Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Nutritional status in hepatic encephalopathy and transjugular intrahepatic portosystemic shunt - TIPS, and strategies to improve the outcomes.

Hepatic encephalopathy (HE) is one of the most severe complications following transjugular intrahepatic portosystemic shunt (TIPS). The identification and treatment of risk factors associated with the development of this complication may reduce the incidence and severity of post-TIPS HE. Several studies have demonstrated that the nutritional status plays a major role in the outcome of the cirrhotic population, particularly those who are decompensated. Although scarce, there are also studies highlighting an association between poor nutritional status, sarcopenia, fragile status, and post-TIPS HE. If these data are confirmed, nutritional support could become a means for decreasing this complication, thereby enhancing the use of TIPs in the treatment of refractory ascites or variceal bleeding. In this review, we will discuss the pathogenesis of HE, the data that supports an association with sarcopenia, nutritional status and frailty and the implications that these conditions have on the use of TIPS in clinical practice.

Sequential teratoma in pediatric patients: causation or coincidence? / Teratoma de aparición secuencial en edad pediátrica: ¿casualidad o causalidad?

We describe the unusual case of a female patient with a history of two mature teratomas non-correlated in terms of location and occurrence. A 12-year-old girl presented at our consultation as a result of a growing tumor in the hypogastric region, with no further clinical signs. She had undergone surgery neonatally due to a mature cystic sacrococcygeal teratoma, which was fully removed. No clinical sequelae were noted and no additional treatment was required over a 10-year follow-up. Radiological examination showed a large 20 × 12 × 18 cm cystic mass extending from the pelvic region to the lower hemiabdomen, associated with two similar small formations adjacent to the right ovary. Tumor markers were negative, and a laparoscopic right salpingoophorectomy was carried out, with an excellent postoperative progression. Pathological examination revealed it was, again, a mature cystic teratoma. The genetic study ruled out causation in this respect.

Describimos el inusual caso de una paciente con antecedente de dos teratomas maduros no relacionados en cuanto a su localización y debut. Una niña de 12 años consultó por la aparición de una tumoración en la región hipogástrica de crecimiento progresivo sin otra clínica asociada. Había sido intervenida por un teratoma quístico maduro sacrococcígeo en el periodo neonatal con su extirpación completa y, ausencia secuelas clínicas y tratamiento adicional durante diez años de seguimiento posterior. Los exámenes radiológicos mostraron una gran masa quística de 20 × 12 × 18 cm que se extendía entre la región pélvica y el hemiabdomen inferior, acompañada por otras dos pequeñas formaciones similares adyacentes al ovario derecho. Los marcadores tumorales resultaron negativos y se llevó a cabo una salpingooforectomía derecha laparoscópica con una excelente evolución postoperatoria. El examen histopatológico, de nuevo, informó la lesión como teratoma quístico maduro. El estudio genético descartó una posible causalidad en este ámbito.

Teratoma de aparición secuencial en edad pediátrica: ¿casualidad o causalidad? / Sequential teratoma in pediatric patients: causation or coincidence?

Describimos el inusual caso de una paciente con antecedente de dos teratomas maduros no relacionados en cuanto a su localización y debut. Una niña de 12 años consultó por la aparición de una tumoración en la regió n hipogástrica de crecimiento progresivo sin otra clínica asociada. Había sido intervenida por un teratoma quístico maduro sacrococcígeo en el periodo neonatal con su extirpació n completa y, ausencia secuelas clínicas y tratamiento adicional durante diez años de seguimiento posterior. Los exámenes radioló gicos mostraron una gran masa quística de 20 × 12 × 18 cm que se extendía entre la región pélvica y el hemiabdomen inferior, acompañada por otras dos pequeñas formaciones similares adyacentes al ovario derecho. Los marcadores tumorales resultaron negativos y se llevó a cabo una salpingooforectomía derecha laparoscópica con una excelente evolución postoperatoria. El examen histopatológico, de nuevo, informó la lesión como teratoma quístico maduro. El estudio genético descartó una posible causalidad en este ámbito.(AU)

We describe the unusual case of a female patient with a history of two mature teratomas non-correlated in terms of location and occurrence. A 12-year-old girl presented at our consultation as a result of a growing tumor in the hypogastric region, with no further clinical signs. She had undergone surgery neonatally due to a mature cystic sacrococcygeal teratoma, which was fully removed. No clinical sequelae were noted and no additional treatment was required over a 10-year follow-up. Radiological examination showed a large 20 × 12 × 18 cm cystic mass extending from the pelvic region to the lower hemiabdomen, associated with two similar small formations adjacent to the right ovary. Tumor markers were negative, and a laparoscopic right salpingoophorectomy was carried out, with an excellent postoperative progression. Pathological examination revealed it was, again, a mature cystic teratoma. The genetic study ruled out causation in this respect.(AU)

The road map toward an hepatitis C virus-free transplant population.

Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)-based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN-based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second-generation direct-acting antiviral agents (DAAs) with superior tolerability and efficacy to IFN-based therapy. These agents have the potential to reduce the number of patients developing HCV-related complications requiring LT and retransplantation, as well as reducing the demand for donor organs. We discuss the pros and cons of pretransplant, peritransplant, and posttransplant therapy with current DAAs, citing available data from clinical trials and real-world experience.

Intensified blood glucose treatment in diabetic patients undergoing a liver transplant: impact on graft evolution at 3 months and at 5 years.

PURPOSE: The debate about the impact of intensified hyperglycemia treatment is still ranging. The main objective was to assess whether intensive glycemic control in hospitalized diabetic patients undergoing a liver transplant is associated with a lower rate of graft rejection at 3 months and at 5 years post-transplant. METHODS: Cross-sectional study comparing a cohort of patients undergoing liver transplant in 2010 and 2011, in whom an intensive insulin protocol was applied, with a retrospective group of patients undergoing a liver transplant in 2005 and 2006, in whom a conventional insulin protocol was applied. Both diabetics and non-diabetics were compared. As intensive insulin therapy is applied mainly in diabetic patients, it is expected that, when comparing both periods, the treatment would only benefit those patients. RESULTS: The logistic regression model showed a statistically significant interaction between the treatment group and the presence of diabetes for the rejection rate 3 months and 5 years post-transplant. At both time points, the intensive insulin treatment group had lower rejection rates in the case of diabetic patients, which did not occur in non-diabetic patients. CONCLUSIONS: Our study shows a decrease in the rate of liver graft rejection in diabetic patients undergoing intensive insulin treatment.

[Surfactant replacement therapy with a minimally invasive technique: Experience in a tertiary hospital]. / Terapia con surfactante con técnica mínimamente invasiva: experiencia en un hospital terciario.

INTRODUCTION: Surfactant delivered using a minimally invasive technique, known as MIST (Minimally Invasive Surfactant Therapy) is a method which allows surfactant to be administered to a patient connected to non-invasive respiratory support. This is an increasingly used therapy in Neonatal Units that reduces the intubation rate and the pathology associated with intubation and allows the surfactant to be administered to the patients who clinically need it. PATIENTS AND METHODS: In years 2013 and 2014 in the Hospital General Universitario de Elche surfactant was delivered using this method to 19 patients, five of whom were 28 or less weeks of gestation age at birth. A comparison is made with a historical cohort consisting of 28 patients with Respiratory Distress Syndrome treated initially with non-invasive respiratory support. RESULTS: No incidents were recorded that caused the interruption of the administration. A reduction in the fraction of inspired oxygen was observed in all cases after surfactant administration. Fewer intubations in the first 72 hours of life were found in the treatment group compared to the control group (42% vs. 54%). DISCUSSION: The experience recorded in the Hospital General Universitario de Elche shows that the administration of surfactant using a MIST technique is a reproducible method of treatment, which allows the surfactant distribution during spontaneous breathing with non invasive respiratory support.

Síndrome PFAPA del adulto / PFAPA syndrome in adults

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Explorando la participación ocupacional en niños con epidermólisis bullosa integrados al sistema educacional chileno / Exploring to occupational participation in children with epidermolisys bullosa integrated into the chilean educational system

El presente estudio explora la participación ocupacional en el área de educación de niños con epidermólisis bullosa (E.B.) en sus tipos distrófica y de la unión, los cuales, dada su condición de salud general son considerados como estudiantes con necesidades educativas especiales (NEE). Con el objetivo de conocer si la integración es satisfactoria y cuenta con los apoyos necesarios, se realiza mediante un estudio de tipo exploratorio cualitativo, un análisis de tres casos según criterios de inclusión establecidos. A través de un análisis pragmático de los datos obtenidos durante el trabajo de campo se realiza el perfil ocupacional inicial del niño (S.C.O.P.E.), instrumento propio del modelo de ocupación humana, desprendiéndose de éste conclusiones, que se estructuran en base al mismo modelo. La importancia y relevancia de estudiar esta temática está dada por la pertinencia de la intervención y el aporte que la terapia ocupacional puede brindar a las personas con E.B., que si bien desde el punto de vista epidemiológico tiene una baja incidencia en la población general, quienes la padecen requieren de un abordaje multidisciplinar e integral, dado por la complejidad de la condición de salud y el impacto que esta provoca en todas las áreas de la ocupación.

