Miocarditis y miocardiopatía inflamatoria confirmadas por biopsia endomiocárdica: perfil clínico y pronóstico / Endomyocardial biopsy-confirmed myocarditis and inflammatory cardiomyopathy: clinical profile and prognosis

Introducción y objetivos La biopsia endomiocárdica (BEM) es la única técnica capaz de establecer el diagnóstico etiológico de pacientes con miocarditis o miocardiopatía inflamatoria (MI). El objetivo de este estudio es conocer el perfil clínico, la evolución y los factores pronósticos de los pacientes con sospecha de miocarditis o MI sometidos a BEM. Métodos Se analizaron retrospectivamente las características clínicas, los hallazgos histológicos y la evolución de todos los pacientes con sospecha de miocarditis o MI sometidos a BEM entre 1997 y 2019 en un hospital terciario español. Se evaluó el rendimiento del diagnóstico histológico mediante los criterios de Dallas frente a los criterios inmunohistoquímicos (IHQ). Resultados Se realizó BEM a 99 pacientes (el 67% varones; edad, 42± 15 años; fracción de eyección media, 34±14%). El 28% presentaba miocarditis o MI confirmada por criterios de Dallas y el 54% aplicando los criterios IHQ (p <0,1). Se diagnosticaron 47 miocarditis linfocitarias, 6 miocarditis eosinofílicas, 3 sarcoidosis y 1 miocarditis de células gigantes. Tras una mediana de seguimiento de 18 meses, 23 pacientes (23%) precisaron trasplante cardiaco o asistencia ventricular o fallecieron. El 21% de los pacientes con miocarditis confirmada mediante IHQ precisó trasplante cardiaco o asistencia o falleció, frente al 7% de aquellos sin inflamación (p=0,056). La fracción de eyección ≤ 30%, un diámetro telediastólico del ventrículo izquierdo ≥60mm y una clase NYHA III-IV iniciales se asociaron con peor pronóstico, especialmente en presencia de inflamación. Conclusiones La BEM permite establecer un diagnóstico etiológico en más de la mitad de los casos de sospecha de miocarditis o MI cuando se emplean técnicas IHQ. La inflamación confirmada por IHQ añade valor pronóstico y permite identificar a los pacientes con mayor probabilidad de sufrir complicaciones (AU)

Introduction and objectives Endomyocardial biopsy (EMB) is the only technique able to establish an etiological diagnosis of myocarditis or inflammatory cardiomyopathy (ICM). The aim of this study was to analyze the clinical profile, outcomes, and prognostic factors of patients with suspected myocarditis/ICM undergoing EMB. Methods We retrospectively analyzed the clinical characteristics, histological findings, and follow-up data of all patients with suspected myocarditis or ICM who underwent EMB between 1997 and 2019 in a Spanish tertiary hospital. The diagnostic yield was compared using the Dallas criteria vs immunohistochemical criteria (IHC). Results A total of 99 patients underwent EMB (67% male; mean age, 42±15 years; mean left ventricular ejection fraction [LVEF], 34%±14%). Myocarditis or ICM was confirmed in 28% with application of the Dallas criteria and in 54% with the IHC criteria (P <.01). Lymphocytic myocarditis was diagnosed in 47 patients, eosinophilic myocarditis in 6, sarcoidosis in 3, and giant cell myocarditis in 1 patient. After a median follow-up of 18 months, 23 patients (23%) required heart transplant (HTx), a left ventricular assist device (LVAD), and/or died. Among the patients with IHC-confirmed myocarditis, 21% required HTx/LVAD or died vs 7% of those without inflammation (P=.056). The factors associated with a worse prognosis were baseline LVEF ≤ 30%, left ventricular end-diastolic diameter ≥ 60mm, and NYHA III-IV, especially in the presence of inflammation. Conclusions EMB allows an etiological diagnosis in more than half of patients with suspected myocarditis/ICM when IHC techniques are used. IHC-confirmed inflammation adds prognostic value and helps to identify patients with a higher probability of developing complications (AU)

Fluorescence labeling of mitochondria in living cells by the cationic photosensitizer ZnTM2,3PyPz, and the possible roles of redox processes and pseudobase formation in facilitating dye uptake.

