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Background: Post-transplant lymphoproliferative disorders represent rare but serious complications of kidney transplantation. Methods: We assessed incidence, risk factors, and outcomes in 21,546 patients receiving grafts between 1990 and 2009. Data were compared by decade of transplant (1990-1999 vs 2000-2009). Patients were followed for at least 12 years over a 32-year study period. Results: In total, 331 patients (1.5%) developed PTLD: 189 of 9740 transplanted in the first decade, and 142 of 11,806 in the second. Incidence decreased significantly (19.40 vs12.02 cases/1000 patients; P < .001). Mean age at diagnosis was 50.2 years (standard deviation 14.7), and the median time from transplant to PTLD diagnosis was 48 months (interquartile range, 14.7-77.5), with no difference between cohorts. The origin of PTLD was mostly (86%) B-cell proliferation. No classical risk factors were reported in 31.7% of affected patients. Compared with 2000 to 2009, in 1990 to 1999 there was a higher frequency of induction therapy (P = .023) and detection of the Epstein-Barr virus in lymphoproliferative tissue (71.3% vs 52.7% P = .019). After diagnosis, 1- and 5-year patient survival was 51% and 38%. Graft survival was 48% and 33%. Survival was stable throughout the study period. Conclusion: Post-transplant lymphoproliferative disorders have a low and decreasing incidence, but the poor prognosis has not changed.

Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results. Patients and methods Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started early. Results A total of 240 transplants were performed in 236 patients (191♂/45♀) over 74 months, mean age 56.3±9.6 years, raw MELD score 15.5±7.7. Predominant etiologies were alcohol (n = 136) and HCV (n = 82), with hepatocellular carcinoma present in 129 (54.7%). Nine patients received combined liver and kidney transplants. The mean operating time was 315±64 min with cold ischemia times of 279±88 min. Thirty-one patients (13.1%) were transfused in the OR (2.4±1.2 units of PRBC). Extubation was immediate (p=0.015) in the fast-track group. Patient survival was 86.8% at 1 year and 78.6% at five years. Conclusion Fast-Tracking of Liver Transplant patients is feasible and can be applied as the standard of care

Sirolimus is used in the immunosuppressive therapeutic treatment of kidney transplant patients. The high pharmacokinetic variability of sirolimus makes pharmacokinetic monitoring and dosage individualization of mmunosuppressive therapy a key process to achieve better efficacy results. The availability of a population pharmacokinetic model can be used to provide better pharmacokinetic adjustment of plasma concentrations of sirolimus and thus achieve greater clinical benefit.We conducted a systematic review of the literature available in the Medline, Embase, and Scopus databases to identify and subsequently analyze population pharmacokinetic models of orally administered sirolimus in adult patients after kidney transplant. The descriptors used MeSH were kidney transplantation, pharmacokinetics, and sirolimus. The following variables from the selected studies were assessed: study population, immunosuppressive treatment, blood sampling times, covariates analyzed, type of pharmacokinetic model, computer software used, estimated pharmacokinetic parameters, interindividual variability of pharmacokinetic parameters, residual variability and mathematical equations of the pharmacokinetic model.A total of 548 results were obtained, excluding 175 records that were identified in more than one database. Finally, seven articles that et the inclusion criteria were selected. Most of the pharmacokinetic models found fit a two-compartment model. The interindividual variability of sirolimus was explained by covariates such as age, weight, liver function, cyclosporine exposure and dose, sirolimus doses, CYP3A5 genetic olymorphisms, serum creatinine, and concomitant treatment.The two-compartment model was the pharmacokinetic model of choice in most of the selected studies. The interindividual variability of the pharmacokinetic parameters of sirolimus is explained by demographic, clinical, genetic, and biochemical variables. The availability of pharmacokinetic models of sirolimus can assist in optimizing therapy in patients after kidney transplant.Sirólimus es un fármaco utilizado en los esquemas terapéuticos inmunosupresores en pacientes con trasplante renal. La elevada variabilidad farmacocinética de sirólimus hace que la monitorización farmacocinética y la individualización posológica de la terapia inmunosupresora sea un proceso crucial para conseguir mejores resultados de eficacia. La disponibilidad de un modelo farmacocinético poblacional permite realizar un mejor ajuste farmacocinético de las concentraciones plasmáticas de sirólimus y así conseguir un mayor beneficio clínico.Método: Se realizó un análisis sistemático de la literatura disponible en las bases de datos Medline, Embase y Scopus para identificar y posteriormente analizar los modelos farmacocinéticos poblacionales de irólimus administrado por vía oral en pacientes adultos con trasplante renal. Se utilizaron como descriptores MeSH: kidney transplantation, pharmacokinetic y sirolimus. De cada artículo seleccionado se evaluó: la población a estudio, el esquema de tratamiento inmunosupresor, los tiempos de muestreo de las extracciones de sangre, las covariables analizadas, el tipo de modelo farmacocinético, el programa informático utilizado, los parámetros armacocinéticos estimados, la variabilidad interindividual de los parámetros farmacocinéticos, la variabilidad residual y las ecuaciones matemáticas del modelo farmacocinético.Se obtuvieron un total de 548 resultados, excluyendo 175 registros tras identificarse en más de una base de datos. Finalmente se seleccionaron siete artículos que cumplían los criterios de inclusión. La mayoría de los modelos farmacocinéticos encontrados siguen un modelo bicompartimental. Covariables como edad, peso, función hepática, exposición y dosis de ciclosporina, dosis de sirólimus, polimorfismos genéticos del CYP3A5, creatinina sérica y tratamiento concomitante explican la variabilidad interindividual de sirólimus.El modelo bicompartimental fue el modelo farmacocinético de elección en la mayoría de los estudios seleccionados. La variabilidad interindividual de los parámetros farmacocinéticos de sirólimus se explica por variables demográficas, clínicas, genéticas y bioquímicas. La disponibilidad de modelos farmacocinéticos de sirólimus permiten ndividualizar la terapia en pacientes con trasplante renal.