This study explores the occupational participation of children with epydermolisys bullosa (E.B.) dystrophic and junctional in the educational area, which because of their health condition, are considered as student with special educational needs (SEN). With the aim to know how satisfactory is the integration and whether it has the necessary support, the study carried out, through a qualitative and exploratory focus, on three selected cases with the established selection criteria. Through a pragmatic analysis of data obtained during the field work, the short child occupational self assessment (S.C.O.P.E.) is used, from the Model of human occupation (M.O.H.O.), some conclusions emerge, which are structured and based on the model announced. The importance and relevance of studying this subject from occupational therapy is given by the pertinence of the intervention and contribution to E.B. in people who live this condition, even though it as a low incidence in general population from an epidemiological perspective, because they need a multidisciplinary and integral intervention to mitigate the impact caused by the disease in all occupational areas.

Liver transplantation and hepatitis C.

Hepatitis C virus (HCV)-related end-stage cirrhosis with/without hepatocellular carcinoma is the primary indication for liver transplantation in many countries. Unfortunately, HCV is not eliminated by transplantation and graft re-infection is the rule, resulting in HCV-related graft disease. The natural history of recurrent hepatitis is variable; overall, progression to cirrhosis occurs in 20-30% and allograft failure in 10% after 5-10 years from transplantation. The use of poor quality organs, particularly from old donors, has a significant negative impact on disease severity and transplant outcome. In contrast, antiviral therapy, particularly if it results in permanent eradication of the virus, is associated with improved histology, reduced rate of graft decompensation and enhanced outcome. Disease monitoring, through protocol liver biopsies and new non-invasive tools, is essential to select patients at need of antiviral therapy. Peginterferon with ribavirin, used similarly to what is done in the non-transplant setting, is currently the treatment of choice; sustained viral response is achieved in about 35% of cases. Side effects, particularly anemia, are extremely frequent and sometimes severe (rejection, de novo autoimmune hepatitis). Retransplantation (RT) is the last option for the small subset of patients with allograft failure due to HCV recurrence who fulfil minimum criteria based on RT survival models.

Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis.

BACKGROUND & AIMS: Multiple instances of DILI in the same patient with drugs of similar structure or function as well as completely unrelated drugs are not well understood and poorly documented. We have sought evidence of the frequency and characteristics of patients who have experienced two DILI episodes due to different drugs. METHODS: All cases of DILI systematically collected in the Spanish DILI Registry between 1994 and 2009 were retrieved. Data on demographics, clinical, laboratory and pathological findings, and outcome were analyzed. RESULTS: Nine patients (mean age 67 years, four women) out of 742, 1.21%, had evidence of two DILI episodes caused by different drugs. In four cases DILI was associated with structurally related drugs and in an additional two cases the drugs had a common target. In another case, unrelated antibiotics were implicated. In only two cases, the two drugs/herbals were not related in structure or function. All but one patient exhibited hepatocellular damage. The type of damage was consistent in both DILI episodes. Four cases presented as autoimmune hepatitis (AIH) in the second episode. CONCLUSIONS: Multiple episodes of DILI in association with different drugs occur infrequently. In each individual, the type of injury was similar during the two DILI episodes, regardless of the causative drug. Second episodes of DILI are more likely to be associated with features of AIH. It remains uncertain if this is drug-induced unmasking of true AIH or DILI with autoimmune features. These cases illustrate the dilemma faced by clinicians in distinguishing these possibilities.

Use of electrical devices reveals our well being.

We want to objectivize the level of activity of elderly persons living independently at home. Most existing monitoring systems are intrusive and/or require a large number of sensors. We hope the "ubiquitous computing" concept could find an application in this context. We proposed to monitor the use of electrical appliances. We built a unique "activity indicator" which integrates all the activities of the person. This was assessed during 6 months within 12 flats occupied by single elderly persons.

