Retrasplante pulmonar con cross-match positivo en trasplante pulmonar primario complicado con rechazo mediado por anticuerpos / Lung Retransplantation with Positive Crossmatch in Primary Lung Transplantation Complicated by Antibody-Mediated Rejection

La hipertensión arterial pulmonar (HAP) representa el 2,6% de los trasplantes pulmonares (TP), con una mediana de supervivencia condi cional (desde los 30 días del TP) de 9,8 años. Son frecuentes, el rechazo celular agudo (ACR) y la disfunción crónica del injerto (CLAD), mientras que es infrecuente el rechazo mediado por anticuerpos (AMR). El retrasplante pulmonar (RTP) constituye el 4% del TP mundial, debido a complicaciones en la vía aérea, disfunción primaria del injerto, ACR y CLAD. Mujer de 22 años, portadora de HAP idiopática (HAPI) desde el año 2013, trasplantada bipulmonar (TBP) en enero de 2018. A los 16 meses presentó neumonía adquirida en la comuni dad. En una internación posterior, presentó ACR y a pesar de pulsos de metilprednisolona, progresó a requerimientos de cánula de alto flujo y ventilación mecánica no invasiva hospitalaria, caída del VEF1, y tomografía de tórax con vidrio esmerilado difuso y engrosamiento irregular reticular del intersticio subpleural; interpretándose como CLAD a predominio de síndrome de bronquiolitis obliterante (BOS), con presencia de anticuerpos específicos contra el donante (DSA). En enero de 2020 se realizó nuevo TP y ante cross-match positivo, se realizó plasmaféresis y reposición de IgG. Al mes del egreso, no se observaron signos de rechazo en control de biopsias transbronquiales. Entre 2 y 10% de los pacientes con indicación primaria de TP por HAPI son sometidos a retrasplante pulmonar (RTP). La presencia de DSA y el miss-match de HLA, no son contraindicaciones para el RTP.

Pulmonary arterial hypertension (PAH) represents 2.6% of lung transplantations (LT), with a conditional median survival (from 30 days after LT) of 9.8 years. Acute cellular rejection (ACR) and chronic lung allograft dysfunction (CLAD) are common; whereas the antibody-mediated rejection (AMR) is not. Lung retransplantation (LR) accounts for 4% of global LTs for complications in the airways, primary allograft dys function, ACR and CLAD. 22-year-old woman with idiopathic PAH (IPAH) since 2013, who underwent a double-lung transplantation (DLT) in January 2018. 16 months after transplantation she presented community-acquired pneumonia. During a subsequent hospitalization, she presented ACR. Despite the fact that she received pulse methylprednisolone, she required high-flow cannula therapy and hospital non-invasive mechanical ventilation; the FEV1 was reduced and she underwent a chest tomography with diffuse ground glass opacities and irregular reticular thickening of the subpleural interstitium; interpreting the predominance of BOS (bronchiolitis obliterans syndrome) as CLAD, with presence of donor-specific antibodies (DSA). In January 2020, she received a new DLT and due to a positive crossmatch, she was treated with plasmapheresis and IgG replacement. One month after hospital discharge, no signs of rejection were observed at the BTB (bone-patellar tendon-bone) control. Between 2 to 10% of patients with primary indication of LT for IPAH are subjected to lung retransplantation (LR). The presence of DSA and HLA (human leucocyte antigen) mismatch aren't contraindications to LR.

Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysis / Registro colaborativo de hipertensión pulmonar en Argentina (RECOPILAR): análisis final

Abstract The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8±18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.

Resumen La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especiali dades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diag nóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.

Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysis.

The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8 ± 18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.

La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especialidades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diagnóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.

Hipertensión arterial pulmonar: Registro de un centro de referencia en Argentina / Pulmonary Arterial Hypertension. A Registry at a Reference Centre in Argentina Introduction and objectives

