy and novel therapies were also mentioned. Besides, a hypothesis that infection triggers autoimmunity in TAO could be speculated, in which TLR4 plays a key role., Conclusion: 1. A hypothesis is put forward that infections can trigger autoimmunity in TAO development, in which TLR4, as a key agent, can activate immune signaling pathways and induce autoimmune cytokines expression. 2. It is suggested to reconsider the association between periodontal diseases and TAO, as they share the same high-risk population. Controlling periodontal disease severity in TAO studies may provide new clues. 3. For TAO treatment, endovascular intervention and autologous cell therapy both showed promising long-term therapeutic effectiveness, in which autologous cell therapy is becoming more popular, although more clinical comparisons are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A case of Buerger's disease is presented where percutaneous endovascular treatment of a concomitant focal stenosis in the superficial femoral artery led to immediate remission of symptoms and aided wound healing. The existence of such lesions should never be underestimated.

One of the challenges of thromboangiitis obliterans (TAO) management is in the patients whose other vascular beds are involved and it remains a challenge to know whether to pursue invasive procedures or to continue medical treatment for such TAO patients. The aim of this review was to investigate reports of the involvement of the visceral vessels in TAO and the related clinical manifestations, management approaches and outcomes. According to our systematic review, the frequency of published articles, the organs most commonly involved were the gastrointestinal tract, the heart, the central nervous system, the eye, the kidneys, the urogenital system, the mucocutaneous zones, joints, lymphohematopoietic system and the ear. Notably, reports of the involvement of almost all organs have been made in relation to TAO. There were several reports of TAO presentation in other organs before disease diagnosis, in which the involvement of the extremities presented after visceral involvement. The characteristics of the visceral arteries looked like the arteries of the extremities according to angiography or aortography. Also, in autopsies of TAO patients, the vascular involvement of multiple organs has been noted. Moreover, systemic medical treatment could lead to the recovery of the patient from the onset of visceral TAO. This study reveals that TAO may be a systemic disease and patients should be aware of the possible involvement of other organs along with the attendant warning signs. Also, early systemic medical treatment of such patients may lead to better outcomes and reduce the overall mortality rate., Competing Interests: The authors declare that there are no conflicts of interest in this work., (© 2019 Fakour and Fazeli.)

Objective: Buerger's disease is one of the worst diseases causing peripheral artery occlusions (especially lower extremity) with increased morbidity and mortality. Endovascular treatment of the diseased arteries gains preference over bypass surgery nowadays. Here, we aimed to present the clinical outcomes of 16 consecutive Buerger's disease patients underwent extended endovascular recanalization which is a new technique to restore direct blood flow to at least one foot artery, with the performance of angioplasty for each tibial and foot artery obstructions., Methods: A total of 16 consecutive patients with confirmed diagnosis of Buerger's disease that percutaneously treated in our center between February 2014 and March 2018 were included in the study. The mean age of the patients was 44.25 ± 4.28 ranging from 36 to 50 years. After physical examination and complementary diagnostic tests, performance of extended angioplasty for occluded arteries was intended to restore direct blood flow to at least one of the blow-the-knee arteries., Results: A successful extended endovascular treatment was performed in 20 of 22 limbs, achieving a technical success of 91%. All patients were successfully discharged without any complication. Mean follow-up duration was 21.43 ± 7.08 months. Reintervention was performed in one patient and minor amputation was needed in one of the failed limbs. Limb salvage rate was 100%. A significant difference was observed based on Rutherford classification, ankle brachial index, direct blood flow to foot, presence of ulcer and rest pain when compared before and after the intervention., Conclusion: We showed successful extended endovascular recanalization of Buerger's disease patients with a high technical success rate and sustained clinical improvement. Extended endovascular recanalization could be a therapeutic option in Buerger's disease patients, since they are not good candidates for surgery.

Purpose: The aim of the study was to evaluate the technical success of the procedure and the clinical efficacy of treatment in patients with thromboangiitis obliterans (TAO) (Buerger's disease) based on a change in the Rutherford classification., Materials and Methods: A total of 28 consecutive patients (26 males, 2 females, mean age 43.3 ± 5.32 years) underwent endovascular recanalization with a diagnosis of TAO, between April 2015 and July 2018. After unsuccessful attempts using the antegrade approach, retrograde approaches were used in 8 patients under ultrasound guidance. Clinical follow-up was routinely performed at 1-month, 3-month, 6-month, and 1-year intervals., Results: A total of 28 TAO patients underwent 40 procedures in 32 limbs. Technical success was achieved in 28 of the 32 limbs (87.5%). In total, 45 of 59 (76.2%) below the knee arteries were treated successfully. One major amputation was performed, providing a 96.8% rate for limb salvage both at 12 and 24 months. Amputation-free survival estimated by Kaplan-Meier analysis was 84% at 12 and 24 months. Primary patency rates at 12, 24, and 36 months were 84%, 78%, and 75%, respectively. Secondary patency rates were 87.5% both at 12 and 24 months., Conclusion: Endovascular treatment is a technically feasible and potentially effective treatment modality for Buerger's disease. Combined antegrade and retrograde interventions in TAO patients may improve technical success and clinical recovery, especially in cases where the antegrade approach has failed.

