Facteurs influençant le retour au travail après transplantation chez 61 patients rénaux ou hépatiques

Le taux de retour au travail après greffe est généralement bas. Or, on sait que le retour au travail après greffe améliore la qualité de vie des transplantés. Le but de notre étude était donc de comprendre les raisons possibles à ce faible taux en montrant les facteurs professionnels, individuels ou médicaux pouvant l'influencer. Parmi les 61 greffés rénaux ou hépatiques suivis au centre de transplantation d'organe (CTO) du CHUV, 39% ont repris le travail après greffe. Trois facteurs étaient significatifs de retour au travail après greffe, à savoir "travail avant greffe", « diplôme » et « âge<45 ans ». Ainsi, il est utile pour la pratique médicale de connaître les facteurs potentiels influençant le retour au travail car cela permet d'évaluer, au stade prégreffe, les chances de retour au travail et si besoin de proposer des mesures spécifiques le favorisant. -- The rate of return to work after transplantation is generally low, however this improves the quality of life of recipients. The aim of our study was to investigate the low rate after transplantation in 61 renal or liver patients followed at the Transplant Center (CTO) of the CHUV in Lausanne, and to analyse the occupational, individual and medical factors which may influence it. 39% of recipients returned to work after transplantation. The factors "being active pre-transplant", "with diploma" and "age< 45 years old" were significantly related to return to work. In conclusion, knowledge of the factors influencing return to work after transplantation are important for medical practice, in order to propose early medico-socio-professional measures in order to maintain workability.

Haematopoietic stem cell transplantation: activity in Switzerland compared with surrounding European countries.

Haematopoietic stem cell transplantation (HSCT) is a highly specialised procedure used to treat malignancies of the lymphohaematopoietic system as well as some acquired and inherited disorders of the blood. This analysis by the Swiss Blood Stem Cell Transplantation Group, based on data from 2008-2011, describes, treatment rates in Switzerland for specific indications and compares this with data from Germany, France, Italy and the Netherlands, corrected for the size of the population. Differences in transplant rates, in rates for particular indications, and in the use of specific transplant technologies such as use of unrelated donors, use of cord blood or mismatched family donors are described. These data are put in correlation with donor availability from international registries and with number of transplant teams and number of procedures per team all corrected for population size.

The experience of transplantation for patients and their significant ones: A difficult encounter of two worlds

Objectives This paper reports on a longitudinal qualitative study exploring concerns of 60 patients before and after transplantation. Methods Semi-structured interviews were conducted without time constraints in a protected space out of the hospital. Qualitative analysis was performed. Results Prior to transplantation, all patients talked freely about negative feelings, stigmatisation, being misunderstood by others, loneliness and culpability caused by increasing physical dependency or abandoned roles. They mentioned alternative ways to cope (magic, spirituality), and even expressed their right to let go. In a subset of 13 patients, significant ones allowed themselves in the interview, or were integrated on the request of the patients. In this modified setting, two illness-worlds were confronted. If common themes were mentioned (e.g., modified life plans, restricted space, physical and psychological barriers), they were experienced differently. Fear of transplantation or guilt towards the donors was overtly expressed, often for the first time. Mutual hiding of anxiety in order to protect loved ones or to prevent loss of control was disclosed. The significant ones talked about accumulated stress and exhaustion related to the physical degradation of the patient, fear of the unpredictable evolution of illness and financial problems, and stressed their difficulty to adapt adequately to the fluctuating state of the patient. After transplantation, other themes emerged, where difficulty in disclosure was observed: intensive care and near death experiences, being a transplanted person, debt to the donor and his/her family, fear of rejection. Conclusions With the self-imposed strategy of hiding concerns to protect one another, a discrepancy between two illness-worlds was created. When concerns were confronted during the interviews, a new mutual understanding emerged. Patients and their families stated the need for sharing concerns in the course of illness.

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure.

