Diabetes Peripheral Vascular Disease Research Articles

ROLE OF FASCIOCUTANEOUS FLAPS AS A METHOD OF SOFT TISSSUE COVERAGE IN TYPE 111 – B OPEN TIBIAL FRACTURES

Abstract Object: To determine the role of fasciocutaneous flap as soft tissue coverage in type 111 – B open tibial Pahore M.K. 1 Assistant Professor Department of Orthopaedic Surgery and Traumatology, Liaquat medical university Hospital Jamshoro Laghari M.A. 2 Associate Professor Department of Orthopaedic Surgery and Traumatology Liaquat Medical University Hospital, Jamshoro Maher I.K. 3 Consultant Orthopaedic Surgeon, Department of Liaquat Medical University Hospital, Jamshoro Mugrai M.K. 4 Associate Professor, Department of Plastic Surgery, Liaquat Medical University, Jamshoro Pirwani M. 5 Associate Professor Department of Orthopaedic Surgery and Traumatology, Liaquat Medical University, Hospital, Jamshoro Memon S.A. 6 Consultant Orthopaedic Surgeon Liaquat Medical University, Jamshoro fractures. An experience by orthopaedic surgeons at LUMHS Jamshoro. Material and Methods: This prospective study was containing 41 patients with type 111 – B fracture of tibia. All cases were managed in department of ortho-paedic surgery and traumatology LUMHS Jamshoro from 2008 – 2012. Patients with diabetes mellitus and peripheral vascular disease were excluded from study. After resuscitation and antibiotic cover debridement done and back slab applied. On next day after routine investigations debridement was done and fracture was stabilized with external fixator. After multiple debride-ments as wound became clean and ready for flap, it is covered with appropriate fasciocuaneous flap. Dress-ing changed after 5 days and stitches removed after 2 weeks. Patients were assessed for their basic data, site of injury, type of fasciocutaneous flap ,their accep-tance and complications. Results: Average age was 31.8 years, According to site of injury 7 (16.66%) cases sustained in proximal tibia, 12 (28.57%) in middle tibia, 17 (40.47%) in dis-tal tibia, 4 (9.52%) in middle 2/3 rd of tibia and 2 (4.76%) in distal 2/3 rd of tiba. The pattern of execu-ted flaps were proximal based medial flaps in 4(9.52), proximal based lateral in 3 (7.14%), distal based med-ial in 8 (19%), distal based lateral in 17 (40.47%), cross leg in 2 (4.76%), sural flap in 2 (4.76%), distal lateral retrograde in 4 (9.52%), random pattern flaps in 2 (4.76%) and soleus muscle flaps in 2 (4.76%) cases. Out of 42 cases 33 (78.57%) were good, 6 (14.28%) fair and 3 (7.14%) poor. Complications noted were marginal necrosis in 6 (14.28%), partial or complete necrosis in 3 (7.14%), superficial infection in 3 (14.28%) and deep infection in 5 (11.9%) cases. Conclusion: It is concluded that fasciocutaneous flap is a simple, safe and cost effective procedure with good acceptance in type 111 – B open tibial fractures. Key Words: Type 111 – B open tibial fractures – soft tissue coverage – fasciocutaneous flaps.

Novel Techniques Using Negative Pressure Wound Therapy for the Management of Wounds With Enterocutaneous Fistulas in a Long-term Acute Care Facility

Patient status and wound condition are important factors to consider when developing an appropriate wound management plan. Comorbid conditions such as diabetes mellitus, obesity, and peripheral vascular disease affect wound healing, as do complications, such as fistulas and infections. This article describes 3 novel techniques, using negative pressure wound therapy with reticulated open-cell foam for managing patients with wounds containing an enterocutaneous fistula.

