Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis / Valor pronóstico de los autoanticuerpos anti-IFI16 en la hipertensión arterial pulmonar y en la mortalidad en los pacientes con esclerodermia sistémica

Objectives: To determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA). Methods: Overall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed. Results: Overall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043). Conclusion: Anti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome. (AU)

Objetivos: Determinar el valor diagnóstico de los autoanticuerpos anti-interferon gamma inducible protein 16 (IFI16) en los pacientes con esclerodermia sistémica (SSc) negativos para todos los autoanticuerpos específicos de SSc (pacientes SSc seronegativos) y evaluar el significado clínico de estos autoanticuerpos, aislados o en combinación con autoanticuerpos anticentrómero (ACA). Métodos: Se incluyeron 58 pacientes SSc seronegativos y 66 pacientes ACA positivos. Todos los pacientes se testaron para los autoanticuerpos anti-IFI16 mediante un ELISA directo «in-house». Las asociaciones entre parámetros clínicos y los autoanticuerpos anti-IFI16 fueron analizadas. Resultados: En total, el 17,2% de los pacientes SSc seronegativos y el 39,4% de los pacientes ACA positivos fueron positivos para anti-IFI16. Los autoanticuerpos anti-IFI16 se detectaron solamente en los pacientes con la forma limitada cutánea de SSc (lcSSc). Se encontró una asociación entre la positividad de anti-IFI16 y la hipertensión arterial pulmonar (HAP) aislada (odds ratio [OR]: 5,07; p=0,014), incluso cuando se ajustó el análisis a la presencia o ausencia de ACA (OR: 4,99; p=0,019). Los pacientes anti-IFI16 positivos mostraron una peor supervivencia general que los pacientes negativos (p=0,032). Las ratios de supervivencia acumulada a 10, 20 y 30 años fueron respectivamente del 96,9, 92,5 y 68,7% para los pacientes anti-IFI16 positivos frente al 98,8, 97,0 y 90,3% para los anti-IFI16 negativos. Los pacientes anti-IFI16 positivos también tenían una supervivencia general menor que los pacientes anti-IFI16 negativos tras ajustar para la presencia o ausencia de ACA mediante análisis multivariado de Cox (hazard ratio [HR]: 3,21; p=0,043)... (AU)

Prognostic value of anti-IFI16 autoantibodies in pulmonary arterial hypertension and mortality in patients with systemic sclerosis.

OBJECTIVES: To determine the diagnostic value of anti-interferon gamma inducible protein 16 (IFI16) autoantibodies in systemic sclerosis (SSc) patients negative for all tested SSc-specific autoantibodies (SSc-seronegative patients) and to evaluate the clinical significance of these autoantibodies, whether isolated or in the presence of anti-centromere autoantibodies (ACA). METHODS: Overall, 58 SSc-seronegative and 66 ACA-positive patients were included in the study. All patients were tested for anti-IFI16 autoantibodies by an in-house direct ELISA. Associations between clinical parameters and anti-IFI16 autoantibodies were analysed. RESULTS: Overall, 17.2% of SSc-seronegative and 39.4% of ACA-positive patients were positive for anti-IFI16 autoantibodies. Anti-IFI16 autoantibodies were found only in patients within the limited cutaneous SSc (lcSSc) subset. A positive association between anti-IFI16 positivity and isolated pulmonary arterial hypertension (PAH) was found (odds ratio [OR]=5.07; p=0.014) even after adjusting for ACA status (OR=4.99; p=0.019). Anti-IFI16-positive patients were found to have poorer overall survival than negative patients (p=0.032). Cumulative survival rates at 10, 20 and 30 years were 96.9%, 92.5% and 68.7% for anti-IFI16-positive patients vs. 98.8%, 97.0% and 90.3% for anti-IFI16-negative-patients, respectively. Anti-IFI16-positive patients also had worse overall survival than anti-IFI16-negative patients after adjusting for ACA status in the multivariate Cox analysis (hazard ratio [HR]=3.21; p=0.043). CONCLUSION: Anti-IFI16 autoantibodies were associated with isolated PAH and poorer overall survival. Anti-IFI16 autoantibodies could be used as a supplementary marker of lcSSc in SSc-seronegative patients and for identifying ACA-positive patients with worse clinical outcome.

The importance of data in Pulmonary Arterial Hypertension: from international registries to Machine Learning. / La importancia de los datos en la hipertensión arterial pulmonar: de los registros internacionales al machine learning.

