Intestinal perforation after pediatric liver transplantation: risk factors and management. / Perforación intestinal tras trasplante hepático pediátrico: factores de riesgo y manejo.

BACKGROUND: Intestinal perforation (IP) after pediatric liver transplant (PLT) is an uncommon complication with high mortality reported. The aim of this study is to identify the risk factors and management of this complication. MATERIALS AND METHODS: Retrospective study of IP after PLT from January 2014 to October 2020. RESULTS: Four intestinal perforations were indentificated in 102 PLT (3,9%). Three patients with BA and one neonate with hemochromatosis (HC) presented this complication. The mean weight of patients with IP was 6.3± 2.5kg (3.1-9) and 19.9 ± 15.4kg for the rest (p< 0.05). All IP with BA had a previous laparotomy. Two living donors and two left lateral reduced liver were implanted. The diagnosis of intestinal perforation was done on day 11 ± 3.3 (8-15 days). Diagnosis was suspected with clinical and biological signs of perforation, CT scan confirmed the diagnosis in patiens with BA and by direct visualization through the mesh for temporary closure in the patient with hemocromatosis. Urgent laparotomy was performed. We identified three colonic perforations, all of them in BA patients and all repaired with direct suture. The patient with HC presented multiple perforations secondary to necrotizing enterocolitis requiring an ileostomy and finally died due to multiorgan failure. CONCLUSION: Intestinal perforation after PLT is an infrequent complication. Age, weight, previous laparotomy and BA could be risk factors for IP in PLT. Urgent laparotomy after diagnosis should be performed in order to reduce mortality. Isolated IP with adequate treatment might not affect long term outcomes after pediatric liver transplantation.

INTRODUCCION: La perforación intestinal (PI) tras trasplante hepático pediátrico (THP) es una complicación poco frecuente, pero con una elevada mortalidad. El objetivo de este estudio es identificar los factores de riesgo y el manejo de esta complicación. MATERIAL Y METODOS: Estudio retrospectivo de la PI tras THP entre enero de 2014 y octubre de 2020. RESULTADOS: Se hallaron 4 perforaciones intestinales en 102 THP (3,9%). Presentaron esta complicación 3 pacientes con atresia biliar (AB) y un neonato con hemocromatosis (HC). El peso medio de los pacientes con PI era de 6,3 ± 2,5 kg (3.1-9) y de 19,9 ± 15,4 kg en el caso del resto (p<0,05). Todos los pacientes con PI y AB habían sido sometidos previamente a laparotomía. Se implantaron 2 hígados de donantes vivos y 2 hígados laterales reducidos izquierdos. El diagnóstico de perforación intestinal se efectúo en el día 11 ± 3,3 (8-15 días), sospechándose con signos clínicos y biológicos de perforación, y confirmándose mediante escáner en los pacientes con AB y mediante visualización directa a través de la malla para el cierre temporal en el paciente con hemocromatosis. Se llevó a cabo laparotomía de urgencia. Se identificaron 3 perforaciones de colon, todas ellas en pacientes con AB y reparadas con sutura directa. El paciente con HC presentaba múltiples perforaciones secundarias a enterocolitis necrotizante que precisaron ileostomía, falleciendo finalmente como consecuencia de un fallo multiorgánico. CONCLUSIONES: La perforación intestinal tras THP es una complicación poco frecuente. La edad, el peso, las laparotomías previas y la AB podrían ser factores de riesgo de PI en el THP. Para reducir la mortalidad, es conveniente practicar una laparotomía de urgencia tras el diagnóstico. Una PI aislada con un adecuado tratamiento puede no influir en los resultados a largo plazo tras un trasplante hepático pediátrico.

