Brachial vein transposition arteriovenous fistulas for hemodialysis access

BackgroundAn arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, offering lower morbidity, mortality, and cost compared with grafts or catheters. Patients with a difficult access extremity have often lost all superficial veins, and even basilic veins may be obliterated. We have used brachial vein transposition AVFs (BVT-AVFs) in these challenging patients and review our experience in this report.MethodsThe study reviewed consecutive patients in whom BVT-AVFs were created from September 2006 to March 2009. Most BVT-AVFs were created in staged procedures, with the second-stage transposition operations completed 4 to 6 weeks after the first-stage AVF operation. A single-stage BVT-AVF was created when the brachial vein diameter was ≥6 mm.ResultsWe identified 58 BVT-AVF procedures, comprising 41 women (71.0%), 28 diabetic patients (48.3%), and 29 (50.0%) had previous access surgery. The operation was completed in two stages in 45 operations (77.6%) and was a primary transposition in 13 patients. However, five of these were secondary AVFs with previous distal AV grafts or AVFs placed elsewhere; effectively, late staged procedures. Follow-up was a mean of 11 months (range, 2.0-31.7 months). Primary patency, primary-assisted patency, and cumulative (secondary) patency were 52.0%, 84.9%, and 92.4% at 12 months and 46.2%, 75.5%, and 92.4% at 24 months, respectively. Harvesting the brachial vein was tedious and more difficult than harvesting other superficial veins. No prosthetic grafts were used.ConclusionBVT-AVFs provide a suitable option for autogenous access when the basilic vein is absent in patients with difficult access extremities. Most patients required intervention for access maturation or maintenance. Most BVT-AVFs were created with staged procedures. Cumulative (secondary) patency was 92.4% at 24 months

Brachial vein transposition arteriovenous fistulas for hemodialysis access

BackgroundAn arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, offering lower morbidity, mortality, and cost compared with grafts or catheters. Patients with a difficult access extremity have often lost all superficial veins, and even basilic veins may be obliterated. We have used brachial vein transposition AVFs (BVT-AVFs) in these challenging patients and review our experience in this report.MethodsThe study reviewed consecutive patients in whom BVT-AVFs were created from September 2006 to March 2009. Most BVT-AVFs were created in staged procedures, with the second-stage transposition operations completed 4 to 6 weeks after the first-stage AVF operation. A single-stage BVT-AVF was created when the brachial vein diameter was ≥6 mm.ResultsWe identified 58 BVT-AVF procedures, comprising 41 women (71.0%), 28 diabetic patients (48.3%), and 29 (50.0%) had previous access surgery. The operation was completed in two stages in 45 operations (77.6%) and was a primary transposition in 13 patients. However, five of these were secondary AVFs with previous distal AV grafts or AVFs placed elsewhere; effectively, late staged procedures. Follow-up was a mean of 11 months (range, 2.0-31.7 months). Primary patency, primary-assisted patency, and cumulative (secondary) patency were 52.0%, 84.9%, and 92.4% at 12 months and 46.2%, 75.5%, and 92.4% at 24 months, respectively. Harvesting the brachial vein was tedious and more difficult than harvesting other superficial veins. No prosthetic grafts were used.ConclusionBVT-AVFs provide a suitable option for autogenous access when the basilic vein is absent in patients with difficult access extremities. Most patients required intervention for access maturation or maintenance. Most BVT-AVFs were created with staged procedures. Cumulative (secondary) patency was 92.4% at 24 months

Does distributed leadership have a place in destination management organisations? A policy-makers perspective

Within an increasingly networked environment and recent transitions in the landscape of funding for destination management organisations (DMOs) and destinations, pooling knowledge and resources may well be seen as a prerequisite to ensuring the long-term sustainability of reshaped, yet financially constrained DMOs facing severe challenges to deliver value to destinations, visitors and member organisations. Distributed Leadership (DL) is a recent paradigm gaining momentum in destination research as a promising response to these challenges. Building on the scarce literature on DL in a DMO context, this paper provides a policy-makers’ perspective into the place of DL in reshaped DMOs and DMOs undergoing transformation and explores current challenges and opportunities to the enactment and practice of DL. The underpinned investigation used in-depth, semi-structured interviews with policy-makers from VisitEngland following an interview agenda based on the DMO Leadership Cycle. Policy-makers within VisitEngland saw a multitude of opportunities for DMOs with regards to DL, but equally, they emphasised challenges acting as barriers to realising the potential benefits of introducing a DL model to DMOs as a response to uncertainty in the funding landscape

Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novo PTEN mutation.

OBJECTIVE: To describe a patient with a multifocal demyelinating motor neuropathy with onset in childhood and a mutation in phosphatase and tensin homolog (PTEN), a tumor suppressor gene associated with inherited tumor susceptibility conditions, macrocephaly, autism, ataxia, tremor, and epilepsy. Functional implications of this protein have been investigated in Parkinson and Alzheimer diseases. METHODS: We performed whole-exome sequencing in the patient's genomic DNA validated by Sanger sequencing. Immunoblotting, in vitro enzymatic assay, and label-free shotgun proteomic profiling were performed in the patient's fibroblasts. RESULTS: The predominant clinical presentation of the patient was a childhood onset, asymmetric progressive multifocal motor neuropathy. In addition, he presented with macrocephaly, autism spectrum disorder, and skin hamartomas, considered as clinical criteria for PTEN-related hamartoma tumor syndrome. Extensive tumor screening did not detect any malignancies. We detected a novel de novo heterozygous c.269T>C, p.(Phe90Ser) PTEN variant, which was absent in both parents. The pathogenicity of the variant is supported by altered expression of several PTEN-associated proteins involved in tumorigenesis. Moreover, fibroblasts showed a defect in catalytic activity of PTEN against the secondary substrate, phosphatidylinositol 3,4-trisphosphate. In support of our findings, focal hypermyelination leading to peripheral neuropathy has been reported in PTEN-deficient mice. CONCLUSION: We describe a novel phenotype, PTEN-associated multifocal demyelinating motor neuropathy with a skin hamartoma syndrome. A similar mechanism may potentially underlie other forms of Charcot-Marie-Tooth disease with involvement of the phosphatidylinositol pathway

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial

Purpose Benefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs . Methods We tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) . Results Unsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (− 1, 21) vs 10 (− 1, to 21) in subphenotype-2; 1.5 (− 1, 21) vs 12 (− 1, to 21) in suphenotype-3, and 0 (− 1, 21) vs 0 (− 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008). Conclusions We reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500