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Companies in the United States are concerned with retaining minority employees to maintain or increase the diversity of their workforce. Here we assess the value of one approach companies have used to retain minority employees: network groups. Based on data obtained from a large company with extensive network groups, this study compares the turnover intentions of minority employees who have joined one of the company's network groups to those who have not joined one of the company's network groups. The data show that employee network groups can be useful in helping companies retain managerial-level minority employees. Extensive recommendations are provided to help organizations maximize the effectiveness of network groups. [ABSTRACT FROM AUTHOR]

Introduction: The majority of children presenting with paroxysmal supraventricular tachycardia (SVT) have either accessory-pathway-mediated tachycardia or AV node reentry tachycardia. The purpose of this study is to report an unusual mechanism of SVT found in children with structurally normal hearts.Methods and Results: Records of all patients undergoing an electrophysiology study (EPS) at our institution between 2000 and 2004 were reviewed to identify those with nonautomatic focal atrial tachycardia (NAFAT). Five patients (three males) with an average age of 13.8 years (median 15 years, range 7-18 years) were identified. All presented with paroxysmal palpitations. They all had structurally normal hearts. At EPS, SVT was reproducibly induced with programmed atrial stimulation (single, double, or triple extrastimuli) in all patients. The average cycle length was 276 +/- 9 ms. Adenosine terminated SVT in 2. A 3-D electro-anatomical system mapping was used in all cases. The right atrium (RA) was mapped in all and the left in two. Foci were mapped to the posterior high RA, lateral RA, lower mid RA septum, inferior to the sinus node, and in the right and left posteroseptal areas. Average number of radiofrequency lesions placed was 8.6 +/- 5. The success rate was 80%; there was one late recurrence. No procedural complications were observed.Conclusions: NAFAT is a rare form of tachycardia that should be considered in the differential diagnosis of children presenting with SVT. It is amenable to mapping and radiofrequency ablation. [ABSTRACT FROM AUTHOR]

Infants and small children with atrioventricular (AV) nodal disease frequently require pacing in order to maintain an adequate heart rate. The maintenance of AV synchrony is physiologically optimal in this setting. Unfortunately, small size and congenital anomalies often preclude the placement of standard transvenous dual chamber pacing systems. We report the case of a small child with a pre-existing dual chamber epicardial pacing system and subsequent ventricular lead dysfunction who underwent implantation of a new single chamber transvenous system which was programmed in VVT (triggered) mode in order to maintain AV synchrony. [ABSTRACT FROM AUTHOR]

Objectives: Chondroblastoma is a rare tumor accounting for 1% of primary bone tumors. Chondroblastoma involving the skull base is exceedingly rare with approximately 60 cases reported. We reviewed our experience with chondroblastoma of the skull base with an emphasis on current lateral skull base approaches and long-term tumor control. Study Design and Setting: A retrospective case review at a tertiary neurotology private practice group was performed over a 20-year period. Five patients were identified with skull base chondroblastoma. All patients underwent surgical intervention, and success of surgery was determined by disease-free status at last follow-up. Mean follow-up time was 5.8 years. Results: Two patients underwent gross tumor removal as primary therapy. One patient underwent partial tumor removal at an outside institution, and follow-up magnetic resonance imaging demonstrated rapid growth of residual tumor. This patient was successfully treated with gross total removal of residual tumor with an infratemporal craniotomy approach. Near total tumor removal was performed in two patients because of intimate involvement of vital structures. At last follow-up, no patient had radiographic evidence of tumor recurrence. There were no significant postoperative complications. Conclusions: Gross total or near total resection of skull base chondroblastomas through lateral skull base approaches results in long-term tumor control and low complication rates. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate whether the administration of ciprofloxacin 0.3%/dexamethasone 0.1% (Ciprodex)-soaked gelfoam during tympanoplasty has adverse effects on graft healing. Records of patients who had undergone tympanoplasty with Ciprodex-soaked gelfoam packing placed in the middle and external ear canal were reviewed. The time to heal for each patient and the number of postoperative perforations/complications were recorded. Sixty-four charts met the inclusion criteria. Most procedures were primary type I tympanoplasties with temporalis fascia grafts. Healing of the tympanic membrane was documented in 95.3% of patients, and mean time to healing was 49 d. Two patients who underwent revision tympanoplasty failed to exhibit healing at any visit after surgery. Postoperative complications were infrequent. Patients with Ciprodex-soaked gelfoam packing placed during tympanoplasty showed an overall rate of healing of 95%. Although this study is limited by its retrospective design, the data suggest that the use of Ciprodex during tympanoplasty has no detrimental effect on postoperative graft healing. [ABSTRACT FROM AUTHOR]