Perforación intestinal tras trasplante hepático pediátrico: factores de riesgo y manejo / Intestinal perforation after pediatric liver transplantation: risk factors and management

Introducción: La perforación intestinal (PI) tras trasplante hepáticopediátrico (THP) es una complicación poco frecuente, pero con unaelevada mortalidad. El objetivo de este estudio es identificar los factoresde riesgo y el manejo de esta complicación. Material y métodos: Estudio retrospectivo de la PI tras THP entreenero de 2014 y octubre de 2020. Resultados: Se hallaron 4 perforaciones intestinales en 102 THP(3,9%). Presentaron esta complicación 3 pacientes con atresia biliar (AB)y un neonato con hemocromatosis (HC). El peso medio de los pacientescon PI era de 6,3 ± 2,5 kg (3.1-9) y de 19,9 ± 15,4 kg en el caso delresto (p<0,05). Todos los pacientes con PI y AB habían sido sometidospreviamente a laparotomía. Se implantaron 2 hígados de donantes vivosy 2 hígados laterales reducidos izquierdos. El diagnóstico de perforaciónintestinal se efectúo en el día 11 ± 3,3 (8-15 días), sospechándose consignos clínicos y biológicos de perforación, y confirmándose medianteescáner en los pacientes con AB y mediante visualización directa a travésde la malla para el cierre temporal en el paciente con hemocromatosis.Se llevó a cabo laparotomía de urgencia. Se identificaron 3 perforacionesde colon, todas ellas en pacientes con AB y reparadas con sutura directa. El paciente con HC presentaba múltiples perforaciones secundarias aenterocolitis necrotizante que precisaron ileostomía, falleciendo finalmente como consecuencia de un fallo multiorgánico.Conclusión: La perforación intestinal tras THP es una complicaciónpoco frecuente. La edad, el peso, las laparotomías previas y la AB podrían ser factores de riesgo de PI en el THP. Para reducir la mortalidad,es conveniente practicar una laparotomía de urgencia tras el diagnóstico.Una PI aislada con un adecuado tratamiento puede no influir en losresultados a largo plazo tras un trasplante hepático pediátrico.(AU)

Background: Intestinal perforation (IP) after pediatric liver trans-plant (PLT) is an uncommon complication with high mortality reported.The aim of this study is to identify the risk factors and management ofthis complication. Material and methods: Retrospective study of IP after PLT fromJanuary 2014 to October 2020. Results: Four intestinal perforations were indentificated in 102 PLT(3,9%). Three patients with BA and one neonate with hemochromatosis(HC) presented this complication. The mean weight of patients with IPwas 6.3 ± 2.5kg (3.1-9) and 19.9 ± 15.4kg for the rest (p< 0,05). AllIP with BA had a previous laparotomy. Two living donors and two leftlateral reduced liver were implanted. The diagnosis of intestinal perforation was done on day 11 ± 3.3 (8-15 days). Diagnosis was suspectedwith clinical and biological signs of perforation, CT scan confirmed thediagnosis in patiens with BA and by direct visualization through themesh for temporary closure in the patient with hemocromatosis. Urgentlaparotomy was performed. We identified three colonic perforations, allof them in BA patients and all repaired with direct suture. The patientwith HC presented multiple perforations secondary to necrotizing enterocolitis requiring an ileostomy and finally died due to multiorgan failure.Conclusion: Intestinal perforation after PLT is an infrequent complication. Age, weight, previous laparotomy and BA could be risk factorsfor IP in PLT. Urgent laparotomy after diagnosis should be performed inorder to reduce mortality. Isolated IP with adequate treatment might notaffect long term outcomes after pediatric liver transplantation.(AU)

El efecto de autolicencia moral: cuando la conducta virtuosa facilita la conducta inmoral / Moral self-licensing effect: When virtuous behavior facilitates immoral behavior

La investigación empírica de las dos últimas décadas, realizada fundamentalmente con muestras de EEUU y de Europa occidental, revela que el hecho de actuar de forma virtuosa puede hacer que posteriormente las personas actúen de forma moralmente más dudosa. A este fenómeno se le ha denominado efecto de autolicencia moral. En el presente artículo se revisa la evidencia empírica sobre dicho efecto, así como las explicaciones teóricas que se han propuesto para el mismo: el modelo de las credenciales morales y el modelo de crédito, en el que se incluyen la teoría de la autorregulación y la teoría de la compleción. Asimismo, se analiza el problema de la posible contradicción entre este efecto y la tendencia a la autoconsistencia moral. Finalmente, se examina la fuerza del efecto y en qué medida este es generalizable a distintas culturas. El artículo se cierra con un apartado de conclusiones en el que se reflexiona sobre las implicaciones del fenómeno (AU)

Empirical research over the past two decades, conducted primarily with samples from the U.S. and Western Europe, reveals that acting virtuously can subsequently cause people to act in a morally more dubious way. This phenomenon has been called the moral self-licensing effect. In this article we review the empirical evidence on this effect, as well as the theoretical explanations that have been proposed for it: the model of moral credentials and the credit model, which includes the theory of self-regulation and the theory of completion. Then, we analize the problem of the possible con-tradiction between this effect and the tendency to moral self-consistence. Finally, we examine the strength of the effect and to what extent it is generalizable to different cultures. The article closes with a section of conclusions in which the implications of the phenomenon are discussed (AU)

Obesity as an adipose tissue dysfunction disease and a risk factor for infections - Covid-19 as a case study.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) disease (COVID-19) is a novel threat that hampers life expectancy especially in obese individuals. Though this association is clinically relevant, the underlying mechanisms are not fully elucidated. SARS CoV2 enters host cells via the Angiotensin Converting Enzyme 2 receptor, that is also expressed in adipose tissue. Moreover, adipose tissue is also a source of many proinflammatory mediators and adipokines that might enhance the characteristic COVID-19 cytokine storm due to a chronic low-grade inflammatory preconditioning. Further obesity-dependent thoracic mechanical constraints may also incise negatively into the prognosis of obese subjects with COVID-19. This review summarizes the current body of knowledge on the obesity-dependent circumstances triggering an increased risk for COVID-19 severity, and their clinical relevance.

Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma. / Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable.

BACKGROUND: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AIM: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. METHODS: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. RESULTS: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. CONCLUSION: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

Factors Related to Non-participation in the Basque Country Colorectal Cancer Screening Programme.

Background: Despite the high participation rates in the Basque Country, colorectal cancer screening programme (Spain), there is still a part of the population that has never participated. Since it is essential to ensure equal access to health services, it is necessary to identify the determinants of health and socio-economic factors related to non-participation in the screening programme. Methods: Cross sectional descriptive study including all invited population in a complete round between 2015 and the first trimester of 2017. Health risk factors available in medical records and their control have been analyzed using univariate and multivariate analyses. Results: 515,388 people were invited at the programme with a 71.9% of fecal immunochemical test participation rate. Factors that increase the risk of non-participation are: being men (OR = 1.10, 95% CI 1.09-1.12); younger than 60 (OR = 1.18, 95% CI 1.17-1.20); smoker (OR = 1.20, 95% CI 1.18-1.22); hypertensive (OR = 1.14, 95% CI 1.12-1.15) and diabetic (OR = 1.40, 95% CI 1.36-1.43); having severe comorbidity (OR = 2.09, 95% CI 2.00-2.19) and very high deprivation (OR = 1.15, 95% CI 1.12-1.17), as well as making <6 appointments to Primary Care in 3 years (OR = 2.39, 95% CI 2.33-2.45). Still, the area under the curve (AUC) indicates that there are more factors related to non-participation. Conclusions: The participation in the Basque Country colorectal cancer-screening Programme is related to some risk factors controlled by Primary Care among others. Therefore, the involvement of these professionals could improve, not only the adherence to the CRC screening, but also other health styles and preventive interventions.

Efficacy and safety of administering oral misoprostol by titration compared to vaginal misoprostol and dinoprostone for cervical ripening and induction of labour: study protocol for a randomised clinical trial.

