Trends in Procedural Management of Meniere's Disease: Analysis of a National Insurance Claims Database.

Objective: This study used a national insurance claims database to analyze trends in procedural management of Meniere's disease. Study Design: Retrospective cohort analysis. Setting: Database study using United States inpatient and outpatient insurance claims submitted from January 2003 to December 2021. Subjects and Methods: The Merative MarketScan Commercial and Medicare Claims Databases were queried for adults (≥18 years) with a diagnosis of Meniere's Disease according to International Classification of Diseases codes. Patients receiving procedures per Current Procedural Terminology codes for endolymphatic sac surgery, vestibular nerve section, labyrinthectomy, and intratympanic dexamethasone or gentamicin were identified. Temporal trends were analyzed by calculating annual percent change (APC) in the proportion of patients receiving procedures using Joinpoint regression. Results: A total of 16,523 unique patients with MD receiving procedural management were identified. From 2003 to 2021, the proportion of patients managed with intratympanic dexamethasone increased (APC 1.76 [95% CI 1.53-1.98], P < .001). The proportion of patients receiving intratympanic gentamicin increased from 2003 to 2015 (APC 4.43 [95% CI 1.29-7.66], P = .008) but decreased from 2015 to 2021 (APC -10.87 [95% CI -18.31 to -2.76], P = .013). The proportion of patients receiving endolymphatic sac surgery (APC: -10.20 [95% CI -11.19 to -9.20], P < .001) and labyrinthectomy (APC: -6.29 [95% CI -8.12 to -4.42], P < .001) decreased from 2003 to 2021. Conclusion: From 2003 to 2021, there has been an increase in the use of intratympanic dexamethasone and a decrease in the use of intratympanic gentamicin, endolymphatic sac surgery, and labyrinthectomy for procedural management of Meniere's Disease.

The association between neighborhood disadvantage and frailty: A retrospective case series.

Background: Frailty predicts poorer outcomes in surgical patients. Recent studies have found socioeconomic status to be an important characteristic for surgical outcomes. We evaluated the association of Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), two geospatial atlases that provide a multidimensional evaluation of neighborhood deprivation, with frailty in a surgery population. Design & methods: A retrospective study of patients undergoing routine frailty screening was conducted 12/2020-8/2022. Frailty was measured using Fried's Frailty Phenotype (FFP) and the five-item Modified Frailty Index (mFI-5). ADI and SVI quartiles were determined using patient residence. Logistic regression models were used to evaluated associations of FFP (frail only vs not frail) and mFI-5 (≥2 vs 0-1) with ADI and SVI (α = 0.05). Results: Of 372 screened patients, 41% (154) were women, median age was 68% (63-74), and 46% (170) identified as non-White. Across ADI and SVI quartiles, higher number of comorbidities, decreasing median income, and frailty were associated with increasing deprivation (p < 0.01). When controlling for age, sex, comorbidities, and BMI category, frailty by FFP was associated with the most deprived two quartiles of ADI (OR 2.61, CI: [1.35-5.03], p < 0.01) and the most deprived quartile of SVI (OR 2.33, [1.10-4.95], p < 0.05). These trends were also seen with mFI-5 scores ≥2 (ADI: OR 1.64, [1.02-2.63], p < 0.05; SVI: OR 1.71, [1.01-2.91], p < 0.05). Conclusions: Surgical patients living in socioeconomically deprived neighborhoods are more likely to be frail. Interventions may include screening of disadvantaged populations and resource allocation to vulnerable neighborhoods.

Male Factor Infertility: What Every OB/GYN Should Know.

Male factor infertility plays a role in approximately 30% of infertility cases. Various causes of male factor infertility exist including congenital, acquired, idiopathic, or environmental factors. Identifying the underlying etiology of male factor infertility is a key step toward providing appropriate counseling, effective treatment options, and improving outcomes for couples with infertility. Although the recent advances and developments in assisted reproductive technology have undoubtedly improved fertility outcomes, clinicians must understand the scope of reproductive urologists in the evaluation and treatment of male infertility to provide comprehensive counseling, appropriate referral, comprehensive evaluation, and correct surgical sperm retrieval techniques when needed.

Ultra-high dose-rate proton FLASH improves tumor control.

BACKGROUND AND PURPOSE: Proton radiotherapy (PRT) offers potential benefits over other radiation modalities, including photon and electron radiotherapy. Increasing the rate at which proton radiation is delivered may provide a therapeutic advantage. Here, we compared the efficacy of conventional proton therapy (CONVpr) to ultrahigh dose-rate proton therapy, FLASHpr, in a mouse model of non-small cell lung cancers (NSCLC). MATERIALS AND METHODS: Mice bearing orthotopic lung tumors received thoracic radiation therapy using CONVpr (<0.05 Gy/s) and FLASHpr (>60 Gy/s) dose rates. RESULTS: Compared to CONVpr, FLASHpr was more effective in reducing tumor burden and decreasing tumor cell proliferation. Furthermore, FLASHpr was more efficient in increasing the infiltration of cytotoxic CD8+ T-lymphocytes inside the tumor while simultaneously reducing the percentage of immunosuppressive regulatory T-cells (Tregs) among T-lymphocytes. Also, compared to CONVpr, FLASHpr was more effective in decreasing pro-tumorigenic M2-like macrophages in lung tumors, while increasing infiltration of anti-tumor M1-like macrophages. Finally, FLASHpr treatment reduced expression of checkpoint inhibitors in lung tumors, indicating reduced immune tolerance. CONCLUSIONS: Our results suggest that FLASH dose-rate proton delivery modulates the immune system to improve tumor control and might thus be a promising new alternative to conventional dose rates for NSCLC treatment.

The FOXM1 Inhibitor RCM-1 Decreases Carcinogenesis and Nuclear ß-Catenin.

The oncogenic transcription factor FOXM1 has been previously shown to play a critical role in carcinogenesis by inducing cellular proliferation in multiple cancer types. A small-molecule compound, Robert Costa Memorial drug-1 (RCM-1), has been recently identified from high-throughput screen as an inhibitor of FOXM1 in vitro and in mouse model of allergen-mediated lung inflammation. In the present study, we examined antitumor activities of RCM-1 using tumor models. Treatment with RCM-1 inhibited tumor cell proliferation as evidenced by increased cell-cycle duration. Confocal imaging of RCM-1-treated tumor cells indicated that delay in cellular proliferation was concordant with inhibition of FOXM1 nuclear localization in these cells. RCM-1 reduced the formation and growth of tumor cell colonies in the colony formation assay. In animal models, RCM-1 treatment inhibited growth of mouse rhabdomyosarcoma Rd76-9, melanoma B16-F10, and human H2122 lung adenocarcinoma. RCM-1 decreased FOXM1 protein in the tumors, reduced tumor cell proliferation, and increased tumor cell apoptosis. RCM-1 decreased protein levels and nuclear localization of ß-catenin, and inhibited protein-protein interaction between ß-catenin and FOXM1 in cultured tumor cells and in vivo Altogether, our study provides important evidence of antitumor potential of the small-molecule compound RCM-1, suggesting that RCM-1 can be a promising candidate for anticancer therapy.