Primary Graft Failure after Heart Transplantation

Primary graft failure (PGF) is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised “marginal donors” to try and bridge the gap between “supply and demand.” One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development

Support from the UK Department of Health through its Health Technology Assessment Programme and Arthritis Research

ABSTRACT. Objective. Our aim was to determine areal bone mineral density (BMD a ) and disease-related factors linked with BMD a in adults with a history of juvenile idiopathic arthritis (JIA). Methods. Men and women with a history of JIA attending a young adult rheumatology clinic in Newcastle, UK, underwent dual energy x-ray absorptiometry (DEXA) of the lumbar spine and total hip. Information was obtained about disease duration and subtype, previous treatment including corticosteroid and methotrexate therapy, and large-joint replacement. Subjects completed the modified Health Assessment Questionnaire (HAQ). Blood was taken for assessment of C-reactive protein, erythrocyte sedimentation rate, and rheumatoid factor (RF). Results. Seventy-one women and 16 men, mean age 28.7 and 31.4 years, and mean disease duration 20.6 and 24.0 years, respectively, were studied. Mean BMD a was 0.982 (Z-score = -0.328; 95% CI -0.657, 0.001) and 1.028 g/cm 2 (Z-score = -0.251; 95% CI -1.266, 0.764) in women and men, respectively, at the spine and 0.817 (Z-score = -0.542; 95% CI -0.975, -0.109) and 0.857 g/cm 2 (Z-score = -0.176; 95% CI -2.323, 1.971) at the hip. After adjusting for age and sex, increasing HAQ score was associated with both lower spine BMD a and hip BMD a . Compared with patients with oligoarticular disease, those with enthesitis-related arthritis had higher BMD a at the spine, while those with extended oligoarticular and polyarticular RF-negative disease had lower hip BMD a . Oral corticosteroids and the presence of a large-joint replacement were associated with lower BMD a at both the spine and hip. Conclusion. There was a trend toward low BMD a in women with a history of JIA. These patients may be at risk of the complications of osteoporosis including fragility fractures and should be considered for targeted preventive measures. (First Release June 15 2011

Low vitamin D and the risk of developing chronic widespread pain: Results from the European male ageing study

© 2016 McCabe et al. Background: The association between low levels of vitamin D and the occurrence of chronic widespread pain (CWP) remains unclear. The aim of our analysis was to determine the relationship between low vitamin D levels and the risk of developing CWP in a population sample of middle age and elderly men. Methods: Three thousand three hundred sixty nine men aged 40-79 were recruited from 8 European centres for a longitudinal study of male ageing, the European Male Ageing Study. At baseline participants underwent assessment of lifestyle, health factors, physical characteristics and gave a fasting blood sample. The occurrence of pain was assessed at baseline and follow up (a mean of 4.3 years later) by shading painful sites on a body manikin. The presence of CWP was determined using the ACR criteria for fibromyalgia. Serum 25-hydroxyvitamin D (25-(OH) D) was assessed by radioimmunoassay. Logistic regression was used to determine the relationship between baseline vitamin D levels and the new occurrence of CWP. Results: Two thousand three hundred thirteen men, mean age 58.8 years (SD = 10.6), had complete pain and vitamin data available and contributed to this analysis. 151 (6.5 %) developed new CWP at follow up and 577 (24.9 %) were pain free at both time points, the comparator group. After adjustment for age and centre, physical performance and number of comorbidities, compared to those in upper quintile of 25-(OH) D (≥36.3 ng/mL), those in the lowest quintile ( < 15.6 ng/mL) were more likely to develop CWP (Odds Ratio [OR] = 1.93; 95 % CI = 1.0-3.6). Further adjustment for BMI (OR = 1.67; 95 % CI = 0.93-3.02) or depression (OR = 1.77; 95 % CI = 0.98-3.21), however rendered the association non-significant. Conclusions: Low vitamin D is linked with the new occurrence of CWP, although this may be explained by underlying adverse health factors, particula rly obesity and depression

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel osteoarthritis risk locus

Osteoarthritis (OA) is a common complex disease with high public health burden and no curative therapy. High bone mineral density (BMD) is associated with an increased risk of developing OA, suggesting a shared underlying biology. Here, we performed the first systematic overlap analysis of OA and BMD on a genome wide scale. We used summary statistics from the GEFOS consortium for lumbar spine (n = 31,800) and femoral neck (n = 32,961) BMD, and from the arcOGEN consortium for three OA phenotypes (hip, ncases=3,498; knee, ncases=3,266; hip and/or knee, ncases=7,410; ncontrols=11,009). Performing LD score regression we found a significant genetic correlation between the combined OA phenotype (hip and/or knee) and lumbar spine BMD (rg=0.18, P = 2.23 × 10-2), which may be driven by the presence of spinal osteophytes. We identified 143 variants with evidence for cross-phenotype association which we took forward for replication in independent large-scale OA datasets, and subsequent meta-analysis with arcOGEN for a total sample size of up to 23,425 cases and 236,814 controls. We found robustly replicating evidence for association with OA at rs12901071 (OR 1.08 95% CI 1.05-1.11, Pmeta=3.12 × 10-10), an intronic variant in the SMAD3 gene, which is known to play a role in bone remodeling and cartilage maintenance. We were able to confirm expression of SMAD3 in intact and degraded cartilage of the knee and hip. Our findings provide the first systematic evaluation of pleiotropy between OA and BMD, highlight genes with biological relevance to both traits, and establish a robust new OA genetic risk locus at SMAD3.This work was funded by the Wellcome Trust (WT098051)

OH reactivity in urban and suburban regions in Seoul, South Korea – an East Asian megacity in a rapid transition

South Korea has recently achieved developed country status with the second largest megacity in the world, the Seoul Metropolitan Area (SMA). This study provides insights into future changes in air quality for rapidly emerging megacities in the East Asian region. We present total OH reactivity observations in the SMA conducted at an urban Seoul site (May-June, 2015) and a suburban forest site (Sep, 2015). The total OH reactivity in an urban site during the daytime was observed at similar levels (∼15 s(-1)) to those previously reported from other East Asian megacity studies. Trace gas observations indicate that OH reactivity is largely accounted for by NOX (∼50%) followed by volatile organic compounds (VOCs) (∼35%). Isoprene accounts for a substantial fraction of OH reactivity among the comprehensive VOC observational dataset (25-47%). In general, observed total OH reactivity can be accounted for by the observed trace gas dataset. However, observed total OH reactivity in the suburban forest area cannot be largely accounted for (∼70%) by the trace gas measurements. The importance of biogenic VOC (BVOCs) emissions and oxidations used to evaluate the impacts of East Asian megacity outflows for the regional air quality and climate contexts are highlighted in this study

Telecommunications and the UK government

The first article in this series reviewed the nature of the UK Post Office's monopoly, its relations with government and a number of forces for change. Since then (September 1977), the UK government has published: the government's response to the Carter Committee's proposals; an appendix to the Carter Report; and a 'White Paper' concerning all nationalized industries. This article reviews the government's response to the Carter Committee against the background of the evidence submitted to the Committee, the government's overall policy towards nationalized industries and the political debate concerning that policy. Finally, subsequent political and union responses to the government's telecommunications policy are reported which may result in considerable change.