BACKGROUND: Among the various methods available, the administration of prostaglandins is the most effective for inducing labour in women with an unfavourable cervix. Recent studies have compared treatment with various titrated doses of oral misoprostol with vaginal misoprostol or dinoprostone, indicating that the use of an escalating dose of an oral misoprostol solution is associated with a lower rate of caesarean sections and a better safety profile. The objective of this study is to assess which of these three therapeutic options (oral or vaginal misoprostol or vaginal dinoprostone) achieves the highest rate of vaginal delivery within the first 24 h of drug administration. METHODS: An open-label randomised controlled trial will be conducted in Araba University Hospital (Spain). Women at ≥41 weeks of pregnancy requiring elective induction of labour who meet the selection criteria will be randomly allocated to one of three groups: 1) vaginal dinoprostone (delivered via a controlled-release vaginal insert containing 10 mg of dinoprostone, for up to 24 h); 2) vaginal misoprostol (25 µg of vaginal misoprostol every 4 h up to a maximum of 24 h); and 3) oral misoprostol (titrated doses of 20 to 60 µg of misoprostol following a 3 h on + 1 h off regimen up to a maximum of 24 h). Both intention-to-treat analysis and per-protocol analysis will be performed. DISCUSSION: The proposed study seeks to gather evidence on which of these three therapeutic options achieves the highest rate of vaginal delivery with the best safety profile, to enable obstetricians to use the most effective and safe option for their patients. TRIAL REGISTRATION: NCT02902653 Available at: https://clinicaltrials.gov/show/NCT02902653 (7th September 2016).

"Non-Touch" Vena Cava Technique as an Improvement in Combined Lung and Liver Procurement in Controlled Donation After Circulatory Death.

The number of organs retrieved from donation after circulatory death (DCD) donors has continued to rise in recent years. The functional superiority of DCD organs is achieved when the lungs are perfused with cold perfusion and livers with normothermic regional perfusion (NRP). Thus, a precise surgical technique is required to combine thoracic and abdominal organ procurement. The technique used at our center consists of a rapid laparotomy and middle sternotomy, then the abdominal aorta (Ao) and abdominal inferior vena cava (VC) are cannulated and the descending thoracic Ao is cross-clamped. NRP is started at that point. As a variation of previously described techniques, the thoracic vena cava is not initially clamped in order to improve the return of blood volume to the NRP circuit. The pulmonary artery is cannulated to flush the lungs and the left atrial appendage is opened for drainage. After 120 minutes, NRP perfusion is stopped and the organs are flushed with cold preservation solution. In 2016, 3 livers and 6 lungs were harvested at our center using the technique described. After a minimum follow-up of 1 year, no evidence of biliary complications was observed. The combined procurement of lungs after room temperature perfusion and liver after NRP without initial clamping of the thoracic VC is feasible, with excellent function post-transplantation.

Disfunción neuromuscular adquirida en la unidad de cuidados intensivos / Acquired neuromuscular dysfunction in the intensive care unit

Introducción: La polineuropatía y la miopatía, agrupadas bajo el término «polineuromiopatía del paciente crítico» (PNMPC), son enfermedades neuromusculares que los pacientes de la unidad de cuidados intensivos (UCI) son susceptibles de presentar. Son enfermedades multifactoriales: la conexión prolongada al ventilador es uno de los factores más comunes. El objetivo de esta revisión ha sido identificar la eficacia de diferentes tratamientos rehabilitadores en pacientes con PNMPC y la relación entre esta y una serie de indicadores hospitalarios. Metodología: Se ha realizado una revisión sistemática de los estudios primarios seleccionados de las bases de datos Medline, Scielo, Web of Science, Cochrane, Cuiden y Science Direct, siguiendo las directrices de la declaración PRISMA, a través de la cual se estableció el protocolo de búsqueda. Resultados y conclusiones: De 161 artículos, solo 10 fueron seleccionados para formar parte de esta revisión, en la cual se estudiaron un total de 717 pacientes ingresados en la UCI. Se ha observado una relación estadísticamente significativa entre la PNMPC y el fallo en la desconexión del ventilador, la mortalidad, el aumento de estancia en UCI y del tiempo que los pacientes necesitan ventilación mecánica. Además, todo ello mejora en este tipo de pacientes con la aplicación de alguna terapia rehabilitadora. El uso de corticoides, por el contrario, no ha demostrado tener relación con la alteración neuromuscular

