Thromboangiitis Obliterans Patients Research Articles

The Role of Gut Microbiota in Thromboangiitis Obliterans: Cohort and Mendelian Randomization Study.

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare vasculitis. Observational epidemiology studies have suggested a relationship between the gut microbiota and TAO. However, due to confounding factors and reverse causality, the causal relationship remains unclear. Based on the assumption of their association, this study sought specific gut microbiota causally linked to TAO. The case-control study was conducted at the Xiangya Hospital of Central South University from November 2022 to January 2023 including twelve TAO patients and nine healthy controls. We conducted a Mendelian randomization (MR) study using summary statistics from a genome-wide association study (GWAS) of gut microbiota and TAO. Considering the scale and accessibility of the data, the MiBioGen consortium served as the exposure, whereas the FinnGen consortium GWAS study served as the outcome. Finally, we compared the results of the MR with those of the case-control studies. The inverse variance weighted (IVW) (OR = 0.119, 95% CI: 0.021-0.688, p = 0.017) and maximum likelihood (ML) (OR = 0.121, 95% CI: 0.020-0.742, p = 0.022) estimates suggest that Ruminiclostridium 5 has a suggestive protective effect on TAO while the IVW (OR = 5.383, 95% CI: 1.128-25.693, p = 0.035) and ML (OR = 5.658, 95% CI: 1.142-28.021, p = 0.034) estimates suggest that Eubacterium (xylanophilum group) has a suggestive risk effect on TAO, and the ML (OR = 0.055, 95% CI: 0.004-0.755, p = 0.030) estimates suggest that Lachnospira has a suggestive protective effect on TAO. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. The results of the case-control study showed that the TAO had a lower relative abundance of Ruminiclostridium 5 (p = 0.015) and Lachnospira (p = 0.048), and a higher relative abundance of Eubacterium (xylanophilum group) (p = 0.029) than the healthy controls. These results were consistent with the MR analysis. Our study demonstrates that Ruminiclostridium 5, Lachnospira, and Eubacterium (xylanophilum group) are causally related to TAO, suggesting their potential significance for the prevention and treatment of TAO.

Toll-like receptor signaling pathway involved in pathogenesis of thromboangiitis obliterans through activating of NF-κB

ObjectivesThe pathogenic mechanisms of Thromboangiitis Obliterans (TAO) are not entirely known and autoimmune inflammation plays a vital role in the initiation and continuance of TAO activity. The authors investigated in this study the role of the TLR signaling pathway in the pathogenesis of TAO. MethodsFirst, the authors detected the expressions of MyD88, TRIF and NF-κB in vascular walls of 46 patients with TAO and 32 patients with trauma and osteosarcoma by western blot assay. Second, the authors detected the cellular localization of MyD88, TRIF and NF-κB in vascular walls of patients with TAO by immunofluorescent assay. ResultsThe protein expressions of MyD88, TRIF and NF-κB were much higher in vascular walls of TAO patients (p < 0.05). Higher expressions of MyD88 and NF-κB were detected both on vascular endothelial and vascular smooth muscle cells of TAO patients. However, higher expression of TRIF was just detected on vascular smooth muscle cells of TAO patients. ConclusionsThese dates suggest that the TLR signaling pathway might play an important role in the pathogenesis of TAO, it might induce vasospasm, vasculitis and thrombogenesis to lead to the pathogenesis and progression of TAO.

Comparative Analysis of Transcriptome Profiles in Patients with Thromboangiitis Obliterans.

