Thromboangiitis Obliterans Research Articles

Vasoactive and Antifibrotic Properties of Cannabinoids and Applications to Vasospastic/Vaso-Occlusive Disorders

Background Management of vasospastic and vaso-occlusive disorders is a complex challenge, with current treatments showing varied success. Cannabinoids have demonstrated both vasodilatory and antifibrotic properties, which present potential mechanisms for therapeutic relief. No existing review examines these effects in peripheral circulation in relation to vasospastic and vaso-occlusive disorders. This study aims to investigate vasodilatory and antifibrotic properties of cannabinoids in peripheral vasculature for application in vasospastic and vaso-occlusive disorders affecting the hand. Methods A systematic search was conducted by 2 independent reviewers across PubMed, Cochrane, Ovid MEDLINE, and CINAHL to identify studies in accordance with the determined inclusion/exclusion criteria. Information regarding study design, medication, dosage, and hemodynamic or antifibrotic effects were extracted. Descriptive statistics were used to summarize study findings as appropriate. Results A total of 584 articles were identified, and 32 were selected for inclusion. Studies were grouped by effect type: hemodynamic (n = 17, 53%) and antifibrotic (n = 15, 47%). Vasodilatory effects including reduced perfusion pressure, increased functional capillary density, inhibition of vessel contraction, and increased blood flow were reported in 82% of studies. Antifibrotic effects including reduced dermal thickening, reduced collagen synthesis, and reduced fibroblast migration were reported in 100% of studies. Conclusion Overall, cannabinoids were found to have vasodilatory and antifibrotic effects on peripheral circulation via both endothelium-dependent and independent mechanisms. Our review suggests the applicability of cannabis-based medicines for vasospastic and vaso-occlusive disorders affecting the hand (eg, Raynaud disease, Buerger disease). Future research should aim to assess the effectiveness of cannabis-based medicines for these conditions.

Exploring Causal Relationships between Circulating Inflammatory Proteins and Thromboangiitis Obliterans: A Mendelian Randomization Study.

Thromboangiitis obliterans (TAO) is a vascular condition characterized by poor prognosis and an unclear etiology. This study employs Mendelian randomization (MR) to investigate the causal impact of circulating inflammatory proteins on TAO. In this MR analysis, summary statistics from a genome-wide association study meta-analysis of 91 inflammation-related proteins were integrated with independently sourced TAO data from the FinnGen consortium's R10 release. Methods such as inverse variance weighting, MR-Egger regression, weighted median approaches, MR-PRESSO, and multivariable MR (MVMR) analysis were utilized. The analysis indicated an association between higher levels of C-C motif chemokine 4 and a reduced risk of TAO, with an odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29-0.67; p = 1.4 × 10-4; adjusted p = 0.013). Similarly, glial cell line-derived neurotrophic factor exhibited a suggestively protective effect against TAO (OR: 0.43, 95% CI: 0.22-0.81; p = 0.010; adjusted p = 0.218). Conversely, higher levels of C-C motif chemokine 23 were suggestively linked to an increased risk of TAO (OR: 1.88, 95% CI: 1.21-2.93; p = 0.005; adjusted p = 0.218). The sensitivity analysis and MVMR revealed no evidence of heterogeneity or pleiotropy. This study identifies C-C motif chemokine 4 and glial cell line-derived neurotrophic factor as potential protective biomarkers for TAO, whereas C-C motif chemokine 23 emerges as a suggestive risk marker. These findings elucidate potential causal relationships and highlight the significance of these proteins in the pathogenesis and prospective therapeutic strategies for TAO.

Integrated network pharmacology and metabolomics reveal vascular protective effects of Ilex pubescens on thromboangiitis obliterans

