Fisiopatología de la hernia diafragmática congénita en el recién nacido / Pathophysiology of congenital diaphramatic hernia in the newborn

La hernia diafragmática congénita es una discontinuidad del diafragma con herniación de los órganos abdominales a la cavidad torácica, actualmente se postula una hipótesis dual para su origen. Su fisiopatología está determinada por la hipoplasia pulmonar, la hipertensión pulmonar y la disfunción ventricular, entender estos elementos es necesario para un adecuado manejo y la mejoría del pronóstico.

Congenital diaphragmatic hernia is a discontinuity of the diaphragm with herniation of the abdominal organs into the thoracic cavity, currently a dual hypothesis for its origin is postulated. Its pathophysiology is determined by pulmonary hypoplasia, pulmonary hypertension and ventricular dysfunction, understanding these elements is necessary for adequate management and improve prognosis.

Hipertensión pulmonar y leiomiomas uterinos, ¿existe relación causal? Serie de casos y revisión fisiopatológica / Pulmonary Hypertension and Uterine Leiomyomas, Is there a Causal Relationship? Case Series and Pathophysiological Review

Introducción: Los leiomiomas uterinos son un tipo de neoplasia benigna de frecuente aparición en mujeres de edad reproductiva, relacionados con enfermedad tromboem- bólica venosa. Este vínculo surge del efecto producido por la compresión de fibromas que genera estasis venosa en la región pelviana. Sin embargo, este pareciera no ser el único factor que lo relaciona con el desarrollo posterior de hipertensión pulmonar, sino que su presencia es gatillo de una serie de fenómenos que influyen sobre la vasculatu - ra pulmonar y también a nivel sistémico. Método: Revisión de una serie de casos (seis) atendidos en nuestra unidad, seguido de una revisión sobre la relación entre leiomio- mas y distintas formas de hipertensión pulmonar con una revisión desde la fisiopatología. Resultado y conclusiones: Encontramos sustento bibliográfico en los múltiples caminos fisiopatológicos que relacionan los mediadores vasculares comunes, que parecieran ser el punto clave en la relación entre estas dos patologías.

Introduction: Uterine leiomyomas are a type of benign neoplasm that frequently appears in women of reproductive age, related to venous thromboembolic disease. This link arises from the effect produced by the compression of fibroids, which generates venous stasis in the pelvic region. However, this seems not to be the only factor that re- lates it to the subsequent development of pulmonary hypertension, but rather its presence is a trigger for a series of phenomena that influence the pulmonary vasculature and also at a systemic level. Method: Review of a series of cases (six) cared for in our unit, followed by a review on the relationship between leiomyomas and different forms of pulmonary hypertension with a review from the pathophysiology. Result and conclusions: We found bibliographic support in the multiple pathophysiological paths that relate the common vascular mediators, which appear to be the key point in the relationship between these two pathologies.

Fisiopatología de la displasia broncopulmonar / Pathophysiology of bronchopulmonary dysplasia

La fisiopatología de la displasia broncopulmonar (DBP) se centra en la interrupción del desarrollo pulmonar durante etapas críticas en las que la histología, anatomía y función celular están en proceso de adaptación para facilitar el intercambio gaseoso eficiente. Este desarrollo, que avanza hacia la etapa alveolar después de la etapa sacular, ocurre simultáneamente con una respuesta inflamatoria y de reparación al daño. Como resultado, se afectan la vía aérea (principalmente a través de la limitación obstructiva), los alvéolos (resultando en hipoxemia) y la vasculatura pulmonar (provocando hipertensión pulmonar).

The pathophysiology of bronchopulmonary dysplasia (BPD) is centered on the disruption of lung development during critical stages where histology, anatomy, and cellular function are adapting to facilitate efficient gas exchange. This development, advancing towards the alveolar stage after the saccular stage, occurs concurrently with an inflammatory and damage repair response. As a result, it affects the airway (primarily through obstructive limitation), alveoli (resulting in hypoxemia), and pulmonary vasculature (leading to pulmonary hypertension).

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.

