Indoxyl Sulfate Upregulates Liver P-Glycoprotein Expression and Activity through Aryl Hydrocarbon Receptor Signaling.

In patients with CKD, not only renal but also, nonrenal clearance of drugs is altered. Uremic toxins could modify the expression and/or activity of drug transporters in the liver. We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: , , , , , , , , , , , , , and We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by in human hepatoma cells (HepG2) without modifying the expression of the other transporters.

Genetic and Functional Profiling of CD16-Dependent Natural Killer Activation Identifies Patients at Higher Risk of Cardiac Allograft Vasculopathy.

Background: Cardiac transplantation is an effective therapy for end-stage heart failure. Because cardiac allograft vasculopathy (CAV) is the major cause of late mortality after heart transplant (HT), there is a need to identify markers that reflect inflammatory or cytotoxic immune mechanisms contributing to its onset. Noninvasive and early stratification of patients at risk remains a challenge for adapting individualized therapy.

Severe right ventricular dysfunction is an independent predictor of pre- and post-transplant mortality among candidates for heart transplantation.

Background: Heart transplantation is the gold-standard treatment for end-stage heart failure. However, the shortage of grafts has led to longer waiting times and increased mortality for candidates without priority.

Aims: To study waiting-list and post-transplant mortality, and their risk factors among patients registered for heart transplantation without initial high emergency procedure.

Severe decrease of cyclosporine levels in a heart transplant recipient receiving the direct thrombin inhibitor argatroban.

This case report is about a suspected interaction between argatroban, a direct thrombin inhibitor, and cyclosporine, which occurred in a 60-year-old patient after a second heart transplantation. We explored 4 possible mechanisms of interaction, which are an analytical interference, an idiopathic hemodilution, an increase of renal and hepatic clearance, and a metabolic drug-drug interaction.

Impact of the early reduction of cyclosporine on renal function in heart transplant patients: a French randomised controlled trial.

Background: Using reduced doses of Cyclosporine A immediately after heart transplantation in clinical trials may suggest benefits for renal function by reducing serum creatinine levels without a significant change in clinical endpoints. However, these trials were not sufficiently powered to prove clinical outcomes.

Methods: In a prospective, multicentre, open-label, parallel-group controlled trial, 95 patients aged 18 to 65 years old, undergoing de novo heart transplantation were centrally randomised to receive either a low (130 < trough CsA concentrations <200 μg/L, n = 47) or a standard dose of Cyclosporine A (200 < trough CsA concentrations <300 μg/L, n = 48) for the three first post-transplant months along with mycophenolate mofetil and corticosteroids.

Short-term results of repeat valve replacement: a predictive factor analysis.

Background And Aim Of The Study: The new-generation bioprostheses are associated with a longer lifespan, and therefore tend to be implanted in younger patients. However, with the increase in life expectancy, the trend is towards a higher rate of repeat valve replacement. Hence, the study aim was to evaluate the present mortality and risk factors for repeat valvular surgery.

Heart transplantation in 7 patients from a single family with limb-girdle muscular dystrophy caused by lamin A/C mutation.

We describe 7 transplanted heart recipients from a single family with limb-girdle muscular dystrophy type 1B linked to a mutation of the LMNA gene in the splice donor site of the exon 9 (IVS 9+1:g>a). These patients did not display higher early postoperative or late complications than other heart transplant recipients at a mean follow-up of 8 years (range 1-17 years). Noticeably, there was no case of rhabdomyolysis and skeletal muscle symptoms were not markedly impaired.

Lower risk of infectious deaths in cardiac transplant patients receiving basiliximab versus anti-thymocyte globulin as induction therapy.

Background: Conventional antibody induction therapy is currently used in heart transplantation despite safety concerns. This 6-month, prospective, randomized, multicenter, open-label study examined whether basiliximab offers a tolerability benefit compared with anti-thymocyte globulin (ATG) while maintaining similar efficacy in de novo heart transplant recipients.

Methods: Adult heart transplant recipients were randomized to receive basiliximab (20 mg on Day 0 and Day 4) or ATG (2.

