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To analyze the determinants that influence the health-related quality of life of people living with HIV in Alicante (Spain).A cross-sectional study was conducted, which recruited 214 Spanish-speaking participants over 18 years of age living with HIV from an outpatient consulting office of the infectious diseases in a hospital in Alicante between 2013 and 2014. A self-administration sociodemographic survey and the Short Form Health Survey (SF-36v2) was used to assess health-related quality of life. This questionnaire measures health on 8domains.70% of the participants were male, 50% had CD4 cell count between 200-499 cells/mmThe socioeconomic level and the presence of clinical factors such as HCV influence the scales of quality of life of physical health among adults living with HIV.

INTRODUCTION Among the strategies designed to optimize the number of existing liver grafts for transplantation, the implementation of the graft assessment process is one of the least explored. The main objective is to identify the risk factors presented by liver donors for «NO validity». Secondly, we analyzed the coincidence between the surgeon's assessment and that of the anatomo-pathologist in the invalid donors. MATERIAL AND METHOD Retrospective study conducted from a prospective database that analyzes 190 liver donors, 95 valid and 95 NOT valid. The variables of each of them corresponding to the donation protocol of the National Transplant Organization are studied. Through a multivariate study we determine the independent risk factors of NO validity. We checked the causes of NO validity argued with the histopathological findings of these grafts. RESULTS The independent risk factors of non-validity in the multivariate study (P < .05) were: dyslipidemia, personal medical history other than cardiovascular and abdominal surgical risk factors, GGT, BrT, and the result of previous liver ultrasound. The 3 most frequent causes of NO validity were: steatosis, fibrosis and macroscopic appearance of the organ. 78% of the biopsies confirmed the NO validity of the graft (in 57.9% of the cases the histological findings coincided with those described by the surgeon). The 22.1% of the biopsies hadnt pathological findings. CONCLUSIONS The determination of the risk factors of NO validity will contribute to the design of future assessment scores that are useful tools in the process of liver graft assessment.).

Bernal-Soriano, Mari Carmen/0000-0002-9174-0068; Berbel, Pere/0000-0001-6124-6037, WOS: 000555874000001, PubMed: 32498666, Background:Thyroxine (T4) to triiodothyronine (T3) deiodination in the hypothalamus/pituitary is mediated by deiodinase type-2 (D2) activity.Dio2((-/-))mice show central resistance to exogenous T4. Patients with resistance to exogenous thyroxine (RETH) have not been described. the aim of this study was to identify hypothyroid patients with thyrotropin (TSH) unresponsiveness to levothyroxine (LT4) and to characterize the clinical, hormonal, and genetic features of human RETH. Methods:We investigated hypothyroid patients with elevated TSH under LT4 treatment at doses leading to clinical and/or biochemical hyperthyroidism. TSH and free T4 (fT4) were determined by chemiluminescence, and total T4, T3, and reverse T3 (rT3) by radioimmunoassay. TSH/fT4 ratio at inclusion and T3/T4, rT3/T4, and T3/rT3 ratios at follow-up were compared with those from patients with resistance to thyroid hormone (RTH) due to thyroid hormone receptor-beta (THRB) mutations.DIO2,including the Ala92-D2 polymorphism, selenocysteine binding protein 2 (SECISBP2), andTHRBwere fully sequenced. Results:Eighteen hypothyroid patients (nine of each sex, 3-59 years) treated with LT4 showed elevated TSH (15.5 +/- 4.7 mU/L; reference range [RR]: 0.4-4.5), fT4 (20.8 +/- 2.4 pM; RR: 9-20.6), and TSH/fT4 ratio (0.74 +/- 0.25; RR: 0.03-0.13). Despite increasing LT4 doses from 1.7 +/- 1.0 to 2.4 +/- 1.7 mu g/kg/day, TSH remained elevated (6.9 +/- 2.7 mU/L). Due to hyperthyroid symptoms, LT4 doses were reduced, and TSH increased again to 7.9 +/- 3.2 mU/L. in the euthyroid/hyperthyrotropinemic state, T3/T4 and T3/rT3 ratios were decreased (9.2 +/- 2.4, RR: 11.3-15.3 and 2.5 +/- 1.4, RR: 7.5-8.5, respectively) whereas rT3/T4 was increased (0.6 +/- 0.2; RR: 0.43-0.49), suggesting reduced T4 to T3 and increased T4 to rT3 conversion. These ratios were serum T4-independent and were not observed in RTH patients. Genetic testing was normal. the Ala92-D2 polymorphism was present in 7 of 18 patients, but the allele dose did not correlate with RETH. Conclusions:Human RETH is characterized by iatrogenic thyrotoxicosis and elevated TSH/fT4 ratio. in the euthyroid/hyperthyrotropinemic state, it is confirmed by decreased T3/T4 and T3/rT3 ratios, and elevated rT3/T4 ratio. This phenotype may guide clinicians to consider combined T4+T3 therapy in a targeted fashion. the absence of germlineDIO2mutations suggests that aberrant post-translational D2 modifications in pituitary/hypothalamus or defects in other genes regulating the T4 to T3 conversion pathway could be involved in RETH., Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos IIIInstituto de Salud Carlos III [PI16/00830]; Rare Diseases Networking Biomedical Research Centre (CIBERER), This work was supported by funding from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (grant PI16/00830 to J.C.M.) and by the Rare Diseases Networking Biomedical Research Centre (CIBERER).

