Citations

Abstract Introduction Peyronie’s Disease (PD) is characterized by a fibrous scar of the tunica albuginea. PD is typically imaged with 2D ultrasound. We propose a classification system of these ultrasound findings in the evaluation of PD. Objective The purpose of this study is to establish a functional sonographic classification system for evaluating PD and to examine the relationship between PD grading and curvature, duration of PD, and vascular erectile status. Methods In our study, 395 patients with PD underwent intracavernosal injection with an erectile agent (ICI) followed by Color Doppler Duplex Ultrasound (CDDU). All CDDU studies were performed by a single examiner and all PD grading was done by two independent reviewers using saved images. Ultrasound findings including peak systolic velocities (PSV) and resistive indices (RIs) were recorded. PD grades of 2D images were classified into three grades: Grade 1 acoustic shadowing without calcification; Grade 2 focal microcalcifications of the tunica, pillars, or septal fibers; Grade 3 confluent calcification of the dorsal, septal, ventral tunica albuginea. Results There were 250 patients classified with Grade 1 (63%) sonographic changes, 75 with Grade 2 (19%), and 70 with Grade 3 (18%). All groups had similar median ages and body mass index (BMI): Grade 1 (59.3 yr), Grade 2 (59 yr) and Grade 3 (60.3 yr), p = 0.711; BMI 27.6, 28.2, 27.7, p = 0.813. Additionally, medical and surgical risk factors for erectile dysfunction were similar across the three groups; these included hypertension, heart disease, diabetes mellitus, hyperlipidemia, smoking history, and history of prostate surgery. Most patients had previously used PDE5-Inhibitors (293/395). History and/or physical findings of Dupuytren’s palmar contracture was noted in 30/395 (7.6%) of men. The median duration of PD was not significantly different across the three groups (12, 12, 14 months p = 0.639). Neither CDDU diagnoses (Table 1) nor curvature varied by sonographic grades (Table 2). Conclusions The scar resulting from PD seals together the outer longitudinal and inner circular layers of the tunica albuginea causing deformity of the erect shaft. PD plaques are usually palpable and associated with focal thickening of the tunica. On 2D ultrasound, the typical appearance is an acoustic shadow. Most of our patients presented with Grade I acoustic shadowing and no calcifications 250/395 (63%). On the other hand, 19% had acoustic plaque shadowing and additional findings of focal tunica or deep microcalcifications and 18% had confluent calcification of the dorsal, septal or ventral tunica. We propose a unique and reproducible classification system for Peyronie's Disease. This grading system is based on grayscale ultrasound of Peyronie’s plaques may serve the purpose of diagnostic evaluation, didactic teaching and integrated research. Disclosure No

Abstract Introduction Peyronie’s disease (PD) is characterized by penile pain, penile deformation and curvature, sexual dysfunction, and psychological implications. Fibrosis and plaque formation are often part of PD pathophysiology. Calcified plaques can alter treatment planning. Penile ultrasound with Doppler (PUS) is used to exclude erectile dysfunction and identify plaques. However, plaque extent and distribution can be obscured by acoustic shadowing, limiting complete plaque characterization. Non-contrast pelvis computed tomography (CT) provides a noninvasive method to identify plaques in 3 dimensions and quantify plaque Ca burden. Objective Our objective was to utilize Agatston Ca scoring measure Ca burden in patients with Peyronie's disease. Methods A retrospective database from 1/1/2017 and 6/30/2021 identified 25 men with calcified plaques on CT after PUS performed by a single urologist. Two abdominal radiologists reviewed CTs in consensus to measure calcified plaque size and distribution on Visage PACS. Semiautomated Agatston Ca scoring values were obtained with Syngo.via. Total Ca volume (mm3), total Ca score were correlated with hourglass deformity on clinical exam, plaque complexity on CT (>2 discrete calcified plaques, circumferential corpus cavernosum involvement, septal involvement), and surgical management using descriptive statistics and t-test. Results Mean Ca volume was 1417 mm3 (range 1.4-5425.7, standard deviation (SD) 1570); mean Ca score was 1691 (range 1.6-6048; SD 1862) with significantly higher Ca volume in patients with complex plaques (265 mm3 vs 472 mm3, p<0.05), and significantly longer plaque dimension for longest plaque dimension measured by CT vs US (31 vs 23, p<0.05). There was no significant difference in Ca volume for nonsurgical vs surgical (1791 vs 893, p=0.06) or for no hourglass vs hourglass deformity (1173 vs 1904, p=0.19). Conclusions CT scan and calcium scoring are useful tools in the assessment of PD. Semiautomated Ca scoring may help noninvasively identify complex calcified penile plaques to guide medical and surgical therapy for Peyronie’s disease. Disclosure No