OBJECTIVE: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. DESIGN AND SETTINGS: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. PATIENTS: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. INTERVENTION: Each patient received the two buffers in a randomized sequence over two consecutive days. MEASUREMENTS AND RESULTS: The following variables were determined: acid-base parameters, lactate production and utilization ((13)C lactate infusion), glucose turnover (6,6(2)H(2)-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5 mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing (13)C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8+/-0.8 vs 7.5+/-0.8 ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0+/-2.6 vs 13.6+/-2.6 mmol/kg per min) were similar. (13)C lactate was used as a metabolic substrate, as shown by (13)CO(2) excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. CONCLUSION: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonate.

Retrospective feasibility study of simultaneous integrated boost in cervical cancer using Tomotherapy: the impact of organ motion and tumor regression.

BACKGROUND: Whole pelvis intensity modulated radiotherapy (IMRT) is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB) to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach. PURPOSE: To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB) regression and motion during chemo-radiotherapy (CRT) for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met. METHODS AND MATERIALS: Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR) were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM) was used to evaluate the degree of motion. The Dice's similarity coefficient (DSC) was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses. RESULTS: The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction between CTV-SIB reduction and OAR dose increase. CONCLUSIONS: The CTV-SIB had important regression and motion during CRT, receiving lower therapeutic doses than expected. The OAR had unpredictable shifts and received higher doses. The use of SIB without frequent adaptation of the treatment plan exposes cervical cancer patients to an unpredictable risk of under-dosing the target and/or overdosing adjacent critical structures. In that scenario, brachytherapy continues to be the gold standard approach.

Lenalidomide maintenance after stem-cell transplantation for multiple myeloma.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebo-controlled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS: We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS: Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β(2)-microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P=0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS: Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.).

Humoral and cellular rejection after combined liver-kidney transplantation in low immunologic risk recipients.

Combined liver-kidney transplantation is considered a low risk for immunologic complication. We report an unusual case of identical ABO liver-kidney recipient without preformed anti-human leukocyte antigen (HLA) antibodies, transplanted across a T- and B-cell-negative cross-match and complicated by early acute humoral and cellular rejection, first in the liver then in the kidney. While analyzing the immunologic complications in our cohort of 12 low-risk combined liver-kidney recipients, only one recipient experienced a rejection episode without detection of anti-HLA antibody over time. Although humoral or cellular rejection is rare after combined kidney-liver transplantation, our data suggest that even in low-risk recipients, the liver does not always systematically protect the kidney from acute rejection. Indeed, the detection of C4d in the liver should be carefully followed after combined liver-kidney transplantation.

High-dose therapy and autologous hematopoietic stem cell transplantation in T-cell lymphoma : a single centre experience

Le diagnostic de lymphome représente 4% de tous les cancers et a une incidence particulièrement élevée dans les pays industrialisés. La proportion de lymphomes T, évaluée en Europe et aux Etats Unis, représente environ 5 à 10% des lymphomes. Alors que des progrès très sensibles ont été apportés dans la prise en charge et le pronostic des lymphomes B agressifs durant ces dernières décennies et en particulier depuis le début des années 2000 avec l'utilisation des anticorps anti-CD20 associés à la chimiothérapie, le pronostic des lymphomes T reste très décevant. La survie globale des lymphomes T à 5 ans est estimée entre 28% et 38%. Le bénéfice réel d'une chimiothérapie intensive suivie d'une autogreffe de cellules souches hématopoïétiques périphériques au terme d'un traitement de chimiothérapie d'induction dans le lymphome T périphérique reste débattu. Les résultats des rares études prospectives et des études rétrospectives à disposition sont discordants. Nous avons donc analysé rétrospectivement 43 patients successifs de mars 2000 à mars 2011, atteints de lymphome T, issus de notre base de données du programme autogreffe lausannois. Nos analyses statistiques permettent, sur la base d'un suivi médian de 63 mois, une estimation à 12 ans, de la survie globale de nos patients à 40%, de la survie sans progression à 34% et de la survie sans événement à 30%. Ces chiffres s'inscrivent parfaitement dans les résultats des études prospectives qui montrent un bénéfice de l'autogreffe dans le lymphome T. Parmi les différents paramètres pronostiques habituellement évalués, l'âge et l'absence de symptômes B au diagnostic sont les seuls paramètres statistiquement significatifs en analyse univariée dans notre cohorte. En effet, Les patients de moins de 50 ans et ceux qui ne présentent pas de symptômes B au diagnostic ont un meilleur pronostic. Nous concluons de cette analyse que les patients traités par chimiothérapie intensive et autogreffe de cellules souches hématopoïétiques périphériques ont une survie moyenne supérieure aux résultats rapportés dans la littérature avec des traitements de chimiothérapie conventionnelle de type CHOP. En effet, on estime à environ 50% les patients répondant à une chimiothérapie conventionnelle de type CHOP.

