Outcomes and Safety of Suprapubic vs Urethral Catheterization Following Pelvic Fascia‒Sparing Robotic Prostatectomy.

INTRODUCTION: Urethral catheter (UC) discomfort remains a burden following robotic-assisted radical prostatectomy (RARP). Suprapubic catheters (SPCs) may reduce patient discomfort and increase satisfaction. Pelvic fascia‒sparing (PFS) RARP reduces the technical challenges of intraoperative SPC placement. We examined postoperative outcomes of SPC vs UC placement following PFS-RARP. METHODS: We conducted a retrospective review of a prospective institutional review board‒approved database of PFS-RARP patients from June 2020 to December 2022 receiving SPC (n = 108) or UC (n = 104) postoperatively. Demographics and clinical and perioperative outcomes were captured. Postoperative patient-reported quality of life was measured using EPIC-CP (Expanded Prostate Cancer Index Composite for Clinical Practice). Patients with intraoperative complications or intraoperative leaks or undergoing salvage prostatectomy were excluded. Univariate and multivariate regression analyses were performed to compare outcomes. RESULTS: No significant differences in demographics or oncologic outcomes existed. There were no differences in complications, including urethral stricture or anastomotic leak. Men receiving SPC vs UC had earlier return to continence (7 vs 16 days, P < .001) and higher continence rates at catheter removal (67.6% vs 43.3%, P = .0003). On adjusted analyses, SPC was an independent predictor of continence at catheter removal (OR 2.21, P = .023). There were no differences between groups in preoperative or postoperative EPIC-CP scores, including no differences in postoperative quality of life (P = .46). CONCLUSIONS: SPC after PFS-RARP is a safe and feasible alternative to UC. SPC is associated with an earlier return to continence and higher continence rates at catheter removal. Use of SPC may increase overall patient satisfaction following PFS-RARP.

Xanthohumol increases death receptor 5 expression and enhances apoptosis with the TNF-related apoptosis-inducing ligand in neuroblastoma cell lines.

High-risk neuroblastoma (NB) is lethal childhood cancer. Published data including ours have reported the anti-proliferative effect of Xanthohumol (XN), a prenylated chalcone, in various cancer types suggesting that XN could be a useful small molecule compound against cancer. The TNF-Related Apoptosis-Inducing Ligand (TRAIL) is an endogenous ligand that is expressed in various immune cells. TRAIL mediates apoptosis through binding of transmembrane receptors, death receptor 4 (DR4) and/or death receptor 5 (DR5). Cancer cells are frequently resistant to TRAIL-mediated apoptosis, and the cause of this may be decreased expression of death receptors. This study aimed to identify combination therapies that exploit XN for NB. First, the effect of XN on cellular proliferation in human NB cell lines NGP, SH-SY-5Y, and SK-N-AS were determined via MTT assay, colony forming assay, and real-time live cell imaging confluency. XN treatment causes a statistically significant decrease in the viability of NB cells with IC50 values of approximately 12 µM for all three cell lines. Inhibition of cell proliferation via apoptosis was evidenced by an increase in pro-apoptotic markers (cleaved PARP, cleaved caspase-3/-7, and Bax) and a decrease in an anti-apoptotic marker, Bcl-2. Importantly, XN treatment inhibited PI3K/Akt pathway and associated with increased expression of DR5 by both mRNA and protein levels. Furthermore, a statistically significant synergistic reduction was observed following combination treatment (50%) compared to either TRAIL (5%) or XN (15%) alone in SK-N-AS cells. Therefore, this study shows XN treatment reduces NB cell growth via apoptosis in a dose-dependent manner, and enhanced growth reduction was observed in combination with TRAIL. This is the first study to demonstrate that XN alters the expression of DR5 as well as the synergistic effect of XN on TRAIL in NB and provides a strong rationale for further preclinical analysis.

Quantifying functional group interactions that determine urea effects on nucleic acid helix formation.

Urea destabilizes helical and folded conformations of nucleic acids and proteins, as well as protein-nucleic acid complexes. To understand these effects, extend previous characterizations of interactions of urea with protein functional groups, and thereby develop urea as a probe of conformational changes in protein and nucleic acid processes, we obtain chemical potential derivatives (µ23 = dµ2/dm3) quantifying interactions of urea (component 3) with nucleic acid bases, base analogues, nucleosides, and nucleotide monophosphates (component 2) using osmometry and hexanol-water distribution assays. Dissection of these µ23 values yields interaction potentials quantifying interactions of urea with unit surface areas of nucleic acid functional groups (heterocyclic aromatic ring, ring methyl, carbonyl and phosphate O, amino N, sugar (C and O); urea interacts favorably with all these groups, relative to interactions with water. Interactions of urea with heterocyclic aromatic rings and attached methyl groups (as on thymine) are particularly favorable, as previously observed for urea-homocyclic aromatic ring interactions. Urea m-values determined for double helix formation by DNA dodecamers near 25 °C are in the range of 0.72-0.85 kcal mol(-1)m(-1) and exhibit little systematic dependence on nucleobase composition (17-42% GC). Interpretation of these results using the urea interaction potentials indicates that extensive (60-90%) stacking of nucleobases in the separated strands in the transition region is required to explain the m-value. Results for RNA and DNA dodecamers obtained at higher temperatures, and literature data, are consistent with this conclusion. This demonstrates the utility of urea as a quantitative probe of changes in surface area (ΔASA) in nucleic acid processes.