Hipertensión pulmonar: señalización mediada por canales de calcio, dianas farmacológicas presentes y futuras / Pulmonary hypertension: calcium channel-mediated signaling, present and future pharmacological targets

La hipertensión arterial pulmonar se caracteriza por una presión arterial pulmonar media y resistencia vascular pulmonar elevadas y remodelado patológico de las arterias pulmonares. La entrada de calcio desde el espacio extracelular al intracelular a través de canales dependientes e independientes de voltaje juega un rol fundamental en el aumento de la contractilidad de las arterias pulmonares y la pérdida de regulación del comportamiento proliferativo de las células de las distintas capas de la pared de las arterias pulmonares. De esta manera, estos canales contribuyen con la vasoconstricción exacerbada de las arterias pulmonares y a su remodelado patológico. El objetivo de esta revisión es recapitular la evidencia obtenida desde modelos celulares y animales respecto a la contribución de los principales canales de calcio de membrana plasmática en estos mecanismos fisiopatológicos claves en el desarrollo de la hipertensión pulmonar, discutiendo su valor potencial como diana farmacológica para terapias presentes y futuras.

Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

El péptido Pro-BNP como predictor de daño cardíaco en pacientes con esclerosis sistémica / Pro-BNP Peptide as a Predictor of Cardiac Damage in Systemic Sclerosis Patients

Introducción: La esclerosis sistémica es una enfermedad crónica del tejido conectivo de carácter autoinmune, de causa desconocida, que produce exceso de colágeno provocando fibrosis en la piel, con afectación de órganos internos. Los anticuerpos frecuentes son: antitopoisomerasa 1 y anticentrómero. Las formas clínicas son la cutánea difusa y cutánea limitada. La prevalencia de la afectación cardíaca varía entre un 8-28 por ciento y en fases tardías la presencia de signos y síntomas cardiovasculares es de mal pronóstico y una de las principales causas de mortalidad. Objetivo: Determinar la asociación entre afectación cardíaca y las formas clínicas, el pro-péptido natriurético cerebral N-terminal (NT-proBNP) y los autoanticuerpos en la esclerosis sistémica. Métodos: Se realizó un estudio descriptivo transversal de un universo de 140 pacientes, la muestra fue de 54 pacientes. Se le realizó ecocardiograma, niveles de NT-proBNP, anti-scl 70, anticentrómero y determinación de formas clínicas a todos los pacientes que cumplieron criterios de inclusión y que fueron atendidos en el Hospital: Hermanos Ameijeiras Habana-Cuba, entre julio de 2016 a diciembre de 2017. Resultados: La edad media fue 51,76 ± 12,82. Sexo femenino en un 96,3 por ciento. El 72,2 por ciento era piel blanca. La afectación cardíaca de la EScd fue de 77,5 por ciento, hormona NT-proBNP tuvo niveles elevados en un 55,0 por ciento. Los anti-scl-70 estuvieron negativos en el 70 por ciento (n = 28) de los pacientes con afectación cardíaca. El anti-centrómero estuvo negativo en el 95,0 por ciento (n = 38). Conclusiones: Se determinó que la afectación cardíaca en pacientes con esclerosis sistémica, es independiente de las formas clínicas y de la presencia de autoanticuerpos. Los pacientes que tuvieron los niveles séricos de NT-proBNP elevados presentaron afectación cardíaca(AU)

Introduction: Systemic sclerosis is a chronic autoimmune connective tissue disease of unknown cause, which produces excess collagen causing fibrosis in the skin, affecting internal organs. Common antibodies are antitopoisomerase 1 and anticentromere. The clinical forms are diffuse cutaneous and limited cutaneous. The prevalence of cardiac involvement varies between 8-28percent and in late stages the presence of cardiovascular signs and symptoms have poor prognosis and one of the main causes of mortality. Objective: To determine the association between cardiac involvement and clinical forms, N-terminal pro-brain natriuretic peptide (NT-proBNP) and autoantibodies in SSc. Methods: A cross-sectional descriptive study of a universe of 140 patients was carried out. Fifty four patients made up the sample. An echocardiogram, NT-proBNP, Anti-scl 70, anticentromere levels and determination of clinical forms were performed on all patients who met the inclusion criteria and who were treated at Hermanos Ameijeiras hospital in Havana, Cuba, from July 2016 to December 2017. Results: The mean age was 51.76 ± 12.82. Female sex accounted 96.3percent. 72.2percent were white skinned. Cardiac involvement of EScd was 77.5percent, NT-proBNP hormone had high levels in 55.0percent. Anti-scl-70 were negative in 70percent (n=28) of patients with cardiac involvement. Anti-centromere (ACT) was negative in 95.0percent (n=38). Conclusions: Cardiac involvement in patients with SS is independent of the clinical forms and the presence of autoantibodies. Patients with elevated NT-proBNP serum levels had cardiac involvement(AU)