Frequency of Conduction Disturbances After Edwards SAPIEN Percutaneous Valve Implantation

Disturbances in atrioventricular conduction and the additional need for a permanent pacemaker are recognized complications after transcatheter aortic valve replacement (TAVR). We analyzed the incidence of postprocedural conduction disorders and the need for permanent pacemaker implantation in patients undergoing TAVR with the Edwards SAPIEN valve. In 125 consecutive patients with symptomatic, severe aortic stenosis undergoing TAVR, a standard 12-lead electrocardiogram was obtained before and serially after the procedure. The cohort was divided into 2 groups with regard to the post-TAVR appearance of conduction disturbances, defined as left bundle branch block, right bundle branch block, fascicular hemiblock, atrioventricular block, and the need for a permanent pacemaker. The patients with and without conduction disturbances were compared. After TAVR, 19 patients (15.2%) met the study definition of a "new conduction defect" and 5 patients (4%) required a permanent pacemaker because of an advanced atrioventricular block. New left bundle branch block appeared in 5 patients (4%) and left anterior hemiblock in 9 (7.2%). No new right bundle branch block or left posterior hemiblock was observed. Although most baseline, echocardiographic, and procedural characteristics were equally distributed, the patients with new conduction disturbances more often had diabetes mellitus and peripheral vascular disease. Also, they more often were taking an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker, and the procedure was performed more often with apical access (12 [63.2%] vs 7 with femoral access [36.8%], p = 0.002). In conclusion, although the incidence of conduction disturbances was high after TAVR using the Edwards SAPIEN valve, with a significant increase in the rate of left bundle branch block and left anterior hemiblock, the need for permanent pacemaker implantation after TAVR with this valve remained low.

Intravenous immunoglobulin-associated renal failure in a patient with post-transfusion purpura.

Intravenous immunoglobulin (IVIG), initially developed for immunodeficiency disorders, has now been used for multiple autoimmune diseases and infections. These are generally well tolerated, with few adverse effects. Acute kidney injury has been described in very rare instances. We report an interesting case of a 59-year-old African American male with a pertinent history of diabetes mellitus, hypertension, endocarditis, and peripheral vascular disease, who was diagnosed with post-transfusion purpura. He was then treated with IVIG and subsequently developed an acute worsening of renal function in a time span of 3 days. The etiology remained elusive even after an extensive workup. Renal biopsy was done finally, which showed findings suggestive of osmotic nephropathy that was traced to the sucrose used as a stabilizing agent in the IVIG. In light of the increasing use of IVIG, it is therefore highly recommended that clinicians are well aware of this side effect of IVIG.

Nitrite/nitric oxide regulation of therapeutic angiogenesis for diabetic ischemic vascular disease

Diabetes is associated with increased incidence of cardiovascular disease along with concomitant peripheral vascular disease contributing to development of PAD and non-healing ulcers of the extremities. Previous work has revealed that NO bioavailability is markedly diminished during diabetes and figures to be a key contributor to increased cardiovascular disease in this metabolic disorder. Our group has determined that the NO/nitrite endocrine system serves as a critical mediator of ischemic vascular remodeling of peripheral limbs and has further revealed the importance of this endocrine system for diabetic vascular disease. Data will be presented demonstrating how nitrite/NO metabolism mediates protection against peripheral tissue ischemia and necrosis during diabetes by stimulating therapeutic angiogenesis in both young and aged diabetic animal models. Nitrite/NO therapeutic angiogenesis during diabetes significantly depends on VEGF induction and activity while also significantly decreasing vascular and ischemic tissue oxidative stress. Importantly, oral sodium nitrite administration to diabetic patients with peripheral tissue ulcers is well tolerated indicating the therapeutic potential of this approach for therapeutic angiogenesis for diabetic peripheral vascular disease.

Endovascular Therapy: Is It Effective in the Diabetic Limb?