The study of labeling selectivity and mechanisms of fluorescent organelle probes in living cells is of continuing interest in biomedical sciences. The tetracationic phthalocyanine-like ZnTM2,3PyPz photosensitizing dye induces a selective violet fluorescence in mitochondria of living HeLa cells under UV excitation that is due to co-localization of the red signal of the dye with NAD(P)H blue autofluorescence. Both red and blue signals co-localize with the green emission of the mitochondria probe, rhodamine 123. Microscopic observation of mitochondria was improved using image processing and analysis methods. High dye concentration and prolonged incubation time were required to achieve optimal mitochondrial labeling. ZnTM2,3PyPz is a highly cationic, hydrophilic dye, which makes ready entry into living cells unlikely. Redox color changes in solutions of the dye indicate that colorless products are formed by reduction. Spectroscopic studies of dye solutions showed that cycles of alkaline titration from pH 7 to 8.5 followed by acidification to pH 7 first lower, then restore the 640 nm absorption peak by approximately 90%, which can be explained by formation of pseudobases. Both reduction and pseudobase formation result in formation of less highly charged and more lipophilic (cell permeant) derivatives in equilibrium with the parent dye. Some of these are predicted to be lipophilic and therefore membrane-permeant; consequently, low concentrations of such species could be responsible for slow uptake and accumulation in mitochondria of living cells. We discuss the wider implications of such phenomena for uptake of hydrophilic fluorescent probes into living cells.

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants.

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P=0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P=0.18), and for grades III-IV was 2.6% vs 11.6% (P=0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P=0.002) and extensive 5% vs 23.6% (P=0.01). OS was 74% vs 76% for BM vs PBSCs (P=0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P=0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P=0.005) respectively. In multivariate analysis, aGvHD II-IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1-5.6, P=0.02) and aGvHD III-IV (HR 8.3 CI 3.4-20.2, P<0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patients.

Percepción de riesgo cardiovascular en una población ambulatoria de la Comunidad de Madrid / Perception of cardiovascular risk in an outpatient population of the Madrid Community

Introducción: Las enfermedades cardiovasculares aportan la mayor carga de mortalidad mundial. Estudiar el grado de conocimiento poblacional de los factores de riesgo y del riesgo cardiovascular es una estrategia preventiva prioritaria. Material y métodos: Estudio transversal con 369 personas. Las variables fueron sociodemográficas, de factores y percepción del riesgo cardiovascular y físicas y antropométricas. El riesgo se estratificó con la tabla SCORE. Resultados: El 49,6% eran hombres y el 50,4%, mujeres. La proporción de diagnóstico fue del 23,8% en HTA, 39% hipercolesterolemia, 31,4% tabaquismo, 26,3% obesidad y 4,6% en diabetes. La concordancia entre riesgo cardiovascular percibido y real fue muy débil. Discusión: La población tiene un buen conocimiento en diabetes y aceptable en HTA e hipercolesterolemia pero bajo en estados prediabéticos y en la percepción del riesgo cardiovascular asociado

Introduction: Cardiovascular diseases are responsible for the largest burden of global mortality. The study of the degree of knowledge of their population risk factors and cardiovascular risk is a priority preventive strategy. Material and methods: A cross-sectional study with 369 people was performed. The sociodemographic variables were cardiovascular risk and perception as well as physical and anthropometric factors. The risk was stratified with the SCORE table. Results: A total of 49.6% were men and 50.4% were women. The proportion of diagnosis was 23.8% in HTA, 39% in hypercholesterolemia, 31.4% in smoking, 26.3% in obesity and 4.6% in diabetes. Concordance between perceived and real cardiovascular risk was very weak. Discussion: The population has good knowledge about diabetes and acceptable knowledge about hypertension, and hypercholesterolemia but knowledge in prediabetic states and perception of the associated cardiovascular risk is low

Ética de la virtud, reencontrando el sentido de la clínica / Virtue ethics, rediscovering the meaning of the clinic

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[Perception of cardiovascular risk in an outpatient population of the Madrid Community]. / Percepción de riesgo cardiovascular en una población ambulatoria de la Comunidad de Madrid.

