Abstract Purpose: We evaluated whether indoleamine 2,3-dioxygenase (IDO1) inhibitor (IDOi) BMS986205 + PD-1 inhibitor nivolumab enhanced T-cell activity and augmented immune-mediated antitumor responses in untreated, resectable head and neck squamous cell carcinoma (HNSCC). We employed response-adaptive surgical timing to identify responders to immunotherapy and enhance their response. Patients and Methods: Patients with HNSCC were 3:1 randomized to receive nivolumab with or without BMS986205 orally daily (NCT03854032). In the combination arm, BMS986205 was initiated 7 days prior to nivolumab. Patients were stratified by human papillomavirus (HPV) status. Response-adaptive surgical timing involved response assessment by radiographic criteria 4 weeks after treatment with nivolumab in both arms. Nonresponders underwent surgical resection, whereas responders received 4 more weeks of randomized therapy before surgery. Biomarker analysis utilized pathologic treatment response (pTR) and RNA sequencing. Results: Forty-two patients were enrolled, and the addition of IDOi to nivolumab did not result in greater rate of radiographic response (P = 0.909). Treatment was well tolerated, with only 2 (5%) patients experiencing grade 3 immune-related adverse events. The addition of IDOi augmented rates of pTR in patients with high baseline IDO1 RNA expression (P < 0.05). Response-adaptive surgical timing demonstrated reliability in differentiating pathologic responders versus nonresponders (P = 0.009). A pretreatment NK cell signature, PD-L1 status, and IFN-γ expression in the HPV− cohort correlated with response. The HPV+ cohort found B-cell and cancer-associated fibroblast signatures predictive of response/nonresponse. Conclusions: Response-adaptive surgical timing enhanced treatment response. IDOi BMS986205 augmented pTR in patients with high IDO1 expression in baseline samples, indicating a need for identifying and targeting resistant nodes to immunotherapy. HPV status–dependent signatures predicting response to immunotherapy in HNSCC warrant further study.

3D printing is a growing tool in surgical education to visualize and teach complex procedures. Previous studies demonstrating the usefulness of 3D models as teaching tools for partial nephrectomy used highly detailed models costing between $250 and 1000. We aimed to create thorough, inexpensive 3D models to accelerate learning for trainees and increase health literacy in patients. Patient-specific, cost-effective ($30–50) 3D models of the affected urologic structures were created using pre-operative imaging of 40 patients undergoing partial nephrectomy at Thomas Jefferson University Hospital (TJUH) between July 2020 and May 2021. Patients undergoing surgery filled out a survey before and after seeing the model to assess patient understanding of their kidney, pathophysiology, surgical procedure, and risks of surgery. Three urological residents, one fellow, and six attendings filled out separate surveys to assess their surgical plan and confidence before and after seeing the model. In a third survey, they ranked how much the model helped their comprehension and confidence during surgery. Patient understanding of all four subjects significantly improved after seeing the 3D model (P < 0.001). The urology residents (P < 0.001) and fellow (P < 0.001) reported significantly increased self-confidence after interacting with the model. Attending surgeon confidence increased significantly after seeing the 3D model (P < 0.01) as well. Cost-effective 3D models are effective learning tools and assist with the evaluation of patients presenting with renal masses, and increase patient, resident, and fellow understanding in partial nephrectomies. Further research should continue to explore the utility of inexpensive models in other urologic procedures.

OBJECTIVE This study sought to validate alternative pain management strategies that can reduce reliance on opioids for postoperative pain management in otology. STUDY DESIGN Prospective cohort study. SETTING Single tertiary-care facility. METHODS Adult patients who underwent outpatient otologic surgery from September 2021 to July 2022 were randomized into treatment cohorts. The opioid monotherapy cohort received a standard opioid prescription. The multimodal analgesia cohort received the same opioid prescription, prescriptions for acetaminophen and naproxen, and additional pain management education with a flyer on discharge. All patients completed a questionnaire 1 week after surgery to evaluate opioid usage and pain scores. RESULTS Eighty-six patients completed the study. The opioid monotherapy cohort (n = 42) and multimodal analgesia cohort (n = 44) were prescribed an average of 42.1 ± 20.4 morphine milligram equivalents (MME) and 38.4 ± 5.7 MME, respectively (p = 0.373). Four patients (9.52%) in the opioid monotherapy cohort required opioid refills compared to 1 patient (2.27%) in the multimodal analgesia cohort (p = 0.156). Multivariate analysis demonstrated that the multimodal analgesia cohort consumed significantly fewer opioids on average than the opioid monotherapy cohort (11.9 ± 15.9 MME vs 22.8 ± 28.0 MME, respectively). There were no significant differences in postoperative rehospitalizations (p = 0.317) or Emergency Department visits (p = 0.150). Pain scores on the day of surgery, postoperative day (POD) 1, POD3, and POD7 were not significantly different between cohorts (p = 0.395, 0.896, 0.844, 0.765, respectively). CONCLUSION The addition of patient education, acetaminophen, and naproxen to postoperative opioid prescriptions significantly reduced opioid consumption without affecting pain scores, refill rates, or complication rates after otologic surgery.