BackgroundIlex pubescens Hook. et Arn (IP), traditionally known for its properties of promoting blood circulation, swelling and pain relief, heat clearing, and detoxification, has been used in the treatment of thromboangiitis obliterans (TAO). Despite its traditional applications, the specific mechanisms by which IP exerts its therapeutic effects on TAO remain unclear. Aim of the studyThis study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches. MethodsIn this study, a rat TAO model was established by injecting sodium laurate through the femoral artery, followed by the oral administration of IP for 7 days. Plasma coagulation parameters were measured to assess the therapeutic effects of IP. The potential influence on the femoral artery and gastrocnemius muscle was histopathologically evaluated. Network pharmacology was employed to predict relevant targets and model pathways for TAO. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was used for the metabolic profile analysis of rat plasma. Immunohistochemistry (IHC) was used to verify the mechanisms by which IP promotes blood circulation in TAO. ResultsThe study revealed that IP improved blood biochemical function in TAO and played a significant role in vascular protection and maintaining normal blood vessels and gastrocnemius morphologies. Network pharmacology showed that IP compounds play a therapeutic role in modulating lipids and atherosclerosis. Metabolomic analysis revealed that the pathways involved in sphingolipid metabolism and steroid biosynthesis were significantly disrupted. The joint analysis showed a strong correlation between lysophosphatidylcholine and IP components, including triterpenoid and iridoid components, which support the curative action of IP through the modulation of sphingolipid metabolism. Furthermore, decreased expression levels of SPHK1/S1PR1, TNF-α, IL-1β, and IL-6 were observed in the IP-treated group, suggesting that IP exerts a protective effect on the vasculature primarily by regulating of the SPHK1/S1PR1 signaling pathway. ConclusionIn this study, we found that IP protects the vasculature against injury and treats TAO by regulating the steady-state disturbance of the sphingolipid pathway. These findings suggest that IP promotes vasculature by modulating sphingolipid metabolism and SPHK1/S1PR1 signaling pathway and reduce levels of inflammatory factors, offering new insights into its therapeutic potential.

Thromboangiitis obliterans: a review

Buerger's disease was initially described by von Winiwarter in 1879 where he described it as thromboangiitis obliterans (TAO), detailing the case of spontaneous gangrene secondary to intimal proliferation. In 1908, Leo Buerger published a complete pathological description based on the amputation of a group of people who later suffered short-term gangrene. Buerger's disease or TAO is defined as a non-atherosclerotic inflammatory vasculitis that affects the small and medium vessels (including arteries and veins) of the lower and upper extremities. Although there are hypotheses about its etiopathogenesis such as the association with exposure to tobacco, few biomedical investigations have been carried out, so its direct causality remains unknown. Diagnosis continues to be a challenge, since the findings tend to be non-specific or inconsistent with suspicion, which is why it is currently based on ruling out other causes such as atherosclerosis and vasculopathies. With current evidence, there are many types of treatments, both pharmacological and non-pharmacological, with the cessation of tobacco consumption having greater evidence of results. It is essential to strengthen basic research as well as clinical trials to standardize management in this type of patient, since it is a disease with a high impact on quality of life.

Abstract 2130: Sex-based Differences In Patients With Thromboangiitis Obliterans (Buerger’s Disease): Insights From Nationwide Inpatient Sample

Introduction: Thromboangiitis obliterans (TAO) has been characterized as an inflammatory disease predominantly affecting young male smokers. The epidemiologic spectrum of TAO has evolved, with increased proportion of women and non-smokers. However, sex-based differences among patients with TAO in real-world datasets remain unclear. Research Question: How do the TAO prevalence and limb amputation rate differ between women and men in a real world dataset? Methods: We assess sex-based differences in a large, administrative Nationwide Inpatients Sample (NIS) 2016-2019. The diagnosis of TAO and variables were identified by ICD-10-CM codes. Univariable comparisons between female and male patients were assessed by Mann-Whitney. Multivariate logistic models were used to analysis associations between sex and TAO prevalence, and cumulative limb amputation, adjusted with demographics characteristics and comorbidities. Results: In this cohort study of patients with TAO (N=836), 301 (36.0%) of them were women and 535 (64.0%) of them were men. TAO prevalence rate showed 96.4% higher in men compared to women ( Fig. 1A , female:7.28%ooo, male: 14.30%ooo, p<0.001), with adjusted odd ratio (OR) at 1.51 ( Fig. 1C , 95% CI, 1.30-1.76; p<0.001) for male. The cumulative limb amputation rate was up to 32.9% in male patients and 20.9% in female patients ( Fig.1B , p<0.001), with adjusted OR at 2.22 ( Fig. 1C , 95% CI; 1.51-3.26; p<0.001) for male patients. Conclusions: Male patients showed significant higher TAO prevalence and cumulative limb amputation rate. Notably, although TAO is a rare vascular disease, the cumulative limb amputation rate was up to 32.9% in male and 20.9% in female patients. The sex-based disparities spur further studies on subgroup analysis, mechanism, health equity and multidisciplinary management for patients with TAO.

