Pharmacologic Treatment of Anti-MDA5 Rapidly Progressive Interstitial Lung Disease.

Purpose of the Review: Idiopathic inflammatory myopathies are a heterogeneous group of autoimmune disorders. The presence of different autoantibodies allows clinicians to define distinct phenotypes. Antibodies against the melanoma differentiation-associated protein 5 gene, also called anti-MDA5 antibodies, are associated with a characteristic phenotype, the clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease. This review aims to analyze the different pharmacological options for the treatment of rapidly progressive interstitial lung disease in patients with anti-MDA5 antibodies. Recent Findings: Evidence-based therapeutic recommendations suggest that the best initial approach to treat these patients is an early combination of immunosuppressive drugs including either glucocorticoids and calcineurin inhibitors or a triple therapy adding intravenous cyclophosphamide. Tofacitinib, a Janus kinase inhibitor, could be useful according to recent reports. High ferritin plasma levels, generalized worsening of pulmonary infiltrates, and ground-glass opacities should be considered predictive factors of a bad outcome. In this scenario, clinicians should consider rescue therapies such as therapeutic plasma exchange, polymyxin-B hemoperfusion, veno-venous extracorporeal membrane oxygenation, or even lung transplantation. Summary: Combined immunosuppressive treatment should be considered the first-line therapy for patients with anti-MDA5 rapidly progressive interstitial lung disease. Aggressive rescue therapies may be useful in refractory patients.

Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population.

BACKGROUND AND OBJECTIVES: To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. MATERIALS AND METHODS: The study included 13,179 workers (73% men; mean age: 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. RESULTS: A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. CONCLUSIONS: In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19%.

Identification of peripheral CD154+ T cells and HLA-DRB1 as biomarkers of acute cellular rejection in adult liver transplant recipients.

Decreasing graft rejection and increasing graft and patient survival are great challenges facing liver transplantation (LT). Different T cell subsets participate in the acute cellular rejection (ACR) of the allograft. Cell-mediated immunity markers of the recipient could help to understand the mechanisms underlying acute rejection. This study aimed to analyse different surface antigens on T cells in a cohort of adult liver patients undergoing LT to determine the influence on ACR using multi-parametric flow cytometry functional assay. Thirty patients were monitored at baseline and during 1 year post-transplant. Two groups were established, with (ACR) and without (NACR) acute cellular rejection. Leukocyte, total lymphocyte, percentages of CD4+ CD154+ and CD8+ CD154+ T cells, human leukocyte antigen (HLA) mismatch between recipient-donor and their relation with ACR as well as the acute rejection frequencies were analysed. T cells were stimulated with concanavalin A (Con-A) and surface antigens were analysed by fluorescence activated cell sorter (FACS) analysis. A high percentage of CD4+ CD154+ T cells (P = 0·001) and a low percentage of CD8+ CD154+ T cells (P = 0·002) at baseline were statistically significant in ACR. A receiver operating characteristic analysis determined the cut-off values capable to stratify patients at high risk of ACR with high sensitivity and specificity for CD4+ CD154+ (P = 0·001) and CD8+ CD154+ T cells (P = 0·002). In logistic regression analysis, CD4+ CD154+ , CD8+ CD154+ and HLA mismatch were confirmed as independent risk factors to ACR. Post-transplant percentages of both T cell subsets were significantly higher in ACR, despite variations compared to pretransplant. These findings support the selection of candidates for LT based on the pretransplant percentages of CD4+ CD154+ and CD8+ CD154+ T cells in parallel with other transplant factors.

Prevalence of hypertrophic cardiomyopathy in a large sample of the Spanish working population. / Prevalencia de la miocardiopatía hipertrófica en una amplia muestra de la población laboral española.

