Demographic Traits, Clinical Status, and Comorbidities of Patients With Thromboangiitis Obliterans in Japan.

BACKGROUND: The latest demographics, clinical and living conditions, and comorbidities of patients with thromboangiitis obliterans (TAO) in Japan are unknown.Methods and Results: We conducted a retrospective cross-sectional survey using the annual database of the Japanese Ministry of Health, Labour and Welfare medical support system for patients with TAO between April 2013 and March 2014. This study included 3,220 patients (87.6% male), with current age ≥60 years in 2,155 patients (66.9%), including 306 (9.5%) patients aged ≥80 years. Overall, 546 (17.0%) had undergone extremity amputation. The median interval from onset to amputation was 3 years. Compared with never smokers (n=400), 2,715 patients with a smoking history had a higher amputation rate (17.7% vs. 13.0%, P=0.02, odds ratio [OR]=1.437, 95% confidence interval [CI]=1.058-1.953). A lower proportion of workers and students was seen among patients after amputation than among amputation-free patients (37.9% vs. 53.0%, P<0.0001, OR=0.542, 95% CI=0.449-0.654). Comorbidities, including arteriosclerosis-related diseases, were found even in patients in their 20-30 s. CONCLUSIONS: This large survey confirmed that TAO is not a life-threatening but an extremity-threatening disease that threatens patients' professional lives. Smoking history worsens patients' condition and extremity prognosis. Long-term total health support is required, including care of extremities and arteriosclerosis-related diseases, social life support, and smoking cessation.

The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?

OBJECTIVE: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. METHODS: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). RESULTS: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. CONCLUSION: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

A systematic review and meta-analysis of early and late outcomes after endovascular angioplasty among patients with thromboangiitis obliterans and chronic limb ischemia.

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.

Assessment of atherectomy treatment for Thromboangiitis Obliterans: A single center experience.

BACKGROUND AND AIMS: Endovascular recanalizaiton (ER) has been proven to be a feasible method for Thromboangiitis Obliterans (TAO). The aims of this study were to evaluate the effectiveness and safety of atherectomy for TAO compared to nonatherectomy ER in our center. METHODS: Patients diagnosed as TAO were reviewed from January 2016 to June 2021 in our center. Basic characteristics of patients before ER and perioperative data were collected and compared between the atherectomy and nonatherectomy groups. The vascular event-free survival and limb salvage were calculated to evaluate the prognosis of TAO patients after ERs. Logistic Regression and Cox Regression were used to identify the risk factors for technical failure and prognosis, respectively. RESULTS: Seventy-two TAO patients with 79 lower limbs who met the criteria were included in this report. Compared with the nonatherectomy group, no significant improvement was identified in ER technical success, vascular event-free survival, or limb salvage in the atherectomy group. The total technical success rate was 91.1% (atherectomy group, 95.2%; nonatherectomy group, 89.7%), and the multiple limb involvement (p = 0.005; odds ratio [OR], 28.16; confidence interval [CI], 3.28-241.55) was the independent risk factor for technical failure. The total vascular event-free survival proportion was 66.05% and 58.40% at 1 and 3 years, respectively. Technical failure (OR, 5.61; 95% CI, 1.57-20.04; p = 0.008), and runoff grade 0 (OR, 3.28; 95% CI, 1.09-9.85; p = 0.034) were independent risk factors for vascular events. The total limb salvage proportion at 1 and 3 years was 95.84% and 92.53%, respectively. Technical failure (OR, 8.54; 95% CI, 1.71-40.73; p = 0.02) was identified as an independent risk factor for above ankle amputation. CONCLUSIONS: No significant difference in prognosis was found between the atherectomy group and the nonatherectomy group during a midterm follow-up. The technical success of ER was crucial for TAO prognosis.

Safety and Effectiveness of Excimer Laser Ablation Combined With Drug-Coated Balloon for Atherosclerotic Obliterans in the Lower Extremity.

