Diagnostic criteria for Buerger's disease: International Consensus of VAS - European Independent Foundation in Angiology/Vascular Medicine.

Buerger's disease (BD) remains a debilitating condition and early diagnosis is paramount for its effective management. Despite many published diagnostic criteria for BD, selective criteria have been utilized in different vascular centers to manage patients with BD worldwide. A recent international Delphi Consensus Study on the diagnostic criteria of BD showed that none of these published diagnostic criteria have been universally accepted as a gold standard. Apart from the presence of smoking, these published diagnostic criteria have distinct differences between them, rendering the direct comparison of patient outcomes difficult. Hence, the expert committees from the Working Group of the VAS-European Independent Foundation in Angiology/Vascular Medicine critically reviewed the findings from the Delphi study and provided practical recommendations on the diagnostic criteria for BD, facilitating its universal use. We recommend that the 'definitive' diagnosis of BD must require the presence of three features (history of smoking, typical angiographic features and typical histopathological features) and the use of a combination of major and minor criteria for the 'suspected' diagnosis of BD. The major criterion is the history of active tobacco smoking. The five minor criteria are disease onset at age less than 45 years, ischemic involvement of the lower limbs, ischemic involvement of one or both of the upper limbs, thrombophlebitis migrans and red-blue shade of purple discoloration on edematous toes or fingers. We recommend that a 'suspected' diagnosis of BD is confirmed in the presence of a major criterion plus four or more minor criteria. In the absence of the major criterion or in cases of fewer than four minor criteria, imaging and laboratory data could facilitate the diagnosis. Validation studies on the use of these major and minor criteria are underway.

An International Delphi Consensus on Diagnostic Criteria for Buerger's Disease.

BACKGROUND: Buerger's disease (BD) remains a debilitating condition. Despite multiple published diagnostic criteria for BD, none is universally accepted as a gold standard. METHODS: We conducted a 2-round modified Delphi consensus study to establish a consensus on the diagnostic. The questionnaire included statements from several commonly used diagnostic criteria for BD. Qualitative and quantitative analysis methods were performed. An agreement level of 70% was applied. RESULTS: Twenty nine experts from 18 countries participated in this study. Overall, 75 statements were circulated in Round 1. Of these, 28% of statements were accepted. Following comments, 21 statements were recirculated in Round 2 and 90% were accepted. Although more than 90% of the experts did not agree that the diagnosis of BD can be based only on clinical manifestation, none of the nonclinical manifestations of BD were agreed as a part of the diagnostic criteria. There was an agreement that a history of tobacco consumption in any form, not necessarily confined to the current use, should be a part of the diagnostic criteria of BD. The history of thrombophlebitis migrans, even if not present at presentation, was accepted as a clue for BD diagnosis. It was also agreed that discoloration of the toes or fingers could be included in the diagnostic criteria of BD. Experts agreed that histology results could differentiate BD from atherosclerosis obliterans and other types of vasculitis. The presence of corkscrew collaterals on imaging and burning pain reached the agreement at the first round but not at the second. There was no consensus regarding age cut-off, the requirement of normal lipid profile, and normal blood glucose for BD diagnosis. CONCLUSIONS: The present study demonstrated discrepancies in the various published diagnostic criteria for BD and their selective utilization in routine clinical practice worldwide. We propose that all published diagnostic criteria for BD be re-evaluated for harmonization and universal use.

Milestones in thromboangiitis obliterans: a position paper of the VAS-European independent foundation in angiology/vascular medicine.

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

Brachio-basilic upper arm transposition fistulas vs. prosthetic brachio-axillary vascular access grafts-Which one is preferred for hemodialysis?

INTRODUCTION: There is still controversy on the use of brachio-basilic upper arm transposition fistula (BBAVF) and prosthetic brachio-axillary vascular access grafts (BAPTFE) in patients with no suitable cephalic veins for creating an autogenous brachio-cephalic fistula. METHODS: In a randomized controlled clinical trial, 60 hemodialysis patients who were not a suitable candidate for BCAVF were randomly assigned into two groups: BBAVF and BAPTFE. The patients were clinically followed up to 1 year and the patency rate and access-related complications were compared between the two groups. FINDINGS: Access failure rate in the BBAVF and BAPTFE groups was 30.0% and 36.6%, respectively. The primary patency time was 232.73 ± 113.36 and 261.53 ± 147.37 days, respectively (P = 0.40). Thrombosis formation and infection were the two main causes for access failure, yet indicating no significant difference between the two groups (P > 0.05). DISCUSSION: BBAVF and BAPTFE have comparable clinical outcomes in short-term follow-up. Therefore, BAPTFE can be used as an alternative vascular access for hemodialysis in patients who are not a suitable candidate for BBAVF.

