Thapa, Prabin

Abstract Disclosure: K.N. Rachmasari: None. P. Thapa: None. D. Sighoko: Employee; Self; Horizon Therapeutics. L. Abdul Jabbar: None. M.N. Stan: None. Objective: To describe the epidemiology of Thyroid Eye Disease (TED). Methods: A population-based cohort of all Olmsted County, Minnesota, residents who had newly diagnosed TED between April 3, 2002, and December 31, 2021, was identified through the medical diagnostic index of the Rochester Epidemiology Project. Individuals aged 18 years and older were included. Incidence rates and point prevalence were calculated. Results: We identified 137 incident patients, of whom 124 (90.5%) were female (p < 0.0001). The overall incidence was 6.24 cases/100,000 person-years in Olmsted County, corresponding to 6.25 cases/100,000 person-years for the US population (age and sex adjusted incidence). Women had higher incidence (10.94 cases/ 100,000 person-years) compared to men (1.22 cases/100,000 person-years). The distribution of incidence rates by ten-year age groups demonstrated peak incidence rates in the age groups 70 to 79 years (17.94 cases/100,000 person-years for women compared with 4.04 cases for men). The majority of cases (77/137) occurred between 50-79 years of age. No clear trend was identified for the yearly incidence between 2002 and 2021. The overall estimated point prevalence per 100,000 was 65.6 (95% CI, 57.8 – 72.9). Prevalence was 117.6 (95% CI, 96.5 – 141.4) for females and 11.2 (95% CI, 5.1 – 21.2) for males (p < 0.0001). Conclusions: Incidence rates for TED remained stable and significant over the last 2 decades. Majority of disease burden is present after the age of 50 with the peak between 70-79 years, a decade later than in the previous study from our population (1). Based on reported incidence and prevalence of Graves’ disease (2), our data indicates that TED continues to affect about 20-30% of that population and appropriate resources should be devoted to furthering education, management, and research into this condition. References: 1. Bartley GB, Fatourechi V, Kadrmas EF, et al. The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota. Am J Ophthalmol 1995;120(4):511-7, doi:10.1016/s0002-9394(14)72666-2 2. Hussain YS, Hookham JC, Allahabadia A, et al. Epidemiology, management and outcomes of Graves' disease-real life data. Endocrine 2017;56(3):568-578, doi:10.1007/s12020-017-1306-5 Presentation: Friday, June 16, 2023

Abstract Funding Acknowledgements Type of funding sources: None. Background Severe aortic-stenosis (AS) is the guideline-based indication for aortic-valve-replacement (AVR) performance, which has markedly increased with transcatheter approaches, suggesting possible increasing AS incidence. However, reported secular trends of AS incidence remain contradictory, uncertain and lacking quantitative Doppler-Echocardiographic ascertainment. Thus, population-based trends in presentation, treatment and outcome are unknown. Methods All adults residents our County (MN,USA) diagnosed with incident (first-diagnosis) severe AS based on quantitative Doppler-Echocardiography (aortic-valve-area≤1cm2, aortic-valve-area-index≤0.6cm2/m2, mean-gradient≥40mmHg, peak-velocity≥4m/s, Doppler-velocity-index≤0.25) between 1997–2016, were accounted for and trends for incidence, presentation, treatment and outcome analysed. Results Incident severe-AS was diagnosed in 1069 community-residents over 20-years. Incidence-rate was 52.5[49.4–55.8] per 100.000 patient/year, slightly higher in male vs. female and was almost unchanged after age and sex adjustment for the US population 53.8[50.6–57.0] per-100000 residents/year. Over 20-years severe AS-incidence remained stable (p = 0.20) but absolute-burden of incident-cases markedly increased (p = 0.0004) due to population growth. Incidence-trend differed by sex, stable in men (incidence-rate-ratio 0.99, p = 0.72) but declining in women: (incidence-rate-ratio 0.93, p = 0.024). AS clinical-presentation, age, symptoms, comorbidity, ventricular size/function, valve-area-index, low-flow or low-ejection-fraction AS, remained stable. Over the study 20 years, AVR performance grew (1997–2001 to 2012–2016, at 3-month:14% to 21%, p = 0.02; at 1-year 19% to 33%,p<0.0001), and was more prompt (from 1.3[0.11–3.3]years in 1997–2001 to 0.48[0.15–2.11]years in 2013–2016, p = 0.001) but severe AS undertreatment remained prominent (>40%). Early-AVR (within 3-months) was associated with survival benefit (adjusted-hazard-ratio 0.55[0.42–0.71], p<0.0001) stable throughout the 20-years. Despite these improvements, overall mortality, 8.3% within 3-months, 17.8% within 1-year, 36% within 3-years, was swift, considerable and unabated (all p≥0.44) throughout the 20-year study. Conclusion Over 20 years, the population incidence of severe-AS remained stable with increased absolute case-burden purely related to population growth. Despite stable severe-AS presentation, AVR performance grew notably, but while declining, undertreatment remained substantial and disease-lethality did not decline. These findings have important population-health management implications.