INTRODUCTION: Cardiovascular diseases are responsible for the largest burden of global mortality. The study of the degree of knowledge of their population risk factors and cardiovascular risk is a priority preventive strategy. MATERIAL AND METHODS: A cross-sectional study with 369 people was performed. The sociodemographic variables were cardiovascular risk and perception as well as physical and anthropometric factors. The risk was stratified with the SCORE table. RESULTS: A total of 49.6% were men and 50.4% were women. The proportion of diagnosis was 23.8% in HTA, 39% in hypercholesterolemia, 31.4% in smoking, 26.3% in obesity and 4.6% in diabetes. Concordance between perceived and real cardiovascular risk was very weak. DISCUSSION: The population has good knowledge about diabetes and acceptable knowledge about hypertension, and hypercholesterolemia but knowledge in prediabetic states and perception of the associated cardiovascular risk is low.

La sífilis y la experimentación en humanos: perspectiva histórica y reflexiones éticas. De la Segunda Guerra Mundial a la actualidad / Syphilis and Human Experimentation From World War II to the Present: A Historical Perspective and Reflections on Ethics

Incluso después de la promulgación del código de Nuremberg las investigaciones sobre sífilis continuaron alejándose en muchas ocasiones de los estándares éticos. En este artículo hemos revisado las investigaciones que sobre esta enfermedad tuvieron lugar después de la Segunda Guerra Mundial, centrándonos en los casos de Guatemala y de Tuskegee. En Guatemala durante los a˜nos 1946 a 1948 se inoculó deliberadamente a más de 1.000 adultos sífilis, cancroide y gonorrea, y se hicieron miles de serologías a poblaciones indígenas o a ni˜nos huérfanos. El experimento Tuskegee sobre sífilis fue realizado entre 1932 y 1972 por el Servicio Público de Salud de los Estados Unidos para estudiar la evolución natural de esta enfermedad en ausencia de tratamiento. Se realizó sobre un grupo de población rural de raza negra y no se interrumpió a pesar de la introducción de tratamientos eficaces para la resolución de la enfermedad durante estos años (1945)

Even after the Nuremberg code was published, research on syphilis often continued to fall far short of ethical standards. We review post-World War II research on this disease, focusing on the work carried out in Guatemala and Tuskegee. Over a thousand adults were deliberately inoculated with infectious material for syphilis, hancroid, and gonorrhea between 1946 and 1948 in Guatemala, and thousands of serologies were performed in individuals belonging to indigenous populations or sheltered in orphanages. The Tuskegee syphilis study, conducted by the US Public Health Service, took place between 1932 and 1972 with the aim of following the natural history of the disease when left untreated. The subjects belonged to a rural black population and the study was not halted when effective treatment for syphilis became available in 1945

Experimentación en sífilis hasta la Segunda Guerra Mundial: historia y reflexiones éticas / Syphilis and Human Experimentation From the First Appearance of the Disease to World War II: A Historical Perspective and Reflections on Ethics

Durante siglos la sífilis ha sido objeto de investigación por parte de los médicos, dado que la etiología, la forma de contagio, la profilaxis y el tratamiento eran desconocidos. En muchas ocasiones las investigaciones se han alejado de los estándares éticos actuales. En este artículo hemos revisado desde un punto de vista histórico y ético las investigaciones que sobre esta enfermedad se han ido realizando a lo largo de los siglos, centrándonos sobre todo en aquellos experimentos realizados en el siglo XX. Describimos con detalle los estudios realizados en los años que tuvieron lugar alrededor de la Segunda Guerra Mundial: experimentos realizados por los médicos norteamericanos en prisiones de Estados Unidos, la sífilis en la Alemania nazi o los ensayos realizados por los japoneses en centros de experimentación creados a tal fin en los territorios ocupados

Physicians have conducted research on syphilis for centuries, seeking to understand its etiology and the means of transmission as well as find ways to prevent and cure the disease. Their research practices often strayed from today's ethical standards. In this paper we review ethical aspects of the long history of research on syphilis with emphasis on the experiments performed in the 20th century. The description of research around the time of World War II covers medical experiments carried out in US prisons and in the experimentation centers established by Japanese doctors in occupied territory, as well as experiments in Nazi Germany and the treatment of syphilitics there

Syphilis and human experimentation from World War II to the present: a historical perspective and reflections on ethics.

Even after the Nuremberg code was published, research on syphilis often continued to fall far short of ethical standards. We review post-World War II research on this disease, focusing on the work carried out in Guatemala and Tuskegee. Over a thousand adults were deliberately inoculated with infectious material for syphilis, chancroid, and gonorrhea between 1946 and 1948 in Guatemala, and thousands of serologies were performed in individuals belonging to indigenous populations or sheltered in orphanages. The Tuskegee syphilis study, conducted by the US Public Health Service, took place between 1932 and 1972 with the aim of following the natural history of the disease when left untreated. The subjects belonged to a rural black population and the study was not halted when effective treatment for syphilis became available in 1945.

