Cardiovascular risk following conversion to belatacept from a calcineurin inhibitor in kidney transplant recipients: a randomized clinical trial

Rationale & Objective: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.Study Design: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.Setting & Participants: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.Intervention: Continuation with a CNI-based regimen or switch to belatacept for 12 months.Outcomes: Comparison of the change in the esti-mated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.Results: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pres-sure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.Limitations: The heterogeneous baseline esti-mated glomerular filtration rate and time from transplantation to trial enrollment in the partici-pants. A limited study duration of 1 year.Conclusions: We found no effects on the calculated CV risk by switching to the belata-cept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.Funding: The trial has received a financial grant from Bristol-Myers Squibb.Trial Registration: EudraCT no. 2013-001178-20.Nephrolog

Comprehensive lung injury pathology induced by mTOR inhibitors

Molecular Targets in Oncology[Abstract] Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall cascade hypothesis of interstitial lung diseases that represents a common, partly underlying synergism among them as well as the lung pathogenesis side effects of mammalian target of rapamycin inhibitors

Hong Kong's foreign direct investment in Guangong Province and its impact in industrial restructuring and the transformation of overseas trade

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN025213 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Cardiac and renal biomarkers in recreational runners following a 21 km treadmill run

10.1002/clc.23459Clinical Cardiology43121443-144

Mid-regional pro-adrenomedullin outperforms N-terminal pro-B-type natriuretic peptide for the diagnosis of acute heart failure in the presence of atrial fibrillation

10.1002/ejhf.1660EUROPEAN JOURNAL OF HEART FAILURE224692-70

Cardiac tamponade complicating leukaemia: immediate chemotherapy or pericardiocentesis?

Although leukaemic infiltration of the pericardium is frequently observed at post-mortem, clinically evident cardiac tamponade is rare. Two cases of cardiac tamponade complicating leukaemia are presented. One patient had cardiac tamponade as the initial presentation of acute lymphoblastic leukaemia and experienced complete resolution of the pericardial effusion within 6 days after chemotherapy without therapeutic pericardiocentesis. The other patient with chronic myeloid leukaemia developed cardiac tamponade requiring pericardiocentesis as the first sign of acute blastic transformation. The roles of early chemotherapy and pericardiocentesis in managing this complication are discussed