Pulmonary hypertension in idiopathic pulmonary fibrosis: prevalence and clinical progress

The aims of the present study are to define the prevalence of pulmonary hypertension (PH) in a cohort of idiopathic pulmonary fibrosis (IPF) patients, to investigate any correlations between systolic pulmonary artery pressure (PAPs) and functional data, to evaluate clinical progress and to compare long-term survival in IPF patients with and without PH. A population of 126 IPF patients was recruited. A high prevalence of PH (39.7%, 50/126), evaluated by echocardiography on the basis of PAPs greater than 36 mmHg, was mainly observed in smokers and female patients. Regression analysis revealed a significant correlation between PAPs greater than 50 mmHg and DLCO/VA (p = 0.0294). Mean PAPs was significantly greater one year after onset of PH (p = 0.01). 11/21 patients with FVC less than 50% had a significant increase in PAPs one year after onset of PH (p = 0.02). There was a highly significant difference between survival of IPF patients with and without PH (p = 0.0001; hazard ratio = 3.56). This study revealed that PH has a high prevalence in patients with IPF and is associated with increased risk of mortality. Early diagnosis of IPF patients with pulmonary hypertension is important, so that they can be enrolled in waiting lists for lung transplant as soon as possible

Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers

PURPOSE Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set. METHODS The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (<50 years for eoBTC, ≥50 years for aoBTC). P values were adjusted for multiple testing and considered significant at Q < 0.05 (molecular comparisons) or Q < 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis. RESULTS The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). FGFR2 fusion (15.7% in eoBTC v 5.9% in aoBTC) and NIPBL fusion (1.1% v 0%) were significantly more prevalent in eoBTC (both Q < 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; Q = 0.01) and T-cell inflammation score (FC, 17.3; Q = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; Q = 0.16), whereas IFG (NES = –1.58; Q = 0.06) and inflammatory response (NES = –1.46; Q = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, P = .004. The median OS by FGFR2 fusion (with fusion v without) was 21.7 versus 15.0 months ( P = .47) for eoBTC and 18.6 versus 12.2 months ( P < .001) for aoBTC. CONCLUSION We identified crucial differences including higher prevalence of FGFR2 fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the FGFR2 fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets. Multiomic analysis shows higher FGFR2 fusions and #immunotherapy marker variations in early-onset biliary cance

Clinical variability of respiratory pulmonary hypertension: implications for diagnosis and management

Pulmonary Hypertension (PH) associated to chronic respiratory diseases is currently classified in the 3(rd) group, as a mild to moderate form of pre-capillary PH that progressively complicates the prognosis of associated pulmonary disease. In clinical practice, however, some unresolved issues in the respiratory PH should be considered: 1) the PH heterogeneity in some respiratory diseases, such as Chronic Obstructive Pulmonary Disease (COPD), where the prevalence of unrecognized left heart disease, or chronic pulmonary thromboembolism may change the clinical classification; 2) the combining form of severe PH which often is not correlated to chronic ventilator impairment, while outcome is strictly related to pulmonary haemodynamics. The recognition of out of proportion respiratory PH in several chronic respiratory diseases which include COPD, Idiopathic Pulmonary Fibrosis (IPF), Combined Pulmonary Fibrosis and Emphysema, Obstructive Sleep Apnea (OSA), Obesity Hypoventilation Syndrome (OHS) may be important for a comprehensive clinical classification of severe respiratory PH, as well as, for the inclusion of these patients in randomized clinical trials on PH targeted therapy