Foot burns: A comparative analysis of diabetic and non-diabetic patients

Introduction: Foot burns represent a small part of the body with many challenges. The impact of diabetes on clinical outcomes adds further issues in management that clinicians must consider in their management. These factors have serious implications on morbidity and long term sequelae. Our aim is to analyse epidemiological trends of foot burns and examine the differences between diabetic and non-diabetics at Concord hospital from 2014 to 2019. Methods: A retrospective audit from 2014–19 at Concord General Repatriation Hospital Burns Unit summarised patient demographics, burn injury, diabetic status, operations and length of stay. All foot burn injuries from 2014–19 of all ages and gender that attended Concord burns hospital were included in this study. Results: We treated 797 patients who presented with foot burns, of which 16.2% were diabetic. The average age was higher in diabetics (60.72 years) than non-diabetics (39.72 years) and more males suffered burns compared to females in both groups (p \u3c 0.001). There was a larger portion of elderly patients (greater than 65 years old, 15.1% of total) who sustained foot burns in the diabetic group compared to the non-diabetic group (p \u3c 0.001). The most affected season was summer (27.0%), but diabetic patients were 1.7 times more likely to sustain injury in winter than non-diabetics. Diabetics were 3.8 times more likely to have contact burns compared to non-diabetic patients (p \u3c 0.001). In a multivariable linear regression analysis, factors that contributed to increased length of stay included elderly status, place of event, diabetic status, number of operations, ICU admission, wound infection, amputation, and admission [F (16, 757 = 41.149, p \u3c 0.001, R2 = 0.465]. Conclusions: With the increase of diabetes, our multidisciplinary approach to diabetic foot care should include nursing, medical and surgical disciplines to identify patients at risk. The data highlights that a focus on prevention and education for diabetes is central to optimize glycaemic control and burn management, whilst providing a multidisciplinary network on discharge

COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β’-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β’-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway

Enhanced Starting Control Scheme for PMM-Based Starter/Generator System for MEA

A control approach for aircraft Starter/Generator (S/G) with Permanent Magnet Machine (PMM) operating in Flux Weakening (FW) mode is presented. The proposed strategy helps the previous approaches which are adopted for the Variable Voltage Bus (VVB) or Voltage Wild Bus (VWB) concept for an aircraft Electric Power System (EPS), to cover a wide speed range in motoring and generation modes. Compared to prior works, the proposed control approach adjusts the q-axis reference voltage with a single current regulator, and the maximum available voltage provided by the converter is used to evaluate the d-axis voltage. By adopting the proposed approach, the DC bus voltage can be fully utilized, increasing aircraft efficiency by allowing the S/G system to operate at a wide range of speeds. The results of the analytical design and the performance of the system were verified by time-domain simulations using MATLAB/Simulink and experiments and compared to the conventional method

Outcomes following anastomotic leak from rectal resections, including bowel function and quality of life

Purpose Anastomotic leak (AL) is an uncommon but potentially devastating complication after rectal resection. We aim to provide an updated assessment of bowel function and quality of life after AL, as well as associated short- and long-term outcomes. Methods A retrospective audit of all rectal resections performed at a colorectal unit and associated private hospitals over the past 10 years was performed. Relevant demographic, operative, and histopathological data were collected. A prospective survey was performed regarding patients’ quality of life and fecal continence. These patients were matched with nonAL patients who completed the same survey. Results One hundred patients (out of 1,394 resections) were included. AL was contained in 66.0%, not contained in 10.0%, and only anastomotic stricture in 24.0%. Management was antibiotics only in 39.0%, percutaneous drainage in 9.0%, operative abdominal drainage in 19.0%, transrectal drainage in 6.0%, combination of percutaneous drainage and transrectal drainage in 2.0%, and combination abdominal/transrectal drainage in 1.0%. The 1-year stoma rate was 15.0%. Overall, mean Fecal Incontinence Severity Instrument scores were higher for AL patients than their matched counterparts (8.06±10.5 vs. 2.92±4.92, P=0.002). Patients with an AL had a mean EuroQol visual analogue scale (EQ-VAS) of 76.23±19.85; this was lower than the matched mean EQ-VAS for non-AL patients of 81.64±18.07, although not statistically significant (P=0.180). Conclusion The majority of AL patients in this study were managed with antibiotics only. AL was associated with higher fecal incontinence scores in the long-term; however, this did not equate to lower quality of life scores

Concurrent Intrathecal and Intravenous Nivolumab in Leptomeningeal Disease: Phase 1 Trial Interim Results

