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.

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.

Unilateral Sympathectomy for Primary Palmar Hyperhidrosis.

BACKGROUND AND OBJECTIVE: Primary palmar hyperhidrosis that arises mostly during puberty and early adolescence has a tremendous impact on the quality of life in patients. This study aimed to investigate the effectiveness of unilateral video-assisted thoracic sympathectomy for dominant hand in these patients. PATIENTS AND METHODS: From July 2010 to June 2013, 52 patients with primary palmar hyperhidrosis underwent unilateral video-assisted thoracoscopic sympathectomy for dominant hand. We analyzed the outcomes regarding the resolution of symptoms, occurrence of complications, recurrence rate, and compensatory hyperhidrosis, and need of operation for opposite side. FINDINGS: All patients were followed up from 6 to 42 months. Palmar hyperhidrosis was completely alleviated and absolute dryness was achieved in all patients at the same hand after the operation. Palmar hyperhidrosis in the opposite hand was cured to a complete dryness in 24 (46.15%) patients. No change happened in the opposite hand in 22 (42.3%) patients, but an increase was seen in 6 (11.53%) patients. Only seven (13.46%) patients needed to undergo contralateral sympathectomy. Compensatory hyperhidrosis occurred in 13 patients (25%) after unilateral sympathectomy. Another five patients (totally 18, 34.6%) were involved with compensatory hyperhidrosis after contralateral sympathectomy. It was mainly on the trunk in all 18 patients. CONCLUSION: Unilateral dominant side thoracoscopic sympathectomy for patients with primary palmar hyperhidrosis is an effective, safe, and minimally invasive procedure. Only a small number of patients will eventually require a contralateral sympathectomy in nondominant hand.

Buerger's disease in the northeast of Iran: Epidemiology and clinical features.

BACKGROUND: The aim of this study is to present our long-term clinical experience in describing a clinical picture of Buerger's disease in our region. MATERIALS AND METHODS: In a retrospective study, files of 225 patients who were admitted to the hospital with diagnosis of thromboangiitis obliterans in a 10 year period from 2000 to 2010 were reviewed. All data including demographic, signs and symptoms, history of previous illness, history of smoking, medications, laboratory tests, angiography, and details of surgical operation were obtained. RESULTS: A total of 222 (98.7%) and 3 (1.3%) of patients were male and female, respectively. Average age of hospitalized patients was 40.7 ± 8.5 (20-62) years. A total of 200 patients (88.9%) were active cigarette smokers while 168 (74.7%) of them were opium addicts. The most prevalent symptoms were chronic ulcers (80%) and claudication (63.6%). Minor and major amputation was required in 113 (50.2%) and 41 (18.4%) patients, respectively. Amputation was carried out on the lower limb (80%), upper limb (4.1%), or on both (15.1%). Also, four patients underwent revascularization through surgical bypass procedures. CONCLUSIONS: The diagnosis and treatment of Buerger's Disease is still a challenge in those communities where the disease is endemic. Therefore, identifying the natural course of the disease can play a pivotal role in the diagnosis and treatment of these patients.

A disease-specific activity score for Thromboangiitis obliterans.

INTRODUCTION: The aim of this study was to find a disease-specific activity score for Thromboangiitis obliterans (TAO). METHODS: About 173 admission records from 125 patients with TAO over the period 2005-2011 were evaluated. The outcome of the patients was categorized as saved-limb or limb-loss. The risk of limb loss associated with each clinical sign or symptom and complete blood count (CBC) data were then assessed. This risk assessment value was multiplied by 100 to obtain the percentage risk, which was then considered to be the risk score. The receiver operating characteristic (ROC) curve was used for demonstrating cut-offs for each score. The reliability of the risk score was evaluated using a split-half reliability test. The divergent validity of the risk score was tested using the Pearson correlation coefficient between the total scores of the patients with and without limb loss. RESULTS: The maximum possible clinical and CBC scores were 221 and 180, respectively, giving a maximum total score of 401. The cut-offs for clinical, laboratory and total score were 115, 75 and 213, respectively. CONCLUSION: Further cohort studies for evaluating the efficacy of different treatments for limb salvage of TAO patients based on these score are suggested.

