Clinical Trial-Ready Patient Cohorts for Multiple System Atrophy: Coupling Biospecimen and iPSC Banking to Longitudinal Deep-Phenotyping.

Multiple system atrophy (MSA) is a fatal neurodegenerative disease of unknown etiology characterized by widespread aggregation of the protein alpha-synuclein in neurons and glia. Its orphan status, biological relationship to Parkinson's disease (PD), and rapid progression have sparked interest in drug development. One significant obstacle to therapeutics is disease heterogeneity. Here, we share our process of developing a clinical trial-ready cohort of MSA patients (69 patients in 2 years) within an outpatient clinical setting, and recruiting 20 of these patients into a longitudinal "n-of-few" clinical trial paradigm. First, we deeply phenotype our patients with clinical scales (UMSARS, BARS, MoCA, NMSS, and UPSIT) and tests designed to establish early differential diagnosis (including volumetric MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, skin biopsy) or disease activity (PBR06-TSPO). Second, we longitudinally collect biospecimens (blood, CSF, stool) and clinical, biometric, and imaging data to generate antecedent disease-progression scores. Third, in our Mass General Brigham SCiN study (stem cells in neurodegeneration), we generate induced pluripotent stem cell (iPSC) models from our patients, matched to biospecimens, including postmortem brain. We present 38 iPSC lines derived from MSA patients and relevant disease controls (spinocerebellar ataxia and PD, including alpha-synuclein triplication cases), 22 matched to whole-genome sequenced postmortem brain. iPSC models may facilitate matching patients to appropriate therapies, particularly in heterogeneous diseases for which patient-specific biology may elude animal models. We anticipate that deeply phenotyped and genotyped patient cohorts matched to cellular models will increase the likelihood of success in clinical trials for MSA.

Workforce Diversity in Female Pelvic Medicine and Reconstructive Surgery: An Analysis of the American Urological Association Census Data.

OBJECTIVE: To describe the current state of workforce diversity in Female Pelvic Medicine and Reconstructive Surgery (FPMRS) using the 2014-2019 American Urological Association (AUA) census data. MATERIALS: We evaluated FPMRS workforce diversity using the AUA census data from 2014 to 2019. Underrepresented in medicine (URiM) groups were categorized as individuals who self-identified as non-Hispanic Black/African American, Hispanic, Multiracial, and Other. The FPMRS workforce was then compared to the overall urologic workforce and the other urologic subspecialties (oncology, pediatric urology, and endourology) and assessed by AUA section. RESULTS: In 2019, 602 urologists self-identified as FPMRS providers. Of these 12.4% (n = 74) were categorized as URiM urologists compared to 8% of the overall urologic workforce. Women who represent 9.9% of all urologists were overrepresented in FPMRS workforce (46.5%). FPMRS had the largest proportion of URiM and women urologists when compared to the other subspecialty areas. CONCLUSION: The FPMRS urologic subspecialty has the highest percentage of women and URiM urologists compared to all other urologic subspecialty areas. Engagement initiatives and targeted programs may offer insights into this trend. Further research is required to determine the impact of such programs in attracting URiM and women to FPMRS.

Comparative Effectiveness of Transurethral Prostate Procedures at Enabling Urologic Medication Discontinuation: A Retrospective Analysis.

OBJECTIVE: To test the hypothesis that transurethral prostate procedures (TUPPs) eliminating tissue result in greater medication discontinuation and lower de novo initiation rates than procedures inducing tissue necrosis. METHODS: Retrospective review of all men undergoing first time TUPPs at a large tertiary center from 2001 to 2016 was completed. Procedure type and urologic medication use before, 3-12 months after, and greater than 12 months after TUPP were analyzed with simple open prostatectomy as a comparator. Tissue-eliminating TUPPs included transurethral resection of the prostate and laser prostatectomy. Tissue-necrosing procedures included microwave therapy (transurethral microwave therapy) and radiofrequency ablation (transurethral needle ablation), which were grouped in analyses. Medication types were 5-alpha reductase inhibitors (5ARI), alpha blockers, anticholinergics, and beta-3 agonists (B3A). RESULTS: A total 5150 TUPPs were analyzed. Preoperative medication use significantly varied across TUPPs for 5ARI (P <.01), alpha-blockers (P .01), and anticholinergics (P .047), but not B3A (P .476). Transurethral resection of the prostate and laser prostatectomy were associated with significantly higher medication discontinuation rates and lower resumption and initiation rates compared to tissue-necrosing procedures. Relative to TUPPs, simple prostatectomy had significantly higher medication discontinuation, as well as the lowest resumption and initiation rates. CONCLUSION: Tissue-eliminating benign prostatic hyperplasia procedures were associated with better medication discontinuation, resumption, and de novo initiation rates compared to tissue-necrosing benign prostatic hyperplasia procedures.

Radiation-induced angiosarcoma after mastectomy and TRAM flap breast reconstruction.

Radiation-induced angiosarcoma of the breast is being reported with increasing frequency as a result of the increased use of radiation therapy in conjunction with breast conservation surgery. However, this entity has not been well documented in patients undergoing mastectomy. The authors present a case of angiosarcoma occurring in a patient 6 years after undergoing mastectomy for invasive duct carcinoma with immediate transverse rectus abdominis musculocutaneous flap reconstruction followed by postoperative radiation therapy. The diagnosis of angiosarcoma was made by skin biopsy performed by the patient's reconstructive surgeon on routine follow-up examination. This is the first reported case of postradiation angiosarcoma occurring in a postmastectomy breast reconstructed with autogenous tissue and it is unusual in that the cancer invaded the musculocutaneous flap. Diagnosis and management recommendations for radiation-induced angiosarcoma are discussed.