ABSTRACT
BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, cureless disease, characterized by increased pulmonary vascular resistance and remodeling, with subsequent ventricular dilatation and failure. New therapeutic targets are being investigated for their potential roles in improving PAH patients' symptoms and reversing pulmonary vascular pathology. METHOD: We aimed to address the available knowledge from the published randomized controlled trials (RCTs) regarding the role of Rho-kinase (ROCK) inhibitors, bone morphogenetic protein 2 (BMP2) inhibitors, estrogen inhibitors, and AMP-activated protein kinase (AMPK) activators on the PAH evaluation parameters. This systematic review (SR) was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CDR42022340658) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Overall, 5092 records were screened from different database and registries; 8 RCTs that met our inclusion criteria were included. The marked difference in the study designs and the variability of the selected outcome measurement tools among the studies made performing a meta-analysis impossible. However, the main findings of this SR relate to the powerful potential of the AMPK activator and the imminent antidiabetic drug metformin, and the BMP2 inhibitor sotatercept as promising PAH-modifying therapies. There is a need for long-term studies to evaluate the effect of the ROCK inhibitor fasudil and the estrogen aromatase inhibitor anastrozole in PAH patients. The role of tacrolimus in PAH is questionable. The discrepancy in the hemodynamic and clinical parameters necessitates defining cut values to predict improvement. The differences in the PAH etiologies render the judgment of the therapeutic potential of the tested drugs challenging. CONCLUSION: Metformin and sotatercept appear as promising therapeutic drugs for PAH. CLINICAL TRIALS REGISTRATION: This work was registered in PROSPERO (CDR42022340658).
Subject(s)
Hypertension, Pulmonary , Metformin , Pulmonary Arterial Hypertension , Humans , Pulmonary Arterial Hypertension/drug therapy , Hypertension, Pulmonary/drug therapy , AMP-Activated Protein Kinases/therapeutic use , Familial Primary Pulmonary Hypertension , Estrogens/therapeutic use , Metformin/therapeutic useABSTRACT
BACKGROUND: Weaning failure is common in mechanically ventilated patients, and if ultrasound can predict weaning outcome remains controversial. The purpose of this study was to evaluate the diaphragmatic function (thickness and excursion) measured by ultrasound as a predictor of the extubation outcome. METHODS: We included 62 mechanically ventilated patients from the chest intensive care unit in this study. Sixty-two patients who successfully passed the spontaneous breathing trial (SBT) were enrolled. The transthoracic ultrasound of the diaphragm was performed during an SBT to the assess diaphragmatic function (excursion and thickness), and they were classified into the successful extubation group and the failed extubation group. RESULTS: There was a statistically significant increase in the successful extubation group in the diaphragmatic excursion and thickness fraction (p<0.001), a statistically significant negative correlation between the diaphragmatic function and the duration of the mechanical ventilation, and a statistically significant negative correlation between the diaphragmatic excursion and the Acute Physiology and Chronic Health Evaluation II. The diaphragmatic excursion cutoff value predictive of weaning was 1.25 cm, with a specificity of 82.1% and a sensitivity of 97.1% respectively, and the diaphragmatic thickness cut-off value predictive of weaning was 21.5%, with a specificity of 60.7% and a sensitivity of 91.2%, respectively. CONCLUSION: The diaphragmatic ultrasonography was found to be a promising tool for predicting the extubation outcome for mechanically ventilated patients.