Introduction The Diabetes Health Profile (DHP‐18), structured in three dimensions (psychological distress (PD), barriers to activity (BA) and disinhibited eating (DE)), assesses the psychological and behavioural burden of living with type 2 diabetes. The objectives were to adapt the DHP‐18 linguistically and culturally for use with patients with type 2 DM in Ecuador, and to evaluate its psychometric properties. Methods Participants were recruited using purposive sampling through patient clubs at primary health centres in Quito, Ecuador. The DHP-18 validation consisted in the linguistic validation made by two Ecuadorian doctors and eight patient interviews. And in the psychometric validation, where participants provided clinical and sociodemographic data and responded to the SF-12v2 health survey and the linguistically and culturally adapted version of the DHP-18. The original measurement model was evaluated with confirmatory factor analysis (CFA). Reliability was assessed through internal consistency using Cronbach’s alpha and test–retest reproducibility by administering DHP-18 in a random subgroup of the participants two weeks after (n = 75) using intraclass correlation coefficient (ICC). Convergent validity was assessed by establishing previous hypotheses of the expected correlations with the SF12v2 using Spearman’s coefficient. Results Firstly, the DHP-18 was linguistically and culturally adapted. Secondly, in the psychometric validation, we included 146 participants, 58.2% female, the mean age was 56.8 and 31% had diabetes complications. The CFA indicated a good fit to the original three factor model (χ2 (132) = 162.738, p −0.40 in two of three hypotheses). Conclusions The original three factor model showed good fit to the data. Although reliability parameters were adequate for PD and DE dimensions, the BA presented lower internal consistency and future analysis should verify the applicability and cultural equivalence of some of the items of this dimension to Ecuador.

Background Liver retransplantation can be classified as urgent (when performed in the first week after the transplantation) or elective, which may be considered as early (first month post-transplantation) or late (after the first month). The time in which retransplantation takes place is determined by the cause that makes it necessary. The goal of this study is to analyze the causes and results of early retransplantation in our center. Methods A retrospective analysis of liver retransplantations performed within the first month after the original transplantation in our center between 2007 and 2017 was carried out. The variables analyzed were demographic, causes of the first transplant and retransplantation, and the complications and mortality resulting from the latter. Results A total of 698 liver transplants were performed, including 67 patients who required retransplantation (8.9%). Among these, 37 were late elective retransplantations and 30 were early retransplantations. Regarding the latter, the causes that led to the first transplant were hepatocellular carcinoma (46.7%) and noncholestatic cirrhosis (30%). On the other hand, the main precipitants of the retransplantation were hepatic artery thrombosis (60%) and primary graft failure (13.3%). The reoperation rate was 16.7%, and the perioperative mortality rate was 16.7%. The 1-, 2-, and 5-year survival rates were 83.3%, 76.7% and 59.9%, respectively. Conclusion Despite the high perioperative morbidity of liver retransplantation, its results in terms of survival are similar to those of the global series of liver transplantation.

Background: Patient adherence to treatment in chronic obstructive pulmonary disease (COPD) is essential to optimize disease management. We aimed to assess the impact of patients' perception of their treatment and disease on adherence and Health-Related Quality of Life (HRQL) in patients attending a community pharmacy, where usually subjects have a better condition than those in clinical settings. Methods: We performed a cross-sectional study of 318 patients with COPD in treatment with inhalers in the last 3 months from 53 community pharmacies. We assessed HRQL with St George's Respiratory Questionnaire (SGRQ). Persistence was assessed from the three previous refills and adherence through the Test of Adherence to Inhalers test. Results: Persistence was achieved by 78.6% of the patients and 58.5% had good adherence. Patients having a multidose DPI and those with MDI showed a 2.8-fold and 4.1-fold increased association, respectively, with intermediate/poor adherence in comparison with those having a single dose DPI. Those patients who did not have knowledge about COPD (aOR 2.106, p = 0.006) and those who thought that the inhaler effectiveness was fair/poor (aOR 2.361, p = 0.006) were more likely to have intermediate/poor adherence. Overall SGRQ score was significantly worse in patients with intermediate/poor adherence (p = 0.036) and in those who thought the inhaler's effectiveness was fair/poor (p < 0.001). Conclusions: The type of inhaler and patients' knowledge and perceptions of their disease and treatment were associated with good adherence and higher HRQL. Clinicians should promote shared-decision making in the choice of inhaler depending on patients' individual abilities and beliefs.

