Citations

AbstractTixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre‐exposure prophylaxis against COVID‐19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID‐19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID‐19 infection, severity of COVID‐19 infection, graft function, and rejection. Safety outcomes included cardiovascular (CV) and hypersensitivity events post tix/cil administration. A total of 410 transplant patients were included in the analysis: 20 heart, 92 liver, 243 kidney, 25 simultaneous pancreas/kidney, 23 simultaneous liver/kidney, and seven simultaneous heart/kidney. Twenty‐seven (6.5%) patients tested positive for COVID‐19 via PCR or antigen test post tix/cil. No apparent difference was observed in patients testing positive for COVID‐19 by type of organ transplant (p = .122). Twenty‐five of the 27 patients testing positive for COVID‐19 reported symptomatic infection, only nine of whom were hospitalized. No patients were mechanically ventilated and no deaths due to COVID‐19 occurred. No significant changes in graft function were observed. Clinically significant rejection was diagnosed and treated in four patients. COVID‐19 breakthrough infection rates remained low in immunocompromised solid organ transplant recipients who received tix/cil. No significant immunologic risks were observed.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) demonstrates high rates of type 2 diabetes mellitus (T2DM) remission, a phenomenon hypothesized to be mediated mainly by weight loss. Compared with procedures that do not bypass the proximal small intestines, such as sleeve gastrectomy (SG), RYGB exhibits weight loss–independent intestinal mechanisms conducive to T2DM remission. We investigated continued diabetes remission (CDR) rates despite weight recurrence (WR) after RYGB compared with an SG cohort. STUDY DESIGN: A retrospective review of patients who underwent successful primary RYGB or SG with a BMI value of 35 kg/m 2 or more and a preoperative diagnosis of T2DM was performed. Patients with less than 5 years of follow-up, absence of WR, or lack of T2DM remission at nadir weight were excluded. After selecting the optimal procedure for glycemic control, rates of CDR were then stratified into WR quartiles and compared. RESULTS: A total of 224 RYGB and 46 SG patients were analyzed. The overall rate of CDR was significantly higher in the RYGB group (75%) compared with the SG group (34.8%; p < 0.001). The odds of T2DM recurrence were 5.5 times higher after SG compared with RYGB. Rates of CDR were stratified into WR quartiles (85.5%, <25%; 81.7%, 25% to 44.9%; 63.2%, 45% to 74.9%; and 60%, >75%). Baseline insulin use, higher preoperative glycosylated hemoglobin, and longer preoperative duration of T2DM were associated with T2DM recurrence, whereas WR was not. CONCLUSIONS: T2DM remission rates after RYGB are maintained despite WR, arguing for a concurrent weight loss–independent metabolic benefit likely facilitated by bypassing the proximal small intestine.

Background: Roux-en-Y gastric bypass (RYGB) has demonstrated excellent glycemic control and type 2 diabetes mellitus (T2DM) remission for patients with obesity and T2DM. Duration of T2DM is a consistent negative predictor of remission after RYGB. However, the exact timing to offer surgical intervention during the course of the disease is not well elucidated. Material and methods: The authors performed a retrospective cohort study between 2008 and 2020 to establish the exact association between duration of T2DM and remission after RYGB. The authors divided our cohort into quartiles of preoperative disease duration to quantify the change in remission rates for each year of delay between T2DM diagnosis and RYGB. The authors also compared the average time to remission and changes in glycemic control parameters. Results: A total of 519 patients (67.2% female; age 53.4±10.7 year; BMI 46.6±8.4 kg/m 2 ) with a follow-up period of 6.6±3.8 years were included. Remission was demonstrated in 51% of patients. Longer duration of T2DM was a significant negative predictor of remission with an estimated decrease in remission rates of 7% for each year of delay [(OR=0.931 (95% CI: 0.892–0.971); P< 0.001)]. Compared to patients with <3 years of T2DM, remission decreased by 37% for patients with 3–6 years, 64% for those with 7–12 years, and 81% for patients with more than 12 years ( P <0.001). Half of the patients reached T2DM remission after 0.5 and 1.1 years, respectively, for the first and second quartiles, while patients in the other quartiles never reached 50% remission. Lastly, The authors noted an overall improvement in all glycemic control parameters for all quartiles at last follow-up. Conclusion: Patients with a recent history of T2DM who undergo early RYGB experience significantly higher and earlier T2DM remission compared to patients with a prolonged history of preoperative T2DM, suggesting potential benefit of early surgical intervention to manage patients with obesity and T2DM.