Reducing the risk of lower extremity amputation in diabetics is a top priority. To make progress in this area, we must bring all options to bear in the treatment of diabetic peripheral vascular disease. The "endovascular promise" of lower morbidity, while attaining the primary clinical goal (in this case, limb salvage), was late to arrive in the treatment of the ischemic diabetic lower extremity. This is due to complex and severe lesion morphologies requiring treatment, as well as the complexity of the vascular disease and the clinical scenario in diabetic critical limb ischemia. Although not without remaining challenges, significant strides have been made in the last 5 years that have increased the role of endovascular therapy in this setting.

Outcomes of Paramedian Forehead and Nasolabial Interpolation Flaps in Nasal Reconstruction<alt-title>PMFF & NLFs</alt-title>

To determine the factors contributing to failure of interpolation flaps in nasal reconstruction. Retrospective medical chart review. Tertiary care academic center. A total of 107 patients with nasal defects needing reconstruction, performed at the University of Arkansas for Medical Sciences, Little Rock. Patients underwent nasal reconstruction with 2-stage paramedian forehead or nasolabial flaps (PMFF and NLF, respectively) from 2002 to 2011. Defect thickness, location, flap type, use of cartilage grafts, and comorbidities, including diabetes mellitus, peripheral vascular or coronary artery disease, and smoking habits, were recorded. Full success, partial failure, or full failure of the respective flap. Eighty-two of the patients (77%) underwent 2-stage PMFF repair and 25 (23%) underwent 2-stage NLF repair. Fifty-eight defects (54%) were full thickness, in which 46 repairs used PMFF and 12 used NLF for reconstruction. The overall failure rate was 6%. Five PMFF failed (6%); 3 of these were used for full-thickness repairs. There was only 1 NLF failure (4%), which was also performed for the repair of a full-thickness defect. Use of cartilage in the reconstruction did not affect failure rates of the different soft tissue flaps. No single comorbidity was noted to have a statistically significant effect on failure rates, although 83% of failures were observed in smokers. The overall success rate of interpolation flaps in nasal reconstruction was 94.4%. Defect thickness, use of a cartilage graft, type of flap used, and presence of comorbidities did not affect outcome. Although the comparison was not statistically significant (P=.21), flap failures were more commonly observed in smokers.

Correlation of Peripheral Arterial Blood Flow with Plasma Chemerin and VEGF in Diabetic Peripheral Vascular Disease

Progressive vasodegeneration in microvascular beds is the major underlying factor in initiation and progression of diabetic complications. Chemerin shows a strong correlation with various facets of the metabolic syndrome, which is associated with dysregulated angiogenesis. VEGF is shown to have an angiogenic role in certain cardiovascular risk factors, including diabetes. Ankle/brachial index is a known approach for assessing lower-limb peripheral vascular disease. This study aimed to elucidate the correlation of ankle/brachial index as a marker of peripheral blood flow with biomarkers of angiogenesis, plasma chemerin and VEGF, in diabetic peripheral vascular disease. Ninety age- and sex-matched females were enrolled in the study: 30 were controls, while 60 had Type 2 diabetes, of whom 30 had controlled diabetes (group II) and 30 had diabetes with peripheral vascular disease (group III) diagnosed by an abnormal ankle/brachial index. Plasma levels of chemerin and VEGF were measured. There was a significant decrease of the ankle/brachial index and significant increase in plasma chemerin and VEGF in diabetic patients with peripheral vascular disease (p < 0.05). A positive correlation was observed between ankle/brachial index, plasma chemerin and VEGF in diabetic patients with peripheral vascular disease. Linear regression analysis revealed that neither chemerin nor VEGF were predictors for ankle/brachial index in diabetic peripheral vascular disease. This study elucidates, for the first time, the rise of plasma levels of chemerin and VEGF, and their positive correlation with ankle/brachial index in diabetic peripheral vascular disease. These findings denote their angiogenic effect of improving the peripheral blood flow in diabetic peripheral vascular disease. Further studies are warranted to examine the exact role of these two biomarkers in diabetic vasculopathy.

