The Correlation of Diabetes Mellitus and Urinary Retention From Intravesical OnabotulinumtoxinA Injection for Overactive Bladder.

IMPORTANCE AND OBJECTIVES: The objective was to determine whether patients with diabetes mellitus (DM) treated with intravesical onabotulinumtoxinA (BoNT) injection for overactive bladder (OAB) had increased urinary retention requiring clean intermittent catheterization (CIC), as well as the impact of disease duration and severity. We hypothesize that patients with DM will have higher rates of retention after BoNT injection. STUDY DESIGN: We performed a retrospective cohort analysis of women in the Kaiser Permanente Southern California Health System who underwent BoNT injection for OAB, excluding women with a history of urinary retention or neurogenic bladder. RESULTS: We identified 565 patients, 410 in the control group and 155 in the DM group. No significant difference was found in the rate of CIC (9% in the control group versus 5.8% in the DM group, P = 0.2), voiding dysfunction, and peak postprocedure postvoid residual volume (PVR). Patients with diabetes had a significantly increased rate of postprocedure urinary tract infection (UTI; 27.6% versus 38.1%, P = 0.02). Urinary tract infection was significantly associated with urinary retention (adjusted odds ratio [OR], 2.26; 95% confidence interval [CI], 1.02-4.99; P = 0.045) and peak PVR ≥200 mL (adjusted OR, 2.42; 95% CI, 1.15-5.06; P = 0.019). Diabetic disease duration and severity were not a predictor of urinary retention, elevated PVR, or voiding dysfunction; however, the presence of ≥1 disease-related complication was a predictor of UTI (adjusted OR, 2.81; 95% CI, 1.34-5.91; P = 0.006). CONCLUSIONS: Diabetic patients had a similar rate of urinary retention requiring CIC after BoNT injection for OAB compared with nondiabetic patients. Diabetic patients had an increased risk of UTI based on disease severity.

Feasibility of combining pelvic reconstruction with gynecologic oncology-related surgery.

INTRODUCTION AND HYPOTHESIS: At our institution, every patient seen by the gynecologic oncology service is screened for pelvic floor dysfunction. This study was aimed at determining if a combined surgical approach by gynecologic oncology and urogynecology services at our institution was feasible and safe for this patient population. METHODS: We performed a retrospective review of patients undergoing combined surgery by gynecologic oncology and urogynecology services at our institution from 2013 to 2021. Perioperative variables, postoperative adverse events, and long-term outcomes were assessed, and descriptive statistics were performed. RESULTS: From 20 December 2013 to 29 January 2021, a total of 102 patients underwent concurrent surgical repair of pelvic organ prolapse and/or stress urinary incontinence. Seventy-three patients (71.6%) had normal/benign pathologic conditions, and 29 (28.4%) had premalignant/malignant pathologic conditions. Ten patients (9.8%) had a postoperative complication, including reoperation for exposed midurethral sling (4.9%), urinary retention requiring midurethral sling release (2.9%), reoperation for hemoperitoneum (1.0%), and anemia requiring blood transfusion (1.0%). Nine complications occurred in patients with benign/normal pathologic conditions (12.3%), and one complication occurred in patients with pre-malignant/malignant pathologic conditions (3.4%). CONCLUSIONS: In our single-institution experience, concurrent gynecologic oncology and pelvic floor reconstructive surgery were safe and feasible in combination with no reported major morbidity events.

A Critical Role of Ser26 Hydrogen Bonding in Aß42 Assembly and Toxicity.

Amyloid ß-protein (Aß) assembly is a seminal process in Alzheimer's disease. Elucidating the mechanistic features of this process is thought to be vital for the design and targeting of therapeutic agents. Computational studies of the most pathologic form of Aß, the 42-residue Aß42 peptide, have suggested that hydrogen bonding involving Ser26 may be particularly important in organizing a monomer folding nucleus and in subsequent peptide assembly. To study this question, we experimentally determined structure-activity relationships among Aß42 peptides in which Ser26 was replaced with Gly, Ala, α-aminobutryic acid (Abu), or Cys. We observed that aliphatic substitutions (Ala and Abu) produced substantially increased rates of formation of ß-sheet, hydrophobic surface, and fibrils, and higher levels of cellular toxicity. Replacement of the Ser hydroxyl group with a sulfhydryl moiety (Cys) did not have these effects. Instead, this peptide behaved like native Aß42, even though the hydropathy of Cys was similar to that of Abu and very different from that of Ser. We conclude that H bonding of Ser26 is the factor most important in its contribution to Aß42 conformation, assembly, and subsequent toxicity.

No Acute Changes in LVEF Observed With Concurrent Trastuzumab and Breast Radiation With Low Heart Doses.

INTRODUCTION/BACKGROUND: Treatment for HER2-postitive breast cancer often includes trastuzumab, breast/chest wall (CW) radiation (RT), and anthracyclines, all of which have cardiac toxicity. We aimed to evaluate the relationship between heart dose and acute left ventricular ejection fraction (LVEF) changes in patients who received concurrent trastuzumab and breast/CW RT with and without anthracycline use. PATIENTS AND METHODS: We retrospectively reviewed all nonmetastatic breast cancer patients from 2008 to 2015 who received concurrent trastuzumab and breast/CW RT. Baseline LVEF was compared with the LVEF closest to treatment completion as well as with the lowest post-treatment LVEF. LVEF changes were correlated with laterality, heart dosimetric parameters, and doxorubicin use. RESULTS: Eighty-eight patients were included in our analysis. The median follow-up was 45 months. Forty-one patients were right-sided and 47 left-sided. Thirty-one patients received doxorubicin, 16 right-sided and 15 left-sided. Mean heart dose was 1.10 Gy and 3.63 Gy for right- and left-sided patients, respectively (P < .001). In the entire cohort, a significant LVEF decrease of 3.0% was observed pre- and post-treatment. There was a significant effect of doxorubicin (P = .013) and a nonsignificant effect of RT laterality (P = .088) on LVEF change. The test of interaction between doxorubicin and laterality was not significant (P = .90). No significant association was found between LVEF change and heart dosimetric parameters, including percent volume of heart receiving 5 Gy (V5), 10 Gy (V10), 20 Gy (V20), and 45 Gy (V45), and maximum dose. Similar results were found when baseline LVEF was compared with the lowest post-treatment LVEF. CONCLUSION: With cardiac doses < 4 Gy, declines in LVEF were not related to tumor laterality or heart dosimetric parameters. Statistically significant LVEF decreases were mainly attributed to doxorubicin.