BACKGROUND AND OBJECTIVES: To date, in Spain, there are no studies that have evaluated the prevalence of hypertrophic cardiomyopathy in the general population. The aim of this study was to assess the prevalence of hypertrophic cardiomyopathy in a large sample of the working population of Spain. MATERIALS AND METHODS: The study included 13,179 workers (73% men; mean age, 40 years) from 5 regions of Spain who, between May 2008 and November 2010, had a medical examination with an electrocardiogram. The workers with suggestive abnormalities in the electrocardiogram or a predisposing medical history (exertional syncope or sudden death of a family member younger than 50 years) were referred for an echocardiographic evaluation. We defined hypertrophic cardiomyopathy as a parietal thickness ≥13mm in any segment of the left ventricle. We estimated the prevalence of hypertrophic cardiomyopathy in the entire sample and in the workers without hypertension. RESULTS: A total of 1008 workers were selected for the echocardiogram, although only 496 (49.2% of those selected) of these attended the appointment. After the echocardiogram, we detected 16 cases of hypertrophic cardiomyopathy, estimating a prevalence of 0.24% for the entire sample. In the subgroup of workers with no hypertension, we observed 10 cases of hypertrophic cardiomyopathy, which corresponds to an estimated prevalence of 0.19%. CONCLUSIONS: In our sample of the working population in Spain, the estimated prevalence of hypertrophic cardiomyopathy was 0.24%. In the subgroup of patients with no hypertension, the estimated prevalence was 0.19%.

Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Uso de cânula rígida com rosca e endoscópio flexível para videolaparoscopia de acesso único em equinos em estação / Use of threaded rigid cannula and flexible endoscope for single access video laparoscopy in standing horses

Com o objetivo de promover, por meio de acesso único e com o uso de endoscópio flexível, ampla exploração da cavidade peritoneal de equinos em estação, foi concebida uma cânula laparoscópica para dar sustentação ao endoscópio e possibilitar o acesso sob visualização. O procedimento foi realizado a partir da fossa paralombar. Após pequena incisão cutânea, o endoscópio foi inserido na cânula e os músculos e o peritônio foram divulsionados mediante rotação da cânula. Logo depois da perfuração do peritônio, foi realizada a exploração da cavidade e a identificação das estruturas. Em seguida à exploração do lado ipsilateral ao acesso, realizou-se a transposição do conjunto cânula/endoscópio ventralmente à porção caudal do cólon descendente, seguida de exploração do lado contralateral. Concluída a técnica, foi executado, para fins de comparação, o mesmo procedimento por meio da fossa paralombar contralateral. Foi possível a transposição do conjunto cânula/endoscópio para o lado contralateral ao acesso em todos os procedimentos. Também foi possível a identificação da maioria das estruturas abdominais tanto pelo acesso esquerdo quanto pelo direito. A abordagem por acesso único mostrou-se viável para a exploração ampla da cavidade peritoneal, demonstrando ser uma alternativa à técnica laparoscópica convencional.(AU)

A laparoscopic cannula was designed to support a single access approach with a flexible endoscope for the wide exploration of the peritoneal cavity of standing horses. It provides support to the endoscope and allows access to the peritoneal cavity with a visual aid. This procedure was performed through the paralumbar fossa. After a small cutaneous incision, the endoscope was inserted into the cannula, and the muscles and peritoneum were divulsed through the rotation of the cannula. After the peritoneal perforation, cavity exploration and identification of structures were performed. After the exploration of the ipsilateral side of the access, the cannula/endoscope was transposed ventrally to the caudal portion of the descending colon; this was followed by the exploration of the contralateral side. Once this process was completed, the same procedure was performed through the contralateral paralumbar fossa for comparison. It was possible to transpose the cannula/endoscope set to the contralateral access side in all procedures. Further, it was possible to identify most of the abdominal structures in both the left and right access. This single access approach proved to be feasible for the extensive exploration of the peritoneal cavity, thereby indicating it can be an alternative to the conventional laparoscopic technique.(AU)

Psoas Muscle Index Does Not Predict Post-Transplant Outcomes: A Series of 57 Liver Transplant Recipients.

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function. Our aim is to evaluate the degree of sarcopenia by measuring the patients on the waiting list for liver transplantation and its influence on the different post-liver transplant outcomes in our group. METHODS: The psoas muscle index (PMI, cm2/m2) was calculated (right psoas muscle area [cm2]/the square of the body height [m2]) in 57 patients on the waiting list for liver transplantation in our center, and the post-transplant variables relevant to our study were collected. RESULTS: The 57 recipients had a mean age of 57 years (range, 35-73) and had a mean of 7.4 months (range, 0-39) on the liver transplant waiting list. The mean psoas muscle index was 2.39 (range, 1-4), and the mean body mass index was 28.01kg/m2 (range, 22-36). After multivariate analysis we found a positive correlation between the PMI and the body mass index of the recipients (r = 0.320, P = .017), intensive care unit length of stay, and donor age (r = 0.319, P = .042), and between cold ischemia time and graft survival (r = 0.366, P = .009). We found no correlation in our sample between PMI and post-liver transplant complications either in terms of graft or patient survival. CONCLUSION: PMI is not representative of total muscle mass and sarcopenia and is not effective in adequately predicting the survival of patients on the waiting list for liver transplantation.

