Effect of Buerger's disease on ocular microvascular structure.

CLINICAL RELEVANCE: Buerger's disease, being a systemic inflammatory vasculopathy, may present with ocular findings. BACKGROUND: This study aims to understand the potential role of optical coherence tomography and angiography findings in evaluating the course of Buerger's disease. METHODS: This was a prospective, cross-sectional study that included 25 patients with Buerger's disease (Group 1) and 51 healthy control participants, of whom 27 were smokers (Group 2) and 24 were non-smokers (Group 3). Following a detailed ophthalmic examination, optical coherence tomography and angiography measurements were conducted on participants. The values of macular superficial and deep capillary plexus, peripapillary capillary plexus vessel density measurements were taken into account from optical coherence tomography angiography measurements. Furthermore, measurements were taken for the parameters of the foveal avascular zone, including its area, perimeter and acircularity index. Additionally, the choriocapillaris flow area was assessed between radii of 1 mm, 2 mm, and 3 mm. RESULTS: In patients with Buerger's disease, the area and perimeter of the foveal avascular zone were higher than in both smoker and non-smoker healthy groups (p < 0.001 for all). The vessel densities in superficial capillary plexus were found to be lower in patients with Buerger's disease compared to both smokers and non-smokers in all regions except the parafovea (p < 0.05 for all). The radial peripapillary capillary plexus vessel densities in the whole retina and peripapillary region were lower than those in the non-smoker group (p < 0.001 and p = 0.008). The choriocapillaris flow areas in all three radius were lower in the smoker group than in the non-smoker group (1 mm, p = 0.01; 2 mm, p = 0.005; 3 mm, p = 0.011). CONCLUSIONS: Buerger's disease extends beyond the extremities, affecting vascular density and tissue perfusion in the optic disc and macula, making it a systemic condition. This disease can have ocular involvement without causing serious ocular findings.

A case of Buerger's disease with vasculopathy and skin fibrosis requiring differential diagnosis from systemic sclerosis.

Buerger's disease is characterized by peripheral ischemia due to occlusion of small- and medium-sized arteries in the extremities. This report describes a case of Buerger's disease in a 51-year-old male who presented with findings resembling systemic sclerosis. The patient exhibited Raynaud's phenomenon in year X-3, which developed to skin hardening, nail avulsion, and ulceration of the right fingers in year X. Diagnostic testing showed positive microvasculopathy on nailfold videocapillaroscopy (NVC) and positive fibrosis on skin biopsy. Although the patient fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for systemic sclerosis, several findings in this case were atypical for systemic sclerosis, including left-right asymmetry in finger involvement, nail loss, and negative autoantibody tests. Contrast-enhanced computed tomography showed poor perfusion of the right ulnar artery, and a heavy smoking history was established in the patient case. Therefore, based on Shionoya's criteria, he was diagnosed with a case of Buerger's disease confined to the upper extremity. Smoking cessation and vasodilator therapy resulted in the prompt resolution of ischemic symptoms, skin hardening, and ulcerations. Furthermore, NVC abnormalities improved, and ulnar artery occlusion showed reperfusion on repeat testing. The present case suggests that hypoxemia-driven microvasculopathy may contribute to vascular occlusion and skin fibrosis observed in this atypical presentation.

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.

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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Gene Therapy of Thromboangiitis Obliterans with Growth Factor Plasmid (VEGF165) and Autologous Bone Marrow Cells.

BACKGROUND: We performed gene therapy for critical limb ischemia in thromboangiitis obliterans (TAO) by the intramuscular administration of plasmids of the vascular endothelial growth factor gene (VEGF 165) with or without bone marrow-derived stem cells. METHODS: The 21 patients were randomly assigned to three groups: A-with dual therapy, cells and plasmid; B-plasmid only; and C-control group, where patients received intramuscular injections of saline. Serum VEGF levels, the ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), and the rest pain measured by the visual analog scale (VAS) were determined sequentially before treatment, and then 1 and 3 months after treatment. RESULTS: In the treatment groups, serum VEGF levels increased by 4 weeks and returned to baseline values after 3 months. ABI after 12 weeks increased by an average of 0.18 in group A, and 0.09 in group B and group C. TcPO2 increased by an average of 17.3 mmHg in group A, 14.1 mmHg in group B, and 10.7 mmHg in group C. The largest pain decrease was observed in group A and averaged 5.43 less pain intensity. CONCLUSIONS: Gene therapy using the VEGF plasmid along with or without bone marrow-derived mononuclear cells administered intramuscularly into an ischemic limb in TAO is a safe and effective therapy.