Thromboangiitis obliterans (TAO) causes vascular insufficiency due to chronic inflammation and abrupt thrombosis of the medium and small arteries of the extremities. In our study, we aimed to determine biomarkers for the diagnosis of TAO by evaluating 15 male TAO patients with Shinoya diagnostic criteria and 5 healthy controls who did not have TAO-related symptoms in their family histories. The Clariom D Affymetrix platform was used to conduct microarray analysis on total RNA extracted from whole blood. A total of 477 genes (FC ≤ 5 or >5) common to the fifteen patient and five control samples were selected using comparative microarray analysis; among them, 79 genes were upregulated and 398 genes were downregulated. According to FC ≤ 10 or >10, in the same TAO patient and control group, 13 genes out of 28 were upregulated, whereas 15 genes were downregulated. The 11 key genes identified according to their mean log2FC values were PLP2, RPL27A, CCL4, FMNL1, EGR1, EIF4A1, RPL9, LAMP2, RNF149, EIF4G2, and DGKZ. The genes were ranked according to their relative expression as follows: FMNL1 > RNF149 > RPL27A > EIF4G2 > EIF4A1 > LAMP2 > EGR1 > PLP2 > DGKZ > RPL9 > CCL4. Using protein-protein interaction network analysis, RPL9, RPL27A, and RPL32 were found to be closely related to EIF4G2 and EIF4A1. The Reactome pathway found pathways linked to 28 genes. These pathways included the immune system, cellular responses to stress, cytokine signaling in the immune system, and signaling by ROBO receptors. By figuring out the protein expression levels of the genes that have been found to explain how TAO disease works at the molecular level, it will be possible to figure out how well these chosen transcripts can diagnose and predict the disease.

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

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. 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. 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. 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.

Salvianolic acid A exerts a protective effect against sodium laurate induced thromboangiitis obliterans in rats

Purpose: To study the potential therapeutic effects of salvianolic acid A (Sal A) on thromboangiitis obliterans (TAO).&#x0D; Methods: An in vitro model of TAO-mimicking endothelial cell damage was established by incubating ECV304 cells with H2O2. An in vivo model of TAO rats was developed via injection of sodium laurate. After treatment with varying doses of Sal A, TAO symptoms were monitored over time and compared. The effects of Sal A on oxidative stress, pyroptosis, inflammation, and thrombosis were assessed using biochemical assays, enzyme-linked immunosorbent assay (ELISA), western blot, and histopathology.&#x0D; Results: Sal A significantly alleviated the inhibition of cell viability induced by H2O2 (p &lt; 0.05). The H2O2-induced increases in levels of ROS, IL-1β, and IL-18 in ECV304 cells were significantly decreased by Sal A (p &lt; 0.05). Moreover, Sal A alleviated TAO symptoms in rats. The enhanced levels of IL-1β, IL-18, NLRP3, and active Caspase-1 observed in TAO rats were reduced by Sal A in vivo (p &lt; 0.05). Moreover, Sal A significantly reduced the size of thrombus in TAO rats. In addition, upregulated levels of ROS were significantly inhibited by Sal A (p &lt; 0.05).&#x0D; Conclusion: Sal A exerts significant therapeutic effects on TAO. This provides mechanistic insights into the clinical effects of RSMA on TAO patients, which might be beneficial in the development of effective drugs against TAO in the future.

Clinical outcomes in patients with infrapopliteal arterial occlusive disease treated by lower extremity bypass surgery: a comparison of atherosclerosis and thromboangiitis obliterans.

Surgical bypasses are commonly utilized for the treatment of infrapopliteal arterial occlusive disease resulting from atherosclerosis (ASO) and thromboangiitis obliterans (TAO), especially when endovascular procedures fail. The aim of this study is to compare the in-hospital and follow-up outcomes of ASO and TAO patients treated with infrapopliteal bypass surgery. A total of 32 infrapopliteal bypasses were analyzed in 18 TAO patients and 14 ASO patients. Preoperative and postoperative arterial Doppler ultrasonography was performed in all patients. The ankle-brachial index (ABI) was calculated preoperatively and postoperatively in all cases. All patients were followed-up for at least one year and clinical outcomes were recorded. Within 1-7 days postoperatively, 4 grafts in TAO patients occluded; nevertheless, 1 graft occlusion occurred in ASO patients. Patency rates at in-hospital were 77.8% and 92.9% in TAO and ASO patients, respectively. In 27 patients with successful infrapopliteal bypass, ABIs and crural peak arterial flow velocities significantly increased at 1-7 days postoperatively. During the period of follow-up, 6 graft occlusions occurred in TAO patients, and one ASO patient died of myocardial infarction. Patency rates at follow-up were 44.5% and 85.7% in TAO and ASO patients. For TAO patients with graft failure, ABIs at follow-up did not statistically differ from those postoperatively; however, they were significantly higher than those preoperatively. Infrapopliteal bypass surgery is a feasible and effective procedure for ASO and TAO patients. Patency rates are lower in TAO than those in ASO during the in-hospital and follow-up period. However, TAO patients had the ischemic symptom relief and the improvement in ABI despite graft occlusion one year postoperatively.