Role of intra-operative duplex ultrasound in living renal donor transplantation

Objective: The treatment of choice in end-stage renal disease is¦transplantation.¦Hemodynamic disturbances can evoke graft loss, while early ultrasound¦identification of vascular problems improves outcome. The primary endpoint¦of this study was to identify differences in post-op complications with and¦without systematic, intraoperative Doppler ultrasound use. A secondary aim¦was to find a predictive resistance index limit which would show where surgical¦reintervention was necessary.¦Methods: Between Jan 2000 and Dec 2010, 108 renal transplants were¦performed from living donors at our institution. In group 1 (n = 67),¦intra-operative duplex ultrasound and intra-parenchymatous resistance index¦measurements assessed patients, while in group 2 (n = 41), no ultrasound was¦performed.¦Results. There were no inter-group differences in the overall post-op¦complication rate or in benefit to graft or patient survival with Doppler use,¦however, significantly more vascular complications (10% vs. 0%, p = 0·02) and¦more acute rejections (37% vs. 10%) occurred in group 2 than in group 1,¦respectively. When the resistance index was <0·5 intra-operatively, immediate¦surgical revision was undertaken to raise the index >0·6.¦Results: There were no inter-group differences in the overall post-op¦complication rate or in benefit to graft or patient survival with Doppler use,¦however, significantly more vascular complications (10% vs. 0%, p = 0·02) and¦more acute rejections (37% vs. 10%) occurred in group 2 than in group 1,¦respectively. When the resistance index was <0·5 intra-operatively, immediate¦surgical revision was undertaken to raise the index >0·6.¦Conclusion: This is the first report demonstrating benefits of systematic¦intraoperative Doppler ultrasound on post-operative complications in renal¦transplantation from living donors. Our results support surgical revision with a¦resistance index <0·5.

Survival impact of lung transplantation for COPD.

Chronic obstructive pulmonary disease (COPD) is the primary indication for lung transplantation (LTx), but survival benefit is still under debate. We analysed the survival impact of LTx in COPD with a new approach, using the BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index. We retrospectively reviewed 54 consecutive lung transplants performed for COPD. The pre-transplant BODE score was calculated for each patient and a predicted survival was derived from the survival functions of the original BODE index validation cohort. Predicted and observed post-transplant survival was then compared. In the subgroups with a BODE score >or=7 and <7, a majority of patients (66% and 69%, respectively) lived for longer after LTx than predicted by their individual BODE index. The median survival was significantly improved in the entire cohort and in the subgroup with a BODE score >or=7. 4 yrs after LTx a survival benefit was only apparent in patients with a pre-transplant BODE score of >or=7. In conclusion, while a majority of COPD patients had an individual survival benefit from LTx regardless of their pre-transplant BODE score, a global survival benefit was seen only in patients with more severe disease. This supports the use of the BODE index as a selection criteria for LTx candidates.

Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation.