Pro-inflammatory responses after peptide-based cancer immunotherapy.

Therapeutic vaccinations are designed to prevent cancer by inducing immune responses against tumor antigens. in cancer cells, tumor-associated antigens (TAA) or tumor-specific (mutated) derived peptides are presented within the clefts of main histocompatibility complex (MHC) class I or class II molecules, they either activate cytotoxic T-lymphocytes (CTLs), CD4+ T or CD8+ T lymphocytes, which release cytokines that can suppress tumor cells growth. In cancer immunotherapies, CD8+ T lymphocytes are a major mediator of tumor repression. The effect of peptide-based vaccinations on cytokines in the activating CD8+ T cell against targeted tumor antigens is the subject of this review. It is believed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12, secreting CTL line by interacting with dendritic cell (DC), supposed to stimulate immune system. Additionally, mechanisms of CTL activation and dysfunction were also studied. According to most of the data resulted from in vivo and in vitro research works, it is assumed that peptide-based vaccines increased IFN-γ, TNF-α, IL-2, and IL-12.

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.

Treatment of non-healing wounds with autologous bone marrow cells, platelets, fibrin glue and collagen matrix.

BACKGROUND AIMS: Recalcitrant diabetic wounds are not responsive to the most common treatments. Bone marrow-derived stem cell transplantation is used for the healing of chronic lower extremity wounds. METHODS: We report on the treatment of eight patients with aggressive, refractory diabetic wounds. The marrow-derived cells were injected/applied topically into the wound along with platelets, fibrin glue and bone marrow-impregnated collagen matrix. RESULTS: Four weeks after treatment, the wound was completely closed in three patients and significantly reduced in the remaining five patients. CONCLUSIONS: Our study suggests that the combination of the components mentioned can be used safely in order to synergize the effect of chronic wound healing.

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.

Safety and efficacy of granulocyte-colony-stimulating factor administration following autologous intramuscular implantation of bone marrow mononuclear cells: a randomized controlled trial in patients with advanced lower limb ischemia.

BACKGROUND AIMS: The aim was to investigate the therapeutic effect of granulocyte-colony-stimulating factor (G-CSF) administration following implantation of autologous bone marrow mononuclear cells (BM MNC) for patients with lower limb ischemia. METHODS: The design was a randomized controlled trial. Fifteen patients with severe chronic limb ischemia were treated with autologous BM MNC [without G-CSF (MNC-G-CSF) or combined with G-CSF administration for 5 days following transplantation (MNC+G-CSF)]. RESULTS: All clinical parameters, including ankle brachial index, visual analog scale and pain-free walking distance, showed a mean improvement from baseline, which was measured at 4 and 24 weeks after transplantation in both groups. However, in three (20%) patients, the clinical course did not improve and limb salvage was not achieved. No significant difference was observed among the patients treated in the MNC-G-CSF and MNC+G-CSF groups. No severe adverse reactions were reported during the study period. No relationship was observed between both the numbers of viable MNC or CD34+ cells and the clinical outcome. CONCLUSIONS: Autologous transplantation of BM MNC into ischemic lower limbs is safe, feasible and efficient for patients with severe peripheral artery disease. However, the administration of G-CSF following cell transplantation does not improve the effect of BM MNC implantation and therefore would not have any beneficial value in clinical applications of such cases.

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.

Resection of a large carotid artery aneurysm under cervical epidural anaesthesia.

Carotid artery aneurysm is a rare arterial aneurysm that should be considered in the differential diagnosis of cervical and posterior pharyngeal masses. The purpose of the present article was to report a carotid artery aneurysm in a patient in whom cervical blockade, the common anaesthetic method, was not possible due to the location of the aneurysm. In this case, the surgeon decided to resect the aneurysm under cervical epidural anaesthesia. As the patient was awake during the operation, the continuous evaluation of her neurological status was possible and thus, it was possible to diagnose insufficient perfusion or brain dysfunction promptly while the carotid artery was clamped. Cervical epidural anaesthesia provides careful monitoring of the neurological function and early diagnosis of possible brain ischaemia. Therefore, the application of this method in resecting carotid artery aneurysm by an experienced anaesthetist is safe and acceptable.

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.

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.

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.

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.

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.

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.

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.