Antineutrophilic Cytoplasmic Antibody–Positive Vasculitis Associated With Thromboangiitis Obliterans in a Middle-Aged Man

Antineutrophilic Cytoplasmic Antibody–Positive Vasculitis Associated With Thromboangiitis Obliterans in a Middle-Aged Man

Identification of S100A8/A9 involved in thromboangiitis obliterans development using tandem mass tags-labeled quantitative proteomics analysis

Thromboangiitis obliterans (TAO) is characterized by inflammation and obstruction of small-and medium-sized distal arteries, with limited pharmacotherapies and surgical interventions. The precise pathogenesis of TAO remains elusive. By utilizing the technology of tandem mass tags (TMT) for quantitative proteomics and leveraging bioinformatics tools, a comparative analysis of protein profiles was conducted between normal and TAO rats to identify key proteins driving TAO development. The results unveiled 1385 differentially expressed proteins (DEPs) in the TAO compared with the normal group-comprising 365 proteins with upregulated expression and 1020 proteins with downregulated expression. Function annotation through gene ontology indicated these DEPs mainly involved in cell adhesion, positive regulation of cell migration, and cytosol. The principal signaling pathways involved regulation of the actin cytoskeleton, vascular smooth contraction, and focal adhesion. The roles of these DEPs and associated signaling pathways serve as a fundamental framework for comprehending the mechanisms underpinning the onset and progression of TAO. Furthermore, we conducted a comprehensive evaluation of the effects of S100A8/A9 and its inhibitor, paquinimod, on smooth muscle cells (SMCs) and in TAO rats. We observed that paquinimod reduces SMCs proliferation and migration, promotes phenotype switching and alleviates vascular stenosis in TAO rats. In conclusion, our study revealed that the early activation of S100A8/A9 in the femoral artery is implicated in TAO development, targeting S100A8/A9 signaling may provide a novel approach for TAO prevention and treatment.

Central Thromboangiitis Obliterans: A Case Report

A 47-year-old woman had inability to speak and swallow that had started 4-5 hours ago. She had necrotic lesions in the toes of both feet and had a history of smoking. Acute and chronic ischemic lesions were diagnosed on imaging. She was diagnosed with thromboangiitis obliter-ans by digital subtraction angiography. This report discusses a rare cause of ischemic stroke and the lack of data on diagnosis and treatment. Key Words: Buerger’s disease, Vasculitis, Stroke, Smoke, Neuroimmunology

Open Lumbar Sympathectomy on Buerger’s Disease: A Case Report

Thromboangiitis obliterans known as Buerger's disease is a nonatherosclerotic, progressive inflammatory disease that affects small and medium arteries in the upper and lower extremities. Strong relationship was found between the development of this disease and the patient's history of smoking. We reported a case of 50-year-old male with progressive pain in fingers of right leg with darkened ulcer. Open lumbar sympathectomy is a procedure that is rarely performed nowadays, but progressive pain in buerger’s disease patients can be managed with this procedure. The aim of sympathectomy is to reduce sympathetic response causing vasodilation effect which will reduce rest pain.

Efficacy and Safety of Autologous Platelet-Rich Plasma Gel in the Treatment of Chronic Skin Ulcerations

Background: Chronic wounds, which are persistent disruptions in skin integrity, represent a significant global health challenge. Various types of ulcers, including venous, arterial, diabetic, pressure, and traumatic ulcers, contribute to personal, professional, and societal burdens. Autologous platelet-rich plasma (PRP) has emerged as a promising therapeutic option by leveraging the growth factors in platelets for tissue regeneration. Methods: This prospective study, conducted from December 2021 to December 2023, enrolled 10 patients with chronic ulcers. The PRP gel was prepared through a systematic process that included blood collection, centrifugation, and activation. Results: The study included 8 males and 2 females, with an average age of 48.8 years. Ulcer etiologies encompassed diabetic foot ulcers, arterial ulcers, and venous ulcers, among others. The initial average surface area of the ulcers was 18.7 cm2. Complete healing was observed in a case of Buerger's disease, while very good healing was achieved in one diabetic foot ulcer, one venous ulcer, and another case of Buerger's disease. Moderate healing was noted in five cases of arterial ulcers, and poor healing was observed in one case of prolidase deficiency. The average surface area post-treatment for all patients was reduced to 8.05 cm2, with no reported pain or adverse effects. Conclusions: Platelet-rich plasma gel emerges as a promising alternative to traditional treatments, potentially lessening the overall impact on healthcare resources and enhancing the quality of life for individuals with chronic ulcers.

