Citations

Background: Owing to reduced bleeding risks, radial is favored over femoral for access site selection in patients referred for coronary angiography, with specific benefits in patients presenting with acute coronary syndrome. However, studies were often limited to patients without coronary artery bypass grafts (CABG), given the technical challenges of the radial approach in these patients. Methods: We evaluated patients with prior CABG undergoing coronary angiography with or without percutaneous coronary intervention (PCI) from 2015-2020 at our institution. We reviewed access site and bleeding outcomes as defined in the NCDR CathPCI registry. Additional outcomes included procedural duration, fluoroscopy time, contrast volume, and clinical events. Results: Of the 1,546 patients studied, 280 (18%) patients had radial access while 1,266 (82%) patients had femoral access. Over the study time period, frequency of radial access for post CABG catheterization procedures increased from 0% in 2015 to 45% in 2020. There were no statistically significant differences in comorbidities, bleeding events, complications, or mortality between radial vs femoral (Table). Fluoroscopy time was higher for radial vs femoral (14.9 mins vs 13.3 mins, p=0.04). Conclusion: Over time, radial access choice in post CABG patients increased, without significant differences with respect to bleeding events or complications as compared to femoral, though at increased fluoroscopy times.

SUMMARY Implant-associated infections (IAIs) pose serious threats to patients and can be associated with significant morbidity and mortality. These infections may be difficult to diagnose due, in part, to biofilm formation on device surfaces, and because even when microbes are found, their clinical significance may be unclear. Despite recent advances in laboratory testing, IAIs remain a diagnostic challenge. From a therapeutic standpoint, many IAIs currently require device removal and prolonged courses of antimicrobial therapy to effect a cure. Therefore, making an accurate diagnosis, defining both the presence of infection and the involved microorganisms, is paramount. The sensitivity of standard microbial culture for IAI diagnosis varies depending on the type of IAI, the specimen analyzed, and the culture technique(s) used. Although IAI-specific culture-based diagnostics have been described, the challenge of culture-negative IAIs remains. Given this, molecular assays, including both nucleic acid amplification tests and next-generation sequencing-based assays, have been used. In this review, an overview of these challenging infections is presented, as well as an approach to their diagnosis from a microbiologic perspective.

Abstract Introduction High medication costs for vaginal estrogen may create a barrier for patients seeking treatment for numerous urinary and vaginal symptoms and lead to poor medication adherence. The Mark Cuban Cost Plus Drug Company (CPD) and GoodRx tools offer patients a method to purchase prescription medications at a discount, which may lead to improved medication adherence and decreased national expenditures on such medications. Objective To compare the pricing of vaginal estrogen as advertised by retail pharmacies, Medicare, and discount listings through CPD and GoodRx. Methods A review of publicly available data from CPD and GoodRx was performed to obtain listed retail and discounted prices for Estrace (topical), Vagifem (tablet), and Premarin (topical). GoodRx prices were obtained using prices from Costco, CVS, Walgreens, and Walmart pharmacies in the most from populous zip code from each of the 3 most populous U.S. states: California, New York, and Texas. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). The Medicare Part D Drug Spending and Utilization data from 2021 were used to report the average spending per dosage unit and total expenditure for each of the listed medications. These data were compared to create an estimate of average national savings after use of CPD and/or GoodRx. Results Average spending per dosage unit for Estrace, Vagifem, and Premarin was lesser when discount tools were used (0.50 $/adu, 3.75 $/adu, and 4.30 $/adu respectively), compared to Medicare pricing (6.14 $/adu, 20.95 $/adu, and 10.10 $/adu respectively) or retail pricing (3.14 $/adu, 10.19 $/adu, and 5.43 $/adu respectively). When adjusted for total dosage units, use of CPD over Medicare pricing for the three medications would result in a combined annual national saving of $64.2M. Use of either CPD or GoodRx compared to retail pricing would similarly result in a combined annual national saving of $39.2M. Conclusions The utilization of CPD and GoodRx in the prescription of vaginal estrogen led to a substantial national average cost savings when compared to retail and Medicare pricing. CPD and GoodRx may offer a way to decrease the cost burden for patients seeking treatment for urinary and vaginal symptoms and significantly reduce national expenditures on medications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: The utilization of CPD and GoodRx in the prescription of vaginal estrogen led to a substantial national average cost savings when compared to retail and Medicare pricing. CPD and GoodRx may offer a way to decrease the cost burden for patients seeking treatment for urinary and vaginal symptoms and significantly reduce national expenditures on medications.