Syphilis and human experimentation from the first appearance of the disease to World War II: a historical perspective and reflections on ethics.

Physicians have conducted research on syphilis for centuries, seeking to understand its etiology and the means of transmission as well as find ways to prevent and cure the disease. Their research practices often strayed from today's ethical standards. In this paper we review ethical aspects of the long history of research on syphilis with emphasis on the experiments performed in the 20th century. The description of research around the time of World War II covers medical experiments carried out in US prisons and in the experimentation centers established by Japanese doctors in occupied territory, as well as experiments in Nazi Germany and the treatment of syphilitics there.

Dermatología en la Alemania nazi / Dermatology in Nazi Germany

Durante la época nazi se llevaron a cabo de forma sistemática experimentos con seres humanos y la eliminación de individuos considerados como no productivos para la sociedad. En dichos actos se vieron involucrados médicos y dermatólogos cuyo nombre está vinculado de una forma u otra a nuestra especialidad, algunos de ellos muy conocidos, como Reiter. Con esta revisión queremos dar a conocer quién hubo detrás de muchos de los nombres que utilizamos para denominar enfermedades, signos clínicos, histológicos y síndromes en nuestra especialidad (AU)

During the Nazi period experimentation on human subjects and the elimination of individuals considered to be unproductive members of society were carried out in a systematic fashion. Involved in these practices were many physicians, including dermatologists whose names are linked in one way or another to their specialty. Some, such as Reiter, are very well known. This review attempts to bring to light the identities behind the names we have given to diseases, clinical and histological signs, and syndromes in dermatology (AU)

Medicina y nazismo. Aprender de la Historia / Nazism and Medicine. Learning from History

En el momento actual siguen vigentes en la asistencia diaria de los pacientes los mismos aspectos éticos presentes durante ese período (límites de la investigación, decisiones al final de la vida, relación del médico con el estado e investigación genética). Conocer el pasado y el papel desempeñado por los médicos nazis refuerza el necesario énfasis en la bioética y en el profesionalismo dentro de la formación de los profesionales sanitarios. Entre 1933 y 1945, en la Alemania nazi médicos y otros profesionales participaron en la esterilización de pacientes portadores de enfermedades genéticas y mentales, en el asesinato de enfermos mentales y de niños con malformaciones, en experimentos científicos y seudocientíficos que no contaban con la voluntad de los participantes, y en el exterminio de otras personas en función de su condición religiosa, política, cultural o de identidad (opositores, judíos, gitanos y homosexuales, entre otros)(AU)

Between 1933-1945 in Nazi Germany, physicians and other professional care providers participated in forced sterilization of patients who were carriers of genetic origin diseases and psychiatric disorders, extermination of children and adults with congenital and mental diseases, “scientific and pseudoscientific” medical experiments without consent and mass extermination of people based on their religion, political, cultural or sexual identity (Jews, gypsies, homosexuals). At present, the same ethical issues present during Nazi Period (research limits, end-life decisions, role of the physician as state or health system servant, and genetic research) continue to be present in routine medical care. Having knowledge of the past and the role played by Nazi doctors reinforces the necessary emphasis on bioethics and professionalism within the training of professional health providers(AU)

[Nazism and medicine. Learning from history]. / Medicina y nazismo. Aprender de la historia.

Between 1933-1945 in Nazi Germany, physicians and other professional care providers participated in forced sterilization of patients who were carriers of genetic origin diseases and psychiatric disorders, extermination of children and adults with congenital and mental diseases, "scientific and pseudoscientific" medical experiments without consent and mass extermination of people based on their religion, political, cultural or sexual identity (Jews, gypsies, homosexuals). At present, the same ethical issues present during Nazi Period (research limits, end-life decisions, role of the physician as state or health system servant, and genetic research) continue to be present in routine medical care. Having knowledge of the past and the role played by Nazi doctors reinforces the necessary emphasis on bioethics and professionalism within the training of professional health providers.

[Dermatology in Nazi Germany]. / Dermatología en la Alemania Nazi.