The effect of different taping techniques on transtibial amputation walking parameters: A case report.

Buerger disease is a nonatherosclerotic, segmental inflammatory disease of the occlusive tract, often involving medium-sized muscular and small-diameter arteries and veins of the extremities. If medical treatment is not successful, amputation is inevitable. The aim of this study was to investigate the effect of different kinesiological taping techniques on walking parameters of transtibial amputee with knee extension limitation. Two different kinesiological taping methods (Kinesio Tape and Dynamic Tape) were applied to the transtibial patient with knee extension limitation. Walking performance of patients was assessed with The Biodex Gait Trainer 2. Gait parameters without tape were as follows: average walking speed 0.38 m/s, average step cycle 0.48 cyl/s, average left step length 50 cm, average right step length 43 cm, coefficient of variation 9% at the left, and coefficient of variation 9% at the right. After applying Kinesio Tape and Dynamic Tape, these values were measured as follows: average walking speed 0.50.56 m/s, average step cycle 0.51.56 cyl/s, average left step length 61-60 cm, average right step length 53-54 cm, coefficient of variation 6%-5% at the left, and coefficient of variation 6%-4% at the right side. Dynamic Tape and Kinesio Tape both had positive effects on active joint motion and walking parameters. Regarding walking speed and step length, Dynamic Tape was found to be more effective than Kinesio Tape. Taping methods applied to amputees have positive effects on range of motion, which in return causes improvements on walking parameters.

Buerger's Disease of Hand; my Experience with Phenol Chemical Neurolysis of Stellate Ganglion: Case Series of Six Patients.

Buerger's disease is common in 74.70% of cases in the lower limb but in 20.20% of cases, it is found in the upper limb or hand. The disease usually starts from pain in the finger/thumb or hand and then to more centrally.Patients presented with pain in the hand with gangrene of fingers. Pain aggravated on lifting hand above the shoulder level or above heart level in upright or lying in the bed, respectively. In almost all patients, there was a history of smoking except one and all patients had involvement of digits of the right or left hand. Diagnosis of Buerger's disease was made based on the history of smoking, weak or absent pulse, lack of bleeding, swelling, edema, blackening, stony hard fingers or thumb on clinical examination, and color Doppler study of the limb.In all patients, Stellate ganglion chemical neurolysis with 8% phenol was done at C7-T1 under fluoroscopic and radiocontrast dye (Iohexol 300) guidance.After successful neurolysis patients got excellent pain relief, their wounds started healing, the vascularity of the diseased part increased and the disease stopped progressing. Stellate ganglion chemical neurolysis with phenol in Peripheral vascular disease or Buerger's disease of hand is an effective method to stop the disease procession, promoting wound healing, controlling ischemic pain, and avoiding surgical amputation.

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.

Is this iatrogenic pathology or rare disease?

The article is devoted to the problem of diagnosis and treatment strategy of Buerger's disease rarely found in the expert and clinical practice, that is inflammatory disease of unknown etiology, affecting mainly small and medium arteries and veins of limbs. Vascular surgeons around the world have been solving this problem for many years, both in terms of timely diagnosis of this disease and its proper pathogenic treatment. The authors of the article described an expert case of Buerger's disease larvated course in 15-years-old girl, which primarily was mistakenly assessed by specialists as iatrogenic pathology of right forearm vessels in injecting aminazin solution that, according to the clinicians' opinion, led to dry gangrene formation of right wrist and its subsequent amputation. The results of the forensic histological study and retrospective analysis of all child's medical documents allowed to correctly diagnose this rare pathology but only on the stage of commission forensic medical examination in the framework of the initiated criminal proceeding against several leading medical organizations in Saint-Petersburg with a pediatric profile. The authors noted the role of routine medical manipulation in manifestation of larvated pathologic process in a teenage girl in addition to full health and well-being. The objective of present article is devoted to understanding this problem.

Ultrasonographic Study of the Corkscrew Arterial Image in Buerger Disease Patients.

