The role of key biomarkers in lymphatic malformation: An updated review.

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways.

Effect of static magnetic field therapy on diabetic neuropathy and quality of life: a double-blind, randomized trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM) that can cause annoying symptoms. To address this condition, several treatment approaches have been proposed, including static magnetic field (SMF) therapy, which has shown promise in treating neurological conditions. Therefore, this study aimed to investigate the effects of SMF therapy on symptomatic DPN and the quality of life (QoL) in patients with type 2 diabetes. METHODS: A double-blind, randomized, placebo-controlled trial was conducted from April to October 2021. Sixty-four DPN patients (20 males, 44 females) were recruited for the study via invitation. The participants were divided into two groups: the magnet group, which used magnetic ankle bracelets (155 mT) for 12 weeks, and the sham group, which used non-magnetic ankle bracelets for the same duration. Neuropathy Symptom Score (NSS), Neuropathic Disability Score (NDS), and Visual Analogue Scale (VAS) were used to assess neuropathy symptoms and pain. In addition, the Neuropathy Specific Quality of Life Questionnaire (Neuro-QoL) tool was used to measure the patients' quality of life. RESULTS: Before treatment, there were no significant differences between the magnet and sham groups in terms of the NSS scores (P = 0.50), NDS scores (P = 0.74), VAS scores (P = 0.17), and Neuro-QoL scores (P = 0.82). However, after 12 weeks of treatment, the SMF exposure group showed a significant reduction in NSS scores (P < 0.001), NDS scores (P < 0.001), VAS scores (P < 0.001), and Neuro-QoL scores (P < 0.001) compared to the baseline. The changes in the sham group, on the other hand, were not significant. CONCLUSION: According to obtained data, SMF therapy is recommended as an easy-to-use and drug-free method for reducing DPN symptoms and improving QoL in diabetic type-2 patients. Trial registration Registered at Iranian Registry of Clinical Trials: IRCT20210315050706N1, 2021/03/16.

Key biomarkers in cerebral arteriovenous malformations: Updated review.

The formation of vascular networks consisting of arteries, capillaries, and veins is vital in embryogenesis. It is also crucial in adulthood for the formation of a functional vasculature. Cerebral arteriovenous malformations (CAVMs) are linked with a remarkable risk of intracerebral hemorrhage because arterial blood is directly shunted into the veins before the arterial blood pressure is dissipated. The underlying mechanisms responsible for arteriovenous malformation (AVM) growth, progression, and rupture are not fully known, yet the critical role of inflammation in AVM pathogenesis has been noted. The proinflammatory cytokines are upregulated in CAVM, which stimulates overexpression of cell adhesion molecules in endothelial cells (ECs), leading to improved leukocyte recruitment. It is well-known that metalloproteinase-9 secretion by leukocytes disrupts CAVM walls resulting in rupture. Moreover, inflammation alters the angioarchitecture of CAVMs by upregulating angiogenic factors impacting the apoptosis, migration, and proliferation of ECs. A better understanding of the molecular signature of CAVM might allow us to identify biomarkers predicting this complication, acting as a goal for further investigations that may be potentially targeted in gene therapy. The present review is focused on the numerous studies conducted on the molecular signature of CAVM and the associated hemorrhage. The association of numerous molecular signatures with a higher risk of CAVM rupture is shown through inducing proinflammatory mediators, as well as growth factors signaling, Ras-mitogen-activated protein kinase-extracellular signal-regulated kinase, and NOTCH pathways, which are accompanied by cellular level inflammation and endothelial alterations resulting in vascular wall instability. According to the studies, it is assumed that matrix metalloproteinase, interleukin-6, and vascular endothelial growth factor are the biomarkers most associated with CAVM and the rate of hemorrhage, as well as diagnostic methods, with respect to enhancing the patient-specific risk estimation and improving treatment choices.

A comprehensive review of the epidemiology and clinical features of 91 cases with Buerger's disease.

BACKGROUND: Thromboangiitis Obliterans (TAO) is a disease of small and medium-sized arteries with an unclear natural course. This study aims to establish a national registry of the disease to gain a better understanding of its epidemiology and clinical course. METHOD: This study was a cohort study of 242 patients with a high probability of TAO admitted to Mashhad University of Medical Sciences (MUMS) hospitals from 2000 to 2015. Of these, 91 patients with a confirmed diagnosis were included in the study (90 males and 1 female) with a mean age of 35 ± 7.8 years. RESULTS: The most common symptom upon onset of the disease was paresthesia (29.7%), followed by cold sensitivity and paresthesia (93.4%) during the progression of the disease and Raynaud syndrome or vasospasm (93.9%) in the active phase. The right lower limb was the most commonly affected limb (46.2%), and presenting ischemic symptoms in 48.4%.Statistics indicated a positive correlation between the duration of Burger's disease and the number of affected limbs (p = 0.001). There was no effect of disease duration on the likelihood of amputations (p = 0.28). CONCLUSION: Some patients may experience mild, subtle symptoms for years before the initial signs and symptoms appear, which can be severe and rapidly progress to the point of requiring amputation.We suggest that the diagnostic criteria for Buerger's disease should be revised in light of the presence of atherosclerosis and its associated risk factors, which present a challenge in terms of diagnosis and treatment. Clinical experience will be of great importance in this regard.