There is a critical need for effective treatments for leptomeningeal disease (LMD). Here, we report the interim analysis results of an ongoing single-arm, first-in-human phase 1/1b study of concurrent intrathecal (IT) and intravenous (IV) nivolumab in patients with melanoma and LMD. The primary endpoints are determination of safety and the recommended IT nivolumab dose. The secondary endpoint is overall survival (OS). Patients are treated with IT nivolumab alone in cycle 1 and IV nivolumab is included in subsequent cycles. We treated 25 patients with metastatic melanoma using 5, 10, 20 and 50 mg of IT nivolumab. There were no dose-limiting toxicities at any dose level. The recommended IT dose of nivolumab is 50 mg (with IV nivolumab 240 mg) every 2 weeks. Median OS was 4.9 months, with 44% and 26% OS rates at 26 and 52 weeks, respectively. These initial results suggest that concurrent IT and IV nivolumab is safe and feasible with potential efficacy in patients with melanoma LMD, including in patients who had previously received anti-PD1 therapy. Accrual to the study continues, including in patients with lung cancer. ClinicalTrials.gov registration: NCT03025256

Beyond BRAFV600: Clinical Mutation Panel Testing by Next-Generation Sequencing in Advanced Melanoma

The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had >1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600and NRAS mutations. Melanomas with BRAFNon-V600mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma

Potential impact of missing outcome data on treatment effects in systematic reviews: imputation study

AbstractObjective To assess the risk of bias associated with missing outcome data in systematic reviews. Design Imputation study. Setting Systematic reviews. Population 100 systematic reviews that included a group level meta-analysis with a statistically significant effect on a patient important dichotomous efficacy outcome. Main outcome measures Median percentage change in the relative effect estimate when applying each of the following assumption (four commonly discussed but implausible assumptions (best case scenario, none had the event, all had the event, and worst case scenario) and four plausible assumptions for missing data based on the informative missingness odds ratio (IMOR) approach (IMOR 1.5 (least stringent), IMOR 2, IMOR 3, IMOR 5 (most stringent)); percentage of meta-analyses that crossed the threshold of the null effect for each method; and percentage of meta-analyses that qualitatively changed direction of effect for each method. Sensitivity analyses based on the eight different methods of handling missing data were conducted. Results 100 systematic reviews with 653 randomised controlled trials were included. When applying the implausible but commonly discussed assumptions, the median change in the relative effect estimate varied from 0% to 30.4%. The percentage of meta-analyses crossing the threshold of the null effect varied from 1% (best case scenario) to 60% (worst case scenario), and 26% changed direction with the worst case scenario. When applying the plausible assumptions, the median percentage change in relative effect estimate varied from 1.4% to 7.0%. The percentage of meta-analyses crossing the threshold of the null effect varied from 6% (IMOR 1.5) to 22% (IMOR 5) of meta-analyses, and 2% changed direction with the most stringent (IMOR 5). Conclusion Even when applying plausible assumptions to the outcomes of participants with definite missing data, the average change in pooled relative effect estimate is substantive, and almost a quarter (22%) of meta-analyses crossed the threshold of the null effect. Systematic review authors should present the potential impact of missing outcome data on their effect estimates and use this to inform their overall GRADE (grading of recommendations assessment, development, and evaluation) ratings of risk of bias and their interpretation of the results

Meta-Analyses Proved Inconsistent in How Missing Data Were Handled Across Their Included Primary Trials: A Methodological Survey

Background: How systematic review authors address missing data among eligible primary studies remains uncertain. Objective: To assess whether systematic review authors are consistent in the way they handle missing data, both across trials included in the same meta-analysis, and with their reported methods. Methods: We first identified 100 eligible systematic reviews that included a statistically significant meta-analysis of a patient-important dichotomous efficacy outcome. Then, we successfully retrieved 638 of the 653 trials included in these systematic reviews' meta-analyses. From each trial report, we extracted statistical data used in the analysis of the outcome of interest to compare with the data used in the meta-analysis. First, we used these comparisons to classify the "analytical method actually used" for handling missing data by the systematic review authors for each included trial. Second, we assessed whether systematic reviews explicitly reported their analytical method of handling missing data. Third, we calculated the proportion of systematic reviews that were consistent in their "analytical method actually used" across trials included in the same meta-analysis. Fourth, among systematic reviews that were consistent in the "analytical method actually used" across trials and explicitly reported on a method for handling missing data, we assessed whether the "analytical method actually used" and the reported methods were consistent. Results: We were unable to determine the "analytical method reviews actually used" for handling missing outcome data among 397 trials. Among the remaining 241, systematic review authors most commonly conducted "complete case analysis" (n=128, 53%) or assumed "none of the participants with missing data had the event of interest" (n=58, 24%). Only eight of 100 systematic reviews were consistent in their approach to handling missing data across included trials, but none of these reported methods for handling missing data. Among seven reviews that did explicitly report their analytical method of handling missing data, only one was consistent in their approach across included trials (using complete case analysis), and their approach was inconsistent with their reported methods (assumed all participants with missing data had the event). Conclusion: The majority of systematic review authors were inconsistent in their approach towards reporting and handling missing outcome data across eligible primary trials, and most did not explicitly report their methods to handle missing data. Systematic review authors should clearly identify missing outcome data among their eligible trials, specify an approach for handling missing data in their analyses, and apply their approach consistently across all primary trials