Introduction: Polyneuropathy and myopathy, grouped under the term «intensive care unit-acquired weakness» (ICUAW), are neuromuscular pathologies to which patients in the intensive care unit (ICU) are susceptible. They are multifactorial pathologies, prolonged connection to a ventilator is one of the most common. The objective of this review was to identify the efficacy of different rehabilitative treatments in patients with ICUAW, and the relationship between ICUAW and a series of indicators. Methods: A systematic review of the primary studies selected from the Medline, Scielo, Web of Science, Cochrane, Cuiden and Science Direct databases was carried out, following the guidelines of the PRISMA statement, by which the search protocol was established. Results and conclusions: Of 161 articles, only 10 were selected to be part of this review, in which a total of 717 patients admitted to the ICU were studied. A statistically significant relationship was observed between ICUAW and failure in ventilator disconnection, mortality, increase in ICU stay and the time that the patients required mechanical ventilation. Moreover, all this improved in this type of patients with the application of a rehabilitation therapy. The use of corticosteroids, was not shown to be related to neuromuscular alteration

Acquired neuromuscular dysfunction in the intensive care unit. / Disfunción neuromuscular adquirida en la unidad de cuidados intensivos.

INTRODUCTION: Polyneuropathy and myopathy, grouped under the term «intensive care unit-acquired weakness¼ (ICUAW), are neuromuscular pathologies to which patients in the intensive care unit (ICU) are susceptible. They are multifactorial pathologies, prolonged connection to a ventilator is one of the most common. The objective of this review was to identify the efficacy of different rehabilitative treatments in patients with ICUAW, and the relationship between ICUAW and a series of indicators. METHODS: A systematic review of the primary studies selected from the Medline, Scielo, Web of Science, Cochrane, Cuiden and Science Direct databases was carried out, following the guidelines of the PRISMA statement, by which the search protocol was established. RESULTS AND CONCLUSIONS: Of 161 articles, only 10 were selected to be part of this review, in which a total of 717 patients admitted to the ICU were studied. A statistically significant relationship was observed between ICUAW and failure in ventilator disconnection, mortality, increase in ICU stay and the time that the patients required mechanical ventilation. Moreover, all this improved in this type of patients with the application of a rehabilitation therapy. The use of corticosteroids, was not shown to be related to neuromuscular alteration.

Linking hearing impairment, employment and education.

OBJECTIVE: To analyse the impact that hearing impairment and other relevant variables have on the education and employment situation of those affected by it in the Principality of Asturias, Spain. METHODS: To achieve this objective, two discrete choice models (probit) are presented. The first one associates, among other variables, hearing impairment with the individual's employment status and in the second model, an ordered multinomial probit model is used to analyse, among other variables, how the impairment affects the individual's level of studies. RESULTS: Although the levels of statistical significance are low, the model's estimates appear to indicate that hearing impairment in Spain increases the probability of being unemployed by 18.4% (P = 0.09). Additionally, the people suffering from such a disability are, compared with the rest of the population, 10.2% (P = 0.05) more likely to have only completed elementary studies without pursuing any further education. CONCLUSIONS: If an individual is able to reach a level of secondary or higher education thus enabling a future incorporation to the work place, a benefit is obviously generated for both the individual as well as society (which has additionally incurred an investment in human capital). In this regard, encouraging the education of hearing-impaired students would profit both the individual (who receives an early integration as a child), which may contribute positively to family and social factors, as well as society who have incurred the investment. Therefore, our result could indicate that programmes created to support individuals with this type of disability represent an increase of welfare both individually and socially.

