[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.

Extracorporeal Mechanical Circulatory Support after Pulmonary Thromboendarterectomy: Experience of One Center.

PURPOSE: Pulmonary thromboendarterectomy (PTE) is the treatment for patients with chronic thromboembolic disease. In the immediate postoperative period, some patients may still experience life-threatening complications such as reperfusion lung injury, airway bleeding, and persistent pulmonary hypertension with consequent right ventricular dysfunction. These issues may require support with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery or lung transplantation. This study aims to analyze our series of PTEs that require ECMO. METHODS: A descriptive and retrospective analysis of all PTE performed at the Favaloro Foundation University Hospital was conducted between March 2013 and December 2023. RESULTS: A total of 42 patients underwent PTE with a median age of 47 years (interquartile range: 26-76). The incidence of patients with ECMO was 26.6%, of which 53.6% were veno-venous (VV) ECMO. Preoperatively, a low cardiac index (CI), high right and left filling pressures, and high total pulmonary vascular resistances (PVRs) were associated with ECMO with a statistically significant relationship. The hospital mortality was 11.9%, and the mortality in the ECMO group was 45.5%, with a statistically significant relationship. Veno-arterial ECMO has a worse prognosis than VV ECMO. CONCLUSIONS: Preoperatively, a low CI, high right and left filling pressures, and high total PVRs were associated with ECMO after PTE.

Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study.

BACKGROUND: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. METHODS: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). RESULTS: At baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72-98%), and 66% (95% CI: 48-90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. CONCLUSION: Our study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.

Differences in health policies for drug availability in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension across Latin America.

Treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in Latin America differs between countries, with regard to disease etiology, health insurance coverage, and drug availability. A group of experts from Latin America, met to share regional experiences and propose possible lines of collaboration. The available evidence, regional clinical practice data, and the global context of the proceedings of the 6th World Symposium on Pulmonary Hypertension, held in Nice, France, in February 2018, were analyzed. Here, we discuss some priority concepts identified that could guide transnational interaction and research strategies in Latin America: (1) despite being evidence-based, the 6th World Symposium on Pulmonary Hypertension proceedings may not be applicable in Latin American countries; (2) proactive identification and diagnosis of patients in Latin America is needed; (3) education of physicians and standardization of appropriate treatment for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is vital; (4) our clinical experience for the treatment strategy for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is based on drug availability in Argentina, Brazil, Colombia and México; (5) there are difficulties inherent to the consultation of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, and access to treatment; (6) the importance of data generation and research of Latin American-specific issues related to pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension is highlighted.

Pulmonary Evaluation of Post-COVID-19 Patients: An Ecuadorian Experience.

Background: Despite the growing concerns related to the potential of long-term pulmonary sequelae due to COVID-19, data about intermediate and long-term changes in the respiratory function of patients who recover is relatively sparse, particularly in developing countries. Objectives: To assess the characteristics and pulmonary function at follow-up in a sample of Ecuadorian patients that recovered from the virus. Methods: We conducted a cross-sectional study that included 43 patients after symptomatic COVID infection, who were evaluated by spirometry, single breath DLCO, and 6MWT. For statistical analysis we performed point biserial correlations, and chi squared tests. Results: Overall, 30.3% of patients (n = 13) reported persistent symptoms, with fatigue being the most common (23.3%, n = 10). Around 34.9% (n = 15) of the sample had a restrictive spirometry pattern, 18.6% (n = 8) had an abnormally decreased adjusted DLCO. A restrictive spirometry pattern was associated with an abnormally low adjusted DLCO (χ2(2) = 11,979, p = 0.001). Conclusion: We found that a considerable proportion of patients presented with persistent symptoms and alterations in pulmonary function following COVID-19, mainly a restrictive respiratory pattern and abnormally low DLCO. Further studies are needed to determine which patients may benefit from the follow-up with specific pulmonary function tests.

[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.

[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.

Transbronchial biopsies' histopathological findings leading to successful late steroid therapy in Covid-19 acute respiratory failure.

We present results from clinical, radiologic, gas exchange, lung mechanics, and fibre-optic bronchoscopy-guided transbronchial biopsies in a case of acute respiratory failure due to SARS-CoV-2 (Covid-19). This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers. The patient's deterioration paralleling the late immuno-pathological findings based the decision to administer intravenous corticosteroids, resulting in clinical, gasometric, and radiologic improvement. We believe that real-time clinicopathological correlation, along with the description of the immunological processes at play, will contribute to the full clinical picture of Covid-19 and might lead to a more rational approach in the precise timing of anti-inflammatory, anti-cytokine, or steroid therapies.

