Evaluating the effects of Cyclosporine A immunosuppression on Mycobacterial infection by inhaling of Cyclosporine A administrated BALB/c mice with live Bacillus Calmette Guérin.

Cyclosporine A (CsA) is an immunosuppressive drug used in organ transplantation and treatment of autoimmune diseases. Effects of CsA on determining the direction of the immune response and pathogenesis of infections by altering immune responses particulary T cells functions have always been questionable. We evaluated the effect of different doses of CsA on course of infection in BALB/c mice infected with live Bacillus Calmette Guérin (BCG) (as an example of Mycobacterial infections). Four groups of mice (n = 5) receiving 5, 25, 125, and 0 mg/kg of CsA, three times a week, were infected with BCG aerosolly. Before BCG inhalation and 40-/60- days post-infection, cell proliferation and CD4+CD25+ cell percentage were evaluated in splenocytes of mice after culture and stimulation with PHA or BCG lysate. The histopathological alterations and bacterial burden were assessed in lung tissue. Cells showed a dose-dependent decrease in proliferation and the percentage of CD4+ CD25+ cells. After BCG infection, in presence of dose 125 mg/kg, there were some exceptions. The number of bacteria and histopathological lesions and inflammation in lung tissues increased in a dose-dependent manner. CsA immunosuppressed BCG infected mice can be used as a safe model for studying Mycobacterium species pathogenesis and related cellular immune responses.

The clinical extremes of autoimmune cholangitis

Autoimmune cholangitis (AIC) was first described in 1987 as immunocholangitis in three women who presented with signs and symptoms of primary biliary cholangitis (PBC), but who were antimitochondrial (AMA) negative and antinuclear antibodies (ANA) positive, and responded to immunosuppressive therapy with azathioprine and prednisolone (1). AIC is a rare chronic cholestatic inflammatory disease characterized by the presence of high ANA or smooth muscle antibodies (SMA) but AMA seronegativity. Histologically, AIC exhibits bile duct injury (2). In terms of therapeutics, in addition to response to ursodeoxycholic acid, a prompt response to corticosteroids has also been reported in earlier stages, distinguishing it from PBC. Herein the authors describe two cases with mixed signs of PBC and autoimmune hepatitis (AIH). The diagnostic differentiation between these diseases (AIC, PBC and AIH) is essential because of the different therapeutic strategies. Our cases highlight the importance of clinician awareness of the autoimmune spectrum of liver diseases (AU)

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Metástasis hepática de origen colorrectal 12 años después de un trasplante hepático / Liver metastasis from colorectal cancer 12 years after liver transplantation

No disponible

Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses

Historically, patients diagnosed with metastatic pancreatic cancer have faced a grim prognosis. The survival benefit seen with systemic chemotherapies and even combinations thereof have been disappointing. However, growing data suggest that the microenvironment of pancreatic cancer may be contributing to this poor prognosis. This microenvironment has a dense fibrotic stroma, and is hypoxic and highly immunosuppressive, all of which pose barriers to treatment. Newer strategies looking to disrupt the fibrotic stroma, target hypoxic areas, and improve local immune responses in the tumor microenvironment are currently undergoing clinical evaluation and seem to offer great promise. In addition to these therapies, preclinical work evaluating novel cytotoxic agents including nanoparticles has also been encouraging. While much research still needs to be done, these strategies offer new hope for patients with pancreatic cancer (AU)

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Primoinfección tuberculosa en pacientes con anti-TNF-α y cribado inicial negativo / Primary tuberculosis infection in patients treated with tumor necrosis factor-alpha antagonists and a negative initial screening

Introducción. A pesar de las medidas de cribado de tuberculosis (TB) siguen detectándose casos en pacientes tratados con anti-TNF-α y cribado inicial negativo, algunos tras largo tiempo de tratamiento, lo que apunta más a una nueva infección. Objetivos. Describir los casos que presumiblemente han desarrollado primoinfección tuberculosa durante el tratamiento con fármacos anti-TNF-α. Métodos. Revisión retrospectiva (1999-2012), seleccionando según los siguientes criterios: a) tratamiento anti-TNF-α; b) cribado de TB inicial negativo; c) TB diagnosticada durante tratamiento anti-TNF-α, y d) sospecha de primoinfección tuberculosa (tras mínimo 12 meses de anti-TNF-α). Se han revisado sus variables clínicas, epidemiológicas, terapéuticas y de desenlace. Resultados. Dos casos de primoinfección tuberculosa de 771 pacientes tratados con anti-TNF-α (0,2%). Una mujer de 41 años y 35 meses de tratamiento con adalimumab y un varón de 37 años y 107 meses de tratamiento con infliximab. La mujer presentó una neumonía y el varón una TB diseminada. Conclusiones. Durante la terapia anti-TNF-α persiste el riesgo de TB a pesar de cribado inicial negativo, por lo que el grado de sospecha debe ser elevado durante todo el tratamiento (AU)

