No description available.

Background: Gram-negative bloodstream infections (BSI) are common complications after kidney transplantation. In this cohort study, we evaluated the long-term effect of Gram-negative BSI on allograft survival in kidney transplant recipients. Methods: Among a cohort of 1820 kidney recipients who were prospectively followed at the Mayo Clinic (Rochester, MN) from January 1, 1996, to December 31, 2007, we identified 120 patients with initial episodes of Gram-negative BSI before allograft failure. Multivariable Cox proportional hazard regression was used to examine the association between Gram-negative BSI, as a time-dependent covariate, and allograft and patient survival. Results: The median age of kidney recipients was 51 years (interquartile range, 39-61 years) and 58% were men. Among patients with Gram-negative BSI, 75% had a urinary tract source of infection and Escherichia coli was the most common microorganism (50%). Gram-negative BSI after transplantation was independently associated with allograft loss due to allograft failure or death (hazard ratio [HR], 2.52; 95% confidence intervals [CI], 1.83-3.47; P<0.001), allograft failure with death-censored (HR, 3.17; 95% CI, 2.11-4.76; P<0.001) and all-cause mortality (HR, 2.25; 95% CI, 1.55-3.26; P<0.001). Conclusions: Prevention and proper management of urinary tract infections in kidney recipients is essential to reduce the risk of more serious complications, including Gram-negative BSI, that are associated with reduced allograft and patient survival.

Introdução: O transplante cardíaco exerce um papel relevante no tratamento da insuficiência cardíaca grave. Dentro dos desfechos desfavoráveis a seus resultados, a falência primária do enxerto é reconhecida, como condição de gravidade e mortalidade elevada. Os fatores implicados no aparecimento da falência primária do enxerto ainda não são bem esclarecidos e sua relevância é pouco estudada. Objetivo: Observar se há associação entre hipernatremia do doador e de outras variáveis com o desenvolvimento da falência primária do enxerto (FPE). Métodos: Foram avaliados, retrospectivamente, 200 pacientes submetidos à cirurgia de Transplante Cardíaco Ortotópico (TxC) no Instituto Dante Pazzanese de Cardiologia (IDPC), no período entre 01/01/2001 e 31/12/2010, sendo cotado os níveis de sódio sérico no doador. Além disto, foram avaliados outros fatores relacionados ao doador, ao receptor e ao procedimento cirúrgico. Após a identificação de que o sódio sérico do doador estava elevado no grupo de receptores com FPE, um ponto de corte foi obtido pela curva ROC. O nível de significância dos testes foi de 5%. Um modelo de regressão logística múltipla foi ajustado para avaliar os efeitos de fatores e covariáveis presentes na FPE. Resultados: Entre os pacientes que desenvolveram falência primária do enxerto, a média do sódio sérico foi de 162,0 mEq/l contra 153,6 mEq/l dos que não apresentaram FPE. O valor de corte pela curva ROC foi de 159 mEq/l. Houve diferença significativa (p< 0,03) entre os dois grupos com aumento de ocorrência de falência primária do enxerto nos pacientes que receberam órgãos oriundos de doadores com sódio sérico >159mEq/l. A outra variável que apresentou valor significativo (p=0,04) foi o tabagismo do doador. Conclusão: Com base nesses achados, observou-se que existe associação entre a elevação do sódio sérico do doador com o desenvolvimento de falência primária do enxerto, após o transplante cardíaco. / Introduction: Cardiac transplantation has a role in the treatment of severe heart failure. Within the unfavorable outcomes to their results, the primary graft failure is recognized as a condition of severity and high mortality. The factors involved in the onset of primary graft failure are still unclear and their relevance is poorly studied. Objective: Observe if there is an association between donor hypernatremia and other variables with the development of primary graft failure (PGF). Methods: We retrospectively evaluated 200 patients who underwent surgery for orthotropic heart transplantation (HT) at the Instituto Dante Pazzanese de Cardiologia (IDPC) in the period between 01/01/2001 and 12/31/2010, and evaluated the serum sodium levels in the donor. Furthermore, we assessed other factors related to the donor, the recipient and the surgical procedure. After identification that the donor serum sodium was higher in the group of receivers with PGF, a cutoff point was obtained by ROC curve. The level of significance of the tests was 5%. A multiple logistic regression model was fitted to assess the effects of factors and covariates present in PGF. Results: Among patients who developed primary graft failure, the mean serum sodium was 162.0 mEq/l versus 153.6 mEq/l of which showed no PGF. The cutoff value for the ROC curve was 159 mEq/l. There was an important difference (p <0.03) between the two groups with increased incidence of primary graft failure in patients who received organs from donors with serum sodium> 159 mEq/l. The other variable that showed a significant value (p = 0.04) was smoking from the donor. Conclusion: Based on these findings, we observed that there is an association between elevated serum sodium from the donor with the development of primary graft failure after heart transplantation.