Introducción y objetivos: En Argentina, no se conocen datos de pacientes con hipertensión pulmonar (HP) con diagnóstico de certeza. El propósito del presente registro fue conocer las características de nuestra población de pacientes con HP del Grupo I de la clasificación de Dana Point 2008, hipertensión arterial pulmonar (HAP), estudiar la supervivencia y las variables asociadas a mayor mortalidad. Métodos: Estudio de cohorte de 134 pacientes admitidos por primera vez en el consultorio de HP de nuestra institución en el período comprendido entre enero/2004 y marzo/2012. Se excluyeron 9 pacientes; total analizado: 125 pacientes. Resultados: Edad promedio: 34 ± 15,7 años y la relación mujer/hombre: 3,8/1. Las etiologías más prevalentes fueron la HAP idiopática (HAPI) (61, 48.8%), asociadas a cardiopatías congénitas (35, 28%) y a colagenopatías (18, 14.4%). La supervivencia libre de trasplante o muerte fue de 63.2%; a 12, 24 y 36 meses la supervivencia fue del 94% (IC95% 88-97), 90% (IC95% 83-94) y 83% (IC95% 75-89), respectivamente. Las variables basales asociadas a mayor mortalidad y/o trasplante fueron la disnea clase funcional III/IV (OR 3.6 IC95% 1.5-8.9, p < 0.01), la distancia recorrida en la prueba de la caminata de 6 minutos menor de 380 m (OR 2.7 IC95% 1.1-6.5 p = 0.023) y el derrame pericárdico (OR 4.2 IC95% 1.3-14.6 p = 0.021). Conclusiones: Esta serie muestra las características y supervivencia actuales de pacientes con HP en un centro de referencia en Argentina. Variables de fácil obtención y reproducción permitieron estratificar subgrupos de mayor riesgo de muerte y/o trasplante en el seguimiento.

Introduction and objectives: There are no data on outcome of patients with pulmonary hypertension (PH) in Argentina. The objective of this registry was to assess the characteristics of patients with PH belonging to the Group I Dana Point's 2008 classification, pulmonary arterial hypertension (PAH), and to identify variables associated with outcomes. Methods: One hundred and thirty four patients were analyzed in a consecutive sequence. After excluding nine patients, 125 patients were analyzed. Results: The patients mean age was 34 years (SD±15,7) and the female/male ratio was 3.8/1. The most prevalent aetiologies were: idiopathic PAH (IHAP) (61, 48.8%), PH associated to congenital heart disease (35, 28%) and PH associated to connective tissue disease (18, 14.4%). Overall survival, excluding transplantation, was 63.2%; at 12, 24 and 36 months survival was 94% (CI 95% 88-97), 90% (CI 95% 83-94) and 83% (CI 75-89), respectively. Baseline variables associated to increased mortality or need for transplantation were functional class III/IV (NYHA) (OR 3.6 CI 95% 1.5-8.9, p <0.01), 6 minute-walk test distance shorter than 380 m (OR 2.7 CI 95% 1.1-6.5 p = 0.023) and pericardial effusion (OR 4.2 CI 95% 1.3-14.6 p = 0.021). Conclusion: This series shows characteristics and survival of patients with pulmonary arterial hypertension at a reference centre in Argentina. Some readily available variables allowed us to stratify subgroups at a higher risk of death and/or transplantation during the follow up.

Hipertensión arterial pulmonar: Registro de un centro de referencia en Argentina

Introducción y objetivos: En Argentina, no se conocen datos de pacientes con hipertensión pulmonar (HP) con diagnóstico de certeza. El propósito del presente registro fue conocer las características de nuestra población de pacientes con HP del Grupo I de la clasificación de Dana Point 2008, hipertensión arterial pulmonar (HAP), estudiar la supervivencia y las variables asociadas a mayor mortalidad. Métodos: Estudio de cohorte de 134 pacientes admitidos por primera vez en el consultorio de HP de nuestra institución en el período comprendido entre enero/2004 y marzo/2012. Se excluyeron 9 pacientes; total analizado: 125 pacientes. Resultados: Edad promedio: 34 ± 15,7 años y la relación mujer/hombre: 3,8/1. Las etiologías más prevalentes fueron la HAP idiopática (HAPI) (61, 48.8%), asociadas a cardiopatías congénitas (35, 28%) y a colagenopatías (18, 14.4%). La supervivencia libre de trasplante o muerte fue de 63.2%; a 12, 24 y 36 meses la supervivencia fue del 94% (IC95% 88-97), 90% (IC95% 83-94) y 83% (IC95% 75-89), respectivamente. Las variables basales asociadas a mayor mortalidad y/o trasplante fueron la disnea clase funcional III/IV (OR 3.6 IC95% 1.5-8.9, p < 0.01), la distancia recorrida en la prueba de la caminata de 6 minutos menor de 380 m (OR 2.7 IC95% 1.1-6.5 p = 0.023) y el derrame pericárdico (OR 4.2 IC95% 1.3-14.6 p = 0.021). Conclusiones: Esta serie muestra las características y supervivencia actuales de pacientes con HP en un centro de referencia en Argentina. Variables de fácil obtención y reproducción permitieron estratificar subgrupos de mayor riesgo de muerte y/o trasplante en el seguimiento.(AU)