Real-world registries have been critical to building the scientific knowledge of rare diseases, including Pulmonary Arterial Hypertension (PAH). In the past 4 decades, a considerable number of registries on this condition have allowed to improve the pathology and its subgroups definition, to advance in the understanding of its pathophysiology, to elaborate prognostic scales and to check the transferability of the results from clinical trials to clinical practice. However, in a moment where a huge amount of data from multiple sources is available, they are not always taken into account by the registries. For that reason, Machine Learning (ML) offer a unique opportunity to manage all these data and, finally, to obtain tools that may help to get an earlier diagnose, to help to deduce the prognosis and, in the end, to advance in Personalized Medicine. Thus, we present a narrative revision with the aims of, in one hand, summing up the aspects in which data extraction is important in rare diseases -focusing on the knowledge gained from PAH real-world registries- and, on the other hand, describing some of the achievements and the potential use of the ML techniques on PAH.

Síndrome de Eisenmenger secundario a comunicación interatrial tipo ostium secundum en mujer adulta / Eisenmenger Syndrome Associated with an ostium secundum Atrial Septal Defect in an Adult Woman

El síndrome de Eisenmenger es la forma más severa de presentación de hipertensión arterial pulmonar secundaria a defectos cardíacos congénitos no reparados, aunque su prevalencia es baja, continúa siendo un reto para los sistemas de salud de los países en vías de desarrollo por su complejidad en el manejo. Presentación del caso. Paciente femenina sin antecedentes médicos conocidos quien consulta por disnea relacionada a los esfuerzos y policitemia. Intervención terapéutica. Se realiza ecocardiograma transesofágico que arroja la presencia de defecto interatrial tipo ostium secundum e hipertensión arterial pulmonar severa, con cortocircuito de derecha a izquierda, se inicia oxigenoterapia y terapia farmacológica. Evolución clínica. Paciente permaneció ingresada presentando notable mejora a la disnea, se le dio de alta con referencia a la clínica de cardiopatías congénitas del adulto en Hospital Nacional Rosales.

Eisenmenger syndrome is the most severe form of pulmonary arterial hypertension secondary to an unrepaired congenital heart disease. Despite the low prevalence, it remains a challenge for the public health service of developing countries due to the complexity of the treatment. Case presentation. A female patient without known medical history, who consults with dyspnea on exertion and polycythemia. Treatment. A transesophageal echocardiogram was performed, showing an ostium secundum atrial septal defect and severe pulmonary arterial hypertension with a right-left shunt. Supplemental oxygen was administrated and pharmacological treatment was started. Outcome. The patient presented remarkable clinical improvement to dyspnea, she was discharged with medical reference to the Adult Congenital Heart Disease clinic at Rosales National Hospital.

Factores pronósticos en el trasplante cardiopulmonar: experiencia a 30 años en un centro de referencia / Prognosis factors in heart–lung transplantation: Thirty years experience in a reference center

Introducción: El trasplante cardiopulmonar (TCP) ha presentado una disminución progresiva en el número de procedimientos. En nuestro país existe poca información al respecto, siendo el objetivo de este estudio analizar la experiencia de un hospital de referencia. Métodos: Estudio observacional unicéntrico de una cohorte histórica en el periodo entre 1990 y 2021. Las asociaciones entre categorías se evaluaron mediante la prueba de X2 o la f de Fisher. La supervivencia se analizó a través del método de Kaplan-Meier. Las diferencias se evaluaron con el estudio de log-rank y el análisis multivariante con el método de Cox. Resultados: Se observó una reducción del número de procedimientos realizados en el último decenio (2000-2009: 19 [44,2%]; 2010-2021: 15 [34,8%]). La mortalidad posoperatoria precoz fue de 23,3%, reduciéndose a 13,3% a partir del 2010. La intrahospitalaria fue de 41%, disminuyendo a 33% en 2010. Los factores asociados a la mortalidad fueron cirugía torácica previa, corticoterapia, circulación extracorpórea (CEC) mayor a 200 min, tiempo de isquemia mayor a 300 min y dehiscencia traqueal (p < 0,005). La supervivencia global a uno, cinco y 10 años fue de 58, 44,7 y 36,1%, respectivamente. Los factores asociados a menores tasas de supervivencia fueron cirugía torácica previa, donante masculino, CEC mayor 200 min, tiempo de isquemia mayor a 300 min, dehiscencia traqueal y diferencia de pesos (p < 0,005). Conclusiones: Existe una disminución en el número de procedimientos, siendo más evidente en la última década, pero evidenciando una mejora tanto de la mortalidad posoperatoria y supervivencia.(AU)