548 Background: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. Methods: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher’s exact test and postoperative survival using Kaplan–Meier survival curves and Cox regression model. Results: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06–5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18–6.04, p = 0.019). Conclusions: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

Background: Mitral valve prolapse (MVP) is responsible for a considerable disease burden but is widely heterogeneous. The lack of a comprehensive prognostic instrument covering the entire MVP spectrum, encompassing the quantified consequent degenerative mitral regurgitation (DMR), hinders clinical management and therapeutic trials. Methods: The new Mitral Regurgitation International Database Quantitative (MIDA-Q) registry enrolled 8187 consecutive patients (ages 63±16 years, 47% women, follow-up 5.5±3.3 years) first diagnosed with isolated MVP, without or with DMR quantified prospectively (measuring effective regurgitant orifice [ERO] and regurgitant volume) in routine practice of 5 tertiary care centers from North America, Europe, and the Middle East. The MIDA-Q score ranges from 0 to 15 by accumulating guideline-based risk factors and DMR severity. Long-term survival under medical management was the primary outcome end point. Results: MVP was associated with DMR absent/mild (ERO <20 mm 2 ) in 50%, moderate (ERO 20–40 mm 2 ) in 25%, and severe or higher (ERO ≥40 mm 2 ) in 25%, with mean ERO 24±24 mm 2 , regurgitant volume 37±35 mL. Median MIDA-Q score was 4 with a wide distribution (10%–90% range, 0–9). MIDA-Q score was higher in patients with EuroScore II ≥1% versus <1% (median, 7 versus 3; P < 0.0001) but with wide overlap (10%–90% range, 4–11 versus 0–7) and mediocre correlation ( R 2 0.18). Five-year survival under medical management was strongly associated with MIDA-Q score, 97±1% with score 0, 95±1% with score 1 to 2, 82±1% with score 3 to 4, 67±1% with score 5 to 6, 60±1% with score 7 to 8, 44±1% with score 9 to 10, 35±1% with score 11 to 12, and 5±4% with MIDA-Q score ≥13, with hazard ratio 1.31 [1.29–1.33] per 1-point increment. Excess mortality with higher MIDA-Q scores persisted after adjustment for age, sex, and EuroScore II (adjusted hazard ratio, 1.13 [1.11–1.15] per 1-point increment). Subgroup analysis showed persistent association of MIDA-Q score with mortality in all possible subsets, in particular, with EuroScore II<1% (hazard ratio, 1.08 [1.02–1.14]) or ≥1% (hazard ratio, 1.11 [1.08–1.13]) and with no/mild DMR (hazard ratio, 1.14 [1.10–1.19]) or moderate/severe DMR (hazard ratio, 1.13 [1.10–1.16], all per 1-point increment with P <0.0001). Nested-model and bootstrapping analyses demonstrated incremental prognostic power of MIDA-Q score (all P <0.0001). Conclusions: This large, international cohort of isolated MVP, with prospective DMR quantification in routine practice, demonstrates the wide range of risk factor accumulation and considerable heterogeneity of outcomes after MVP diagnosis. The MIDA-Q score is strongly, independently, and incrementally associated with long-term survival after MVP diagnosis, irrespective of presentation, and is therefore a crucial prognostic instrument for risk stratification, clinical trials, and management of patients diagnosed with all forms of MVP.