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.

[Sarcoidosis. Clinical presentation and prognosis]. / Sarcoidosis. Presentación clínica y pronóstico.

We analyzed clinical characteristics of 26 patients with suggesting clinical picture and histopatological diagnosis of sarcoidosis. We identified mortality-related variables in the follow-up. We examined clinical data and several complementary tests. Follow-up was performed by clinical consultation and telephonic interview. The patients mean age was 42.6 ± 12.7 years old, and 53.8% were female. Pulmonary affection was present in 88.4% of patients and extrapulmonary manifestation were seen in 30.7%. Radiological stage II was the most frequent (34.7%). The predominant spirometric abnormality was a low carbon monoxide diffusing capacity (DLCO) in 56.5% of cases. Pulmonary hypertension was found in 34.7% of cases. Steroid therapy was performed in 69.2%. The follow-up was completed in 96.1% of patients with a mean of 98 ± 73 months (range 3 to 228). The mortality rate was 23% (n = 6). The factors significantly associated with mortality were: blood arterial gases with lower partial oxygen pressure (41.5 mm Hg vs. 73.3 mm Hg; p = 0.041); higher partial carbon dioxide pressure (59.5 mm Hg vs. 39.6 mm Hg; p = 0.0008); presence of pulmonary hypertension (83.3% vs. 16.6%; p = 0.001) and higher pulmonary capillary wedge pressure (12.5 mm Hg vs. 9.5 mm Hg; p = 0.041). There was a tendency to higher mortality in patients with radiological stage III/IV (66% vs. 27%; p = 0.082) and lower DLCO (33.5% vs. 51.4%; p = 0.087). Clinical characteristics and long-term prognosis in our serie differed from others publications in international literature. Mortality-related factors were associated with severity of disease.

[Serious and consecutive airway complications after lung transplantation]. / Complicaciones graves y sucesivas de la vía aérea en trasplantada pulmonar.

Airway complications are relatively frequent after lung transplantation and represent a great challenge to the medical team. In spite of the development of different modalities of bronchoscopic treatment and a lower incidence of complications with new surgical techniques, morbidity and mortality are still elevated. We present the case of a woman who underwent right lung transplantation who afterward developed four severe and consecutive airway complications that solved with a successful therapy approach.

Tromboendarterectomía pulmonar en hipertensión pulmonar tromboembólica crónica. Experiencia binacional Uruguay-Argentina / Pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension. Binational experience Uruguay-Argentina / Tromboendarterectomia pulmonar na hipertensão pulmonar tromboembólica crônica. Experiência binacional Uruguai-Argentina

Introducción: La tromboendarterectomía pulmonar (TEA) es la principal herramienta terapéutica en hipertensión pulmonar tromboembólica crónica (HPTEC), potencialmente curativa. Se analiza la experiencia de 13 años de TEAs de pacientes uruguayos en el marco del convenio con el Hospital Universitario Fundación Favaloro (HUFF-Argentina). Metodología: Estudio analítico, observacional y retrospectivo de todas las TEAs realizadas entre 2011 y 2023. Resultados: Se realizaron 15 TEAs. 46 ± 17 años, 67% hombres. Diez pacientes tenían antecedentes de enfermedad tromboembólica previa y 8 hipercoagulabilidad. El tiempo desde el inicio de los síntomas al diagnóstico fue de 36 (22-78) meses. Ochenta por ciento se encontraba en CF III, con una distancia total recorrida en la prueba de la marcha de 6 minutos de 375 (272-458) metros, severidad ecocardiográfica (TAPSE/PAPs 0,22 ± 0,08 mm/mmHg) y hemodinámica (RVP 11 ± 5 UW) que mejoraron significativamente en el posoperatorio temprano. La mortalidad intrahospitalaria fue del 20% que se mantuvo en el seguimiento de 34 (7-97) meses excepto un paciente que murió por una nueva embolia de pulmón a los 3 años. Todos los fallecidos tenían una hemodinamia preoperatoria significativamente más grave (RVP 19 ± 6 UW, índice cardíaco 1,5 ± 0,4 L/min/m2). Seis sobrevivientes (50%) presentaron HP residual asociada a una mayor PAPm y RVP preoperatorias y menor recuperación funcional y ecocardiográfica a corto plazo (P <0,05), dos de los cuales recibieron terapia específica posterior al procedimiento. Conclusiones: La TEA determinó mejoría clínica, ecocardiográfica y hemodinámica. Seis supervivientes (50%) normalizaron la hemodinamia de reposo. La severidad hemodinámica preoperatoria dado por las lesiones obstructivas y microangiopatía distales se asoció con una alta tasa de complicaciones y mortalidad perioperatorias. La reducción del retardo en el diagnóstico y tratamiento junto con una mayor tasa de TEAs/año podrían reducir las complicaciones y mejorar el pronóstico.