Objectives: Variations in management of sinusitis in primary care settings can be associated with inappropriate antibiotic prescriptions and delays in treatment. The objective of this study was to identify patient and provider characteristics associated with possible inaccurate diagnosis and management of sinusitis. Methods: We performed a cross-sectional retrospective analysis using an established regional healthcare database of patients who received a diagnosis of sinusitis between 2011 and 2022 from a non-otolaryngologist provider. Patient’s comorbidities, insurance status, chronicity of sinusitis, and prescriptions were included. We noted if patients were referred to an otolaryngology practice and if they received a diagnosis of sinusitis from an otolaryngologist. Results: We analyzed 99 581 unique patients and 168 137 unique encounters. The mean age was 41.5 (±20.4 years) and 35.7% were male. Most patients had private insurance (88.5%), acute sinusitis (81.2%), and were seen at a primary care office (97.8%). Approximately 30% of patients were referred to an otolaryngology practice for sinusitis. Of referred patients, 50.6% did not receive a diagnosis of sinusitis from an otolaryngology practice. Patients without a sinusitis diagnosis by an otolaryngology practice received significantly more mean courses of antibiotics (5.04 vs 2.39, P < .0001) and oral steroids (3.53 vs 2.08, P < .0001). Conclusions: Over half of the patients referred to an otolaryngology practice from primary care for sinusitis did not receive a diagnosis of sinusitis from an otolaryngology practice. Further research should investigate implications for increased healthcare costs and inappropriate prescription trends associated with the management of sinusitis.

Abstract Introduction There has been significant ongoing debate on the role and utility of prednisone post-vasectomy reversal to improve sperm counts and long-term patency. However, there are relatively limited data available on the efficacy, with essentially no data available on pregnancy outcomes. Objective To report outcomes of randomized, clinical trial evaluating varying protocols for prednisone administration post vasectomy reversal. Methods A randomized, controlled trial was performed (NCT04788823) with an anticipated 100 men randomized to one of four prednisone protocols post vasectomy reversal: no treatment (Control), prednisone 20 mg taper over 1 month beginning the first month post-op and then every other month x 6 months (High Dose), prednisone 20 mg taper over 1 month if declining sperm counts or a 0 count were identified (PRN), and prednisone 5 mg daily x 1 week, followed by no treatment x 1 week, continued for 6 months (Low Dose). Randomization tables were created a priori to ensure an equal representation of differing durations of time since the original vasectomy as well as an equal distribution of VV/VV vs VV/EV vs EV/EV procedures. All men had semen analyses obtained monthly for a first 12 months. Surveys were sent periodically to follow-up on subsequent pregnancies. Inclusion criteria included having a female partner &lt;36 years of age with no known fertility factors. Results A total of 75 men were ultimately enrolled due to interim findings suggesting inferiority of the High Dose and PRN treatment arms and decision to close those arms before completing full enrollment. Final enrollment included: Control (n=25), High Dose (n=14), PRN (n=11), and Low Dose (n=25). The mean patient age was 38.5 years, mean partner age 29.6, and mean time since vasectomy 6.3 years (SD 5.0). 82% of men underwent VV/VV, while 15% VV/EV, and 3% EV/EV. All men underwent successful anastomosis bilaterally with no cases of one-sided or no anastomosis performed. At a mean follow-up of 16.5 months (range 7.6 to 25.1), an overall patency (sperm observed on sample) rate of 93% was noted (Control 96%, High Dose 93%, PRN 100%, Low Dose 88%, p=0.41). The mean sperm concentration post-op was 34.4 million/ml (Control 24.0, High Dose 38.4, PRN 21.0, Low Dose 49.8, p=0.33). Patency rates at 6- and 12-months were: 6-months (Control 88%, High Dose 80%, PRN 83%, Low Dose 94%, p=0.75); 12-months (Control 75%, High Dose 71%, PRN 75%, Low Dose 91%). Mean sperm concentrations at 6- and 12-months were: 6-months (Control 15.7, High Dose 21.5, PRN 6.9, Low Dose 25.7, p=0.50); 12-months (Control 12.6 million/ml, High Dose 17.1, PRN 36.1, Low Dose 50.4, p=0.64) At the 6-month post-op time point, the overall rate of pregnancy was 47%, with notable differences between cohorts: Control 57%, High Dose 10%, PRN 38%, and Low Dose 67%, p=0.02. No patients discontinued prednisone due to side effects. Conclusions Prednisone taper protocols appear to reduce the likelihood for pregnancy following vasectomy reversal. Use of low-dose prednisone results in non-statistically higher rates of patency at 6- and 12-months, mean sperm concentration at 6- and 12-months, and pregnancy at 6-months. Overall results suggest superiority of either no prednisone post-vasectomy reversal or a low dose protocol but argue against the use of higher dosages at any time due to its negative impacts on pregnancy rates despite maintained sperm counts. Disclosure No.