Introduction: Heart–lung transplantation has shown a progressive decrease in the number of procedures. There is a lack of information about this field in Spain. The main goal of this study is to analyze the experience of a national reference hospital. Methods: We performed a retrospective study of a historical cohort of heart–lung transplanted patients in a single center, during a 30 years period (from 1990 to 2021). The associations between variables were evaluated using the χ2 test or Fisher's exact test. Survival was analyzed using the Kaplan–Meier method. Differences were evaluated using the log-rank test and multivariate analysis with the Cox method. Results: A decrease in the number of procedures performed in the last decade was observed [2000–2009: 19 procedures (44.2%); 2010–2021: 15 procedures (34.8%)]. Early postoperative mortality was 23.3%, falling to 13.3% from 2010. In-hospital mortality was 41%, falling to 33% from 2010. Main factors related to higher mortality: previous thoracic surgery, corticosteroid therapy, extracorporeal circulation (ECLS) greater than 200 min, ischemia time greater than 300 min, and tracheal dehiscence (p < 0.005). Overall survival at one, five, and ten years was 58%, 44.7%, and 36.1%, respectively. Factors associated with lower survival rates: previous thoracic surgery, male donor, extracorporeal circulation greater than 200 min, ischemia time greater than 300 min, tracheal dehiscence and weight difference (p < 0.005). Conclusions: There has been a progressive decrease in the number of heart–lung transplantations, being more evident in the last decade, but showing an improvement in both mortality and survival.(AU)

Prognosis factors in heart-lung transplantation: 30 years experience in a reference center.

INTRODUCTION: Heart-lung transplantation has shown a progressive decrease in the number of procedures. There is a lack of information about this field in Spain. The main goal of this study is to analyze the experience of a national reference hospital. METHODS: We performed a retrospective study of a historical cohort of heart-lung transplanted patients in a single center, during a 30 years period (from 1990 to 2021). The associations between variables were evaluated using the χ2 test or Fisher's exact test. Survival was analyzed using the Kaplan-Meier method. Differences were evaluated using the log-rank test and multivariate analysis with the Cox method. RESULTS: A decrease in the number of procedures performed in the last decade was observed [2000-2009: 19 procedures (44.2%); 2010-2021: 15 procedures (34.8%)]. Early postoperative mortality was 23.3%, falling to 13.3% from 2010. In-hospital mortality was 41%, falling to 33% from 2010. Main factors related to higher mortality: previous thoracic surgery, corticosteroid therapy, extracorporeal circulation (ECLS) greater than 200 min, ischemia time greater than 300 min, and tracheal dehiscence (p < 0.005). Overall survival at one, five, and ten years was 58%, 44.7%, and 36.1%, respectively. Factors associated with lower survival rates: previous thoracic surgery, male donor, extracorporeal circulation greater than 200 min, ischemia time greater than 300 min, tracheal dehiscence and weight difference (p < 0.005). CONCLUSIONS: There has been a progressive decrease in the number of heart-lung transplantations, being more evident in the last decade, but showing an improvement in both mortality and survival.

Hipertensión arterial pulmonar en pacientes con dermatomiositis juvenil y esclerosis sistémica en un centro pediátrico de tercer nivel

INTRODUCCIÓN: La hipertensión arterial pulmonar puede estar asociada secundariamente a enfermedades del tejido conectivo. Entre estas enfermedades, predominan la esclerosis sistémica y la dermatomiositis juvenil. MATERIALES Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y transversal. Se incluyeron todos los pacientes con diagnóstico de dermatomiositis juvenil y esclerosis sistémica que acudieron a nuestro hospital. Posteriormente se verificaron los niveles de presión arterial pulmonar mediante ecocardiografía. RESULTADOS: Se incluyeron 58 pacientes, de los cuales sólo 17 pacientes tuvieron ecocardiografía diagnóstica. Entre ellos, dos pacientes presentaron hipertensión arterial pulmonar. CONCLUSIÓN: La detección oportuna de la hipertensión arterial pulmonar en las enfermedades del tejido conectivo es esencial. Generalmente es asintomático. Es necesario adherirse al protocolo internacional que sugiere realizar ecocardiografía en todos los pacientes con dermatomiositis juvenil y esclerosis sistémica.

INTRODUCTION: Pulmonary arterial hypertension may be secondary associated with connective tissue diseases. Among these diseases, systemic sclerosis and juvenile dermatomyositis predominate. MATERIALS AND METHODS: A retrospective, descriptive and cross-sectional study was carried out. All patients with a diagnosis of juvenile dermatomyositis and systemic sclerosis who attended our hospital were included. Pulmonary arterial pressure levels were subsequently verified by echocardiography. RESULTS: 58 patients were included, of which only 17 patients had a diagnostic echocardiography. Among them, two patients presented pulmonary arterial hypertension. CONCLUSION: Timely detection of pulmonary arterial hypertension in connective tissue diseases is essential. It is generally asymptomatic. It is necessary to adhere to the international protocol that suggests performing echocardiography in all patients with juvenile dermatomyositis and systemic sclerosis.

