Perinatal Outcomes after Fetal Endoscopic Tracheal Occlusion for Isolated Congenital Diaphragmatic Hernia: Rapid Review / Resultados perinatais após oclusão traqueal endoscópica fetal por hérnia diafragmática congênita isolada: Revisão rápida

Abstract Objective To compare the perinatal outcomes of fetuses with isolated congenital diaphragmatic hernia after fetal endoscopic tracheal occlusion (FETO) and antenatal expectant management. Data sources In this rapid review, searches were conducted in the MEDLINE, PMC, EMBASE and CENTRAL databases between August 10th and September 4th, 2020. Randomized controlled trials (RCTs), quasi-RCTs or cluster-RCTs published in English in the past ten years were included. Study selection We retrieved 203 publications; 180 studies were screened by abstract. Full-text selection was performed for eight studies, and 1 single center RCTmet the inclusion criteria (41 randomized women; 20 in the FETO group, and 21 in the control group). Data collection Data collection was performed independently, by both authors, in two steps (title and abstract and full-text reading). Data synthesis There were no cases of maternal mortality. The mean gestational age at delivery was of 35.6±2.4 weeks in the intervention group, and of 37.4±1.9 weeks among the controls (p<0.01). Survival until 6 months of age was reported in 50% of the intervention group, and in 5.8% of the controls (p<0.01; relative risk: 10.5; 95% confidence interval [95%CI]: 1.5-74.7). Severe postnatal pulmonary hypertension was found in 50% of the infants in the intervention group, and in 85.7% of controls (p=0.02; relative risk: 0.6; 95%CI: 0.4-0.9). An analysis of the study indicated some concerns of risk of bias. The quality of evidence was considered moderate to low. Conclusion Current evidence is limited but suggests that FETO may be an effective intervention to improve perinatal outcomes.

Resumo Objetivo Comparar os resultados perinatais de fetos com hérnia diafragmática congênita após oclusão traqueal endoscópica fetal (OTEF) e conduta expectante pré-natal. Fontes dos dados Nesta revisão rápida, pesquisas foram conduzidas nas bases de dados MEDLINE, PMC, EMBASE e CENTRAL entre 10 de agosto de 2020 e 4 de setembro de 2020. Ensaios clínicos randomizados (ECRs), quase-ECRs e ECRs em cluster publicados em inglês nos últimos dez anos foram incluídos. Seleção dos estudos Foram recuperadas 203 publicações; 180 destas foram triadas pelo resumo. Fez-se a leitura do texto completo de 8 estudos, e 1 ECR cumpriu os critérios de inclusão (41 mulheres aleatorizadas; 20 no grupo OTEF e 21 no grupo de controle). Coleta de dados A coleta de dados realizada independentemente pelos dois autores, em duas etapas (título e resumo, e leitura do texto completo). Síntese dos dados Não houve casos de mortematerna. A idade gestacionalmédia no parto foi de 35,6±2,4 semanas no grupo de intervenção, e de 37,4±1,9 semanas entre os controles (p<0,01). A sobrevida até 6 meses de idade foi relatada em 50% do grupo de intervenção, e em 5,8% dos controles (p<0,01; risco relativo: 10,5; intervalo de confiança de 95% [IC95%]: 1,5-74,7). Hipertensão pulmonar grave ocorreu em 50% dos lactentes do grupo de intervenção, e em 85,7% dos controles (p = 0.02; risco relativo: 0,6; IC95%: 0,4-0,9). Uma análise do estudo indicou algumas preocupações quanto ao risco de viés. A qualidade da evidência foi considerada de moderada a baixa. Conclusão As evidências atuais são limitadas,mas sugeremque a OTEF pode ser uma intervenção eficaz para melhorar resultados perinatais.