Differences in autoimmunity factors based on the activity of thromboangiitis obliterans.

OBJECTIVE: The treatment of Buerger's disease (BD) presents a medical problem as its etiology is still unclear. In this study, our objective was to evaluate the serum levels of autoimmune markers in patients with different clinical features of BD. METHODS: In this study, 80 BD patients were categorized in three groups using a cross-sectional design: migratory thrombophlebitis, cold sensitivity, and skin discoloration (mild symptoms); chronic ulcers, claudication, and burning pain of the feet at night (moderate symptoms); pain at rest and spontaneous gangrene (severe symptoms). Enzyme-linked immunosorbent assay was performed to measure antibodies against immunoglobulin M rheumatoid factor (IgM RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptide (anti-CCP), antiphospholipid antibodies (APA), anti-cardiolipin antibodies (ACLA), anti-double stranded DNA (anti-dsDNA), and extractable nuclear antigen (ENA) profile. RESULTS: Patients with severe symptoms showed the lowest age (p=0.031), ESR (p<0.001), and highest prevalence of ischemia (p<0.001). In all the patients, the serum levels of ANA and IgM RF were higher than 1 U and 15 IU/mL, respectively. However, the progression of the disease from mild to moderate did not affect these markers significantly (p>0.05). Other markers were negative in patients with BD. CONCLUSION: The findings of this study indicate that BD may closely be correlated to transient autoimmune phenomena, despite the fact that further research is required to investigate how transient unspecific autoimmune reactions contribute to the BD pathogenesis.

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 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.

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.

Chronic hemodialysis access-induced distal ischemia (HAIDI): distinctive form of a major complication.

PURPOSE: Hemodialysis access-induced distal ischemia (HAIDI) is an uncommon but potentially devastating complication. HAIDI is classified as acute, subacute and chronic based upon the time of onset. The aim of this study was to determine the prevalence, severity, patients' characteristics and the underlying etiologic mechanism of chronic HAIDI using color Doppler ultrasonography (CDUS). METHODS: Between June and August 2010, 676 hemodialysis patients with arteriovenous access (AVA) were evaluated for clinical evidence of chronic HAIDI. In the case-control part of the study, CDUS findings were compared between ischemic patients and asymptomatic matched controls. Also, patients with chronic HAIDI were followed up until February 2014, access ligation, kidney transplantation or death. RESULTS: Eighteen chronic HAIDI patients were diagnosed (2.66%). Cold hand and cold sensation were the most common signs and symptoms of hand ischemia, respectively. Fifteen patients were classified in stage 1. Patients with proximal autogenous arteriovenous fistula, younger age, more previous AVAs and less access age were more likely to develop chronic HAIDI. Excessive fistula flow was found in the majority of ischemic patients (83.3%). The mean fistula flow was significantly higher in cases compared to controls (p=0.001). Eleven patients with chronic HAIDI were successfully treated by conservative measures alone until the end of follow-up (n=3), kidney transplantation (n=4) or death (n=4). CONCLUSIONS: CDUS is a useful adjunctive diagnostic tool to determine the etiology of chronic HAIDI. Conservative measures combined with close follow-up can be used as the first step in the management of chronic HAIDI patients with mild symptoms.

Preperitoneal tunneling-a novel technique in peritoneal dialysis catheter insertion.

INTRODUCTION: This study describes a new preperitoneal tunneling (PPT) method for inserting a peritoneal dialysis catheter (PDC), thereby lessening surgical complications and increasing the catheter's survival. METHODS: This new technique was used in 23 cases from December 2005 to January 2007 and followed up until March 2011 (63 months). The procedure was performed laparoscopically under local (16 cases) or general (7 cases) anesthesia by one surgeon. Catheter survival is reported by Kaplan-Meyer analysis. RESULTS: The catheters were mechanically obstructed in 2/23 cases (8.7%); and were withdrawn due to a peritonitis in 2 cases and inadequacy of peritoneal dialysis in 1 case. Ten patients received kidney transplantation and six died before completing this follow-up period. The patients still reaped the benefits of the PDC until receiving a kidney transplant or death. The 5-year survival rate of the catheter was 89%. No incidence of catheter migration, omental wrapping, herniation or leakage was noticed. CONCLUSION: Preperitoneal tunneling is a simple and safe method for insertion of PDC, and can effectively prevent catheter migration, dislocation and omental wrapping.