6070 Background: Indoleamine 2,3-dioxygenase (IDO) catalyzes the degradation of tryptophan to kynurenine. In order to improve the clinical efficacy of PD-1 inhibition, we designed a novel neoadjuvant trial to test the immunological and therapeutic effects of nivolumab (nivo) and the IDO inhibitor BMS986205 in combination in previously untreated HNSCC utilizing an interim radiographic assessment to determine response treatment prior to surgery. Methods: We conducted an investigator-initiated, multi-institutional, two-arm, 3:1 randomized neoadjuvant trial in patients with previously untreated HNSCC of any stage who were candidates for complete surgical resection. Patients were stratified by HPV status. Patients in arm A received 480 mg of nivolumab alone. Subjects in arm B received BMS986205 100 mg po qday beginning 1 week prior to nivolumab 480 mg. Both groups were evaluated at week 5 with CT scans. Radiographic response was evaluated at both the primary site and any involved lymph nodes. Patients with at least a 10% reduction in volume at either the primary or lymph nodes with no evidence of progression continued on to a second cycle of the assigned treatment. Patients with stable disease or progression proceeded to surgery at week 5 without additional study treatment. Imaging, blood and tumor were obtained pretreatment and post treatment and used for immunological correlatives. 2 blinded independent pathologist provided pathologic treatment effect (pTE) scores for primary tumor and lymph nodes. The primary endpoint was radiographic response leading to additional study treatment. Results: 42 patients were randomized and completed treatment to the primary endpoint evaluation including 22 HPV+ oropharyngeal HNSCC. Four patients did not proceed with planned surgery: 2 progression, 1 patient preference, and 1 toxicity. 3 patients in Arm B developed hepatitis with 2 subjects having a delay in surgery. 36% of patients (n=4) in Arm A (nivo alone) and 42% of patients (n= 13) in Arm B (nivo+IDO) were considered radiographic responders and continued to a second cycle of therapy (p= 1.0). Pathologic treatment effect (pTE) was significantly higher in subjects who were treated with a second cycle: median of 85% pTE (responders) compared to median of 5% pTE (nonresponders) at the primary site (p=0.018) with 6/16 (38%) subjects in the radiographic responders and 1/20 (5%) in radiographic non-responders demonstrating a CR at the primary site. In the lymph node compartment, the median pTE was 73% compared to 23% in radiographic responders vs non-responders (p=0.04). Conclusions: In previously untreated HNSCC, nivolumab +/- IDO inhibitor demonstrated a significantly greater pTE after a second dose in radiographic responders. The addition of IDO-inhibitor to anti-PD1 did not result in a significant increase in radiographic or pathologic response over nivolumab alone. NCT03854032. Clinical trial information: NCT03854032.

3D printing has been growing in many surgical fields including Urology. The primary use has been to print kidneys with tumors to better understand anatomy and to assist with surgical planning and education. Previous studies that utilized 3D printing of kidneys for partial nephrectomies have been limited by the cost and complexity of model creation, rendering them highly impractical to be used on a routine basis. Using a simpler and more cost-effective design and materials allow the 3D kidney models to be used in a wider range and number of patients. We describe our streamlined process to create 3D kidney models costing $30 on average and we believe this process can be repeated by others.

STUDY OBJECTIVES The objective was to determine the prevalence and predictors of comorbid insomnia in patients presenting for sleep surgery evaluation. The insomnia severity index (ISI) was utilized to evaluate patients' insomnia severity. METHODS A retrospective chart review was performed in patients presenting to an otolaryngology sleep surgery clinic; patients also completed a sleep history questionnaire. Patients were divided between those with and without clinically significant insomnia defined as ISI ≥ 15. RESULTS A total of 119 patients were included in the study: 50 (42%) with an ISI ≥ 15 and 69 (58%) with an ISI < 15. Clinically significant insomnia was associated with respiratory disturbance index (P = .028) but not apnea-hypopnea index or SaO2 nadir (P > .05). Clinically significant insomnia was associated with frequency of wake ups (P = .008), time to fall back asleep (P = .049), history of continuous positive airway pressure device use (P = .012), Epworth Sleepiness Scale (P = .008), and Sino-nasal Outcome Test (SNOT-22) (P < .001). CONCLUSIONS Patients reporting to a sleep surgery clinic are at an elevated risk for comorbid insomnia. The relationship between increased respiratory event-related arousals and nonsleep SNOT-22 scores to related sleep-maintenance insomnia supports the connection between insomnia, nasal obstruction, and continuous positive airway pressure intolerance. CITATION Sagheer SH, Scott ER, Ananth A, Boon M, Huntley C. Incidence and predictors of comorbid insomnia in a sleep surgery clinic. J Clin Sleep Med. 2021;17(11):2165-2169.