Antiplatelet Therapy, Diabetic Neuropathy and Peripheral Vascular Disease: A Unitary Approach

Although pathologically not necessarily the same, germane to both diabetic neuropathy and peripheral vascular disease is the morbid vascular complication of diabetes mellitus. As it appears, strict glycemic control alone is unable to neither prevent nor promote recovery of diabetic microvascular complications, thus the need to seek other treatment strategies. In addressing the vascular complications, a unitary approach between diabetic neuropathy, peripheral vascular disease and antiplatelet therapy is in order. Notably, the fine balance between platelet/coagulation and fibrinolysis systems are dominantly shifted to acceleration of the platelet/coagulation system in diabetes mellitus. Not only platelet homophilic aggregation, but also platelet heterophilic aggregation with neutrophils or monocytes in inflammatory conditions is observed. Hyperglycemia also induces overproduction of reactive oxygen species by multiple pathomechanisms that injure endothelial cells and reduce nitric oxide which eventually reduce the blood flow in microvessels. Among other antiplatelet agents, cilostazol is a novel antiplatelet agent that has been found to have beneficial effects in macrovascular events like stroke and peripheral vascular diseases. In peripheral vascular disease clinical trials, there is robust data that cilostazol is efficacious in improving walking speed. Also, cilostazol increases nerve blood flow/nerve conduction, and inhibits reduction in pericyte area of endoneurial microvessels in animal models of diabetic neuropathy. Clinical trials on diabetic polyneuropathy alone or in combination with peripheral vascular disease indicate clinical improvement in blood flow, but not necessarily in neuropathy parameters. Since a neurodegenerative process is equally as important a pathomechanism, the effect of antiplatelet therapy in diabetic neuropathy should be examined in long-term clinical trials that may potentially unfold its benefits over time.

Long-Term Outcomes of Percutaneous Coronary Intervention (PCI) in Octogenarians with Chronic Kidney Disease

Background: Few studies have examined the long-term outcomes of percutaneous coronary intervention (PCI) in octogenarians (>80 years old) with chronic kidney disease (CKD). The aim of this study was to evaluate the long-term outcomes of octogenarians with CKD (eGFR < 60mL/min/1.73m2) undergoing PCI in our hospital. Methods: Retrospective data was collected for 319 consecutive patients who underwent PCI during January 2003 to December 2009. Patients were stratified on the presence of CKD (n=143) or no CKD (n=176) as defined by estimated GFR using the MDRD equation and followed for a mean of 33 months. The CKD group had higher rates of diabetes mellitus (40.4% versus 23.4%, p= <0.05), hypertension (98.6% versus 93.8%, p= <0.05), and peripheral vascular disease (19.6% versus 8.5%, p= <0.05). Other characteristics were similar among the groups. The primary outcome of the study was to compare the in-stent restenosis in octogenarians with and without CKD. All cause mortality and bleeding events post stenting were also compared.Results: A total of 59 patients developed in-stent restenosis: 16.6 % (n=29) in non CKD [17.3% with BMS (Bare metal Stents) and 14.3 % with DES (Drug Eluting Stents)] and 21 % (n=30) in the CKD group (22.8% with BMS and 16.7 % with DES) (P=0.31). There was no association of stent type and all cause death in either group; all cause death was significantly higher in the CKD patients. There was no significant difference in bleeding complications in CKD compared with non CKD groups (11.4% versus 10.5%, p= 0.85). However, CKD patients on aspirin and clopidogrel had a significantly higher incidence of bleeding (60% versus 40%, p=<0.001). Conclusion: As previously shown, CKD patients have a higher mortality than those without kidney disease. Long-term outcomes of BMS are comparable to DES in octogenarians with CKD. BMS may be preferable in CKD patients in order to avoid prolonged dual anti-platelet therapy with its attendant higher risk of bleeding in this group.

