Pathologic classification of antibody-mediated rejection correlates with donor-specific antibodies and endothelial cell activation.

Background: Humoral immune responses during heart transplantation may result in antibody-mediated rejection (AMR), which is now taken into account on endomyocardial biopsy (EMB) specimens and ranked according to the pathologic AMR (pAMR) grades of the International Society for Heart and Lung Transplantation classification. This classification might benefit from new immunohistological markers and validation by others biomarkers, namely donor-specific antibodies (DSA).

Methods: From the 293 protocol EMBs performed in 113 patients in our institution during a 1-year period for this prospective study, 280 EMB specimens were available with both histology and immunohistochemistry.

Expression of calcineurin activity after lung transplantation: a 2-year follow-up.

The objective of this pharmacodynamic study was to longitudinally assess the activity of calcineurin during the first 2 years after lung transplantation. From March 2004 to October 2008, 107 patients were prospectively enrolled and their follow-up was performed until 2009. Calcineurin activity was measured in peripheral blood mononuclear cells.

Ciclosporin population pharmacokinetics and Bayesian estimation in thoracic transplant recipients.

Background And Objectives: Therapeutic drug monitoring of ciclosporin has been recognized as an essential tool in the management of allograft transplant recipients, as it could help improve their outcome. However, there is still no consensus about the optimal method for monitoring ciclosporin after thoracic transplantation. Better knowledge of the pharmacokinetics of ciclosporin in thoracic transplant patients and design of tools dedicated to ciclosporin monitoring could help its practice and its outcome in this population of patients.

Pulmonary resection after lung transplantation in cystic fibrosis patients.

Pulmonary resection after lung transplantation in end-stage cystic fibrosis presents unique challenges, and scant literature exists to guide physicians. We retrospectively reviewed 78 transplants for cystic fibrosis performed between 2003 and 2008. Fourteen patients underwent posttransplantation pulmonary resection.

Risk factors for post-transplant lymphoproliferative disease in patients with cystic fibrosis.

The objective of this study was to retrospectively analyze risk factors associated with post-transplant lymphoproliferative disease (PTLD) in a cohort of 112 lung transplant recipients with cystic fibrosis (CF). Prior to transplantation, patients were tested for Epstein-Barr virus (EBV), human herpesvirus (HHV types 1, 2, 3, 6, and 8), herpes zoster virus, and cytomegalovirus (CMV) serologies. PTLD diagnosis was established based on increased EBV viral charge plus clinical/radiographic findings and confirmed by biopsy.

Pharmacological considerations for azole antifungal drug management in cystic fibrosis lung transplant patients.

This paper aims to present our experience in the pharmacological approach of the management of azole antifungal drugs in cystic fibrosis lung transplant patients. Cystic fibrosis (CF) lung transplantation is associated with multi-factorial care management, because of immunosuppressive requirements, risk of infections, frequency of gastro-oesophageal reflux disease, hepatic alterations and CF pharmacokinetics (PK) specificities that result in important PK variability. CF is associated with frequent colonization of the airways by filamentous fungi, especially by Aspergillus species.

Effect of cytochrome P450 2C19 genotype on voriconazole exposure in cystic fibrosis lung transplant patients.

Purpose: Voriconazole is widely used to treat invasive aspergillosis after lung transplantation. In cystic fibrosis patients, the interindividual variability in drug disposition complicates the optimal voriconazole dosing and increases the risk of toxicity. The objective of this retrospective study was to evaluate the influence of CYP2C19 genotype on voriconazole response in lung transplant patients with cystic fibrosis.

Safe management of tacrolimus together with posaconazole in lung transplant patients with cystic fibrosis.

Oral posaconazole (PSZ), an azole antifungal drug, was recently introduced for the treatment of invasive fungal infections. The prescription of PSZ together with the immunosuppressant tacrolimus (TRL) was evaluated in 14 lung transplant patients with cystic fibrosis. PSZ inhibited CYP3A4 TRL metabolism, resulting in a decrease of TRL dose by a factor of 3, with tapering to a mean of 2 mg/d.

Mechanical ventricular assistance in heart failure: pathology of the cardiac apex removed during device implantation.

Background: Ventricular assistance device (VAD) implantation provides large ventricular core biopsies available for pathological assessment. We present here the pathological data from 60 apex removed during a 7-year-period in a single institution.

Results: The most frequent specific lesions were ischemic myocardial damage.

Cardiac stem cells in the real world.

Objective: Cardiac stem cell transplantation as a potential means of regenerating infarcted myocardium is currently receiving a great deal of interest. However, data on these endogenous cardiac precursors are primarily derived from animal studies, and their clinical relevance still remains elusive.

Methods: We prospectively screened 32 endomyocardial biopsies harvested from heart transplant recipients (off rejection episodes) and 18 right appendage biopsies collected during coronary artery bypass surgery, and processed the tissue specimens for the immunohistochemical detection of markers of stemness (c-kit, MDR-1, Isl-1), hematopoietic origin (CD45), mast cells (tryptase), endothelial cells (CD105), and cardiac lineage (Nkx2.

Unilateral pulmonary edema after pulmonary embolism in a bilateral lung transplant patient.

We report a case of unilateral pulmonary edema due to the decompensation of an asymptomatic ipsilateral pulmonary venous stenosis by a contralateral pulmonary embolism. Emergency surgery included pulmonary embolectomy and refashioning of the stenotic pulmonary venous anastomosis.

Human leukocyte antigen sensitization in ventricular assist device recipients: a lesser risk with the DeBakey axial pump.

Background: Previous reports, all concerning pulsatile devices, have indicated an increased risk of development of circulating antileukocyte antigen (HLA; human leukocyte antigen) antibodies during ventricular assist device (VAD) support. We investigated sensitization in patients implanted with the DeBakey VAD (MicroMed Technology, Inc, Houston, TX) axial flow pump as a bridge to heart transplantation.

Methods: Inclusion criteria for this prospective study were the following.

Acute vascular humoral rejection in a sensitized cardiac graft recipient: diagnostic value of C4d immunofluorescence.

A 37-year-old female patient had a cardiac transplantation for dilated cardiomyopathy. She was sensitized by two pregnancies showing anti-human leukocyte antigen I and II antibodies. The pretransplantation crossmatch was negative, but she developed acute humoral rejection characterized by vascular C4d deposits, arteriolitis, and intravascular leukocyte accumulation and adhesion in venules.

Human leukocyte antigen-G expression after heart transplantation is associated with a reduced incidence of rejection.

Background: Human leukocyte antigen (HLA)-G, a nonclassic major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface, is known to protect the fetus from maternal cellular immunity. In a preliminary study, we showed that HLA-G is expressed in the hearts of some patients after heart transplantation.

Methods And Results: In the present study, a larger number of patients was investigated to confirm this finding and to look for possible correlations between HLA-G expression and the number and types of rejection.