A high concentration of TGF-ß correlates with opportunistic infection in liver and kidney transplantation.

Transforming growth factor-ß (TGF-ß) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-ß following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients. Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-ß concentration in the supernatant from the activated WPB. Recipients showed higher TGF-ß concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-ß than those without OI. A concentration of TGF-ß > 363.25 pg/ml in liver and TGF-ß > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations. TGF-ß could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.

Severe COVID-19 after liver transplantation, surviving the pitfalls of learning on-the-go: Three case reports.

BACKGROUND: The novel coronavirus 2019 (COVID-19) pandemic has dramatically transformed the care of the liver transplant patient. In patients who are immunosuppressed and with multiple comorbidities, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased severity and mortality. The main objective of this report is to communicate our experience in the therapeutic management of SARS-CoV-2 infection in 3 liver transplant patients. Secondly, we stress the management and investigation of the contagious spreading into a liver transplant ward. CASE SUMMARY: The patients were two women (aged 61 years and 62 years) and one man (aged 68 years), all of them having recently received a liver transplant. All three patients required intensive care unit admission and invasive mechanical ventilation. Two of them progressed severely until death. The other one, who received tocilizumab, had a good recovery. In the outbreak, the wife of one of the patients and four healthcare professionals involved in their care were also infected. CONCLUSION: We illustrate in detail the evolution of a nosocomial COVID-19 outbreak in a liver transplant ward. We believe that these findings will contribute to a better understanding of the natural history of the disease and will improve the treatment of the liver transplant patient with COVID-19.

[Azoles of then and now: a review]. / Azoles de antes y ahora: una revisión.

The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.

Azoles de antes y ahora: una revisión / Azoles of then and now: a review

Resumen Los azoles son fármacos que inhiben la enzima 14α-esteroldemetilasa, impidiendo la unión de ergosterol; esto altera la estructura y función de la pared celular fúngica. Especialmente el grupo de los triazoles: fluconazol, itraconazol, voriconazol, posaconazol e isavuconazol, son una alternativa farmacológica para el tratamiento de la enfermedad fúngica invasora causada por Aspergillus spp, Candida spp, Cryptococcus spp, patógenos emergentes como los Mucorales, y de micosis endémicas como las ocasionadas por Histoplasma spp y Coccidioides spp. Los efectos adversos de los triazoles son menos frecuentes comparados con los ocasionados por anfotericina B, un antifúngico de uso común para estas micosis. Los principales efectos adversos de los triazoles son hepáticos, gastrointestinales y cardiovasculares como la prolongación del intervalo QT. Las interacciones farmacológicas son usuales y se presentan con moléculas que usan sustratos del citocromo CYP3A4, lo que incluye anti-retrovirales, anti-tuberculosos e inmunomoduladores. En este trabajo se revisan la historia, características farmacológicas y los ensayos clínicos que evidencian su eficacia clínica en los diferentes escenarios clínicos.

Abstract The azoles are drugs that inhibit the 14α-sterol-demethylase enzyme preventing the binding of ergosterol, altering the functionality and structure of the fungal cell wall. Especially the group of triazoles: fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole, are a pharmacological alternative for the treatment of the invasive fungal disease, caused by Aspergillus spp, Candida spp, Cryptococcus spp, by emerging pathogens for example, the Mucoral and finally of endemic mycosis as those caused by Histoplasma spp. and Coccidioides spp. The adverse effects of the triazoles are less frequent compared to those caused by amphotericin B, the main ones being hepatics, gastrointestinals and cardiovasculars, such as the prolongation of the QT interval. The pharmacological interactions are common and occur with molecules that use the substrates of the CYP3A4 cytochrome, for example: antiretroviral, anti-tuberculous and immunomodulators. The history, pharmacological characteristics and clinical trials are reviewed.

Controlled donation after circulatory death up to 80 years for liver transplantation: Pushing the limit again.