Angiotensin-(1-7) improves endothelium-dependent vasodilation in rats with monocrotaline-induced pulmonary arterial hypertension / 生理学报

In this study, we used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) to investigate the role and mechanism of angiotensin (Ang)-(1-7) in regulating pulmonary artery diastolic function. Three weeks after subcutaneous injection of MCT or normal saline, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were detected using a right heart catheter. Vascular endothelium-dependent relaxation was evaluated by acetylcholine (ACh)-induced vasodilation. The relaxation function of vascular smooth muscle was evaluated by sodium nitroprusside (SNP)-induced vasodilation. Human pulmonary artery endothelial cells (HPAECs) were incubated with Ang-(1-7) to measure nitric oxide (NO) release levels. The results showed that compared with control rats, RVSP and RVHI were significantly increased in the MCT-PAH rats, and both ACh or SNP-induced vasodilation were worsened. Incubation of pulmonary artery of MCT-PAH rats with Ang-(1-7) (1 × 10-9-1 × 10-4 mol/L) caused significant vaso-relaxation. Pre-incubation of Ang-(1-7) in the pulmonary artery of MCT-PAH rats significantly improved ACh-induced endothelium-dependent relaxation, but had no significant effect on SNP-induced endothelium-independent relaxation. In addition, Ang-(1-7) treatment significantly increased NO levels in HPAECs. The Mas receptor antagonist A-779 inhibited the effects of Ang-(1-7) on endothelium-dependent relaxation and NO release from endothelial cells. The above results demonstrate that Ang-(1-7) promotes the release of NO from endothelial cells by activating Mas receptor, thereby improving the endothelium-dependent relaxation function of PAH pulmonary arteries.

Panax notoginseng saponins improve monocrotaline-induced pulmonary arterial hypertension in rats by inhibiting ADAM10/Notch3 signaling pathway / 生理学报

In this study, we investigated the effects of Panax notoginseng saponins (PNS) on pulmonary vascular remodeling and ADAM10/Notch3 pathway in pulmonary arterial hypertension (PAH). PAH rat model was established, and male Sprague Dawley (SD) rats were randomly divided into control group, monocrotaline (MCT) group and MCT+PNS group, with 10 rats in each group. Rats in the control group were intraperitoneally injected with equal volume of normal saline. Rats in the MCT group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with the same volume of normal saline every day. Rats in the MCT+PNS group was injected intraperitoneally with 60 mg/kg MCT on the first day, and then with 50 mg/kg PNS every day. The modeling time of each group lasted for 21 days. After the model was established, the mean pulmonary artery pressure (mPAP) was measured by right heart catheterization technique, the right ventricular hypertrophy index (RVHI) was calculated, the microscopic morphology and changes of pulmonary vascular wall were observed by HE and Masson staining, and the expressions of ADAM10, Notch3, Hes-1, P27, PCNA, Caspase-3 proteins and mRNA in pulmonary vascular tissue of rats were detected by Western blot and qPCR. The expression and localization of Notch3 and α-SMA were detected by immunofluorescence staining. The protein expression of ADAM10 was detected by immunohistochemical staining. The results showed that compared with the control group, mPAP, RVHI, pulmonary vessels and collagen fibers in the MCT group were significantly increased, the expressions of ADAM10, Notch3, Hes-1, and PCNA protein and mRNA were significantly increased, while the expressions of P27 and Caspase-3 protein and mRNA were decreased significantly. Compared with the MCT group, mPAP and RVHI were significantly decreased, pulmonary vessels were significantly improved and collagen fibers were significantly reduced, the expressions of protein and mRNA of ADAM10, Notch3, Hes-1, and PCNA were decreased in MCT+PNS group, but the expressions of protein and mRNA of P27 and Caspase-3 were increased slightly. The results of immunofluorescence showed that Notch3 and α-SMA staining could overlap, which proved that Notch3 was expressed in smooth muscle cells. The expression of Notch3 in the MCT group was increased significantly compared with that in the control group, while PNS intervention decreased the expression of Notch3. Immunohistochemical staining showed that compared with the control group, the amount of ADAM10 in the MCT group was increased significantly, and the expression of ADAM10 in the MCT+PNS group was decreased compared with the MCT group. These results indicate that PNS can improve the PAH induced by MCT in rats by inhibiting ADAM10/Notch3 signaling pathway.

