Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

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Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part I: technological concepts and evolution.

Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates geared to simplified preparation without biochemical blood handling. In this initial article, we describe the conceptual and technical evolution from fibrin glues to platelet concentrates. This retrospective analysis is necessary for the understanding of fibrin technologies and the evaluation of the biochemical properties of 3 generations of surgical additives, respectively fibrin adhesives, concentrated platelet-rich plasma (cPRP) and PRF. Indeed, the 3-dimensional fibrin architecture is deeply dependent on artificial clinical polymerization processes, such as massive bovine thrombin addition. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization.     

ARCHITECT® urine-neutrophil gelatinase-associated lipocalin (u-NGAL) assay as new prognostic marker for clear cell Renal Cell Carcinoma (ccRCC) (preliminary results)

International Urology and Nephrology - Biomarkers for the diagnosis and monitoring treatment response of kidney cancer are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) is a...     

Conservative treatment for postintubation tracheobronchial rupture

BACKGROUND: Postintubation tracheobronchial rupture is usually responsible for unstable intraoperative or postoperative conditions, and its management is discussed. We insist on conservative treatment as a viable alternative after late diagnosis of postintubation tracheobronchial rupture. METHODS: We conducted a retrospective study including 14 consecutive patients treated between April 1981 and July 1998. RESULTS: Twelve tracheobronchial ruptures occurred after intubation for general surgery and two after thoracic surgery. In all cases, the tear consisted of a linear laceration of the posterior membranous wall of the tracheobronchial tree ranging from 2 to 6 cm. One death occurred in a very weak patient unfit to undergo a redo operation for surgical repair. Seven patients were treated conservatively and cured without sequelae. Six patients underwent surgical repair, of whom 2 were diagnosed and repaired intraoperatively. CONCLUSIONS: Aggressive surgical repair is not always mandatory after delayed diagnosis of iatrogenic tracheobronchial rupture. Conservative treatment must often be considered, except after lung resection.     

The association between killer‐cell immunoglobulin‐like receptor (KIR) and KIR ligand genotypes and the likelihood of BK virus replication after kidney transplantation

BK virus is a common opportunistic post‐transplantation viral infection. Although some risk factors have been studied in this context, the contribution of NK cells has not been assessed in detail. In a group of kidney transplant recipients, we studied the association between (i) the likelihood of BK virus replication during the two‐year period after kidney transplantation and (ii) the genotypes of the killer cell immunoglobulin‐like receptor (KIR) repertoire and their human leukocyte antigen (HLA) ligands. Other clinical factors (such as defective organ recovery and immunosuppressive treatment) were also assessed. BK virus replication was observed in 43 of the 103 recipients (41%). Patients with BK virus replication in the plasma were more likely to display defective organ recovery in the first seven days post‐transplantation. BK virus replication was not associated with Missing KIR ligands. However, BK virus replication was more frequent in patients with responsive NK cells (i.e. when a ligand for activating KIRs was not homozygous in the recipient and present in the donor). Our results suggest that defective organ recovery and the recipient's activating KIR repertoire may be related (depending on HLA ligands present in the couple recipient / donor) to the reactivation of BK virus replication after kidney transplantation.     

Predictive Modeling of Tacrolimus Dose Requirement Based on High‐Throughput Genetic Screening

Any biochemical reaction underlying drug metabolism depends on individual gene–drug interactions and on groups of genes interacting together. Based on a high‐throughput genetic approach, we sought to identify a set of covariant single‐nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C₀) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable‐selection strategy to reinforce the stability of the variable‐selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C₀ per dose with a maximum of 44 gene variants (p‐value <0.001 with a permutation test). These models included molecular networks of drug metabolism with oxidoreductase activities and the multidrug‐resistant ABCC8 transporter, which was found in the most stringent model. Finally, we identified an intronic variant of the gene encoding SLC28A3, a drug transporter, as a key gene involved in Tac metabolism, and we confirmed it in an independent validation cohort.