Development of a core outcome set for venous leg ulceration (CoreVen) research evaluations (protocol)

BackgroundA venous leg ulcer is a chronic leg wound caused by poor venous blood circulation in the lower limbs. It is a recurring condition causing pain, malodour, reduced mobility, and depression. Randomised controlled trials evaluating treatments for venous leg ulcers provide important evidence to inform clinical decision-making. However, for findings to be useful, outcomes need to be clinically meaningful, consistently reported across trials, and fully reported. Research has identified the large number of outcomes reported in venous leg ulcer trials, impacting both synthesis of results, and clinical decision-making. To address this, a core outcome set will be developed. A core outcome set is an agreed standardised set of outcomes which should be, as a minimum, measured and reported in all trials which evaluate treatment effectiveness for a given indication. A core outcome set has the potential to reduce research waste, improve the utility of RCTs, reduce reporting bias, facilitate treatment comparisons across different sources of evidence and expedite the production of systematic reviews, meta-analyses and evidence-based clinical guidelines.AimThe aim of this project is to develop a core outcome set for research evaluating the effectiveness of interventions for treating venous leg ulceration.MethodsThrough a scoping review of the literature on venous leg ulceration, we will firstly identify a list of candidate outcome domains (broad categories in relation to what is being measured) from randomised controlled trials and qualitative research, and outcomes (specific methods in relation to what is being measured). In two further stages, we will use the resulting lists of outcome domains and outcomes to design two online surveys. A range of stakeholders will be invited to participate in the surveys and they will be asked to indicate which outcome domains and outcomes are most important and should be considered as core in future research reports.     

Angiolipoma of the buccal mucosa: a possible role of mast cell-derived VEGF in its enhanced vascularity

A case of angiolipoma occurring in the buccal mucosa of a 69-year-old male is described. The patient had noticed a painless mass in his buccal mucosa for 2 years. The surgically removed tumor, measuring 9 mm in diameter, was mainly located in the submucosal layer with focal expansion into the muscle layer. Histologically, the tumor was well-demarcated and composed of proliferations of mature fat cells and fibrous connective tissue containing many small blood vessels, which were evenly distributed. There was diffuse infiltration of a large number of mast cells, which were immunopositive for vascular endothelial growth factor (VEGF) especially around blood vessels, suggesting that VEGF produced by mast cells in angiolipomas plays an important role in the vascular proliferation in this particular tumor.     

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6.

alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. METHODS: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed. RESULTS: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was < or = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. CONCLUSION: This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.     

Coronary reperfusion with a new catheter in six patients with acute occlusion after angioplasty

A new catheter was used in an attempt to re-establish coronary flow in six patients with acute occlusion after angioplasty and prior to emergency coronary artery bypass surgery. All patients suffered from severe chest pain, and the electrocardiogram showed signs of acute transmural ischemia. A reperfusion catheter manufactured by Advanced Cardiovascular Systems (ACS) has 36 side holes spirally arranged along the distal 10 cm. It is introduced over an exchange wire. After the catheter was positioned across the occlusion, five patients had complete relief of chest pain, and another patient had partial relief. The electrocardiogram normalized in all six patients (in one only initially). Two patients developed a limited myocardial infarction, but four did not. The time between introduction of the reperfusion catheter and aorta cross clamping varied between 1.5 and 6.5 hours, and there were no complications related to its use. We conclude that the ACS reperfusion catheter is useful in re-establishing coronary blood flow after failed angioplasty and prior to emergency coronary artery bypass surgery.     

Current determinants of 30-day and 3-month mortality in over 2000 aortic valve replacements: Impact of routine laboratory parameters.