Abstract Introduction Krabbe Disease (KD) or globoid cell leukodystrophy is a rare autosomal recessive lysosomal storage disorder affecting approximately 1 in 100,000 people worldwide. GALC gene mutations associated with KD involve a galactosylceramidase deficiency, which damages the oligodendrocytes and Schwann cells. Therefore, nervous system demyelination is a hallmark of KD. While only a few infants survive beyond two years in early-onset Krabbe disease, patients with late-onset Krabbe Disease exhibit a milder phenotype and longer life expectancy. Late-onset KD symptoms include progressive muscle weakness and stiffness, developmental regression, behavioral changes, dementia, hearing loss, vision problems, and seizures. Only a few cases of sexual dysfunction associated with KD have been reported in literature but they highlight the wide-ranging impact of this condition on young adults and adults. Objective This review aims to examine sexual dysfunction in KD, as reported in literature. We employ a broad definition of sexual dysfunction (erectile dysfunction, dyspareunia, orgasmic disorder, muscle weakness, etc.) and its incidence in both sexes with KD. A comprehensive review of this topic has not yet been conducted, and we offer here preliminary information for healthcare providers when addressing sexual concerns in patients with lysosomal storage disorders. Methods A literature search was conducted by two separate investigators who independently screened studies and abstracted data. Data sources included peer reviewed publications from the following databases: PubMed, Scopus, Web of Science, EMBASE, Cochrane, Google Scholar and Clinical trials.gov. There were no restrictions on language nor date of publication. The search algorithm utilized to generate the review list was: (Globoid cell leukodystrophy OR Galactosylcerebrosidase deficiency OR Galactosylceramidase deficiency OR Krabbe disease OR Late-onset Krabbe disease OR GALC mutation). Results were further filtered by article type, restricting articles to Case Reports, Clinical Trials, Reviews, and Systematic Reviews. Results were then screened for reports containing data on sexual dysfunction in patients with KD. Results A total of four case reports and one review paper contained reports of sexual dysfunction in KD patients. All cases involved late-onset Krabbe disease, characterized by a milder and more insidious presentation. Genitourinary symptoms reported included urinary incontinence (N=3) and erectile dysfunction (N=2), however, there were no reports (N=0) of symptoms related to female sexual dysfunction. Other symptoms commonly reported in late-onset KD that might be linked to sexual function were ataxia, spasticity and weakness of lower limbs (N=3), and sensory dysfunction due to peripheral neuropathy (N=4). Conclusions This pioneering review reveals that patients with KD experience symptoms of sexual dysfunction. While the rarity of KD makes it challenging to study it clinically, sexual dysfunction may be consistent with the known pathophysiology of late-onset KD. This review also highlights that sexual dysfunction in female patients with KD is an under-investigated component of the disease presentation. Future clinical research into this important comorbidity, especially in female patients where the literature is lacking, may improve the care of patients with KD. Disclosure No.

Abstract Objectives The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs. Results Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97–0.99], and HCQ and SSZ use were risk factors (HR = 1.81, 95% CI = 1.24–2.64, and HR = 3.79, 95% CI = 1.69–8.42, respectively). Glucocorticoid use was a risk factor for a severe BI (HR = 3.61, 95% CI = 1.09–11.8). Non-white ethnicity (HR = 2.61, 95% CI = 1.03–6.59) was a risk factor for hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%). Conclusion Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs.

Abstract Objectives To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. Methods Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. Results We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10–15] IIMs vs 13 [11–15] non-IIM AIRDs vs 15 [13–17] nrAIDs vs 17 [15–18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10–15) IIMs vs 15 (13–17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. Conclusion Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs.

