Understanding a decade of safety reporting for sacral neuromodulation in the Food and Drug Administration Manufacturer and User Facility Device Experience database.

INTRODUCTION: Over 350 000 sacral neuromodulation (SNM) devices have been implanted since approval by the Food and Drug Administration (FDA) in 1998. SNM technology and clinical applications have evolved, with minimal safety updates after initial trials. We aim to provide an updated overview of real-world SNM safety. These insights will guide informed consent, preoperative counseling, and patient expectation-setting. MATERIALS AND METHODS: The FDA Manufacturer and User Facility Device Experience (MAUDE) database is a repository for medical device safety reports. We performed MAUDE categorical (1/1/98-12/31/10) and keyword (1/1/11-9/30/21) searches for "Interstim." A random sample of 1000 reports was reviewed and categorized by theme. To corroborate our MAUDE database analysis, a legal librarian searched the Public Access to Court Electronic Records (PACER) database, as well as Bloomberg Law's dockets database for all lawsuits related to SNM devices. RESULTS: Our search of the MAUDE database returned 44 122 SNM-related adverse events (AEs). The figure illustrates the prevalence of event categories in the random sample. The largest proportion of reports (25.6%) related to a patient's need for assistance with device use, followed by loss/change of efficacy (19.0%). Interestingly, a fall preceded issue onset in 32% of non-shock pain, 30% of lead/device migration, and 27% of painful shock reports. Our legal search revealed only four lawsuits: one for patient complications after an SNM device was used off-label, one case of transverse myelitis after implant, one for device migration or poor placement, and the fourth claimed the device malfunctioned requiring removal and causing permanent injury. CONCLUSIONS: This review confirms the real-world safety of SNM devices and very low complication rates as seen in the original clinical trials. Our findings indicate that 43.2% (95% confidence interval 40.1%-46.3%) of SNM "complications" are not AEs, per se, but rather reflect a need for improved technical support or more comprehensive informed consent to convey known device limitations to the patient, such as battery life. Similarly, the number of lawsuits is shockingly low for a device that has been in the market for 24 years, reinforcing the safety of the device. Legal cases involving SNM devices seem to relate to inappropriate patient selection-including at least one case in which SNM was used for a non-FDA approved indication-lack of appropriate follow-up, and/or provider inability to assist the patient with utilizing the device after implantation.

PSA density is associated with BPH cellular composition.

BACKGROUND: Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making. METHODS: The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression. RESULTS: The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml2 associated with a glandular composition of ≤30% with 76% sensitivity. CONCLUSIONS: PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.

Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes.

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy.