The Role of Serial Right Heart Catheterization Survey in Patients Awaiting Heart Transplant on Ventricular Assist Device.

Current guidelines recommend serial right heart catheterization (RHC) to survey pulmonary hypertension in patients awaiting heart transplant. However, the role and impact of this surveillance is unclear in patients with a left ventricular assist device (LVAD). We reviewed our surveillance RHC protocol to determine whether useful data were obtained to justify the risks of serial invasive procedures (i.e., excessive bleeding). Between January 2015 and December 2018, 78 patients who received an LVAD as bridge-to-transplant (BTT) were included in this study. Routine RHC surveillance was performed every 6 months. Hemodynamic variables were retrospectively collected and reviewed. In 78 patients, 205 RHCs were analyzed. Median patient age was 54 years (IQR 46-61), and 64 (82%) were male. Thirty-six patients (46%) had pulmonary vascular resistance (PVR) ≤ 3 Wood units (WUs), and 42 patients (54%) had PVR > 3 WUs before LVAD. After LVAD implantation, mean PVR decreased by 36% from 3.8 ± 2.1 to 2.4 ± 1.1 WUs (p < 0.001) at 6 months and stabilized below 3 WUs at all post-LVAD time points. Four patients (11%) with pre-LVAD PVR ≤ 3 and 16 patients (38%) with a pre-LVAD PVR > 3 had PVR > 3 at least once during RHC survey. Of the 56 (76%) transplanted patients, six (40%) of 15 patients with a post-LVAD PVR >3 at least once developed moderate-to-severe right ventricular dysfunction. Although PVR significantly decreased after LVAD implant, PVR values fluctuated, particularly for those with pre-LVAD PVR > 3.0 WUs. Routine RHC appears valid for all BTT patients.

Engineering 'Enzymelink' for screening lead compounds to inhibit mPGES-1 while maintaining prostacyclin synthase activity.

Aim: This study investigated our Enzymelinks, COX-2-10aa-mPGES-1 and COX-2-10aa-PGIS, as cellular cross-screening targets for quick identification of lead compounds to inhibit inflammatory PGE2 biosynthesis while maintaining prostacyclin synthesis. Methods: We integrated virtual and wet cross-screening using Enzymelinks to rapidly identify lead compounds from a large compound library. Results: From 380,000 compounds virtually cross-screened with the Enzymelinks, 1576 compounds were identified and used for wet cross-screening using HEK293 cells that overexpressed individual Enzymelinks as targets. The top 15 lead compounds that inhibited mPGES-1 activity were identified. The top compound that specifically inhibited inflammatory PGE2 biosynthesis alone without affecting COX-2 coupled to PGI2 synthase (PGIS) for PGI2 biosynthesis was obtained. Conclusion: Enzymelink technology could advance cyclooxygenase pathway-targeted drug discovery to a significant degree.

Predicting Chronic Subdural Hematoma Resolution and Time to Resolution Following Surgical Evacuation.

Background: Growing evidence suggests that chronic subdural hematoma (CSDH) may have long-term adverse effects even after surgical evacuation. Hematoma recurrence is commonly reported as a short-term, postoperative outcome measure for CSDH, but other measures such as hematoma resolution may provide better insight regarding mechanisms behind longer-term sequelae. This study aims to characterize postoperative resolution times and identify predictors for this relatively unexplored metric. Methods: Consecutive cases (N = 122) of burr hole evacuation for CSDH by a single neurosurgeon at Columbia University Irving Medical Center from 2000 to 2019 were retrospectively identified. Patient characteristics, presenting factors, and date of hematoma resolution were abstracted from the electronic health record. Outcome measures included CSDH resolution at 6 months, surgery-to-resolution time, and inpatient mortality. Univariate and multivariate analyses were performed to determine predictors of outcome measures. Results: Hematoma resolution at 6 months was observed in 58 patients (47.5%), and median surgery-to-resolution time was 161 days (IQR: 85-367). Heavy drinking was predictive of non-resolution at 6 months and longer surgery-to-resolution time, while increased age was predictive of non-resolution at 6 months. Antiplatelet agent resumption was associated with non-resolution at 6 months and longer surgery-to-resolution time on univariate analysis but was not significant on multivariate analysis. Conclusion: Postoperative resolution times for most CSDHs are on the order of several months to a year, and delayed resolution is linked to heavy drinking and advanced age. Subsequent prospective studies are needed to directly assess the utility of hematoma resolution as a potential metric for long-term functional and cognitive outcomes of CSDH.

Differential expression of microRNA and arachidonic acid metabolism in aspirin-treated human cardiac and peri-cardiac fat-derived mesenchymal stem cells.

Aspirin is a widely used drug with anti-coagulating and anti-inflammatory effects on atherosclerotic vascular disease. The goal of this study was to investigate expression of microRNA (miR) in association with changes in arachidonic acid (AA) metabolism in cardiac and surrounding fat mesenchymal stem cells (MSCs) treated with or without aspirin. Aspirin-targeted endogenous lipid metabolites that impact specific miRNA expression were examined by mass spectrometry. The pattern of miR expression was characterized using a microarray of 1100 miRs. There were a dozen miRs expressed differentially in MSCs from human myocardium and peri-myocardial fat tissue at baseline, including hsa-miR-1307-3p, 765, 4739, 3613-3p, 4281, 6816-5p, 2861, and 146b-5p. After exposure to aspirin, cardiac MSCs expressed an array of of miRs (eg, hsa-miR-4734, 10a-5p, 4267, 3197, and 3182), while generation of their endogenous AA metabolites was depressed. However, in the peri-cardiac adipose tissue-derived MSCs, treatment with the same doses of aspirin caused mild changes in the miR expression levels. In conclusion, MSCs from human myocardium and peri-myocardial fat tissue respond differentially to aspirin treatment by alterations in miR expression and AA metabolism. The study further raises an intriguing issue as to whether the copious amounts of aspirin taken worldwide by patients with cardiovascular disease may have direct impacts on their heart repair processes by regulation of stromal cell miR expression and AA metabolism.