Our main objective was to compare liver transplant (LT) results between donation after circulatory death (DCD) and donation after brainstem death (DBD) in our hospital and to analyze, within the DCD group, the influence of age on the results obtained with DCD donors aged >70 years and up to 80 years. All DCD-LTs performed were analyzed prospectively. The results of the DCD group were compared with those of a control group who received a DBD-LT immediately after each DCD-LT. Later, the results obtained within the DCD group were analyzed according to the age of the donors, considering 2 subgroups with a cut-off point at 70 years. Survival results for LT with DCD and super rapid recovery were not inferior to those obtained in a similar group of patients transplanted with DBD livers. However, the cost of DCD was a higher rate of biliary complications, including ischemic cholangiopathy. Donor age was not a negative factor.

The distance from the peroneal tendons sheath to the sural nerve at the posterior tip of the fibula decreases from proximal to distal.

PURPOSE: The aim of this study is to compare the distance from the peroneal tendons sheath to the sural nerve in different points proximally and distally to the tip of the fibula. METHODS: Ten fresh-frozen lower extremities were dissected to expose the nerves and tendons. Having the posterior tip of the fibula as a reference, the distance between the tendons sheath and the sural nerve was measured in each point with a tachometer with three independent different observers. Two measures were taken distally at 1.5 and 2 cm from fibula tip and 3 measures were performed proximally at 2, 3, and 5 cm from fibula tip. Data were described using means, standard deviations, medians, and minimum and maximum values. RESULTS: The average distance between distance between the fibula tip and sural nerve is 16.6 ± 4.4 mm. The average distance between peroneal tendons sheath and the sural nerve at 5 cm, 3 cm, and 2 cm from the proximal fibular tip was 29.6 ± 3.2 mm, 24.2 ± 3.6 mm, and 19.7 ± 2.7 mm, respectively. The average distance between the peroneal tendons sheath and the sural nerve at 2 cm and 1.5 cm distal to fibular tip was 9.1 ± 3.5 mm and 7.8 ± 3.3 mm, respectively. CONCLUSION: The distance from the peroneal tendons sheath to the sural nerve decreases from proximal to distal. As the distance between the peroneal tendons sheath and the sural nerve decreases from proximal to distal, performing the tendoscopy portal more distally would increase the risk of nerve iatrogenic injury.

Role of 18F-FDG PET/CT vs CT-scan in patients with pulmonary metastases previously operated on for colorectal liver metastases.

OBJECTIVE: There is currently no conclusive scientific evidence available regarding the role of the 18F-FDG PET/CT for detecting pulmonary metastases from colorectal cancer (PMCRC) in patients operated on for colorectal liver metastases (CRLM). In the follow up of patients who underwent surgery for CRLM, we compare CT-scan and 18F-FDG PET/CT in patients with PMCRC. METHODS: We designed the study prospectively performing an 18F-FDG PET/CT on all patients operated on for CRLM where the CT-scan detected PMCRC during the follow up. We included patients who were operated on for PMCRC because the histological findings were taken as a control rather than biopsies. RESULTS: Of the 101 pulmonary nodules removed from 57 patients, the CT-scan identified a greater number (89 nodules) than the 18F-FDG PET/CT (75 nodules) (p < 0.001). Sensitivity was greater with the CT-scan (90 vs 76%, respectively) with a lower specificity (50 vs 75%, respectively) than with the 18F-FDG PET/CT. There were no differences between positive-predictive value and negative-predictive value. The 18F-FDG PET/CT detected more pulmonary nodules in four patients (one PMCRC in each of these patients) and more extrapulmonary disease in six patients (four mediastinal lymph nodes, one retroperitoneal lymph node and one liver metastases) that the CT-scan had not detected. CONCLUSION: Although CT-scans have a greater capacity to detect PMCRC, the 18F-FDG PET/CT could be useful in the detection of more pulmonary and extrapulmonary disease not identified by the CT-scan. Advances in knowledge: We tried to clarify the utility of 18F-FDG PET/CT in the management of this subpopulation of patients.