Objective: We investigated the long-term results of autologous bone marrow mononuclear cells (ABMMNCs) implantation in patients with Buerger's disease (BD)., Methods: Twenty-eight patients (25 males and 3 females) who had BD and critical unilateral limb ischemia were investigated between April 2003 and August 2005. The patients were administered multiple injections of CD34+ and CD45+ positive ABMMNCs into the gastrocnemius muscle, the intermetatarsal region, and the dorsum of the foot (n=26) or forearm (n=2) and saline injection into the contralateral limb., Results: The mean follow-up time was 139.6±10.5 months. No complication related to stem cell therapy was observed during the follow-up. The ankle-brachial pressure index evaluated at 6 months and 120 months was compared to the baseline scores (p<0.001 and p=0.021, respectively). Digital subtraction angiography (DSA) was performed for all patients at baseline, 6 months, and 120 months. The angiographic improvement was 78.5% and 57.1% at 6 and 120 months, respectively. Patients demonstrated a significant improvement in the quality of life parameters at 6 months compared to baseline (p=0.008) and 120 months compared to the baseline (p=0.009). The 10-year amputation-free rate was 96% (95% CI=0.71-1) in ABMMNC-implanted limbs and 93% (95% CI=0.33-0.94) in saline-injected limbs (p=1)., Conclusion: Autologous stem cell therapy could be an alternative therapeutic method for BD at long-term follow-up.

Buerger's disease, also known as thromboangiitis obliterans, is a severe invalidating systemic vascular disease. To one of the modern methods, which is distinguished by its radically new principles of action, as well as holding much promise for further study and application in treatment of patients with lower limb chronic ischaemia induced by thromboangiitis obliterans belongs the use of genetically engineered complexes based on vascular endothelial growth factor VEGF-165 ('Neovasculgen'). 'Neovasculgen' is a genetically engineered complex being a circular DNA (native plasmid on the CELO vector and Ad5), carrying the human VEGF-165 gene, encoding VEGF synthesis. Injection of this drug to the ischaemised tissues of lower extremities ensures long-term synthesis of vascular endothelial growth factor 165 leading to the development of an additional collateral vascular network and consequently to increased perfusion of tissues with oxygen and decreased degree of ischaemia. Presented herein is a clinical case report of a successful therapeutic outcome achieved in a patient suffering for a long time from thromboangiitis obliterans (Buerger's disease) and treated with genetically engineered complexes based on vascular endothelial growth factor ('Neovasculgen') used as a component of comprehensive conservative therapy.

Background: Thromboangiitis obliterans, also known as Buerger's disease, is a non-atherosclerotic, segmental inflammatory pathology that most commonly affects the small- and medium-sized arteries, veins, and nerves in the upper and lower extremities. The etiology is unknown, but involves hereditary susceptibility, tobacco exposure, immune and coagulation responses. In many cases, there is no possibility of revascularization to improve the condition. Stem cell therapy is an option for patients with severe complications, such as ischemic ulcers or rest pain., Objectives: To assess the effectiveness and safety of stem cell therapy in individuals with thromboangiitis obliterans (Buerger's disease)., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 17 October 2017. The review authors searched the European grey literature OpenGrey Database, screened reference lists of relevant studies and contacted study authors., Selection Criteria: Randomized controlled trials (RCTs) or quasi-RCTs of stem cell therapy in thromboangiitis obliterans (Buerger's disease)., Data Collection and Analysis: The review authors (DC, DM, FN) independently assessed the studies, extracted data and performed data analysis., Main Results: We only included one RCT (18 participants with thromboangiitis obliterans) comparing the implantation of stem cell derived from bone marrow with placebo and standard wound dressing care in this review. We identified no studies that compared stem cell therapy (bone marrow source) versus stem cell therapy (umbilical cord source), stem cell therapy (any source) versus pharmacological treatment and stem cell therapy (any source) versus sympathectomy. Ulcer healing was assessed in the form of ulcer size. The mean ulcer area decreased more in the stem cell implantation group: from 5.04 cm 2 (standard deviation (SD) 0.70) to 1.48 cm 2 (SD 0.56) compared with the control group: mean ulcer size area decreased from 4.68 cm 2 (SD 0.62) to 3.59 cm 2 (SD 0.14); mean difference (MD) -2.11 cm 2 , 95% confidence interval (CI) -2.49 to -1.73; 1 study, 18 participants; very low-quality evidence. Pain-free walking distance showed more of an improvement in the stem cell implantation group: from mean of 38.33 meters (SD 17.68) to 284.44 meters (SD 212.12) compared with the control group: mean walking distance increased from 35.66 meters (SD 19.79) to 78.22 meters (SD 35.35); MD 206.22 meters, 95% CI 65.73 to 346.71; 1 study; 18 participants; very low-quality evidence.Outcomes such as rate of amputation, pain, amputation-free survival and adverse effects were not assessed.The quality of evidence was classified as very low, with only one study, small numbers of participants, high risk of bias in many domains and missing information regarding tobacco exposure status., Authors' Conclusions: Very low-quality evidence suggests there may be an effect of the use of bone marrow-derived stem cells in the healing of ulcers and improvement in the pain-free walking distance in patients with Buerger's disease. High-quality trials assessing the effectiveness of stem cell therapy for treatment of patients with thromboangiitis obliterans (Buerger's disease) are needed.

