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.

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.

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.

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.

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.

Sera of patients with thromboangiitis obliterans activated cultured human umbilical vein endothelial cells (HUVECs) and changed their adhesive properties.

INTRODUCTION: The aim of this study was to investigate the impact of thromboangiitis obliterans (TAO) sera on activation of primary cultures of human umbilical vein endothelial cells (HUVECs) as a model for vascular endothelial cells. METHODS: Study subjects included 21 TAO patients as the case group and 20 healthy smokers and 17 healthy non-smokers as control groups. Case and control groups were matched based on their age, socioeconomic status and smoking habit. HUVECs were incubated with the sera of case and control groups and gene expression of intercellular adhesion molecule (ICAM-1) and vascular adhesion molecule (VCAM-1) were evaluated by real-time polymerase chain reaction, TaqMan method. RESULTS: The expression of ICAM-1 and VCAM-1 were significantly higher in HUVECs after incubation with TAO sera compared to control groups (P < 0.05). VCAM-1 had a significant correlation with duration of smoking (P < 0.001, R = 0.672), while the expression of ICAM-1 had a significant correlation with the number of cigarettes smoked daily (P = 0.04, R = 0.421). CONCLUSION: Sera from TAO patients could activate HUVECs. This same activation might occur in vivo by the responsible cytokines, in particular those released from activated platelets, free oxygen radicals, and possibly low levels of nitric oxide (NO) of the sera of TAO patients, as a consequences of chronic cigarette smoking and of endothelial NO synthase polymorphism. Therefore, plasma exchange might be helpful in acute phase of the disease for saving the limbs and administration the combinations of exogenous NO with anti-oxidants might be helpful in long-term management of TAO patients to reduce the risk and rate of amputation.

Investigation of the expression of mediators of neovascularization from mononuclear leukocytes in thromboangiitis obliterans.

The aim of this study was to investigate the expression of the cytokines, chemokines and effective molecules of peripheral blood mononuclear cells (PBMCs) that play a role in neovascularization in thromboangiitis obliterans (TAO). Lymphocytes from TAO patients (n = 20) and control subjects (healthy smokers [n = 16] and non-smokers [n = 17]) were evaluated using realtime polymerase chain reaction in order to examine the mRNA expression of CXCL1 and interleukin 8 (IL-8; inducers of collateral development by recruitment of circulating progenitor cells [CPCs]), endothelial cell growth factor A (VEGF-A) and inducible nitric oxide synthase (iNOS; inducers of angiogenesis) and interferon gamma (IFN-γ) and vascular endothelial growth factor receptor 1 (VEGFR-1; inhibitors of angiogenesis). CXCL1 expression was significantly higher in the TAO patients than control subjects. The expressions of IL-8, VEGFR-1 and IFN-γ were significantly higher in the TAO patients and smokers than in non-smokers. However, no differences in iNOS and VEGF-A expression were noted. In conclusion, PBMCs from TAO patients expressed cytokines that potentially recruit CPCs and promote arteriogenesis. However, TAO patients typically have low CPC levels, perhaps due to high oxidative stress. Further studies are recommended in order to investigate the efficacy of antioxidant therapy on the outcome of TAO before administration of angiogenic factors.

Comparison of Conventional Angiographic Findings between Trauma Patients with or without Runoff.

OBJECTIVE: To compare the conventional angiographic findings in extremity trauma patients with or without runoff. METHODS: This was cross-sectional study including all the patients with extremity trauma who underwent conventional angiography during the 2 year period from 2011 to 2013 in Angiography departments of Mashhad University of Medical Sciences. Mechanism of trauma, type of injury and angiographic findings were recorded in a questionnaire for each patient. After completion of treatment and discharge, the treatment type was added. The characteristics as well as clinical findings were compared between those who were diagnosed to have arterial runoff ad those who did not. RESULTS: One hundred and forty eight traumatic patients including 15 female with age range of 11-82 years and 133 men ranging from 25 to 40 years were enrolled. Abnormal angiographic findings were provided in 99 (66.9%) patients including cutoff with distal runoff (n=60, 60.6% of abnormalities), cut off without distal runoff (n=21, 21.2%) and spasm (n=14, 14.1%) and other findings (n=4, 4%). Fifty one cases were treated under open surgery and amputation of traumatic limb was done for 13 patients. Amputation rate was higher in patients with cutoff and without runoff than those with cutoff and runoff (33.3% vs. 6.78%; p=0.002). CONCLUSION: Causes and types of traumatic arterial injury in our study were different with other reports. It was shown that angiographic findings were less important in prognosis and management of patients. Patients with spasm in angiographic findings had a better prognosis than other patients and mostly did not need any vascular surgery. The presence or absence of a distal run off in primary angiographic findings can have a predictive value in the final amputation rate.

Subciliary Approach for Inferior Orbital Rim Fractures; Case Series and Literature Review.

