Current Practices of Organ Donation and Transplantation Among Different French-Speaking Countries and Regions

peer reviewedaudience: researcher, professional, studentThe aim of the “Transplantation Sans Frontières” (TSF) questionnaire, which was sent to French-speaking centers in 6 different countries and regions, was to establish the current status of organ donation and transplantation in their environments. It was also to examine ways to collaborate and exchange scientific information, teaching, and training in the field of organ transplantation. The French Society of Transplantation and the Agency of Biomedicine already offer specific programs to expand local activities, and the World Health Organization (WHO) regulates them. Therefore, TSF could be a coordinating platform in the near future

Une cause inhabituelle d'altération neurologique Postopératoire : La Pneumocéphalie

La pneumocéphalie postopératoire est une complication fréquente chez le traumatisé crânien mais relativement rare de la chirurgie intracrânienne. Nous présentons le cas d’un malade de 8 ans qui, après exérèse d’une volumineuse tumeur de 3ème ventricule, a développé une pneumocéphalie importante révélée par un retard de réveil avec mydriase bilatérale aréactive. A travers cette observation et une revue de la littérature, les caractéristiques cliniques, physiopathologiques et thérapeutiques de cette complication seront discutées

Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients

Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 × 107 transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n=19, P=0.002, r=0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients

Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis

BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Machines de perfusion rénale : mécanismes d'action, indications et mise en œuvre

International audienceDe tous temps, la transplantation s'est heurtée aux conséquences des lésions d'ischémie-reperfusion, mais l'emploi actuel de greffons dits marginaux, provenant de donneurs à critères étendus (DCE), pour faire face à la pénurie d'organes, les rend encore plus critiques, nous obligeant à revisiter les concepts de préservation d'organes. La préservation statique (PS) à 4 °C a été pendant longtemps la méthode de référence du fait de sa simplicité et des résultats acceptables avec des greffons de bonne qualité. La préservation dynamique par machine de perfusion (PMP) du greffon rénal revient sur le devant de la scène. Son efficacité est désormais établie de façon formelle pour les greffons de donneurs à critères étendus (> 60ans ou > 50ans avec deux des trois facteurs de risque suivants : décès par accident vasculaire cérébral [AVC], hypertension artérielle [HTA], créatininémie> 132 μmol/l) et ceux décédés après arrêt cardiaque. Elle permet de réduire le taux de non-fonction primaire, de reprise retardée de fonction (RRF), le nombre de séances de dialyse en cas de RRF. Le principal essai randomisé disponible a même démontré une amélioration significative de la survie du greffon rénal à un et trois ans. Les mécanismes d'action sont encore incomplètement compris, mais le principal est vraisemblablement une meilleure protection de la barrière endothéliale, qui reste le lieu du premier « choc » entre donneur et receveur. L'on dispose aujourd'hui d'arguments scientifiques (expérimentaux et cliniques) et économiques irréfutables pour développer l'emploi des machines de perfusion en transplantation rénale. Il est désormais fortement recommandé de perfuser les greffons rénaux prélevés sur des DCE, depuis l'explantation jusqu'à la greffe. Ne pas le faire entraîne une perte de chances pour le receveur. La préservation sur machine est obligatoire pour les greffons de donneurs décédés par arrêt cardiaque, dans le cadre du protocole français. La complexité de la méthode n'est qu'apparente et ne résiste pas à l'expérience et aux bénéfices pour les patients