Role of endogenous adenosine as a predictive marker of vasoplegia during cardiopulmonary bypass and postoperative severe systemic inflammatory response.

Objective: Systemic inflammatory response (SIRS) and severe SIRS (SIRS with organ dysfunction) occurring after cardiopulmonary bypass (CPB) are common causes of morbidity and mortality among cardiac surgical patients. These syndromes are often preceded by a profound vasodilation, characterized by vasoplegia occurring during surgery. Many substances have been implicated in their pathophysiology.

Non-invasive diagnostic of cardiac allograft vasculopathy by 31P magnetic resonance chemical shift imaging.

Background: Coronary angiography is still the gold standard for the diagnosis of cardiac allograft vasculopathy (CAV) for which alternative non-invasive diagnostic approaches are currently investigated. In this study, we assessed whether 31P magnetic resonance chemical shift imaging can diagnose CAV by studying variations in cardiac high-energy phosphates in a population of adult heart transplant recipients.

Methods And Results: CAV was defined by coronary angiography as the presence of diffuse coronary irregularities with significant concentric narrowing on epicardial or distal coronary arteries.

31P MRS of heart grafts provides metabolic markers of early dysfunction.

Objective: Early graft failure (EGF) is a life-threatening event still accounting for a significant percentage of early deaths after heart transplantation. We tested whether selected metabolic markers, including high-energy phosphate concentrations measured ex vivo in pre-transplant heart grafts by (31)P magnetic resonance spectroscopy (MRS) are related with early post-transplant outcome.

Methods: During a 3-year period, 26 heart grafts harvested in the vicinity of the transplantation centre were studied.

Complete atrioventricular block decreases left ventricular assist device flow rate.

A 52-year-old man, living at home, had been on left ventricular assistance for 15 months with a Novacor pump (Worldheart, Ottawa, ON, Canada). Following the onset of effort dyspnea that had recently become worse, he was admitted to the hospital. A review of the pump showed that its flow rate had significantly decreased.

Primary valvular surgery in octogenarians: perioperative outcome.

Background And Aim Of The Study: Cardiac surgery in octogenarians is now performed routinely, and generally results in a good improvement in functional capacity. The study aim was to evaluate operative mortality and to identify preoperative and postoperative risk factors of mortality.

Methods: A total of 200 consecutive patients (79 males, 121 females; mean age 83 years; range: 80-90 years) who underwent valvular surgery at the authors' institution between 1991 and 2002 was reviewed.

Valvular surgery in octogenarians: operative risks factors, evaluation of Euroscore and long term results.

Objectives: In the last decade, cardiac surgery in octogenarians is becoming a routinely performed procedure in our Western countries. The functional benefit of this surgery had already been proved. The aim of this study was to evaluate operative mortality, to identify pre- and post-operative risk factors of early and late mortality, to assess the Euroscore count in this high-risk group of patient and to evaluate late results of this surgery.

Toxoplasma gondii retinochoroiditis after cardiac transplantation.

Purpose: To report 4 cases of Toxoplasma gondii retinochoroiditis in patients having recently undergone cardiac transplantation.

Methods: Review of medical records for 4 patients presenting retinochoroiditis and evidence of T. gondii infection.

Transdiaphragmatic hernia 1 year after heart transplantation following implantable LVAD.

Complications after ventricular assist devices placement most frequently consist of bleeding, infection, and thromboembolic events. We describe a late complication after transplantation caused by transdiaphragmatic connection of the device placed in the abdominal position that presented as an acute pulmonary syndrome, misleading initial diagnosis.

Q fever endocarditis: over 14 years of surgical experience in a referral center for rickettsioses.

Background And Aim Of The Study: Q fever endocarditis caused by Coxiella burnetii is the most important etiology of negative blood culture endocarditis. Without specific clinical findings, diagnosis is difficult and prevalence of this life-threatening disease is underestimated.

Methods: Q fever endocarditis was assessed in 19 patients (15 men, four women; age range: 36-79 years) by evaluating clinical and echocardiographic criteria and specific serology.