Reduction in mortality associated with secondary cytomegalovirus prophylaxis after solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) is the most important viral pathogen in solid organ transplant (SOT) recipients. The role of secondary CMV prophylaxis in this population remains unclear. METHODS: Retrospective cohort study in a single center. SOT recipients treated for CMV infection from 2007 to 2014 were studied to determine the efficacy and safety of secondary prophylaxis and its impact on graft loss and mortality. The outcome variable was CMV replication in the first 3 months after the end of therapy. Secondary variables were crude mortality and graft lost censored at 5 years after transplantation. Propensity score for the use of secondary prophylaxis was used to control selection bias. RESULTS: Of the 126 treated patients, 103 (83.1%) received CMV secondary prophylaxis. CMV relapse occurred in 44 (35.5%) patients. The use of secondary prophylaxis was not associated with fewer relapses (34.0% in patients with prophylaxis vs 42.9% in those without prophylaxis, P = .29). After a mean follow-up of 32.1 months, graft loss was not different between both groups but patient mortality was significantly lower in patients who received secondary prophylaxis (5.8% vs 28.6%, P = .003). CONCLUSION: Secondary prophylaxis did not prevent CMV infection relapse but it was associated with improved patient survival.

Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation.

OBJECTIVES: To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). METHODS: We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. RESULTS: We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p <0.001) within the 6 months prior to the onset of late IPA. After multivariate adjustment, previous occurrence of IRE (OR 19.26; 95% CI 2.07-179.46; p 0.009) was identified as an independent risk factor for late IPA. CONCLUSION: More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

More Than 1000 Kidney Transplants Performed in Pamplona, Navarra: Data From the Collaborative Transplant Study.

INTRODUCTION: The Kidney Transplant Program started at the Clinica Universidad de Navarra (Pamplona, Spain) in September of 1969. The 1000th kidney transplant was performed in September 2015. Data from kidney transplants have been included in the Collaborative Transplant Study since 1983. MATERIALS AND METHODS: Data on patient and graft survival of the 635 kidney transplants (557 first kidney transplants and 78 second kidney transplants) performed in the Clinica Universidad de Navarra between 1990 and 2014, as well as the estimated average life of the grafts are described and compared with data from the more than 150,000 European kidney transplants included in the Collaborative Transplant Study in the same period. RESULTS: Data of our patient and graft survival are statistically significantly better (P < .05) than those of the over 150,000 European transplants analyzed in the Collaborative Transplant Study in the same period. The estimated half-life of the kidney transplants performed in our Center is 18.5 years for first transplants and 15.7 years for second transplants, compared to 13.9 and 11.2 years, respectively, calculated for the European transplants. CONCLUSIONS: Data obtained from the Collaborative Transplant Study confirm excellent graft survival in our Center with an estimated half-life higher than that of the European transplants included in this study.

Short-Term Outcomes of 100 Consecutive Kidney Transplantations in a 3-Year Period: A Single-Center Experience.

BACKGROUND: The results of kidney transplantation have improved significantly in the last decade with patient and graft survival rates that range from 92% to 95%. METHODS: We analyzed the clinical results in the last 100 consecutive patients with a follow-up of 6-42 months at our institution. We also made a general evaluation of the patients before surgery as candidates for transplantation and divided them into 3 groups (good, moderate, and poor). RESULTS: We had 8 living donors and 92 cadaveric kidney transplantation cases. Principal cause of donor death was cerebrovascular disease accounting for 64%. Mean age of recipients was 55.1 ± 12.9 years with a total of 65 males. Currently there are 96 functioning allografts. During this 3-year period, 2 patients suffered graft loss and 2 patients died with a functioning allograft. We studied whether there were statistically significant differences in renal function (Modification of Diet in Renal Disease Study Equation [MDRD]) at 12 months and at last visit with respect to the evaluation of recipient as candidate for renal transplantation. CONCLUSION: Our observations suggest great improvement of early results of renal transplantation in recent years, including complex cases. In this 3-year period we had a patient survival rate of 98% and a graft survival rate of 96% of cases. Further dedicated prospective studies that aim to evaluate or to propose possible recipient-related predictors for kidney transplantation outcomes in different populations are needed.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

¿Ha llegado el momento de buscar la escala de Wells 4.0? / Is time to search the Wells Score 4.0?

