Inova Health Care Services

Prostate cancer is one of the most frequently diagnosed cancers in men. Prostate tumor staging and disease aggressiveness are evaluated based on the Gleason scoring system, which is further used to direct clinical intervention. The Gleason scoring system provides an estimate of tumor aggressiveness through quantitation of the serum level of prostate specific antigen (PSA) and histologic assessment of Grade Group, determined by the Gleason Grade of the tumor specimen.

To improve our understanding of the proteomic characteristics differentiating low- versus high-grade prostate cancer tumors, we performed a deep proteomic characterization of laser microdissected epithelial and stromal subpopulations from surgically resected tissue specimens from patients with Gleason 6 (n = 23 specimens from n = 15 patients) and Gleason 9 (n = 15 specimens from n = 15 patients) prostate cancer via quantitative high-resolution liquid chromatography-tandem mass spectrometry analysis.

In total, 789 and 295 grade-specific significantly altered proteins were quantified in the tumor epithelium and tumor-involved stroma, respectively. Benign epithelial and stromal populations were not inherently different between Gleason 6 versus Gleason 9 specimens. Notably, 598 proteins were exclusively significantly altered between Gleason 9 (but not Gleason 6) tumor-involved stroma and benign stroma, including several proteins involved in cholesterol biosynthesis and nucleotide metabolism.

Proteomic alterations between Gleason 6 versus Gleason 9 were exclusive to the disease microenvironment, observed in both the tumor epithelium and tumor-involved stroma. Further, the molecular alterations measured in the tumor-involved stroma from Gleason 9 cases relative to the benign stroma have unique significance in disease aggressiveness, development, and/or progression. Our data provide supportive evidence of a need for further investigations into targeting stromal reservoirs of cholesterol and/or deoxynucleoside triphosphates in PCa tumors and further highlight the necessity for independent examination of the TME epithelial and stromal compartments.

Pulmonary hypertension (PH) is associated with morbidity and mortality in patients with interstitial lung disease (ILD). Several prediction models have been proposed to predict PH in ILD patients. We sought to discern how previously described prediction models perform in predicting PH in patients with ILD.

Patients with ILD who completed a baseline right heart catheterization, from Inova Fairfax Hospital, Northwestern Memorial Hospital, and Asan Medical Center in Korea were enrolled. The performance of various prediction models (FORD model, the FORD calculator, the PH-ILD Detection tool, and the mean pulmonary artery pressure prediction model) were assessed using receiver operating characteristic (ROC) curves and area under the receiver operating characteristic curve (AUROC). There were four definitions of pulmonary hypertension against which the models were evaluated.

There were a total of 192 patients with ILD, of whom 32.8% (n = 63/192) met the modified 5th world symposium on PH definition of precapillary PH. Among the models assessed, the FORD calculator had an AUROC (0.733) that was marginally highest. Subgroup analysis revealed that the FORD index had the highest AUROC (0.817) in patients with idiopathic pulmonary fibrosis, while the FORD calculator had the highest AUROC (0.751) in patients with non-IPF ILD.

The FORD model can be used to predict group 3 PH in both IPF patients and non-IPF ILD patients. It could serve as a tool for ILD patient selection for right heart catheterization as well as an enrichment tool for clinical trials targeting the pulmonary vasculature.

The relationship between psychological health and cardiovascular health (CVH) during pregnancy is not well characterized.

The purpose of this study was to perform a cross-sectional analysis in order to assess the relationships between psychological distress and CVH among pregnant individuals in the United States.

U.S. National Health Interview Survey (2013-2018) data were used for the analyses. The sample included all pregnant participants aged ≥18 years, but excluded those with missing data for the exposure, outcome, or covariates. Psychological health was measured with the 6-item Kessler scale, and severe psychological distress was defined as 6-item Kessler scale ≥13. CVH was quantified using the American Heart Association's Life's Essential 8; as detailed dietary data were unavailable, a 7-item score was used (higher scores indicated worse CVH). Multivariable Poisson regression tested associations between severe psychological distress and CVH, adjusting for potential confounders including age, race/ethnicity, sexual orientation, education level, family income, any known cardiovascular conditions, and insurance.

Among 1,110 pregnant individuals (representing >1.5 million pregnant individuals each year of the survey), 3.5% reported severe psychological distress (95% CI: 2.2%-5.5%), 21.7% reported moderate psychological distress (95% CI: 18.8%-24.9%), and 74.9% reported either mild or no psychological distress (95% CI: 71.4%-78.0%). Individuals reporting moderate psychological distress (adjusted rate ratio: 1.25 [95% CI: 1.13-1.38], P < 0.001) or severe psychological distress (adjusted rate ratio: 1.42 [95% CI: 1.20-1.68], P < 0.001) had lower CVH scores compared to those with mild or no psychological distress. A stepwise relation was observed between the severity of psychological distress and CVH.

We observed a strong association between psychological distress and suboptimal CVH during pregnancy, highlighting the need to manage psychological health along with CVH in pregnant individuals.