Context.— In women, radical cystectomy includes removal of the bladder, uterus, fallopian tubes, ovaries, and anterior vaginal wall, yet contiguous extension of urothelial carcinoma to all pelvic organs is rare and routine removal may be unnecessary. Objective.— To study pelvic organ involvement in women at radical cystectomy and investigate oncologic outcomes. Design.— Women with bladder cancer who underwent radical cystectomy at the Mayo Clinic and University of Toronto (1980–2018) were evaluated. Cancer-specific survival (CSS) was estimated with the Kaplan-Meier method; comparisons were made with the log-rank test. Associations with CSS were evaluated with Cox proportional hazard modeling. Results.— A total of 70 women with pT4a and 83 with pT3b cancer were studied. Organs involved were vagina (n = 41 of 70; 58.6%), uterus (n = 26 of 54; 48.1%), cervix (n = 15 of 54; 27.8%), fallopian tubes (n = 10 of 58; 17.2%), and ovaries (n = 7 of 58; 12.1%); 22 of 58 patients (37.9%) had &gt;1 organ involved. Of 70 with pT4a cancer, 64 were available for survival analysis by 3 pelvic organ groups: vaginal only, vaginal and/or cervical/uterine, and vaginal and/or cervical/uterine and/or fallopian tubes/ovarian involvement. Three-year CSS for vaginal involvement only was 39%; it was 14% if cervical/uterine involvement, and &lt;1% if fallopian tube/ovarian involvement was included (P = .02). Among 20 women with pT4aN0/Nx and vaginal involvement only, 3-year CSS for vaginal involvement was 50%, whereas among 48 women with pT3bN0/Nx cancer, 3-year CSS was 58%, P = .70. Conclusions.— Isolated vaginal involvement should be separated from uterine and/or adnexal extension of urothelial carcinoma at pathologic staging. Direct ovarian extension is rare and routine removal may be unnecessary.

Background Intracranial aneurysms are reported in 6%–10% of patients with bicuspid aortic valve (BAV), and routine intracranial aneurysm surveillance has been advocated by some. We assessed the prevalence and features of the most important patient‐outcome: aneurysmal sub‐arachnoid hemorrhage (aSAH), as compared with controls without aSAH, and tricuspid aortic valve (TAV) with aSAH. Methods and Results Adult patients with accurate diagnosis of aSAH and at least one echocardiogram between 2000 and 2019 were identified from a consecutive prospectively maintained registry of aSAH admissions. Controls without a diagnosis of SAH were age‐ and sex‐matched. BAV prevalence was confirmed echocardiographically. Severity of aSAH was categorized using modified Fisher and World Federation of Neurological Scale. Neurologic outcome was assessed using modified Rankin score. A total 488 aSAH cases and 990 controls were identified and BAV status was confirmed. Prevalence of BAV in patients with aSAH was 1.2% (6/488) versus 3.5% (35/990) in controls, P =0.01. BAV+aSAH were noted to be younger than TAV+aSAH (56±11 versus 68±14; P =0.03) with smaller aneurysms (5±2 versus 7±4; P =0.31). The severity of aSAH was lesser in BAV+aSAH than TAV (modified Fisher grade>2 50% versus 74%; P =0.19, World Federation of Neurological Scale grade>3 17% versus 36%; P =0.43). BAV+aSAH had less severe neurologic disability (modified Rankin score 3%–6 33% versus 49% in TAV; P =0.44) and comparable in‐hospital mortality rates ( P =0.93). BAV had lower odds for aSAH on multivariate analysis (odds ratio 0.23[CI 0.08–0.65]; P =0.01). Conclusions Prevalence of BAV was 3 times lower in the aSAH registry than in controls without aSAH. BAV+aSAH had clinically smaller aneurysms, clinically smaller bleeds, and better neurologic outcome as compared with TAV+aSAH, which needs to be confirmed in larger studies. These findings argue against routine surveillance for intracranial aneurysms in patients with BAV without aortic coarctation.