Effect of low dose aspirin and dipyridamole on primary patency of arteriovenous grafts in hemodialysis patients: a randomized double-blind placebo-controlled trial.

BACKGROUND: There is some evidence for the efficacy of antiplatelet therapies in increasing the vascular access patency duration or decreasing the thrombosis of arteriovenous grafts. OBJECTIVE: To determine the effect of low dose aspirin and dipyridamole on primary patency of arteriovenous grafts in hemodialysis patients. METHODS: This randomized, double-blind, placebo-controlled trial was done at Imam Reza Hospital in Mashhad, Iran from September 10, 2015 to July 05, 2016. Sixty hemodialysis patients, after the placement of a new arteriovenous graft, were divided into three study groups which including; Group 1, who received 80 mg aspirin tablet daily, Group 2 received 80 mg aspirin plus 75 mg dipyridamole daily and Group 3 received placebo daily. Primary unassisted patency was recorded in follow-up until 12 months and the outcomes were analysed using one-way ANOVA test. RESULTS: Primary patency time in Group 1 (Aspirin) was 324.75±147.00 day and for Group 2 (Aspirin + Dipyridamole) was 399.05±92.09 day and for Group 3 (Placebo) was 383.55±108.23 day. There were no significant differences between the 3 groups (p>0.05). Successful dialysis was done in 16.7% in Group 1, 37.5% in Group 2 and 45% in Group 3 from brachial arteriovenous grafts after 1-year follow-up (p=0.746). CONCLUSIONS: In treating dialysis patients, treatment with low dose aspirin and dipyridamole is not effective on increasing the synthetic grafts primary patency duration. TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the Trct id: TCTR20160920003. FUNDING: The authors received no financial support for the research, authorship, and/or publication of this article.

Hypothenar Hammer Syndrome: Surgical Approach in Patients Presenting with Ulnar Artery Aneurysm.

Hypothenar hammer syndrome is an uncommon condition but of high clinical importance due to ischemia-related complications. In this article, we discuss about our surgical approach to deal with hypothenar hammer syndrome patients suffering from ulnar artery aneurysm, which is surgical exploration and end-to-end anastomosis of the ulnar artery.

Topical propolis improves wound healing in patients with diabetic foot ulcer: a randomized controlled trial.

In this randomized controlled trial, diabetic patients with foot ulcers (Wagner grades 1 and 2) were randomly assigned to conventional therapies for diabetic foot ulcer plus topical propolis ointment (5%; twice daily) or conventional therapies alone. The process of ulcer healing was observed during 4 weeks and compared between the two groups regarding the size, erythema, exudates, white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). The process of ulcer size reduction during the four-week period of study was significantly different between the groups. However, this difference was not significant between the third and fourth weeks. There was no significant difference between two groups regarding erythema and exudate reduction as well as WBC count and ESR. Administration of topical propolis ointment in addition to the conventional treatments of diabetic foot ulcer could reduce the size of ulcers with Wagner grades 1 and 2.

Unexpected Inflammation in the Sympathetic Ganglia in Thromboangiitis Obliterans.

The aim of this study was to inspect more closely the microscopic and molecular sympathetic ganglia histology in thromboangiitis obliterans (TAO). The paraffin block and frozen RNAlater-treated tissue of the lumbar sympathetic ganglia of 19 TAO Caucasian male patients were evaluated. The gene expression of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) markers in the frozen RNAlater-treated sympathetic ganglia tissues were evaluated by real-time polymerase chain reaction. Unexpectedly, lymphocyte infiltration was observed in all of the histological sections, ranging from scattered to moderate lymphocyte infiltration. In seven patients, five of them underwent below-knee amputation, neutrophil infiltration was observed in addition to lymphocyte infiltration. The gene expression of the CD8 marker in all of the samples with the expression of CD4 markers in only four tissue samples was demonstrated. The expression of CD8 in comparison to CD4 was approximately 4.37-fold changes using Pfaffle method. It appears that inflammation of the sympathetic ganglia plays a role in the pathophysiology of TAO and its outcome. Sympathetic ganglia inflammation may be responsible for general vasoconstriction, vascular inflammation, and the increased risk of thrombotic events, by activating the platelets. The dominant infiltration of T cytotoxic lymphocytes and neutrophils in sympathetic ganglia may probably support the idea of possible intracellular infectious pathogen trigger for TAO and consequently infiltration of pathogen-specific T cells into the sympathetic ganglia in TAO.

Thoracic aortic involvement in cystic echinococcosis: A case report.