Summary Introduction: Pulmonary thromboendarterectomy (PTE) is the main therapeutic tool for chronic thromboembolic pulmonary hypertension (CTEPH), and is potentially curative. The experience of 13 years of PTEs on Uruguayan patients under the agreement with the University Hospital Fundación Favaloro (HUFF-Argentina) is analyzed. Methodology: Analytical, observational, and retrospective study of all PTEs performed between 2011 and 2023. Results: Fifteen PTEs were performed. Age was 46 ± 17 years, 67% male. Ten patients had a history of prior thromboembolic disease, and 8 had hypercoagulability. The time from symptom onset to diagnosis was 36 (22-78) months. Eighty percent were in NYHA Functional Class III, with a total distance walked in the 6-minute walk test of 375 (272-458) meters, echocardiographic severity (TAPSE/sPAP 0,22 ± 0,08 mm/mmHg), and hemodynamic severity (PVR 11 ± 5 WU) which significantly improved in the early postoperative period. In-hospital mortality was 20% and remained at a follow-up of 34 (7-97) months, except for one patient who died from a new pulmonary embolism at 3 years. All deceased patients had significantly more severe preoperative hemodynamics (PVR 19 ± 6 WU, cardiac index 1,5 ± 0,4 L/min/m²). Six survivors (50%) presented with residual PH associated with higher preoperative mPAP and PVR and lower short-term functional and echocardiographic recovery (P <0,05), two of whom received specific therapy post-procedure. Conclusions: PTE resulted in clinical, echocardiographic, and hemodynamic improvement. Six survivors (50%) normalized resting hemodynamics. Preoperative hemodynamic severity due to distal obstructive lesions and microangiopathy was associated with a high rate of perioperative complications and mortality. Reducing the delay in diagnosis and treatment and a higher rate of PTEs/year could reduce complications and improve prognosis.

Introdução: A tromboendarterectomia pulmonar (TEP) é a principal ferramenta terapêutica na hipertensão pulmonar tromboembólica crônica (HPTEC), potencialmente curativa. Analisa-se a experiência de 13 anos de TEPs em pacientes uruguaios no âmbito do convênio com o Hospital Universitário Fundação Favaloro (HUFF-Argentina). Metodologia: Estudo analítico, observacional e retrospectivo de todas as TEPs realizadas entre 2011 e 2023. Resultados: Foram realizadas 15 TEPs. Idade de 46 ± 17 anos, 67% homens. Dez pacientes tinham antecedentes de doença tromboembólica prévia e 8 hipercoagulabilidade. O tempo desde o início dos sintomas até o diagnóstico foi de 36 (22-78) meses. Oitenta por cento encontravam-se em Classe Funcional III, com uma distância total percorrida no teste de caminhada de 6 minutos de 375 (272-458) metros, gravidade ecocardiográfica (TAPSE/sPAP 0,22 ± 0,08 mm/mmHg) e hemodinâmica (RVP 11 ± 5 UW) que melhoraram significativamente no pós-operatório precoce. A mortalidade intra-hospitalar foi de 20% e manteve-se no seguimento de 34 (7-97) meses, exceto um paciente que faleceu por uma nova embolia pulmonar aos 3 anos. Todos os falecidos apresentavam hemodinâmica pré-operatória significativamente mais grave (RVP 19 ± 6 UW, índice cardíaco 1,5 ± 0,4 L/min/m²). Seis sobreviventes (50%) apresentaram HP residual associada a maior PAPm e RVP pré-operatórias e menor recuperação funcional e ecocardiográfica a curto prazo (P <0,05), dois dos quais receberam terapia específica pós-procedimento. Conclusões: A TEP resultou em melhora clínica, ecocardiográfica e hemodinâmica. Seis sobreviventes (50%) normalizaram a hemodinâmica de repouso. A gravidade hemodinâmica pré-operatória devido a lesões obstrutivas e microangiopatia distal foi associada a uma alta taxa de complicações e mortalidade perioperatória. A redução do atraso no diagnóstico e tratamento juntamente com uma maior taxa de TEPs/ano poderia reduzir as complicações e melhorar o prognóstico.