Infliximab and adalimumab are monoclonal antibodies against tumor necrosis factor (anti-TNF) used to manage inflammatory bowel disease (IBD). Therapeutic Drug Monitoring (TDM) has been proven to prevent immunogenicity, to achieve better long-term clinical results and to save costs in IBD treatment. The aim of this study was to conduct a systematic review on cost-effectiveness analyses of studies that apply TDM of anti-TNF in IBD and to provide a critical analysis of the best scientific knowledge available in the literature. The quality of the included studies was assessed using Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Cost-effectiveness of the TDM strategies was presented as total costs, cost savings, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER). Thirteen studies that examined the health economics of TDM of anti-TNF in IBD from 2013 to 2021 were included. Eight of them (61.5%) achieved a score between 17 and 23 on the CHEERS checklist. The comparison between the TDM strategy and an empirical strategy was cost saving. The ICER between reactive TDM and an empirical strategy was dominated (favorable) by reactive TDM, whereas the ICER value for proactive TDM compared to an empirical strategy ranged from EUR 56,845 to 3,901,554. This systematic review demonstrated that a TDM strategy is cost-effective or cost-saving in IBD. S.M.-M. received a predoctoral fellowship from Miguel Hernandez University (“Ayudas a la contratación de personal investigador en formación 2021”). Sí

