Pulmonary artery denervation versus conventional therapies for PAH: a systematic review and updated network meta-analysis.

AIMS: A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta-analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies. METHODS AND RESULTS: According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta-analyses. Data were extracted and curated for Bayesian network meta-analysis. The primary outcome was the change in the 6-min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (-77.76 m, 95% CI: -102.04 to -54.34 m), Macitentan (-65.32 m, 95% CI: -95.34 to -36.1 m), Bosentan (-64.5 m, 95% CI: -94.7 to -35.07 m), Iloprost (-62.66 m, 95% CI: -99.48 to -27.13 m), Oxygen (-62.42 m, 95% CI: -100.01 to -25.78 m), Treprostinil (-62.01 m, 95% CI: -89.04 to -35.61 m), Riociguat (-60.59 m, 95% CI: -86.11 to -35.98 m), Selexipag (-47.2 m, 95% CI: -85.61 to -10.19 m), Sildenafil (-44.92 m, 95% CI: -74.43 to -16.15 m), or Sitaxsentan (-39.53 m, 95% CI: -78.99 to -0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re-hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions. CONCLUSIONS: Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual-drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

Metabolic dysfunction-associated steatotic liver disease-related hepatic fibrosis increases risk of insulin resistance, type 2 diabetes, and chronic kidney disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) (previously called nonalcoholic fatty liver disease, NAFLD) is associated with cardiometabolic risk factors and chronic kidney disease (CKD). However, evidence is lacking regarding whether the severity of fibrosis is affected by these risk factors and diseases and to what degree. We aimed to determine the correlation between these factors and vibration-controlled transient elastography-determined liver stiffness measurements (LSMs) and controlled attenuation parameter (CAP) values in a sample of the US population. Data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey were pooled. The association between LSM and cardiometabolic risk factors and CKD was assessed using generalized linear or logistic regression analyses. In multivariate regression analyses, CAP and BMI were adjusted as confounders. Of 3647 participants, 2079 (57.1%) had NAFLD/MASLD [weighted prevalence 54.8%; 95% confidence interval (CI) 51.8-57.9%]; the weighted prevalence of significant fibrosis (LSM ≥ 7.9 kPa) was 9.7% (95% CI 8.2-11.3%). Log LSM was associated with higher levels of homeostatic model assessment of insulin resistance ( ß â€…= 2.19; P  = 0.017), hepatic steatosis (CAP > 248 dB/m) [odds ratio (OR) 3.66; 95% CI 2.22-6.02], type 2 diabetes (OR 2.69; 95% CI 1.72-4.20), and CKD (OR 1.70; 95% CI 1.24-2.34). These correlations did not change notably after adjustments were made for waist circumference, CAP, and BMI. LSM and CAP, although influenced by waist circumference and BMI, are good indicators of hepatic fibrosis and steatosis. LSM is associated with insulin resistance, diabetes, and CKD independent of hepatic steatosis and obesity.