Rationale: Buerger disease (BD) is a nonatherosclerotic, inflammatory, segmental vascular occlusive disease, which affects small and medium-sized arteries and veins and is triggered by substantial tobacco exposure. Angiographic findings consistent with BD are required for diagnosis. Laser Doppler flowmetry (LDF) and laser speckle contrast imaging (LSCI) could represent potential noninvasive alternative techniques to angiography., Patient Concerns: We report the case of a 49-year-old smoker who developed an ischemic ulcer in the distal segment of the second finger of the left hand. He had no medical history., Diagnoses: In our vascular center, LDF and LSCI are conducted routinely for digital artery disease diagnosis. LDF was indicative of digital obstructive artery disease (DOAD). Postocclusive reactive hyperemia, assessed by LCSI, demonstrated no skin blood flow (SBF) perfusion in the distal phalanx of the thumb, index, middle, and auricular fingers. Angiography confirmed BD, showing distally located multisegmental vessel occlusion and corkscrew collaterals in this patient's hands., Interventions: Ilomedine treatment was initiated and smoking cessation was definitive., Outcomes: Recently, the patient had an improvement in clinical condition despite the persistence of a small zone of necrosis of the left index finger 28 days post-treatment., Lessons: Our observation suggests that where suspicion of BD is based on clinical criteria, combining LDF and LSCI could represent a noninvasive, safe means of reaching BD diagnosis. Further clinical trials are necessary to confirm this novel observation.

Angiitis-induced critical limb ischemia (AICLI) patients constitute a remarkable proportion of no-option critical limb ischemia (CLI) patients. Stem cell therapy has become an innovative and promising option for no-option CLI patients. As one of these promising stem cell therapies, purified CD34+ cell transplantation (PuCeT) has shown favorable short-term results. However, the long-term efficacy of PuCeT has yet to be reported. This study evaluates the long-term efficacy of PuCeT in AICLI patients. Twenty-seven AICLI patients were enrolled from May 2009 to December 2011. Granulocyte colony-stimulating factor (G-CSF) and enoxaparin sodium were administered for 5 days. On day 5, CD34+ cell isolation was performed, and cells were transplanted by intramuscular injection. The primary endpoint, major-amputation-free survival rate (MAFS), as well as secondary endpoints, such as peak pain-free walking time (PPFWT) and the Wong-Baker FACES pain rating scale score (WFPRSS), were routinely evaluated during the 5-year follow-up period. The endpoints were as follows: the MAFS was 88.89%; PPFWT increased from 3 ± 3 to 17 ± 6 minutes; WFPRSS decreased from 7 ± 2 to 0.3 ± 1.7; the ulcer healing rate was 85.71%; the recurrence rate was 11.11%; and SF-36v2 scores were significantly improved at 5 years after PuCeT. The rate of labor recovery 5 years after PuCeT was 65.38%, and no severe adverse effect was observed during the treatment. PuCeT demonstrated long-term efficacy and durability as a treatment of AICLI not only in achieving limb salvage but also in recovering the labor competence and improving the quality of life of patients. Stem Cells Translational Medicine 2018;7:583-590., (© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Thromboangiitis obliterans (TAO), also known as Buerger's Disease, is an occlusive vasculitis linked with high morbidity and amputation risk. To date, TAO is deemed incurable due to the lack of a definitive treatment. The immune system and inflammation are proposed to play a central role in TAO pathogenesis. Due to their immunomodulatory effects, mesenchymal stromal cells (MSCs) are the subject of intense research for the treatment of a wide range of immune-mediated diseases. Thus far, local intramuscular injections of autologous or allogeneic MSCs have shown promising results in TAO. However, sequential intravenous allogeneic MSC administration has not yet been explored, which we hypothesized could exert a systemic anti-inflammatory effect in the vasculature and modulate the immune response. Here, we report the first case of a TAO patient at amputation risk treated with four sequential intravenous infusions of bone marrow-derived allogeneic MSCs from a healthy donor. Following administration, there was significant regression of foot skin ulcers and improvements in rest pain, Walking Impairment Questionnaire scores, and quality of life. Sixteen months after the infusion, the patient had not required any further amputations. This report highlights the potential of sequential allogeneic MSC infusions as an effective treatment for TAO, warranting further studies to compare this approach with the more conventionally used intramuscular MSC administration and other cell-based therapies.