Background Bilateral retinoblastoma (Rb) treatment remains a challenge for ophthalmologists and pediatric oncologists despite new therapeutic strategies for eye preservation. The purpose of this work is to evaluate treatment outcomes in patients who underwent eye salvage treatment at a single-center prior to the chemotherapy in situ era. Procedure We followed a cohort of 88 consecutive Rb patients diagnosed at Hospital Infantil de Mexico between November 2000 and June 2014. Eye salvage treatment consisted of systemic chemotherapy plus focal therapy planned by a multidisciplinary team. Unresponsive tumors were treated with episcleral brachytherapy and external beam radiotherapy (EBRT). Results A total of 96 eyes underwent eye salvaging therapy. Seventy-eight eyes (81%) were salvaged. Seven patients (8%) required brachytherapy and 34 patients (39%) underwent EBRT. Thirty-three of 78 preserved eyes (42%) achieved normal visual acuity: 5/27 (20%) in radiated patients and 28/51 (61%) in nonradiated patients. Eight patients developed secondary primary malignancies; however, those treated with EBRT did not have a significantly increased risk when compared with nonirradiated patients (OR: 1.66; P = 0.492). The overall survival rate was 86% (95% CI, 76%-92%) after a mean follow-up of 10 years. Conclusions Eye preservation, long-term tumor control, and functional visual acuity could be maintained in many child and adolescent Rb survivors. Our data suggest that ocular radiotherapy can be used as consolidation treatment when other recently developed therapies with potentially fewer side effects are not available. Multidisciplinary management of Rb is mandatory to obtain cancer control during eye salvage treatment.

11th Congress of the Andalusian Society of Organ and Tissue Transplantation. Liver transplantation., [Background] The presence of collateral circulation in liver cirrhosis patients with portal hypertension is quite frequent due to re-permeabilization of closed embryonic channels. In some cases, these shunts could measure over 1 cm wide, therefore, containing a significative blood flow. Its management during liver transplantation could be challenging due to possible complications resulting from either ligation of the shunts or from ignoring them. We present the case of a patient with recurrent hepatic encephalopathy (HE) and a large spontaneous portosystemic shunt (SPSS) who submitted to liver transplant and review the literature identifying options, complications, and outcomes with the aim of facilitating decision making., [Material and Methods] A 68-year-old, Spanish man diagnosed with liver cirrhosis with portal hypertension and recurrent episodes of HE is proposed for LT. The patient’s Child-Pugh score was A6-B7, and the Model for End-stage Liver Disease score was 12. Preoperatively, a computed tomography scan showed a large SPSS running to the inferior cava vein. During the surgery, a small-sized portal vein and a large shunt measuring almost 3 cm wide were identified. After reperfusion, portal vein flow was 1000 to 1100 mL/min. Owing to the previous HE and the risk of low portal flow, the shunt was closed increasing the portal flow to 1800 mL/min. The patient was discharged without any complications., [Conclusions] The presence of large SPSSs are frequent during LT. Decision making intraoperatively can be challenging due to possible complications derived from ligation of the SPSS or from ignoring it. Either preoperative assessment of a further HE risk or portal vein flow measurement after reperfusion are essential to achieve a correct resolution.

Objective To assess the importance of intraoperative portal vein flow measurement during liver transplantation in relation to postoperative complications and graft and patient survival. Materials and methods Retrospective review including 291 patients who had all the information and covering a period of 10 years (2007–2017). Using a receiver operating characteristic curve, a cut-off point that would have the greatest impact on the probability of being alive at 5 years was established. In relation to this value, 2 groups were formed (low and high flow) and demographic variables, intraoperative variables, postoperative complications, and graft and patient survival were compared. Results A portal flow of 123 mL/min per100 g of liver tissue was established (area under the curve = 0.58), obtaining a low-flow (n = 129) and a high-flow group (n = 162). The 2 groups were similar in their preoperative characteristics, except for a higher proportion of preoperative ascites, a higher Model for End-Stage Liver Disease score and a lower weight of donors in the high-flow group. The arterial and portal flows were significantly higher in the high-flow group. In the postoperative period, the high-flow group presented a higher rate of ascites. The 5-year survival rate of patients was significantly higher in the high-flow group (76% vs 84%, P = .03). Conclusions Patients undergoing liver transplantation with an intraoperative portal vein flow measurement >123 mL/min per 100 g present a greater 5-year survival rate.

Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation.This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders.Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation.Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.