Introduction. Despite screening for latent tuberculosis (TB), new cases of TB infection are detected in patients treated with anti-TNF-α and negative initial screening, some of them after long treatment, which points more to a new infection. Objectives. To describe the cases that have presumably developed a primary tuberculous infection during treatment with anti-TNF-α drugs. Methods. Retrospective audit (1999-2012). Inclusion criteria were: a) anti-TNF-α treatment; b) initial latent TB screening negative; c) TB diagnosed during anti-TNF-α treatment; d) suspected primary TB infection (diagnosis after at least 12 months on anti-TNF-α). Clinical, epidemiological, therapeutic and outcome variables were reviewed. Results. Two cases of primary TB infection were found out of of 771 anti-TNF-α treated patients (0.2%). One woman aged 41 suffered TB pneumonia after 35 months of treatment with adalimumab, and a male aged 37 who developed disseminated TB after 107 months of treatment with infliximab. Conclusions. Although uncommon, during TNF antagonist therapy, TB risk persists despite negative initial screening, so clinicians should be aware of TB during the entire treatment (AU)

XXV Congreso de la Sociedad Española de Trasplante Hepático (SETH) / No disponible

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Registro Español de Trasplante Cardiaco. XXIV Informe Oficial de la Sección de Insuficiencia Cardiaca y Trasplante Cardiaco de la Sociedad Española de Cardiología (1984-2012) / Spanish Heart Transplantation Registry. 24th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2012)

Introducción y objetivos. Este artículo presenta las características y los resultados del trasplante cardiaco en España desde que empezó su actividad en mayo de 1984. Métodos. Se realiza un análisis descriptivo de las características de receptores, donantes, procedimiento quirúrgico y resultados de los trasplantes cardiacos realizados en España hasta el 31 de diciembre de 2012. Resultados. Durante 2012 se han realizado 247 procedimientos, con lo que en la serie histórica constan 6.775 trasplantes. En los últimos años, se observa un empeoramiento del perfil clínico tanto de los receptores (el 34% mayores de 60 años, el 22% con insuficiencia renal grave, el 17% con diabetes mellitus insulinodependiente, el 29% con cirugía cardiaca previa y el 16% con ventilación mecánica), como de los donantes (el 38% mayores de 45 años y el 26% con discordancia de peso > 20%) y del procedimiento (el 29% con tiempo de isquemia > 4 h y el 36% en procedimientos urgentes). La supervivencia a 1, 5, 10 y 15 años ha sido del 78, el 67, el 53 y el 38% respectivamente. Estas cifras permanecen estables desde 1995. Conclusiones. La actividad del trasplante cardiaco en España permanece estable en los últimos años, con alrededor de 250 procedimientos al año. A pesar del claro empeoramiento en las características de donantes, receptores y tiempos quirúrgicos, se mantienen unos resultados en mortalidad comparables a los de nuestro entorno (AU)

Introduction and objectives. The present article reports the characteristics and results of heart transplantation in Spain since this therapeutic modality was first used in May 1984. Methods. We summarize the main features of recipients, donors, and surgical procedures, as well as the results of all heart transplantations performed in Spain until December 31, 2012. Results. A total of 247 heart transplantations were performed in 2012. The whole series consisted of 6775 procedures. Recent years have seen a progressive worsening in the clinical characteristics of recipients (34% aged over 60 years, 22% with severe kidney failure, 17% with insulin-dependent diabetes, 29% with previous heart surgery, 16% under mechanical ventilation) and donors (38% aged over 45 years, 26% with recipient: donor weight mismatch>20%), and in surgical conditions (29% of procedures at >4 h ischemia and 36% as emergency transplantations). The probability of survival at 1, 5, 10, and 15 years of follow-up was 78%, 67%, 53%, and 38%, respectively. These results have remained stable since 1995. Conclusions. In recent years, the number of heart transplantations/year in Spain has remained stable at around 250. Despite the worsening of recipient and donor clinical characteristics and of time-to-surgery, the results in terms of mortality have remained stable and compare favorably with those of other countries (AU)

Características de los pacientes con supervivencia mayor de 20 años tras un trasplante cardiaco / Characteristics of patients with survival longer than 20 years following heart transplantation