PURPOSE: To evaluate the safety and effectiveness of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for atherosclerotic obliterans (ASO) of the lower extremities. MATERIALS AND METHODS: From June 2019 to December 2020, all eligible patients were enrolled. Demographics, characteristics of lesions, complications, and follow-up information were collected and analyzed. The primary endpoint was major amputation-free survival (MAFS). Secondary endpoints included technical success, primary patency, bailout stent, distal embolization, target lesion reintervention (TLR), and ulcer healing rate. Major amputation-free survival and primary patency were calculated by Kaplan-Meier analysis. RESULTS: A total of 71 patients were enrolled. Forty-eight (81.7%) patients presented critical limb ischemia (CLI) and 48.6% of them was calcification class 4 according to Peripheral Arterial Calcium Scoring System (PACSS). Chronic totally occluded (CTO) disease was the most common lesion in 66.0% of them and superficial femoral artery (SFA) was the most common segment in 59.6%. Technical success rate was 93.0%. One-year follow-up was finished in 25 (35.2%) patients. The primary patency and MAFS were 92.0%±27.6% and 96.0%±20.0% at 12 months, respectively. During the mean follow-up of 9.4±4.3 months, clinically-driven TLR occurred in 2 (2.8%) patients, and major and minor amputation occurred in 2 (2.8%) and 1 (1.4%) patient, respectively. CONCLUSION: The early results demonstrated that ELA was an effective treatment in de novo, in-stent restenosis (ISR) and CTO lesions. Meanwhile, ELA could prepare the lumen for the use of DCB and reduce the implantation of stents, especially in segments unsuitable for stenting. Mid-term and long-term results need to be awaited.

A Multicenter Prospective Interventional Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans.

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 (TcPO2). 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 TcPO2. 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.

A comprehensive review of the epidemiology and clinical features of 91 cases with Buerger's disease.

BACKGROUND: Thromboangiitis Obliterans (TAO) is a disease of small and medium-sized arteries with an unclear natural course. This study aims to establish a national registry of the disease to gain a better understanding of its epidemiology and clinical course. METHOD: This study was a cohort study of 242 patients with a high probability of TAO admitted to Mashhad University of Medical Sciences (MUMS) hospitals from 2000 to 2015. Of these, 91 patients with a confirmed diagnosis were included in the study (90 males and 1 female) with a mean age of 35 ± 7.8 years. RESULTS: The most common symptom upon onset of the disease was paresthesia (29.7%), followed by cold sensitivity and paresthesia (93.4%) during the progression of the disease and Raynaud syndrome or vasospasm (93.9%) in the active phase. The right lower limb was the most commonly affected limb (46.2%), and presenting ischemic symptoms in 48.4%.Statistics indicated a positive correlation between the duration of Burger's disease and the number of affected limbs (p = 0.001). There was no effect of disease duration on the likelihood of amputations (p = 0.28). CONCLUSION: Some patients may experience mild, subtle symptoms for years before the initial signs and symptoms appear, which can be severe and rapidly progress to the point of requiring amputation.We suggest that the diagnostic criteria for Buerger's disease should be revised in light of the presence of atherosclerosis and its associated risk factors, which present a challenge in terms of diagnosis and treatment. Clinical experience will be of great importance in this regard.

Acute phase reactant proteins in Buerger's disease: Is it a systemic disease?

Aim: The aim of this study was evaluating acute phase reactant (APR) proteins including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), fibrinogen, complement C3, hepcidin, and albumin in patients suffering from Buerger's disease (BD) compared to controls.Methods: The APRs were evaluated in 92 cases of BD patients and 90 healthy age and sex matched controls of blood from Iran and Turkey. The diagnosis was done according to Shionoya's criteria. However, patients with age less than 40 were included, instead of those less than 50. The diagnosis was confirmed by angiography or CT angiography. The patients were categorized into active and quiescent phases of the disease according to clinical manifestation. Patients with rest pain, non-healing ulcer, and gangrene were categorized in the active phase of the disease and the patients with unchanged claudication for more than 6 months without trophic lesions or gangrene were categorized in the quiescent phase of the disease.Results: The serum level of PTX3, hsCRP, fibrinogen, C3, and hepcidin in BD was significantly higher than controls (p < 0.004). Also, albumin in the BD group was significantly lower than controls (p < 0.001). In patients that categorized in the active phase, fibrinogen, C3, and hsCRP were significantly higher and albumin was significantly lower compared to patients in the quiescent phase. No significant difference was found between the level of PTX3 and hepcidin in the patients in active and quiescent phases of the disease.Conclusion: The pattern of the level of APRs in BD seems more likely systemic inflammatory disorder than atherosclerosis obliterans. More clinical trials for evaluating the efficacy of anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and corticosteroids as a part of management of BD are required. Also, according to low level of albumin in TAO, a protein rich diet might be beneficial for BD patients in the active phase of their disease.

miR-100 alleviates the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting MMP9.