Introduction: Currently, kidney transplantation is the treatment of choice for patients with kidney disease who require replacement therapy. Dialysis is a necessary step, but not mandatory prior to transplantation. There is the possibility of pre-emptive transplantation or transplantation in pre-dialysis, that is, without previous dialysis. The aim of the present study is to evaluate the result of our experience with a pre-emptive kidney transplant from a deceased donor. Materials and methods: Retrospective, observational, matched cohort study. We compared 66 pre-emptive with 66 non pre-emptive recipients, who received a first renal graft performed at our centre, matched by age and gender of donors and recipients, time of transplant, immunological risk, immunosuppression and cold ischaemia time.Early graft loss, incidence of acute rejection, delayed graft function, renal function at 12 and 36 months and graft and recipient survival were assessed in this period. Results: The percentage of recipients who presented early graft loss, delayed graft function and acute rejection was similar in both groups. No differences were observed in their renal function at 12 and 36 months after transplantation, as well as the actuarial survival of patients (p = 0.801) and grafts (p = 0.693) in the studied period. The total calculated cost of the period on dialysis for the control group was 8,033,893.16 euros. Conclusions: Pre-emptive transplantation can yield comparable outcomes to those for post-dialysis kidney transplantation, and results in better quality of life for patients with end-stage kidney disease, as well as a reduced cost. Resumen: Introducción: Actualmente, el trasplante renal es el tratamiento de elección para pacientes con enfermedad renal que requieren terapia de sustitución. La diálisis es un paso necesario, pero no obligatorio, previo al trasplante. Existe la posibilidad del trasplante renal anticipado o en pre-diálisis, es decir, sin diálisis previa. El objetivo del presente estudio es evaluar el resultado de nuestra experiencia en el trasplante renal anticipado con donante cadáver. Materiales y métodos: Estudio observacional retrospectivo de tipo cohortes emparejadas. Seincluyó a 66 receptores de trasplante renal en situación pre-diálisis, frente a un grupo control de 66 pacientes ya en diálisis que recibieron un primer injerto renal, emparejados por edad y sexo de donante y receptor, momento del trasplante, riesgo inmunológico, inmunosupresión y tiempo de isquemia fría. Se evaluó la pérdida precoz del injerto, incidencia de rechazo agudo, función retrasada del injerto, función renal a los 12 y 36 meses y supervivencia de injerto y receptor en ese periodo. Resultados: El porcentaje de receptores que presentaron pérdida precoz del injerto, función retrasada del injerto y rechazo agudo fue similar en ambos grupos. Tampoco se observaron diferencias en la función renal a los 12 ni a los 36 meses después del trasplante, ni en lasupervivencia actuarial de pacientes (p = 0,801) e injertos (p = 0,693).El coste total del tratamiento renal sustitutivo en el grupo control fue: 8033893.16 euros. Conclusiones: El trasplante renal de donante cadáver ofrece a los pacientes en situación de prediálisis resultados superponibles a los de receptores en diálisis, además de ser económicamente rentable. Keywords: Pre-emptive renal transplant, Deceased donor, Patient and graft survival, Dialysis, Psychological aspects, Palabras clave: Trasplante renal anticipado, Donante cadáver, Supervivencia injerto y receptor, Diálisis, Impacto psicológico

Resumen: Introducción: Actualmente, el trasplante renal es el tratamiento de elección para pacientes con enfermedad renal que requieren terapia de sustitución. La diálisis es un paso necesario, pero no obligatorio, previo al trasplante. Existe la posibilidad del trasplante renal anticipado o en prediálisis, es decir, sin diálisis previa. El objetivo del presente estudio es evaluar el resultado de nuestra experiencia en el trasplante renal anticipado con donante cadáver. Materiales y métodos: Estudio observacional retrospectivo de tipo cohortes emparejadas. Se incluyó a 66 receptores de trasplante renal en situación de prediálisis, frente a un grupo control de 66 pacientes ya en diálisis que recibieron un primer injerto renal, emparejados por edad y sexo de donante y receptor, momento del trasplante, riesgo inmunológico, inmunosupresión y tiempo de isquemia fría. Se evaluó la pérdida precoz del injerto, incidencia de rechazo agudo, función retrasada del injerto, función renal a los 12 y 36 meses y supervivencia de injerto y receptor en ese período. Resultados: El porcentaje de receptores que presentaron pérdida precoz del injerto, función retrasada del injerto y rechazo agudo fue similar en ambos grupos. Tampoco se observaron diferencias en la función renal a los 12 ni a los 36 meses después del trasplante, ni en la supervivencia actuarial de pacientes (p = 0,801) e injertos (p = 0,693).El coste total del tratamiento renal sustitutivo en el grupo control fue de 8.033.893,16 euros. Conclusiones: El trasplante renal de donante cadáver ofrece a los pacientes en situación de prediálisis resultados superponibles a los de receptores en diálisis, además de ser económicamente rentable. Abstract: Introduction: Currently, kidney transplantation is the treatment of choice for patients with kidney disease who require replacement therapy. Dialysis is a necessary step, but not mandatory prior to transplantation. There is the possibility of pre-emptive transplantation or transplantation in pre-dialysis, that is, without previous dialysis. The aim of the present study is to evaluate the result of our experience with a pre-emptive kidney transplant from a deceased donor. Materials and methods: Retrospective, observational, matched cohort study. We compared 66 pre-emptive with 66 non pre-emptive recipients, who received a first renal graft performed at our centre, matched by age and gender of donors and recipients, time of transplant, immunological risk, immunosuppression and cold ischaemia time.Early graft loss, incidence of acute rejection, delayed graft function, renal function at 12 and 36 months and graft and recipient survival were assessed in this period. Results: The percentage of recipients who presented early graft loss, delayed graft function and acute rejection was similar in both groups. No differences were observed in their renal function at 12 and 36 months after transplantation, as well as the actuarial survival of patients (P = 0.801) and grafts (P = 0.693) in the studied period. The total calculated cost of the period on dialysis for the control group was 8,033,893.16 euros. Conclusions: Pre-emptive transplantation can yield comparable outcomes to those for post-dialysis kidney transplantation, and results in better quality of life for patients with end-stage kidney disease, as well as a reduced cost. Palabras clave: Trasplante renal anticipado, Donante cadáver, Supervivencia injerto y receptor, Diálisis, Impacto psicológico, Keywords: Pre-emptive renal transplant, Deceased donor, Patient and graft survival, Dialysis, Psychological aspects