Utilidad de la ergoespirometría en el diagnóstico precoz de hipertensión pulmonar en pacientes con esclerodermia / Role of cardiopulmonary exercise test in early diagnosis of pulmonary hypertension in scleroderma patients

Introducción: La hipertensión arterial pulmonar (HAP) es una enfermedad grave y progresiva, con elevada mortalidad. El diagnóstico precoz e inicio de tratamiento temprano mejora el pronóstico. Los pacientes con esclerodermia tienen riesgo elevado de desarrollar HAP. La única estrategia de cribado establecida y validada (ecocardiograma y/o algoritmo DETECT) reconoce la enfermedad cuando ya está avanzada, a pesar de encontrarse en una fase preclínica. La ergoespirometría (CPET) detecta afectación vascular pulmonar en fases más precoces.MétodosEstudio prospectivo de los 52 pacientes consecutivos diagnosticados de esclerodermia en nuestra área sanitaria, durante 2 años (2018 y 2019). A todos se les realizó CPET, además del cribado sistemático anual. Se comparó la sensibilidad para detectar HAP del cribado actual frente a la CPET. Para confirmar la presencia de HAP se realizó un cateterismo cardiaco derecho (CCD). En caso de mantener la sospecha de HAP en CPET, pero con CCD en reposo no confirmatorio, se continuó con CCD de esfuerzo.ResultadosSe realizaron 52 CPET, de las cuales 16 indicaron HAP. El CCD de reposo confirmó HAP en 5 pacientes y el CCD de esfuerzo en otros 7 (sensibilidad diagnóstica de CPET junto con el cateterismo de reposo y esfuerzo del 100%). De esos 16 pacientes, DETECT habría identificado 10, de los cuales el CCD de reposo confirmó HAP en 3 y el de esfuerzo en otros 2 (sensibilidad del algoritmo diagnóstico establecido según guías del 70%).ConclusionesLa CPET y el CCD de esfuerzo podrían reconocer HAP más precozmente que el cribado establecido en pacientes con esclerodermia, permitiendo adelantar el diagnóstico. (AU)

Introduction: Pulmonary arterial hypertension (PAH) is a severe, high mortality and progressive disease. Early diagnosis and treatment improves the prognosis. Patients with scleroderma disease presents high risk of developing PAH. Established screening strategies – echocardiogram and DETECT algorithm – recognize the disease when it is already advanced. Cardiopulmonary exercise testing (CPET) detects pulmonary vascular injury in earlier stages.MethodsProspective study of 52 consecutive patients diagnosed of scleroderma in our health area, during 2 years (2018 and 2019). All of them undergo CPET, in addition to the annual systematic screening. Sensitivity of current PAH screening is compared to CPET. To confirm the presence of PAH, right heart catheterization (RHC) is performed. In case of suspected PAH in CPET, but non-confirmatory right heart catheterization at rest, patients carried out exercise RHC.ResultsFifty-two CPET were performed, of which 16 suggested PAH. Resting RHC confirmed PAH in 5 patients and exercise RHC in 7 (diagnostic sensitivity of CPET together with rest and exercise catheterization of 100%). Of these 16 patients, DETECT had identified 10, of whom resting RHC confirmed PAH in 3 and exercise RHC in 2 (guideline-based diagnostic algorithm sensitivity 70%).ConclusionsCPET and exercise RHC could detect PAH earlier than established screening in patients with scleroderma disease, allowing early diagnosis. (AU)

Usefulness of genetics for clinical reclassification and refinement of prognostic stratification in pulmonary arterial hypertension.

INTRODUCTION AND OBJECTIVES: Risk stratification in pulmonary arterial hypertension (PAH) is essential to provide more aggressive treatment for patients at higher risk. Nevertheless, recently introduced simplified prognostic tools neglect the genetic background. Additionally, pulmonary veno-oclusive disease (PVOD) has never been considered in risk assessment strategies. METHODS: We analyzed consecutive patients in the Spanish registry of PAH (REHAP) genetically tested, between 2011 and 2022. We applied the 4-strata COMPERA 2.0 model, comparing these results with an amplified score including genetics. Cox regression models were compared using Harrel c-statistics. The application of the model was specifically tested in PVOD before inclusion. RESULTS: We identified 298 patients tested genetically among the group of idiopathic, familial, drug-induced PAH and PVOD patients in the REHAP registry. When we analyzed only patients with all available variables of interest at baseline (World Health Organization functional class, 6-minute walk test, B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide) and included in the 4-strata model (n=142), after a median follow-up of 58.2 months, 17.6% of patients died and 11.3% underwent lung transplant. The application of the 4-strata model in our population demonstrated a good prognostic capacity (Harrel c of 0.689), which was not improved by the introduction of genetics (c-index 0.690). This last model showed a tendency for a better identification of patients at intermediate-low and intermediate-high risk, and no differences between intermediate-high and high-risk strata. CONCLUSIONS: In this work, the addition of genetics to the COMPERA 4-strata model achieved a similar global prognostic capacity but changed the identification of different risk strata in a cohort of young genetically tested patients.