654 Background: MSI and TMB correlate with ICI efficacy. We assessed the association between TMB and MSI with outcomes in pts with aUC treated with anti-PD1/L1 in a ‘real-world’ cohort. We hypothesize that pts with high TMB and MSI-high (H) have better outcomes with ICI. Methods: In this retrospective study we included pts from 13 sites treated with ICI for aUC. We calculated overall response rate (ORR), median overall and progression-free survival (mOS, mPFS) using KM method from ICI start. TMB and MSI were assessed by NGS. TMB was analyzed as dichotomous (≥10 vs <10 mut/Mb) and continuous variable. The analysis was stratified by therapy line (1L/upfront, 2+L). Multivariable models were adjusted by Khaki factors for 1L/upfront and Bellmunt factors for 2+L. We separately analyzed pts on maintenance avelumab (mAV). MSI is reported with descriptive statistics only. Results: 342 pts were treated with ICI 1L/upfront or 2+L (69% pure UC, median age at ICI start 69, 77% men, 90% White, 16% upper tract primary, 12% liver metastases [mets], 78% ECOG PS 0-1). Median f/u from ICI start was 34 months (mo). ORR was 36% (95%CI 26-46%) in pts with TMB≥10 vs 30% (95%CI 23-36%) with TMB<10 (OR=1.4 [95%CI 0.8-2.5] p=0.3). ORR was 75% (6/8) in pts with MSI-H and 30% (60/200) with MSI stable (MSI-S). mPFS was similar between TMB≥10 and <10 groups (6 vs 4 mo; HR=0.88 [95%CI 0.61-1.26] p=0.48) and between MSI-H and MSI-S (5 mo). mOS was numerically longer (not significant) in pts with TMB≥10 vs TMB<10: 25 vs 21 mo; (HR=0.7 [95%CI 0.50-1.09] p=0.12) and with MSI-H and MSI-S (NR and 20 mo). A significant association was found between TMB (continuous variable) and OS (HR=0.97 [95%CI 0.95-0.99] p=0.01). TMB analyses by therapy line are shown in Table. In the 1L/upfront setting (N=144), ORR 71% (5/7) vs 33% (45/135), mPFS 5 and 4 mo, mOS NR and 22 mo for MSI-H and MSI-S, respectively. Pts on mAV (n=77) were 77% men, 92% White, 16% upper primary, 13% liver mets, 84% ECOG PS 0-1 with median f/u 15 mo from avelumab start; mOS was NR for MSI-H and 24 mo for MSI-S; mPFS was 4 mo for both groups. Of 3 pts on mAV with MSI-H: 1 CR, 2 SD; of 58 pts with MSI-S: 4CR, 4PR, 24 SD, 21 PD, 5 unknown. Conclusions: MSI-H had numerically higher ORR and higher TMB was associated with longer OS with ICI, but further validation is needed. Limitations: retrospective design, small sample size for MSI-H cases, lack of randomization and central scan review, selection/confounding. [Table: see text]

AbstractBackground and ObjectivesTranscranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have evidence for their potential in the treatment of substance use disorders (SUD). Medication for addiction treatment (MAT) is underutilized and not always effective. We identified randomized controlled trials (RCTs) and case studies that evaluated the effectiveness of TMS or tDCS used concurrently with MAT in SUD treatment.MethodsA systematic review of published literature following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines was conducted on 6/1/2023 by a medical librarian. Craving‐related scales were extracted for an effect size calculation. The Physiotherapy Evidence Database (PEDro) scale assessed study quality.ResultsEight studies (7 RCT, 1 case) including 253 individuals were published from 2015 to 2022, 5 of which had available data for meta‐analysis. TMS or tDCS combined with MAT significantly reduced craving‐related measures relative to sham stimulation (Hedges' g = −0.42, confidence interval: −0.73 to −0.11, p < .01). Opioid use disorder, methadone, and the dorsolateral prefrontal cortex were the most commonly studied SUD, MAT, and target region.Discussion and ConclusionsOur results show a significant effect; however, is limited by a small number of studies with heterogeneous methodology across intervention methods and SUDs. Additional trials are needed to fully assess the clinical impact and mechanisms of combined brain stimulation and pharmacotherapy. We discuss a possible mechanism for synergism from these treatment combinations.Scientific SignificanceAdds the first systematic review of combination treatment with TMS or tDCS and MAT in SUD patients to the literature and estimates its overall effect size.