363 Background: 3D printing is a growing tool in surgical education due to the ability to visualize organs, tissue, and masses from multiple angles before operating on a patient. Previous studies using highly detailed and expensive 3D models costing between $1,000-250 per model have been shown to enhance patient and trainee comprehension of tumor characteristics, goals of surgery, and planned surgical procedure for partial nephrectomies. In our study we aim to use simpler and less expensive models in a greater range of patients receiving partial nephrectomies to determine the use of 3D models in patient, resident, and fellow education. Methods: 3D models of the effected kidney, mass, renal artery, and renal vein were created using preoperative imaging of undergoing partial nephrectomies at Thomas Jefferson University Hospital (TJUH) costing $35 per model. Residents and fellows filled out 3 surveys assessing their surgical plan and their confidence in the chosen plan at 3 time points: 1) Before seeing the model, 2) After seeing the model before surgery, and 3) After surgery. Ten patients filled out 2 surveys about their understanding of the kidney, their disease, the surgery they will undergo, and the risks involved with surgery before and after seeing the model. Results: Based on surveys to assess for surgical plan and confidence given to resident and fellow surgeons before and after seeing the 3D model, confidence significantly increased. Surveys given after surgery assessing anatomic and surgical comprehension found that resident and fellow surgeons rated the helpfulness of the models on their anatomical comprehension 7.6 out of 10 and the help of the models on their surgical confidence 7 out of 10. Patient understanding of their kidney, disease, and surgery significantly increased after seeing the 3D model, but the risks associated with surgery did not significantly increase. The extent that the model helped the patients learn about the kidney, their disease, the surgery, and the risks related to surgery were rated an average of 8.33, 9.67, 9.5, and 8.83 out of 10, respectively. Conclusions: Patient-specific 3D models for partial nephrectomies increase resident and fellow confidence in surgical approach and helped patients learn about their disease and feel comfortable going into surgery. Thus, it is important to continue to explore 3D models as an educational tool for both trainees and patients and potentially include 3D models as part of the standard of care. Further research could continue to explore the utility of 3D models as a pre-operative educational tool for both patients and trainees in other surgical fields.

You have accessJournal of UrologyEducation Research I (PD02)1 Sep 2021PD02-03 ASSESSING THE EDUCATIONAL IMPACT OF 3D PRINTED MODELS ON RESIDENT, FELLOW, AND PATIENT EDUCATION FOR PARTIAL NEPHRECTOMIES E. Reilly Scott, Andrea Quinn, Samuel Morano, Alice Karp, Erica Mann, Kaitlyn Boyd, Abhay Singh, Thenappan Chandrasekar, Mark J. Mann, Edouard Trabulsi, Vishal Desai, and Costas Lallas E. Reilly ScottE. Reilly Scott More articles by this author , Andrea QuinnAndrea Quinn More articles by this author , Samuel MoranoSamuel Morano More articles by this author , Alice KarpAlice Karp More articles by this author , Erica MannErica Mann More articles by this author , Kaitlyn BoydKaitlyn Boyd More articles by this author , Abhay SinghAbhay Singh More articles by this author , Thenappan ChandrasekarThenappan Chandrasekar More articles by this author , Mark J. MannMark J. Mann More articles by this author , Edouard TrabulsiEdouard Trabulsi More articles by this author , Vishal DesaiVishal Desai More articles by this author , and Costas LallasCostas Lallas More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001966.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 3D printing is a growing tool in surgical education with the ability to visualize and teach complex procedures from multiple angles. Previous studies using highly detailed and expensive 3D models costing between $250-1000 demonstrated 3D models as useful teaching tools for partial nephrectomy for patient and trainee education. We aimed to create a less expensive and simpler 3D model to encourage these learning opportunities in a greater range of patients undergoing robotic partial nephrectomy. METHODS: Patient-specific, cost-effective 3D models of the affected urologic structures were created using preoperative imaging of 22 patients undergoing partial nephrectomies at Thomas Jefferson University Hospital between July 2020 and January 2021. The total cost for each model was $35-50. Patients receiving the surgery filled out two surveys about their understanding of their kidney, pathophysiology, surgical procedure, and risks before and after seeing the model. Three urological residents and one fellow filled out separate surveys to assess their surgical plan and confidence in the chosen surgical plan before and after seeing the model. Residents and fellows filled out a third survey after surgery ranking how much the model helped their comprehension and confidence during surgery on a scale of 1 to 10 (1=not helpful; 10=extremely helpful). RESULTS: 20 of the 22 patients filled out both surveys. Patient understanding of their kidney, disease, surgery, and risk all significantly improved after seeing the 3D model (p<.001). Urology residents and fellows filled out both pre-surgical surveys for 19 and 18 cases, respectively. Both residents (p<.001) and fellows (p<.01) reported increased self-confidence following seeing the model. Following surgery, the residents rated how much the model increased their comprehension and confidence 7.7 and 7.1 out of 10, respectively. The fellow rated increased comprehension and confidence 6.6 and 6.7 out of 10, respectively. CONCLUSIONS: Cost-effective 3D models could become part of standard of care as learning tools to increase patient, resident, and fellow understanding in robotic partial nephrectomies. Further research should continue to explore the utility of 3D models as a pre-operative educational tool for both patients and trainees in other Urologic procedures. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e38-e38 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information E. Reilly Scott More articles by this author Andrea Quinn More articles by this author Samuel Morano More articles by this author Alice Karp More articles by this author Erica Mann More articles by this author Kaitlyn Boyd More articles by this author Abhay Singh More articles by this author Thenappan Chandrasekar More articles by this author Mark J. Mann More articles by this author Edouard Trabulsi More articles by this author Vishal Desai More articles by this author Costas Lallas More articles by this author Expand All Advertisement PDF downloadLoading ...