[Role of cardiopulmonary exercise test in early diagnosis of pulmonary hypertension in scleroderma patients]. / Utilidad de la ergoespirometría en el diagnóstico precoz de hipertensión pulmonar en pacientes con esclerodermia.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a severe, high mortality and progressive disease. Early diagnosis and treatment improves the prognosis. Patients with scleroderma disease presents high risk of developing PAH. Established screening strategies - echocardiogram and DETECT algorithm - recognize the disease when it is already advanced. Cardiopulmonary exercise testing (CPET) detects pulmonary vascular injury in earlier stages. METHODS: Prospective study of 52 consecutive patients diagnosed of scleroderma in our health area, during 2 years (2018 and 2019). All of them undergo CPET, in addition to the annual systematic screening. Sensitivity of current PAH screening is compared to CPET. To confirm the presence of PAH, right heart catheterization (RHC) is performed. In case of suspected PAH in CPET, but non-confirmatory right heart catheterization at rest, patients carried out exercise RHC. RESULTS: Fifty-two CPET were performed, of which 16 suggested PAH. Resting RHC confirmed PAH in 5 patients and exercise RHC in 7 (diagnostic sensitivity of CPET together with rest and exercise catheterization of 100%). Of these 16 patients, DETECT had identified 10, of whom resting RHC confirmed PAH in 3 and exercise RHC in 2 (guideline-based diagnostic algorithm sensitivity 70%). CONCLUSIONS: CPET and exercise RHC could detect PAH earlier than established screening in patients with scleroderma disease, allowing early diagnosis.

Experiencia clínica en hipertensión arterial pulmonar en un hospital general de tercer nivel / Clinical experience in pulmonary arterial hypertension in a general tertiary hospital

Introducción: La hipertensión arterial pulmonar es una enfermedad rara. Cursa con aumento progresivo de la resistencia vascular pulmonar e insuficiencia ventricular derecha y muerte precoz. Los tratamientos específicos han mejorado la esperanza de vida aunque el pronóstico a largo plazo sigue siendo desfavorable con una mortalidad del 40% a los tres años.Materiales y métodos: El estudio es descriptivo observacional trasversal y retrospectivo realizado en un hospital general de tercer nivel entre mayo de 2004 y agosto de 2020. Se midió la capacidad funcional (CF), la presión arterial pulmonar media, el test de la marcha de los 6 minutos (PM6M) entre otras variables. Se recogieron variables de tratamiento farmacológico específico y efectos adversos, así como la adherencia farmacológica.Resultados: La población fue de 27 pacientes, la mayoría mujeres con edad media de 62 años. Más del 80% de los pacientes presentaban CF II-III y PM6M de riesgo intermedio. Los tratamientos en primera línea y monoterapia mayoritarios fueron el sildenafilo y bosentán con un grado de recomendación de Ia, seguidos de ambrisentán. Los otros grupos de fármacos fueron minoritarios en los pacientes. No se encontraron diferencias estadísticamente significativas en la variación del PM6M, sí hubo variación de PAPm de forma positiva. Conclusiones: Todos los pacientes llevaban en tratamiento específico más de tres años, aunque sería necesario ampliar el tamaño muestral. En cuanto a la seguridad los efectos adversos fueron de grado leve y la adherencia al tratamiento elevada. (AU)

Introduction: Pulmonary arterial hypertension is a rare disease. It results a progressive increase in pulmonary vascular resistance and in right ventricular failure and early death. Specific treatments have improved the life expectancy of patients but the long-term prognosis remains poor, resulting in a high mortality of 40% at 3 years. Materials and methods: The research conducted is descriptive, cross-sectional and retrospective. It was carried out in a third level general hospital between May 2004 and August 2020. The measured variables were functional capacity (CF), PAPm, 6-minute walk test (PM6M) and other clinical parameters. Variables related to specific pharmacological treatment and adverse effects, as well as pharmacological adherence were also collected. Results: The study population was 27 patients, most of them women, with an average age of 62 years. More than 80% of patients presented CF II-III and PM6M of moderate risk. First-line and monotherapy treatments were mainly sildenafil and bosentan, with an Ia recommendation level. Ambrisentan was also a first-line treatment. The other drug groups were in the minority among patients. On the other hand, no statistically significant differences in PM6M variation were found, although there was positive variation in PAPm. Conclusions: The patients had been on specific treatment for more than three years. In terms of safety, adverse effects were minor and adherence to treatment high. (AU)

