Conversion from calcineurin inhibitors to belatacept-based immunosuppressive therapy skews terminal proliferation of non-classical monocytes and lowers lymphocyte counts.

Belatacept, a modified form of CTLA-Ig that blocks CD28-mediated co-stimulation of T cells, is an immune-suppressant that can be used as an alternative to calcineurin inhibitors (CNIs). In kidney transplant recipients, belatacept has been associated with improved renal function and reduced cardiovascular toxicity. Monocytes as well as T-lymphocytes play causal roles in the pathophysiology of atherosclerotic disease. We hypothesized that the beneficial impact of the use of belatacept over CNIs on cardiovascular risk could be partly explained by the impact of belatacept therapy on these circulating leukocytes. Hence, we phenotyped circulating leukocytes in transplanted patients with a stable renal function that were randomized between either continuation of CNI or conversion to belatacept in two international studies in which we participated. In 41 patients, we found that belatacept-treated patients consistently showed lower numbers of B-lymphocytes, T-lymphocytes as well as CD14-negative monocytes (CD14NM), especially in non-diabetic patients. Our observation that this decrease was associated to plasma concentrations of TNFα is consistent with a model where CD14NM-production of TNFα is diminished by belatacept-treatment, due to effects on the antigen-presenting cell compartment.

Narrative medicine: A comparison of terminal cancer patients' stories from a Dutch hospice with those of Anatole Broyard and Christopher Hitchens.

Not all physicians readily discuss death with their terminal patients. To explore whether physicians discuss dying with their terminal patients and to pursue an in-depth understanding of patients' perceptions of death, we interviewed terminal cancer patients in a Dutch hospice and compared their stories to quotes from two autobiographies on dying from cancer, Christopher Hitchens' Mortality and Anatole Broyard's Intoxicated by my illness. This narrative medicine study could potentially teach physicians they should discuss impending death to prevent the use of an invasive medical treatment that typically extends the quantity, but not the quality, of life.