Introdução: O transplante cardíaco exerce um papel relevante no tratamento da insuficiência cardíaca grave. Dentro dos desfechos desfavoráveis a seus resultados, a falência primária do enxerto é reconhecida, como condição de gravidade e mortalidade elevada. Os fatores implicados no aparecimento da falência primária do enxerto ainda não são bem esclarecidos e sua relevância é pouco estudada. Objetivo: Observar se há associação entre hipernatremia do doador e de outras variáveis com o desenvolvimento da falência primária do enxerto (FPE). Métodos: Foram avaliados, retrospectivamente, 200 pacientes submetidos à cirurgia de Transplante Cardíaco Ortotópico (TxC) no Instituto Dante Pazzanese de Cardiologia (IDPC), no período entre 01/01/2001 e 31/12/2010, sendo cotado os níveis de sódio sérico no doador. Além disto, foram avaliados outros fatores relacionados ao doador, ao receptor e ao procedimento cirúrgico. Após a identificação de que o sódio sérico do doador estava elevado no grupo de receptores com FPE, um ponto de corte foi obtido pela curva ROC. O nível de significância dos testes foi de 5%. Um modelo de regressão logística múltipla foi ajustado para avaliar os efeitos de fatores e covariáveis presentes na FPE. Resultados: Entre os pacientes que desenvolveram falência primária do enxerto, a média do sódio sérico foi de 162,0 mEq/l contra 153,6 mEq/l dos que não apresentaram FPE. O valor de corte pela curva ROC foi de 159 mEq/l. Houve diferença significativa (p< 0,03) entre os dois grupos com aumento de ocorrência de falência primária do enxerto nos pacientes que receberam órgãos oriundos de doadores com sódio sérico >159mEq/l. A outra variável que apresentou valor significativo (p=0,04) foi o tabagismo do doador. Conclusão: Com base nesses achados, observou-se que existe associação entre a elevação do sódio sérico do doador com o desenvolvimento de falência primária do enxerto, após o transplante cardíaco. / Introduction: Cardiac transplantation has a role in the treatment of severe heart failure. Within the unfavorable outcomes to their results, the primary graft failure is recognized as a condition of severity and high mortality. The factors involved in the onset of primary graft failure are still unclear and their relevance is poorly studied. Objective: Observe if there is an association between donor hypernatremia and other variables with the development of primary graft failure (PGF). Methods: We retrospectively evaluated 200 patients who underwent surgery for orthotropic heart transplantation (HT) at the Instituto Dante Pazzanese de Cardiologia (IDPC) in the period between 01/01/2001 and 12/31/2010, and evaluated the serum sodium levels in the donor. Furthermore, we assessed other factors related to the donor, the recipient and the surgical procedure. After identification that the donor serum sodium was higher in the group of receivers with PGF, a cutoff point was obtained by ROC curve. The level of significance of the tests was 5%. A multiple logistic regression model was fitted to assess the effects of factors and covariates present in PGF. Results: Among patients who developed primary graft failure, the mean serum sodium was 162.0 mEq/l versus 153.6 mEq/l of which showed no PGF. The cutoff value for the ROC curve was 159 mEq/l. There was an important difference (p <0.03) between the two groups with increased incidence of primary graft failure in patients who received organs from donors with serum sodium> 159 mEq/l. The other variable that showed a significant value (p = 0.04) was smoking from the donor. Conclusion: Based on these findings, we observed that there is an association between elevated serum sodium from the donor with the development of primary graft failure after heart transplantation.