Introduction and objectives: There are no data on outcome of patients with pulmonary hypertension (PH) in Argentina. The objective of this registry was to assess the characteristics of patients with PH belonging to the Group I Dana Points 2008 classification, pulmonary arterial hypertension (PAH), and to identify variables associated with outcomes. Methods: One hundred and thirty four patients were analyzed in a consecutive sequence. After excluding nine patients, 125 patients were analyzed. Results: The patients mean age was 34 years (SD±15,7) and the female/male ratio was 3.8/1. The most prevalent aetiologies were: idiopathic PAH (IHAP) (61, 48.8%), PH associated to congenital heart disease (35, 28%) and PH associated to connective tissue disease (18, 14.4%). Overall survival, excluding transplantation, was 63.2%; at 12, 24 and 36 months survival was 94% (CI 95% 88-97), 90% (CI 95% 83-94) and 83% (CI 75-89), respectively. Baseline variables associated to increased mortality or need for transplantation were functional class III/IV (NYHA) (OR 3.6 CI 95% 1.5-8.9, p <0.01), 6 minute-walk test distance shorter than 380 m (OR 2.7 CI 95% 1.1-6.5 p = 0.023) and pericardial effusion (OR 4.2 CI 95% 1.3-14.6 p = 0.021). Conclusion: This series shows characteristics and survival of patients with pulmonary arterial hypertension at a reference centre in Argentina. Some readily available variables allowed us to stratify subgroups at a higher risk of death and/or transplantation during the follow up.(AU)

[Pharmacological and mechanical thrombolysis in submassive pulmonary embolism]. / Trombolisis farmacológica y mecánica en tromboembolismo pulmonar submasivo.

Thromboembolic pulmonary disease is challenging for physicians when diagnosed in acute, sub-acute and chronic clinical patients, not only due to its morbi-mortality, but also because of its complex therapeutic management. Severity of the acute condition and potential commitment of right ventricular systolic function require therapeutic strategies, sometimes combined, in order to change the disease's course, optimizing patient survival. Pharmacological and mechanical thrombolysis are useful therapeutic tools for patients suffering from severe acute pulmonary embolism. This study refers to a young woman who developed a sub-massive pulmonary embolism, of sub-acute onset. She underwent the combined sequential therapeutic strategy of pharmacological and mechanical thrombolysis with successful outcome.

Trombolisis farmacológica y mecánica en tromboembolismo pulmonar submasivo / Pharmacological and mechanical thrombolysis in submassive pulmonary embolism

La enfermedad tromboembólica pulmonar, en sus formas aguda, subaguda o crónica, presenta dificultades para su tratamiento y tiene elevada morbimortalidad. La gravedad del evento agudo y su potencial compromiso sobre la función del ventrículo derecho necesitan estrategias terapéuticas, a veces combinadas, para cambiar el curso de la enfermedad a favor de la supervivencia del paciente. Las trombolisis farmacológica y mecánica son instrumentos útiles para tratar un evento embólico pulmonar agudo grave. Se presenta el caso de una joven que desarrolló una embolia pulmonar submasiva de instalación subaguda en quien la terapia combinada y secuencial trombolítica, farmacológica y mecánica, fue exitosa.

Thromboembolic pulmonary disease is challenging for physicians when diagnosed in acute, sub-acute and chronic clinical patients, not only due to its morbi-mortality, but also because of its complex therapeutic management. Severity of the acute condition and potential commitment of right ventricular systolic function require therapeutic strategies, sometimes combined, in order to change the disease´s course, optimizing patient survival. Pharmacological and mechanical thrombolysis are useful therapeutic tools for patients suffering from severe acute pulmonary embolism. This study refers to a young woman who developed a sub-massive pulmonary embolism, of sub-acute onset. She underwent the combined sequential therapeutic strategy of pharmacological and mechanical thrombolysis with successful outcome.