Rationale: Lung adenocarcinoma histology and clinical outcome are heterogeneous and associated with tumor invasiveness.Objectives: We hypothesized that invasiveness is associated with a distinct molecular signature and that genes differentially expressed in tumor or adjacent stroma will identify cell surface signal transduction and matrix remodeling pathways associated with the acquisition of invasiveness in lung adenocarcinoma.Main Results: Microarray analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and invasive adenocarcinoma and adenocarcinoma-mixed type with BAC features identified transcriptional profiles of lung adenocarcinoma invasiveness. Among the signature set that was lower in adenocarcinoma-mixed compared with BAC was the type II transforming growth factor beta (TGF-beta) receptor, suggesting downregulation of TGFbetaRII is an early event in lung adenocarcinoma metastasis. Immunostaining in independently acquired specimens demonstrated a correlation between TbetaRII expression and length of tumor invasion. Repression of TGFbetaRII in lung cancer cells increased tumor cell invasiveness and activated p38 mitogen-activated protein kinases. Microarray analysis of invasive cells identified potential downstream mediators of TGFbetaRII with differential expression in lung adenocarcinomas.Conclusions: The repression of type II TGF-beta receptor may act as a significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis. [ABSTRACT FROM AUTHOR]

Abstract Background For agricultural systems to achieve climate-smart objectives, including improved food security and rural livelihoods as well as climate change adaptation and mitigation, they often need to be take a landscape approach; they must become ‘climate-smart landscapes’. Climate-smart landscapes operate on the principles of integrated landscape management, while explicitly incorporating adaptation and mitigation into their management objectives. Results An assessment of climate change dynamics related to agriculture suggests that three key features characterize a climate-smart landscape: climate-smart practices at the field and farm scale; diversity of land use across the landscape to provide resilience; and management of land use interactions at landscape scale to achieve social, economic and ecological impacts. To implement climate-smart agricultural landscapes with these features (that is, to successfully promote and sustain them over time, in the context of dynamic economic, social, ecological and climate conditions) requires several institutional mechanisms: multi-stakeholder planning, supportive landscape governance and resource tenure, spatially-targeted investment in the landscape that supports climate-smart objectives, and tracking change to determine if social and climate goals are being met at different scales. Examples of climate-smart landscape initiatives in Madagascar’s Highlands, the African Sahel and Australian Wet Tropics illustrate the application of these elements in contrasting contexts. Conclusions To achieve climate-smart landscape initiatives widely and at scale will require strengthened technical capacities, institutions and political support for multi-stakeholder planning, governance, spatial targeting of investments and multi-objective impact monitoring.

Objective: Several approaches can be used in the surgical treatment of vestibular schwannoma (VS), and the best approach remains uncertain in the literature. This systematic review and meta-analysis aim to compare the translabyrinthine approach (TLA) with the retrosigmoid approach (RSA) for VS in terms of postoperative complications., Data Sources: PubMed, Web of Science, Embase, and Cochrane., Review Methods: The primary outcome was cerebrospinal fluid (CSF) leak; secondary outcomes were facial nerve dysfunction (FND), length of stay (LOS), and meningitis. Statistical analysis was performed using RStudio 2024.04.1 + 748. Heterogeneity was assessed with I² statistics. We performed sensitivity analysis with subgroup analysis and meta-regression. Risk of bias was assessed using ROBINS-I., Results: Out of 1140 potential articles, 21 met the inclusion criteria. Among the 4572 patients, 2687 and 1885 patients in the TLA and RSA groups, respectively. No significant differences were found in CSF leak (odds ratio [OR] 1.03; 95% confidence interval [CI] 0.81,1.32; P = .794) or meningitis (OR 1.05; 95% CI 0.45, 2.43; P = .73). Meta-regression showed no association with CSF leak and the number of cases per center or publication year. The TLA is associated with a shorter LOS (MD -1.20; 95% CI -1.39, -1.01; P < .01) and a higher chance of having and HB 4 or lower compared to patients who underwent RSA (OR 0.30; 95% CI 0.10, 0.89; P = .03)., Conclusion: There was no difference in the odds of CSF leak or meningitis between the groups. In addition, the TLA has a shorter LOS and a higher chance of a better facial nerve outcome compared to the RSA., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Systemic lupus erythematosus (SLE) is a heterogenous autoimmune disease that affects multiple organs, including the heart. The mechanisms of myocardial injury in SLE remain poorly understood. In this study, we engineered human cardiac tissues and cultured them with IgG from patients with SLE, with and without myocardial involvement. IgG from patients with elevated myocardial inflammation exhibited increased binding to apoptotic cells within cardiac tissues subjected to stress, whereas IgG from patients with systolic dysfunction exhibited enhanced binding to the surface of live cardiomyocytes. Functional assays and RNA sequencing revealed that, in the absence of immune cells, IgG from patients with systolic dysfunction altered cellular composition, respiration and calcium handling. Phage immunoprecipitation sequencing (PhIP-seq) confirmed distinctive IgG profiles between patient subgroups. Coupling IgG profiling with cell surfaceome analysis identified four potential pathogenic autoantibodies that may directly affect the myocardium. Overall, these insights may improve patient risk stratification and inform the development of new therapeutic strategies., (© 2024. The Author(s).)