Resección laparoscópica asistida de leiomiosarcoma hepático primario: un abordaje seguro en una tumoración infrecuente / Laparoscopically assisted resection of a primary hepatic leiomyosarcoma: A safe approach in a rare malignancy

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La Problemática Familiar y la Migración de los Adolescentes / Family Problems and Migration of Adolescents

Resumen: Este artículo aborda la problemática familiar, su relación con la migración de los padres y el deseo de migrar o no de los adolescentes de 12 a 18 años, en la comunidad rural de San Mateo Ozolco, municipio de Calpan, en el estado de Puebla, México. Se inició la investigación con un estudio exploratorio, a través de entrevistas a 10 informantes clave; se aplicó el Instrumento de Problemas Familiares a 121 estudiantes de secundaria y bachillerato. La población se dividió para su estudio considerando sus intenciones de migrar o no migrar, permitiendo con esto una diferenciación de las familias, después se relacionó con la problemática familiar, asimismo se dividió la población en hijos de padres migrantes y no migrantes para poder ver su correspondencia con los problemas familiares. Los resultados indican que la interacción familiar negativa y la agresión familiar, están influyendo en la decisión de migración de los adolescentes.

Abstract: This article deals with family issues, its relationship between the migration of parents and the adolescents' desire to migrate or not in the rural community of San Mateo Ozolco in state of Puebla, Mexico. Research began with an exploratory study, through interviews with 10 key informants; the Family Problems Instrument was applied to 121 middle and high school students. The population was divided for further detail, considering the intentions to migrate or not, allowing a differentiation between families and their relationship to family problems. Also, the population was divided into children of migrant and non migrant parents to see their correspondence with family problems. The results indicate that the Family Negative interaction and the Family Aggression are influencing the migration decision of adolescents.

Metástasis hepática y pancreáticas de un tumor fibroso solitario / Liver and pancreatic metastasis of a solitary fibrous tumour

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Successful embolization of a cytomegalovirus-related duodenal ulcer in a kidney-pancreas transplant recipient.

One of the complications that can occur in pancreas transplant is a massive intestinal hemorrhage, although such a hemorrhage is very rarely caused by ulcers due to cytomegalovirus infection. Treatment is fundamentally based on relaparatomy, although in some cases interventional radiology can be an efficient alternative because it allows the exact bleeding point to be located and therapeutic embolization to be performed. In this case, a man with diabetes type 1 who was given a simultaneous kidney-pancreas transplant had an ulcer due to cytomegalovirus infection develop in the duodenal graft (in the early postoperative period), causing a severe hemorrhage in the lower part of the gastrointestinal tract that was controlled via selective embolization of a branch of the pancreaticoduodenal artery.

Outcome of strict patient selection for surgical treatment of hepatic and pulmonary metastases from colorectal cancer.

BACKGROUND: Surgery is currently the only potentially curative treatment for hepatic or pulmonary metastases from colorectal cancer. However, the benefit of surgery and the criteria for the inclusion of patients developing hepatic and pulmonary metastases are not well defined. OBJECTIVE: The aim of this study was to describe the outcome for patients who undergo surgery for both hepatic and pulmonary metastases from colorectal cancer, to present a set of preoperative criteria for use in patient selection, and to analyze potential prognostic factors related to survival. DESIGN: This was an observational study with retrospective analysis of data collected with a prospective protocol. SETTINGS: This investigation was conducted at a tertiary centre. PATIENTS: Between January 1996 and January 2010, of 319 patients who underwent surgery for hepatic metastases from colorectal cancer, 44 also had resection of pulmonary metastases. A set of strict selection criteria established by a panel of liver surgeons, chest surgeons, oncologists, and radiologists was used. MAIN OUTCOME MEASURES: Survival was estimated with the Kaplan-Meier method, and univariate analyses were performed to evaluate potential prognostic factors for survival, including variables related to patient, primary tumour, hepatic, and pulmonary metastases and chemotherapy. RESULTS: The 44 patients received a total of 53 pulmonary resections: 36 patients had 1, 7 patients had 2, and 1 patient had 3 resections. There was no postoperative mortality and the morbidity rate after pulmonary resection was 1.8%. No patient was lost to follow-up. Overall survival was 93% at 1 year, 81% at 3 years, and 64% at 5 years. Factors related to poor prognosis in the univariate analysis were presence of more than 1 pulmonary metastasis (p = 0.04), invasion of the surgical margin (p = 0.006), and administration of neoadjuvant chemotherapy (p = 0.01 for hepatic metastases and p = 0.02 for pulmonary metastases). LIMITATIONS: The study was limited by its observational nature and the relatively small number of patients. CONCLUSION: In patients with hepatic and pulmonary metastases from colorectal cancer selected according to strict inclusion criteria, surgical treatment performed in a specialized center is a safe option that offers prolonged survival.