Abstract Background: Ovarian cancer ranks fifth in cancer deaths among women. The gold standard of care for advanced disease includes cytoreductive surgery along with adjuvant or neoadjuvant platinum/taxane-based chemotherapy. Although response to this treatment is high, chemotherapy-induced nausea and vomiting due to platinum agents and allergic reactions due to both agents are common. For nearly half a century, the glucocorticoid (GC) dexamethasone (DEX) has been administered as part of supportive care. However, there have periodically been questions about the possible deleterious effects of DEX on chemotherapy response, especially in solid tumors. Methods: Platinum-sensitive, glucocorticoid receptor (GRα) expressing ovarian cancer cells were exposed to DEX prior to chemotherapy and clonogenic survival was assessed. The effects of DEX on cell cycle and apoptosis were assessed by flow cytometry. Changes in the tumor cell transcriptome after acute DEX treatment were determined by RNA sequencing. Mice bearing orthotopic ovarian cancer patient-derived xenografts (PDXs) were treated with chemotherapy ± DEX to assess changes in chemotherapy response in vivo. Findings: DEX pre-treatment decreased platinum cytotoxicity in ovarian cancer cell lines in vitro and diminished platinum response in some PDXs analyzed for chemotherapy response ex vivo. RNA-seq analysis revealed changes in transcripts encoding proteins involved in platinum detoxification and TNFα pro-survival signaling. In ovarian cancer PDXs, DEX decreased platinum response in one model and had limited impact on both platinum and platinum/taxane chemotherapy in three distinct studies. Interpretation: DEX appears to modulate chemotherapy response in some settings in vitro and ex-vivo. The impact of DEX on chemotherapy response in vivo appears to be limited. However, further investigation of this question in vivo in non-immunosuppressed murine models appears warranted. Citation Format: Annapoorna Venkatachalam, Cristina Correia, Cordelia D. Mcgehee, Sarah Finstuen-Magro, Jamison VanBlaricom, Paula A. Schneider, Kevin L. Peterson, Ethan P. Heinzen, Melissa C. Larson, Xiaonon Hou, Ann L. Oberg, Saravut John Weroha, Scott H. Kaufmann. Impact of dexamethasone on chemotherapy response in ovarian cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5058.

OBJECTIVE Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein–2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS The authors created a polydopamine (PDA)–infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 μg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4–5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS Implantation of rhBMP-2–adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.

Background Larger within‐patient variability of lipid levels has been associated with increased risk of cardiovascular disease (CVD); however, measures of lipid variability require ≥3 measurements and are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record–based population cohort and assessed associations with incident CVD. Methods and Results We identified all individuals ≥40 years of age who resided in Olmsted County, MN, on January 1, 2006 (index date), without prior CVD, defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or CVD death. Patients with ≥3 measurements of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, or triglycerides during the 5 years before the index date were retained. Lipid variability was calculated using variability independent of the mean. Patients were followed through December 31, 2020 for incident CVD. We identified 19 652 individuals (mean age 61 years; 55% female), who were CVD‐free and had variability independent of the mean calculated for at least 1 lipid type. After adjustment, those with highest total cholesterol variability had a 20% increased risk of CVD (Q5 versus Q1 hazard ratio, 1.20 [95% CI, 1.06–1.37]). Results were similar for low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Conclusions In a large electronic health record–based population cohort, high variability in total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol was associated with an increased risk of CVD, independent of traditional risk factors, suggesting it may be a possible risk marker and target for intervention. Lipid variability can be calculated in the electronic health record environment, but more research is needed to determine its clinical utility.