SMOKING AND BUERGER’S DISEASE: FROM HYPOTHESES TO EVIDENCE SYNTHESIS

Early after the definition of thromboangiitis obliterans (TAO), it was noticed that TAO patients are almost always tobacco smokers. Later on, the relationship between continued smoking and TAO prognosis was documented. Consequently, smoking came to be considered as the main cause of TAO. However, it is still unknown why, amongst millions of smokers, only a small number develop TAO. It also remains unknown why, of the TAO patients who continue smoking, only half of them show aggravation and undergo amputations. The aims of this review are to investigate evidence in support of or against the relationship between TAO and smoking, according to the TAO-related literature published from 1908 to January 2022, and to discover the possible role of smoking in TAO pathophysiology. Taken together, it appears that smoking predisposes TAO patients toward the potential harmful effects of the main aetiology and helps the main aetiology to develop vascular lesions. Therefore, smoking cessation would almost always be helpful for improving the prognosis of TAO patients and reducing disease manifestation. However, concluding that smoking is not the main aetiology of TAO would open a new door to finding the true main aetiology of TAO and to discovering the appropriate treatment and medical management of patients who fail to stop smoking.

Covid-19 infection and Buerger`s syndrome: A case report

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the recent global pandemic, with increasing number of cases reported globally. Our understanding of this novel respiratory virus deepens, it is increasingly clear that its effects extend beyond that of the respiratory system and can be extended to the almost all organ systems. SARS-CoV-2 causes lung inflammation which progresses to cytokine storm in the most severe cases. The lungs of patients with COVID-19 show extensive alveolar and interstitial inflammation. COVID-19 causes a spectrum of complications, with frequent involvement of the hemostatic system and there is a high incidence of venous thromboembolism in hospitalized COVID-19 patients, particularly those with severe illness. There is evidence of current body knowledge that COVID-19 induced by microvascular angiopathy can lead to a wide range of tissue pathology and clinical complications, such as Kawasaki disease, Buerger’s syndrome and other systemic inflammatory disorders. Thromboangiitis obliterans (TAO) or Buerger’s disease is a segmental occlusive inflammatory condition of arteries and veins, characterized by thrombosis and recanalization of the affected vessels. Limb infection at diagnosis was associated with a 4-fold higher risk of amputation. Smoking cessation was strongly associated with a lower rate of vascular events and amputation. TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. We present a case of a 53-years-old male with positive SARS-CoV-2 PCR test. Furter examination showed that patient had pneumonia, moreover, based on the duplex scan results the diagnosis of thromboangiitis obliterans (TAO) or Buerger’s disease was confirmed. This disease itself is associated with a high risk of thrombosis and alongside with COVID-19 can cause unpredictable outcome. Patient underwent the day-round observation, received the appropriate treatment and was successfully discharged from the hospital on the day 11.

Integrated analysis of long non-coding RNA-microRNA-mRNA competing endogenous RNAregulatory networks in thromboangiitis obliterans

ABSTRACT Thromboangiitis obliterans (TAO) is a non-atherosclerotic, segmental, chronic vascular inflammatory disease. Our aim was to explore the underlying mechanisms of long non-coding RNA (lncRNA)-related competing endogenous RNAs (ceRNAs) in TAO. Six blood samples were collected from patients with TAO and healthy individuals (three for each category). Total RNA was extracted from the blood of each participant and sequenced. Differentially expressed lncRNAs (DE-lncRNAs) and miRNAs (DE-miRNAs) were screened, and ceRNA networks associated with TAO were constructed. Thereafter, the genes in the ceRNA network were subjected to functional analyses. Finally, a ceRNA relationship (lncRNA NEAT1-hsa-miR-1-3p-mRNA GNA12) was selected for further validation. Analysis revealed that 347 DE-lncRNAs (150 downregulated and 197 upregulated) and 16 DE-miRNAs (3 downregulated and 13 upregulated) were identified in TAO. Further, TAO-associated ceRNA networks, which included 219 lncRNAs, 6 miRNAs, and 53 mRNAs, were proposed and subjected to gene annotation and pathway analysis. Additionally, NEAT1 and GNA12 levels were significantly upregulated, while miR-1-3p levels were evidently downregulated in TAO patients, as compared with those in healthy controls. Dual luciferase reporter assays showed that NEAT1, miR-1-3p, and GNA12 interacted with each other. We report potential TAO-associated ceRNA regulatory networks and suggest activation of NEAT1/miR-1-3p/GNA12 signaling as a novel mechanism for TAO progression.