Purpose: In the past 2 years, nearly all 50 states have debated bills seeking to ban minors' access to gender-affirming medical interventions, with many being passed into law. This study documents gender-diverse youths' (GDY) and their caregivers' experiences as they grapple with how such laws impact their families. Methods: Sixteen GDY and 16 caregivers participating in a longitudinal study of the impact of gender-affirming care on GDYs' well-being were interviewed about how the legal and social discourse was impacting them and their families. When interviewed, some participants had completed only the initial intake, others had completed the intake and an initial medical consultation, and a few had recently started gender-affirming hormones. Thematic analysis was used to identify common threads in the youths' and caregivers' experiences. Results: Four main themes were identified: Direct effects of losing access to gender-affirming medical interventions, reflecting how losing access to care would impact well-being; growing hostility toward the gender-diverse community, noting increasing social negativity; personal and social upheaval, reflecting the many aspects of families' lives affected; and galvanization into social action, documenting drives to effect social change. Conclusion: Laws banning gender-affirming medical interventions impact GDY and their families beyond limiting access to medical care. They increase the social stressors, cause social network disruptions, increase hostility toward the gender-diverse community, and lead some GDY and caregivers to engage more politically to protect their community. Gender-affirming health care providers need to recognize how the social and political environment impact GDY and their families to provide high-quality, person-centered care.

Objective: To evaluate quality-of-life outcomes for patients with vestibular schwannomas (VS) undergoing a middle cranial fossa (MCF) approach., Study Design: Prospective study from 2018 to 2023., Setting: Tertiary academic institution., Patients: Adults with sporadic VS., Interventions: MCF., Main Outcome Measures: The primary outcome measure was the change in preoperative and 1-year postoperative Penn Acoustic Neuroma Quality-of-life (PANQOL) scores. Secondary outcome measures included hearing preservation and facial nerve function., Results: Of the 164 patients who underwent MCF for sporadic VS, 78 patients elected to voluntarily complete preoperative PANQOL assessments prior to surgery. Seventy-one (91%) of those 78 patients completed postoperative PANQOL surveys. Fifty (70%) of the respondents were female and the median age was 48 years (range, 27-71 years). Overall, at 1-year postsurgery, a minimal clinically important difference (MCID) was obtained in the hearing (mean difference, 10.5; 95% confidence interval [CI], 4.3-16.7) and anxiety (mean difference, 18.8; 95% CI, 11.7-25.9) domains. For patients with hearing preservation (n = 48, 68%), MCIDs were reached in the hearing (mean difference, 13.4; 95% CI, 6.3-20.6), anxiety (mean difference, 20.8; 95% CI, 11.8-29.9), energy (mean difference, 13.7; 95% CI, 3.6-23.8), pain (mean difference, 13.7; 95% CI, 3.6-23.8) domains, and overall PANQOL scores (mean difference, 12.7; 95% CI, 7.1-18.3). Postoperatively, 64 (90%) patients maintained a House-Brackmann I., Conclusions: To our knowledge, this is the largest study examining disease-specific QOL for VS patients undergoing MCF. Based on our institution's experience, MCF approach for small VS is associated with clinically meaningful improvements in QOL, hearing preservation, and excellent facial nerve outcomes., (Copyright © 2024, Otology & Neurotology, Inc.)