OBJECTIVES: To report the outcome of subciliary approach for inferior orbital rim fractures in a series of Iranian patients. METHODS: This was prospective cross-sectional, being performed  during  a 12-month  period during  2013 in plastic surgery department  of Emamreza Hospital of Mashhad. We included 12 patients with traumatic inferior orbital rim fractures who underwent surgical repair through subciliary approach. All the patients were followed for 12 months and were evaluated regarding paresthesia and function as well as presence of a visible scar and lower-eyelid malposition. RESULTS: There were 9 (75.0%) men and 3 (25.0%) women among the patients with mean age of 26.3±10.6 (range 16-48) years. Of the 12 patients treated with the subciliary approach, 4 (33.3%) experienced complications. One (8.3%) patient showed 1.5 mm sclera at the end of one year follow-up. No ectropion or entropion was reported in our series. In contrast to 3 (25.0%) cases of lower lid visible scar, there was no occurrence of hypertrophic scar. CONCLUSION: It would be expected that the transorbital approach as it offers good visualization of anterior fractures would result in good outcomes in cases of orbital rim and f loor fracture.

Comparision of vacuum-asisted closure and moist wound dressing in the treatment of diabetic foot ulcers.

BACKGROUND: Vacuum-assisted closure (VAC) is a new method in wound care which speeds wound healing by causing vacuum, improving tissue perfusion and suctioning the exudates. This study aims to evaluate its efficacy in the treatment of diabetic foot ulcers. MATERIALS AND METHODS: Thirteen patients with diabetic foot ulcers were enrolled in the moist dressing group, and 10 patients in the VAC group. The site, size and depth of the wound were inspected and recorded before and every three days during the study period. Patient satisfaction and formation of granulation tissue were also assessed. RESULTS: Improvement of the wound in the form of reducing the diameter and depth and increasing proliferation of granulation tissue was significant in most of the patients of the VAC group after two weeks. Satisfaction of patients in the VAC group was evaluated as excellent as no amputation was done in this group. Wagner score was reduced in both the study groups, although this decrement was not significant in the moist dressing group. CONCLUSION: VAC appears to be as safe as and more efficacious than moist dressing for the treatment of diabetic foot ulcers.

Natural history definition and a suggested clinical approach to Buerger's disease: a case-control study with survival analysis.

The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.

Does a species of Rickettsia play a role in the pathophysiology of Buerger's disease?

Rickettsia is an intracellular pathogen that attaches to vascular endothelial cell membranes and its genome integrates into the DNA of the host and thereby inhibits apoptosis of the endothelial cells. Rickettsia can infect the body following a flea/louse bite. Rickettsia was suggested as one etiology of Buerger's disease long ago. We report a patient with Buerger's disease for whom a left below-knee amputation was done. Twenty-five biopsies for DNA extraction were obtained from the arteries, veins and microvasculature of the amputated limb. Three samples were positive for Rickettsia. The finding may explain the proliferation of endothelial cells in the pathology of Buerger's disease, segmental nature of the disease, involving small- and medium-sized vessels, and the prevalence of Buerger's disease among the low socioeconomic class of the society. Understanding the infectious etiology of Buerger's disease would be invaluable, since early antibiotic therapy or even vaccination might have prevented the limb loss in the current and other cases of Buerger's disease. The authors suggest that paraffin blocks of Buerger's disease biopsies be investigated for Rickettsia infection, focusing specifically on the area of endothelial cell proliferation for DNA extraction. These results should be compared with other biopsies from a variety of other peripheral vascular diseases.

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.

Oral metronidazole as antibiotic prophylaxis for patients with nonperforated appendicitis.

BACKGROUND: The rate of wound infection after appendectomy without antibiotic prophylaxis is 10%-30%. The role of prophylactic antibiotic therapy in nonperforated appendicitis is still controversial. Metronidazole is against anaerobic organisms and its bioavailability after oral and parenteral administration has been shown to be similar. The objective of the present study is to compare the infective complications rate after open appendectomy for nonperforated appendicitis receiving either oral or intravenous metronidazole as prophylaxis. METHODS AND MATERIALS: From June 2007 to July 2009 in a randomized controlled trial, 204 patients with nonperforated appendicitis underwent an open appendectomy; 122 male and 82 female with mean age of 25 years. Among these, 102 (case group) received oral metronidazole and in 102 (control group) metronidazole was administered intravenously before surgery. The rate of wound infection and duration of the postoperative hospital stay was studied in the two groups. RESULTS: The rate of wound infection was not significantly different in the two groups. (6% and 4% in study and control group, respectively, P = 0.861). Also the hospital stay was equal in two groups (2.3 days and 2.7 days in study and control group, respectively, P = 0.293). CONCLUSION: Single dose of oral metronidazole prior to operation can provide a sufficient prophylaxis for nonperforated appendicitis; so, it can be substitute the parental route of antibiotic administration.