The aim of the study was to evaluate the clinical features and long-term therapeutic outcome of giant prolactinoma (gPRLoma) in men and to compare them with those of a group of male patients with non-gPRL macroprolactinomas (non-gPRLomas). A retrospective and multicenter study of gPRLomas in men diagnosed in a 20-year period was performed. Clinical data and treatment outcome were registered. The diagnosis of gPRLoma was established when the maximal tumor diameter was ≥40 mm or the tumor had ≥20 mm of suprasellar extension associated to hyperprolactinemia (PRL>1000 ng/ml). Non-gPRLoma was considered when tumor diameter was ≥ 10 mm and1 year and no radiological evidence of pituitary tumor) was achieved in 2 (8.7%) gPRLoma patients and in 2 (4.8%) non-gPRLoma patients (NS). gPRLomas in men are usually diagnosed at a mean age of 40 years, an age similar to that of non-gPRLomas. The only clinical difference with non-gPRLomas is their greater prevalence of visual disturbances. The therapeutic approaches and tumor outcomes were similar to those obtained in patients with non-gPRLomas. Complete cure in gPRLoma is rare, but similar to that achieved in non-gPRLomas, reached in less than 10% of patients.

Between 1991 and 2013, 1,000 liver transplantations were performed at Virgen del Rocio Hospital (Seville, Spain). A retrospective study was conducted, analyzing the characteristics of recipients and donors, indications, surgical technique, complications and survival in 2 different stages (1991-2002 vs. 2003-2013) coinciding with the implementation of the MELD scale as a prioritization model. The most frequent indication were of hepatopathy of hepatocellular origin in 48.8%. There was a significant increase in the indications for hepatocarcinoma (8.6% and 24.1% P=0.03), and the rate of retransplantation (5.9% vs 9.6%, P=0.04). There was a change in the age of donation, going from 27.7 years in 1990 to 62.9 years in 2012 (P=0.001). The percentage of patients who did not require blood transfusion doubled (6.16 vs. 14.31%, P=.001). Survival of all patients after one, 5 and 10 years was 77, 63.5 and 51.3%, respectively.

Introduction: Prostate-specific antigen (PSA) is the main tool for early detection, risk stratification and monitoring of prostate cancer (PCa). However, there are controversies about the use of PSA as a population screening test because of the high potential for overdiagnosis and overtreatment associated. The net benefit of screening is unclear and according to the available recommendations, it should be offered to well-informed men with an adequate health status and a life-expectancy of at least 10 years or to men at elevated risk of having PCa. In addition, the factors that influence test results are unclear, as is impact of false positive or negative results on patient health. Our objective is to assess the clinical and analytical factors associated with the presence of false positive and false negative results and the diagnostic/therapeutic process followed by these patients. Methods and analysis: A prospective observational cohort study will be carried out. We will include a cohort of patients with a positive PSA result (1.081 patients) and a sample of patients with negative results (572 patients); both will be followed for 2 years by reviewing medical records to assess the variables associated with these results, as well as characteristics of patient management after a positive PSA value. We will include those patients with a PSA determination from 2 hospitals in the Valencian Community. Patients who have been previously diagnosed with prostate cancer or who are being followed for previous high PSA values will be excluded. Discussion: The study will estimate the frequency of false positive and false negative PSA results in routine clinical practice, and allow us to quantify the potential harm caused. Study registration: Clinicaltrials.gov (https://clinicaltrials.gov/): NCT03978299, June 7, 2019.

Introduction The greater survival of transplanted patients is accompanied by an increase in the rate of de novo malignancies (NM), which are the most frequent late-onset complication. We can distinguish between non-melanoma skin cancers (NMSC), post-transplant lymphoproliferative disorders (PTLD) and solid organ cancers (SOC). Our objective is to determine the incidence of the different types of NM, the time elapsed until diagnosis and survival rates in our setting. Methods We conducted a retrospective study of 1071 liver transplant patients from 1990 to 2015 at our center. We analyzed the demographic variables, incidence of NM and survival. Results 184 NM developed in 1071 transplant patients (17%), specifically 19% of the males and 13% of the females (P = .004). The most frequent NM were NMSC (29%), lung (18%), head and neck (16%), PTLD (10%) and gastrointestinal (8%). The median time of diagnosis was 7.9 years in NMSC, 3.9 years in PTLD and 9.8 years in SOC. Patients with NMSC had significantly better survival than those with PTLD or SOC. The incidence of de novo tumors (excluding NMSC) was 1889/100,000 transplants/year. By gender, lung cancer was the most common TOS in men and breast cancer in women. Conclusion In our setting, excluding NMSC, the incidence is 8.8 times greater than estimations for the general population, with a high rate of lung cancer, so we should implement preventive and diagnostic strategies.