yes / Type 2 diabetes (T2DM) confers increased risk of endothelial dysfunction, coronary heart disease, and vulnerability to vein graft failure after bypass grafting, despite glycaemic control. This study explored the concept that endothelial cells (EC) cultured from T2DM and nondiabetic (ND) patients are phenotypically and functionally distinct. Cultured human saphenous vein- (SV-) EC were compared between T2DM and ND patients in parallel. Proliferation, migration, and in vitro angiogenesis assays were performed; western blotting was used to quantify phosphorylation of Akt, ERK, and eNOS. The ability of diabetic stimuli (hyperglycaemia, TNF-α, and palmitate) to modulate angiogenic potential of ND-EC was also explored. T2DM-EC displayed reduced migration (~30%) and angiogenesis (~40%) compared with ND-EC and a modest, nonsignificant trend to reduced proliferation. Significant inhibition of Akt and eNOS, but not ERK phosphorylation, was observed in T2DM cells. Hyperglycaemia did not modify ND-EC function, but TNF-α and palmitate significantly reduced angiogenic capacity (by 27% and 43%, resp.), effects mimicked by Akt inhibition. Aberrancies of EC function may help to explain the increased risk of SV graft failure in T2DM patients. This study highlights the importance of other potentially contributing factors in addition to hyperglycaemia that may inflict injury and long-term dysfunction to the homeostatic capacity of the endothelium.

No description available.

EINLEITUNG: Die externe Stabilisierung von Venengrafts soll die Scherkräfte auf die Venenwand vermindern und dadurch die Ausbildung einer Neointimaproliferation reduzieren. In experimentellen Modellen wurde diese Hypothese im Kurzzeitversuch überprüft. Es fanden sich in diesem Zeitraum widersprüchliche Ergebnisse. Ziel unserer Untersuchung war es, in einem neuen Modell der arterialisierten segmentalen Vena-jugularis-Transposition auf die infrarenale Aorta den Einfluss einer externen Fibrinkleberstabilisierung auf die Neointimabildung des Venengrafts im Langzeitversuch darzustellen. MATERIAL UND METHODEN: Männlichen Wistar-Ratten wurden Segmente der Vena jugularis entnommen und in Flussrichtung, nach Entfernen eines Aortensegmentes, in die infrarenale Aorta eingebracht. Somit entspricht dieses einem Venenbypassmodell mit komplett arterialisiertem Venengraft. Vor

Introduction Bypass surgery for infrainguinal disease is indicated when a patient presents with chronic (disabling claudication or chronic limb-threatening ischaemia) or acute ischemia. Duplex ultrasound surveillance can be used in the follow-up period to detect grafts in risk of failure. If detected before occlusion occurs an intervention can prolong patency. Aim The purpose of this study was to evaluate the outcome of the procedure, whether there are factors associated with no improvement, and to elucidate the value of routine ultrasound surveillance. Methods Patients who underwent lower extremity bypass surgery at Falu hospital between 2010 and 2020 were identified from the national registry Swedvasc. Clinical outcome was based on change in the Rutherford classification. Duplex ultrasound measured peak systolic velocities. A significant stenosis was defined as a 2-3.5-fold increase in ratio of adjacent velocities in the bypass. For a non-significant stenosis, the ratio had to be increased but by less than 2 times. Results 114 patients underwent bypass surgery. Mean age was 70 years. Postoperative surveillance was carried out for 78 patients. Of these, 40 (51.3%) presented with an abnormality and further 30 of them (75%) received further intervention. There was a correlation between cardiac risk and outcome at the 30-day follow-up. For the majority of the not-surveilled, a major adverse event occurred within 1 year. Conclusions Bypass surgery was beneficial for the majority. Cardiac risk was a negative predictor for outcome. Most patients attending the surveillance benefited from early detection of risk of graft failure. To improve its value and efficacy, guidelines are needed within the clinic.