Antecedentes: El modelo de Wells para la trombosis venosa profunda presenta problemas para su implementación en las áreas de urgencias hospitalarias debido, fundamentalmente, a la complejidad de su aplicación. Objetivo: Evaluar si la inclusión del dímero D como un predictor podría repercutir en una simplificación de dicho modelo. Pacientes y métodos: Sobre una base de datos retrospectiva de pacientes estudiados por trombosis venosa profunda se aplicó un modelo de regresión logística en el que se incluyeron los 10 predictores del modelo de Wells y el resultado del dímero D. El diagnóstico se realizó con una ecografía de compresión con señal Doppler. El dímero D se determinó mediante una técnica cuantitativa de látex, una técnica de inmunofiltración o una técnica turbidimétrica. Resultados: Se estudiaron 577 pacientes (mujeres: 54,1%) con una edad media de 66,7 (14,2) años y un porcentaje de trombosis venosa profunda del 25,1%. Solo 4 variables resultaron independientes, construyéndose un modelo ponderado con una mayor capacidad predictiva (área bajo la curva) que el modelo original (0,844 vs. 0,751, p < 0,001). Ambos modelos mostraron una seguridad aceptable, con una tasa de fracasos similar (0,8% vs. 1%). El modelo simplificado permitió seleccionar a un mayor porcentaje de pacientes en los que podría no haberse realizado la prueba de imagen (20,6% vs. 15,8%, p = 0,039). Conclusiones: La introducción del dímero D en un modelo de regresión permite simplificar el modelo de Wells y mantener su misma eficacia y seguridad, lo que podría mejorar su implementación en las áreas de urgencias hospitalarias (AU)

Background: Wells score for deep vein thrombosis presents problems for implementation in the hospital emergencies, mainly due to the complexity of its enforcement. Objective: To assess whether the inclusion of D-dimer as a predictor might lead to a simplification of this clinical decision rule. Patients and methods: A database of deep vein thrombosis patients was studied by logistic regression model in which the 10 predictors in the Wells score and the dimer D were included. The diagnosis was made with compression ultrasonography with Doppler signal. D-dimer was determined by a quantitative method of latex, a technique immunofiltration or a turbidimetric technique. Results: 577 patients (54.1% women) were studied, with a mean age of 66.7 (14.2) years. 25.1% were diagnosed with deep vein thrombosis. Only four variables were independent, building a weighted model with greater predictive ability (area under the curve) than the original model (0.844 vs. 0.751, p<0.001). Both models showed an acceptable safety, with a similar rate of failure (0.8% vs. 1%). The simplified model allowed to select a higher percentage of patients who could have benefited from the non performance of the imaging test (20.6% vs. 15.8%, p=0.039). Conclusions: The introduction of D-dimer in a regression model simplifies the Wells score and maintain the same efficacy and safety, which could improve its implementation in the hospital emergencies (AU)

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

Is time to search the Wells Score 4.0? / ¿Ha llegado el momento de buscar la escala de Wells 4.0?

BACKGROUND: Wells score for deep vein thrombosis presents problems for implementation in the hospital emergencies, mainly due to the complexity of its enforcement. OBJECTIVE: To assess whether the inclusion of D-dimer as a predictor might lead to a simplification of this clinical decision rule. PATIENTS AND METHODS: A database of deep vein thrombosis patients was studied by logistic regression model in which the 10 predictors in the Wells score and the dimer D were included. The diagnosis was made with compression ultrasonography with Doppler signal. D-dimer was determined by a quantitative method of latex, a technique immunofiltration or a turbidimetric technique. RESULTS: 577 patients (54.1% women) were studied, with a mean age of 66.7 (14.2) years. 25.1% were diagnosed with deep vein thrombosis. Only four variables were independent, building a weighted model with greater predictive ability (area under the curve) than the original model (0.844 vs. 0.751, p<0.001). Both models showed an acceptable safety, with a similar rate of failure (0.8% vs. 1%). The simplified model allowed to select a higher percentage of patients who could have benefited from the non performance of the imaging test (20.6% vs. 15.8%, p=0.039). CONCLUSIONS: The introduction of D-dimer in a regression model simplifies the Wells score and maintain the same efficacy and safety, which could improve its implementation in the hospital emergencies.