BACKGROUND AND OBJECTIVES: Donor cytomegalovirus seropositivity was reported to improve leukemia outcomes in HLA-A2 identical hematopoietic cell transplant (HCT) recipients, due to a possible cross-reactivity of donor HLA-A2-restricted CMV-specific T cells with minor histocompatibility (H) antigen of recipient cells. This study analyzed the role of donor CMV serostatus and HLA-A2 status on leukemia outcomes in a large population of HLA-identical HCT recipients. DESIGN AND METHODS: Leukemia patients transplanted between 1992 and 2003 at the Fred Hutchinson Cancer Research Center were categorized as standard risk [leukemia first remission, chronic myeloid leukemia in chronic phase (CML-CP)] and high risk (advanced disease) patients. Time-to-event analysis was used to evaluate the risk of relapse and death associated with HLA-A2 status and donor CMV serostatus. RESULTS: In standard risk patients, acute leukemia (p<0.001) and sex mismatch (female to male, p=0.004)) independently increased the risk of death, while acute leukemia increased the risk of relapse (p<0.001). In high risk patients acute leukemia (p=0.01), recipient age > or = 40 (p=0.005) and herpes simplex virus (HSV) seropositivity (p<0.001) significantly increased the risk death; HSV seropositivity (p=0.006) increased the risk of relapse. Donor CMV serostatus had no significant effect on mortality or relapse in any HLA group. INTERPRETATION AND CONCLUSION: This epidemiological study did not confirm the previously reported effect of donor CMV serostatus on the outcomes of leukemia in HLA-A2-identical HCT recipients. Addressing the question of cross-reactivity of HLA-A2-restricted CMV-specific T cells with minor H antigens in a clinical study would require knowledge of the patient's minor H antigen genotype. However, because of the unbalanced distribution of HLA-A2-restricted minor H antigens in the population and their incomplete identification, this question might be more appropriately evaluated in in vitro experiments than in a clinical study.

Clinical consequences of sensitisation to minor histocompatibility antigens before allogeneic bone marrow transplantation.

To study sensitisation to minor histocompatibility antigens (mHag) before and after BMT, we measured antidonor CTL activity in five patients who had rejected their graft, and in a control group of 10 leukemic patients who engrafted without complications. All patients were transplanted with marrow from an HLA-identical sibling. Fourteen patients were conditioned with cyclophosphamide (120 mg/kg) and TBI (1350 cGy) and received a T cell-depleted graft, while one patient with aplastic anaemia received cyclophosphamide alone and unmanipulated marrow. Before transplantation, anti-donor CTL activity was detected in two of the 15 patients. These patients rejected their grafts at days 21 and 58, respectively. In the other three patients who rejected their grafts at days 41, 60 and 250, CTL activity was found only after transplantation. In contrast, no anti-donor CTLs could be detected at any time in the 10 patients who engrafted permanently. We have identified some of the mHags recognised during graft rejection by cloning and subsequent specificity analysis of the recipient CTLs. In the patient who rejected at day 41 without detectable immunisation before BMT, the response was directed against HA-1, a minor antigen known to play a role in GVHD. In the other combinations, a significant part of the CTL activity was directed against the male antigen H-Y. In the patient who rejected the marrow of her HLA-identical brother at day 250, two clones recognised H-Y, while five others recognised at least three distinct autosomal mHags. This patient had an HLA-identical sister who expressed only one autosomal mHag that had been recognised by one single T cell clone. After re-transplantation with the marrow of this second donor, the CTL activity could no longer be detected and the patient engrafted without further complications.

Large scale purification of presynaptic plasma membranes from Torpedo marmorata electric organ

The presynaptic plasma membrane (PSPM) of cholinergic nerve terminals was purified from Torpedo electric organ using a large-scale procedure. Up to 500 g of frozen electric organ were fractioned in a single run, leading to the isolation of greater than 100 mg of PSPM proteins. The purity of the fraction is similar to that of the synaptosomal plasma membrane obtained after subfractionation of Torpedo synaptosomes as judged by its membrane-bound acetylcholinesterase activity, the number of Glycera convoluta neurotoxin binding sites, and the binding of two monoclonal antibodies directed against PSPM. The specificity of these antibodies for the PSPM is demonstrated by immunofluorescence microscopy.

A spatial accommodation by neighboring cells is required for organ initiation in Arabidopsis.

Lateral root formation in plants can be studied as the process of interaction between chemical signals and physical forces during development. Lateral root primordia grow through overlying cell layers that must accommodate this incursion. Here, we analyze responses of the endodermis, the immediate neighbor to an initiating lateral root. Endodermal cells overlying lateral root primordia lose volume, change shape, and relinquish their tight junction-like diffusion barrier to make way for the emerging lateral root primordium. Endodermal feedback is absolutely required for initiation and growth of lateral roots, and we provide evidence that this is mediated by controlled volume loss in the endodermis. We propose that turgidity and rigid cell walls, typical of plants, impose constraints that are specifically modified for a given developmental process.