Vascular calcification in diabetic foot and its association with calcium homeostasis

Introduction:Vascular calcification (VC), long thought to result from passive degeneration, involves a complex process of biomineralization resembling osteogenesis, frequently observed in diabetes and is an indicator of diabetic peripheral vascular disease with variable implications.Aim and Objective:To study the association between vascular calcification and calcium homeostasis in diabetic patients with foot ulcers without stage 4, 5 chronic kidney disease.Materials and Methods:A total of 74 patients with diabetic foot ulcer were enrolled, and VC was detected by X-ray and Doppler methods. Serum calcium, phosphate, alkaline phosphatase (ALKP), fasting and post-prandial glucose levels, and glycosylated hemoglobin (HbA1C) were recorded. Serum iPTH and 25 (OH) vitamin D were estimated by immune radiometric assay and radioimmunoassay, respectively. Data was analyzed by SPSS 16.0.Results:Vascular calcification was present in 42% of patients. Significant difference in the mean (±SD) of vitamin D, HbA1C, and eGFR was observed in VC +ve compared to VC –ve. There was no significant association of age, duration, BMI, PTH, Ca, PO4, ALKP with that of VC incidence. Severe vitamin D deficiency was more common in VC +ve (51.6%) compared to in VC –ve (18.6%). Sub-group analysis showed that the risk of VC was significantly higher (RR = 2.4, P < 0.05, 95% C.I. = 0.058-2.88) in patients with vitamin D < 10 ng/ml compared to others.Conclusion:Vitamin D deficiency could be a risk for vascular calcification, which possibly act through receptors on vascular smooth muscle cells or modulates osteoprotegerin/RANKL system like other factors responsible for VC in diabetic foot patients.

Diabetisches Fußsyndrom

Diabetic foot syndrome is a major complication for patients with diabetes mellitus. About 25% of the 6 million patients with diabetes in Germany will suffer from diabetic foot syndrome at some point during the course of disease. Diabetic neuropathy and peripheral vascular disease are the main causative factors in the pathogenesis of diabetic foot ulcers. The mortality rate of these patients is more than twice as high as that of the average population. 25% of costs incurred by patients with diabetes are spent on diabetic foot ulcers, and 50% of hospital days are attributed to the treatment of the diabetic foot syndrome. This syndrome is also the most common cause of non-traumatic amputations. Both the risk of amputation and mortality are much increased in case of peripheral vascular disease. Hence, the aim is to lower the still high number of amputations in Germany by appropriate preventive measures as well as by multidisciplinary diagnostics and therapy.

Advances in the Treatment of Peripheral Vascular Disease in Diabetes and Reduction of Major Amputations