Trombolisis farmacológica y mecánica en tromboembolismo pulmonar submasivo / Pharmacological and mechanical thrombolysis in submassive pulmonary embolism

La enfermedad tromboembólica pulmonar, en sus formas aguda, subaguda o crónica, presenta dificultades para su tratamiento y tiene elevada morbimortalidad. La gravedad del evento agudo y su potencial compromiso sobre la función del ventrículo derecho necesitan estrategias terapéuticas, a veces combinadas, para cambiar el curso de la enfermedad a favor de la supervivencia del paciente. Las trombolisis farmacológica y mecánica son instrumentos útiles para tratar un evento embólico pulmonar agudo grave. Se presenta el caso de una joven que desarrolló una embolia pulmonar submasiva de instalación subaguda en quien la terapia combinada y secuencial trombolítica, farmacológica y mecánica, fue exitosa.(AU)

Thromboembolic pulmonary disease is challenging for physicians when diagnosed in acute, sub-acute and chronic clinical patients, not only due to its morbi-mortality, but also because of its complex therapeutic management. Severity of the acute condition and potential commitment of right ventricular systolic function require therapeutic strategies, sometimes combined, in order to change the disease´s course, optimizing patient survival. Pharmacological and mechanical thrombolysis are useful therapeutic tools for patients suffering from severe acute pulmonary embolism. This study refers to a young woman who developed a sub-massive pulmonary embolism, of sub-acute onset. She underwent the combined sequential therapeutic strategy of pharmacological and mechanical thrombolysis with successful outcome.(AU)

Trombolisis farmacológica y mecánica en tromboembolismo pulmonar submasivo. / [Pharmacological and mechanical thrombolysis in submassive pulmonary embolism].

Thromboembolic pulmonary disease is challenging for physicians when diagnosed in acute, sub-acute and chronic clinical patients, not only due to its morbi-mortality, but also because of its complex therapeutic management. Severity of the acute condition and potential commitment of right ventricular systolic function require therapeutic strategies, sometimes combined, in order to change the diseases course, optimizing patient survival. Pharmacological and mechanical thrombolysis are useful therapeutic tools for patients suffering from severe acute pulmonary embolism. This study refers to a young woman who developed a sub-massive pulmonary embolism, of sub-acute onset. She underwent the combined sequential therapeutic strategy of pharmacological and mechanical thrombolysis with successful outcome.

Hipertensión pulmonar grave reversible asociada al uso de dasatinib en un paciente con leucemia mieloide crónica / Reversible Severe Pulmonary Arterial Hypertension Associated to Dasatinib in a Chronic Myeloid Leukaemia Patient

La hipertensión arterial pulmonar (HAP) es una enfermedad rara caracterizada por un incremento progresivo de las resistencias vasculares pulmonares que lleva a la falla cardíaca derecha y muerte prematura. La enfermedad puede ser idiopática o asociada a otras condiciones como la hipertensión portal, el virus de la inmunodeficiencia humana, las enfermedades del tejido conectivo, las cardiopatías congénitas con cortocircuitos de izquierda a derecha o asociadas a diferentes toxinas o drogas. Se han realizado avances en el tratamiento farmacológico enfocados en el remodelado de la vasculatura pulmonar. En este sentido, se encuentran en evaluación los inhibidores de la tirosina kinasa (ITK). El imatinib es un ITK selectivo aprobado para el tratamiento de la leucemia mieloide crónica (LMC) que ha demostrado beneficios en el tratamiento de la HAP en estudios de fase II. Paradójicamente, el ITK dasatinib, también aprobado para el tratamiento de la LMC, ha sido asociado a HAP, falla ventricular derecha y a derrame pleural, lo que sugiere la posibilidad de un efecto adverso a nivel pulmonar vinculado con esta droga.

Pulmonary arterial hypertension is a rare disease that is characterized by a progressive increase in vascular pulmonary resistance, chronic right ventricle failure and premature death. Pulmonary arterial hypertension can be either idiopathic or associated to other conditions such as portal hypertension, human immunodeficiency virus, connective tissue diseases, congenital systemic-to-pulmonary shunts or associated to different drugs/toxins. Encouraging progress has been made by targeting the main vasoproliferative aspects of the disease. Tyrosine kinase inhibitors (TKI) are promising emerging therapeutics. Imatinib, a selective TKI approved for the treatment of chronic myeloid leukaemia, has demonstrated some efficacy in treating pulmonary arterial hypertension in a phase II study. However, the TKI dasatinib, also approved for therapy of chronic myeloid leukaemia, has been linked to reversible pulmonary arterial hypertension and right ventricular failure, with pleural effusion, suggesting the possibility of drug-related pulmonary arterial hypertension.