Prevalencia de infecciones asociadas al donante en receptores de trasplante pulmonar

Resumen La complicación infecciosa es la más frecuente posterior a un trasplante. Existe una limitada descripción respecto a la prevalencia de infecciones asociadas al donante (IAD) en receptores de trasplante de pulmón (TxP). Hay reportes de dicha situación de un 7,6%, con documentación de fracaso profiláctico de 5,6%. Objetivo: estimar la frecuencia de infecciones asociadas al donante tras el TxP y su desenlace en términos de supervivencia global (SG). Materiales y métodos: estudio observacional, descriptivo, llevado a cabo en un centro trasplante de Argentina entre los meses de enero 2018 a junio 2020. Se incluyó a todos los pacientes trasplantados en dicho intervalo, y se contabilizaron a todos aquellos con IAD definida/probada. Resultados: en el periodo antedicho se realizaron 65 TxP en 64 individuos (un caso se realizó trasplante y posterior retrasplante en el mismo periodo de estudio). La mediana de edad fue de 39 (12 - 72) años. La fibrosis quística constituyó el principal motivo de TxP (26,2%). En 61/65 (94%) se aislaron gérmenes de muestras biológicas procedentes del donante: en el líquido de conservación 78,6%, secreciones del donante 73,7%, muestras quirúrgicas 21,3% y en hemocultivos 4,9%. Se identificaron IAD en 2/61 casos (prevalencia de 3,1%; IC 95% 0,4-10,7%), con una mediana de SG postrasplante de 12 meses, y una SG del 98,4% (IC 95% 91,7 - 99,9%). Conclusión: la prevalencia de IAD en receptores de TxP en la presente serie fue del 3,1%, superior a lo documentado en trasplantes de órganos sólidos en general (< 1%), aunque menor a la encontrada en los pocos reportes publicados (7,6%).

Prevalence of Donor-Associated Infections in Lung Transplant Recipients

Abstract The infectious complication is the most common condition after a transplantation. There is a limited description regarding the preva lence of donor-associated infections (DAIs) in lung transplant (LTx) recipients. There are reports of DAIs in LTx recipients of 7.6%, with documented prophylactic failure of 5.6%. Objective: to estimate the frequency of donor-associated infections after lung transplantation and their outcome in terms of overall survival (OS). Methodology: an observational, descriptive study, carried out in a transplant center in Argentina between January 2018 and June 2020. The study included all the patients who underwent a transplantation within such period and those with defined/proven DAIs. Results: during the aforementioned period, 65 LTx were performed in 64 individuals (one patient underwent transplantation and subsequent retransplantation in the same study period). The median age was 39 (12-72) years. Cystic fibrosis was the main reason for transplantation (26.2%) In 61/65 cases (94%), germs were isolated from biological samples collected from the donor: 78.6% in the preservation liquid, 73.7% in donor secretions, 21.3% surgical samples, and 4.9% blood cultures. Donor-associated infections were identified in 2/61 cases (prevalence of 3.1%; 95% CI: 0.4-10.7%), with a median posttransplant OS of 12 months, and an OS of 98.4% (95% CI: 91.7-99.9%). Conclusion: the prevalence of DAIs in LTx recipients in the present series was 3.1%: higher than the figures documented for solid organ transplants in general (< 1%), but lower than the numbers found in the few published reports (7.6%).

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.

[Role of prostacyclin and its derivatives in the treatment of pulmonary arterial hypertension]. / Rol de la prostaciclina y sus derivados en el tratamiento de la hipertensión arterial pulmonar.

Pulmonary arterial hypertension (PAH) is defined as a group of diseases characterised by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and death. A dysregulation of prostacyclin metabolic pathways has been demonstrated in patients with PAH and in experimental models. Recently, therapy with continuous intravenous prostacyclin (epoprostenol) has been shown to improve symptoms and prognosis in New York Heart Association (NYHA) functional class III and IV patients with different types of PAH. However, epoprostenol administration requires invasive methods with a permanent intravenous catheter and is associated with several side effects and potentially serious complications. Other modes of prostacyclin therapies are being considered using stable prostacyclin analogues administered by inhalation (iloprost), subcutaneously (treprostinil) or orally (beraprost). Over the last years, different multicenter international double-blind trials have demonstrated the efficacy of those novel prostacyclin analogues in PAH compared to conventional therapy promising a better future for these patients.