In recent years, life expectancy has increased in many societies consequent to better health conditions. Although the trends of decreasing mortality rates from ischemic heart disease and stroke have continued into the 21st century, both causes continue to be the biggest killers in the Western societies. No change is predicted in the foreseeable future and consequently both these conditions contribute significantly to the burden of disease. 1 Diabetes is considered a cardiovascular disease equivalent and with diabetes patients share the benefits of the improved approach to the treatment of cardiovascular disease. However, because of the longer life span and disease duration, other chronic complications such as peripheral arterial disease (PAD) may well become more evident. In a recent survey, PAD was present in 21% of newly diagnosed type 2 diabetic patients 2 and in about 50% of the patients admitted to a diabetic foot clinic on account of a new foot ulcer. It is interesting to emphasize that half of those patients had concomitant peripheral neuropathy. 3 Neuropathy can mask the classic PAD symptoms as claudication, thereby delaying a diagnosis. On the other hand, the presence of PAD may limit the use of total contact cast that is considered the “gold standard” treatment for neuropathic ulcerations. PAD alone is responsible for the increased risk of lower limb amputation observed in patients with diabetes. 4,5 In type 1 diabetes, the overall 25-year cumulative incidence of lower extremity amputation (LEA) is 10.1%. History of heavy smoking, high HbA1c, presence of hypertension are all factors related to PAD and major determinants associated with LEA. 6 In addition, major complex gender differences exist in diabetes-related LEA: Men are more likely to undergo LEA. 7 The presence of a foot infection increases the risk of LEA. A multidisciplinary approach to diabetic foot problems is mandatory to reduce the frequency of LEA, particularly when PAD is complicated by the presence of infected foot ulcers. 8 Today significantly better outcomes are expected for patients with diabetes affected by critical limb ischemia (CLI) based on improved technical options in peripheral revascularization, new options in antibiotic therapy, and aggressive wound debridement and wound care. Until recently, open peripheral arterial bypass has been the firstline surgical treatment option for PAD. Although open bypass is associated with successful results, the invasive nature of the surgery can limit optimal overall outcome. Endovascular procedure is less invasive; however, it reaches similar limb salvage rates in patients with CLI, 9 with the added benefits of fewer wound complications and a shorter hospital stay. As expected, endovascular therapy is increasingly being considered as a first-line treatment option in carefully selected PAD diabetic patients. With the widespread adoption of endovascular therapy, there has been a profound shift in practice patterns for lower extremity PAD. In the past decade, there has been a consistent increase in the number of patients treated by peripheral transluminal angioplasty because of CLI. 10 Hong et al 10 reported that in the general population the average annual number of endovascular interventions is increased by 78% while there is a concomitant decrease in open bypass by 20%. The same authors found that the trends in amputation were consistent with the increase in endovascular therapy. The number of major amputations (ankle to above-the-knee level) decreased by 21% and the number of minor amputations, defined as involving the toe and forefoot, showed a moderate decrease of 5%. Although better outcomes for CLI have been observed in the general population, the LEA observed in patients with diabetes are reportedly reduced, unchanged, or even increased. A recent survey conducted in England reported that the number and incidence of amputations decreased in the aging nondiabetic population whereas the overall population

Letter: Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:390-6)

Letter: Diabetic Polyneuropathy and Cardiovascular Complications in Type 2 Diabetic Patients (Diabetes Metab J 2011;35:390-6)

An appraisal of serum preptin levels in PCOS

Plasma preptin levels were higher in women with PCOS compared with the control group (mean±SD, 823.2±140.7 vs. 324.9±147.3 pg/mL). This article suggests a potential role of preptin in the pathogenesis of PCOS.

Advances in treatment of diabetic foot ulcers

Diabetic foot is a major health problem all over the world. Approximately 15% of the 200 million people with diabetes worldwide will develop a foot ulcer during their lifetime. Major amputation is a feared complication of diabetes. Many patients who undergo an amputation have a history of ulceration. More than 60% of non-traumatic amputations in the western world are carried out in diabetes patients. Major amputations increase morbidity and mortality and reduce the patient's quality of life. An important prelude to diabetic foot treatment is the differing diagnosis of neuropathic and neuroischemic foot. Treatment of a neuropathic plantar ulcer must correct pathological plantar distribution of pressures. Surgical treatment of deformities, with or without ulcerations, is an effective therapy. Charcot neuroarthropathy is a particular complication of neuropathy wich may lead to fragmentation or destruction of joints and bones. Additionally, in the diabetic population peripheral vascular disease (PVD) is the main risk factor for amputation. If PVD is not diagnosed, treatment of the ulcer cannot be successful. In diabetic patients PVD is distal, but often fully involves the femoral, popliteal and tibial vessels. It can be successfully treated with either open surgical or endovascular procedures. Finally, infection is a serious complication of diabetic foot. Phlegmon or necrotizing fascitis are not only limb-threatening problems, but also life-threatening ones. In this case emergency surgery is mandatory.

