Characteristics Associated with Treatment Response and Satisfaction in Women Undergoing OnabotulinumtoxinA and Sacral Neuromodulation for Refractory Urgency Urinary Incontinence.

PURPOSE: We sought to identify clinical and demographic characteristics associated with treatment response and satisfaction in women undergoing onabotulinumtoxinA and sacral neuromodulation therapies. MATERIALS AND METHODS: We analyzed data from the ROSETTA (Refractory Overactive Bladder: Sacral NEuromodulation versus BoTulinum Toxin Assessment) trial. Baseline participant characteristics and clinical variables were associated with 2 definitions of treatment response, including 1) a reduction in mean daily urgency incontinence episodes during 6 months and 2) a 50% or greater decrease in urgency incontinence episodes across 6 months. The OAB-S (Overactive Bladder-Satisfaction) questionnaire was used to assess satisfaction. RESULTS: A greater reduction in mean daily urgency incontinence episodes was associated with higher HUI-3 (Health Utility Index-3) scores in the onabotulinumtoxinA group and higher baseline incontinence episodes (each p <0.001) in the 2 groups. Increased age was associated with a lesser decrease in incontinence episodes in the 2 groups (p <0.001). Increasing body mass index (adjusted OR 0.82/5 points, 95% CI 0.70-0.96) was associated with reduced achievement of a 50% or greater decrease in incontinence episodes after each treatment. Greater age (adjusted OR 0.44/10 years, 95% CI 0.30-0.65) and a higher functional comorbidity index (adjusted OR 0.84/1 point, 95% CI 0.71-0.99) were associated with reduced achievement of a 50% or greater decrease in urgency incontinence episodes in the onabotulinumtoxinA group only (p <0.001 and 0.041, respectively). In the onabotulinumtoxinA group increased satisfaction was noted with higher HUI-3 score (p = 0.002) but there was less satisfaction with higher age (p = 0.001). CONCLUSIONS: Older women with multiple comorbidities, and decreased functional and health related quality of life had decreased treatment response and satisfaction with onabotulinumtoxinA compared to sacral neuromodulation for refractory urgency incontinence.

Isolated pleural effusion in severe ovarian hyperstimulation: A case report.

Assisted reproductive technology programs use controlled ovarian hyperstimulation to maximize pregnancy rates. Severe ovarian hyperstimulation syndrome is a well-known risk. Pleural effusion often accompanies severe ovarian hyperstimulation syndrome. We describe 2 cases of isolated hydrothorax without concomitant ascites and review the literature of this rare finding.

The rate of internalization of the mannose 6-phosphate/insulin-like growth factor II receptor is enhanced by multivalent ligand binding.

The cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) undergoes constitutive endocytosis, mediating the internalization of two unrelated classes of ligands, mannose 6-phosphate (Man-6-P)-containing acid hydrolases and insulin-like growth factor II (IGF-II). To determine the role of ligand valency in M6P/IGF-II receptor-mediated endocytosis, we measured the internalization rates of two ligands, beta-glucuronidase (a homotetramer bearing multiple Man-6-P moieties) and IGF-II. We found that beta-glucuronidase entered the cell approximately 3-4-fold faster than IGF-II. Unlabeled beta-glucuronidase stimulated the rate of internalization of 125I-IGF-II to equal that of 125I-beta-glucuronidase, but a bivalent synthetic tripeptide capable of occupying both Man-6-P-binding sites on the M6P/IGF-II receptor simultaneously did not. A mutant receptor with one of the two Man-6-P-binding sites inactivated retained the ability to internalize beta-glucuronidase faster than IGF-II. Thus, the increased rate of internalization required a multivalent ligand and a single Man-6-P-binding site on the receptor. M6P/IGF-II receptor solubilized and purified in Triton X-100 was present as a monomer, but association with beta-glucuronidase generated a complex composed of two receptors and one beta-glucuronidase. Neither IGF-II nor the synthetic peptide induced receptor dimerization. These results indicate that intermolecular cross-linking of the M6P/IGF-II receptor occurs upon binding of a multivalent ligand, resulting in an increased rate of internalization.

Neuroendocrine small cell uterine cervix cancer in pregnancy: long-term survival following combined therapy.

A 22-year-old woman carrying twin gestations at 30 weeks presented with preterm labor and a prolapsing cervical mass. Following Cesarean section birth, she was treated with multiagent chemotherapy followed by pelvic radiotherapy for a Stage IIA small cell cancer of the uterine cervix. She is without evidence of disease 5.5 years after diagnosis and is the first reported long-term survivor of a small cell cervical carcinoma diagnosed during pregnancy.