OBJECTIVE: Thromboangiitis obliterans is a nonatherosclerotic segmental inflammatory disease, and miR-100 plays an anti-inflammatory role in chronic inflammation. Therefore, we hypothesized that miR-100 might alleviate the inflammatory damage and apoptosis of H2O2-induced ECV304 cells and aimed to investigate the relationship between miR-100 and thromboangiitis obliterans and the related molecular mechanism. METHODS: Cell counting kit-8 was used to detect cell viability, and the expression of inflammatory factors and oxidative stress was measured by ELISA. TUNEL assay was used to detect the apoptosis of human umbilical vein endothelial cells after induction by H2O2. Furthermore, the interaction between miR-100 and matrix metalloproteinase-9 was verified by dual-luciferase assay. Quantitative reverse transcription polymerase chain reaction and western blot were used to detect the expression of the adhesion factors, apoptosis-related proteins and Notch pathway-related protein. RESULTS: The results revealed that miR-100 was decreased in H2O2-induced human umbilical vein endothelial cells. Overexpression of miR-100 attenuated inflammatory response and cell apoptosis in H2O2-induced human umbilical vein endothelial cells. The overexpression of miR-100 inhibited matrix metalloproteinase-9 expression in H2O2-induced human umbilical vein endothelial cells. miR-100 inhibited H2O2-induced human umbilical vein endothelial cell inflammation, oxidative stress, and cell apoptosis via inactivation of Notch signaling by targeting matrix metalloproteinase. CONCLUSIONS: Our study demonstrated that miR-100 reduced the inflammatory damage and apoptosis of H2O2-induced human umbilical vein endothelial cells via inactivation of Notch signaling by targeting matrix metalloproteinase. These findings suggested that miR-100 might be a novel therapeutic target for the prevention of thromboangiitis obliterans.

Surgical Treatment Options for Buerger's Disease (Experience with 315 Cases in Iran).

Background: Buerger's disease (thromboangiitis obliterans) may be a rare peripheral vascular disease that sometimes affects young male smokers. This study presents surgical treatment options for 315 Buerger's patients during a period of 18 years from 2002 to 2020. Methods: In this cross-sectional study, 315 newly diagnosed Buerger patients in a period of 18 years (by Census sampling) were evaluated. Data included age, sex, cigarette smoking status, clinical presentation, the affected limb (right or left, upper or lower extremities), and the performed therapeutic procedures such as angiography of limb arteries, amputation, sympathectomy, and vascular bypass surgery, which were collected in a data sheet. Vascular reconstruction was done if there were suitable inflow and outflow arteries. Sympathectomy was performed for the patients who were unsuitable for revascularization. All analyzes were performed using SPSSV.18 software package (SPSS Inc., Chicago, IL). Data are presented as frequency, mean ± variance (SD). Results: The mean age of patients was 42.6±9 years old, ranging from (26-75). There were 309 (98.1%) males and 6 (1.9%) females. The most common symptom was ulcer 252 (80%), and the most commonly involved arteries were the dorsal pedis (N=231; 73.4%) and posterior tibialis (N=225; 71.5%). Vascular bypass surgery, sympathectomy, and amputation were performed for patients who met surgical indications. Aortofemoral (N=9) and femoropopliteal (N=24) bypass procedures were done in 2.8% and 7.6% of patients respectively. Of nine patients who underwent aorto-femoral bypass procedure, 6 cases presented with leg claudication, 3 with an ulcer, and 3 with the Raynaud phenomenon. The digital loss rate was 9.6% (N=9) in toes and 1% (N=3) in fingers. Conclusion: As most of the Buerger patients have multi arterial involvement, bypass surgery or sympathectomy can't help treat these patients more than cigarette smoking or pharmaceutical therapy.

Women and Pregnancy in Thromboangiitis Obliterans.

Data regarding women and thromboangiitis obliterans (TAO) are conflicted, and a few cases of pregnancy have been described. We aimed to describe the interplay between TAO and pregnancies. Among 224 TAO patients, 22.8% were women. Demographic data, clinical manifestations, and outcomes were similar between men and women. Twenty-one (41.2%) women had 48 pregnancies. Thirty-six (75%) pregnancies with on term and complication free delivery occurred. None of the patients experienced a disease flare of TAO during pregnancy. TAO does not seem to affect pregnancy complications, and pregnancy does not seem to interfere with the course of TAO.

Endovascular Treatment of Critical Limb Ischemia in Buerger Disease (Thromboangiitis Obliterans) With Midterm Follow-Up: A Viable Option When Bypass Surgery Is Not Feasible.