Resumen: El objetivo del presente estudio fue evaluar las concentraciones valle (Cpvalle) y la pauta posológica de tacrolimus tras la conversión de Prograf o Advagraf a Envarsus (nueva forma farmacéutica con tecnología Meltdose que mejora la absorción de fármacos liposolubles) en pacientes con trasplante renal estable, y su función renal.Se seleccionaron los pacientes trasplantados renales estables que fueron convertidos a Envarsus. Se definieron dos periodos: basal y conversión (Envarsus), y se estratificaron en función de la forma farmacéutica utilizada en el periodo basal. Se incluyeron 61 pacientes (24 con Advagraf y 37 con Prograf), con una edad media de 52 años. El tiempo medio postrasplante en el momento de la conversión a Envarsus fue de 76,3 meses y el seguimiento medio en el periodo basal y conversión fue de 10,1 y 11,6 meses, respectivamente.En el grupo Prograf y Envarsus las medianas Cpvalle fueron 6,6 vs 6,4 ng/ml (p = 0,636), con una dosis diaria media que disminuyó significativamente de 3 a 2 mg (p

The aim of this study was to evaluate the trough concentrations (Cptrough) and the tacrolimus dosage regimen after the conversion of Prograf or Advagraf to Envarsus (new pharmaceutical form with MeltDose technology that improves the absorption of fat-soluble drugs) in patients with stable renal transplantation, and their renal function.We selected stable renal transplant patients who were converted to Envarsus. Two periods were defined: Baseline and Conversion (Envarsus) and they were stratified according to the pharmaceutical form used in the Baseline period. Sixty-one patients were included (24 with Advagraf and 37 with Prograf), with an average age of 52 years. The mean post-transplant time at the time of conversion to Envarsus was 76.3 months and the mean follow-up in the Baseline and Conversion period was 10.1 months and 11.6 months, respectively.In the Prograf and Envarsus group, the Cptrough medians were 6.6 vs 6.4 ng/ml (p = .636), with a mean daily dose that decreased significantly from 3 mg to 2 mg (p