Osteomyelitis in elderly patients

Older adults are predisposed to osteomyelitis either because of an increased incidence of associated disorders (e.g., peripheral vascular disease, diabetes mellitus, malnutrition and poor dentition) or because of surgical procedures that are frequently performed in the elderly population (e.g., dental extractions, open-heart surgery, and prosthetic joint replacement or osteosynthesis). Two types of haematogenous osteomyelitis that are seen in the elderly are vertebral and long bone osteomyelitis. The most common pathogen is Staphylococcus aureus. Osteomyelitis secondary to contiguous foci of infection can occur in older adults without vascular insufficiency (secondary to pressure ulcers) or with vascular insufficiency due to diabetes mellitus or peripheral vascular disease from atherosclerosis. Chronic osteomyelitis may be defined as osteomyelitis that has a duration of more than 6 weeks or that recurs or is not cured after the initial infection. Chronic osteomyelitis may be associated with certain surgical procedures (e.g., sternal osteomyelitis after open-heart surgery or implant-related infections after orthopaedic and traumatological procedures), poor dentition or dental extraction (mandibular osteomyelitis), and, more commonly, with systemic disorders (e.g., peripheral vascular disease and diabetes mellitus). Acute osteomyelitis can in some cases be cured with antimicrobial therapy alone but surgical management is often required and includes extensive debridement, obliteration of dead spaces, stabilisation, adequate soft tissue coverage, and restoration of an effective blood supply. Chronic osteomyelitis may be caused by S. aureus or coagulase negative staphylococci, but is often due to gram-negative organisms. Because of the presence of infected bone fragments without a blood supply (sequestra), cure with antibiotic therapy alone is rare, if ever, possible and adequate surgical debridement is the cornerstone of therapy. Bone repair and bone mineral density may be significantly retarded and may be corrected by eliminating risk factors, supplementing the diet with calcium, bisphosphonates, and/or vitamin D, and treating with testosterone and/or estrogen when deficient. Sodium fluoride treatment and anabolic steroids may be used as alternatives. Septic arthritis is a medical emergency, and prompt recognition and rapid and aggressive treatment are critical to ensuring a good prognosis. The treatment of septic arthritis includes appropriate antimicrobial therapy and joint drainage. Adverse effects of prescribed antibacterials occur more often in the elderly patient than in young adults. The physician can help to minimise the incidence of adverse effects and improve outcomes by being aware of the principles of clinical pharmacology, the characteristics of specific drugs, and the special physical, psychological and social needs of older patients, Figure ​Figure1,1, ​,2,2, ​,3,3, ​,44. Figure 1 Septic knee prosthesis. The arrow shows the bone loss, due to infection and loosening of the implant. Figure 2 X-ray after septic prosthesis removal and antibiotic-loaded spacer implant Figure 3 Total knee re-implantation after 3 months. Note the filling of the bone defect in medial aspect of the tibial plateau Figure 4 Control after 2 years

A Randomised Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy (IMRT) for Early Breast Cancer: Interim Results at 2 Years Follow-Up.

Abstract Background: This large single centre trial was designed to investigate whether correction of dose inhomogeneities using IMRT reduces late toxicity and improves quality of life in patients with early breast cancer. We report interim results at 2 years follow-up.Materials and Methods: Standard tangential breast radiotherapy plans of 1145 trial patients were assessed for dose inhomogeneity as defined by ICRU recommendations. Patients with inhomogeneous plans were randomised to either IMRT or standard radiotherapy. Patients with homogenous plans were treated with standard radiotherapy, but were followed up within the trial as per randomised patients. The primary endpoint of the trial was photographic assessment of breast shrinkage. Secondary endpoints included photographic assessment of final cosmesis, clinical assessment of toxicity, and patient-reported symptoms and quality of life. All endpoints were scored using validated assessment methods. Data were collected on potential confounding factors which included: age at randomisation, smoking history, body mass index, co-morbidity such as diabetes mellitus, cardiovascular and peripheral vascular disease, use of hormones and/or chemotherapy, treated breast volume, and presence or absence of breast boost.Results: 330/1145 (29%) of patients had adequate dosimetry with standard 2D radiotherapy and were not randomised. In the 815 randomised patients, dosimetry was significantly improved in the interventional (IMRT) arm compared to the control. Currently, data from 632 randoimsed patients who have reached 2 years of follow up have been analysed. This interim analysis demonstrates that the incidence of telangiectasia in the control arm was significantly greater than in the interventional group (P = 0.024). Pre-radiotherapy surgical cosmesis significantly affected photographic assessment of final cosmesis, and clinical assessment of breast shrinkage and induration (P &amp;lt; 0.0001). In randomised patients who had good surgical cosmesis, there was a significant difference improvement in final cosmesis with the use of IMRT (P = 0.038). The quality of life data has not been analysed at this stage.Discussion: This trial shows that the use of forward-planned IMRT can significantly improve dose homogeneity, and suggests that this translates into improvements in late toxicity at only 2 years from completion of radiotherapy. Surgical cosmesis appears to be a very important determinant of overall final cosmesis after 2 years of follow-up, and may mask any beneficial effects of IMRT at this early stage. It is highly likely that these trial patients will have not expressed their final level of toxicity at 2 years post-radiotherapy, and re-analysis is planned at 5 years from completion of radiotherapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 71.