El receptor nuclear NOR-1 (Neuron-derived Orphan Receptor-1) en el remodelado vascular patológico / Nuclear receptor NOR-1 (Neuron-derived Orphan Receptor-1) in pathological vascular remodelling and vascular remodelling

En el remodelado vascular patológico juegan un papel clave las células vasculares y su interacción con las células inflamatorias y del sistema inmune. En este proceso intervienen una gran cantidad de genes y proteínas regulados de forma coordinada por un reducido número de factores de transcripción. En los últimos años las investigaciones sobre una pequeña subfamilia de factores de transcripción, la subfamilia NR4A, han tenido un gran impacto sobre nuestra comprensión de la biología vascular. Los receptores NR4A1 (Nur77), NR4A2 (Nurr1) y NR4A3 (NOR-1) son productos de genes de respuesta temprana cuya expresión es inducida por múltiples estímulos fisiopatológicos y físicos. Su amplia distribución en los diferentes tejidos y células los sitúan en el control de numerosos procesos como la diferenciación, la proliferación, la supervivencia y la apoptosis celular, así como la inflamación y el metabolismo de lípidos y carbohidratos. Esta revisión analiza el papel de estos receptores, particularmente de NOR-1, en el remodelado vascular patológico asociado a la aterosclerosis, el aneurisma de aorta abdominal y la hipertensión arterial pulmonar. (AU)

Vascular cells and their interaction with inflammatory cells and the immune system play a key role in pathological vascular remodeling. A large number of genes and proteins regulated in a coordinated manner by a small number of transcription factors are involved in this process. In recent years, research on a small subfamily of transcription factors, the NR4A subfamily, has had a major impact on our understanding of vascular biology. The NR4A1 (Nur77), NR4A2 (Nurr1) and NR4A3 (NOR-1) receptors are products of early response genes whose expression is induced by multiple pathophysiological and physical stimuli. Their wide distribution in different tissues and cells places them in the control of numerous processes such as cell differentiation, proliferation, survival and apoptosis, as well as inflammation and the metabolism of lipids and carbohydrates. This review analyzes the role of these receptors, particularly NOR-1, in pathological vascular remodeling associated with atherosclerosis, abdominal aortic aneurysm and pulmonary arterial hypertension. (AU)

Hipertensión arterial pulmonar / Pulmonary arterial hypertension

La hipertensión arterial pulmonar (HAP) es una enfermedad rara caracterizada por un remodelado adverso del árbol arterial que conlleva un aumento de las resistencias vasculares con el subsecuente incremento de la poscarga del ventrículo derecho y el desarrollo, finalmente, de insuficiencia cardiaca. El curso de la enfermedad conlleva un mal pronóstico, al que se asocia el retraso en el diagnóstico e inicio de tratamiento motivado por la clínica inespecífica y el desconocimiento de la entidad. Las recomendaciones más recientes se centran en optimizar el diagnóstico precoz diferencial frente a otras causas de hipertensión pulmonar, con el fin de iniciar un tratamiento adecuado utilizando como referencia la estimación de riesgo de mortalidad del paciente. En los últimos años, con la mejora en el proceso diagnóstico, la aparición de nuevos tratamientos específicos y la creación de unidades de referencia especializadas en esta enfermedad, se ha conseguido mejorar el pronóstico y la calidad de vida de los pacientes con HAP. (AU)

Pulmonary arterial hypertension (PAH) is a rare disease characterized by adverse remodeling of the arterial tree leading to increased vascular resistance with subsequent increase in right ventricular afterload and eventual development of heart failure. The nonspecific clinical manifestations and lack of knowledge of pathology lead to a poor prognosis associated with delay in diagnosis and initiation of treatment. The most recent recommendations focus on optimizing the early differential diagnosis with other causes of pulmonary hypertension to initiate appropriate treatment based on the mortality risk estimation. In the last years, with the improvement in the diagnostic process, the emergence of new specific treatments, and the creation of specialized referral units for this pathology, the prognosis, and quality of life of patients with PAH have improved significantly. (AU)

Nuclear receptor NOR-1 (Neuron-derived Orphan Receptor-1) in pathological vascular remodelling and vascular remodelling. / El receptor nuclear NOR-1 (Neuron-derived Orphan Receptor-1) en el remodelado vascular patológico.