Impact of Hepatic Artery Thrombosis on the Success of a Liver Transplant Because of Hepatocellular Carcinoma.

BACKGROUND: Hepatic artery thrombosis is one of the most serious complications after liver transplant. Our objective is to evaluate the impact of arterial thrombosis on the postoperative evolution of a series of patients who received transplants because of hepatocellular carcinoma. METHODS: A retrospective study of 100 consecutive hepatocellular carcinoma liver transplants was performed from January 2011 to November 2017. RESULTS: Of the 100 transplant recipients, we have observed hepatic artery thrombosis in 4 of them, 3 premature and 1 delayed. All of them received retransplants after diagnosis by hepatic artery ultrasonography and arteriography. The descriptive analysis showed a significant relationship between the appearance of hepatic artery thrombosis with variables of postoperative severity, such as arrhythmias, atelectasis, pleural effusion, hemodialysis requirement, acute kidney failure, and respiratory failure. Although patients with hepatic artery thrombosis had a longer mean hospital stay, this was not statistically significant. There was decreased graft survival and overall survival of patients who experienced hepatic artery thrombosis. CONCLUSION: Although the incidence of hepatic artery thrombosis has been relatively low (4%), the early detection of risk factors, such as arterial anatomic anomalies that condition a complex anastomosis, should draw our attention, thus having at our disposal strict ultrasonography and arteriography surveillance protocols as well as prophylactic anticoagulation guidelines for receptors at risk.

Performance, carcass yield, and meat quality of broilers supplemented with organic or inorganic zinc / Desempenho, rendimento e qualidade da carne de frangos de corte suplementados com zinco orgânico ou inorgânico

A total of 640 one-day-old Cobb broiler chicks, half male and half female, were reared up to 49 days of age. A completely randomized 2 × 4 factorial design was used. Experimental treatments consisted of four levels of organic zinc supplementation and one control (inorganic zinc supplementation) and two levels of sex (female and male), with four replicates of 16 birds per experimental plot. Animal performance, carcass and cut yields, and meat quality were evaluated. Feed intake increased with zinc supplementation. Broilers that received the lowest level of organic zinc showed better feed conversion than those fed an equivalent level of inorganic zinc. Increased levels of organic zinc reduced the abdominal fat content in females but impaired the oxidative stability of meat. The results showed that male broilers have better performance, carcass yield, and meat quality than females and that organic zinc improves broiler feed conversion and reduces abdominal fat but increases lipid oxidation in meat.(AU)

Foram alojados 640 pintainhos de corte, sendo metade de machos e metade de fêmeas, da linhagem Cobb, de um a 49 dias de idade. Foi adotado um delineamento inteiramente ao acaso, em esquema fatorial 2 × 4. Os tratamentos experimentais consistiram em quatro níveis de suplementação de zinco orgânico e um controle inorgânico, e diferentes sexos, com quatro repetições de 16 aves por parcela experimental. Foram avaliados o desempenho, a característica da carcaça e dos cortes, bem como a qualidade de carne dos frangos. O aumento dos níveis de zinco elevou o consumo de ração dos frangos. Os frangos que receberam zinco orgânico na exigência mínima apresentaram melhor conversão alimentar comparados àqueles que receberam ração de fonte inorgânica. O aumento nos níveis de zinco orgânico proporcionou redução no teor de gordura abdominal para fêmeas, mas níveis de zinco orgânico prejudicaram a estabilidade oxidativa da carne. Conclui-se que frangos machos apresentam melhor desempenho, carcaça e qualidade de carne em relação às fêmeas, e que o zinco orgânico melhora a conversão alimentar dos frangos, reduz a gordura abdominal, porém eleva a oxidação lipídica da carne.(AU)

Comparative Study of Infliximab Versus Adalimumab in Refractory Uveitis due to Behçet's Disease: National Multicenter Study of 177 Cases.

OBJECTIVE: To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first-line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to Behçet's disease (BD). METHODS: We conducted an open-label multicenter study of IFX versus ADA for BD-related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first-line biologic agent based on physician and patient agreement. Patients received 3-5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4-8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups. RESULTS: The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best-corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042). CONCLUSION: Although both IFX and ADA are efficacious in refractory BD-related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow-up.