Cystic echinococcosis is a common parasitic disease in some areas and involves different organs with different presentations. Rural areas in our country are endemic with this disease. We present a case of echinococcal aortic involvement that was diagnosed incidentally by a routine chest radiogram as a mediastinal mass. Cystic echinococcosis was established as final diagnosis after magnetic resonance imaging (MRI) and ELISA studies. The patient was treated surgically through a thoracotomy and her aortic defect was repaired during the operation. She has been asymptomatic and complication free in physical examination and imaging study in follow up periods after two years. Awareness of various presentations of the disease is necessary for physicians who are occupied in endemic areas. It is rational to treat echinococcal cysts adjacent to the great vessels with the cooperation of a vascular surgeon.

Renal artery aneurysm rupture during post-partum period: A case report.

Renal artery aneurysm has an incidence of lower than one in 1000 of the general population. The risk of aneurysm rupture increases during pregnancy due to hormonal and hemodynamic changes. Therefore, these patients often refer to physicians with abdominal pain that is followed by shock. We report the case of a 41-year-old multiparous woman who was referred with symptoms of epigastric pain and hemorrhagic shock, a week after her vaginal delivery. She was diagnosed with renal artery aneurysm in ultrasonography. The patient underwent laparotomy and nephrectomy so that she was discharged from hospital with a good general health condition. Imaging measures in a timely manner, carried out by qualified individuals considering a patient's history and clinical situation is very effective in diagnosis and treatment of post-partum abdominal pain.

Rickettsia infection could be the missing piece of the Buerger's disease puzzle.

BACKGROUND: Rickettsia was suggested as a possible etiology of Buerger's disease (BD) in the 1980s but this suggestion was never ruled out or proven. Recently, we found evidence of Rickettsia by polymerase chain reaction in 3 out of 25 biopsy samples from the amputated limb of a young man diagnosed with BD. The aim of this paper was to investigate the presence of anti-rickettsial antibodies in the sera of BD patients. METHODS: To detect the IgG class antibody against Rickettsia rickettsii, which has cross reactions with the spotted fever group (RSFG), and Rickettsia typhi, which has cross reactions with typhus fever group, the sera of patients and controls were diluted to 1:64 and analyzed by indirect micro fluorescence immunoassay (MIF). RESULTS: The MIF study showed that 26 of the 28 patients were positive for Rickettsia rickettsii antibodies and MIF had the same appearance as the positive control, which was provided with the kit. In all members of the healthy control group, Rickettsia rickettsii was negative and had the appearance of the negative control. Rickettsia typhi was negative for all patients and members of the control group. CONCLUSIONS: A species of Rickettsia associated with the RSFG, which might not be pathogenic for the entire population, may induce BD in the context of a specific genetic or environmental background. RSFG infection could explain key questions about BD, including its gender and geographical distribution, clinical manifestation, angiography pattern, and pathological findings. Evaluating antibodies against RSFG in BD patients from different countries is now highly recommended.

Effect of Folic Acid therapy on Homocysteine Level in patients with Atherosclerosis or Buerger's Disease and in Healthy individuals: A clinical trial.

BACKGROUND: Hyperhomocysteinemia is considered a risk factor for atherosclerosis and some other vascular diseases such as Buerger's disease. OBJECTIVE: The aim of this study was to measure the Homocysteine levels in 3 different groups of participants (Buerger's disease, atherosclerosis patients, and healthy cases) and determine the therapeutic effect of folic acid therapy on homocysteine levels for these three groups. METHODS: This nonrandomized clinical trial study was conducted in the vascular and endovascular surgery research center of Mashhad University of Medical Sciences in Mashhad, Iran. This interventional study consisted of 44 participants of which 22 patients had Buerger's disease and a control group of 22 healthy individuals, all of which were enrolled in this study. All of the study's participants had their serum homocysteine levels measured both before and after 12 weeks of folic acid (5mg/day) therapy. The data analysis used fo data analysis was a Chi square and t-test or their non-parametrical equivalents for data analysis by means of Statistical Package for the Social Sciences (SPSS) version 16. RESULTS: The homocysteine levels were found to be significantly higher in patients with Buerger's disease as compared to other groups before treatment with folic acid (Buerger = 21.8 ± 8.5 Mm/L, atherosclerosis = 17.3 ± 6.9, healthy = 13.8 ± 3.1; p < 0.001). After treatment with folic acid at 5 mg/daily for 12 weeks, the new plasma homocysteine levels did not show any significant difference (p = 0.38) between the Buerger's disease group (14.6 ± 4.5 Mm/L) and atherosclerosis group (13.9 ± 4.7), but it was found to besignificantly higher in both groups when compared to the healthy group (10.7 ± 3.9, p<0.05). The plasma homocysteine level was reduced significantly when compared to its initial level in all 3 groups. The comparison of differences among three groups was found not to be significant (p=0.41). CONCLUSIONS: It seems that supplementary therapy with folic acid at a dose of 5 mg daily may reduce the serum homocysteine levels significantly and may have a role in the development of vascular diseases such as Buerger's disease. We suggest that folic acid should be considered as a routine agent in the Buerger's disease therapeutic regime. CLINICAL TRIAL REGISTRATION: The trial was registered at the Thai Clinical Trials Registry (http://www.clinicaltrials.in.th) with the ID: TCTR20160601003. FUNDING: This study was not funded by any organization.