Background. As of December 31, 2018, Spain's National Transplant Organization estimated that there were 61,764 people under renal replacement therapy across the country. Of this population, 33,784 (54.7%) had a functioning kidney graft. Methods. Through the use of a survey to all Spanish hospitals involved in kidney transplantations, we studied the distribution of these recipients nationally, along with who was monitoring them and how. Data collected include the ratio of recipients to transplant nephrologists, median number of recipients followed in each center, and median number of transplant nephrologists per hospital. Of the 806 centers in the Spanish hospital network, 43 (5.3%) were involved in kidney transplants, including 39 transplant hospitals and 4 associated hospitals. The median number of transplants per center was 800 (interquartile range [IQR] = 510-1200). There were 3 nephrologists (IQR 2-5), and the ratio of recipients to transplant nephrologists was 270 (IQR = 190-323). Results. There were no significant differences in these data between autonomous communities, except in the case of the Canary Islands, which had a significantly lower ratio of recipients to transplant nephrologists (146; IQR = 100-185) compared with the rest of the country (ratio 277; IQR = 207-329; P < .001). Of the 39 hospitals, 29 (74.4%) referred patients to centers that did not perform transplants. Conclusions. All in all, few Spanish hospitals perform kidney transplants. The ratio of recipients to transplant nephrologists is very high, compelling most hospitals to refer patients to nontransplant hospitals for follow-up. There are important differences in the distribution of recipients in hospitals in the Canary Islands vs the rest of the country, a difference that is undoubtedly attributable to its geographic peculiarities.

Background & aims Few studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. Methods The ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21–30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. Results The low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. Conclusions This single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.

Adalimumab is a monoclonal antibody used for inflammatory bowel disease. Due to its considerably variable pharmacokinetics, the loss of response and the development of anti-antibodies, it is highly recommended to use a model-informed precision dosing approach. The aim of this study is to evaluate the predictive performance of different population-pharmacokinetic models of adalimumab for inflammatory bowel disease to determine the pharmacokinetic model(s) that best suit our population to use in the clinical routine. A retrospective observational study with 134 patients was conducted at the General University Hospital of Alicante between 2014 and 2019. Model adequacy of each model was evaluated by the distribution of the individual pharmacokinetic parameters and the NPDE plots whereas predictive performance was assessed by calculating bias and precision. Moreover, stochastic simulations were performed to optimize the maintenance doses in the clinical protocols, to reach the target of 8 mg/L in at least 75% of the population. Two population-pharmacokinetic models were selected out of the six found in the literature which performed better in terms of adequacy and predictive performance. The stochastic simulations suggested the benefits of increasing the maintenance dose in protocol to reach the 8 mg/L target.

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.

To evaluate the efficacy and safety of high-flow nasal cannula (HFNC) oxygen therapy in patients in acute respiratory failure due to acute heart failure (AHF) refractory to conventional oxygen therapy or noninvasive ventilation.Prospective observational study of patients with AHF and respiratory failure attended in an emergency department whose condition worsened after they were admitted to a short-stay unit, leading to use of HFNCs. Efficacy was assessed using a modified Borg dyspnea scale and oxygenation variables on discharge from the emergency department. Data were recorded after 24 hours on conventional oxygen therapy and after 60 and 120 minutes and 24 hours of HFNC therapy. Safety outcomes were the degree of patient comfort and the frequency of adverse events.Prospective observational study of patients with AHF and respiratory failure attended in an emergency department whose condition worsened after they were admitted to a short-stay unit, leading to use of HFNCs. Efficacy was assessed using a modified Borg dyspnea scale and oxygenation variables on discharge from the emergency department. Data were recorded after 24 hours on conventional oxygen therapy and after 60 and 120 minutes and 24 hours of HFNC therapy. Safety outcomes were the degree of patient comfort and the frequency of adverse events.HFNC oxygen therapy offers a treatment alternative for patients with acute respiratory failure due to AHF.Valorar la eficacia y seguridad de la terapia de alto flujo con cánulas nasales (TAFCN) en pacientes con insuficiencia respiratoria aguda (IRA) secundaria a insuficiencia cardiaca aguda (ICA) y refractaria al tratamiento con oxigenoterapia convencional o ventilación no invasiva.Estudio observacional prospectivo de pacientes con ICA e IRA atendidos en un servicio de urgencias, con ingreso posterior en una unidad de corta estancia, que, tras 24 horas presentaron empeoramiento y a los que se administró TAFCN. Para evaluar la eficacia se utilizó la escala de disnea modificada de Borg y la oxigenación al alta de urgencias, a las 24 h de tratamiento con oxigenación convencional y a los 60, 120 minutos y 24 h de iniciada la TAFCN. Para evaluar la seguridad se midió grado de confort y eventos adversos producidos.Se recogieron 44 pacientes con edad media de 84 (7) años, 75 % mujeres. El uso de la TAFCN supuso una mejoría significativa en los parámetros clínicos y gasométricos (basal, 60 min, 120 min y 24 h), en la escala de disnea y confort, oximetría y cociente de oxigenación y una disminución de la frecuencia respiratoria (p0,05). No hubo cambios significativos en la presión arterial de dióxido de carbono. El efecto secundario más frecuente fue el calor (20,4%).La TAFCN es una alternativa para el tratamiento de los pacientes con IRA secundaria a ICA.

Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population.Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors.IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3.IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.Objetivo: El interferon-pegilado (IFN-PEG) junto a ribavirina ha sido el principal tratamiento de la infeccion por el virus de la hepatitis C (VHC) de la ultima decada. Los agentes antivirales de accion directa actuales han mejorado los resultados de la terapia, pero tambien han aumentado el costo y la gestion de la complejidad del tratamiento. El presente estudio analiza factores geneticos de los pacientes, asi como predictores virales y clinicos de respuesta sostenida viral (RSV) al tratamiento con IFN-PEG y ribavirina en poblacion Espanola. Métodos: Estudio farmacogenetico, multicentrico, prospectivo, observacional de cohortes realizado en 12 hospitales diferentes de 12 comunidades autonomas diferentes. Se incluyeron un total de 98 pacientes con RVS y 106 sin SVR al tratamiento con IFNPEG y ribavirina. Se seleccionaron 33 polimorfismos de nucleotido unico ubicados en 24 genes diferentes relacionados con la respuesta inflamatoria, inmunologica y viral. Los datos clinicos y virales tambien se analizaron como candidatos predictores de RVS. Resultados: Los genotipos IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) y TNFRSF1B (rs1061622), asi como los haplotipos TNFRSF1B / IL-10 / TNF(-308) no-TTG y TNFRSF1B / IL-10 / IL-4 no-TTC junto con la menor edad, menor carga de ARN-VHC basal, valores elevados de colesterol LDL en suero basal, genotipos VHC2 y 3 y bajo grado de fibrosis basal (0-2) se asociaron con una RVS en el analisis univariante. Los predictores independientes de RVS en el analisis multivariante fueron el genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 no-TTC junto con los bajos niveles basales de VHCARN y los genotipos virales VHC2 y 3. Conclusiones: El genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 haplotipos no-TTC, la carga viral basal baja y los genotipos del VHC2 y 3 pueden ayudar a predecir una buena respuesta a la terapia con IFN-PEG y ribavirina en poblacion espanola.

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

In peritoneal metastasis condition, the fact that most of the disease is limited to the peritoneal cavity laid the foundations for a surgical treatment, including intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of this study was to evaluate the impact of the surgical procedures implied in open HIPEC technique, referred to laparotomy procedures followed by an intraperitoneal hyperthermic instillation (LIHI) on oxaliplatin tissue distribution and elimination. To delimit the influence of this procedure alone, oxaliplatin was administered as an intravenous (iv) bolus in both groups. An experimental model in Wistar rats was employed, and LIHI was evaluated as a dichotomous covariate by using a population pharmacokinetic (PK) approach. Rats were randomized in two groups receiving 1.5 mg iv oxaliplatin alone or 1.5 mg iv oxaliplatin under LIHI conditions, carrying out a hyperthermic 5% dextrose instillation. The oxaliplatin plasma concentrations were characterized by an open two-compartment PK model. Results concluded that surgical conditions affect the oxaliplatin elimination and distribution from blood to peripheral tissues, increasing the systemic drug exposure. Concretely, oxaliplatin peripheral volume of distribution, and clearance decreased by 48.6% and 55.3%, respectively, compared to the control group that resulted in a two-fold increase of the area under the concentration time curve. Comparison in clinical practice of oxaliplatin PK parameters obtained after iv administrations with those obtained after HIPEC interventions must be done carefully. This would limit the use of iv PK parameters to simulate new scenarios for oxaliplatin in HIPEC.