Trasplante pulmonar en Uruguay: avances en curso para la consolidación del programa / Lung transplant in Uruguay: progress in motion for the consolidation of the program / Transplante pulmonar no Uruguai: avanços atuais para a consolidação del programa

Introducción: en Uruguay funciona desde el año 2003 un programa de trasplante pulmonar (TP) mediante un convenio binacional con la República Argentina, con Fundación Favaloro, centro regional de referencia. Objetivos: describir los resultados del programa y herramientas en curso para mejorar la procuración pulmonar en Uruguay. Material y método: estudio descriptivo, retrospectivo, entre 2003 y 2017. Recopilación de datos del registro electrónico y análisis mediante SPSS. Resultados: ingresaron a lista 70 pacientes, 27 fueron trasplantados, 95% se reinsertaron a actividades sociales o laborales. Las etiologías fueron enfisema (33%), fibrosis quística (26%) y fibrosis pulmonar idiopática (11%). Las complicaciones más frecuentes fueron infecciones respiratorias y alteraciones de la vía aérea. La mortalidad postrasplante es 34% y la supervivencia mediana condicional supera los ocho años. La elevada mortalidad en lista (32%) impulsó el establecimiento de nuevas estrategias de procuración pulmonar. Destacamos: seguimiento longitudinal de pacientes, modificación de umbral de convocatoria, realización de maniobras de reclutamiento alveolar, realización sistemática de fibrobroncoscopía; minimización de tiempos de traslado y entrenamiento de equipo quirúrgico uruguayo para ablación. La procuración pulmonar pasó de 0 por millón de población (pmp) en 2014 y 2015 a 1,8 pmp en 2017. Conclusiones: el Programa Uruguayo de Trasplante Pulmonar ha tenido importantes avances. Los últimos dos años han sido claves para el crecimiento de la procuración pulmonar. Los resultados, la sobrevida y la morbimortalidad son comparables a los descritos internacionalmente. Las perspectivas a futuro serán consolidar el programa en un centro de referencia y realización de ablación e implante en nuestro territorio. (AU)

Introduction: a program for Lung Transplant (LT) has been operative in Uruguay since 2003, by means of a bi-national agreement with Fundación Favaloro, a regional reference center in Argentina. Method: descriptive, retrospective study performed between 2003 and 2017. Data in the electronic register was compiled and analyzed using SPSS (Statistical Package for the Social Sciences). Results: 70 patients were entered in the list, 27 of which underwent transplant surgery, 95% of them resumed social like and/or work. Etiologies included emphysema (33%), cystic fibrosis (26%) and idiopathic pulmonary fibrosis (11%). The most frequent complications were respiratory infections and alterations in the airway. Post-transplant mortality is 34% and conditional median survival is higher than 8 years. The increased mortality in the list (32%) encouraged development of new strategies for lung procurement. The following facts are pointed out: longitudinal follow-up of patients, modification of the calling threshold, the performance of alveolar recruitments maneuvers, the systematic performance of fibrobroncoscopy, minimization of transport times and training of the Uruguayan surgical team for ablation. Lung procurement increased from 0 per million of population (pm) in 2014 to 1.8 pmp in 2017. Conclusions: the Uruguayan program for LT has evidenced significant progress. The last two years have been essential for the increase of lung procurement. Results, survival and morbi-mortality are comparable to those described globally. Future perspectives will focus on consolidating the program in a reference center and performing ablation and implants in our country.