Assessment of risk factors for bronchopulmonary dysplasia with pulmonary hypertension and construction of a prediction nomogram model / 中华儿科杂志

Objective: To explore the risk factors of pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD), and to establish a prediction model for early PH. Methods: This was a retrospective cohort study. Data of 777 BPD preterm infants with the gestational age of <32 weeks were collected from 7 collaborative units of the Su Xinyun Neonatal Perinatal Collaboration Network platform in Jiangsu Province from January 2019 to December 2022. The subjects were randomly divided into a training cohort and a validation cohort at a ratio of 8∶2 by computer, and non-parametric test or χ2 test was used to examine the differences between the two retrospective cohorts. Univariate Logistic regression and multivariate logistic regression analyses were used in the training cohort to screen the risk factors affecting the PH associated with BPD. A nomogram model was constructed based on the severity of BPD and its risk factors,which was internally validated by the Bootstrap method. Finally, the differential, calibration and clinical applicability of the prediction model were evaluated using the training and verification queues. Results: A total of 130 among the 777 preterm infants with BPD had PH, with an incidence of 16.7%, and the gestational age was 28.7 (27.7, 30.0) weeks, including 454 males (58.4%) and 323 females (41.6%). There were 622 preterm infants in the training cohort, including 105 preterm infants in the PH group. A total of 155 patients were enrolled in the verification cohort, including 25 patients in the PH group. Multivariate Logistic regression analysis revealed that low 5 min Apgar score (OR=0.87, 95%CI 0.76-0.99), cesarean section (OR=1.97, 95%CI 1.13-3.43), small for gestational age (OR=9.30, 95%CI 4.30-20.13), hemodynamically significant patent ductus arteriosus (hsPDA) (OR=4.49, 95%CI 2.58-7.80), late-onset sepsis (LOS) (OR=3.52, 95%CI 1.94-6.38), and ventilator-associated pneumonia (VAP) (OR=8.67, 95%CI 3.98-18.91) were all independent risk factors for PH (all P<0.05). The independent risk factors and the severity of BPD were combined to construct a nomogram map model. The area under the receiver operating characteristic (ROC) curve of the nomogram model in the training cohort and the validation cohort were 0.83 (95%CI 0.79-0.88) and 0.87 (95%CI 0.79-0.95), respectively, and the calibration curve was close to the ideal diagonal. Conclusions: Risk of PH with BPD increases in preterm infants with low 5 minute Apgar score, cesarean section, small for gestational age, hamodynamically significant patent ductus arteriosus, late-onset sepsis, and ventilator-associated pneumonia. This nomogram model serves as a useful tool for predicting the risk of PH with BPD in premature infants, which may facilitate individualized early intervention.

Classification, diagnosis and treatment status of pulmonary hypertension from 2012 to 2019: a single center study in Yunnan province / 中华心血管病杂志

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

Classification, diagnosis and treatment status of pulmonary hypertension from 2012 to 2019: a single center study in Yunnan province / 中华心血管病杂志