Introducción y objetivos. Los receptores de trasplante cardiaco que sobreviven más de 20 años están aumentando. Poco se conoce de su seguimiento, sus comorbilidades y su mortalidad. Identificar predictores de larga supervivencia puede guiar la selección de candidatos para los donantes disponibles. Métodos. Se revisó la información sobre la clase funcional, las comorbilidades y la mortalidad de pacientes trasplantados antes de 1992. Para identificar los predictores de supervivencia > 20 años, se construyó un modelo de regresión logística utilizando las variables asociadas a supervivencia en el análisis univariable. Resultados. Se comparó a 39 supervivientes con seguimiento > 20 años (el 26% del total) con 90 pacientes que sobrevivieron entre 1 y 20 años. Las principales complicaciones fueron hipertensión, disfunción renal, infecciones y neoplasias. Tras 30 meses de seguimiento, 6 murieron, lo que implica una mortalidad del 6%/año (frente a un 2,5-3% en los años 1 a 19). Las principales causas de muerte fueron infección (50%), cáncer (33%) y vasculopatía del injerto (17%). Los supervivientes eran más jóvenes y delgados, y tenían cardiopatía no isquémica y menos isquemia en cirugía. La regresión logística identificó la edad del receptor < 45 años (odds ratio = 3,9; intervalo de confianza del 95%, 1,6-9,7; p = 0,002) y la miocardiopatía idiopática (odds ratio = 3; intervalo de confianza del 95%, 1,4-7,8; p = 0,012) como predictores independientes de supervivencia > 20 años. Conclusiones. En nuestra serie, más del 25% sobrevive más de 20 años con el mismo injerto y lleva vida independiente a pesar de las comorbilidades. La edad del receptor < 45 años y la miocardiopatía idiopática se asociaron a larga supervivencia. Estos datos pueden ayudar a la asignación de donantes (AU)

Introduction and objectives. The number of heart-transplant recipients exceeding 20 years of follow-up is steadily increasing. However, little is known about their functional status, comorbidities, and mortality. Identifying the predictors of prolonged survival could guide the selection of candidates for the low number of available donors. Methods. Functional status, morbidities, and mortality of heart-transplant patients between 1984 and 1992 were analyzed. To identify predictors of 20-year survival, a logistic regression model was constructed using the covariates associated with survival in the univariate analysis. Results. A total of 39 patients who survived 20 years (26% of patients transplanted before 1992) were compared to 90 recipients from the same period who died between 1 and 20 years post-transplantation. Major complications were hypertension, renal dysfunction, infections, and cancer. After a mean follow-up of 30 months, 6 survivors had died, yielding a mortality rate of 6% per year (vs 2.5%-3% in years 1-19). Causes of mortality were infection (50%), malignancy (33%), and allograft vasculopathy (17%). Long-term survivors were younger and leaner, and had nonischemic cardiomyopathy and lower ischemic time. Logistic regression identified recipient age <45 years (odds ratio=3.9; 95% confidence interval, 1.6-9.7; P=.002) and idiopathic cardiomyopathy (odds ratio=3; 95% confidence interval, 1.4-7.8; P=.012) as independent predictors for 20-year survival. Conclusions. One fourth of all heart-transplant patients in our series survived >20 years with the same graft, and most enjoy independent lives despite significant comorbidities. Recipient age <45 years and idiopathic cardiomyopathy were associated with survival beyond 2 decades. These data may help decide donor allocation (AU)

Brote de leishmaniasis cutánea en el municipio de Fuenlabrada / Outbreak of Cutaneous Leishmaniasis in Fuenlabrada, Madrid

Introducción: La leishmaniasis, infección endémica en España, está causada por protozoos del género Leishmania. Durante los años 2010-2012 hubo un brote de leishmaniasis cutánea y visceral en Fuenlabrada, Madrid. Objetivos: Describir los casos de leishmaniasis cutánea (LC) diagnosticados durante 17 meses en el Servicio de Dermatología del Hospital de Fuenlabrada. Material y métodos: Estudiamos variables epidemiológicas, clínicas, histológicas, microbiológicas y terapéuticas de cada caso. Resultados: Se recogieron 149 pacientes. Encontramos una incidencia similar en varones que en mujeres, la edad más frecuente fue entre 46-60 años. El tiempo de evolución presentaba un pico de máxima frecuencia entre los 2 y 6 meses. La forma clínica más habitual fue la de pápulas y placas eritematosas sin costra (52%). En el 57% de los casos las lesiones eran múltiples. La localización más común fue en áreas fotoexpuestas. El estudio histológico mostró en el 67% de los pacientes una dermatitis granulomatosa no necrotizante sin parásitos con tinciones habituales. La reacción en cadena de la polimerasa (PCR) para Leishmania confirmó el diagnóstico en el 98% de los casos. En los demás el estudio histológico de la piel identificó cuerpos de leishmanias. Los antimoniales pentavalentes intralesionales fueron los fármacos más empleados (76%), con resultado satisfactorio. Conclusiones: Presentamos una serie amplia de casos de LC en el contexto de un brote. La forma más habitual fue la aparición de múltiples pápulas, y la forma histológica la dermatitis granulomatosa no necrotizante, en la que no se observaron leishmanias. La PCR en piel fue la prueba más importante para alcanzar el diagnóstico (AU)

