Summary Background Autochthonous (locally acquired) hepatitis E is increasingly recognised in developed countries, and is thought to be a porcine zoonosis. A range of extra‐hepatic manifestations of hepatitis E infection have been described, but have never been systematically studied. Aim To report the extra‐hepatic manifestations of hepatitis E virus. Methods Retrospective review of data of 106 cases of autochthonous hepatitis E (acute n = 105, chronic n = 1). Results Eight (7.5%) cases presented with neurological syndromes, which included brachial neuritis, Guillain‐Barré syndrome, peripheral neuropathy, neuromyopathy and vestibular neuritis. Patients with neurological syndromes were younger (median age 40 years, range 34–92 years, P = 0.048) and had a more modest transaminitis (median ALT 471 IU/L, P = 0.015) compared to cases without neurological symptoms [median age 64 years (range 18–88 years), median ALT 1135 IU/L]. One patient presented with a cardiac arrhythmia,twelve patients (11.3%) presented with thrombocytopenia, fourteen (13.2%) with lymphocytosis and eight (7.5%) with a lymphopenia, none of which had any clinical consequence. Serum electrophoresis was performed in 65 patients at presentation, of whom 17 (26%) had a monoclonal gammopathy of uncertain significance. Two cases developed haematological malignancies, acute myeloid leukaemia and duodenal plasmacytoma, 18 and 36 months after presenting with acute hepatitis E infection. Conclusions A range of extra‐hepatic manifestations can occur with hepatitis E. Neurological and haematological features of hepatitis E infection are relatively frequent in this UK cohort, and result in significant morbidity which warrants further study.

Immunosuppression with SRL may provide an opportunity to avoid long-term exposure to the nephrotoxicity of CNI. Thus, we have initiated an experimental protocol of IL-2r antibody induction , prednisone, MMF and SRL in pediatric renal transplant recipients (median age 15.5 yr, IQR 8.5, range 1.3-21.7). The recipients were treated with daclizumab every2 wk for the first 2 months, prednisone on a tapering schedule, MMF at 1200 mg/m 2 /dayand SRL given b.i.d. The SRL was dosed to achieve defined target whole blood 12-h trough levels. We performed 24 SRL PK profiles in 13 stable pediatric renal transplant recipients at 1 and 3 months post-transplant. Half-life (T 1/2 ) and terminal T 1/2 were 9.7 (7.1-24.6) and 10.8 (4.4-95.2) hours (median, range) respectively at month 1, and were 9.6 (5-17.8) and 12.1 (4.7-71.0) hours respectively at month 3. SRL trough levels correlated with AUC (r 2 = 0.84, p < 0.001). There was no relationship between SRL and 2 mycophenolic acid (MPA) AUC values (r 2 = 0.04). During the first 3 months post-transplant only one patient experienced severe neutropenia and another patient had subclinical (histologic) evidence of a mild acute rejection episode with no change in renal function. We conclude that the T 1/2 of SRL in pediatric renal transplant recipients not treated with CNI is much shorter than what has been reported for adults, due to rapid metabolism. We conclude that children require SRL dosing every12 h, higher doses and frequent drug monitoring to achieve target SRL concentrations. Previously, young children were reported to have poor short and long-term graft survival. Proposed reasons for this poor survival included an hypothesized heightened immune response, especially in infants (4,5). However, other causes were likely more important. Children are known to have higher rates of drug metabolism, particularly with respect to key cytochrome enzymes compared with adults (6-12). Faster drug metabolism is very likely the reason why cyclosporine T 1/2 is notoriously shorter in children compared with adults. One study determined that cyclosporine T 1/2 was 9.3 h in children, compared with 16-27 h in adults (13). KeywordsTherefore, it is possible that lack of pediatric-specific PK information previously led to insufficient provision of these drugs to children. Thus, suboptimal immunosuppression, rather than an inherent immune hyper-responsiveness, may have been the cause of higher rejection rates previously seen in young children. Improved age-specific dosing, therefore, may have been instrumental in the recently observed improved outcomes in children (14,15).We have initiated an experimental protocol of IL-2r antibody induction, prednisone, MMF and SRL in pediatric renal transplant recipients, including SRL PK studies at 1 and 3 months after transplantation. The goal of this study is to assess SRL PK in children on a CNI-free protocol, and to determine whether these pediatric renal transplant recipients require different doses or dosing schedules of SRL. Patients and methodsAll P...

ObjectivesTo determine why so few patients with chronic heart failure in England, Wales and Northern Ireland take part in cardiac rehabilitation.DesignTwo-stage, postal questionnaire-based national survey.Participants and settingStage 1: 277 cardiac rehabilitation centres that provided phase 3 cardiac rehabilitation in England, Wales and Northern Ireland registered on the National Audit of Cardiac Rehabilitation register. Stage 2: 35 centres that indicated in stage 1 that they provide a separate cardiac rehabilitation programme for patients with heart failure.ResultsFull data were available for 224/277 (81%) cardiac rehabilitation centres. Only 90/224 (40%) routinely offered phase 3 cardiac rehabilitation to patients with heart failure. Of these 90 centres that offered rehabilitation, 43% did so only when heart failure was secondary to myocardial infarction or revascularisation. Less than half (39%) had a specific rehabilitation programme for heart failure. Of those 134 centres not providing for patients with heart failure, 84% considered a lack of resources and 55% exclusion from commissioning contracts as the reason for not recruiting patients with heart failure. Overall, only 35/224 (16%) centres provided a separate rehabilitation programme for people with heart failure.ConclusionsPatients with heart failure as a primary diagnosis are excluded from most cardiac rehabilitation programmes in England, Wales and Northern Ireland. A lack of resources and direct exclusion from local commissioning agreements are the main barriers for not offering rehabilitation to patients with heart failure.

Thirty-four children were entered into a pilot trial of calcineurin inhibitor avoidance after living-donor kidney transplantation, the CN-01 study. Patients were treated with anti-CD25 mAb, prednisone, mycophenolate mofetil, and sirolimus. Twenty patients were maintained on the protocol for up to 3 yr of follow-up. One enrolled patient did not receive the transplant because of a donor problem, eight terminated because of one or more rejection episodes, four terminated because of adverse events, and one was lost to follow-up. Two grafts were lost, one as a result of chronic rejection and the other as a result of posttransplantation lymphoproliferative disorder. There were no deaths. The 6-and 12-mo acute rejection rates were 21.8 and 31.5%, respectively. GFR were stable throughout the course of the study, with a slight downward trend by 6 mo after transplantation followed by a slight upward trend to a mean of 70 ml/min thereafter. Early surveillance graft biopsies frequently showed focal interstitial mononuclear cellular infiltrates without overt vasculitis or tubulitis, but these infiltrates disappeared without treatment. Anti-HLA class I and II antibodies were detected in three patients before transplantation, and all three had acute rejections, including the two patients who lost their grafts. De novo anti-HLA Ab production occurred in only one patient after transplantation. There were two episodes of Epstein Barr virus-related posttransplantation lymphoproliferative disorder, one of which developed after the patient had been terminated from the study. It is concluded that calcineurin inhibitor-free immunosuppression can be safe and effective in pediatric living-donor renal transplantation. However, further modifications that are designed to lessen early rejection rates and decrease complications should be tested before this approach is used routinely.