To date, there is still no treatment protocol for patients with thromboangiitis obliterans (TAO) who are also afflicted with critical limb ischemia (CLI). Smoking cessation on its own cannot be considered a treatment for the purposes of salvaging a limb of a TAO patient with CLI. The aim of this review was to evaluate different studies of various treatment protocols for avoiding amputation in TAO patients. A systematic search for relevant studies dating from 1990 to the end of 2016 was performed on the PubMed, SCOPUS, and Science Direct databases. Only 24 studies fulfilled the inclusion criteria, of which only one was a randomized controlled trial (RCT). The remaining studies were quasi-experimental with various treatments and follow-up durations. Therefore, meta-analysis was not performed. Judging from the major amputation rates after the suggested treatments were performed, no treatment was particularly effective. This review demonstrated that more standard RCTs are needed to resolve this treatment issue involved in TAO. In addition, because health insurance coverage for TAO patients differs by country, regional cost-benefit and cost-efficacy studies of the suggested treatments for TAO are highly recommended., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Buerger's disease or thombo-angiitis obliterans disease is a small vessel's vasculitis, frequently observed in young and smoker's males. Diagnosis is based on both clinical and radiological arguments. There is no specific treatment designed for this disease. We report the case of 43 years old patient presenting with an acute kidney injury associated with Buerger's disease. We reviewed the different case of kidney disease in this rare disease., (Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Wounds refractory to standard treatment in patients with thromboangiitis obliterans (TAO, Buerger's disease) are associated with amputation, other morbidity and mortality. The purpose of this study was to investigate the effect of hyperbaric oxygen treatment (HBOT) in patients with TAO., Materials and Methods: Ninety-seven patients with TAO with ischaemic wounds treated between January 2007 and July 2016 were included in this dual-centre, non-randomised, retrospective study. Patients receiving HBOT in addition to conventional treatment were enrolled in an HBOT group ( n = 47) and those receiving conventional treatment alone in a non-HBOT group ( n = 50). All patients were Rutherford grade III at the time of enrolment., Results: Significant improvement in the major amputation rate was observed in the HBOT group 10 months after starting treatment (2/47 vs. 13/50, P = 0.007). Numbers of patients progressing to Rutherford grade I (27/47 vs. 17/50, P = 0.035), numbers of patients healing completely (21 vs. 11, P = 0.031 and pain scores (visual analogue scale; 1, range 0-8 vs. 6, range 0-9, P < 0.001) were also significantly improved in the HBOT group., Conclusion: The addition of HBOT to conventional treatment in TAO patients with non-healing ischaemic wounds and severe extremity pain, conferred significant benefits in terms of wound healing and rest pain control. Multi-centre, prospective, randomized studies with blinded outcome analysis are now needed to elicit more reliable results., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

Background: For patients with thromboangiitis obliterans (TAO), revascularization with bypass or angioplasty is frequently not feasible due to the poor outflow of the distal small vessels. We evaluated the long-term results of our experience treating patients with TAO with autologous bone marrow-derived mononuclear cells (ABMMNCs) to determine the safety and efficacy of ABMMNC therapy in patients with critical limb ischemia due to TAO., Methods: This was a retrospective chart review from a single university hospital vascular surgery center between January 2005 and July 2006. Patients were treated with smoking cessation and either aspirin (100 mg/day) alone or aspirin and ABMMNC injection according to patient preference. Groups were compared for demographics, clinical characteristics, and short-term and long-term results., Results: Of 59 patients with TAO who were treated, 19 patients elected aspirin alone and 40 patients elected aspirin and ABMMNC injection. No patients suffered perioperative complications and 49 (83%) patients remained smoke-free for 10 years. The 10-year amputation-free survival was 85.3% (29/34) in patients treated with ABMMNCs compared to 40% (6/15) in patients treated with aspirin alone (p = 0.0019). Ulcer area (p < 0.0001), toe-brachial index (TBI; p < 0.0001), transcutaneous oxygen pressure (TcPO 2 ; p < 0.0001), and pain score (p < 0.0001) were also significantly improved with ABMMNC treatment, although there was no difference in mean ankle-brachial index (ABI; p = 0.806)., Conclusions: In patients with critical limb ischemia due to TAO, ABMMNC treatment was safe and effective. ABMMNC treatment significantly improved amputation-free survival, ulcer healing, and pain, although there is no difference in ABI compared to treatment with aspirin alone.

Purpose: When critical limb ischemia (CLI) occurs in patients with thromboangiitis obliterans (TAO) or Buerger's disease, smoking cessation alone may be insufficient to relieve rest pain and promote wound healing. Accordingly, adjunctive measures are warranted to restore adequate blood flow required for limb salvage. This study aimed to evaluate the feasibility and efficacy of percutaneous transluminal angioplasty (PTA) for the treatment of patients with TAO and CLI. In addition, a review of the literature on endovascular management of TAO is included., Methods: Between April 2012 and June 2017, all patients with TAO and CLI who underwent PTA were studied retrospectively. Patient demographics, presentation, procedural details, and clinical response were recorded. Patients were monitored at 1 week, 1, 2, 3, and 6 months after revascularization and at least every 6 months thereafter., Results: Thirteen patients with TAO and CLI, who presented with rest pain only (n = 1), ischemic ulcer (n = 4), or gangrene (n = 8) underwent endovascular interventions with primary and assisted primary technical success of 85% and 92%, respectively. A below-knee amputation was eventually done in the only patient with technical failure (limb salvage rate: 92%). Following the procedures, 11 patients had clinical response, one of whom also received intra-arterial vasodilator to achieve complete symptom relief. The other patient who failed PTA underwent a successful lumbar sympathectomy. In addition, all ulcers healed and eight minor amputations were performed due to already established gangrene. During follow-up (mean: 19.4 months), four patients needed reintervention. Patients who continued to smoke experienced more severe ischemia ( P = .017) and were more likely to require reintervention ( P = .009)., Conclusion: Percutaneous transluminal angioplasty can be considered as a technically feasible and potentially effective treatment for patients with TAO and CLI, as well as a last resort for limb salvage when other options have failed. However, reintervention may be required, especially in patients who continue smoking.