A Prospective Study of Surgical Revascularization in Patients of Buerger's Disease from North India

Introduction: Buerger's disease, also known as thromboangiitis obliterans (TAO), is vasculitis of small- and medium-sized arteries and veins, which may involve both upper and lower extremities. It is strongly related to smoking and fairly common in the Indian subcontinent. Diagnosis is based on history, clinical examination, and angiography. The single most important modality of treatment is smoking cessation. As only few patients have suitable anatomy for surgical revascularization, the aim of this study is to evaluate the feasibility and outcome of surgical revascularization in TAO patients of North India. Methods: This is a prospective observational study involving 50 patients of TAO diagnosed by modified Shionoya criteria who underwent surgical revascularization. Computed tomographic angiography was done in all patients to see their suitability for surgical revascularization. Graft patency at 6 months postsurgery, pre- and post-operative ankle–brachial pressure index (ABPI), and visual analog scale (VAS) score for pain were calculated and compared. Results: All patients were male bidi smokers, with a mean age of 29.8 ± 9.5 years. Intermittent claudication was present in 42%, rest pain in 58%, and ulcer in 40%. Most common area of blockage was tibioperoneal trunk (62%) and tibial arteries (52%). The most frequent bypass procedure was popliteotibial done in 32 (64%) patients, followed by femoropopliteal bypass in 8 (16%) patients. Majority of our patients were symptom free at 6 months postsurgery. The mean VAS score for pain at the time of presentation was 6.08 ± 1.77, which decreased to 1.62 ± 1.23 at the end of 6 months. The mean preoperative ABPI was 0.45 ± 0.12 which improved to 0.73 ± 0.09 at 6 months postsurgery. A total of 46 (92%) limbs were salvaged while overall our graft patency rate was 70% at 6 months. Conclusion: We conclude that surgical revascularization is feasible in properly selected patients of TAO with acceptable results.

Digital ischaemia aetiologies and mid-term follow-up: A cohort study of 323 patients.

Upper extremity digital ischaemia (UEDI) is a rare heterogeneous condition whose frequency is 40 times less than that of toe ischaemia. Using a large cohort, the aim of this study was to evaluate aetiologies, prognosis and midterm clinical outcomes of UEDI.All patients with UEDI with or without cutaneous necrosis in a university hospital setting between January 2000 to December 2016 were included. Aetiologies, recurrence of UEDI, digital amputation and survival were analyzed retrospectively.Three hundred twenty three patients were included. UEDI due to cardio-embolic disease (DICE) was the highest occurring aetiology with 59 patients (18.3%), followed by DI due to Systemic Sclerosis (SSc) (16.1%), idiopathic causes (11.7%), Thromboangiitis obliterans (TAO) (9.3%), iatrogenic causes (9.3%), and cancer (6.2%). DICE patients tended to be older and featured more cases with arterial hypertension whereas TAO patients smoked more tobacco and cannabis. During follow-up, recurrences were significantly more frequent in SSc than in all other tested groups (P < .0001 vs idiopathic and DICE, P = .003 vs TAO) and among TAO patients when compared to DICE patients (P = .005). The cumulated rate of digital amputation was higher in the SSc group (n = 18) (P = .02) and the TAO group (n = 7) (P = .03) than in DICE (n = 2).This retrospective study suggests that main aetiologies of UEDI are DICE, SSc and idiopathic. This study highlights higher frequency of iatrogenic UEDI than previous studies. UEDI associated with SSc has a poor local prognosis (amputations and recurrences) and DICE a poor survival. UEDI with SSc and TAO are frequently recurrent.

Effect of cannabis consumption on characteristics and evolution of thromboangitis obliterans.