Liver transplantation for hilar cholangiocarcinoma.

The most appropriate treatment for Klatskin tumor (KT) with a curative intention is multimodal therapy based on achieving resection with tumour-free margins (R0 resections) combined with other types of neoadjuvant or adjuvant treatment (the most important factor affecting KT survival is the possibility of R0 resections, achieving 5-year survival rate of 40%-50%). Thirty to forty percent of patients with KT are inoperable and present a 5-year survival rate of 0%. In irresectable non-disseminated KT patients, using liver transplantation without neoadjuvant treatment, the 5-year survival rate increase to 38%, reaching 50% survival in early stage. In selected cases, with liver transplantation and neoadjuvant treatment (chemotherapy and radiotherapy), the actuarial survival rate is 65% at 5 years and 59% at 10 years. In conclusion, correct staging, neoadjuvant treatment, living donor and priority on the liver transplant waiting list may lead to improved results.

Influence of human leukocyte antigen mismatching on rejection development and allograft survival in liver transplantation: is the relevance of HLA-A locus matching being underestimated?

The influence of HLA matching on liver transplant is still controversial, as studies have failed to demonstrate an adverse effect of HLA mismatching on transplant outcome. We examined the effect of HLA mismatching on transplant outcome in a series of 342 consecutive liver transplants (224 finally analyzed). HLA typing was performed by serological and molecular methods. HLA-A matching was associated with an increased chronic rejection incidence (P=0.04). Indeed, HLA-A match also demonstrated a significant impact on allograft survival (P=0.03), confirming previous observation concerning to rejection, as complete HLA-A mismatching favored a better liver transplant outcome. Analysis of HLA-A+B+DR matching also demonstrated a significant impact on graft survival (P<0.05). Multivariate Cox regression analysis confirmed the effect of HLA-A and DPB1 matching as independent risk factors for graft loss. Another independent factor was a positive pre-transplant crossmatch. In conclusion, liver transplant outcome has not been found to be improved by HLA matching, however a poorer HLA compatibility favored a better graft survival and decreased rejection incidence, with a special relevance for HLA-A matching.

El trasplante hepático aumenta la resecabilidad R0 y la supervivencia de los pacientes con tumor de Klatskin irresecable no diseminado / Liver transplantation increases R0 resection and survival of patients with a non-disseminated unresectable Klatskin tumour