OBJECTIVE. Thromboangiitis obliterans (TAO) is an occlusive inflammatory disease affecting small- and medium-sized vessels that causes decrease in life quality and eventually limb loss. The only proven treatment method is smoking cessation, but it may be insufficient for limb salvage in patients with critical limb ischemia. In this single-center retrospective study, the feasibility and efficiency of endovascular treatment in TAO were evaluated. MATERIALS AND METHODS. After approval of the local institutional review board, 41 patients who underwent endovascular treatment of TAO between January 2014 and June 2019 were evaluated retrospectively. Technical success and procedure-related complications were recorded. Decrease in Rutherford classification score, relief of pain, and wound healing were evaluated to determine clinical success. Primary patency, limb salvage rate, and amputation-free survival were also evaluated. RESULTS. A total of 45 limbs were treated during the study period. Technical success was achieved in 82.2% of procedures. Mean follow-up was 29.8 months. Clinical improvement was achieved in 35 limbs. Three patients underwent major amputation and 12 patients underwent minor amputation. Amputation-free survival and limb salvage were both 93.3% at both 1 and 2 years. Reintervention was performed in 14 patients because of occlusion and clinical relapsing of the symptoms. CONCLUSION. Endovascular treatment of TAO is feasible, has a potential to prevent limb amputation in patients with critical limb ischemia, and has acceptable technical success and limb salvage rates. Because there is no consensus in treatment of TAO, prospective comparative studies are needed to determine the effectiveness of an endovascular approach.

Current Trends in Epidemiology and Clinical Features of Thromboangiitis Obliterans in Japan　- A Nationwide Survey Using the Medical Support System Database.

BACKGROUND: The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively.Methods and Results:This retrospective study used the Japanese Ministry of Health, Labour and Welfare (JMHLW) medical support system database and associated health insurance data. The number of medical financial support recipients registered as TAO patients and estimated prevalence of TAO decreased from fiscal year (FY) 2000 (10,089 and 7.95 [95% confidence interval, CI: 7.79-8.10] per 100,000 population) to FY 2010 (7,147 and 5.58 [95% Cl: 5.45-5.71] per 100,000) and leveled off until 2014. The prevalence of TAO among patients with peripheral arterial occlusive diseases declined from 7.15% (95% Cl: 7.00-7.31) in FY 2008 to 6.12% (95% Cl: 5.98-6.26) in FY 2014. Clinicodemographic features were obtained from 89 new recipients in FY 2013 and 2014: 12 (13%) women, 36 (40%) aged ≥50 years, 26 (29%) had probable onset age ≥50 years, 7 (8%) were non-smokers, and 12 (13%) had arteriosclerosis-related comorbidities. The symptoms were similar regardless of registration age, smoking history, or sex. Although 40 (45%) had digit ulcers, only 12 (13%) fulfilled Shionoya's criteria. They rarely had infrapopliteal lesions combined with upper extremity involvement or phlebitis. CONCLUSIONS: The prevalence of TAO has decreased in Japan. In the current diagnosis of TAO, various clinical characteristics including late onset, arteriosclerotic factors, non-smoking, or mild symptoms should be considered.

Humoral and cellular immune response to Buerger's disease.

OBJECTIVE: Thromboangiitis obliterans is a nonatherosclerotic occlusive disease, affecting small to moderate sized arteries of the upper and lower extremities, leading to progressive inflammation and clot formation. However, the role of humoral and cell-mediated immunity in the development of this disease has not been clearly identified. The present study was intended to investigate the humoral and cellular immune response in patients with Buerger's disease with different disease severity. METHODS: In an observational study, 80 male patients with Buerger's disease were included and categorized into three groups (mild, moderate, and severe) based on clinical manifestations. After blood sampling, cellular phenotypes were determined, and erythrocyte sedimentation rate, immunoglobulins (Ig) A, M, G, and E, as well as C3 and C4 components of the complement system and complement hemolytic activity (CH50) were measured. RESULTS: The mean age of the patient was 42.85 ± 8.39 years. Pulse abnormality, cold intolerance, and claudication were the most common symptoms. Eleven (13.75%), 46 (57.50%), and 23 (28.75%) patients had mild, moderate, and severe symptoms. Regression analyses showed that the presence of severe symptoms was significantly associated with elevated erythrocyte sedimentation rate and C4 levels (p < 0.05). CONCLUSION: Buerger's disease in severe cases was associated with increased erythrocyte sedimentation rate and abnormal C4 levels. The alterations in these inflammatory biomarkers might be due to a secondary inflammatory response to the presence of ulcer or gangrene and the inflammatory process in patients with severe symptoms.

Unexpected inflammation in the sympathetic ganglia in thromboangiitis obliterans: more likely sterile or infectious induced inflammation?