Thromboangiitis obliterans is an occlusive vasculopathy affecting small- and medium-size arteries. It can result in severe ischemic status. Thrombophlebitis can be associated. The exact etiology has still to be elucidated. Smoking is the main contributing factor. Diagnosis is based on clinic and paraclinic context, as well as exclusion of other vascular pathologies. Its management consists in complete smoking cessation and instauration of vasodilator treatment. Revascularization is an option that has to be evaluated on a case by case basis. New promising therapeutic approaches are emerging., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: This study sought to compare the outcomes of endovascular recanalization (ER) vs autogenous venous bypass (AVB) for tibioperoneal arterial occlusion in thromboangiitis obliterans patients with critical lower limb ischemia., Methods: A total of 90 limbs in 75 patients, successfully treated with ER (ER group, 35 patients, 43 limbs) and AVB (AVB group, 40 patients, 47 limbs) for tibioperoneal arterial occlusions from January 2009 to December 2015 in a single institution, were retrospectively analyzed. The characteristics and outcomes were compared between the two groups. The primary outcome was the amputation-free survival rate during follow-up; the secondary outcomes were patency rates, immediate failure, periprocedural complications, and rates of reintervention. Univariate and multivariate analysis to identify potentially significant predictors of amputation-free survival and primary patency in the whole study group was performed., Results: Not all patients in the ER group were bypass candidates because of unavailable runoff arteries or adequate conduit for bypass. Other baseline characteristics were similar between groups. Patients in the ER group had a much higher incidence of immediate failure (36.36% in femoropopliteal segment and 65.52% in tibioperoneal segment vs 14.89% in AVB bypass; P = .03 and < .001). Although patients in the ER group had a significantly higher rate of reintervention (62.79% vs 27.66%; P < .001) associated with a significantly lower primary patency rate (18.96% in femoropopliteal segment and 14.37% in tibioperoneal segment vs 60.41% in AVB bypass; P = .008 and < .001) and secondary patency rate (33.85% in femoropopliteal segment and 21.29% in tibioperoneal segment vs 68.78% in AVB bypass; P = .04 and .002) at 3 years, the amputation-free survival in the ER group and AVB group was similar at 1 year (92.9% vs 93.2%; P = .81) and 3 years (87.8% and 90.6%; P = .66). Univariate and multivariate analysis showed that the presence of gangrene was independently associated with major amputation (hazard ratio, 2.24; 95% confidence interval, 1.33-4.3; P = .02); however, the presence of active ulcer was the only risk factor for poorer primary patency during follow-up (hazard ratio, 1.86; 95% confidence interval, 0.55-5.6; P = .04)., Conclusions: ER is a valid strategy for limb salvage in thromboangiitis obliterans patients who are unsuitable for bypass, contributing an acceptable amputation-free survival as high as with AVB, even though it is associated with lower patency rates and a higher rate of reintervention., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate outcomes of contemporary endovascular therapy and intravascular ultrasound (IVUS) findings in thromboangiitis obliterans (TAO) patients., Methods: Between April 2007 and January 2016, 20 patients (mean age 45±8 years; 16 men) underwent endovascular therapy for TAO-related lesions in 25 consecutive limbs. Subjects exhibited a broad array of clinical symptoms, including critical limb ischemia (n=15) and claudication (10) in the lower (n=20) and upper (n=5) limbs., Results: Procedure success was achieved in 24 (96%) limbs (complete success in 16 and partial success in 8), all of which exhibited improvements of at least 1 grade of the Rutherford category. Kaplan-Meier analysis showed that reintervention-free rates were 81.9% (95% CI 0.586 to 0.928) at 6 months and 71.7% at 10 months (95% CI 0.473 to 0.862). IVUS was performed in 20 limbs and revealed unique findings, including the "bull's-eye" appearance, "lotus-root" appearance, and "bunch of grapes" appearance. During a mean follow-up of 26±19 months, the limb salvage rate was 100% with no deaths., Conclusion: Contemporary endovascular therapy might be able to serve as a potential option for TAO patients with lower and upper limb symptoms. Liberal application of IVUS could help us understand the pathology of TAO to support endovascular therapy for TAO.

Thromboangiitis obliterans (Buerger's disease) is a rare, nonatherosclerotic segmental inflammatory vasculitis that commonly involves small- and medium-sized vessels. Ischemic tenderness impairs patient quality of life and places patients at high risk for amputation. The only definitive known treatment is smoking cessation. Far-infrared (FIR) therapy has shown promising effects on blood flow and healing, but its use in patients with Buerger's disease has not been reported. A 31-year-old man with a 15-pack-year history of smoking, no drug abuse, and no other significant medical history, trauma, or family history diagnosed with thromboangiitis obliterans presented for care at the authors' clinic. Claudication with severe tenderness of both legs and an ischemic ulcer over the right big toe were noted. After surgical debridement of the devitalized tissue, the patient received FIR therapy (5-25 µm, peak at 8.2 µm) applied 25 cm above the surface of the ischemic wound for 40 minutes, 3 times per week. The patient also tapered his smoking. The wound started to heal; granulation tissue was evident and, after 8 weeks, the right lower extremities gradually rewarmed from 24° C to 28° C as measured on the dorsal foot. His pain level decreased from 8 to 5. FIR therapy was continued until the patient stopped smoking (8 months). At the 10-month follow-up visit, the wound had healed completely and resting pain had improved. The results of this case study suggest additional research to explore the potential effects of FIR on patients with thromboangiitis obliterans is warranted.