espanolIntroduccion: el sindrome linfoproliferativo postrasplante (SLPT) es una complicacion infrecuente que ensombrece el pronostico de los pacientes sometidos a un trasplante hepatico (TH). Su patogenia es multifactorial, siendo sus dos principales factores de riesgo la inmunodepresion y la infeccion del virus de EpsteinBarr (VEB); sin embargo, en actualidad se piensa que puede estar relacionada con otros factores. Metodos: estudio observacional en el que hemos analizado de forma retrospectiva 851 casos que fueron sometidos a un trasplante hepatico, de los cuales diez casos han desarrollado un SLPT. Se han analizado sus caracteristicas clinicopatologicas y el tratamiento recibido. Resultados: la incidencia del SLPT ha sido del 1,2% (10/851) y el tiempo medio de presentacion desde el TH hasta el diagnostico, de 36 meses (rango 1,2-144 meses). El lugar de presentacion ha sido extranodal en todos los casos, siendo mas frecuente la localizacion intestinal. Siete casos presentaron un SLPT monomorfo, todos ellos linfomas diferenciados de celulas B. El 50% de la serie presento seronegatividad para el virus de Epstein-Barr. La supervivencia global ha sido del 50%. Entre estos pacientes, hemos observado tres casos de curacion completa, un caso de estabilizacion de la enfermedad y otro caso de recurrencia. Conclusion: el SLPT es una complicacion infrecuente que supone una amenaza para la vida del paciente. Para poder instaurar un diagnostico precoz y un tratamiento que pueda modificar el curso de la enfermedad, es fundamental la identificacion de los pacientes en riesgo. Englishntroduction: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Methods: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. Results: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. Conclusion: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.

Objective Acromegaly associated to schizophrenia was first reported ~60 years ago, and so far, it is unclear whether this association is causal or not. Our aim was to report new cases with both clinical entities and to discuss the potential pathophysiological mechanisms of this association. Methods Three new cases and data from literature are reviewed. Results We report 2 males and 1 female diagnosed with schizophrenia and treated for several years with antipsychotics who developed acromegaly due to a growth hormone (GH)-secreting pituitary macroadenoma. In all cases, the diagnosis of schizophrenia preceded acromegaly with mean disease duration of ~12 years. Antipsychotic therapy was different in every patient. Two patients underwent transsphenoidal surgery. Histopathological study showed mixed GH- and prolactin-secreting adenoma in 1 patient and pure GH-secreting adenoma in the other patient. Several pathophysiological mechanisms related to alterations in dopaminergic neurotransmission due to psychiatric disease itself or its pharmacological treatment are proposed and discussed as likely linkage between schizophrenia and acromegaly. Conclusion These case reports suggest that schizophrenia and/or its antipsychotic therapy in the long term might be in relation with the development of GH-secreting pituitary adenomas.

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are chromaffin-cell tumors that arise from the adrenal medulla and extra-adrenal paraganglia, respectively. The dysfunction of genes involved in the cellular response to hypoxia, such as VHL, EGL nine homolog 1, and the succinate dehydrogenase (SDH) genes, leads to a direct abrogation of hypoxia inducible factor (HIF) degradation, resulting in a pseudo-hypoxic state implicated in PCC/PGL development. Recently, somatic post-zygotic mutations in EPAS1 (HIF2A) have been found in patients with multiple PGLs and congenital erythrocytosis. We assessed 41 PCCs/PGLs for mutations in EPAS1 and herein describe the clinical, molecular and genetic characteristics of the 7 patients found to carry somatic EPAS1 mutations; 4 presented with multiple PGLs (3 of them also had congenital erythrocytosis), whereas 3 were single sporadic PCC/PGL cases. Gene expression analysis of EPAS1-mutated tumors revealed similar mRNA EPAS1 levels to those found in SDH-gene- and VHL-mutated cases and a significant up-regulation of two hypoxia-induced genes (PCSK6 and GNA14). Interestingly, single nucleotide polymorphism array analysis revealed an exclusive gain of chromosome 2p in three EPAS1-mutated tumors. Furthermore, multiplex-PCR screening for small rearrangements detected a specific EPAS1 gain in another EPAS1-mutated tumor and in three non-EPAS1-mutated cases. The finding that EPAS1 is involved in the sporadic presentation of the disease not only increases the percentage of PCCs/PGLs with known driver mutations, but also highlights the relevance of studying other hypoxia-related genes in apparently sporadic tumors. Finally, the detection of a specific copy number alteration affecting chromosome 2p in EPAS1-mutated tumors may guide the genetic diagnosis of patients with this disease.

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Aims To assess treatment outcome in male patients with micro- and macroprolactinomas. Design Multicentre and retrospective study. Patients Eighty-eight male patients (15 micro- and 73 macroprolactinomas), aged 40·3 ± 14·7 years, were studied. Time of follow-up ranged from 3 to 244 months. Methods Clinical, hormonal and radiological data were registered at diagnosis and follow-up. Treatment outcome was evaluated in relation to the modality of therapy (dopamine agonists, surgery and radiation therapy). Results Dopamine agonists normalized prolactin levels in 73·3% and 65·2% of patients with micro- and macroprolactinomas, respectively. Disappearance of tumour was reached in 53·3% and 28·3% of subjects with micro- and macroprolactinomas, respectively. Tumour absence at last visit was achieved in 7 of 14 patients with macroprolactinoma and treated by means of dual therapy (dopamine agonists and neurosurgery) and in 9 of 13 patients with macroprolactinoma managed with triple therapy (dopamine agonists, neurosurgery and radiation therapy). Normalization of prolactin levels at last visit was present in 68·9%, 79·6% and 69·2% of patients treated by medical therapy, dual therapy and triple therapy, respectively (differences not significant). Multivariate logistic regression analysis showed that the time on therapy was the only significant variable related to tumour disappearance. Conclusion We conclude that medical therapy normalizes prolactin and reduces tumour size in the majority of men with prolactinomas. The addition of pituitary surgery with or without radiation therapy does not offer significant advantages over medical therapy with dopamine agonists in male patients with macroprolactinomas.