La prédiction du devenir du greffon et de sa survie permettrait d’optimiser la prise en charge des patients transplantés. Le suivi des patients transplantés rénaux inclue des mesures répétées de marqueurs longitudinaux tels que la créatinine sérique et l’exposition aux médicaments immunosuppresseurs. L’approche statistique récemment proposée des modèles conjoints permet d’analyser la relation entre un processus longitudinal et la survenue d’un événement clinique. Dans la première partie de ce travail de thèse, nous avons utilisé les modèles conjoints à classes latentes pour étudier l’impact du profil de créatinine sérique au cours des 18 premiers mois post-greffe sur la survie du greffon à long terme. Dans la cohorte étudiée, trois groupes homogènes caractérisés par une trajectoire spécifique de l’évolution de la créatinine sérique en fonction du temps et un risque d’échec de greffe spécifique ont été identifiés. Les probabilités individuelles de l’échec de greffe pendant les 10 premières années post-transplantation ont été calculées sur la base du modèle conjoint développé. Chez les patients qui n’avaient pas développé d’anticorps anti-HLA spécifiques du donneur, le risque d’échec de greffe en fonction du temps était prédit avec un niveau de performance satisfaisant en termes de spécificité, sensibilité et précision.L’utilité clinique de cet outil devra être évaluée avec une approche dynamique. Dans une seconde partie, les modèles non linéaires à effets mixtes combinés avec l’approche des modèles de mélange a été utilisée pour analyser (i) l’association entre la variabilité de l’exposition au tacrolimus au cours du temps et l’adhésion au traitement rapportée par le patient et (ii) l’impact de cette variabilité d’exposition sur le risque de rejet aigu. Ce modèle a montré un effet significatif de la variabilité de l’exposition au cours du temps du tacrolimus sur la survenu de rejet aigu au-delà de 3 mois post-transplantation. Au contraire, aucune association entre l’adhésion et la variabilité de l’exposition au tacrolimus d’une part, et le risque de rejet aigu d’autre part n’a été observée dans cette étude qui n’incluait que des patients modérément non-adhérents. Ce résultat pose la question de l’impact d’une non adhésion modérée sur le devenir du greffon. / Prediction of graft outcome would be useful to optimize patient care. Follow-up of kidneytransplant patients include repeated measurements of longitudinal markers, such as serum creatinine and immunosuppressive drug exposure. Recently proposed joint models areappropriate to analyze relationship between longitudinal processes and time-to-event data. In the first part of present work, we used the approach of joint latent class mixed models tostudy the impact of time-profiles of serum creatinine collected within the first 18 months after kidney transplantation on long-term graft survival. The studied cohort was parted into three homogenous classes with a specific time-evolution of serum creatinine and a specific risk of graft failure. The individual predicted probabilities of graft failure up to 10 years posttransplantation, calculated from this joint model were satisfying in terms of sensitivity, specificity and overall accuracy, for patients who had not developed de novo donor specificanti-HLA antibodies. The clinical usefulness of developed predictive tooI needs to beevaluated with a dynamic approach. In the second part, non-linear mixed effects models witha mixture of distribution for random effects were used to investigate (i) the associationbetween variability over time of tacrolimus exposure and self-reported drug adherence and(ii) the impact of this variability on the acute rejection risk. This model found a significantimpact of tacrolimus time-exposure variability on acute rejection onset beyond 3 months posttransplantation. On the contrary, no association between adherence and (i) variability oftacrolimus time-exposure and (ii) acute rejection was observed in our study which included moderate non-adherent patients only. This result questions the impact of moderate nonadherence on graft outcome.