Objective: To analyze the classification, diagnosis and treatment status of patients with pulmonary hypertension (PH) in Yunnan province. Methods: This was a retrospective study. Hospitalized patients with PH at Yan'an Affiliated Hospital of Kunming Medical University from January 2012 to December 2019 were enrolled. The clinical data of enrolled patients, including demographic data, comorbidities, targeted drug therapy, echocardiography and right heart catheterization results, were obtained through the electronic medical record system. The composition ratio of PH, diagnosis and treatment were analyzed. Results: A total of 13 590 patients with PH were enrolled, accounting for 3.09% (13 590/440 056) of the total number of hospitalizations during the same period. The composition of PH was predominantly pulmonary arterial hypertension (PAH) (55.50% (7 542/13 590)), followed by pulmonary hypertension (PH) caused by left heart disease (24.16% (3 284/13 590)). Among them, PAH could be subdivided into four types: idiopathic pulmonary arterial hypertension (IPAH), PAH associated with connective tissue disease, PAH associated with portal hypertension, and PAH associated with congenital heart disease (CHD-PAH), with CHD-PAH as the predominating type (98.09% (7 398/7 542). Patients with PAH were predominantly adolescents. In hospitalized patients with PH, from 2012 to 2019, the proportion of children and adolescents showed a decreasing trend from year to year, and the proportion of middle-aged and older adults showed a significant increasing trend, and the proportion of female patients showed a gradual decreasing trend, and the proportion of patients with comorbid hypertension, diabetes mellitus, coronary artery disease, arrhythmia, and pneumonia showed an increasing trend. A total of 1 034 patients (7.61% (1 034/13 590)) underwent right heart catheterization. The concordance rate between echocardiographic and right heart catheterization findings was (86.98% (875/1 006)). A total of 2 574 (18.94%) of PH patients were treated with PAH targeted drugs, of which 58.16% (1 497/2 574) were treated with monotherapy. Among the PH patients treated with PAH targeted drugs, the majority of patients were PAH patients (86.44% (2 225/2 574)), and 83.53% (2 150/2 574) patients treated with PAH targeted drugs were CHD-PAH. Conclusions: Hospitalized PH patients in our center between 2012 and 2019 are predominantly CHD-PAH, and the proportion of patients receiving right heart catheterization and targeted drug therapy is relatively low. The percentage of middle-aged and elderly PH patients shows an increasing trend from year to year, as well as the percentage of those with concomitant comorbidities.

Diagnosis and treatment of a child with alveolar capillary dysplasia with misalignment of pulmonary veins due to variant of FOXF1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the diagnosis, treatment and genetic characteristics of a neonate with severe pulmonary hypertension and respiratory failure.@*METHODS@#Perinatal history, clinical manifestations, laboratory finding and diagnosis and treatment data of the child were collected. Whole exome sequencing was carried out for the child, and Sanger sequencing was used to verify the candidate variants.@*RESULTS@#The female neonate has developed progressive respiratory failure and refractory pulmonary hypertension shortly after birth. Conventional treatment such as mechanical ventilation, vasoactive drugs, and inhaled nitric oxide were ineffective. She has developed sustained pulmonary hypertension after weaning from extracorporeal membrane oxygenation therapy, and had died after the treatment had ceased. Whole exome sequencing revealed that she has harbored a heterozygous de novo variant of c.682_683insGCGGCGGC (p.G234Rfs*148) of the FOXF1 gene, which was predicted as pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG), with evidence items of PVS1_Strong+PM2_Supporting+PS2. Based on her clinical manifestations and result of genetic testing, the child was diagnosed with alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV).@*CONCLUSION@#Discovery of the c.682_683insGCGGCGGC (p.G234 Rfs*148) variant of the FOXF1 gene has expanded the mutational spectrum of the FOXF1 gene, which has facilitated implementation of specific treatment and provided a basis for clinical diagnosis and genetic counseling.

Research progress on the mechanism of phenotypic transformation of pulmonary artery smooth muscle cells induced by hypoxia / 浙江大学学报·医学版

Phenotypic transformation of pulmonary artery smooth muscle cells (PASMCs) is a key factor in pulmonary vascular remodeling. Inhibiting or reversing phenotypic transformation can inhibit pulmonary vascular remodeling and control the progression of hypoxic pulmonary hypertension. Recent studies have shown that hypoxia causes intracellular peroxide metabolism to induce oxidative stress, induces multi-pathway signal transduction, including those related to autophagy, endoplasmic reticulum stress and mitochondrial dysfunction, and also induces non-coding RNA regulation of cell marker protein expression, resulting in PASMCs phenotypic transformation. This article reviews recent research progress on mechanisms of hypoxia-induced phenotypic transformation of PASMCs, which may be helpful for finding targets to inhibit phenotypic transformation and to improve pulmonary vascular remodeling diseases such as hypoxia-induced pulmonary hypertension.

Multidisciplinary approach for the management of term pregnancy complicated by Eisenmenger syndrome / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pregnancy in patients with Eisenmenger syndrome (ES) is associated with high maternal mortality rates of 30%‒50%, or even up to 65% in the case of a cesarean section (Yuan, 2016). Here, we report a case of term pregnancy complicated with ES and severe pulmonary artery hypertension (PAH), which was managed by a multidisciplinary team (MDT) and resulted in an uncomplicated delivery via elective cesarean section. The goal of this study is to emphasize the importance of multidisciplinary approach in the management of pregnancy with ES, which can profoundly improve maternal and infant outcomes.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).@*METHODS@#A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.@*RESULTS@#The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).@*CONCLUSIONS@#Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.