INTRODUCTION: The aim of this study was to determine if the inflammation of the sympathetic ganglia (SG) in thromboangiitis obliterans (TAO) is induced by an infectious pathogen inside or if it is a reactive sterile inflammation. METHODS: For the purpose of this study, the gene expression of high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), toll-like receptor 9 (TLR9), and the receptor for advanced glycation end-products (RAGE) were evaluated on the complementary DNA (cDNA) of the SG tissues of 24 TAO patients and two controls with hyperhidrosis by real-time polymerase chain reaction (PCR) and analysed by the Pfaffl method. RESULTS: The gene expression of HMGB1 and TLR9 increased by about 25- and 2-fold changes in the SG of the TAO patients, respectively. However, there was no change in the gene expression of TLR4 or RAGE. CONCLUSION: It appears that the inflammation in the SG of TAO patients is more likely a sterile inflammation, and its trigger may be mitochondrial DNA (mtDNA). Cadmium in cigarettes could be responsible for the induction of mtDNA release to the cell cytoplasm. In addition, the high expression of HMGB1 may play a role in the pathogenesis of TAO and may be responsible for both clinical manifestation of the disease and the imaging findings. Moreover, HMGB1 may be a target for treatment protocols for TAO. Further studies are highly recommended.

[Comprehensive treatment of a patient with Buerger's disease using genetically engineered complexes VEGF-165]. / Kompleksnoe lechenie patsienta s bolezn'iu Biurgera s primeneniem genno-inzhenernykh konstruktsii VEGF-165.

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.

Alleviation of A disintegrin and metalloprotease 10 (ADAM10) on thromboangiitis obliterans involves the HMGB1/RAGE/ NF-κB pathway.

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a nonatherosclerotic inflammatory disease that influences medium- and small-sized blood vessels of extremities. However, mechanisms underlying TAO are still unclear. As a mediator associated with inflammation, A disintegrin and metalloprotease 10 (ADAM10) was hypothesized to play inhibitory roles in the development of TAO. Thus, the objective of this study is to investigate the effects of ADAM10 in a sodium laurate-induced TAO rat model and elucidate underlying mechanisms. Male Wistar rats were randomly divided into four groups (n = 6) for treatment: sham-operated (SHAM), TAO model (TAO), ADAM10 low dose injection (3 mg/kg; ADAM10-LD) and ADAM10 high dose injection (6 mg/kg; ADAM10-HD). After 14-day treatment, color Doppler ultrasound and hematology analysis indicated TAO rats displayed higher whole blood viscosity and blood platelet count compared with those in the SHAM group. Histologic evaluation and transmission electron microscopy revealed that the ultrastructural damages of vascular smooth muscle and endothelial cells were observed in TAO rats, such as fractured endoplasmic reticulum, decreased cell counts, and fibrillation. On the other hand, the typical signs and symptoms of TAO rats were significantly alleviated via ADAM10 treatment with a dose-dependent pattern. Real-time PCR and western blot results revealed that the expression of high-mobility-group box 1 (HMGB1), receptor for advanced glycation end-products (RAGE) and nuclear factor-kappa B (NF-κB) increased in TAO rats whereas decreased by ADAM10 treatment in both mRNA and protein levels. In conclusion, the results suggest ADAM10 alleviates symptoms of sodium laurate-induced TAO in rats via the RAGE/NF-κB signaling pathway and provides insight into the molecular basis and a potential therapeutic strategy for TAO.

Endovascular Therapy Outcomes and Intravascular Ultrasound Findings in Thromboangiitis Obliterans (Buerger's Disease).

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.

Chronic lower extremity wound infection due to Kerstersia gyiorum in a patient with Buerger's disease: a case report.

BACKGROUND: Kerstersia gyiorum is an extremely rare pathogen of human infection. It can cause chronic infection in patients with underlying conditions. It can easily be misdiagnosed if proper diagnostic methods are not used. CASE PRESENTATION: A 47-year-old male patient with a history of Buerger's Disease for 28 years presented to our hospital with an infected chronic wound on foot. The wound was debrided, and the specimen was sent to Microbiology laboratory. Gram staining of the specimen showed abundant polymorphonuclear leukocytes and gram-negative bacilli. Four types of colonies were isolated on blood agar. These were identified as Kerstersia gyiorum, Proteus vulgaris, Enterobacter cloacae, Morganella morganii by Maldi Biotyper (Bruker Daltonics, Germany). The identification of K. gyiorum was confirmed by 16S ribosomal RNA gene sequencing. The patient was successfully recovered with antimicrobial therapy, surgical debridement, and skin grafting. CONCLUSIONS: This is the first case of wound infection due to K. gyiorum in a patient with Buerger's Disease. We made a brief review of K. gyiorum cases up to date. Also, this case is presented to draw attention to the use of new and advanced methods like MALDI-TOF MS and 16S rRNA gene sequencing for identification of rarely isolated species from clinical specimens of patients with chronic infections and with chronic underlying conditions.