Introduction Orthotropic liver retransplantation (RT) is the therapeutic option for the failure of an allograft. Patient and graft survival rates after RT are inferior to primary liver transplantation (OLT). Because of the limited number of donors, it is essential that we optimize their use. We reviewed 68 consecutive retransplantations to evaluate their results. Materials and methods Using registry data from our Liver Transplantation Unit, we performed a retrospective cohort study of adult RT between 1991 and 2010. Patients were divided into 2 groups (urgent vs elective RT) to compare the utility of RT. We also analyzed data collected at the time of RT, including age, gender, indications for primary OLT and RT (hepatitis C virus [HCV]+ and HCV-). At various stages (1991-2000, 2001-2006, and 2007-2010), we calculated probability survival curves according to the Kaplan-Meier method with comparisons using the log-rank test. Results Among 771 adult liver transplantations, 68 (8.8%) underwent late secondary OLT. 21 (31%) cases were urgent and 47 elective RT (69%). Vascular complications was the most common cause for urgent RT, and chronic rejection, for elective RT. Differences were also detected in the overall survival of RT patients; mortality was significantly lower among the urgent procedures (15% vs 47.8%). Significantly differences were also detected in overall survival for RT patients between 2007 and 2010 (81.7% with urgent RT and 76.5% with elective situations). Conclusion These data confirmed the utility of RT in elective and emergency situations. Overall survival of elective RT patients has improved in recent years. Liver RT requires a multidisciplinary team to decide the inclusion and prioritization of elective RT cases on the OLT waiting list.

Solid organ transplant recipients (SOTR) are at risk of serious influenza-related complications. The impact of respiratory co-infection in SOTR with 2009 pandemic influenza A(H1N1) is unknown. A multicentre prospective study of consecutive cases of pandemic influenza A(H1N1) in SOTR was carried out to assess the clinical characteristics and outcome and the risk factors for co-infection. Overall, 51 patients were included. Median time from transplant was 3.7years, 5.9% of the cases occurred perioperatively and 7.8% were hospital-acquired. Pneumonia was diagnosed in 15 (29.4%) patients. Ten cases were severe (19.6%): 13.7% were admitted to intensive care units, 5.9% suffered septic shock, 5.9% developed acute graft rejection and 7.8% died. Co-infection was detected in 15 patients (29.4%): eight viral, six bacterial and one fungal. Viral co-infection did not affect the outcome. Patients with non-viral co-infection had a worse outcome: longer hospital stay (26.2±20.7 vs. 5.5±10.2) and higher rate of severe diseases (85.7% vs. 2.3%) and mortality (42.8% vs. 2.3%). Independent risk factors for non-viral co-infection were: diabetes mellitus and septic shock. Other factors associated with severe influenza were: delayed antiviral therapy, diabetes mellitus, time since transplantation

Information about infections unrelated to acquired immunodeficiency syndrome (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce. The aims of this study were to describe the prevalence, clinical characteristics, time of onset, and outcomes of bacterial, viral, and fungal infections in HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and to identify risk factors for developing severe infections. We studied 84 consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17 sites in Spain between 2002 and 2006 and were followed until December 2009. The median age was 42 years, and 76% were men. The median follow-up was 2.6 years (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%) had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes simplex virus infections, and 16 (19%) had fungal infections (7 cases were invasive). Nine patients (11%) developed 10 opportunistic infections with a 44% mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the first month after transplantation, and 53 (45%) occurred after the sixth month. Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died, and the deaths were related to severe infections in 7 cases (19%). Severe infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9, 95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe infections included a pretransplant Model for End-Stage Liver Disease (MELD) score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of severe and opportunistic infections are high in HIV/HCV-coinfected liver recipients and especially in those with a history of AIDS, a high MELD score, or non-tacrolimus-based immunosuppression.