Smoking tobacco products is the leading cause of preventable death worldwide. Coordinated efforts have successfully reduced tobacco cigarette smoking in the United States; however, electronic cigarettes (e-cigarette) and other electronic nicotine delivery systems (ENDS) recently have replaced traditional cigarettes for many users. While the clinical risks associated with long-term ENDS use remain unclear, advancements in preclinical rodent models will enhance our understanding of their overall health effects. This review examines the peripheral and central effects of ENDS-mediated exposure to nicotine and other drugs of abuse in rodents and evaluates current techniques for implementing ENDS in preclinical research.

Summary We have demonstrated previously that histone deacetylase (HDAC6) expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) New Zealand Black (NZB)/White F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for 5 weeks. As the mice aged, we determined autoantibody production and cytokine levels by enzyme-linked immunosorbent assay (ELISA) and renal function by measuring proteinuria. At the termination of the study, we performed a comprehensive analysis on B cells, T cells and innate immune cells using flow cytometry and examined renal tissue for immune-mediated pathogenesis using immunohistochemistry and immunofluorescence. Our results showed a reduced germinal centre B cell response, decreased T follicular helper cells and diminished interferon (IFN)-γ production from T helper cells in splenic tissue. Additionally, we found the IFN-α-producing ability of plasmacytoid dendritic cells was decreased along with immunoglobulin isotype switching and the generation of pathogenic autoantibodies. Renal tissue showed decreased immunoglobulin deposition and reduced inflammation as judged by glomerular and interstitial inflammation. Taken together, these studies show selective HDAC6 inhibition decreased several parameters of disease pathogenesis in lupus-prone mice. The decrease was due in part to inhibition of B cell development and response.

Histone deacetylase 6 (HDAC6) is a Class IIb HDACs enzyme primarily residing in the cytoplasm. HDAC6 alters gene transcription by removing acetyl groups from lysine residues on transcription factors. We, and others, have previously demonstrated that HDAC6 expression is increased in systemic lupus erythematosus (SLE) patients and animal models of lupus and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Importantly, we sought to delineate the cellular and molecular mechanism(s) of action for the HDAC6 inhibitor. We treated 20-week-old early-diseased NZB/W F1 (lupus) female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for five weeks. At the termination of the study, our results showed a reduced germinal center B cell response, decreased T follicular helper cells and diminished IFN-g production from T helper cells in splenic tissue. Additionally, we found the IFNa-producing ability of plasmacytoid dendritic cells was decreased along with immunoglobulin isotype switching and the generation of pathogenic autoantibodies. Renal tissue showed decreased immunoglobulin deposition and reduced inflammation as judged by glomerular and interstitial inflammation. Taking together, these studies show selective HDAC inhibition decreased several parameters of disease pathogenesis in lupus prone mice. The decrease was in part due to inhibition of autoreactive B cell differentiation. Studies are currently underway to define further the mechanism of how HDAC6 inhibits auto-reactive B cell differentiation.