Hipertensión pulmonar grave reversible asociada al uso de dasatinib en un paciente con leucemia mieloide crónica

La hipertensión arterial pulmonar (HAP) es una enfermedad rara caracterizada por un incremento progresivo de las resistencias vasculares pulmonares que lleva a la falla cardíaca derecha y muerte prematura. La enfermedad puede ser idiopática o asociada a otras condiciones como la hipertensión portal, el virus de la inmunodeficiencia humana, las enfermedades del tejido conectivo, las cardiopatías congénitas con cortocircuitos de izquierda a derecha o asociadas a diferentes toxinas o drogas. Se han realizado avances en el tratamiento farmacológico enfocados en el remodelado de la vasculatura pulmonar. En este sentido, se encuentran en evaluación los inhibidores de la tirosina kinasa (ITK). El imatinib es un ITK selectivo aprobado para el tratamiento de la leucemia mieloide crónica (LMC) que ha demostrado beneficios en el tratamiento de la HAP en estudios de fase II. Paradójicamente, el ITK dasatinib, también aprobado para el tratamiento de la LMC, ha sido asociado a HAP, falla ventricular derecha y a derrame pleural, lo que sugiere la posibilidad de un efecto adverso a nivel pulmonar vinculado con esta droga.(AU)

Pulmonary arterial hypertension is a rare disease that is characterized by a progressive increase in vascular pulmonary resistance, chronic right ventricle failure and premature death. Pulmonary arterial hypertension can be either idiopathic or associated to other conditions such as portal hypertension, human immunodeficiency virus, connective tissue diseases, congenital systemic-to-pulmonary shunts or associated to different drugs/toxins. Encouraging progress has been made by targeting the main vasoproliferative aspects of the disease. Tyrosine kinase inhibitors (TKI) are promising emerging therapeutics. Imatinib, a selective TKI approved for the treatment of chronic myeloid leukaemia, has demonstrated some efficacy in treating pulmonary arterial hypertension in a phase II study. However, the TKI dasatinib, also approved for therapy of chronic myeloid leukaemia, has been linked to reversible pulmonary arterial hypertension and right ventricular failure, with pleural effusion, suggesting the possibility of drug-related pulmonary arterial hypertension.(AU)

[Treatment of compression of the left main coronary artery in patients with pulmonary hypertension]. / Tratamiento de la compresión del tronco de la arteria coronaria izquierda en pacientes con hipertensión pulmonar.

Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.

Tratamiento de la compresión del tronco de la arteria coronaria izquierda en pacientes con hipertensión pulmonar / Treatment of compression of the left main coronary artery in patients with pulmonary hypertension

La angina de pecho es un síntoma frecuente en pacientes con hipertensión pulmonar (HP) de cualquier etiología. Aunque su fisiopatología no está aclarada, las causas propuestas son: la isquemia subendocárdica por aumento del estrés parietal del ventrículo derecho, la dilatación de la arteria pulmonar por incrementos transitorios de la presión pulmonar y la compresión extrínseca del tronco de la arteria coronaria izquierda (TCI) por la arteria pulmonar (AP) dilatada. Se presentan tres casos que muestran la relación entre la angina de pecho y la compresión del TCI en pacientes con HP asociada a cardiopatías congénitas, tratados mediante implante de stent coronario.

Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.

[Update in the diagnosis and treatment of pulmonary hypertension]. / Actualización en el diagnóstico y tratamiento de la hipertensión pulmonar.

The term pulmonary hypertension includes a heterogeneous group of disorders which produce an obstructive remodeling of the lung vessels characterized by a steady rise in pulmonary arterial pressure. The ensuing morbidity and mortality of this disease result from the failure of the right ventricle to compensate this increase in the after-load. The conditions to achieve an optimum treatment of pulmonary hypertension patients are: a clinical presumption and early diagnosis, an adequate stratification based on the underlying causes and the different vascular territories involved, the response to therapy and the degree of severity, the selection of the different therapeutic alternatives and their timely indication. These recommendations are aimed at the general practitioner and their objective is to facilitate the early detection, diagnosis and treatment of pulmonary hypertension patients, representing a major change in the prognosis. Moreover, as the diagnostic evaluation requires complementary tests that are not usually available in all medical centers, they can also be used as the basis to request a timely referral to institutions with the adequate complexity.