Introduction: Leishmaniasis, an endemic infection in Spain, is caused by protozoan parasites of the Leishmania genus. Between 2010 and 2012, there was an outbreak of cutaneous and visceral leishmaniasis in Fuenlabrada, Madrid. Objectives: To describe the cases of cutaneous leishmaniasis diagnosed over a 17-month period at the dermatology department of Hospital de Fuenlabrada. Material and methods: We analyzed the epidemiological, clinical, histological, and microbiological features of each case and also evaluated the treatments administered and outcomes. Results: We studied 149 cases. The incidence of cutaneous leishmaniasis showed a peak in the age range between 46 and 60 years and was similar in men and women. At the time of consultation, the lesions had been present for between 2 and 6 months in the majority of patients. The most common clinical presentation was with erythematous plaques and papules without crusts (52% of cases). Lesions were most often located in sun-exposed areas and were multiple in 57% of patients. In 67% of cases, the histological study showed non-necrotizing granulomatous dermatitis with no evidence of parasites using conventional staining methods. Diagnosis was confirmed by polymerase chain reaction (PCR) in 98% of patients. In the remaining cases, the histological study revealed Leishman-Donovan bodies in the skin. Intralesional pentavalent antimonials were the most commonly used drugs (76% of cases) and produced satisfactory results. Conclusions: We have presented a large series of cases of cutaneous leishmaniasis diagnosed in the context of an outbreak. Multiple papules were the most common clinical presentation, with histology that showed non-necrotizing granulomatous dermatitis with no evidence of parasites. PCR of skin samples was the test that most frequently provided the diagnosis (AU)

Fascitis necrotizante en una paciente con inmunodeficiencia común variable / Necrotising fasciitis in a patient with common variable immunodeficiency

La fascitis necrotizante es una infección grave que cursa con necrosis de los tejidos y afectación sistémica, con un curso rápido y desenlace fatal. Aunque es una entidad poco frecuente debe ser sospechada y tratada con celeridad, porque de ello depende el pronóstico. El tratamiento se basa en la actuación quirúrgica inmediata, antibioterapia de amplio espectro y medidas de soporte en una unidad de cuidados críticos. Presentamos el caso de una paciente que ingresó en reanimación tras desbridamiento quirúrgico por sospecha de fascitis necrotizante y que presentaba además una inmunodeficiencia común variable o hipogammaglobulinemia caracterizada por un déficit de linfocitos B y tratamiento con metotrexato por enfermedad de Crohn. Ambas producían déficit inmunológico. Tras 11 días de tratamiento pudo ser dada de alta con mejoría clínica, analítica y hemodinámica(AU)

Necrotizing fasciitis is a severe infection that leads to necrosis of the tissues and systemic involvement, with a rapid progress and a fatal outcome. Although this condition is rare, it must be suspected and rapidly treated, as the prognosis depends on this. The treatment is based on immediate surgery, wide spectrum antibiotic treatment, and support measures in a critical care unit. We present the case of a patient who was admitted to Recovery room after surgical debridement due to suspicion of fasciitis. The patient also had a common variable immunodeficiency or hypogammaglobulinaemia, characterised by a B lymphocyte deficiency, as well as on treatment with methotrexate for Crohn's disease. Both produced an immune deficiency. After 11 days of treatment there was a clinical, analytical and haemodynamic improvement, and she was discharged(AU)

Resposta imunológica em camundongos com tríplice infecção com cepas do Trypanosoma cruzi em diferentes biodemas frente ao uso de imunossupressores / Immune response in mice with triple infection with strains of Trypanosoma cruzi in different biodemes forward to immunosuppressants