Si-Miao-Yong-An Decoction alleviates thromboangiitis obliterans by regulating miR-548j-5p/IL-17A signaling pathway.

Thromboangiitis obliterans (TAO) is a rare, chronic, progressive, and segmental inflammatory disease characterized by a high rate of amputation, significantly compromising the quality of life of patients. Si-Miao-Yong-An decoction (SMYA), a traditional prescription, exhibits anti-inflammatory, anti-thrombotic, and various other pharmacological properties. Clinically, it was fully proved to be effective for TAO therapy, but the specific therapeutic effect of SMYA on TAO has been unknown. Thus, deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely important. In this study, we observed elevated levels of IL-17A in the peripheral blood mononuclear cells (PBMCs) of TAO patients, whereas the expression of miR-548j-5p was significantly decreased. A negative correlation between the levels of miR-548j-5p and IL-17A was also demonstrated. In vitro experiments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels, whereas downregulation of miR-548j-5p showed the opposite effect. Using a dual luciferase assay, we confirmed that miR-548j-5p directly targets IL-17A. Furthermore, serum containing SMYA effectively decreased IL-17A levels by increasing the expression of miR-548j-5p. More importantly, the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular tissues. In conclusion, SMYA significantly enhances the expression of miR-548j-5p, thereby reducing the levels of the target gene IL-17A and alleviating TAO. Our research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO.

Short-term efficacy of endovascular procedures for lower extremity thromboangiitis obliterans (Buerger's disease).

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

Isolated visceral manifestation of Buerger's disease presenting as intestinal obstruction: a case report.

Introduction and importance: Buerger's disease is an uncommon segmental nonatherosclerotic vasculitis essentially affecting small to medium-sized arteries and veins of upper and lower extremities and can lead to limb amputation. Visceral vessel involvement is quite rare accounting for 2% of cases presenting with acute abdomen due to mesenteric ischemia. Moreover, isolated visceral involvement is even rare. Case presentation: A 42-year-old gentleman, a chronic smoker, presented with abdominal pain associated with nausea and vomiting and loose stool of 2 months duration. Magnetic resonance enterography revealed segmental circumferential wall thickening with stricture in the mid part of the jejunum with lymphadenopathy features of possible inflammatory bowel disease (Crohn's disease). Furthermore, intraoperative surgical findings were also suggestive of Crohn's disease. However, histologic findings were consistent with thromboangiitis obliterans. Discussion: Thromboangiitis obliterans can present with inflammatory vascular lesions without necrosis in the early stage to varying degrees of recanalisation, gangrene, and amputation in the late stage. It rarely involves the brain, heart, and abdominal viscera. The visceral involvement may be in the form of intestinal obstruction or mesenteric ischemia or can mimic Crohn's in a background of smoking. Conclusion: This case report will help to learn more about the rarer intestinal presentation of intestinal Buerger's disease. It can present with features of bowel ischemia, obstruction or Crohn's. So, histology would play a pivotal role in differentiating the diagnostic dilemma.

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

BACKGROUND: Ilex 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 STUDY: This study aims to uncover the underlying mechanisms in the therapeutic effects of IP on TAO, employing network pharmacology and metabolomic approaches. METHODS: In 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. RESULTS: The 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-1ß, 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. CONCLUSION: In 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.

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.

Critical Limb Ischemia Due to Suspected Buerger's Disease in an Adolescent Patient: A Case Report.

Buerger's disease is a segmental and inflammatory syndrome affecting relatively young individuals primarily and occurs with occlusion of small to medium-sized vessels in their extremities. The typical age for symptoms to appear is between 35 and 50 years in smoking patients. The disease is not manifested in children or the elderly. The only recognized successful treatment for it is immediate termination of smoking. In this report, we describe the case of a 16-year-old male suffering from this condition and referred from the pediatric department to our clinic, followed by a literature review of Buerger's disease reported in adolescent patients.

Painful Raynaud's mimics.

Raynaud's syndrome is a common finding in many autoimmune conditions. Accurately diagnosing Raynaud's, and differentiating it from mimicking conditions, is imperative in rheumatologic diseases. Raynaud's syndrome and Raynaud's mimickers, especially painful Raynaud's mimickers, can prove a diagnostic challenge for the practicing rheumatologist. Painful Raynaud's mimickers can lead to increased patient stress and unnecessary medical work up; Healthcare providers need to be aware of Raynaud's mimickers when evaluating patient concerns of skin color changes and pain. The present narrative review aims to highlight Raynaud's syndrome, important painful mimickers that may be seen, diagnosis, and updated management recommendations.

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

OBJECTIVES: The 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. METHODS: First, 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. RESULTS: The 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. CONCLUSIONS: These 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.