During the Nazi period experimentation on human subjects and the elimination of individuals considered to be unproductive members of society were carried out in a systematic fashion. Involved in these practices were many physicians, including dermatologists whose names are linked in one way or another to their specialty. Some, such as Reiter, are very well known. This review attempts to bring to light the identities behind the names we have given to diseases, clinical and histological signs, and syndromes in dermatology.

Relationship among changes in hematocrit, albumin and corticosteroid dose on the disposition of tacrolimus during the first six months following renal transplantation.

Tacrolimus is a macrolide immunosuppressant that is safe and effective for the prevention of rejection after kidney transplantation. The oral bioavailability of tacrolimus averages 20% to 25%; however, the inter-individual variability in this parameter is large. Because of the poor correlation of dose to blood concentration between patients, the variability in pharmacokinetics and a relatively narrow therapeutic window, therapeutic drug monitoring of tacrolimus trough whole blood concentrations must be a standard practice. The objective of this evaluation was to determine the relationship among changes in hematocrit, albumin, and corticosteroid dosing on the disposition of tacrolimus during 6 months of treatment in renal transplant recipients. Blood samples for the determination of trough tacrolimus concentrations were taken immediately prior to the morning dose, samples were collected according to the request of the attending physician. Clinical and dosage data were reviewed 6 months after transplantation. The analysis was conducted including 11 patients who were analyzed for hematocrit and albumin at the same time they are measured tacrolimus blood levels. The mean age was 25.3 years (range 17 to 41 years) 4 of the patients were female. Levels of tacrolimus, hematocrit and albumin over the first 24 weeks post-transplant were documented and the estimated relative clearance of tacrolimus were calculated. Statistical evaluation of the data indicates poor correlation between relative clearance and both hematocrit and albumin levels and the mean oral steroid dose. This observation is of clinical significance because dose adjustment may be required to maintain blood concentrations within thetherapeutic range in patients in whom hematocrit or albumin concentrations are changing.

Aprendizaje basado en la resolución de problemas: una experiencia práctica / Problem-based-solving learning: a practical experience

El aprendizaje basado en la resolución de problemas incorpora herramientas metodológicas capaces de facilitar la consecución de los objetivos propuestos para la formación de los futuros médicos dentro del marco de la docencia universitaria en el Espacio Europeo de Educación Superior. Promueve una formación más activa, flexible y práctica, que concede mayor protagonismo al trabajo personal tutorizado(aprendizaje autodirigido), en detrimento de las clásicas clases teóricas, eminentemente expositivas, en las que el papel del estudiante es, en general, más pasivo. La Unidad de Medicina de Familia de la Universidad Autónoma de Madrid incorporó el aprendizaje basado en la resolución de problemas en el desarrollo de la asignatura optativa ‘Atención Primaria y Medicina de Familia’, ofertada como optativa a los alumnos de segundo ciclo de licenciatura (cursos 4.º a 6.º)desde el curso 2005-2006. Intentamos con ella promover la formación de médicos capaces de aprender y mantener su competencia durante toda su vida profesional, no sólo en lo referido a la adquisición/integración de conocimientos científicos suficientes, sino también en cuanto al desarrollo de las habilidades necesarias para su adecuada aplicación práctica considerando a cada paciente de modo integral como realidad biopsicosocial, en un contexto sanitario definido, sin olvidar los aspectos bioéticos implícitos al quehacer del médico (respeto hacia el paciente y compromiso social). Revisamos en este artículo el diseño práctico de la asignatura (AU)

Learning based on problem-solving incorporates methodological tools that make it easier to fulfill the aims set for the training of future physicians within the framework of university education in the European Higher Education Area. It encourages a more active, flexible and practical training, which grants a leading role to tutor-guided personal work(self-directed learning) rather than the classical theoretical, eminently expository, classes, in which the student generally played a more passive role. The Family Medicine Unit at the Universidad Autónoma de Madrid has included learning based on problem-solving as part of the elective subject ‘Primary Care and Family Medicine’, which is optional for students in the second cycle of their degree (years 4 to 6),since the academic year 2005-2006. By so doing our aim is to try to promote the training of physicians who are capable of learning and maintaining their competence throughout their entire career. This must not only involve the acquisition/integration of sufficient scientific knowledge but also the development of the skills needed to be able to apply them in a practical sense by considering each patient in a integral manner as a biopsychosocial reality, within a particular health care context. And we must not forget the bioethical aspects that are implicit in the doctor’s work (respect for the patient and social compromise). In this article, we review the practical design of the subject (AU)