Um fator determinante e importante que contribui para a gravidade da doença de Chagas é a ocorrência de múltiplas infecções pelo Trypanosoma cruzi nos indivíduos residentes em áreas endêmicas. Estudos experimentais comprovam o aumento da morbidade pelas reinfecções sucessivas com diferentes cepas e permitem caracterizar as cepas re-inoculadas e avaliar a influência das múltiplas infecções nas lesões tissulares. A presença de múltiplas infecções poderia também influenciar no grau de agravamento e reativação da doença de Chagas em pacientes portadores de HIV e/ou imunossuprimidos, em casos de transplantes, nos quais pode haver uma reativação de cepas virulentas levando a complicações nos indivíduos infectados. O presente estudo tem como objetivo avaliar a resposta imunopatológica em camundongos triplamente infectados com diferentes cepas do T. cruzi tratados com diferentes drogas imunossupressoras. Camundongos isogênicos da linhagem Balb/c foram infectados sucessivamente com cepas do T. cruzi de diferentes biodemas: 1- cepa Colombiana (Biodema Tipo III – T. cruzi I); 2- Cepa 21SF (Biodema Tipo II – T. cruzi II) 50 dias após; 3); 3- Cepa Y (Biodema Tipo I, Z2b) 20 dias depois; para cada cepa houve também um grupo experimental de infecção única, como controle. Após 20 dias da última infecção, os camundongos sobreviventes foram submetidos a dois esquemas de tratamento: Esquema 1: Betametasona (2mg/kg/dia) e Ciclofosfamida (250 mg/kg/dia) durante 4 semanas; Esquema 2: Azatioprina (2mg/kg), Betametasona (1mg/kg) e Ciclosporina (16mg/kg, 10mg/kg, 8mg/kg, 6mg/kg) durante 4 semanas. Como parâmetros foram analisados: parasitemia, mortalidade, estudo histopatológico; exame sorológico, dosagem de isótipos de imunoglobulinas (método de ELISA) e teste cutâneo (hipersensibilidade tardia). No presente estudo foi observada uma reativação da parasitemia e da mortalidade em camundongos com triplíce infecção e tratados com Betametasona e Ciclofosfamida. Concomitantemente, com a reagudização da infecção pelo T. cruzi neste grupo, observou-se uma intensificação do parasitismo tissular, um aumento do processo inflamatório mononuclear, espessamento da matriz extracelular e macrofagotropismo com o aparecimento de ninhos parasitários com formas amastigotas do T. cruzi no fígado e no baço. O tratamento combinado com Azatioprina, Ciclosporina e Betametasona em camundongos triplamente infectados, por cepas do T. cruzi de diferentes biodemas, não determinou um aumento significativo da parasitemia e da mortalidade. Entretanto, o estudo histopatológico destes animais mostrou um aumento da infiltração mononuclear perivascular no miocárdio e músculo esquelético, áreas focais de destruição tissular e presença de arterite e arteriolite. Os resultados do exame sorológico anti-T. cruzi demonstraram que o tratamento com imunossupressores (Betametasona e Ciclofosfamida; Azatioprina, Betametasona e Ciclosporina) em camundongos triplamente infectados determinou uma redução da titulação de anticorpos anti-T. cruzi nos dois grupos de tratamento, quando comparados ao grupo de animais triplamente infectados e não tratados. Os resultados demonstraram que camundongos triplamente infectados e tratados com Betametasona e Ciclofosfamida, apresentaram uma diminuição nos níveis de IgG1, IgG2a, IgM e IgG2b estatisticamente significante, quando comparados ao grupo infectado sem tratamento. Nos camundongos triplamente infectados e tratados com Azatioprina, Betametasona e Ciclosporina foi observado um aumento nos níveis de IgG2a e uma diminuição nos níveis de IgG2b quando comparados aos níveis deste isótipo nos outros grupos. O resultado do teste de hipersensibilidade tardia através o teste cutâneo com medição da espessura da pata apresentou diferença significante no ponto de 48h nos grupos de camundongos triplamente infectados não tratados, camundongos tratados com Betametasona e Ciclofosfamida e no grupo de camundongos tratados com Azatioprina, Betametasona e Ciclosporina. No presente estudo, a imunossupressão com Betametasona e Ciclofosfamida determinou uma reativação da fase aguda em camundongos, comparável ao visto em pacientes imunossuprimidos. Concomitantemente houve uma diminuição significante das imunoglobulinas do soro, indicando a importância da resposta humoral no controle da infecção. O tratamento com Azatioprina, Betametasona e Ciclosporina em camundongos cronicamente infectados pelo T. cruzi pode influenciar no agravamento das lesões imunopatológicas características de uma reação de hipersensibilidade tardia, principalmente no miocárdio, embora sem determinar a reagudização da infecção pelo T. cruzi.