Background: Thromboangiitis obliterans (TAO) is a distal non atherosclerotic thrombotic vasculitis affecting tobacco smokers. The role of cannabis co-exposure remains controversial. The study aims to assess how cannabis consumption influences clinical presentation and outcome of TAO in tobacco smokers. Patients and methods: TAO patients, according to Papa's criteria, were included in a retrospective bicentric study between the 1st January 2003 and the 1st march 2020. Clinical characteristics, arterial involvement at TAO diagnosis, vascular event and amputations during follow-up were analyzed according to cannabis consumption. Results: Seventy-three patients with TAO patients were included. Forty-five patients were in Tobacco group (T) and 28 in Tobacco and cannabis group (T&C). Tobacco exposure was less important in T&C group than in T group (19.4±11.3 vs 31.6±16.6 pack-years) (p=0.005) and patients in T&C group were younger at TAO diagnosis than in T group (p=0.008). Patients in T&C group presented more claudication (33.3% vs 8.9%, p=0.01) and less upper limbs resting ischemia (25.9% vs 51.1%, p=0.04) than patients in the T group. No differences were found between groups with regard to arterial distribution. Amputation rate for patients who had at least one major or minor amputation did not differ between T and T&C group (25% vs 14.8%, p=0.38). Conclusions: Cannabis consumption was associated with a younger age of TAO onset. However, it does not affect amputation-free survival, Tobacco exposure is less important in T&C patients; data of this bicentric study suggest that cannabis could be a cofactor of tobacco which accelerates TAO onset.

Thromboangiitis obliterans plasma-derived exosomal miR-223-5p inhibits cell viability and promotes cell apoptosis of human vascular smooth muscle cells by targeting VCAM1

Background: Exosomes-encapsulated microRNAs (miRNAs) have been established to be implicated in the pathogenesis of different diseases. Nevertheless, circulating exosomal miRNAs of thromboangiitis obliterans (TAO) remains poorly understood. This study aimed to explore the effects of exosomal miRNAs associated with TAO on human vascular smooth muscle cells (HVSMCs). Methods: The exosomes were isolated from the plasma of TAO patients and normal controls and then were sent for small RNA sequencing. Differentially expressed miRNAs (DE-miRNAs) were identified by bioinformatics analysis and were confirmed by RT-qPCR. After that, PKH67 staining was used to label exosomes and co-cultured with HVSMCs. Cell viability and apoptosis were, respectively, tested by CCK-8 assay and flow cytometry. Finally, dual-luciferase reporter assay was used to confirm the downstream targets of miR-223-5p. Results: A total of 39 DE-miRNAs were identified between TAO patients and normal controls, of which, miR-223-5p was one of the most significantly up-regulated miRNAs. TAO plasma-derived exosomes or miR-223-5p mimics inhibited cell viability of HVSMCs and promoted cell apoptosis. The pro-apoptotic effect of TAO plasma-derived exosomes was alleviated by miR-223-5p inhibitor. Additionally, the expressions of VCAM1 and IGF1R were down-regulated by exosomes and miR-223-5p mimics, and were abrogated by miR-223-5p inhibitor. Dual-luciferase report showed that VCAM1 was the target of miR-223-5p. Conclusions: Our findings imply that circulating exosomal miR-223-5p may play an essential role in the pathogenesis of TAO, and provide a basis for miR-6515-5p/VCAM1 as novel therapeutic targets and pathways for TAO treatment.

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

The epidemiology and clinical features of thromboangiitis obliterans (TAO) in Japan have not been updated extensively. 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. 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.

The IL-33/sST2 Axis in Thromboangiitis Obliterans.