Tromboendarterectomía pulmonar: tratamiento de elección para la hipertensión pulmonar tromboembólica crónica / Pulmonary thromboendarterectomy is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension

La tromboendarterectomía pulmonar es la terapéutica de elección para pacientes con hipertensión pulmonar tromboembólica crónica. Objetivos: Reportar la experiencia en tromboendarterectomía pulmonar a 18 años de seguimiento. Material y Métodos: Se analizaron retrospectivamente 41 pacientes entre Noviembre 1992 y Agosto 2010.Criterios de inclusión: presión arterial pulmonar media >30 mmHg y resistenciavascular pulmonar (RVP) >300 dinas/sg. cm-5. La angiografía pulmonar determinó la factibilidad quirúrgica. La supervivencia se calculó utilizando el método de Kaplan-Meier y para comparar 2 grupos log-rank test.Resultados: El 44% de los pacientes estaban en clase funcional IV. Los cambios hemodinámicos posteriores a la tromboendarterectomía fueron significativos p <0.001. La PAPm 53 ± 2 a 29 ± 2 mmHg, la RVP 857 ± 65 a 245 ± 25 dinas/sg. cm-5 y el IC 2,3 ± 0,1a 3 ± 0,1. La mortalidad hospitalaria fue 15%, en CF II-III 4% y en CF IV 33% (p=0.01). La mortalidad alejada fue 11%. El 93% de los pacientes mejoró su clase funcional. La supervivencia global a 1, 2, 5, 10 años fue del 85%, 82%, 75% y 71% respectivamente.La supervivencia por clase funcional mostró diferencias significativas (p=0.02). Conclusión: En nuestra experiencia la tromboendarterectomía pulmonar mostró beneficios en esta población de alto riesgo.

Pulmonary thromboendarterectomy is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension. Objective: To report our 18-years experience in pulmonary thromboendarterectomy. Material and Methods: Forty one patients were analyzed between November/1992 andAugust/2010. Inclusion criteria: mean pulmonary artery pressure (PAPm) >30 mmHg and pulmonary vascular resistance (PVR) >300 dinas/sec.cm-5. Pulmonary angiography determined the surgical feasibility. Survival was calculated using the Kaplan-Meiermethod and to compare the 2 groups log rank test. results: Pulmonary thromboendarterectomy is the treatment of choice for patients with chronicthromboembolic pulmonary hypertension. Objective: To report our 18-years experience in pulmonary thromboendarterectomy. Material and Methods: Forty one patients were analyzed between November/1992 andAugust/2010. Inclusion criteria: mean pulmonary artery pressure (PAPm) >30 mmHg and pulmonary vascular resistance (PVR) >300 dinas/sec.cm-5. Pulmonary angiography determined the surgical feasibility. Survival was calculated using the Kaplan-Meiermethod and to compare the 2 groups log rank test. Results: Forty four percent of the patients were classified in class IV. The hemodynamic changesafter pulmonary thromboendarterectomy were significant (p < 0.001). PAPm 53 ± 2 vs. 29 ± 2 mm Hg, PVR 857 ± 65 vs. 245 ± 25 dinas/sec. cm-5 and CI 2.3 ± 0.1 vs. 3 ± 0.1. In-hospital mortality was 15%; in classes II - III was 4%, and in class IV 33% (p = 0.01). Late mortality was 12%. Ninety three percent of the patients improved their functional class. Overall survival at 1,2, 5 and 10 years was 85%, 82%, 75% and 71% respectively. Survival according to functional class showed significant differences (p = 0.02).Conclusion: In our experience pulmonary thromboendarterectomy showed benefits even in thishigh risk population.

Open lung biopsy for diffuse disease in patients with and without previously transplanted solid organs.