Exercise Training Improved Pulmonary Gas Exchange Abnormalities in Pulmonary Hypertension due to Heart Failure: A Case Report

Abstract Heart failure (HF) is the most common cause of pulmonary hypertension (PH), and reduced exercise capacity and exertional dyspnea are the most frequent concerns in patients with PH-HF. Indeed, carbon dioxide end-tidal partial pressure (PETCO 2 ) during exercise is a well-established noninvasive marker of ventilation/perfusion ratio in PH. We aimed to evaluate the effect of aerobic exercise training on PETCO 2 response during exercise in a 59-year-old woman with PH secondary to idiopathic dilated cardiomyopathy. The patient with chronic fatigue and dyspnea at mild-to-moderate efforts was admitted to a cardiorespiratory rehabilitation program and had her cardiorespiratory response to exercise assessed during a cardiopulmonary exercise testing performed before and after three months of a thrice-weekly aerobic exercise training program. Improvements in aerobic capacity (23.9%) and endurance time (37.5%) and reduction in ventilatory inefficiency (-20.2%) was found after intervention. Post-intervention improvements in PETCO 2 at ventilatory anaerobic threshold (23.3%) and change in PETCO 2 kinetics pattern, with progressive increases from rest to peak of exercise, were also found. Patient also improved breathing pattern and timing of ventilation. This case report demonstrated for the first time that aerobic exercise training might be able to improve PETCO 2 response during exercise in a patient with PH-HF.

Inactivated Pseudomonas aeruginosa inhibits hypoxia-induced pulmonary hypertension by preventing TGF-beta1/Smad signaling

Pseudomonas aeruginosa is one of the common colonizing bacteria of the human body and is an opportunistic pathogen frequently associated with respiratory infections. Inactivated P. aeruginosa (IPA) have a variety of biological effects against inflammation and allergy. Transforming growth factor-β (TGF-β) signaling plays a critical role in the regulation of cell growth, differentiation, and development in a wide range of biological systems. The present study was designed to investigate the effects of IPA on TGF-β/Smad signaling in vivo, using a hypoxia-induced pulmonary hypertension (PH) rat model. Sprague Dawley rats (n=40) were exposed to 10% oxygen for 21 days to induce PH. At the same time, IPA was administered intravenously from day 1 to day 14. Mean pulmonary artery pressure (mPAP) and the right ventricle (RV) to left ventricle plus the interventricular septum (LV+S) mass ratio were used to evaluate the development of PH. Vessel thickness and density were measured using immunohistochemistry. Primary arterial smooth muscle cells (PASMCs) were isolated and the proliferation of PASMCs was assayed by flow cytometry. The production of TGF-β1 in cultured supernatant of PASMCs was assayed by ELISA. The expression levels of α-smooth muscle actin (α-SMA), TGF-β1 and phospho-Smad 2/3 in PASMCs were assayed by western blot. Our data indicated that IPA attenuated PH, RV hypertrophy and pulmonary vascular remodeling in rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-β1/Smad signaling. In conclusion, IPA is a promising protective treatment in PH due to the inhibiting effects on TGF-β1/Smad 2/3 signaling.

Riociguat para el tratamiento hipertensión pulmonar tromboembólica crónica / Riociguat for the treatment of chronic thromboembolic pulmonary hypertension

Antecedentes. Riociguat es un miembro de una nueva clasede compuestos (estimuladores de la guanilatociclasa solubles), se ha demostrado en estudios clínicos previos el beneficio en el tratamiento dela hipertensión pulmonar tromboembólica crónica. Métodos. En esta fase 3, multicéntrico, aleatorizado, doble-ciego, controlado con placebo,se asignó aleatoriamente a 261 pacientes con inoperable hipertensión pulmonar tromboembólica crónica o la hipertensión pulmonar persistente o recurrente realizada una endarterectomía pulmonar para recibir placebo o riociguat. El punto final primario fueel cambio desde el inicio hasta el final de la semana16 en la distancia caminada en 6 minutos. Los puntos finales secundarios incluyeron cambios des de el inicio de la resistencia vascular pulmonar, Nivel N-terminal pro-péptido natriurético cerebral(NT-proBNP), la organización mundial de la salud(OMS) clase funcional, nos demuestra el tiempo hasta el empeoramiento clínico, en la escala de Borg de la disnea, tomando las variables de calidad de vida y la seguridad...