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.

A newly designed SIPC device for management of lymphoedema.

PURPOSE: Using (Sequential) intermittent pneumatic compression (SIPC) is one of the most appropriate nonsurgical treatments for lymphoedema. In this study, we introduce a new mode for SIPC and evaluate its clinical results with higher pressures. METHODS: Participants included 43 lower limb lymphoedema patients who underwent high pressure SIPC. Limb circumference pre- and post-SIPC were evaluated. RESULTS: The mean reduction of the affected limb oedema was approximately 75%, which is regarded as a good response to the short-term treatment. Patients with disease duration more than 20 years didn't show a good or excellent response. Also the foot area had the least degree of reduction of oedema. CONCLUSION: We concluded that, the suggested mode may provide more acceptable results compared with the other This mode allows unidirectional forward lymph flow and associated high pressure usage well tolerated in chronic cases of the disease.

Laparoscopic correction of peritoneal catheter dysfunction.

PURPOSE: To present our experiences with laparoscopic repair of peritoneal catheter dysfunction METHODS: Total of 24 patients with peritoneal catheter malfunction were considered for two-port laparoscopic manipulation. Two patients with unsuccessful result in the first trial and 3 patients with successful peritoneal dialysis results were reoperated because of catheter dysfunction. RESULTS: The success rates at the first and second manipulation was 79% and 80%. The most frequent cause of catheters dysfunction was migration of catheters out of the true pelvis. During the follow up, 8 patients were referred for renal transplantation, 8 underwent hemodialysis and 5 continued with normal catheter function. The mean longevity of the catheters after laparoscopic correction was 42 months. One year longevity rate as measured as 79%. CONCLUSION: Laparoscopy is the procedure of choice even in recurrent cases, for correction of malfunctioning continuous ambulatory peritoneal catheters, because this procedure is the only technique that can detects pathologic causes of catheters malfunction and can resolve those problems at the same time.

Preventable trauma death in Tehran: an estimate of trauma care quality in teaching hospitals.

OBJECTIVE: The purpose of this study was estimate the number of preventable trauma deaths in teaching hospitals in Tehran. METHODS: We evaluated the complete prehospital, hospital, and postmortem data of 70 trauma patients who had died during a 1-year period in two of the largest university hospitals in Tehran with a multidisciplinary panel of experts. RESULTS: Panel members identified 26% of all trauma deaths as preventable deaths. From 31 non-central nervous system-related deaths, 17 and 6 cases were identified as surely preventable and probably preventable, respectively. In central nervous system-related deaths, 5% of the deaths overall (2 of 38 cases) were identified as surely preventable or probably preventable. Sixty-four cases of medical errors were identified in 31 trauma deaths and 80% of these errors were directly related to the death of the patients. CONCLUSION: The high preventable trauma death rate in our teaching hospitals indicates that a relatively significant percentage of trauma fatalities could have been prevented by improving prehospital and in-hospital trauma care.

Prehospital trauma care in Tehran: potential areas for improvement.

OBJECTIVE: To evaluate the existing prehospital trauma care system in Tehran, Iran. METHODS: This was a cross-sectional study in which all trauma-related dispatches of Tehran's emergency medical services (EMS) system were evaluated-during 18 randomly selected days from September 22,1997, to March 17,1998. Emergency medical technicians completed a checklist for all trauma cases, and the criteria for this performance evaluation were different partial time intervals in each dispatch and different procedures that had been done for the patients. RESULTS: The means of the "dispatch-beginning-to-scene-arrival interval" and "scene-arrival-to-scene-leaving interval" were 10 and 18 minutes, respectively (median: 10 minutes, range 0-55 minutes for the first; and median: 15 minutes, range 1-165 minutes for the second time interval). The mean of the "dispatch-beginning-to-hospital-arrival interval" was 45 minutes (median: 42 minutes, range: 5-170 minutes). Among advanced life support (ALS) procedures that include cardiac monitoring, intratracheal intubation, intravenous fluid therapy, nasogastric tube insertion, defibrillation, and tracheostomy, only intravenous fluid therapy had been administered for the patients. The patients, however, had received different kinds of basic life support (BLS) that include initial evaluation, bleeding control, oxygen administration, splinting, suction use, and cardiopulmonary resuscitation. CONCLUSION: The prolonged response, scene, and dispatch-beginning-to-hospital-arrival intervals compared with those for a developed EMS system indicate one potential area for improvement. Furthermore, significant differences in the field of prehospital care (conducting no ALS procedure) showed that ambulance equipment and training of EMS personnel are two other potential sites for improvement.