Objective: Thromboangiitis obliterans (Buerger disease) is known as an intractable vascular disease that has been reported as thrombosis in distal arteries and occasional venous occlusion, as well as inflammatory changes in the thrombus and vascular wall. Patients often require limb amputation due to limb necrosis. Corkscrew (CS), a small arterial coiling, is an important diagnostic finding that was mainly found with angiography. Recently, however, it can also be identified using a modern ultrasonographic technique. Methods: In these 22 cases, in 48 areas of study, we used the ultrasonographic technique to identify the CS, which allowed us to observe its relationship with the surrounding nerves and arteries. Results: In all cases, it was possible to identify the CS easily and it was confirmed that the CS and the nerve were carried down in their sheath. The sites of the CS existed in areas other than the area around the occluded main arteries and some CS that ran inside the nerve (16 areas) and some CS that accompanied the outside of the nerve (10 areas) were confirmed, suggesting the CS work as collateral blood supply vessels, with well-developed normal vessel-like anatomy. Conclusion: When we observe the CS, it is important to observe not only around the main trunk artery but also areas where nerves mainly run, even if they do not accompany the main trunk artery. (This is a translation of Jpn J Vasc Surg 2023; 32: 345-350.).

Research Progress in the Treatment of Thromboangiitis Obliterans with Traditional Chinese and Western Medicine

Research Progress in the Treatment of Thromboangiitis Obliterans with Traditional Chinese and Western Medicine

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.

Клинический случай облитерирующего тромбангиита у мужчины средних лет

The article presents a clinical case of a patient with thromboangiitis obliterans with such obvious clinical manifes tations as cyanosis, numbness of the toes, intermittent claudication, trophic changes in the skin of the hands, feet and legs. Despite the verified diagnosis and the patient’s adherence to treatment, a progressive course of the disease is noted.

The Role of Lumbar Sympathectomy in the Management of Buerger's Disease: A Systematic Review

Introduction Lumbar sympathectomy has been explored to manage Buerger's disease (BD) with varying success rates, but the results are often controversial. Despite the substantial morbidity associated with BD, there is a scarcity of comprehensive reviews on the topic. The current study is a systematic review of the efficacy of lumbar sympathectomy in the management of BD. Methods A meticulous systematic exploration was conducted across reputable databases and search platforms. The search strategy employed the following keywords:(lumbar sympathetic OR sympathectomy OR lumbar sympathetic block) AND (Buerger's disease OR Buerger OR thromboangiitis obliterans OR lower limb disease). Out of 42 identified studies, 16 were excluded during the initial screening phase. Following initial and full-text screenings, 10 studies remained eligible. The assessment of studies regarding the inclusion criteria was conducted independently by two authors, with a third author intervening to arbitrate any discrepancies. Results The demographic characteristics revealed that all participants were male, with a mean age of 38.9 years. Smoking prevalence among the cases was notably high (99%). Chemical sympathectomy was the predominant intervention, employed in 87.8% of cases, while surgical sympathectomy was utilized in only 12.2% of cases. Among the cases, 8.7% achieved complete resolution from the disease, while 91.3% reported partial relief. Conclusion Lumbar sympathectomy can be a viable treatment option for BD with fair outcomes. Nevertheless, smoking cessation remains the primary factor impeding disease progression and aggressiveness.

Abstract 18185: A Multicenter Prospective Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans

Background: Thromboangiitis obliterans (TAO) can develop critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has demonstrated long-term efficacy and safety in patients with CLTI, particularly those with TAO. To expand BM-MNC implantation in clinical practice, further evidence is required in CLTI patients with TAO. We aimed to determine the efficacy of BM-MNC implantation in a prospective trial. Methods: This multicenter, prospective, interventional trial was performed under an advanced medical care program. We enrolled 22 patients with CLTI and skin perfusion pressure (SPP) &lt;30 mmHg; they underwent BM-MNC implantation within 28 days (Figure.1). The follow-up period was 180 days, and the primary endpoint was an improvement in the SPP value in the affected target limb 180 days after the implantation. One patient dropped out from the follow-up. Results: The mean age was 47.6 years (male: 90.5%, Fontaine classification IV: 57.1%). The SPP value significantly improved on day 180 (p&lt;0.001) (Figure. 2). The secondary endpoints, i.e., numerical rating scale scores and transcutaneous oxygen pressure values significantly improved within day 180. The 3-year major amputation-free and overall survival probability in the safety analysis set were 95.5% and 89.5%, respectively (Figure. 3). No severe adverse events occurred. Conclusions: We believe that the BM-MNC implantation will likely become a feasible and safe therapy for CLTI patients caused by TAO.