Safety and Efficacy of Early Everolimus When Calcineurin Inhibitors Are Not Recommended in Orthotopic Liver Transplantation.

Our aim was to study the safety and efficacy of immunosuppression with everolimus (EVL) within the 1st month after orthotopic liver transplantation (LT) when calcineurin inhibitors are not recommended. For this purpose, 28 recipients who had been treated with EVL within the 1st month after adult LT were eligible to enter in a retrospective multicenter study. Patients were followed up for 12 months after LT. EVL therapy was initiated at a median of 14 days (range, 4-24) after LT. The reason for early EVL was neurotoxicity in 14 cases, renal dysfunction in 12, and acute cellular rejection combined with renal impairment in 2. In 23 patients, immunosuppression was EVL + mycophenolate mofetil/mycophenolate sodium + steroids, and EVL + tacrolimus + steroids/mycophenolate sodium was used in 4 cases. Neurotoxicity disappeared in all patients. Renal function in patients with renal impairment improved from a median of 32 mL/min/1.73 m2 at the moment of implementation of EVL to 62 mL/min/1.73 m2 at 1 year. Four patients (14.3%) developed acute cellular rejection. We observed incisional hernia in 4 patients (14.3%), hematologic complications in 6 (21.4%), proteinuria in 2 (7.1%), edema and/or effusions in 8 (28.6%), and dyslipidemia in 12 (42.8%). No arterial complications were observed. EVL was withdrawn in 5 patients during the 1st year after LT. One-year patient survival was 92.7%. In conclusion, use of EVL within the 1st month after LT when calcineurin inhibitors are not recommended seems to be an effective therapeutic option with an acceptable safety profile.

Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [(18)F]-tetrafluoroborate.

BACKGROUND: [(18)F]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99m)Tc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [(18)F]-tetrafluoroborate in non-human primates with PET and to estimate the absorbed dose in organs. METHODS: Whole-body PET imaging was done in a Siemens ECAT HR+ scanner in two male Macaca fascicularis monkeys. After an i.v. injection of 24.93 ± 0.05 MBq/kg of [(18)F]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [(18)F]-fluoride under acidic conditions, eight sequential images from the head to the thigh (five beds) were collected for a total duration of 132 min. The whole-body emission scan was reconstructed applying attenuation and scatter corrections. After image reconstruction, three-dimensional volumes of interest (VOIs) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and the organ residence times were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the OLINDA/EXM software and the standard human model. RESULTS: [(18)F]-tetrafluoroborate was able to discriminate clearly the thyroid gland with an excellent signal-to-noise ratio. Most of the radiotracers (residence time) are localised in the organs that express NIS (stomach wall, salivary glands, thyroid, olfactory mucosa), are involved in excretion (kidneys and bladder), or reflect the vascular phase (heart and lungs). Considering the OLINDA source organs, the critical organs were the stomach wall, thyroid and bladder wall, with absorbed doses lower than 0.078 mGy/MBq. The effective dose was 0.025 mSv/MBq. CONCLUSIONS: [(18)F]-tetrafluoroborate is a very useful radiotracer for PET thyroid imaging in primates, with a characteristic biodistribution in organs expressing NIS. It delivers an effective dose slightly higher than the dose produced by (99m)Tc-pertechnetate but much lower than that produced by radioiodine in the form of (131)INa, (123)INa, or (124)INa.

Acute Antibody-Mediated Rejection as Cause of Late Liver Allograft Failure: A Case Report.