OBJECTIVE: Haematological and biochemical measurements are performed routinely before surgery to exclude organ malfunction and blood cell and coagulation abnormalities. We aimed to test routinely obtained laboratory data as factors predicting operative risk. METHODS: Between 1996 and 2003, 2198 patients underwent aortic valve replacement (AVR) (908 of them with concomitant CABG) in our institute. The mean age of the study population was 69+/-11 years (range 13-91, 43% female). Clinical and laboratory parameters based on the consolidated data mart set were evaluated by multiple logistic regression analysis. RESULTS: The overall operative mortality (within 30 days) was 3.8% and the mortality after 3 months was 5.9%. In addition to clinical characteristics, the following laboratory values were identified as independent predictors of 30-day mortality: fasting blood glucose, antithrombine III, partial thromboplastine time and creatinine kinase. As independent predictors of 3-month mortality, the following laboratory values were indentified: fasting blood glucose, serum creatinine, antithrombine III, partial thromboplastine time, lactate dehydrogenase, sodium concentration and serum proteins. The discriminative power of the models increased if laboratory parameters were included in addition to preoperative clinical characteristics (from 0.75 to 0.79 and from 0.75 to 0.78 for 30-day and 3-month mortality, respectively). The discriminative power using the logistic EuroScore was lower (0.71 and 0.7, for 30-day and 3-month mortality, respectively). CONCLUSIONS: Laboratory parameters as objective markers for organ function and nutritional status are useful data for the prediction of 30-day and 3-month mortality after aortic valve replacement. Using modern methods of information technology, these valuable data which are stored electronically in most hospitals, can be used efficiently for research and quality control.     

Body composition of patients on a very low-protein diet: a two-year survey with DEXA.

BACKGROUND: It has been reported that patients on a very-low-protein diet (VLPD) maintain a satisfactory nutritional status because of a conserved adaptive metabolic response. However, only few studies have examined the course of nutritional status and body composition in the long term (2 years). METHODS: Thirteen stable patients (8 men; age, 55 +/- 12 years; glomerular filtration rate (GFR), 15 +/- 5 mL/min) receiving a VLPD (0.3 g/kg/day protein) supplemented with amino acids and ketoanalogues (SVLPD) were studied for 2 years. A joint visit with a physician and a dietitian and routine blood and urine analyses were performed every month. Dual-energy x-ray absorptiometry (DEXA), which was used to assess modification of body composition, and GFR (urinary 51Cr-EDTA) and urinary urea and creatinine excretion, which were used to assess nutritional status and compliance to the diet, were assessed every 3 months. RESULTS: GFR, albumin, and prealbumin levels remained stable. Urea urinary excretion decreased at 3 months and then slightly increased at 2 years, but the calculated protein intake remained low at 0.38 +/- 0.1 g/kg/day. Energy intake remained close to 30 kcal/kg/day. No significant change was observed for total fat mass or percent fat mass. After an initial decrease, lean body mass stabilized at 6 months and then increased significantly from 6 to 24 months (P =.02, paired t-test); the mean increase during this period was of 2 kg, that is, 4.6%. Urinary creatinine excretion showed the same profile. Total bone mass, lumbar or hip site bone mass, and Z-score significantly decreased from T0 to 1 and 2 years (P <.05). CONCLUSION: This study confirms that a supplemented VLPD is nutritionally safe for a long period, but attention must be paid to bone mass.     

Morphological study of some hypothalamic centers in rats after deafferentation of the mediobasal hypothalamus

The volume of the nuclei and nucleoli of certain hypothalamic centers (SON, PVN, SCN, AN, VMN) was determined in control rats and in rats after deafferentation of the mediobasal hypothalamus. Sex differences were found in the parvocellular formations of the control animals: The volumes of nuclei and nucleoli of neurons of AN and VMN, and also of the nucleolus of SCN neurons were larger in females than in males. After deafferentation of the mediobasal hypothalamus the volume of the cell nuclei was increased, especially in hypothalamic formations located outside the isolated zone. This increase was more clearly defined in rats constantly in a state of estrus after the operation. Statistically significant differences between volumes of both nuclei and nucleoli of the cells in subgroups of rats with permanent estrus and with permanent diestrus were found only in the case of SCN. No such differences were found for AN, despite the considerable difference in the constant of luteinizing hormone in the pituitary of the same rats. It is suggested that gonadotropin releasing factors are not produced by the cells of AN and that control over the succession of phases of the sex cycle may be exerted by SCN.Laboratory of Neuroendocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 352–354, March, 1980.