Descripción de cuatro casos de histoplasmosis importada en Navarra / Imported histoplasmosis in Navarra: presentation of four cases

Objetivo. La histoplasmosis es una infección fúngica causada por el hongo dimórfico Histoplasma capsulatum. En los últimos años, su incidencia en Espa¿na ha aumentado debido, principalmente, a la mayor presencia de población inmigrante procedente de América y al incremento de viajes a dicho continente por turismo o cooperación. Nuestro objetivo ha sido revisar las características clínicas de los casos de histoplasmosis diagnosticados en nuestro centro en los últimos 6 años. Casos clínicos. Se diagnosticaron 4 casos pertenecientes a 4 pacientes de origen sudamericano, 3 de los cuales eran VIH positivos y 1 diagnosticado de dermatomiositis y en tratamiento con fármacos inmunosupresores. El diagnóstico de laboratorio se llevó a cabo mediante estudio anatomopatológico y microbiológico, mediante cultivo y PCR específica directa de la muestra. Discusión. Al tratarse de una infección importada es necesario tener un alto índice de sospecha y realizar una anamnesis detallada, para llegar a su diagnóstico. Es una infección a tener en cuenta en el diagnóstico diferencial del síndrome febril en pacientes inmunodeprimidos, tanto VIH positivos como en tratamiento inmunosupresor, que sean originarios de zonas endémicas o que tengan antecedentes de estancia en ellas(AU)

Objetive. Histoplasmosis is a fungal infection caused by the dimorphic fungi Histoplasma capsulatum. Its incidence in Spain has increased in recent years, mainly due to the increased presence of immigrants from Latin America and increased travel to the continent for tourism and cooperation. Our aim was to review the clinical characteristics of cases of histoplasmosis diagnosed in our hospital during the last six years. Case Reports. We diagnosed 4 cases from 4 patients from South America, 3 ofwhomwere HIV positive and 1 diagnosed with dermatomyositis was treated with immunosuppressive drugs. The laboratory diagnosis was carried out by histological and microbiological study, by culture and specific PCR directly on the sample. Discussion. As it is an imported infection there needs to be a high level of suspicion and a detailed history taken to get a diagnosis. This infection requires a differential diagnosis between febrile syndrome in immunosuppressed patients, both HIV positive and immunosuppressive therapy, which originate from endemic areas, or who have a history of staying in them(AU)

Registro Español de Trasplante Cardiaco. XXI Informe Oficial de la Sección de Insuficiencia Cardiaca y Trasplante Cardiaco de la Sociedad Española de Cardiología (1984-2009) / Spanish Heart Transplantation Registry. 21st Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2009)

Introducción y objetivos. El propósito de este artículo es presentar los resultados del trasplante cardiaco desde que se inició esta modalidad terapéutica en España en mayo de 1984. Métodos. Se ha realizado un análisis descriptivo de todos los trasplantes cardiacos realizados hasta el 31 de diciembre de 2009. Resultados. El número total de trasplantes fue de 6.048. El perfil clínico medio del paciente que se trasplantó en España en 2009 fue el de un varón de 53 años, diagnosticado de cardiopatía isquémica no revascularizable con depresión grave de la función ventricular y situación funcional avanzada, al que se implantó un corazón procedente de un donante fallecido por hemorragia cerebral, con una media de edad de 37 años y un tiempo en lista de espera de 106 días. El tiempo medio de supervivencia se ha incrementado con los años. Así, mientras en el total de la serie la probabilidad de supervivencia tras 1, 5, 10 y 15 años es del 78, el 67, el 53 y el 40% respectivamente, en los últimos 5 años la probabilidad de supervivencia tras 1 y 5 años es del 85 y el 73% respectivamente. La causa más frecuente de fallecimiento es el fallo agudo del injerto (17%), seguido de infección (16%), un combinado de enfermedad vascular del injerto y muerte súbita (14%), tumores (12%) y rechazo agudo (8%). Conclusiones. La supervivencia obtenida en España con el trasplante cardiaco, sobre todo en los últimos años, lo sitúa como el tratamiento de elección para cardiopatías irreversibles en situación funcional avanzada y sin otras opciones médicas o quirúrgicas establecidas (AU)

Introduction and objectives. The purpose of this report is to present the results obtained with heart transplantation in Spain from the first use of this therapeutic modality in May 1984. Methods. A descriptive analysis of all heart transplantations performed up to December 31, 2009 is presented. Results. In total, 6048 transplants were carried out. The typical clinical profile of a Spanish heart transplant patient in 2009 was that of a 53-year-old male who had been diagnosed with nonrevascularizable ischemic heart disease and who had severely impaired ventricular function and a poor functional status. The implanted heart typically came from a donor who had died from a brain hemorrhage (mean age 37 years) and the average time on the waiting list was 106 days. Mean survival time has increased progressively over the years. Whereas for the whole time series, the probability of survival at 1, 5, 10 and 15 years was 78%, 67%, 53% and 40%, respectively, for the past 5 years, the probability of survival at 1 and 5 years was 85% and 73%, respectively. The most frequent cause of death was acute graft failure (17%), followed by infection (16%), the combination of graft vascular disease and sudden death (14%), tumor (12%) and acute rejection (8%). Conclusions. The survival rates obtained in Spain with heart transplantation, especially in recent years, make the procedure the treatment of choice for patients who have irreversible heart failure and a poor functional status and for whom there are few other established medical or surgical options (AU)