BACKGROUND: Despite now being an infrequent complication in liver transplantation (LT) recipients, acute liver failure is still associated with high mortality. CASE REPORT: Here we report a case of acute liver failure 11 months after AB0-compatible LT in a hepatitis C-positive 50-year-old male recipient caused by late antibody-mediated rejection (AMR). De novo donor-specific antibodies appeared later in a previously negative donor-recipient crossmatch, leading to a rapid deterioration of liver function. CONCLUSIONS: We highlight the importance of an accurate diagnosis and an early therapeutic intervention. The analysis of this case brings novel and generalizable insights to the differential diagnosis of acute liver failure after LT.

Analysis of adult 20-year survivors after liver transplantation.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for chronic and acute liver failure; however, the status of long-term survivors and allograft function is not well known. AIM: To evaluate the clinical outcome and allograft function of survivors 20 years post-LT, cause of death during the same period and risk factors of mortality. METHODS: A retrospective study was conducted from prospective, longitudinal data collected at a single center of adult LT recipients surviving 20 years. A comparative sub-analysis was made with patients who were not alive 20 years post-transplantation to identify the causes of death and risk factors of mortality. RESULTS: Between 1988 and 1994, 132 patients received 151 deceased-donors LT and 28 (21%) survived more than 20 years. Regarding liver function in this group, medians of AST, ALT and total bilirubin at 20 years post-LT were 33 IU/L (13-135 IU/L), 27 (11-152 IU/L) and 0.6 mg/dL (0.3-1.1 mg/dL). Renal dysfunction was observed in 40% of patients and median eGFR among 20-year survivors was 64 mL/min/1.73 m(2) (6-144 mL/min/1.73 m(2)). Sixty-one percent of 20-year survivors had arterial hypertension, 43% dyslipidemia, 25% de novo tumors and 21% diabetes mellitus. Infections were the main cause of death during the 1st year post-transplant (32%) and between the 1st and 5th year post-transplant (25%). After 5th year from transplant, hepatitis C recurrence (22%) became the first cause of death. Factors having an impact on long-term patient survival were HCC indication (p = 0.049), pre-transplant renal dysfunction (p = 0.043) and long warm ischemia time (p = 0.016); furthermore, post-transplant factors were diabetes mellitus (p = 0.001) and liver dysfunction (p = 0.05) at 1 year. CONCLUSION: Our results showed the effect of immunosuppression used during decades on long-term outcome in our LT patients in terms of morbidity (arterial hypertension, diabetes mellitus, dyslipidemia and renal dysfunction) and mortality (infections and hepatitis C recurrence).

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Immunosuppression based on everolimus in liver transplant recipients with severe early post-transplantation neurotoxicity.

The immunosuppressive management of liver transplant recipients suffering early calcineurin inhibitor-induced neurotoxicity is a challenge in daily clinical practice. We have assessed the use of everolimus as the main immunosuppressant in patients presenting severe neurotoxicity in the early post-transplantation period. From October 1988 to October 2012, 10 patients in our center received everolimus because of severe neurotoxicity in the 1st 3 months after transplantation. We analyzed several variables associated with this treatment, including patient characteristics, time from liver transplantation to conversion to everolimus, immunosuppression regimens before and after conversion, treatment efficacy, adverse events, and discontinuation after conversion. Median follow-up after conversion to everolimus was 27 months (range, 1-63 mo). Neurotoxic events were: akinetic mutism in 4 patients, repeated convulsions in 3, cerebrovascular accident in 1, Guillain-Barré syndrome in 1, and disabling tremor in 1. Treatment with calcineurin inhibitors was discontinued in all patients. Post-conversion regimens consisted of everolimus plus mycophenolate mofetil (MMF) plus steroids in 7 patients, everolimus plus MMF in 1, everolimus plus steroids in 1, and everolimus alone in 1. Liver function was maintained for ≥1 month in all patients except 1, who presented a severe rejection that was treated with steroid bolus and Neoral cyclosporine. Neurologic function was fully recovered in 8 patients. In 1 patient with akinetic mutism and another with convulsions, tacrolimus was reintroduced at 2 months and 1 month, respectively, after resolution of the neurotoxic event. Everolimus is feasible and effective as the main immunosuppressant in patients suffering severe neurotoxicity during the 1st 3 months after transplantation. It allows neurologic function to be recovered while maintaining adequate liver function.

Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report.

Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

Experiencia con rosiglitazona como tratamiento rediferenciador en un caso de carcinoma papilar de tiroides con metástasis pulmonares y ausencia de captación de radioyodo / Redifferentiation therapy with rosiglitazone in a case of differentiated thyroid cancer with pulmonary metastases and absence of radioiodine uptake

En el manejo de los pacientes con recidiva o metástasis de carcinoma diferenciado de tiroides, el tratamiento con radioyodo (RDI) es un tratamiento efectivo. Sin embargo, algunos de estos pacientes, a pesar de tener niveles elevados de TGB en sangre, no presentan captación de RDI en el rastreo corporal y, por tanto, pierden la capacidad de responder al tratamiento con él. Actualmente se están estudiando diferentes fármacos con posible efecto rediferenciador, entre los que se encuentran la rosiglitazona y diferentes retinoides. Su objetivo es aumentar la captación de RDI por las células tumorales. Se presenta el caso de una paciente que se sometió a tratamiento con rosiglitazona como tratamiento rediferenciador (8mg/día durante 2 meses) y con se logró captación de RDI por las metástasis pulmonares, con posterior disminución del tamaño de las mismas(AU)

Treatment with radioiodine (RDI) has been shown to be an effective option in patients with differentiated thyroid cancer with recurrent or metastatic disease. However, in spite of having elevated levels of thyroglobulin in blood, in some of these patients, the whole body scan does not detect radioiodine uptake due to loss of differentiation of the neoplastic cells, thus leading to loss of efficacy of the treatment. That is why drugs with potential differentiating properties, like rosiglitazone or retinoids, are being studied. The aim of these drugs is to improve RDI uptake by the tumor cells. In this work, we have described the case of a patient in whom uptake of RDI by the pulmonary metastases, with subsequent decrease of their size, was achieved after treatment with rosiglitazone (8mg/day for 2 months) as redifferentation therapy(AU)

A prospective, multicenter study of once-daily extended-release tacrolimus in de novo liver transplant recipients.

To minimize noncompliance in organ transplantation, a new formulation was developed of once-daily extended-release (EXTD) tacrolimus. To analyze the efficacy and safety of this new drug formulation in de novo liver transplant recipients, a prospective, multicenter study was performed in six centers in Spain. The primary objective of the study was to evaluate the incidence of biopsy-proven acute rejection episodes (BPAR) according to the BANFF criteria during the first 3 months of immunosuppression with the EXTD formulation of tacrolimus. Fifty-two patients received a mean initial dose of 10.0 ± 3.8 mg that was gradually reduced to 7.1 ± 4.0 mg, achieving stable mean blood levels of 8.6 ± 3.7 ng/mL at 3 months. BPAR was reported in seven (13%) patients, but patient and graft survivals were 100%. After transplantation liver function improved and was stably maintained throughout the study. At 3 months, mean bilirubin levels were 2.1 ± 5.5 mg/dL and mean alanine aminotransferase and aspartate aminotransferase were 61.6 ± 75.2 U/L and 55.2 ± 76.9 U/L, respectively. Mean serum creatinine of 0.8 ± 0.3 mg/dL pretransplant increased to 1.1 ± 0.4 mg/dL after 3 months (P < .0001). There was no significant increase in the rate of hypertension from pretransplant levels: 30% at baseline versus 31% at 3 months. Mean glucose levels did not change significantly throughout the study. There were no cases of hepatitis C virus relapse. EXTD tacrolimus demonstrated excellent stability in blood trough levels with a good efficacy and safety profile in de novo liver transplant recipients that was similar to the well-described properties of standard-release twice-daily formulation of tacrolimus.