Riesgo dinámico en cáncer diferenciado de tiroides: comparación entre pacientes ablacionados con aquellos no ablacionados de bajo riesgo y riesgo intermedio de recurrencia

RESUMEN El enfoque actual de los pacientes con carcinoma diferenciado de tiroides (CDT) es individualizado de acuerdo al riesgo de recurrencia (RR) de la enfermedad. La clasificación estática del RR inicial podría mejorarse al aplicar el denominado riesgo dinámico, que resulta de adicionar al RR, los hallazgos que surgen durante el seguimiento. Los objetivos de este trabajo fueron comparar pacientes ablacionados de bajo RR y riesgo intermedio estático que recibieron ablación inmediatamente luego de la cirugía vs. los no ablacionados de bajo riesgo dinámico. Secundariamente, comparar la población de pacientes ablacionados de bajo riesgo estático vs. los no ablacionados de bajo riesgo dinámico. Se incluyeron 412 pacientes, 309 ablacionados (Grupo 1: G1), y 103 no ablacionados (Grupo 2: G2). El G1 también incluyó a 29 pacientes que fueron ablacionados al observar el riesgo dinámico (Tg bajo terapia hormonal > 5 ng/ml). La frecuencia de respuesta estructural incompleta (REI) al inicio y al final del seguimiento fue mayor en el grupo de pacientes ablacionados de bajo RR y riesgo intermedio estático comparados con los no ablacionados de bajo riesgo dinámico (11,3% vs 0,9%: p=<0,001). La frecuencia de respuesta excelente al final del seguimiento fue mayor en los no ablacionados de bajo riesgo dinámico vs. ablacionados de bajo RR y riesgo intermedio estático (72,8% vs 62,1%: p=0,058). En conclusión, los pacientes ablacionados de bajo RR y riesgo intermedio presentaron una mayor frecuencia de REI que los no ablacionados adecuadamente seleccionados, al tener en cuenta el RR inicial. En cambio, al comparar pacientes ablacionados de bajo RR estático vs. no ablacionados de bajo riesgo dinámico, la REI fue similar. Estos resultados avalan la conducta de no ablacionar a aquellos pacientes de riesgo intermedio de recurrencia que presentan en el seguimiento un bajo riesgo dinámico.

ABSTRACT The current approach of patients with differentiated thyroid carcinoma (DTC) is individualized according to the risk of recurrence (RR) of the disease. The static classification of the initial RR could be improved by applying the dynamic risk of recurrence to decide remnant ablation. The dynamic risk definition arise from the findings obtained during the initial follow-up. The aim of this manuscript is to compare the response to treatment in patients with low and intermediate static RR in whom the decision for radioiodine remnant ablation (RRA) was performed immediately after surgery with those non-ablated patients with low dynamic RR. Secondary, to compare the responses to treatment in ablated patients with low static RR compared with those non-ablated low dynamic RR. We included 412 patients, they were divided in two groups Group 1 (G1): n=309 ablated patients and Group 2 (G2): n=103 non-ablated patients. G1 also included 29 patients who received remnant ablation considering the dynamic risk (Tg levels > 5 ng/ml). The initial structural incomplete response (SIR) was greater in G1 compared with G2 (11.3% vs 0.9%: p = <0.001). The frequency of an excellent response at the end of follow-up was similar in G2 compared with low initial RR of G1 (72.8% vs. 62.1%: p = 0.058). In conclusion, low and intermediate static RR ablated patients had a higher frequency of SIR compared with non-ablated patients in the dynamic risk assessment. In contrast, the frequency of SIR was similar when ablated patients of low static RR were compared with those non-ablated patients of low dynamic risk. These results show how the dynamic RR helps to move those intermediate RR patients on the low RR decreasing the need for RRA.

Early Outcomes of Liver Transplantation Using Donors After Circulatory Death in Patients With Hepatocellular Carcinoma: A Comparative Study.