Critical limb ischemia (CLI) due to Buerger's disease is a major unmet medical need with a high incidence of morbidity. This phase II, prospective, nonrandomized, open-label, multicentric, dose-ranging study was conducted to assess the efficacy and safety of i.m. injection of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSC) in CLI due to Buerger's disease. Patients were allocated to three groups: 1 and 2 million cells/kg body weight (36 patients each) and standard of care (SOC) (18 patients). BMMSCs were administered as 40-60 injections in the calf muscle and locally, around the ulcer. Most patients were young (age range, 38-42 years) and ex-smokers, and all patients had at least one ulcer. Both the primary endpoints-reduction in rest pain (0.3 units per month [SE, 0.13]) and healing of ulcers (11% decrease in size per month [SE, 0.05])-were significantly better in the group receiving 2 million cells/kg body weight than in the SOC arm. Improvement in secondary endpoints, such as ankle brachial pressure index (0.03 [SE, 0.01] unit increase per month) and total walking distance (1.03 [SE, 0.02] times higher per month), were also significant in the group receiving 2 million cells/kg as compared with the SOC arm. Adverse events reported were remotely related or unrelated to BMMSCs. In conclusion, i.m. administration of BMMSC at a dose of 2 million cells/kg showed clinical benefit and may be the best regimen in patients with CLI due to Buerger's disease. However, further randomized controlled trials are required to confirm the most appropriate dose. Stem Cells Translational Medicine 2017;6:689-699., (© 2016 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Objective: Chronic wounds are a major cause of morbidity and mortality. Approximately 20% to 23% of nonhealing wounds that are refractory to vascular intervention have other causes, including vasculitis, pyoderma gangrenosum, and other autoimmune diseases. The purpose of this article was to review the literature across medical and surgical specialties with regard to refractory chronic wounds associated with vasculitis and autoimmune diseases and to delineate clinical outcomes of these wounds in response to vascular and other interventions., Methods: An electronic search encompassing MEDLINE, PubMed, Cochrane Library, and Scopus was completed using the following search terms: rheumatoid arthritis; systemic sclerosis; systemic lupus erythematosus; antineutrophil cytoplasmic antibody-associated vasculitis; mixed connective tissue disease; antiphospholipid syndrome; pyoderma gangrenosum; thromboangiitis obliterans; cryoglobulinemia; hydroxyurea; sickle cell; atrophie blanche; livedoid vasculitis; cholesterol emboli; calciphylaxis; antiphospholipid antibodies; prothrombotic; combined with the terms: chronic wound and leg ulcer. Full-text articles published in English up to March 1, 2016, that investigated the clinical outcomes of chronic wounds associated with autoimmune diseases were included. Review articles and evaluations of management of chronic wounds were also reviewed. Primary outcomes included in the review were amputation, ulcer healing, reduction in wound size, overall survival, and freedom from reintervention. Owing to the heterogeneity of data reporting among articles, qualitative analysis is also reported., Results: Vasculitis and autoimmune diseases play a role in 20% to 23% of patients with chronic lower extremity ulcers. Furthermore, patients with autoimmune disease have a significantly high rate of split thickness skin graft failure (50% compared to 97% in patients without autoimmune disease; P = .0002). The management of leg ulcers associated with autoimmune diseases is discussed., Conclusions: Autoimmune and vasculitic causes should be considered in patients with chronic wounds who do not respond to appropriate vascular intervention and standard local wound care. A multidisciplinary approach with the involvement of rheumatologists allows investigation for underlying systemic disease and improves clinical outcomes for many of these challenging patients., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Ischemic wounds unresponsive to standard treatment in thromboangiitis obliterans are associated with amputation, morbidity, and mortality. In this study, hyperbaric oxygen therapy was added to standard treatment of 36 patients with thromboangiitis obliterans with ischemic ulcerated wounds in the extremities. Full recovery was observed in 52.7% of cases (25% at discharge, 27.7% during follow-up). Resting pain after treatment decreased significantly compared to pretreatment levels based on visual analog scale scores (7.1 ± 1.7 vs 2.2 ± 3.0, P = .0001). Mean wound area also decreased significantly after treatment (22.6 ± 17.5 vs 13.02 ± 16.5, P = .0001). The number of patients requiring no assistance during routine daily activities increased significantly (25% vs 55.5%, P = .001). All patients were at Fontaine stage IV before hyperbaric oxygen therapy. The number of patients at stage IIB increased significantly after treatment, while that of patients at stage IV decreased significantly (0% vs 47.2%, P = .0001, and 100% vs 47.2%, P = .0001, respectively). None of our patients was able to walk without pain before treatment; however, walking distance was significantly extended in 16 patients who were capable of walking (0 vs 190.6 ± 129.4 meters, P = .0001). In addition, 11.1% of patients underwent major amputation during follow-up.