Riociguat para el tratamiento de la hipertensión arterial pulmonar / Riociguat for the treatment of pulmonary arterial hypertension

Antecedentes Riociguat es un estimulador de la guanilatociclasa soluble, el cual se ha demostrado en unensayo de fase 2 el beneficio en el tratamiento dela hipertensión arterial pulmonar...

Additive effect of phosphodiesterase inhibitors in control of pulmonary hypertension after congenital cardiac surgery in children

Control of residual pulmonary arterial hypertension [PAH] after closure of left to right shunts in children is still a challenging issue. The purpose of this study was to compare the effect of two phosphodiesterase inhibitors in pediatric cardiac surgical patients. A total of 48 postoperative children were enrolled in the study between 2008 and 2010. Patients were stratified based upon choice of pulmonary vasodilator into three equal groups [n=16]; Milrinone group received intravenous milrinone [0.75 micro/kg/min], Sildenafil group received oral sildenafil [0.3 mg/kg every 3 hours] and the Combination group received both medications. Demographic variables and types of congenital anomalies were not different among the 3 groups. Patients in the Combination group had higher preoperative pulmonary artery to aortic [PA/AO] pressure ratios compared to other two groups [P=0.001]. Postoperatively, patients in Milrinone group incurred lower systolic PA and PA/AO pressures compared to Sildenafil group [P=0.014, 0.003], but it was the same in Sildenafil and Combination group [P=0.2; 0.330 respectively]. Pulmonary hypertensive crisis was noted in 6 patients in Sildenafil group, and 3 patients in Combination group [P=0.02]. Significant rise in PA pressure was noticed after discontinuation of drug in Milrinone group [P=0.001], which was not observed in the Combination group [P= 0.6]. No mortality was noticed in any of the groups. Intravenous milrinone is more effective than oral sildenafil in control of postoperative PAH and elimination of pulmonary hypertensive crisis. Combination of two drugs reduces the risk of rebound pulmonary arterial hypertension after discontinuation of milrinone

Constrição ductal fetal / Fetal ductal constriction

A constrição do ducto arterioso fetal é uma condição que pode comprometer o bem estar fetal e neonatal, representado pela hipertensão pulmonar persistente do neonato. Seu diagnóstico é através da ecocardiografia-Doppler fetal e a correção de suas causas são fundamentais para uma gestação fisiológica.

The constriction of the fetal ductus arteriosus is a condition that can compromise fetal and neonatal well-being, represented by persistent pulmonary hypertension of the newborn. Its diagnosis by fetal Doppler echocardiography and the correction of underlying causes are fundamental to physiological pregnancy.

Sildenafil prevents the increase of extravascular lung water and pulmonary hypertension after meconium aspiration in newborn piglets

Meconium aspiration syndrome causes respiratory failure after birth and in vivo monitoring of pulmonary edema is difficult. The objective of the present study was to assess hemodynamic changes and edema measured by transcardiopulmonary thermodilution in low weight newborn piglets. Additionally, the effect of early administration of sildenafil (2 mg/kg vo, 30 min after meconium aspiration) on this critical parameter was determined in the meconium aspiration syndrome model. Thirty-eight mechanically ventilated anesthetized male piglets (Sus scrofa domestica) aged 12 to 72 h (1660 ± 192 g) received diluted fresh human meconium in the airway in order to evoke pulmonary hypertension (PHT). Extravascular lung water was measured in vivo with a PiCCO monitor and ex vivo by the gravimetric method, resulting in an overestimate of 3.5 ± 2.3 mL compared to the first measurement. A significant PHT of 15 Torr above basal pressure was observed, similar to that of severely affected humans, leading to an increase in ventilatory support. The vascular permeability index increased 57 percent, suggesting altered alveolocapillary membrane permeability. Histology revealed tissue vessel congestion and nonspecific chemical pneumonitis. A group of animals received sildenafil, which prevented the development of PHT and lung edema, as evaluated by in vivo monitoring. In summary, the transcardiopulmonary thermodilution method is a reliable tool for monitoring critical newborn changes, offering the opportunity to experimentally explore putative therapeutics in vivo. Sildenafil could be employed to prevent PHT and edema if used in the first stages of development of the disease.