Une attention particulière doit être accordée aux jeunes patients transplantés du rein, qui sont prioritaires en France dans l’attribution de greffon rénal. Les objectifs de cette thèse étaient 1) d’étudier la dynamique du risque instantané de la perte du greffon en fonction de l’âge courant après la transplantation chez les jeunes ; 2) de réaliser un revue systématique des modèles de prédiction de perte du greffon rénal tout âge confondu; et 3) de développer et valider un modèle de prédiction adapté à cette jeune population. Pour répondre aux objectifs 1 et 3, nous avons utilisé les données des registres nationaux français REIN et CRITAL qui incluent de manière exhaustive tous les patients transplantés rénaux pédiatriques. Pour l’Objectif 1, une méthode statistique en deux étapes a permis de mettre en évidence une augmentation accrue du risque instantané de perte du greffon au moment de l’adolescence. Pour l’Objectif 2, une revue systématique des articles publiés entre 2005 et 2015 a montré qu’aucun outil prédictif de la perte du greffon n’avait été spécifiquement proposé pour les patients pédiatriques, ni aucun outil de prédiction dynamique tout âge confondu. Pour l’Objectif 3, nous avons développé et validé par validation croisée interne un modèle de prédiction dynamique de perte du greffon pour les jeunes transplantés, à partir d’un modèle conjoint à effets aléatoires partagés. Ce modèle incluait des prédicteurs classiques à l’inclusion défini par le 90ième jour après la transplantation (des caractéristiques du receveur (sexe, âge à la transplantation, durée de dialyse pré-greffe, maladie rénale initiale, nadir du DFGe entre la transplantation et J90), du donneur (âge, type), et de la transplantation (durée d’ischémie froide, nombre d’incompatibilités HLA, statut donneur/receveur pour sérologie CMV)). Le modèle incluait également la trajectoire du DFG estimé après la transplantation, en supposant que le risque instantané de perte du greffon dépendait à la fois du niveau courant du DFG mais aussi de sa pente courante. Nos résultats indiquent que ce modèle avait de bonnes performances prédictives (AUC à 5 ans variant de 0.75 à 0.86 selon les temps de prédiction après la transplantation), bien meilleures que le modèle de Cox classique ne tenant compte que des prédicteurs à l’inclusion (AUC à 5 ans variant de 0.56 à 0.62). Ce modèle permettant la mise à jour à chaque visite clinique après la transplantation, du risque futur de la perte du greffon en fonction de toutes les valeurs observées précédentes du DFG, devra être validé sur d’autres populations que la population française. Nous pensons en effet qu’un tel outil pourrait à terme être utile dans le suivi clinique des jeunes patients transplantés rénaux. / Particular attention should be paid to young patients transplanted from the kidney, which have priority in France in the assignment of renal graft. The objectives of this thesis were 1) to study the dynamics of the hazard of graft failure by current age after transplantation in young people; 2) to carry out a systematic review of prediction models for renal graft failure at all ages; and (3) to develop and validate a prediction model for this young population. To achieve Objectives 1 and 3, we used data from the French national registries REIN and CRISTAL, which included all pediatric renal transplant patients. For Objective 1, a two-stage statistical method revealed an increase in the hazard of graft failure during adolescence. For Objective 2, a systematic review of articles published between 2005 and 2015 showed that no predictive tool for graft failure has been specifically proposed for pediatric patients, as well as no dynamic predictive model for any age. For Objective 3, we developed and validated using internal cross-validation a dynamic prediction model of graft failure for young transplanted patients, using a joint model with shared random effects. This model included standard baseline predictors at the 90th day after transplantation (characteristics of the recipient (sex, age at transplantation, pretrasplant dialysis duration, primary renal disease, nadir of eGFR at J90), the donor (age and type), and transplantation (duration of cold ischemia, number of HLA incompatibilities, donor/recipient cytomegalovirus (CMV) serology status). The model also included the trajectory of GFR estimated after transplantation, assuming that the hazard of graft failure depended on both the current value of eGFR and its current slope. Our results indicate that this model had good predictive performances (AUC at 5 years ranging from 0.75 to 0.86 according to the time at prediction after transplantation), which were much better than the standard Cox model accounting for baseline predictors only (5-year AUC variant from 0.56 to 0.62). This model which allows the prediction of graft failure to be updated at each clinical visit after transplantation based on all previous observed values of eGFR, should be validated on populations other than the French population. We believe that such a tool could ultimately be useful in the clinical follow-up of young kidney transplanted patients.