Background: The aim of this paper was to evaluate the efficacy of percutaneous transluminal angioplasty and the intra-arterial infusion of thrombolytic drugs in the treatment of lower extremity (LE) arterial occlusion during thromboangiitis obliterans (TO)., Methods: Between February 2008 and October 2013, 13 consecutive patients with TO and LE arterial occlusion underwent 18 sessions of PTA. One LE was affected in 11 patients and both LEs in two patients. An antegrade approach with transfemoral access was used in 17 procedures, and a retrograde approach via the contralateral common femoral artery (CFA) in one procedure. Under fluoroscopic guidance, a 260 cm wire (0.014 inch diameter), with a stiff body and a soft tip, was passed through the occlusion, followed by a 2.5-4 mm deep balloon, and the occlusions were dilated. After dilation, the deep balloon was removed and the straight tip of a thrombolysis catheter inserted, through which to intra-arterially infuse the thrombolytic drug., Results: Percutaneous transluminal angioplasty (PTA) was successful in 39 of the 61 LE occluded arteries, so the technical success was 63.9%. No mortality or serious complication related to PTA was observed. There were significant differences between The Ankle Brachial Index (ABI) at the time of admission (1st-ABI), immediately after the first PTA (2nd-ABI), and at the time of patient discharge (3rd-ABI) (P=0.000). The self-reported maximum walking distance (SRMWD) before and after PTA were also significantly different (P=0.000). All the patients were followed-up for a mean period of 28.4±11.2 months (13-46 months)., Conclusions: PTA using a deep balloon combined with the intra-arterial infusion of thrombolytic drugs is an effective and safe treatment for TO in patients to recanalize the occluded LE vessels.

Objective: To evaluate the long-term clinical effect of autologous peripheral blood mononuclear cells (PB-MNC) on critical limb ischemia (CLI) in patients with thromboangiitis obliterans (TAO) patients., Methods: The clinical data of 22 patients with CLI caused by TAO from July 2004 to May 2013 were analyzed retrospectively, 22 patients were divided into 2 groups; out of them 12 cases in one group were treated with granulocyte colony-stimulating factor (G-CSF)-mobilized autologous peripheral blood mononuclear cells (auto-PBMNC group), 10 cases in another group received conservative treatment (CT group). The log-rank test was used to compare the long-term outcomes in auto-PBMNC group and CT group., Results: The wound healing rate (P=0.016) and CLI-free rate (P=0.013) were significantly higher in PB-MNC group compared with that in CT group. No difference was found in amputation rates between the 2 groups (major amputation: P=0.361, minor and major amputation: P=0.867). No patients died or no serious adverse events occurred during the follow-up period., Conclusion: The auto-PBMNC therapy can significantly promote the wound healing, and protect against CLI in TAO patients, but the risk of amputation is not low in comparison with conservative treatment.

Unlabelled: One problem of vascular angiogenesis therapy is the lack of reliable methods for evaluating blood flow in the microcirculation. We aimed to assess whether (99m)Tc-macroaggregated albumin perfusion scintigraphy ((99m)Tc-MAA) predicts quantitated blood flow after therapeutic angiogenesis in patients with peripheral artery disease., Methods: Forty-six patients with peripheral artery disease were treated with bone marrow mononuclear cell implantation (BMCI). Before and 4 wk after BMCI, blood flow was evaluated via transcutaneous oxygen tension (TcPO2), ankle-brachial index, intravenous (99m)Tc-tetrofosmin perfusion scintigraphy ((99m)Tc-TF), and intraaortic (99m)Tc-MAA., Results: Four weeks after BMCI, TcPO2 improved significantly (20.4 ± 14.4 to 36.0 ± 20.0 mm Hg, P < 0.01), but ankle-brachial index did not (0.65 ± 0.30 to 0.76 ± 0.24, P = 0.07). Improvement in (99m)Tc-TF count (0.60 ± 0.23 to 0.77 ± 0.29 count ratio/pixel, P < 0.01) and (99m)Tc-MAA count (5.21 ± 3.56 to 10.33 ± 7.18 count ratio/pixel, P = 0.02) was observed in the foot region but not the lower limb region, using both methods. When these data were normalized by subtracting the pixel count of the untreated side, the improvements in (99m)Tc-TF count (-0.04 ± 0.26 to 0.08 ± 0.32 count ratio/pixel, P = 0.04) and (99m)Tc-MAA count (1.49 ± 3.64 to 5.59 ± 4.84 count ratio/pixel, P = 0.03) in the foot remained significant. (99m)Tc-MAA indicated that the newly developed arteries were approximately 25 μm in diameter., Conclusion: BMCI induced angiogenesis in the foot, which was detected using (99m)Tc-TF and (99m)Tc-MAA. (99m)Tc-MAA is a useful method to quantitate blood flow, estimate vascular size, and evaluate flow distribution after therapeutic angiogenesis., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger's disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28-63 years; male, 91.9%) with Buerger's disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9-23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI.