Cambio climático y piel: retos diagnósticos y terapéuticos / Climatic Change and Skin: Diagnostic and Therapeutic Challenges

Numerosos científicos informan de una tendencia actual al calentamiento global y a la disminución de las precipitaciones. Su cuantía, sus causas y la influencia de la actividad humana son motivo de controversia. Un aumento de la temperatura podría incrementar la prevalencia de algunas patologías cutáneas; más personas padecerían piel sensible y una mayor xerosis cutánea por disminución de la humedad relativa. Las alteraciones de la función de la barrera cutánea aumentarían la gravedad y prevalencia de la dermatitis atópica. La mayor proporción de radiación UVB que alcanza la superficie terrestre, unida a hábitos poblacionales de aumento de fotoexposición, junto con una fotoprotección incorrecta, hacen esperables mayores tasas de cáncer cutáneo y de fotoenvejecimiento. Además, los hábitats de diversos vectores de patologías infecciosas están cambiando. Afrontar estos problemas, en caso de que se produjesen, será un reto para el dermatólogo, que tendrá una importante labor de prevención, diagnóstico y tratamiento precoz de estas patologías (AU)

Scientifics are warning us about a global warming tendency and diminished rainfalls. Quantity, causes and human activity influence remain controversial. Warming could increase prevalence of some cutaneous pathology. Sensible skin and skin xerosis would be more prevalent if relative humidity decreases. Alterations of skin barrier`s function would increase seriousness and prevalence of atopic dermatitis. Furthermore, the higher UVB proportion reaching Earth′s surface, in conjunction with increased sunbathing population habits, will increase cutaneous cancer and photoaging rates without a correct photoprotection. Also, habitats of some infectious diseases` vectors are changing. The facing of these problems will be a real challenge for the dermatologist, who will have a very important role on prevention, diagnoses and early treatment of them (AU)

Endonasal phototherapy with Rhinolight for the treatment of allergic rhinitis.

Allergic rhinitis, although not life threatening, significantly affects the quality of the patient's daily life. The three major steps in the treatment of the condition are avoidance of allergens, treatment of symptoms (in particular, antihistaminics and topical nasal corticosteroids) and specific immunotherapy. Avoidance of the allergen is usually not possible and symptom relief is often limited, despite the availability of a number of pharmacological options. Specific immunotherapy demands a high level of cooperation on the part of the patient for at least 3 years. Endonasal phototherapy with the Rhinolight device (Rhinolight Ltd, Szeged, Hungary) for the treatment of immunoglobulin E-mediated allergic rhinitis is a new option that utilizes the immunosuppressive effects of UV radiation. The method directs a combination of UV-B (5%), UV-A (25%) and visible light (70%) into the nasal cavity, and its effectiveness has been demonstrated in one double-blind, placebo-controlled study. The results of additional studies have been presented at various medical conferences and in abstracts. Reports in the literature confirm that phototherapy is a well-established and successful treatment of atopic dermatitis and other skin diseases.

Identificación de las diferentes variantes geneticas del VIH-1 en niños de procedencia no española / HIV-1 genetic variability in non Spaniard infected children

Introducción: la prevalencia de las nuevas infecciones por subtipos distintos de B del VIH-1 y recombinantes entre subtipos del VIH-1 se está incrementando en Europa occidental. Esto se debe principalmente a los movimientos migratorios desde zonas donde estas variantes genéticas son endémicas. Existe una amplia base teórica sobre la probablemente peor respuesta inmunovirológica de los subtipos distintos de B del VIH-1, pero esto no se ha demostrado en la experiencia clínica. Objetivos: identificar las diferentes variantes genéticas del VIH-1 y su evolución clínica en una serie de niños infectados por VIH-1 de procedencia no española. Pacientes y método: estudio retrospectivo de las historias clínicas y caracterización del subtipo del VIH-1 en 12 pacientes infectados entre enero de 1988 y diciembre de 2006, menores de 18 años al diagnóstico y de procedencia no española. Resultados: se aisló un subtipo del VIH-1 distinto de B en 5 (42%) niños: el recombinante CRF2_AG se aisló en 3 casos (Guinea Ecuatorial), el subtipo C en 1 (Guinea Ecuatorial) y el recombinante CRF13_cpx en 1 (India). Discusión: debido al aumento creciente de la inmigración y de las adopciones internacionales, es previsible que asistamos a un incremento en el número de infecciones pediátricas por VIH-1 de subtipos distintos de B y recombinaciones del VIH-1. La caracterización del subtipo genético del VIH-1 debería realizarse dentro de la rutina clínica en niños infectados o expuestos al VIH-1 cuyo origen sea de áreas geográficas con alta prevalencia de subtipos distintos del B. Estudios con un mayor número de pacientes permitirían detectar, en caso de que las hubiera, diferencias en la evolución clínica, inmunológica y virológica (AU)