Background Optimal glenosphere positioning in reverse shoulder arthroplasty (RSA) remains highly debated. We aimed to characterize the association between the prosthesis scapular neck angle (PSNA) and postoperative range of motion (ROM) and clinical outcome scores. Methods A retrospective review of 284 RSAs using a single design with minimum 2-year follow-up was performed. Glenosphere tilt was measured postoperatively using PSNA. ROM and functional outcome scores were assessed preoperatively and at latest follow-up. The PSNA was dichotomized to inferior or superior groups (>90° vs ≤ 90°, respectively) and stratified into quartiles; ROM and outcome score measures were compared between groups controlling for inferior glenosphere overhang. Results No range of PSNA was consistently associated with superior ROM, clinical outcome scores, or rates of complications including scapular notching. However, greater preoperative to postoperative improvement in active FE was found for superiorly (PSNA ≤ 90°) versus inferiorly tilted glenospheres (37° ± 33° vs 53° ± 35°, P = 0.005) and the greater improvement in active FE (57° ± 35°, P = 0.004) was further isolated to the first quartile (mean 85.1° ± 3.5°). Discussion A lack of variation in clinical outcomes based on PSNA suggests negligible short-term (median follow-up 3.1 years) clinical significance when glenosphere tilt falls within the distribution of this cohort (mean 92.6° ± 6.2°).

Abstract Introduction Selective serotonin reuptake inhibitors (SSRIs) and, to a lesser extent, serotonin‐norepinephrine reuptake inhibitors (SNRIs) are the cornerstone of pharmacotherapy for children and adolescents with anxiety and depressive disorders. These medications alleviate symptoms and restore function for many youths; however, they are associated with a distinct adverse effect profile, and their tolerability may complicate treatment or lead to discontinuation. Yet, SSRI/SNRI tolerability has received limited attention in the pediatric literature. Methods This review examines the early‐ (e.g., activation, gastrointestinal symptoms, sedation) and late‐emerging (e.g., weight gain) adverse effects of SSRIs and some SNRIs in pediatric patients. Results We provide a framework for discussing SSRI/SNRI tolerability with patients and their families and describe the pharmacologic basis, course, and predictors of adverse events in youth. Strategies to address specific tolerability concerns are presented. For selected adverse events, using posterior simulation of mean differences over time, we describe their course based on Physical Symptom Checklist measures in a prospective, randomized trial of anxious youth aged 7–17 years who were treated with sertraline ( n = 139) or placebo ( n = 76) for 12 weeks in the Child/Adolescent Anxiety Multimodal Study (CAMS). Main Results In CAMS, the relative severity/burden of total physical symptoms ( p < 0.001), insomnia ( p = 0.001), restlessness ( p < 0.001), nausea ( p = 0.002), abdominal pain ( p < 0.001), and dry mouth ( p = 0.024) decreased from baseline over 12 weeks of sertraline treatment, raising the possibility that these symptoms are transient. No significant changes were observed for sweating ( p = 0.103), constipation ( p = 0.241), or diarrhea ( p = 0.489). Finally, we review the antidepressant withdrawal syndrome in children and adolescents and provide guidance for SSRI discontinuation, using pediatric pharmacokinetic models of escitalopram and sertraline—two of the most used SSRIs in youth. Conclusion SSRI/SNRIs are associated with both early‐emerging (often transient) and late‐emerging adverse effects in youth. Pharmacokinetically‐informed appraoches may address some adverse effects and inform SSRI/SNRI discontinuation strategies.