Thromboangiitis obliterans (Buerger's disease) is systemic vasculitis with predominant development of thrombotic occlusions of small-to-medium diameter arteries of distal portions of both upper and lower limbs. A distinctive feature of Buerger's disease from other vasculitides is the involvement of the venous bed into the pathological process in the form of migrating thrombophlebitis. The disease is encountered more often in young adult males, predominantly tobacco smokers. The clinical pattern is presented by symptoms of increasing insufficiency of blood supply of tissues of extremities. The diagnosis is made by means of ruling out other vascular diseases (atherosclerosis, diabetes mellitus, systemic diseases of connective tissue, hypercoagulation conditions) based on clinical and laboratory findings, as well as modern methods of visualization, including multislice spiral computed tomographic angiography. Of special importance is a pathomorphological examination aimed at detecting the signs specific for Buerger's disease: arteries showing intimal hyperplasia (from stenosis to complete obliteration according to the capillary angiomatosis type, vascular "recalibration", obliteration of lumens by thrombi, lack of calcification of the tunica media; venous alterations are presented by panphlebitis with intimal hyperplasia, and occlusion with thrombi. Treatment is aimed at eliminating the aetiological stimulus (i. e, smoking), improving blood circulation by means of regular, dosed physical exercises, and administration of anti-ischaemic agents (analogues of prostaglandins, calcium channel antagonists, antiaggregants and anticoagulants). Failure of conservative treatment failed should be followed by making a decision to perform revascularization (endovascular interventions, bypass reconstructive operations, arterialization of the venous blood flow of the foot, resection of the posterior tibial veins, transplantation of the greater omentum onto the crus).

Objective: To investigate the efficiency of autologous peripheral blood stem cell transplantation (APBSCT) to treat severe the lower limbs ischemia caused by thromboangiitis obliterans (TAO)., Patients and Methods: From April 2007 to December 2014, a total of 64 patients with TAO (80 affected limbs) received APBSCT at our hospital. The treatment effect was evaluated by subjective indicators including pains and cold sensation of the affected limbs, combined with objective indicators including claudication distance, ankle brachial index (ABI), transcutaneous oxygen pressure (TcPO2) and skin temperature., Results: Five patients (with 5 affected limbs) suffered from necrosis below the middle of the leg 4 weeks after transplantation and received amputation. For the remaining 59 patients (75 affected limbs), pain and cold sensation of the affected limbs were improved with varying extent 3 months after transplantation; there were statistically significant differences in pain score and cold sensation score of the affected limbs before and after APBSCT (p<0.05). Claudication distance, ABI, TcPO2 and skin temperature were also improved. Claudication distance increased from 85.69 m ± 43.48 m to 36.5 ± 9.88 mmHg, and the skin temperature of the lower limbs increased from 27.70 °C ± 0.53 °C to 33.49 °C ± 0.60 °C. All four indicators were considerably improved after APBSCT (p<0.05). Arteriography was performed for 75 affected limbs in 59 patients 6 months after transplantation and found that new collateral vessels were formed in the affected limbs. No patients were complicated by retinal hyperplasia, malignant tumors, myocardial infarction and cerebral infarction during the follow-up examinations; no patients underwent symptom aggravation during 9-48 month follow-up (average, 28.5 months)., Conclusions: APBSCT is an easy, safe and reliable treatment for ischemia of lower limbs, especially for those with poor distal arterial outflow tract in the lower limbs that do not permit bridging.

Thromboangiitis obliterans (TAO) is a rare disease of unknown etiology that results in the occlusion of limb arteries located distally to the elbow and knee. Despite the fact that more than one hundred years have passed since its first description, knowledge on the pathogenesis of TAO and precipitating factors is still limited. Due to a lack of decisive noninvasive diagnostic methods and geographical differences in the prevalence of this condition, data on TAO epidemiology also remains sparse. This review presents important evidence on the pathogenesis and the course of the condition, as well as diagnostic modalities, with a focus on differential diagnosis. Theories on the pathogenesis of TAO include the theory of an infectious disease, coagulation disorders and injury to vascular endothelium resulting in activation of the inflammatory response. Differential diagnosis should exclude thoracic outlet syndrome, blue toe syndrome, infectious endocarditis, popliteal entrapment syndrome, Takayasu disease, primary and secondary systemic vasculitis, antiphospholipid syndrome, infection with the anaerobic Clostridium sp. bacilli and some less common conditions.

To day there appears to be a consensus to recognize thromboangiftis obliterans (Buerger's disease) as a distinct clinical and pathological entity, characterized by an inflammatory occlusive vasculitis of the small and medium-sized arteries and veins that affects young adult smokers. The strong link with smoking is one of the unique features of thromboangiitis obliterans. Once the disease has became established stepping smoking is the only effective way to prevent evolution of the disease and to reduce the risk of major amputations. Ischaemia of the lower and upper limbs and superficial thrombophlabitis are the essential features of the clinical presentation. However the diagnosis of thromboangiitis is rendered difficult by the lack of specific clinical, radiological, biological and histapathological features. Thus the diagnosis is funded on a probabilistic approach. Discontinuation of tobacco use and to day cannabis are the cornerstone of therapeutic management of patients with thromboangiitis. In patients with ischaemic lesions local care is the other main component of therapeutic management, infusion of iloprost had demonstrated some efficacy.

Thromboangiitis obliterans (Buerger's disease) is a vasculitis with undulating clinical course multisegmentarily affecting small and medium-sized arteries and veins. The disease is closely linked to tobacco-use. Increasing knowledge of autoimmunologic mechanisms in the complex pathophyiology of the disease let to the formulation of an autoimmunity-hypothesis now serving as a new paradigma. New treatment options comprise progenitor-cell-therapy, immunoadsorption, use of sendothelin-receptor-blocking agent Bosentan, and prescriptions of antiphosphodiesterase-V-inhibitors., (© Georg Thieme Verlag KG Stuttgart · New York.)