Introdução: desde 2003 funciona no Uruguai um programa de Transplante Pulmonar (TP) através de um convenio binacional com Argentina, com Fundación Favaloro, centro regional de referência. Objetivos: descrever os resultados do programa e as ferramentas que estão sendo utilizadas para melhorar a procuração pulmonar no Uruguai. Materiais e métodos: estudo descritivo, retrospectivo do período 2003-2017. Coleta de dados do registro eletrônico e análise com o programa SPSS. Resultados: ingressaram à lista 70 pacientes; 27 foram transplantados dos quais 95% voltaram a atividades sociais e/ou de trabalho. As etiologias foram enfisema (33%), fibrose cística (26%) e fibrose pulmonar idiopática (11%). As complicações mais frequentes foram as infecções respiratórias e alterações da via aérea. A mortalidade pós-transplante foi de 34% e a sobrevida mediana condicional foi superior a 8 anos. Dada la elevada mortalidade na lista de espera (32%) novas estratégias de procuração pulmonar foram estabelecidas. Destacamos: seguimento longitudinal dos pacientes, modificação do umbral de convocatória, realização de manobras de recrutamento alveolar, realização sistemática de fibrobroncoscopia, minimização dos tempos de traslado e capacitação da equipe uruguaia de cirurgia em ablação. A procuração pulmonar passou de 0 por milhão de habitantes (pmp) em 2014 e 2015 a 1.8 pmp em 2017. Conclusões: o Programa Uruguaio de TP mostrou importantes avanços. Os últimos 2 anos foram fundamentais para o crescimento da procuração pulmonar. Os resultados, a sobrevida e a morbimortalidade são comparáveis aos descritos na literatura internacional. As perspectivas para o futuro são consolidar o programa em um centro de referência e a realização de ablação e implante no nosso território.

Identificar la enfermedad crónica de montaña en Jujuy (Argentina) / Identify chronic mountain disease in Jujuy (Argentina)

Introducción: La enfermedad crónica de montaña (ECM) o Enfermedad de Monge es un síndrome clínico observado en personas que vivieron largo tiempo en grandes altitudes. Se caracteriza por eritrocitosis excesiva, hipoxemia, presencia o no de hipertensión pulmonar o insuficiencia cardíaca o ambas, con o sin patología pulmonar. Este síndrome incluye cefalea, alteraciones neurológicas, trastornos del sueño y del aparato digestivo, astenia y disnea. Hasta nuestro conocimiento, no hay referencias bibliográficas que describan esta enfermedad en habitantes de la provincia de Jujuy en la República Argentina. Objetivo: Describir una serie de casos de presentación típica de enfermedad crónica de montaña en habitantes en localidades de altura, de la provincia de Jujuy. Material y método: Diseño de estudio: Estudio descriptivo, de serie de casos, transversal. Población de estudio: Se evaluaron 8 pacientes durante el período comprendido entre los años 2010 y 2011, con diagnóstico de enfermedad crónica de montaña; todos residentes de localidades de altura de la referida provincia. La edad promedio fue de 46 ± 15 años, representando el sexo masculino el 87.5% de esta serie. No se aplicaron criterios de inclusión y exclusión, los pacientes no firmaron consentimiento informado. Lugar: Todos los pacientes fueron evaluados en la región de Humahuaca (2900 metros sobre el nivel del mar). Para esta altitud la oximetría de pulso esperada es de 92%; esta población de estudio mostró, en promedio, un valor de SpaO2 inferior. Se calculó el score de Qinghai, diseñado para clasificar la severidad de la enfermedad crónica de montaña el cual, además, permite comparar casos de enfermedad crónica de montaña entre diferentes regiones. Este score considera una variedad de síntomas y la concentración de hemoglobina. Resultados: El 87.5% de los participantes tenía un índice de masa corporal ≥ 25 kg/m², de los cuales el 71.4% eran obesos (≥ 30 kg/m²). Se constataron un caso de várices de vena safena externa con úlceras en ambos miembros inferiores y un evento de varicorragia grave; un caso de enfermedad pulmonar obstructiva crónica con enfisema en la tomografía computada de tórax; un caso de síndrome metabólico y síndrome de apnea hipopnea obstructiva del sueño. Un paciente presentaba elevación de la presión sistólica del ventrículo derecho (44 mmHg) evaluado por ecocardiograma Doppler con SpaO2 promedio en reposo de 89%. En un paciente se encontró hiperuricemia (10.81 mg/dl); y en otro se completó la evaluación hematológica mediante medulograma observándose aumento de la serie eritroblástica con maduración preservada. La espirometría fue normal en todos los participantes, excepto en el paciente con diagnóstico de EPOC. Se realizó en todos una prueba de marcha de los 6 minutos en aire ambiente. Conclusiones: Esta serie permite describir las características de pacientes con diagnóstico de enfermedad crónica de montaña con criterios clínicos y score específico, en habitantes de altura de la provincia de Jujuy. En este sentido son necesarias políticas de salud acordes a la región montañosa donde se habitan estos individuos y disponer de tecnología adecuada para lograr un diagnóstico precoz y tratamiento adecuado.