Introduction Orthotopic liver retransplantation (re-OLT) is the therapeutic option for hepatic graft failures. Survival after re-OLT is poorer than after primary OLT. Given that there is an organ shortage, it is essential that we optimize our use of this scarce resource. We evaluated the results of re-OLT among 58 consecutive Re-OLT. Materials and Methods Using registry data from our Liver Transplantation Unit, we performed a retrospective cohort study of adult urgent versus elective re-OLT between 1991 and 2008. We recorded the indications for the initial OLT, and the intervals from OLT to re-OLT as well as age and gender. Using the Rosen model to stratify patients into low-intermediate-, and high-risk groups we calculated survivals. Results Among 661 adult liver transplantations, 56 patients (8.4%) underwent late re-OLT at a median of 654.4 days post-OLT. There were 17 (29%) urgent re-OLT and 41 elective cases (71%). Vascular complications were the most common cause of urgent re-OLT (64%); elective re-OLT was primarily due to chronic rejection (56.1%). Overall survival for retransplanted patients was significantly lower among urgent procedures (82.4% vs 48.8%), as well as for overall survival after re-OLT for patients with hepatitis C virus (HCV) versus other etiologies. Conclusion These data confirmed the utility of retransplantation in elective and emergency situations. Liver re-transplantation has a high morbidity and mortality. It requires multidisciplinary experience to decide inclusion and prioritization criteria for re-OLT, especially among patients with HCV.

Introduction: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. Material and methods: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean ± standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. Results: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. Conclusion: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival.

Background & Aims: The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/ HIV-coinfected patients. Methods: This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. Results: Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p = 0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. Conclusions: The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The object of this study was to evaluate the viral factor, especially the quasispecies, as predictive of sustained virologic response. We studied the quasispecies, genotype, viral load, and hepatitis C (HCV) cAg in 41 patients with chronic hepatitis C treated with interferon and in 84 with interferon and ribavirin. In the interferon group, responders presented a lower viral load. From logistic regression analysis of patients treated with interferon plus ribavirin, independent predictors for sustained virologic response were genotype 3a, a low baseline viral load andor=3 bands quasispecies. Genotype and viral load presented higher specificity and positive predictive value than did quasispecies. In patients with genotype 1, viral loador=5 x 10(5) IU/mL andor=3 quasispecies were predictive for sustained virologic response. In conclusion, the predictive factors of virologic response are genotype, viral load, and quasispecies. Quasispecies did not improve on the genotype or the viral load as predictors of virologic response.

Although the drug problem is more present among men, women are an increasing group and a vulnerable subgroup, since many of them are involved in motherhood. In this paper, the partial results of an ethnographic study on maternal role-related perceptions, beliefs and attitudes are presented, as well as the context in which women with small children and are undergoing or underwent treatment for alcohol or drug addiction live. Mothers undergoing treatment participated in interviews about their maternal role and how it developed in a family context marked by violence, affective experiences and drug use.

Summary Despite advances in prevention, cytomegalovirus (CMV) recurrence is an important challenge in high-risk organ recipients. The present study prospectively evaluates the impact of CMV-specific T-cell immune response and secondary prophylaxis on the risk of recurrence in a cohort of CMV high-risk organ recipients and whether it is possible to determine a safe standardized viral load value below which CMV disease is unlikely. Thirty-nine recipients were included. Thirty-six had primary infections, and 88.9% recurred. Rate and duration of recurrent CMV infection was similar in patients with and without secondary prophylaxis: 57.9% vs. 53.6%, P = 0.770 and 16 vs. 15 days, P = 0.786, respectively. The only factor independently associated with no episodes of CMV recurrence was the acquisition of CMV-specific T-cell immune response (OR: 0.151, 95% CI: 0.028–0.815; P = 0.028). Cytomegalovirus diseases (N = 5) occurred in patients with CMV viral load above 1500 IU/ml who did not follow the planned monitorization schedule. Our observations suggest that episodes of recurrent CMV infection are common after preemptive therapy despite secondary prophylaxis and that CMV-specific T-cell immune response is associated with a decreased risk of recurrent infections. Preemptive therapy may be safe in patients at high risk for CMV infection with strict close monitoring of the CMV viral load.

Liver transplantation for the treatment of patients with advanced liver disease is organized according to a waiting list taking into account different criteria. The agreed distribution model in Andalusia assumes that sometimes an organ is extracted in a different province to that where the implantation is to be performed (shipping), which, therefore, increases the graft ischemic time. The aim of the present study was to determine whether transportation of the organ and being harvested by a team other than the implantation team have a negative effect on final patient survival.

Objective The objective of this study was to analyze survival, and mortality, rates as well as its causes during the month following liver transplantation with respect to the model for end-stage liver disease (MELD) model. Material and Methods We reviewed the mortality at 24 and 48 hours as well as 1 and 4 weeks of 380 transplanted patients over the past 7 years with regard to the MELD score. Results The mean patient age was 55 years. Among subjects with MELD score ≤ 15 (n = 142; 37.36%), there were 34 deaths (23.94%), including 7 (4.92%) who died during the first month. The mean cause of death during this period was hemorrhage (n = 3; 8.8%). Among those with MELD scores between 16 and 18 (n = 76; 20%), the mortality rate increased to 23.68% (n = 18), including 3 who died during the first month (3.94%) with 1 case due to hemorrhage. Among the cohort with MELD scores between 19 and 21 (n = 78; 20.52%), 25 (32.05%) died, including 9 during the first month (11.53%). The most frequent cause of death was septic shock (n = 5; 20%). The mortality rate among patients with a MELD score between 22 and 24 was 22% (n = 11), of which 8% (n = 4) died in the month. The mean cause of death during this period was multiple organ dysfunction (n = 2; 18.1%). The patient group with a MELD score >24 had a 32.3% mortality rate (n = 11); 4 patients died during the first month following transplantation (11.76%). The most frequent cause of death was hemorrhage (n = 2; 18.1%). Conclusions Survival during the first month did not seem to be related to the MELD score at the time of transplantation, nor did we observe a direct correlation between the MELD score and the overall risk of mortality.

Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with

Community-acquired pneumonias are difficult to diagnose. For this reason, we have attempted to evaluate the correct diagnosis by using noninvasive methods which are easy to follow outside the hospital environment. To achieve this, 165 patients exhibiting the clinical and roentgenographic symptoms characteristic of pneumonia, have been studied from a bacteriologic, serologic, and statistical stand point. The correct diagnosis was made in 75 percent of the cases. Of the total 124 cases, 69 (41.8 percent) were of bacterial origin. Streptococcus pneumoniae was the most common agent, followed by Gram-negative bacilli. In 73 cases showing positive serologic evidence, 22 (42 percent) could be attributed to the so-called atypical pneumonias, 18.18 percent to the viral, and 1.21 percent to the mycotic.

Many problems may arise when defining whether adrenal lesions are primary to the adrenal glands or represent other tissue, whether they are benign or malignant and whether they are functioning or nonfunctioning. Adrenal imaging complements the clinical and hormonal evaluation of these patients. We present a patient with lumbar pain and bilateral adrenal masses.

Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency mainly manifests with symptoms and signs of hyperandrogenism, which are usually obvious in women and sometimes obvious in children or adolescents, but are rarely observed in adult men especially with increasing age. Male pattern alopecia is considered an androgenetic and age-related symptom. However, its early appearance should raise the suspicion of an underlying endocrinological disease, and biochemical screening should be done.Here we present the case of 2 siblings (female and male) where the man complains about premature alopecia.Molecular study of CYP21A2 revealed that both siblings were compound heterozygotes for the mild mutation (V281L) and for a novel nonsense mutation (Y336X).Given the high prevalence of carriers with severe mutations, we discuss the risk for such patients of conceiving a child with a classical disease and the need for a reliable molecular diagnosis in order to provide accurate genetic counselling.

A study of the distribution of HIV-1 subtypes in the native and immigrant populations of Eastern Andalusia (Southern Spain) was conducted to determine any changes between 1983 and 2001 and to identify antiretroviral resistance mutations in non-B subtype strains among the immigrant population. The study included 111 native patients from Eastern Andalusia: 94 infected with HIV before 1996 and 17 infected since 1996. A parallel study was conducted on 26 HIV-positive immigrants from Africa. Subtyping was done with the heteroduplex mobility assay. Resistance mutations were determined by line probe assay. A total of 137 patients were studied: 9.2% had subtype A (n = 12), 80.8% subtype B (n = 105), and 1.5% subtype C (n = 2). Among the Eastern Andalusia population infected before 1996, 10.9% had non-B subtypes, compared with 23.5% of those infected after that year. The greatest percentage of non-B subtypes (52.4%) was found among the immigrant population. Resistance mutation K70R was detected in one of the six immigrants with non-B subtype and M41L in another. There has been a slight increase in the diversity of HIV-1 subtypes in Eastern Andalusia over the past few years, possibly influenced by non-B subtypes introduced by immigrants from sub-Saharan Africa.

This study was carried out to determine the prevalence of hepatitis C virus (HCV) antibodies and the epidemiologic factors associated with HCV infection in patients with chronic renal failure before the onset of ESRD. Sex, age, type of renal disease, level of renal function, and history of blood transfusions and invasive procedures were analyzed in 226 patients with renal disease, compared with a population of 1,244 normal subjects and 124 patients with impaired immunity (patients having autoimmune diseases and receiving chemotherapy treatment). Eighteen seropositive patients with renal disease (prevalence, 7.9%) were found, which was significantly higher than the prevalence in the normal population (1.03% in blood donors, 0.98% in pregnant women; P0.001, chi 2). There was no significant association of sex, number of blood transfusions, or history of invasive procedures with the presence of HCV antibodies. The prevalence of HCV antibodies was higher (16.6%) in patients with glomerulonephritis compared with patients diagnosed with interstitial nephritis, pyelonephritis, nephrosclerosis, diabetes mellitus, polycystic kidney, and miscellaneous renal diseases (P0.01, chi 2). There was a higher prevalence of HCV antibodies in patients with creatinine clearance lower than 30 mL/min (13%) compared with patients with creatinine clearance higher than 30 mL/min (2.7%) (P0.01, chi 2). These data suggest that HCV infection may be associated with the pathogenesis of glomerulonephritis. Alternatively, glomerulonephritis or severe renal insufficiency may increase the likelihood of HCV infection.