Extent and Severity of Coronary Disease and Mortality in Patients with End-Stage Renal Failure Evaluated for Renal Transplantation

The purpose of this study is to explore the relationship between coronary artery disease (CAD), transplantation status and subsequent mortality in end-stage renal disease (ESRD) patients undergoing evaluation for renal transplantation. Two hundred fifty-three ESRD patients at high risk for CAD underwent coronary angiography as part of a renal transplant evaluation. The cohort was divided into three groups: Group 1 (n = 127) had no vessels with >or=50% stenosis, Group 2 (n = 56) had one vessel with >or=50% stenosis and Group 3 (n = 70) had two or more vessels with >or=50% stenosis. Long-term survival was determined; median follow-up was 3.3 years. The baseline characteristics were similar except for older age and higher proportion of diabetes mellitus, dyslipidemia and peripheral vascular disease in Groups 2 and 3 patients as compared to Group 1. Survival was worse in Group 3 compared to Group 1 (p < 0.0001). Each of the three subgroups had better survival with renal transplantation than those who did not undergo transplantation (p < 0.0001). Although the degree of CAD is related to subsequent mortality, transplantation is associated with better survival regardless of the extent and severity of CAD. Thus, the presence of CAD should not exclude ESRD patients from consideration for this therapy.

Increased prevalence of elevated urinary albumin excretion rate in type 2 diabetic patients suffering from ischemic foot lesions.

Present cross-sectional clinical study was aimed at the evaluation the prevalence of cardiovascular risk factors in Type 2-diabetics suffering from different clinical manifestations of diabetic foot lesions due to peripheral vascular disease and/or diabetic neuropathy. 1025 non-insulin-dependent (Type 2) diabetics (NIDDM) of both sexes were investigated. Patients were classified in Type II diabetes without peripheral vascular disease and foot lesions (group 0, controls), with macroangiopathic related foot lesions (group 2), with neuropathic foot lesions (group 3), and with mixed neuropathic-ischemic foot lesions (group 4). Apart from urinary albumin excretion rate (UAE), the following micro- and macroangiopathic risk factors and diseases were taken into account: Hypertension, degree of metabolic control (HbA1c), lipid concentrations, duration of diabetes, retinopathy, clinical nephropathy. In the total population the UAE was significantly (p < 0.01) correlated with duration of diabetes, serum creatinine, hypertension, age, lipid concentrations, HbA1c and insulin requirement. In comparison to Type II diabetic patients without peripheral vascular disease (group 0) and with neuropathic foot lesions (group 3), subjects with ischemic (group 2) and mixed neuropathic-ischemic foot lesions demonstrated an increased prevalence of pathological UAE, which was associated with a higher frequency of clinical nephropathy, retinopathy, an older age and longer duration of diabetes. It is concluded that microalbuminuria in Type 2 diabetes reflects both the existence of diabetic nephropathy and peripheral vascular disease which is often associated with the insulin resistance syndrome.