INTRODUCTION: Donation after circulatory death (DCD) has increased in the last decade, although a slight increase in surgical complications has been reported in liver transplantation (LT). Therefore, DCD is not overall recommended because it entails an added risk. However, DCD in selected patients shows acceptable results. OBJECTIVE: The objective was to analyze the characteristics, early outcomes, and survival at 1 year post-LT from a single institute (January 2015 to May 2017). MATERIALS AND METHODS: We included 18 DCD-LTs and compared them with a control group of 18 donation after brain death (DBD) LTs. We analyzed pre- and posttransplant variables related to donors, recipients, and intraoperative early outcomes within patients transplanted due to hepatocellular carcinoma (HCC). A descriptive analysis, Mann-Whitney U test, χ2, or Fisher test was performed when appropriate, as well as multivariate analysis in case of statistical significance. A variable is considered as statistically significant when it reaches a value of P < .05. RESULTS: In DBD, we found a lower length of stay in the intensive care unit before retrieval and a higher rate of alcoholism and diabetes mellitus, Model for End-Stage Liver Disease score, and Child B and C score (P < .05). Most of the DCD were originally from the same LT recipient center, and a higher donor mean post-LT alanine aminotransferase level was found (P < .05). Survival for the DBD group was 88% and 75% in the DCD group at 1 year post-LT, being not significant (NS). CONCLUSION: HCC recipients who are transplanted with good quality DCD livers do no worse than those transplanted with livers from DBD donors, although a good selection of them is crucial.

A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating MHC class I-related chain A.

The major histocompatibility complex (MHC) class I-related chain A (MICA) is induced upon stress, and labels malfunctioning cells for their recognition by cytotoxic lymphocytes. Alterations in this recognition and also abnormal natural killer (NK) functions have been found in systemic lupus erythematosus (SLE). MICA can be shed from cells, subsequently acting as a soluble decoy receptor (sMICA). Our purpose was to study circulating sMICA levels in relationship with the activation of innate pathways in PBMC in a cohort of lupus patients. NK cells were characterized by flow cytometry. Gene expression of Toll-like receptors (TLR), interferon (IFN)-I sensitive genes and MICA were separately analyzed in monocytes, T cells and B cells. Serum sMICA was measured with enzyme-linked immunosorbent assay (ELISA). In our cohort, NK cell counts dropped in relationship with disease activity. sMICA showed an inverse trend with NK cell counts, as well as a significant association with activity indices, but not with complement decrease. Levels of sMICA associated to proteinuria and active nephritis. A multivariate regression model revealed anti-nuclear antibody (ANA) titres, the up-regulation of TLR-4 in T cells and lower vitamin D as predictors of sMICA enhancement. Interestingly, vitamin D showed an inverse association with proteinuria and a strong correlation with T cell MICA mRNA levels. According to our data, circulating sMICA identifies a subgroup of lupus patients with low vitamin D, innate activation of T cells and nephritis. We propose that lymphocyte shedding could account for the enhancement of sMICA and reflect an immune evasion mechanism driving disease activation in lupus.

Liver Transplantation for Fulminant Hepatic Failure Due to Heat Stroke: A Case Report.

Heat stroke is a condition caused by an excessive increase in body temperature in a relatively short period of time, and is clinically characterized by central nervous system dysfunction, including delirium, seizures, coma, and severe hyperthermia. In this context, the resulting fulminant hepatic failure makes liver transplant the best choice when there are no guarantees of better results with conservative treatment. We present our experience in this case, possible alternative choices, and the current role of liver transplantation in the resolution of fulminant liver failure due to heat stroke. CASE REPORT: We report the case of a 32-year-old man with a history of malabsorption syndrome and unconfirmed celiac disease controlled with a gluten-free diet, who, while working on a typical summer midday in southern Spain (approximately 40°C), abruptly presented with loss of consciousness, coma, and a temperature of 42°C, as well as seizures at the initial medical assessment that subsided after the administration of diazepam. On the third day, the patient presented with multiple organ dysfunction syndrome, requiring mechanical ventilation, hemodialysis, and inotropic support. He did not improve with the support of conservative treatment, therefore it was decided to perform an urgent liver transplant, after which he recovered completely. CONCLUSIONS: Liver transplantation should be a main choice of treatment for cases in which, despite intensive medical treatment, there is still clinical and analytical evidence of massive and/or irreversible hepatocellular damage.

Orthotopic Liver Transplantation With Elderly Donors (Over 80 Years of Age): A Prospective Evaluation.