BackgroundUntil recently, it remains unknown whether thromboangiitis obliterans (TAO) is a type of systemic vasculitis. A high level of IL-33 and its soluble decoy receptor sST2 in the acute phase of systemic vasculitis has been demonstrated.MethodsThe serum level of IL-33 and sST2 in 50 TAO patients, 20 age- and smoking habit-matched controls and 19 age-matched non-smoker controls was evaluated.ResultsThe mean level of IL-33 in TAO, smokers and non-smokers was 370.2±61.7ng/mL,132.14±2.6ng/mL and 11.3±0.38ng/mL, respectively. The IL-33 was significantly higher in the TAO than in either control groups (p < 0.001). The IL-33 in the acute phase of TAO was significantly higher than in the patients in the quiescent phase of the disease (p = 0.019). Also, IL-33 in the patients with gangrene was significantly higher than in the patients with non-healing ulcers (p = 0.021). The sST2 in the TAO patients was 49.3±5.58ng/mL, and in smoker and non-smoker controls, it was 45.3±6.3ng/mL and 4.11±0.17ng/mL, respectively. No significant difference was found between the patients and smoker control groups (p = 0.87). The mean ratio of IL-33/sST2 was 27.89±10.44 in the TAO group and, in smokers and non-smokers, it was 2.85±0.48 and 2.84±0.14, respectively. A significantly high level of IL-33/sST2 ratio was observed in TAO patients in both the active and quiescent phases of the disease in comparison to both control groups (p<0.001).ConclusionThe regulation pattern of IL-33/sST2 was different in TAO in comparison to autoimmune vasculitis.

Long-Term Clinical Outcomes of Autologous Bone Marrow Mononuclear Cell Implantation in Patients With Severe Thromboangiitis Obliterans.

Patients with severe Buerger disease, also known as thromboangiitis obliterans (TAO), are at risk of major limb amputation. It has been shown that autologous bone marrow mononuclear cell (BM-MNC) implantation improves the condition of critical limb ischemia in TAO patients. This study was conducted to further clarify the long-term (>10 years) results of autologous BM-MNC implantation in patients with TAO.Methods and Results:An observational study was conducted of the long-term results of BM-MNC implantation in 47 lower limbs of 27 patients with TAO. The mean (±SD) follow-up period was 12.0±8.6 years. There was no major amputation event up to 10 years of follow-up in patients treated with BM-MNC implantation. The overall amputation-free survival rates were significantly higher in patients who underwent BM-MNC implantation than in internal controls and historical controls. There was no significant difference in amputation-free survival rates between the historical and internal controls. There was also no significant difference in overall survival between patients who underwent BM-MNC implantation and the historical controls. BM-MNC transplantation successfully prevented major limb amputation over a period of >10 years in patients with severe TAO who had no other therapeutic options.

Assessment of T helper 17-associated cytokines in thromboangiitis obliterans.

BackgroundThe management of thromboangiitis obliterans (TAO) remains a medical challenge because of its unknown etiology. It is also not known whether it is a systemic or localized disease or a type of autoimmune vasculitis.MethodsIn this study, we evaluated the serum level of IL-17 and IL-23 which increase in both systemic inflammation and autoimmunity, in 60 TAO patients and 30 age- and smoking habit-matched controls. Also, IL-22, which has reported high level during infection but not in autoimmunity, was evaluated.ResultsThe serum levels of IL-17, IL-22 and IL-23 were significantly higher in the TAO patients in comparison with the controls (P<0.001). Notably, the serum levels of IL-17, IL-22 and IL-23 were highest in the patients with the chief complaint of chronic ulcer and lowest in the patients with gangrene (P<0.05). Also, the serum level of IL-22 was significantly higher in the anemic patients in comparison with the non-anemic patients (P=0.03).ConclusionOwing to our findings, TAO appears more likely to be a systemic disorder rather than a localized vasculopathy. Therefore, treatment protocols based on systemic treatment of TAO patients may be more helpful than localized treatment, such as bypass surgery and endovascular procedures. Also, according to our findings regarding the high level of IL-22, the trigger of TAO development may be an infectious pathogen. However, additional research is highly recommended to investigate whether TAO is an infectious disease or an infectious-induced autoimmunity.

Visceral bed involvement in thromboangiitis obliterans: a systematic review.

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.

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

IntroductionThe 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.MethodsFor 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.ResultsThe 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.ConclusionIt 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.

Endovascular Recanalization of Thromboangiitis Obliterans (Buerger's Disease) in Twenty-Eight Consecutive Patients and Combined Antegrade-Retrograde Intervention in Eight Patients.

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. A total of 28 consecutive patients (26 males, 2 females, mean age 43.3 ± 5.32years) 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. 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 24months. Amputation-free survival estimated by Kaplan-Meier analysis was 84% at 12 and 24months. Primary patency rates at 12, 24, and 36months were 84%, 78%, and 75%, respectively. Secondary patency rates were 87.5% both at 12 and 24months. 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.