Diagnostic value of computerized tomography venography in detecting stenosis and occlusion of subclavian vein and superior vena in chronic renal failure patients.

INTRODUCTION: Currently, venography is the standard diagnostic method to examine veins before implementing access, which is invasive in nature. Computerized tomography venography (CTV) can simultaneously indicate deep and superficial venous systems in the upper extremity and their relation to the surrounding anatomical structures; however, its diagnostic value in the detection of central venous disease has yet to be defined. The aim of this study was to determine the diagnostic value of CT venography compared to venography in the diagnosis of stenosis and the occlusion of subclavian veins and the superior vena in renal failure patients. METHODS: This cross-sectional study was conducted from January to September 2015 on patients with chronic renal failure undergoing upper extremity venography at the Radiology Department of Imam Reza Hospital in Mashhad, Iran. We excluded patients with catheters in their jugular and subclavian vein routes, venous hypertension with reverse-function fistula, or sensitivity to contrast agents. Several factors, including age, gender, catheterization record in jugular and subclavian veins, and fistula record in the upper extremity, as well as clinical symptoms consisting of edema, dermatitis, and ulcers in these organs, were recorded in the corresponding form. Then, the patients consecutively underwent indirect venography and CT venography and traces of stenosis (more than 50%) or complete occlusion in the subclavian vein and superior vena were recorded. The data were analyzed using SPSS software by the chi-squared test, and sensitivity, specificity, and positive and negative predictive values were calculated by means of MedCalc Online, version 16.2. RESULTS: The study was conducted on 40 patients (26 males and 14 females) with a mean age of 46.7 ± 10.4 years. In this study, 58 subclavian veins, as well as 32 superior vena cava, were studied. The results showed that the diagnostic value of CTV in the detection of subclavian stenosis had a sensitivity and a specificity of 88.2 and 97.5%, respectively. Moreover, in the superior vena cava, the greatest CTV diagnostic sensitivity and specificity was related to vein stenosis detection (sensitivity = 88.8%; specificity = 100%). CONCLUSION: It seems that the CTV, based on its high sensitivity, specificity, and predictive value, can be used as an efficient tool in the study of stenosis in subclavian veins and superior vena in patients undergoing venography.

Investigation of the Etiology of Anemia in Thromboangiitis Obliterans.

During a review of patients admitted with thromboangiitis obliterans (TAO), there was evidence of normochromic normocytic anemia and abrupt changes in hemoglobin (Hgb) levels in patients with several hospital admissions. Therefore, the evidence of hemolytic anemia was evaluated based on 37 banked plasma samples taken from Caucasian male TAO patients during disease exacerbation between 2012 and 2014. The patients' hospital records, including clinical manifestations and complete blood count, were evaluated. The following tests were performed on all samples: indirect antiglobulin test (IAT), C-reactive protein (CRP), high-sensitivity CRP (hsCRP), lactate dehydrogenase (LDH), haptoglobin, indirect bilirubin, d-aspartate aminotransferase (AST), and d-alanine aminotransferase (ALT). The mean age of the patients was 40 ± 7 years. Two patients underwent below-knee amputation. The mean hospital-documented Hgb of the patients was 12.9 ± 2.6 g/dL. CRP and IAT were positive in 75.6 and 70.2% of the samples, respectively. The tests and corresponding results were as follows: hsCRP, 14.07 ± 2.37 µg/mL; LDH, 2,552 ± 315 u/L; haptoglobin, 2.27 ± 1.1 g/L; indirect bilirubin, 0.09 ± 0.04 mg/dL; AST, 67 ± 7 u/L; and ALT, 26 ± 3 u/L. There was a significant inverse correlation between hsCRP and hospital-documented Hgb level (p = 0.03). Anemia with the positive IAT in most of the samples, high LDH and AST, and normal ALT are suggestive of hemolytic anemia. Normal indirect bilirubin is consistent with intravascular hemolysis. The positive CRP and elevated haptoglobin levels could be due to systemic inflammation in TAO. However, it is not known if an autoantigen or an infectious antigen is responsible for TAO systemic inflammation and induction hemolytic anemia. As such, the underlying mechanism of anemia in TAO could be part of the footprint of its main etiology.

