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.

Tenecteplase (TNK) has recently become a compelling alternative to alteplase. This study aims to compare the usage trends and outcomes of TNK versus alteplase in acute ischemic stroke.

We conducted retrospective analysis using the Cosmos Epic database to include ischemic stroke patients treated with intravenous thrombolysis between 1 and 1-2016 and 12-31-2023. The primary outcomes were 1) trend in the usage of alteplase vs. TNK and 2) home discharge. Secondary outcomes included 90-day mortality, in-hospital mortality, and rates of intracranial hemorrhage.

The study included 71,150 patients (mean age, 67.46 years; 50.2 % male; mean NIH Stroke Scale score, 4.34; 73 % White). A total of 52591 patients (73 %) were treated with alteplase. Over the study period, the use of alteplase decreased, whereas TNK usage increased, surpassing alteplase by mid-2022. The rate of home discharge was higher in the TNK group (59.3 % vs. 58 %; P = .002), and TNK was associated with home discharge (odds ratio [OR], 1.17; 95 % CI, 1.12-1.22). There was no significant association between TNK and 90-day mortality. Intracranial hemorrhage was more common in the TNK group. In a sensitivity analysis restricted to patients who received endovascular therapy, TNK was associated with higher odds of home discharge, lower odds of in-hospital mortality, and higher odds of intracranial hemorrhage.

Since 2022, the utilization of TNK for acute ischemic stroke in the US has increased significantly. TNK was associated with a higher likelihood of home discharge compared to alteplase. These findings support the use of TNK in clinical practice.