Efectividad del tratamiento de las úlceras venosas con vendaje compresivo multicapa asociado a protección de la piel perilesional con Cavilon® (película barrera no irritante) / Effectiveness of the association of multilayer compression therapy and periwound protection with Cavilon® (no sting barrier film) in the treatment of venous leg ulcers

Introducción: el adecuado tratamiento de las úlceras de extremidad inferior de etiología venosa es fundamental para mejorar la calidad de vida de los pacientes. El uso de terapia compresiva con vendaje multicapa es el tratamiento que mejores resultados presenta. En la práctica, se utiliza en combinación con unos adecuados cuidados locales de la herida y de la piel perilesional. El objetivo del estudio fue evaluar la efectividad clínica de un vendaje multicapa de compresión y el impacto de la utilización de la película barrera Cavilon® en úlceras vasculares de origen venoso.Metodología: ensayo clínico controlado, aleatorizado, abierto, multicéntrico y pragmático en España. Todos los pacientes incluidos fueron tratados con terapia de compresión con el mismo vendaje multicapa y asignados aleatoriamente al grupo de intervención, tratados con la PBNI Cavilon®,o al grupo control. Se realizaron un máximo de 13 visitas de estudio separadas entre ellas por una semana. El estudio fue evaluado y aprobado por los comités éticos de investigación clínica (CEIC) de los siete centrosparticipantes. Resultados: participaron 98 pacientes en el estudio (49 en elgrupo intervención y 49 como control). Tras cuatro semanas, el grupo intervención presentó una reducción media (DE) del tamaño de úlcerasuperior al grupo control (56,7% (30,3) vs. 45,5% (47,4); p = 0,087).A las 12 semanas de tratamiento, las diferencias observadas fueron estadísticamente significativas (83,4% (31,1) vs. 71,6% (44,1); p = 0,046) (..) (AU)

Aim: appropriate treatment of venous leg ulcers is essential to improve the quality of life of patients. Compression therapy using multilayer bandages show to the best clinical results. In practice, it is used in combination with a suitable local care of the wound and periwound skin. The aim of this study was toevaluate the clinical effectiveness of a multi-layer compression bandageand the impact on it of the use of barrier film Cavilon® in venous leg ulcers. Methods: controlled clinical trial, randomized, open, multicentre and pragmaticin Spain. All included patients were treated with compression therapy with the same multilayer bandages and randomized to the intervention group, treated with NSBF Cavilon®, or to the control group. Up to 13 weekly visits were performed. The study was reviewed and approved by the institutional research board (IRB) of the 7 participating centres. Results: ninety eight patients were included in the study (49 in the intervention group and 49 in control group).At 4 weeks of treatment, the intervention group showed a mean ulcer size reduction (SD) greater than the control group (56.7% (30.3) vs. 45.5% (47.4),(p=0.087). At 12 weeks of treatment, differences were statistically significant(83.4% (31.1) vs. 71.6% (44.1), p=0.046). In the intervention group, 69.4%of patients reduced the ulcer area * 50% in the first 4 weeks of treatment,instead of 46.9% of patients in the control group (p <0.01). Conclusions: the clinical effectiveness of a multi-layer compression bandage (Coban® 2) in patients with venous leg ulcers, assessed in terms of percentage reduction of area, is increased by concomitant use of a protective treatment of periwound skin withNSBF (Cavilon®) (AU)

Indications for and results of liver retransplantation.

Liver retransplantation (LReTx) is the therapeutic option for the irreversible failure of a hepatic graft. Our aim was to evaluate the rate of and indications for LReTx and actuarial patient survivals. Among 1260 LTx were 79 LReTx (6.3%). During the first LTx, there were no apparent differences between patients who did or did not required LReTx. The most frequent reasons were hepatic artery thrombosis (31.6%), recurrence of the VHC cirrhosis (30.4%), and primary graft failure (21.5%). The actuarial survivals at 1 and 5 years were 83% and 69% among those without LReTx versus 71% and 61% among early LReTx, and 64% and 34% among late LReTx (P < .001). Although there exists high morbidity and mortality with LReTx, it seems that this therapeutic alternative continues to be valid for patients with early hepatic loss, but not when the graft loss was late. It becomes necessary to define the minimal acceptable results that patient can benefit from LReTx.