Association of the five gene related endothelial cell dysfunction polymorphisms with Buerger's disease development.

BACKGROUND: The aim of this study was to evaluate the impact of the polymorphisms of four genes related to vascular endothelium dysfunction on the development and outcome of Buerger's disease (BD). The genes studied were eNOS-786 T>C, eNOS894 G>T, ET-1 8000 T>C, PAI-1 4G/5G and ACE I/D. METHODS: Polymerase chain reaction and restriction fragment analysis were used to detect eNOS-786 T>C, eNOS894 G>T, ET-1 8000 T>C, PAI-1(4G/5G) and ACE(I/D) polymorphisms in 36 BD patients and 36 healthy individuals matched for race, age and gender. A decision tree for predicting BD was drawn using Rapidminer 5.3 software. RESULTS: The frequency of eNOS-T786C alleles was significantly different between the BD group and the healthy controls (P<0.001, OR:6.1). The frequency of PAI-1(4G/5G) alleles was significantly different between the BD group and the healthy controls (P=0.005, OR:4.9). The frequency of eNOS G894T alleles was not statistically different between BD and the healthy controls (P=0.09). No significant difference between allele frequency of ACE(I/D) was found (P=0.07). There was, also, no significant difference between the allele frequency of ET-1 8000 T>C (P=0.1). In logistic regression analysis, the C allele for eNOS-786 and 4G/4G for PAI-1 were significant for predicting BD. According to the decision tree, the proportion of the current gene-polymorphisms likely to develop BD was calculated as maximum 27.7%. CONCLUSIONS: It seems that eNOS-T786C, PAI-1(4G/5G) are important polymorphisms in developing BD. However, the decision tree might give confidence to the families of BD patients that if they maintain a healthy lifestyle, they may not develop BD.

Isolated Splenic Vein Thrombosis: 8-Year-Old Boy with Massive Upper Gastrointestinal Bleeding and Hypersplenism.

We present an 8-year-old boy who was referred to our center with the complaint of upper gastrointestinal bleeding and was diagnosed with hypersplenism and progressive esophageal varices. Performing a computerized tomography (CT) scan, we discovered a suspicious finding in the venography phase in favor of thrombosis in the splenic vein. Once complementary examinations were done and due to recurrent bleeding and band ligation failure, the patient underwent splenectomy. And during the one-year follow-up obvious improvement of the esophageal varices was observed in endoscopy.

Mechanisms of thrombosis, available treatments and management challenges presented by thromboangiitis obliterans.

Thromboangiitis obliterans (TAO) is a thrombotic-occlusive and an inflammatory peripheral arterial disease with unidentified aetiology. Thrombotic events can lead to limb loss in TAO patients, who are typically young male smokers of low socioeconomic status. It is still unknown whether the initial process is thrombosis or inflammation, so it is difficult to ascertain whether managing inflammation or thrombosis improves the outcome of the disease. In this review, the possible mechanisms of thrombosis in TAO are evaluated; the treatments, based on the discussed mechanisms of thrombosis in TAO, are then reviewed and the challenges and limitations associated with the management of TAO are discussed.

Comparing color Doppler ultrasonography and angiography to assess traumatic arterial injuries of the extremities.

BACKGROUND: Traumatic events are one of the major causes of arterial injuries. Physical examination is not a good predictor of the extent of injuries and arteriography is considered as the gold standard for this purpose. In the recent years, noninvasive modalities are increasingly replacing diagnostic arteriography. Color Doppler ultrasonography (USG) is an excellent method to investigate arterial diseases. OBJECTIVES: The present study aimed to evaluate the diagnostic value of color Doppler USG compared to conventional angiography in traumatic arterial injuries of extremities. PATIENTS AND METHODS: Seventy-five patients with extremity trauma suspicious for arterial injury were examined by color Doppler USG just before angiography. Doppler pattern and flow states were assessed, then angiography was performed. The results of duplex USG were compared with angiography. RESULTS: Color Doppler USG had a sensitivity of 95% and specificity of 98% in diagnosis of arterial injury. Positive and negative predictive values of Doppler USG were 92.5% and 94.2%, respectively. CONCLUSIONS: Color Doppler USG can be used as a reliable modality with acceptable sensitivity and specificity values to screen hemodynamically stable patients with limb trauma suspicious for arterial injury.