Abstract Introduction The Mark Cuban Cost Plus Drug Company (CPD) is an online retailer launched in January 2022 that sells generic prescription medications directly to consumers at cost of ingredients and manufacturing plus a fixed 15% margin in addition to a small pharmacy dispensing fee and shipping fee. GoodRx is an online tool which offers coupons redeemable at pharmacies for discounts on prescription medications. The combination of these two tools offers physicians a way to provide prescription medications to patients at lower costs, which may lead to improved medication adherence and lower medication expenditures nationally. Objective To compare the cost of various erectile dysfunction medications when purchased through retail pharmacies, reimbursed through Medicare, or obtained utilizing CPD and GoodRx. Methods A review of publicly available data from CPD and GoodRx was performed to obtain average retail and discounted prices for generic sildenafil, tadalafil, and vardenafil. GoodRx prices were obtained using prices from Costco, CVS, Walgreens, and Walmart pharmacies in the most from populous zip code from each of the 3 most populous U.S. states: California, New York, and Texas. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). The Medicare Part D Drug Spending and Utilization data from 2021 were used to report the average spending per dosage unit and total expenditure for each of the listed medications. These data were compared to create an estimate of average national savings after use of CPD or GoodRx. Results Average spending per dosage unit for sildenafil, tadalafil, and vardenafil was less when GoodRx or CPD were used (0.28 $/adu, 0.31 $/adu, and 6.17 $/adu respectively), compared to Medicare pricing (2.14 $/adu, 8.08 $/adu, and 27.84 $/adu respectively) or retail pricing (0.52 $/adu, 2.82 $/adu, and 8.35 $/adu respectively). When adjusted for total dosage units, use of CPD over Medicare pricing for the three medications would result in a combined annual national saving of $149M. Use of either CPD or GoodRx compared to retail pricing would similarly result in a combined annual nation saving of $40M. Conclusions The utilization of CPD and GoodRx in the prescription of common erectile dysfunction medications may lead to significant reductions in pricing compared to retail and Medicare estimates. Knowledge of these prescription tools may lead to significant reductions in national expenditures on medications and decreased cost burden for patients seeking treatment. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

Abstract Introduction High medication costs for vaginal estrogen may create a barrier for patients seeking treatment for numerous urinary and vaginal symptoms and lead to poor medication adherence. The Mark Cuban Cost Plus Drug Company (CPD) and GoodRx tools offer patients a method to purchase prescription medications at a discount, which may lead to improved medication adherence and decreased national expenditures on such medications. Objective To compare the pricing of vaginal estrogen as advertised by retail pharmacies, Medicare, and discount listings through CPD and GoodRx. Methods A review of publicly available data from CPD and GoodRx was performed to obtain listed retail and discounted prices for Estrace (topical), Vagifem (tablet), and Premarin (topical). GoodRx prices were obtained using prices from Costco, CVS, Walgreens, and Walmart pharmacies in the most from populous zip code from each of the 3 most populous U.S. states: California, New York, and Texas. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). The Medicare Part D Drug Spending and Utilization data from 2021 were used to report the average spending per dosage unit and total expenditure for each of the listed medications. These data were compared to create an estimate of average national savings after use of CPD and/or GoodRx. Results Average spending per dosage unit for Estrace, Vagifem, and Premarin was lesser when discount tools were used (0.50 $/adu, 3.75 $/adu, and 4.30 $/adu respectively), compared to Medicare pricing (6.14 $/adu, 20.95 $/adu, and 10.10 $/adu respectively) or retail pricing (3.14 $/adu, 10.19 $/adu, and 5.43 $/adu respectively). When adjusted for total dosage units, use of CPD over Medicare pricing for the three medications would result in a combined annual national saving of $64.2M. Use of either CPD or GoodRx compared to retail pricing would similarly result in a combined annual national saving of $39.2M. Conclusions The utilization of CPD and GoodRx in the prescription of vaginal estrogen led to a substantial national average cost savings when compared to retail and Medicare pricing. CPD and GoodRx may offer a way to decrease the cost burden for patients seeking treatment for urinary and vaginal symptoms and significantly reduce national expenditures on medications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