Tratamiento de la infección por el virus de la hepatitis C tras el trasplante hepático / No disponible

Como consecuencia de la reinfección del injerto y la recidiva de la enfermedad primaria sobre el injerto, el pronóstico a largo plazo de los pacientes trasplantados por cirrosis secundaria a la infección crónica por el virus de la hepatitis C (VHC) es inferior al obtenido por receptores de trasplante no infectados por dicho virus. Salvo en limitadas ocasiones, en las que se logra la erradicación del VHC antes del trasplante en el contexto de un tratamiento antiviral, no disponemos de medios eficaces para prevenir la reinfección del injerto. Una vez realizado el trasplante, las estrategias para evitar la pérdida del injerto como consecuencia de la progresión de la hepatitis C incluyen el tratamiento antiviral, tanto en una fase temprana (primeras 4-6 semanas cuando no hay aún pruebas de daño histológico) como tardía cuando la hepatitis C ya está plenamente establecida, y el tratamiento adecuado de todas las condiciones que se asocian con una mayor progresión de la enfermedad. El tratamiento antiviral temprano se encuentra limitado no solamente por su baja aplicabilidad, sino también por su baja tolerancia y escasa eficacia (respuesta virológica sostenida en torno < 20%). El tratamiento de la hepatitis C establecida, sobre todo en pacientes en los que se demuestra progresión de la enfermedad a partir de las biopsias de protocolo, es la alternativa con una mejor relación coste-eficacia, con una eficacia en torno al 35% cuando se utiliza interferón pegilado en combinación con ribavirina. Los efectos secundarios, tales como citopenias e incluso rechazo, representan la principal limitación y obligan a la retirada prematura del tratamiento en un 30% de casos. El tratamiento adecuado de la inmunodepresión es el segundo pilar para evitar una progresión acelerada de la hepatitis C del injerto (AU)

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Indications for and results of liver retransplantation.

Liver retransplantation (LRT) is the only therapeutic option for the irreversible failure of a hepatic graft. The aim of this study was to evaluate our rate, indications, postoperative morbidity and mortality and patient survival at one and 5 years after LRT. 1,260 liver transplants (LT) were performed between 1991 and 2006, 79 were LRT (6.3%). During the first LT, there were no apparent differences between patients who did or did not require LRT. The most common reasons for LRT were hepatic artery thrombosis (31.6%), recurrence of hepatitis C virus cirrhosis (30.4%) and primary graft non function (21.5%). The actuarial survival rates at one and 5 years were 83% and 69% among those without LRT versus 71% and 61% among those with early LRT, and 64% and 34% among those with late LRT (p < 0.001). Although high morbidity and mortality were associated with LRT, it seems that this therapeutic option is valid for patients with early hepatic loss, although not when the graft loss is late. It becomes necessary to define the minimal acceptable results so that patients can benefit from LRT.

VOCs and PAHs emissions from creosote-treated wood in a field storage area.

In this study, the emissions of volatile organic compounds (VOCs, in this case aromatic hydrocarbons containing one benzene ring and furans) and polycyclic aromatic hydrocarbons (PAHs) from wood recently treated with creosote are examined. The VOCs and PAHs were identified and quantified in the gas phase. Additionally, the PAHs were quantified in the particulate phase. Glass multi-sorbent tubes (Carbotrap, Carbopack X, Carboxen-569) were used to hold the VOCs. The analysis was performed using automatic thermal desorption (ATD) coupled with capillary gas chromatography/mass spectrometry (GC/MS). PAHs vapours were collected on XAD-2 resin, and particulate matter was collected on glass fibre filters. The PAHs were analysed using GC/MS. The main components of the vapours released from the creosote-treated wood were naphthalene, toluene, m+p-xylene, ethylbenzene, o-xylene, isopropylbenzene, benzene and 2-methylnaphthalene. VOCs emission concentrations ranged from 35 mg m(-3) of air on the day of treatment to 5 mg m(-3) eight days later. PAHs emission concentrations ranged from 28 microg m(-3) of air on the day of treatment to 4 microg m(-3) eight days later. The air concentrations of PAHs in particulate matter were composed predominantly of benzo[b+j]fluoranthene, benzo[a]anthracene, chrysene, fluoranthene, benzo[e]pyrene and 1-methylnaphthalene. The emission concentrations of particulate polycyclic aromatic hydrocarbons varied between 0.2 and 43.5 ng m(-3). Finally, the emission factors of VOCs and PAHs were determined.