EmPHasis-10 health-related quality of life score predicts outcomes in patients with idiopathic and connective tissue disease-associated pulmonary arterial hypertension: results from a UK multi-centre study

Health-related quality of life (HRQoL) scores assess symptom burden in pulmonary arterial hypertension (PAH) but data regarding their role in prognostication and risk stratification are limited. We assessed these relationships using the emPHasis-10 HRQoL measure. 1745 patients with idiopathic or connective tissue disease-associated PAH who had completed emPHasis-10 questionnaires between 2014–17 at 6 UK referral centres were identified. Correlations with exercise capacity and WHO functional class (FC) were assessed, and exploratory risk stratification thresholds were tested. Moderate correlations were seen between emPHasis-10 scores and 6-minute walk distance (r=−0.546), incremental shuttle walking distance (r=−0.504) and WHO FC (r=0.497; p all <0.0001). Distribution of emPHasis-10 differed significantly between each WHO FC (p all <0.0001). At multivariate analysis, emPHasis-10, but not WHO FC, was an independent predictor of mortality. In a risk stratification approach, scores of 0–16, 17–33 and 34–50 identified incident patients with one-year mortality of 5%, 10% and 23%, respectively. Survival of patients in WHO FC III could be further stratified using an emPHasis-10 score ≥34 (p<0.01). At follow-up, patients with improved emPHasis-10 had improved exercise capacity (p<0.0001), and patients who transitioned risk groups demonstrated similar survival to patients originally in those risk groups. The emPHasis-10 score is an independent prognostic marker in patients with idiopathic or connective tissue disease-associated PAH. It has utility in risk stratification in addition to currently used parameters. Improvement in emPHasis-10 score is associated with improved exercise capacity

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

CD103+ tumor-infiltrating lymphocytes are tumor-reactive intraepithelial CD8+ T cells associated with prognostic benefit and therapy response in cervical cancer

Contains fulltext : 178711.pdf (Publisher’s version ) (Open Access)Human papilloma virus (HPV)-induced cervical cancer constitutively expresses viral E6/E7 oncoproteins and is an excellent target for T cell-based immunotherapy. However, not all tumor-infiltrating T cells confer equal benefit to patients, with epithelial T cells being superior to stromal T cells. To assess whether the epithelial T cell biomarker CD103 could specifically discriminate the beneficial antitumor T cells, association of CD103 with clinicopathological variables and outcome was analyzed in the TCGA cervical cancer data set (n = 304) and by immunohistochemistry (IHC) in an independent cohort (n = 460). Localization of CD103+ cells in the tumor was assessed by immunofluorescence. Furthermore, use of CD103 as a response biomarker was assessed in an in vivo E6/E7+ tumor model. Our results show that CD103 gene expression was strongly correlated with cytotoxic T cell markers (e.g. CD8/GZMB/PD1) in the TCGA series. In line with this, CD103+ cells in the IHC series co-expressed CD8 and were preferentially located in cervical tumor epithelium. High CD103+ cell infiltration was strongly associated with an improved prognosis in both series, and appeared to be a better predictor of outcome than CD8. Interestingly, the prognostic benefit of CD103 in both series seemed limited to patients receiving radiotherapy. In a preclinical mouse model, HPV E6/E7-targeted therapeutic vaccination in combination with radiotherapy increased the intratumoral number of CD103+ CD8+ T cells, providing a potential mechanistic basis for our results. In conclusion, CD103 is a promising marker for rapid assessment of tumor-reactive T cell infiltration of cervical cancers and a promising response biomarker for E6/E7-targeted immunotherapy