Analysis on missed diagnosis or misdiagnosis of anomalous origin of left coronary artery from pulmonary artery by echocardiography from one single medical center / 中华心血管病杂志

Objectives: To analyze the reasons of missed diagnosis or misdiagnosis on anomalous origin of left coronary artery from pulmonary artery (ALCAPA) by echocardiography. Methods: This is a retrospective study. Patients with ALCAPA who underwent surgical treatment in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from August 2008 to December 2021 were included. According to the results of preoperative echocardiography and surgical diagnosis, the patients were divided into confirmed group or missed diagnosis/misdiagnosis group. The results of preoperative echocardiography were collected, and the specific echocardiographic signs were analyzed. According to the experience of the doctors, the echocardiographic signs were divided into four types, namely clear displayed, vague/doubtful displayed, no display and no notice, and the display rate of each sign was calculated (display rate=number of clearly displayed cases/total number of cases×100%). By referring the surgical data, we analyzed and recorded the pathological anatomy and pathophysiological characteristics of the patients, and the rate of missed diagnosis/misdiagnosis of echocardiography in patients with different characteristics was compared. Results: A total of 21 patients were enrolled, including 11 males, aged 1.8 (0.8, 12.3) years (range 1 month to 47 years). Except for one patient with anomalous origin of left anterior descending artery, the others were all originated from the main left coronary artery (LCA). There were 13 cases of ALCAPA in infant and children, and 8 cases of adult ALCAPA. There were 15 cases in the confirmed group (diagnostic accuracy was 71.4% (15/21)), and 6 cases in the missed diagnosis/misdiagnosis group (three cases were misdiagnosed as primary endocardial fibroelastosis, two cases were misdiagnosed as coronary-pulmonary artery fistula; and one case was missed diagnosis). The working years of the physicians in the confirmed group were longer than those in the missed diagnosis/misdiagnosed group ((12.8±5.6) years vs. (8.3±4.7) years, P=0.045). In infants with ALCAPA, the detection rate of LCA-pulmonary shunt (8/10 vs. 0, P=0.035) and coronary collateral circulation (7/10 vs. 0, P=0.042) in confirmed group was higher than that in missed diagnosis/misdiagnosed group. In adult ALCAPA patients, the detection rate of LCA-pulmonary artery shunt was higher in confirmed group than that in missed diagnosis/misdiagnosed group (4/5 vs. 0, P=0.021). The missed diagnosis/misdiagnosis rate of adult type was higher than that of infant type (3/8 vs. 3/13, P=0.410). The rate of missed diagnosis/misdiagnosis was higher in patients with abnormal origin of branches than that of abnormal origin of main trunk (1/1 vs. 5/21, P=0.028). The rate of missed diagnosis/misdiagnosis in patients with LCA running between the main and pulmonary arteries was higher than that distant from the main pulmonary artery septum (4/7 vs. 2/14, P=0.064). The rate of missed diagnosis/misdiagnosis in patients with severe pulmonary hypertension was higher than that in patients without severe pulmonary hypertension (2/3 vs. 4/18, P=0.184). The reasons with an echocardiography missed diagnosis/misdiagnosis rate of≥50% included that (1) the proximal segment of LCA ran between the main and pulmonary arteries; (2) abnormal opening of LCA at the right posterior part of the pulmonary artery; (3) abnormal origin of LCA branches; (4) complicated with severe pulmonary hypertension. Conclusions: Echocardiography physicians' knowledge of ALCAPA and diagnostic vigilance are critical to the accuracy of diagnosis. Attention should be paid to the pediatric cases with no obvious precipitating factors of left ventricular enlargement, regardless of whether the left ventricular function is normal or not, the origin of coronary artery should be routinely explored.

Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study

Abstract Background Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods Twenty pigs were randomly assigned to Control group (n = 10), which received saline solution; or to Sildenafil group (n = 10), which received sildenafil orally (100 mg). After 30 minutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4 µg.kg-1.h-1) for 180 minutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNFα, IL-1β, IL6, and IL10) and troponin I response. Results Significant hemodynamic alterations were observed after 30 minutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19 ± 2 mmHg to LPS30 52 ± 4 mmHg, p< 0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411 ± 29 to LPS180 334 ± 49, p< 0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35 ± 4 mmHg at LPS30, p< 0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Manejo anestésico en paciente politraumatizado con corazón univentricular y síndrome de Eisenmenger secundario, caso clínico / Case Report: Anesthetic management of a poly-trauma patient with a univentricular heart and secondary Eisenmenger syndrome

We present the case of a 26 year old polytrauma patient with a left intra-articular distal radial fracture, with an uncorrected late univentricular heart with severe pulmonary hypertension, subsequent Eisenmenger syndrome and supraventricular tachycardia managed with metoprolol. We find this case particularly interesting given the need for osteosynthesis with the obstacle of a non-palliated congenital heart disease in an adult; whose anesthetic implications required particular considerations in order to avoid fatal outcomes in the perioperative setting. Ultimately the patient underwent regional anesthesia with careful hemodynamics monitoring, leading to a satisfactory outcome.

Presentamos el caso de un paciente politraumatizado de 26 años con fractura de radio distal intraarticular izquierda, corazón univentricular tardío no corregido con hipertensión pulmonar severa, posterior síndrome de Eisenmenger y taquicardia supraventricular manejado con metoprolol. Este caso nos parece especialmente interesante dada la necesidad de osteosíntesis con el obstáculo de una cardiopatía congénita no paliada en un adulto; cuyas implicaciones anestésicas requirieron consideraciones particulares para evitar desenlaces fatales en el perioperatorio. Finalmente, el paciente se sometió a anestesia regional con un control hemodinámico cuidadoso, lo que llevó a un resultado satisfactorio.

Asistencia del recién nacido con hernia diafragmática congénita / Care of newborns with congenital diaphragmatic hernia / Cuidados ao recém-nascido com hérnia diafragmática congênita

La hernia diafragmática congénita es un defecto en el diafragma que lleva a la herniación del contenido abdominal a la cavidad torácica durante el período intrauterino. La morbimortalidad está determinada por la asociación con otras malformaciones, el grado de hipoplasia pulmonar y la presencia de hipertensión pulmonar secundaria. Presenta una incidencia estimada de 1 cada 2.500-3.000 recién nacidos vivos, constituyendo en un 60% una malformación aislada. Es una patología evolutiva que puede ser diagnosticada a partir de la semana 20-24, la ubicación más habitual es la posterolateral izquierda. Se trata de una patología que requiere ingreso a cuidados intensivos al nacimiento y luego de lograda la estabilización del paciente es de sanción quirúrgica. Los objetivos de este trabajo son conocer las características generales de la patología para sistematizar el manejo logrando así un óptimo asesoramiento de los padres a nivel prenatal y seguimiento postnatal del recién nacido.

Congenital diaphragmatic hernia is a defect in the diaphragm that leads to herniation of theabdominal contents of the thoracic cavity during the intrauterine period. Morbidity and mortality are determined by the association with other malformations, the degree ofpulmonary hypoplasia and the presence of secondary pulmonary hypertension.It has an estimated incidence of 1 every 2,500-3,000 live newborns, and in 60% of the cases it is an isolated malformation. It is an evolutionary pathology that can be diagnosed from week 20-24; it is most commonly located in the left posterolateral. It is a pathology that requires intensive care at birth and after delivery and once the patient has been stabilized, surgical action is required. The objectives of this work are to understand the general characteristics of the pathology in order to refine its manipulation and achieve optimal counseling for parents at the newborn's prenatal and postnatal stages.

A hérnia diafragmática congênita é um defeito no diafragma que leva à herniação doconteúdo abdominal para a cavidade torácica durante o período intrauterino. A morbimortalidade é determinada pela associação com outras malformações, pelo grau de hipoplasia pulmonar e pela presença de hipertensão pulmonar secundária. Apresenta uma incidência estimada de 1 a cada 2.500-3.000 nascidos vivos, constituindo-se em 60% uma malformação isolada. É uma patologia evolutiva que pode ser diagnosticada a partir da semana 20-24 e a localização mais comum é o póstero-lateral esquerdo. É uma patologia que requer internação em terapia intensiva ao nascimento e após o parto. Uma vez que o paciente for estabilizado, é necessária ação cirúrgica. Os objetivos deste paper são conhecer as características gerais da patologia para melhorar o seu manejo, obtendo assim um aconselhamento ideal para os pais no nível pré-natal e no acompanhamento do crescimento pós-natal do recém-nascido.