Introducción La indicación de trasplante hepático (TH) en el tumor de Klatskin (TK) no está establecida debido a la discrepancia en los resultados de las series publicadas. Objetivo Presentar los resultados del TH en pacientes con TK irresecable no diseminado y compararlos con los obtenidos en los pacientes no resecados y con resección del tumor. Pacientes y método Hemos tratado 75 pacientes con TK. La edad media fue de 62±11 años (rango: 38–88) y 50 fueron varones (66%). Veinte pacientes se consideraron inoperables. Se realizó resección del tumor (RT) en 29 de los 55 pacientes operados, TH en 11 casos (en tumores irresecables no diseminados) y tratamiento paliativo en los 15 pacientes con TK irresecables diseminados. Resultados En el grupo TH no hubo mortalidad postoperatoria (primer mes) y presentaron una supervivencia a 1, 3 y 5 años del 95, el 59 y el 36% con una supervivencia libre de enfermedad (SLE) del 75, el 40 y el 20%. Los pacientes con RT presentaron una supervivencia del 80, el 52 y el 38%, con una SLE del 65, el 35 y el 19%, sin diferencias respecto al grupo TH. Los pacientes con tumor irresecable que quedaron con tratamientos paliativos presentaron una supervivencia inferior a la de los pacientes con tumores irresecables que recibieron TH (p<0,001).Conclusiones En pacientes con TK irresecable no diseminado, el TH consigue una supervivencia similar a la obtenida en los casos resecables con la resección hepática R0, y mejora claramente la esperanza de vida de estos pacientes con tratamientos paliativos (AU)

Introduction There are no established indications for Liver transplant (LT) in patients with a Klatskin tumour (KT) due to the differences in the published results. Objective To report on our patients who have non-disseminated unresectable KT and who were given a LT, and to compare results with those of patients who have had tumour resection and those who have not. Patients and method We have treated 75 patients diagnosed with KT. The mean age was 62±11 years (range: 38–88 years) and 50 were males (66%). Twenty patients were inoperable. Of the 55 patients who underwent surgery: tumour resection (TR) was performed in 29 cases; there was no tumour dissemination in 11 unresectable cases and therefore these patients were added to the LT waiting list and the remaining 15 unresectable cases had tumour dissemination and remained on palliative treatment.ResultsIn the LT group there was no postoperative mortality (during the first month) and the survival rate was 95%, 59% and 36% with a disease-free survival of 75%, 40% and 20%; whereas the patients given RT had a survival rate of 80%, 52% and 38% at 1, 3 and 5 years, with a disease-free survival of 65%, 35% and 19%, without any differences compared to the LT group. Patients with unresectable tumour left on palliative therapy had a lower survival than the unresectable who underwent LT (p<0.001).Conclusions In patients with non-disseminated unresectable KT, LT has a similar survival to that obtained in cases with resectable R0 liver resection. LT improves the survival rate achieved using palliative treatment in patients with non-disseminated unresectable KT (AU)

[Liver transplantation increases R0 resection and survival of patients with a non-disseminated unresectable Klatskin tumour]. / El trasplante hepático aumenta la resecabilidad R0 y la supervivencia de los pacientes con tumor de Klatskin irresecable no diseminado.

INTRODUCTION: There are no established indications for Liver transplant (LT) in patients with a Klatskin tumour (KT) due to the differences in the published results. OBJECTIVE: To report on our patients who have non-disseminated unresectable KT and who were given a LT, and to compare results with those of patients who have had tumour resection and those who have not. PATIENTS AND METHOD: We have treated 75 patients diagnosed with KT. The mean age was 62 + or - 11 years (range: 38-88 years) and 50 were males (66%). Twenty patients were inoperable. Of the 55 patients who underwent surgery: tumour resection (TR) was performed in 29 cases; there was no tumour dissemination in 11 unresectable cases and therefore these patients were added to the LT waiting list and the remaining 15 unresectable cases had tumour dissemination and remained on palliative treatment. RESULTS: In the LT group there was no postoperative mortality (during the first month) and the survival rate was 95%, 59% and 36% with a disease-free survival of 75%, 40% and 20%; whereas the patients given RT had a survival rate of 80%, 52% and 38% at 1, 3 and 5 years, with a disease-free survival of 65%, 35% and 19%, without any differences compared to the LT group. Patients with unresectable tumour left on palliative therapy had a lower survival than the unresectable who underwent LT (p<0.001). CONCLUSIONS: In patients with non-disseminated unresectable KT, LT has a similar survival to that obtained in cases with resectable R0 liver resection. LT improves the survival rate achieved using palliative treatment in patients with non-disseminated unresectable KT.