BACKGROUND: Our main objective was to assess the clinical outcomes obtained in a single orthotopic liver transplant (OLT) hospital with donors ≥80 years of age compared to a control group of patients subjected to OLT during the same period of time with donors who were under 65 years of age. METHODS: A prospective analysis was carried out on all the OLTs performed using liver grafts from donors in a state of brain death and with an age of ≥80 years (study group) between April 2007 and January 2015. The results of the study group (n = 36) were compared with those of a control group of patients less than 65 years of age receiving transplants with grafts. RESULTS: A total of 51 potential donors ≥80 years were assessed, with a total of 36 liver transplants being carried out and their results were compared with a control group of 283 patients receiving transplants. The median follow-up time of the patients in the series was 36 months (range: 24-120 months). Graft survival at 1, 2, and 3 years was 77%, 72%, and 62%, respectively, among the patients in the study group and 79%, 73%, and 65% among the patients in the control group, and there were no statistically significant differences. Patient survival at 1, 2, and 3 years was 86%, 82%, and 75%, respectively, among the patients in the study group and 82%, 76%, and 72% among the patients in the control group, also without there being any statistically significant differences. CONCLUSIONS: There is no age limit for liver transplant donors. The use of octogenarian donors makes it possible to increase the pool of donors while providing enough safety for the recipient.

Respuesta parcial a lenvatinib como segunda línea de tratamiento en cáncer diferenciado avanzado de tiroides / Partial response to lenvatinib as a second line of treatment in advanced differentiated cancer of thyroid

RESUMEN Las metástasis a distancia ocurren en alrededor del 10% de los pacientes con cáncer diferenciado de tiroides (CDT), y cerca de la mitad de estos casos serán refractarios al radioyodo (RAIR). Sorafenib fue el primer inhibidor multicinasa (IMK) aprobado por la FDA para su uso en cáncer diferenciado de tiroides RAIR avanzado y progresivo, y hasta el momento es el único aprobado por la ANMAT en nuestro país para esta indicación. Lenvatinib es el segundo IMK aprobado por la FDA para este grupo de pacientes, y es una alternativa terapéutica que debe ser considerada, debido a su disponibilidad como fármaco de uso compasivo en nuestro país. Presentamos nuestra experiencia con el uso de lenvatinib como segunda línea de tratamiento en una paciente con CDT progresivo previamente tratado con sorafenib.

ABSTRACT Distant metastases occur in around 10% of patients with differentiated thyroid cancer (DTC), and half of these cases will become refractory to radioiodine therapy (RAIR). Sorafenib was the first multikinase inhibitor (MKI) approved by the FDA for patients with differentiated advanced and progressive RAIR thyroid cancer, and it is the only one approved by ANMAT in our country for this indication. Lenvatinib is the second MKI approved by the FDA for this group of patients, and is a therapeutic alternative that should be considered, due to its availability as a compassive use drug in our country. We present our experience with the use of lenvatinib as a second line of treatment in a patient with DTC with advanced and progressive disease under treatment with sorafenib.

Liver Transplantation in Patients With Hepatocellular Carcinoma Outside the Milan Criteria After Downstaging: Is It Worth It?

BACKGROUND: The outcome of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) is excellent if it is performed within the Milan criteria (ie, single tumor less than 5 cm or 3 tumors less than 3 cm each one and no macrovascular invasion). However, after a few studies, it has become possible to have a similar survival expanding those criteria. The aim of this study is to evaluate the survival of patients with advanced HCC who, after downstaging, did not met the Milan criteria although they were within the "up to seven" benchmark, and were transplanted at our center in the last 5 years. PATIENTS AND METHODS: This is a retrospective study of patients who underwent OLT for HCC in the last 5 years in our center exceeding Milan criteria despite remaining within the "up to seven" benchmark. An observational study of associated factors with overall survival based on patient characteristics after OLT was performed. For the statistical study, the statistical program SPSS v. 17.0 (Chicago, Illinois, United States) was used. RESULTS: We studied 95 patients who had been transplanted for HCC in this period, 11 of whom met the study requirements. There were 10 (91%) males and 1 female. The mean age of the patients was 54.73 ± 8.75 years, with an average waiting list time of 279 days. Nine patients had a Child A status, with a mean Model for End-stage Liver Disease score of 9.64 (range, 6 to 16). The most frequent etiology of cirrhosis was hepatitis C virus infection in 6 patients (50%) followed by hepatitis B virus infection and ethanolic and cryptogenic cirrhosis. Ten patients (91%) had at least one pretransplantation transarterial chemoembolization. The survival of patients after 1 year was 75%, whereas after 4 years that rate decreases to 25%. At this time, we do not have any patients with a 5-year survival rate. The longest survival rate is 55 months. CONCLUSIONS: Although the expanded indication of transplantation in HCC raises controversies, especially after downstaging, it is possible to provide acceptable survival rates for patients within the expanded criteria of "up to seven" after locoregional therapies. The performance of a liver transplant in the patient profile shown in this article should also be evaluated from the perspective of the relative lack of organs for transplantation.