Objective: The objective of this study was to develop a nomogram to predict long-term facial nerve (FN) function after vestibular schwannoma (VS) resection., Methods: A retrospective cohort study of two tertiary academic skull base referral centers was performed. Consecutive adults > 18 years of age with sporadic unilateral VS who underwent resection between September 2016 and May 2021 were included. FN function in the immediate postoperative period and at the most recent evaluation was measured., Results: A total of 306 patients (mean age 49 years, 63% female) were included, with a mean follow-up of 18 months. The mean maximum tumor diameter was 19 mm (range 1-50 mm), and 80 (26.1%) tumors were > 25 mm. Overall, 85% of patients showed good immediate postoperative FN function (House-Brackmann [HB] grade I or II) and 89% maintained good FN function at > 12 months of follow-up. An intraoperative FN electromyographic (EMG) response ≥ 100 µV to 0.05 mA of stimulation (OR 18.6, p < 0.001) was the strongest predictor of good HB grade in the immediate postoperative period. EMG response ≥ 100 µV (OR 5.70, p < 0.001), tumor size ≤ 25 mm (OR 3.09, p < 0.05), and better immediate postoperative HB grade (OR 1.48, p = 0.005) predicted good long-term FN function on multivariable analysis. A point-of-care nomogram based on these data predicted long-term FN function with a sensitivity of 89% and specificity of 69%., Conclusions: Better immediate postoperative HB grade, intraoperative FN EMG response ≥ 100 µV, and tumor size ≤ 25 mm strongly predicted good long-term FN function after VS resection. A point-of-care nomogram based on these variables could serve as a useful tool for postoperative counseling and prognosis of long-term FN recovery.

Background: Ménière's disease (MD) is a disorder of the inner ear that causes episodic bouts of severe dizziness, roaring tinnitus, and fluctuating hearing loss. To date, no targeted therapy exists. As such, we have undertaken a large whole genome sequencing study on carefully phenotyped unilateral MD patients with the goal of gene/pathway discovery and a move towards targeted intervention. This study was a retrospective review of patients with a history of Ménière's disease. Genomic DNA, acquired from saliva samples, was purified and subjected to whole genome sequencing., Results: Stringent variant calling, performed on 511 samples passing quality checks, followed by gene-based filtering by recurrence and proximity in molecular interaction networks, led to 481 high priority MD genes. These high priority genes, including MPHOSPH8, MYO18A, TRIOBP, OTOGL, TNC, and MYO6, were previously implicated in hearing loss, balance, and cochlear function, and were significantly enriched in common variant studies of hearing loss. Validation in an independent MD cohort confirmed 82 recurrent genes. Pathway analysis pointed to cell-cell adhesion, extracellular matrix, and cellular energy maintenance as key mediators of MD. Furthermore, the MD-prioritized genes were highly expressed in human inner ear hair cells and dark/vestibular cells, and were differentially expressed in a mouse model of hearing loss., Conclusion: By enabling the development of model systems that may lead to targeted therapies and MD screening panels, the genes and variants identified in this study will inform diagnosis and treatment of MD., (© 2024. The Author(s).)

In this paper, we introduce a new, open-source software developed in Python for analyzing Auditory Brainstem Response (ABR) waveforms. ABRs are a far-field recording of synchronous neural activity generated by the auditory fibers in the ear in response to sound, and used to study acoustic neural information traveling along the ascending auditory pathway. Common ABR data analysis practices are subject to human interpretation and are labor-intensive, requiring manual annotations and visual estimation of hearing thresholds. The proposed new Auditory Brainstem Response Analyzer (ABRA) software is designed to facilitate the analysis of ABRs by supporting batch data import/export, waveform visualization, and statistical analysis. Techniques implemented in this software include algorithmic peak finding, threshold estimation, latency estimation, time warping for curve alignment, and 3D plotting of ABR waveforms over stimulus frequencies and decibels. The excellent performance on a large dataset of ABR collected from three labs in the field of hearing research that use different experimental recording settings illustrates the efficacy, flexibility, and wide utility of ABRA.