Vascular cells and their interaction with inflammatory cells and the immune system play a key role in pathological vascular remodeling. A large number of genes and proteins regulated in a coordinated manner by a small number of transcription factors are involved in this process. In recent years, research on a small subfamily of transcription factors, the NR4A subfamily, has had a major impact on our understanding of vascular biology. The NR4A1 (Nur77), NR4A2 (Nurr1) and NR4A3 (NOR-1) receptors are products of early response genes whose expression is induced by multiple pathophysiological and physical stimuli. Their wide distribution in different tissues and cells places them in the control of numerous processes such as cell differentiation, proliferation, survival and apoptosis, as well as inflammation and the metabolism of lipids and carbohydrates. This review analyzes the role of these receptors, particularly NOR-1, in pathological vascular remodeling associated with atherosclerosis, abdominal aortic aneurysm and pulmonary arterial hypertension.

Disfunción ventricular derecha en paciente adulto con comunicación interventricular posinfarto / Right ventricular dysfunction in adult patient with post-infarction ventricular septal defect

RESUMEN Introducción: La disfunción ventricular derecha es la alteración aguda o crónica de la morfología y función de dicha estructura, de origen multifactorial. En los últimos años existe consenso acerca de su función como determinante del estado funcional y factor pronóstico en diversas enfermedades. Objetivo: Destacar la importancia del manejo multidisciplinario y algunas de las opciones terapéuticas que se les pueden brindar a estos pacientes. Presentación del caso: Paciente de 58 años de edad, con antecedentes de salud aparente, que acudió al Servicio de emergencias, donde se le diagnosticó un infarto agudo de miocardio de topografía inferior. Se trasladó a la unidad de cuidados intensivos quirúrgicos del Servicio de Cirugía Cardiovascular debido a una complicación mecánica por comunicación interventricular. Se recibió con elementos clínicos de insuficiencia cardíaca aguda clase funcional IV. Progresivamente presentó deterioro del estado hemodinámico por lo que requirió el uso de apoyo vasoactivo con norepinefrina; hipoxia, hipercapnia, presiones venosas centrales entre 15 y 18 cmH2O y elementos clínicos de disfunción de ventrículo derecho; se decidió instrumentar vía aérea, administrar sedación y relajación por asincronías a paciente ventilado. Sin otra opción que el tratamiento quirúrgico se llevó a discusión donde se decidió esperar a la mejoría del estado hemodinámico con tratamiento médico. Conclusiones: Las enfermedades cardiovasculares no dejan de aparecer en escenarios cada vez más complejos con elevada morbimortalidad. Se evidencia la importancia del consenso clínico-quirúrgico en el momento de la toma de decisiones.

ABSTRACT Introduction: Right ventricular dysfunction is the acute or chronic alteration of the morphology and function of this structure, of multifactorial origin. In recent years there is consensus about its role as a determinant of functional status and prognostic factor in various diseases. Objective: Highlight the importance of multidisciplinary management and some of the therapeutic options that can be provided to these patients. Case Presentation: A 58-year-old patient with an apparent health history went to the Emergency Service, where he was diagnosed with an acute myocardial infarction of lower topography. He was transferred to the surgical intensive care unit of the Cardiovascular Surgery Service due to a mechanical complication from ventricular septal defect. He was received presenting clinical elements of acute heart failure functional class IV. He progressively presented deterioration of the hemodynamic state, so it required the use of vasoactive support with norepinephrine; hypoxia, hypercapnia, central venous pressures between 15 and 18 cmH2O and clinical elements of right ventricular dysfunction; it was decided to implement airway, administer sedation and relaxation by asynchrony to ventilated patient. With no other option than surgical treatment, it was brought to discussion and it was decided to wait for the improvement of the hemodynamic state with medical treatment. Conclusions: Cardiovascular diseases do not cease to appear in increasingly complex scenarios with high morbidity and mortality. The importance of clinical-surgical consensus at the time of decision-making is evident.

Biomarcadores biológicos en las enfermedades respiratorias / Biological Biomarkers in Respiratory Diseases

En los últimos años la llamada «medicina personalizada o de precisión» ha irrumpido con fuerza en el manejo de las enfermedades, entre ellas las respiratorias. La posibilidad de implantar esta forma de trabajar pasa indefectiblemente por el hallazgo y validación de biomarcadores biológicos que se relacionen bien con el diagnóstico, tratamiento o pronóstico de los pacientes respiratorios. En este sentido, la mayoría de enfermedades respiratorias o grupo de las mismas ya cuentan con biomarcadores biológicos de mayor o menor fiabilidad, y se están realizando un gran número de estudios en busca de nuevos de estos indicadores. El objetivo de la presente revisión es poner al día al lector y analizar la literatura científica existente sobre la existencia y validez diagnóstica, terapéutica o pronóstica de los biomarcadores biológicos más importantes en la actualidad en las principales enfermedades respiratorias, así como sobre los retos futuros en este sentido. (AU)