Double flap patch closure of VSD with elevated pulmonary vascular resistance: an experience at AFIC/NIHD

To determine the 30 days outcome measured in terms of morbidity and mortality in cases of ventricular septal defect [VSD] with increased pulmonary vascular resistance [PVR] managed with double flap patch closure. Case series. Armed Forces Institute of Cardiology [AFIC/NIHD], Rawalpindi, from December 2005 to December 2008. Forty patients with VSD having PVR 9.58 + 4.33 wood units underwent double flap patch closure. The patch was fenestrated as one half of the expected aortic annulus diameter. A separate flap patch 5 mm larger than fenestration was attached to superior upper one third margins of fenestration. The patch was placed with flap to open towards the left ventricular apex. Modified ultra filtration [MUF] was employed in every case and sildenafil was given postoperatively. The age of patients ranged from 1 to 28 years with a mean of 6.66 + 5.70 years. There were 22 males and 18 females. All patients were weaned off from inotropic and ventilatory support as earlier as possible postoperatively with intensive care unit [ICU] stay of 77.15 + 54.56 hours. Postoperative pulmonary artery pressures were reduced to 42.63 + 10.86 mmHg as compared to pre-operative pulmonary artery pressures of 88.3 + 15.2 mmHg. Postoperatively 11 patients with suprasystemic pulmonary artery pressures and desaturation went into pulmonary hypertensive crisis in which immediate 2D echo evidenced the functioning flap valve with right to left shunt. There was only one death [early] out of 40 patients with an overall mortality of 2.5% along with limited morbidity. Double flap patch is an inexpensive, easy to construct technique with low morbidity and mortality in cases of VSD with raised PVR

Traque-oclusão intra-útero: técnica cirúrgica assistida à corticoterapia promove aumento nos receptores de VEGF (Vascular Endothelial Growth Factor) em pulmões de fetos de ratas / In utero tracheal occlusion: surgical approach associated to steroid treatment increase VEGF (Vascular Endothelial Growth Factor) receptors in lungs of fetal rats

A hérnia diafragmática congênita (HDC) causa hipoplasia e hipertensãopulmonar e em geral leva a alta morbidade e mortalidade neonatal. Traqueo-oclusão fetal (TO) e corticoterapia pré-natal são alternativas para acelerar o crescimento pulmonar fetal e diminuir a hipoplasia na HDC. A produção de VEGF (Vascular Endothelial Growth Factor) está relacionada com a maturidade pulmonar e sofre alterações na HDC ainda não elucidadas.Materiais e métodos: Seis grupos de 12 fetos de ratos Spreague-Dawley foram comparados: TO, Sham, Controle, TO+Dex, Sham+Dex e Controle+Dex. No dia 18,5º foi realizada TO come sem corticoterapia utilizando dexametasona. No 21,5º dia gestacional os pesos corporal e...

Congenital diaphragmatic hernia (CDH) presents with hypoplastic lungs and usually leads to pulmonary hypertension and high neonatal mortality. Fetal tracheal occlusion (TO) and prenatal corticotherapy are alternatives to accelerate fetal pulmonary growth and decrease hypoplasia in CDH. VEGF (Vascular Endothelial Growth Factor)production and surfactant production by type II pneumocytes are related with pulmonary maturity and are altered in CDH, but little has been described about VEGF receptors. Our objective wasto quantify the receptors of VEGF (VEGFR) and type II pneumocytes, verifying the effects of TO and corticotherapy on normal lungs of fetal rats...