Cochlear hair cell stereocilia bundles are key organelles required for normal hearing. Often, deafness mutations cause aberrant stereocilia heights or morphology that are visually apparent but challenging to quantify. Actin-based structures, stereocilia are easily and most often labeled with phalloidin then imaged with 3D confocal microscopy. Unfortunately, phalloidin non-specifically labels all the actin in the tissue and cells and therefore results in a challenging segmentation task wherein the stereocilia phalloidin signal must be separated from the rest of the tissue. This can require many hours of manual human effort for each 3D confocal image stack. Currently, there are no existing software pipelines that provide an end-to-end automated solution for 3D stereocilia bundle instance segmentation. Here we introduce VASCilia, a Napari plugin designed to automatically generate 3D instance segmentation and analysis of 3D confocal images of cochlear hair cell stereocilia bundles stained with phalloidin. This plugin combines user-friendly manual controls with advanced deep learning-based features to streamline analyses. With VASCilia, users can begin their analysis by loading image stacks. The software automatically preprocesses these samples and displays them in Napari. At this stage, users can select their desired range of z-slices, adjust their orientation, and initiate 3D instance segmentation. After segmentation, users can remove any undesired regions and obtain measurements including volume, centroids, and surface area. VASCilia introduces unique features that measures bundle heights, determines their orientation with respect to planar polarity axis, and quantifies the fluorescence intensity within each bundle. The plugin is also equipped with trained deep learning models that differentiate between inner hair cells and outer hair cells and predicts their tonotopic position within the cochlea spiral. Additionally, the plugin includes a training section that allows other laboratories to fine-tune our model with their own data, provides responsive mechanisms for manual corrections through event-handlers that check user actions, and allows users to share their analyses by uploading a pickle file containing all intermediate results. We believe this software will become a valuable resource for the cochlea research community, which has traditionally lacked specialized deep learning-based tools for obtaining high-throughput image quantitation. Furthermore, we plan to release our code along with a manually annotated dataset that includes approximately 55 3D stacks featuring instance segmentation. This dataset comprises a total of 1,870 instances of hair cells, distributed between 410 inner hair cells and 1,460 outer hair cells, all annotated in 3D. As the first open-source dataset of its kind, we aim to establish a foundational resource for constructing a comprehensive atlas of cochlea hair cell images. Together, this open-source tool will greatly accelerate the analysis of stereocilia bundles and demonstrates the power of deep learning-based algorithms for challenging segmentation tasks in biological imaging research. Ultimately, this initiative will support the development of foundational models adaptable to various species, markers, and imaging scales to advance and accelerate research within the cochlea research community.

Background: Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF)., Methods and Results: Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST., Conclusions: Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Age-related hearing loss (ARHL) is a common sensory impairment with complex underlying mechanisms. In our previous study, we performed a meta-analysis of genome-wide association studies (GWAS) in mice and identified a novel locus on chromosome 18 associated with ARHL specifically linked to a 32 kHz tone burst stimulus. Consequently, we investigated the role of Formin Homology 2 Domain Containing 3 (Fhod3), a newly discovered candidate gene for ARHL based on the GWAS results. We observed Fhod3 expression in auditory hair cells (HCs) primarily localized at the cuticular plate (CP). To understand the functional implications of Fhod3 in the cochlea, we generated Fhod3 overexpression mice (Pax2-Cre+/-; Fhod3Tg/+) (TG) and HC-specific conditional knockout mice (Atoh1-Cre+/-; Fhod3fl/fl) (KO). Audiological assessments in TG mice demonstrated progressive high-frequency hearing loss, characterized by predominant loss of outer hair cells, and a decreased phalloidin intensities of CP. Ultrastructural analysis revealed loss of the shortest row of stereocilia in the basal turn of the cochlea, and alterations in the cuticular plate surrounding stereocilia rootlets. Importantly, the hearing and HC phenotype in TG mice phenocopied that of the KO mice. These findings suggest that balanced expression of Fhod3 is critical for proper CP and stereocilia structure and function. Further investigation of Fhod3 related hearing impairment mechanisms may lend new insight towards the myriad mechanisms underlying ARHL, which in turn could facilitate the development of therapeutic strategies for ARHL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Boussaty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Age-related hearing loss (ARHL) is a prevalent concern in the elderly population. Recent genome-wide and phenome-wide association studies (GWASs and PheWASs) have delved into the identification of causative variants and the understanding of pleiotropy, highlighting the polygenic intricacies of this complex condition. While recent large-scale GWASs have pinpointed significant SNPs and risk variants associated with ARHL, the detailed mechanisms, encompassing both genetic and epigenetic modifications, remain to be fully elucidated. This review presents the latest advances in association studies, integrating findings from both human studies and model organisms. By juxtaposing historical perspectives with contemporary genomics, we aim to catalyze innovative research and foster the development of novel therapeutic strategies for ARHL., Competing Interests: Declaration of interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Cystic vestibular schwannomas (cVSs) have more variable and less favorable clinical outcomes after microsurgical resection compared with solid VS (sVS). This study compares the preoperative presentation and postoperative outcomes between cVS and sVS., Study Design: Retrospective cohort study., Setting: Two tertiary skull base referral centers., Methods: Consecutive adult patients who underwent VS resection from 2016 to 2021 were included. Univariate and multivariate analyses compared differences in baseline symptoms and postoperative outcomes between cVS and sVS., Results: There were a total of 315 patients (64% female; mean age, 54 yrs) and 46 (15%) were cystic. cVS were significantly larger than sVS (maximum diameter, 28 vs. 18 mm, p < 0.001) and had higher rates of dysphagia and dysphonia preoperatively (p < 0.02). cVSs were more likely to undergo translabyrinthine resection (76 vs. 50%, p = 0.001) and have a higher rate of subtotal resection (STR) compared with sVS (30 vs. 13%, p = 0.003). At latest follow-up, fewer cVS achieved good facial nerve (FN) outcome (House-Brackmann [HB] I/II) (80 vs. 90%, p = 0.048). Subanalysis of cVS and sVS matched in tumor size, and surgical approach did not show differences in the rate of STR or FN outcomes (HB I/II, 82 vs. 78%, p = 0.79)., Conclusion: In this large multi-institutional series, cVSs represent a distinct entity and are characterized by larger tumor size and higher incidence of atypical symptoms. Although cVSs were more likely to undergo STR and portend worse FN outcomes than sVSs, this may be due to their larger tumor size rather than the presence of the cystic component., Competing Interests: Conflicts of interest and source of funding: None declared., (Copyright © 2023, Otology & Neurotology, Inc.)