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area. (AU)

[Translated article] Biological Biomarkers in Respiratory Diseases / Biomarcadores biológicos en las enfermedades respiratorias

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area. (AU)

En los últimos años la llamada «medicina personalizada o de precisión» ha irrumpido con fuerza en el manejo de las enfermedades, entre ellas las respiratorias. La posibilidad de implantar esta forma de trabajar pasa indefectiblemente por el hallazgo y validación de biomarcadores biológicos que se relacionen bien con el diagnóstico, tratamiento o pronóstico de los pacientes respiratorios. En este sentido, la mayoría de enfermedades respiratorias o grupo de las mismas ya cuentan con biomarcadores biológicos de mayor o menor fiabilidad, y se están realizando un gran número de estudios en busca de nuevos de estos indicadores. El objetivo de la presente revisión es poner al día al lector y analizar la literatura científica existente sobre la existencia y validez diagnóstica, terapéutica o pronóstica de los biomarcadores biológicos más importantes en la actualidad en las principales enfermedades respiratorias, así como sobre los retos futuros en este sentido. (AU)

Biological Biomarkers in Respiratory Diseases. / Biomarcadores biológicos en las enfermedades respiratorias.

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area.

Pulmonary arterial hypertension. / Hipertensión arterial pulmonar.

Pulmonary arterial hypertension (PAH) is a rare disease characterized by adverse remodeling of the arterial tree leading to increased vascular resistance with subsequent increase in right ventricular afterload and eventual development of heart failure. The nonspecific clinical manifestations and lack of knowledge of pathology lead to a poor prognosis associated with delay in diagnosis and initiation of treatment. The most recent recommendations focus on optimizing the early differential diagnosis with other causes of pulmonary hypertension to initiate appropriate treatment based on the mortality risk estimation. In the last years, with the improvement in the diagnostic process, the emergence of new specific treatments, and the creation of specialized referral units for this pathology, the prognosis, and quality of life of patients with PAH have improved significantly.

Características clínicas, evolución y tratamiento de hipertensión arterial pulmonar en un hospital peruano de referencia / Clinical characteristics, evolution and treatment of pulmonary arterial hypertension at a Peruvian referral hospital

RESUMEN Objetivo: Describir las características epidemiológicas y clínicas, la evolución y el tratamiento de los pacientes con hipertensión arterial pulmonar. Materiales y métodos: Estudio descriptivo que incluyó a 47 pacientes con diagnóstico primario de hipertensión pulmonar. Resultados: La edad promedio de los pacientes fue de 48 años, y el 91,49 % fueron mujeres. El promedio de seguimiento fue 39 meses. Los tipos predominantes de hipertensión arterial pulmonar fueron los siguientes: asociada a cardiopatía congénita (48,93 %), asociada a enfermedad del tejido conectivo (21,28 %) e hipertensión idiopática (17,02 %). En el 78,72 % de los pacientes se empleó la monoterapia (principalmente con sildenafilo), y en 21,28 % de los casos se usó la terapia combinada secuencial (sildenafilo más bosentan). Durante el seguimiento, el 70,21 % tuvo por lo menos una hospitalización y cinco pacientes fallecieron, lo que significó una mortalidad total acumulada de 10,64 %. Conclusiones: La hipertensión arterial pulmonar afecta predominantemente a personas jóvenes y de sexo femenino. La cardiopatía congénita es la principal etiología asociada. La monoterapia con sildenafilo es el tratamiento específico que se utiliza con más frecuencia. La mortalidad encontrada fue menor a la reportada en otros estudios.

ABSTRACT Objective: To describe the clinical and epidemiological characteristics, evolution and treatment of patients with pulmonary arterial hypertension. Materials and methods: A descriptive study that included 47 patients with a primary diagnosis of pulmonary arterial hypertension. Results: The average age of the patients was 48 years and 91.49 % were females. The average follow-up was 39 months. The main types of pulmonary arterial hypertension were the one associated with congenital heart diseases (48.93 %), the one associated with connective tissue diseases (21.28 %) and idiopathic hypertension (17.02 %). Monotherapy (mainly with sildenafil) and sequential combination therapy (sildenafil plus bosentan) were used in 78.72 % and 21.28 % of the patients, respectively. During the follow-up, 70.21 % of the patients were hospitalized at least once and five patients died, resulting in a cumulative total mortality of 10.64 %. Conclusions: Pulmonary arterial hypertension predominantly affects young people and females. The main associated etiology is congenital heart disease. The most frequently used specific treatment is sildenafil monotherapy. The mortality rate was lower than that reported in other studies.