Introduction: The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, beause of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant’s response remain undocumented. Aims: To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. Patients and method: Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. Results: HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtyoe C in one (Equatorial Guinea) and CRF13_cpx in last one (India). Discussion: Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient’s clinical, immunological and virological evolution (AU)

Photoaging: mechanisms and repair / Photoaging: mechanisms and repair

Aging is a complex, multifactorial process resulting in several functional and esthetic changes in the skin. These changes result from intrinsic as well as extrinsic processes, such as ultraviolet radiation. Recent advances in skin biology have increased our understanding of skin homeostasis and the aging process, as well as the mechanisms by which ultraviolet radiation contributes to photoaging and cutaneous disease. These advances in skin biology have led to the development of a diversity of treatments aimed at preventing aging and rejuvenating the skin. The focus of this review is the mechanism of photoaging and the pathophysiology underlying the treatments specifically designed for its prevention and treatment. LEARNING OBJECTIVES: At the conclusion of this learning activity, participants should be familiar with the mechanism of photoaging, the treatments for photoaging, and the data that supports the use of these treatments...

Xenotrasplante renal cerdo hDAF-babuino. Experiencia y revisión / Renal xenotrasplantation of HDAF pig to baboons. Experience and review

INTRODUCCIÓN: El xenotrasplante renal puede representar la solución a la creciente demanda de órganos. Presentamos nuestra experiencia y revisamos el estado actual del xenotrasplante. MATERIAL Y MÉTODO: Hemos realizado 20 xenotrasplantes de riñón de cerdo transgénico hDAF a babuino con cuatro protocolos de inmunosupresión. Todos los receptores recibieron GAS 914.Grupo A: Ciclofosfamida, Ciclosporina, Micofenolato y Corticosteroides (n=10).Grupo B: Ciclofosfamida, Ciclosporina, FTY 720 y Corticosteroides (n=3).Grupo C: Basiliximab, Ciclosporina, FTY 720 y Corticosteroides (n=3).Grupo D: Basiliximab, FTY 720, Everolimus y Corticosteroides (n=4). RESULTADOS: La supervivencia de los xenoinjertos osciló entre 1 y 31 días. La supervivencia en relación con los protocolos de inmunosupresión no fue significativamente diferente: A) 7 días, B) 8días, C) 8 días, D) 9 días. CONCLUSIONES: 1. Los tiempos de isquemia fría influyen en la función inicial de los riñones, no en su evolución final. 2. El rechazo hiperagudo ha sido superado con la utilización de cerdos transgénicos, produciéndose el fracaso por rechazo humoral agudo, no controlado con los protocolos de inmunosupresión actuales. 3. Es preciso investigar y desarrollar otros protocolos de inmunosupresión que nos permitan un mejor conocimiento de la fisiología del xenoinjerto y de su potencial riesgo de transmisión de enfermedades (AU)

SUMMARY: The renal xenotrasplant could be the solution on the demand of organs for transplantation. We present here our experience and review the actual status of the xenotransplant. METHODS: We have done 20 xenotransplants from transgenic pig h DAF to baboons, with four protocols of inmunosupression. All the hosts were treated with GAS 914.Group A: Cyclophosphamide, Cyclosporine, Mycophenolate, and Steroids (n=10).Group B: Cyclophosphamide, Cyclosporine, FTY 720, and Steroids (n=3). Group C: Basiliximab, Cyclosporine, Mycophenolate, and Steroids (n=3). Group D: Basiliximab, FTY 720, Everolymus, and Steroids (n=4). RESULTS: The duration of the xenografts ranged between 1 and 31 days. The function of the xenografts in relation to the type of inmunosupression were not significantly different: A) 7 days, B) 8 days, C) 8 days, and D) 9 days. CONCLUSIONS: 1. The cold ischemic time of the graft, has influence in the initial function of the kidneys but not in the evolution and duration of the graft. 2. The hyperacute rejection has been overcome with the utilization of transgenic pigs. The graft failure was due to acute humoral rejection that was not aborted by the actual inmunosupressors. 3. It is necessary to develop new inmunosupression protocols, through new knowledge of their pharmacology and the physiology of the xenografts, and at the same time it is important to avoid the potential risk of transmission of animal infections (AU)