Background Calcineurin inhibitors (CNI) have failed to improve long-term outcomes in renal transplantation. Anti-proliferative and anti-angiogenic effects of mammalian target of rapamycin inhibitors (m-TOR) without nephrotoxicity could improve long-term survival in selected transplant recipients. Methods We examined the evolution of 98 low–immunological risk renal transplant recipients on m-TOR monotherapy: 7 patients had induction without CNI and 91 were switched to m-TOR at 12 (p25–p75: 4–36) months after transplant. Results Median follow-up time was 46 (p25–p75: 28.5–72.0) months. Fifteen recipients dropped out of the study (15.3%): 8 patients (8.2%) had to change their immunosuppressive treatment because of complications and 7 (7.1%) lost their grafts as a result of chronic rejection (4 cases) or death with a functioning graft (3 cases). At the end of follow-up, 83 of 98 (84.6%) recipients remained on monotherapy. The rates of recipient and graft survivals were 100% and 98.8% at 2 years and 96.9% and 93.5% at 4 years; the percentages of patients on monotherapy after 2 and 4 years were 95.2% and 85.2%, respectively. Renal function improved significantly and proteinuria decreased but not significantly. Those patients switched to m-TOR significantly received more erythropoietin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and hypotensive agents than before starting m-TOR, whereas there were no significant changes related to the use of statins, body weight, or percentage of diabetic patients. No case of non-compliance was reported. Conclusions This study supports the safety and efficacy of monotherapy with m-TOR in selected renal transplant recipients.

To check the correlation between gastric intolerance and hypertension intracranial pressure and their association with the clinical parameters and severity indexes in patients with severe head injury (HI); to evaluate the advantages of transpyloric feeding.Prospective and observational clinical study.Intensive Care Unit (ICM) of a General University Hospital.25 brain injured patients requiring sedation, mechanical ventilation and hypertensión intracranial monitoring.Analysis of the incidence of delayed gastric emptying (area under the curve (AUC60)) and of gastrointestinal intolerance; study of their correlation with hypertension intracranial, severity indexes and sedative medication administered; evaluation of the alternative effectiveness of transpyloric feeding.44% of the patients showed GI, which was measured by means of the paracetamol test (AUC60). The sedative medication was related to IG (p0.005), HIC (p0.01) and AUC60 (p0.01). Of the severity indexes, there was a correlation between Glasgow Coma Score and AUC60 (p0.01); the Marshall score HIC (p0.005) and AUC60 (p0.01). Of the quantitative variables, we found a correlation between HIC and IG (p0.001), HIC and pneumonia (p0.01), IG as well pneumonia (p0.001), and AUC60 (p0.001) and AUC60 and pneumonia (p0.05).Enteral intolerance in patients with HI is due to delayed gastric emptying (DGE) which is proportional to the severity of the head injury and to the intensity of the systemic response. The high incidence of GI makes transpyloric feeding advisable in order to attain the nutritional objective and to reduce the risk of aspirative nosocomial pneumonia.

Objectives. To evaluate the efficacy and safety of high-flow nasal cannula (HFNC) oxygen therapy in patients in acute respiratory failure due to acute heart failure (AHF) refractory to conventional oxygen therapy or noninvasive ventilation. Methods. Prospective observational study of patients with AHF and respiratory failure attended in an emergency department whose condition worsened after they were admitted to a short-stay unit, leading to use of HFNCs. Efficacy was assessed using a modified Borg dyspnea scale and oxygenation variables on discharge from the emergency department. Data were recorded after 24 hours on conventional oxygen therapy and after 60 and 120 minutes and 24 hours of HFNC therapy. Safety outcomes were the degree of patient comfort and the frequency of adverse events. Results. Forty-four patients with a mean (SD) age of 84 (7) years (75% women) were enrolled. Significant improvements were observed after HFNC oxygen therapy (baseline vs 60 and 120 minutes and baseline vs 24 hours) on clinical outcomes and oxygenation as well as decrease in respiratory frequency (P