BACKGROUND: Studies on whether surgical lung biopsy (SLB) modifies the treatment of patients with diffuse lung disease are conflicting, and information is limited on whether it alters treatment in solid-organ transplant recipients. Our objective was to determine and compare the rate of treatment change after SLB for diffuse lung disease in patients with and without a history of solid-organ transplantation. METHODS: Patients undergoing SLB for diffuse lung disease between March 2004 and March 2009 were identified. A retrospective review was performed. RESULTS: Sixty patients had SLB. Thirty-four patients (57%) had solid-organ transplantation. Twenty of 60 patients (33%) had a change in treatment as a result of the findings of the SLB. No significant differences in the treatment change rate were found between the transplant and nontransplant groups (10 of 34 versus 10 of 26; p = 0.46). Transplant patients were more likely to be on mechanical ventilation at the time of SLB (12 of 34 versus 3 of 26; p = 0.03). Mechanical ventilatory support at the time of SLB was associated with increased postoperative complications (odds ratio, 6.20; 95% confidence interval [CI], 1.70 to 22.66; p = 0.006) and in-hospital mortality (odds ratio, 9.75; 95% CI, 2.54 to 37.38; p = 0.001). Being on mechanical ventilation (hazard ratio, 3.91; 95% CI, 1.40 to 10.93; p = 0.009), a diagnosis of cancer (hazard ratio, 13.20; 95% CI, 2.87 to 60.78; p = 0.001), and a history of solid-organ transplantation (hazard ratio, 5.52; 95% CI, 1.08 to 28.14; p = 0.04) were independent predictors of survival. CONCLUSIONS: Surgical lung biopsy changes treatment in one third of patients, with no significant difference between patients without transplantation and solid-organ transplant recipients. Patients who undergo SLB while on mechanical ventilation have a significantly increased risk of postoperative complications and death.

Programa de trasplante pulmonar en Uruguay: Nuestra experiencia con un centro regional de referencia / Lung transplant program in Uruguay: our experience with a regional reference center

El Uruguay es un país con 3 millones de habitantes que no cuenta con un programa de trasplante pulmonar propio. En este contexto se ha optado por generar un acuerdo para su realización en un centro de referencia regional como la Fundación Favaloro de la República Argentina. En este trabajo se muestra la experiencia de este programa durante 4 años. Hasta el momento se han trasplantado 20% de los pacientes alistados y la mortalidaden lista de espera ha sido elevada. La principal limitante ha sido la dificultad para obtener donantes pulmonares óptimos para el implante. La flexibilización en la selección, con la utilización de donantes marginales o la utilización de donantes en asistolia pueden en el futuro mejorar esta situación.

Uruguay, a country with three million- inhabitants does not have its own lung transplant program. Therefore an agreement has been reached for transplants, to be performed in the regional reference center called Favaloro Foundation in Argentine. The experience of the program for the first four years is presented in this paper. Twenty percent of the waiting list patients have been transplanted so far; the mortality of the patients on the waiting list was high. The main limitation of the program has been the difficulty to get optimal lung donors.The selection of donors who either meet marginally the transplant requirements or are in asystolic arrest will make the program more flexible and may improve current results.

[Editorial situation of seven Latin American journals on respiratory diseases]. / Estudio situacional de siete revistas latinoamericanas de Neumología.

A survey was conducted in a meeting sponsored by ALAT (Latin American Association of Thoracic Diseases). Each of the seven editors reported about their journal and answered a questionnaire. The improvement in knowledge divulgation is the main motivation of respiratory societies to edit their own journals. To disseminate medical knowledge and report experiences, are the main motivations of authors to submit papers. The most common deficiency of submitted manuscripts is a bad compliance with journal requirements. An improvement in the relationship between author-editor-reviewer should be the best strategy to enhance the quality of the manuscripts. Suggestions to improve the Latin American journals included to professionalize editorial work, to increase the meticulousness of manuscripts reviewers and to reinforce international norms for editing medical journals. Some major problems reported were a lack of a regular and adequate periodicity in publishing the issues, lack of original papers submitted that mean a "milestone" for the specialty a low percentage of submitted papers rejection and a high and frequent turnover of editors. Although several journals are available in electronic indices, they should be maintained in their printed form. Each journal should have printed its subscription fee, even considering that its subscription is included in the annual society membership fee. The feasibility to generate a multinational Latin American Journal on Respiratory Diseases should be explored.

Situational study of seven Latin-American pulmonology journals.