Establishment of a multi-strategy platform for quality control and quality markers screen of Mailuoshutong pill.

Thromboangiitis obliterans (TAO) is a non-atherosclerotic segmental inflammatory occlusive disease with a high recurrence rate, high disability rate, difficulty to cure, and poor prognosis. It has been clinically proven that Mailuoshutong pill (MLSTP) is an effective traditional Chinese medicine for treating TAO. As MLSTP contains hundreds of chemical components, the quality control of which is a challenge in the development of reliable quality evaluation metrics. This study aimed to evaluate the quality uniformity of MLSTP by establishing a multi-strategy platform. In the present study, the key targets and signaling pathways of MLSTP treating TAO were predicted by network pharmacology. It was further shown by in vivo validation experiments that MLSTP exerted therapeutic effects on TAO by modulating the PI3K-AKT signaling pathway, VEGF signaling pathway, and HIF-1 signaling pathway. In addition, UPLC fingerprints of MLSTP were established and screened for potential Q-markers of MLSTP in combination with network pharmacology results. Six components, including chlorogenic acid, liquiritin, paeoniflorin, calycosin-7-glucoside, berberine, and formononetin, were selected as potential quality markers (Q-markers) in MLSTP. Finally, the quantitative analysis of multi-components by single marker (QAMS) method was established to quantitatively analyze the six potential Q-markers, and the results were consistent with those obtained by the external standard method (ESM). Taken together, the multi-strategy platform established in this study would be conducive to the Q-markers screening and quality control of MLSTP, improving the quality standard of MLSTP and providing favorable assurance for the clinical management of TAO.

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.

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

Abstract Objectives The 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. Methods First, 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. Results The 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. Conclusions These 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.

Top 100 cited articles in the thromboangiitis obliterans: a bibliometric analysis and visualized study.

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

Knowledge Mapping of Global Status and Trends for Thromboangiitis Obliterans: A Bibliometrics and Visual Analysis.

Objective: Thromboangiitis obliterans (TAO) is a segmental nonatherosclerotic inflammatory vascular disease characterized by recurrent progressive inflammatory reactions and thrombosis in the small and medium-sized arteries and veins of the extremities. However, there are few bibliometric studies on TAO. Therefore, this study was employed to generalize the research status, hotspots and development trends of TAO-related research. Methods: The data from 1999 to 2022 were collected from the Web of Science core collection database, and analyzed through bibliometrics software. VOSviewer was utilized to carry out academic collaboration between different countries/regions, institutions, and authors, visualization map of co-cited authors, journals, reference, and co-occurring keywords. CiteSpace was used to analyze the dual-map of journals, keyword bursts, and timeline of keywords. Bar and pie charts in this study were statistically analyzed and graphed through Microsoft Excel 2021. Scimago Graphica was applied to map the academic collaboration between different countries/regions. Results: A total of 553 literatures were involved in this study. Japan at the leading global position not only in the number of publications, but also total citations, average citations and H-index. Institution with the major contribution to TAO research is Mashhad University of Medical Sciences, and Nagoya University. Annals of Vascular Surgery, Angiology, Journal of Vascular Surgery are the main publication channel for articles related to TAO. Fazeli, B., Iwai, T., and Kihara, Y. are major contributors in this field. The studies on TAO keywords could be grouped into four clusters: Etiology, Mechanism, Cell therapy and Clinical therapy. Conclusion: Although the number of TAO publications has fluctuated over the past 20 years, it has generally shown a steady upward trend. Etiology and treatment research on TAO and some keywords such as trail, therapy, outcome, management, stem cells, angioplasty, and activation will become a hot spot in the future.

Efficacy of Supervised Exercise Therapy for Intermittent Claudication in a Case With Buerger's Disease.

Herein, we report a case of intermittent claudication (IC) caused by Buerger's disease (thromboangiitis obliterans {TAO}), which we treated using supervised exercise therapy (SET). The patient was a 58-year-old male with a history of smoking who presented with IC and resting pain in the right lower extremity, which had led to necrosis of the right first toe eight years prior to presentation. The non-healing right first toe was amputated and the patient underwent angiogenesis therapy in the right lower extremity. Despite continued strict smoking cessation and antiplatelet medication, the patient presented with IC of the left lower extremity eight years after the previous symptoms. Therefore, the patient underwent SET once a week (40 min per session) for five months, resulting in a total of 21 sessions. Consequently, the patient's walking ability and quality of life (QoL) significantly improved. These results suggest that SET is an effective treatment for TAO-induced IC. However, further studies are required to demonstrate its efficacy.