TPS587 Background: Biliary tract cancer (BTC) is characterized by generally poor prognoses with limited treatment options. Systemic chemotherapy usually begins with gemcitabine, platinum agents, and a checkpoint inhibitor followed by 5-FU and oxaliplatin, irinotecan or a taxane. Presently, there is no consensus second-line therapy for patients with BTC. The DLL/Notch signaling pathway has been described to be a major driver of cholangiocarcinogenesis and VEGF-A overexpression has been reported in BTC tumors, correlating with stage, metastasis, and prognosis of the disease. CTX-009 is a recombinant bispecific antibody that binds both delta-like ligand-4 (DLL4) and vascular endothelial growth factor A (VEGF-A). The antibody simultaneously inhibits the DLL4-Notch 1 and VEGF A-VEGF receptor signaling pathways. Methods: COMPANION-002 (CTX-009 -002) is an open-label, randomized, controlled study in patients in second line advanced or metastatic BTC. To be eligible, patients must have radiologically documented progression after a prior gemcitabine and platinum containing chemotherapy regimen as first line therapy for locally advanced unresectable or metastatic disease. 150 patients will be randomized in a 2:1 ratio to receive either CTX-009 plus paclitaxel or paclitaxel alone. The stratification factors to be used at randomization include stage (locally advanced vs. metastatic), anatomic subsite of primary tumor (intrahepatic cholangiocarcinoma vs. other, i.e. extrahepatic cholangiocarcinoma, gallbladder, or ampullary), and Eastern Cooperative Oncology Group (ECOG) Performance status (0 vs. 1). Patients will be treated in 28-day cycles, with CTX-009 administered at 10 mg/kg IV on Day 1 and 15, and paclitaxel administered at 80 mg/m2 on days 1, 8, and 15. The patients randomized to paclitaxel arm can crossover after disease progression if selection criteria continue to be met. The primary objective of the study is to assess the efficacy of CTX-009 in combination with paclitaxel vs. paclitaxel alone, as measured by Overall Response Rate (ORR) assessed by an Independent Central Radiology (ICR) review. Key secondary objectives include overall survival, progression-free survival, and duration of response. Clinical trial information: 251040.

Background: Approximately 90% of patients who undergo arthroscopic rotator cuff repair (RCR) are satisfied with their pain levels and function after surgery. However, a subset of patients experience continued symptoms that warrant revision surgery. Preoperative risk factors for RCR failure requiring revision surgery have not been clearly defined. Purpose: To (1) determine the rate of RCR failure requiring revision surgery and (2) identify risk factors for revision surgery, which will help surgeons to determine patients who are at the greatest risk for RCR failure. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review and meta-analysis in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were performed. The initial search resulted in 3158 titles, and 533 full-text articles were assessed for eligibility. A total of 10 studies met the following inclusion criteria: (1) human clinical studies, (2) arthroscopic RCR, (3) original clinical research, and (4) evaluation of preoperative risk factors for revision. Results: After a full-text review, a total of 16 risk factors were recorded and analyzed across 10 studies. Corticosteroid injection was the most consistent risk factor for revision surgery, reaching statistical significance in 4 of 4 studies, followed by workers’ compensation status (2/3 studies). Patients with corticosteroid injections had a pooled increased risk of revision surgery by 47% (odds ratio, 1.44 [95% CI, 1.36-1.52]). Patients with workers’ compensation had a pooled increased risk of revision surgery by 133% (odds ratio, 2.33 [95% CI, 2.09-2.60]). Age, smoking status, diabetes, and obesity were found to be risk factors in half of the analyzed studies. Conclusion: Corticosteroid injections, regardless of the frequency of injections, and workers’ compensation status were found to be significant risk factors across the literature based on qualitative analysis and pooled analysis. Surgeons should determine ideal candidates for arthroscopic RCR by accounting for corticosteroid injection history, regardless of the frequency, and insurance status of the patient.