OBJECTIVE: To characterize the situation of pulmonology journals published in Latin America. METHODS: A survey was conducted in a meeting sponsored by the Latin American Thoracic Society. Each journal editor presented a report and answered a questionnaire. RESULTS: Improving information acquisition is the main motivation for pulmonology societies to edit their own journals, whereas disseminating medical knowledge and reporting experiences are the main motivations for authors to submit papers. The most common failing in the manuscripts submitted is poor compliance with the journal guidelines. Improving author-editor-reviewer relationships would be the best strategy for improving the quality of manuscripts. Suggestions for improving Latin American journals included the following: promoting professionalism in editorial tasks; encouraging manuscript reviewers to be more meticulous; and embracing international norms for editing medical journals. The following major problems were reported: a lack of regular, appropriate periodicity of issues; a shortage of original papers that are considered 'milestones' in the specialty; a low rejection rate for submitted papers; a high turnover of editors. CONCLUSION: Based on our findings, we can make the following recommendations: although many journals are available in electronic form, they should also be maintained in print form; each journal should divulge its subscription fee, even if it is included in the annual society membership dues; although each Latin American country might decide to publish its own pulmonology journal, the feasibility of publishing a multinational Latin American pulmonology journal should be explored.

Estudio situacional de siete revistas latinoamericanas de neumonología / Editorial situation of seven journals on respiratory diseases from Latin America

Objetivo: Caracterizar la situación de las revistas sobre enfermedades respiratorias publicadas en América Latina. Método: Se efectuó una encuesta en una reunión organizada por ALAT (Asociación Latinoamericana de Tórax). Cada editor presentó un informe sobre la revista a su cargo y contestó un cuestionario. Resultados: La principal motivación de las Sociedades de Enfermedades Respiratorias para publicar sus propias revistas es mejorar la adquisición de conocimientos. Las principales motivaciones de los autores para escribir artículos serían difundir el conocimiento médico e informar sobre una experiencia. La deficiencia más frecuente de los manuscritos enviados, es la falta de cumplimiento con las normas de publicación de la revista. El logro de una mejoría en la relación autor-editor-revisor, sería la mejor estrategia para mejorar la calidad de los manuscritos. Entre las sugerencias para mejorar las revistas latino-americanas destacaron: a) profesionalizar el trabajo editorial; b) aumentar la meticulosidad de los revisores de los manuscritos y c) insistir en el cumplimiento de las normas internacionales de edición de revistas médicas. Algunos de los principales problemas informados fueron: a) carencia de periodicidad regular y adecuada en la publicación de cada número de las revistas; b) carencia de manuscritos originales que signifiquen un aporte de real impacto para la especialidad; c) bajo porcentaje de rechazo de manuscritos enviados para su eventual publicación; d) el recambio de editores es elevado y frecuente. Recomendaciones: a) las revistas deberían mantener su formato impreso en papel, aunque estén disponibles en índices electrónicos; b) cada revista debería tener impreso el costo de su suscripción, aunque esté incluido en la cuota anual de membresía de la sociedad; c) no obstante cada país de América Latina pueda decidir publicar su propia revista de enfermedades respiratorias, debe explorarse la factibilidad de generar una revista multinacional...

The situation of respiratory diseases journals published in Latin America was analized by the editors of these journals, convoked by ALAT (Latin American Association of Thoracic Diseases) al Lima, Peru, on February 4th, 2007. Each editor presented a report about his/her journal and answered a survey about to get better manuscripts. Results of the survey improve information acquisition would be the main motivation of national respiratory societies for editing their own journals Disseminate medical knowledge and report an experience, would be the main motivations of authors to submit papers. The most frequent deficiency of manuscripts submitted is bad adherence to journal's requirements. An improvement in the relationship between author-editor-reviewer should be the best strategy to enhance the quality of the manuscripts. Suggestions on how to improve the Latin American journals included: a) professionalize editorial work; b) increase meticulousness of manuscripts reviewers and c) reinforce international norms for editing medical journals. Major problerns reported by editors a) Lack of a regular and adequate periodicity (at least quarterly) in publishing the issues: b) Lack of original papers submitted that mean a "milestone" for the specialty; c) Low percentage of rejection in submitted papers (5 to 39%) indicating an scarce capacity to select excellent papers; d) high and frequent turnover of editors (each two years) which implies a poor accomplishment of editorial regulations and policies. Recommendations a) Although several journals are available in electronic indices, they should be maintained in their printed form, because it is unknown for how long the information could be preserved in an electronic support; b) Each journal should have printed its subscription fee, in spite its subscription is included in the annual society membership fee...