Improving the management of metastasis in pancreatic neuroendocrine tumors (PanNETs) is critical, as nearly half of patients with PanNETs present with liver metastases, and this accounts for the majority of patient mortality. We identified angiopoietin-2 (ANGPT2) as one of the most upregulated angiogenic factors in RNA-Seq data from human PanNET liver metastases and found that higher ANGPT2 expression correlated with poor survival rates. Immunohistochemical staining revealed that ANGPT2 was localized to the endothelial cells of blood vessels in PanNET liver metastases. We observed an association between the upregulation of endothelial ANGPT2 and liver metastatic progression in both patients and transgenic mouse models of PanNETs. In human and mouse PanNET liver metastases, ANGPT2 upregulation coincided with poor T cell infiltration, indicative of an immunosuppressive tumor microenvironment. Notably, both pharmacologic inhibition and genetic deletion of ANGPT2 in PanNET mouse models slowed the growth of PanNET liver metastases. Furthermore, pharmacologic inhibition of ANGPT2 promoted T cell infiltration and activation in liver metastases, improving the survival of mice with metastatic PanNETs. These changes were accompanied by reduced plasma leakage and improved vascular integrity in metastases. Together, these findings suggest that ANGPT2 blockade may be an effective strategy for promoting T cell infiltration and immunostimulatory reprogramming to reduce the growth of liver metastases in PanNETs.

Objective: Increased institutional surgical resection case volume for vestibular schwannomas (VSs) has been associated with improved patient outcomes, including reduced risk of prolonged hospital stay and readmission. Socioeconomic disparities in the pursuit of care at these high-volume institutions remain unknown., Study Design: Retrospective cohort epidemiological study., Setting: National Cancer Database, a hospital-based registry of over 1,500 facilities in the United States., Patients: Adult VS patients (age, >18 years) treated surgically., Interventions: High- versus low-volume facilities, defined using a facility case volume threshold of 25 cases per year. A risk-adjusted restricted cubic spline model was previously used to identify this risk threshold beyond which the incremental benefit of increasing case volume began to plateau., Main Outcome Measures: Sociodemographic factors, including race, ethnicity, income, insurance status, and rurality. Multivariable analyses were adjusted for patient and tumor characteristics, including age, sex, Charlson-Deyo score, and tumor size., Results: A totoal of 10,048 patients were identified (median [interquartile range] age = 51 [41-60] years, 54% female, 87% Caucasian). Patients with Spanish/Hispanic ethnicity (OR = 0.71, 95% confidence interval [CI] = 0.52-0.96), income below median (OR = 0.63, 95% CI = 0.55-0.73]), and Medicare, Medicaid, or other government insurance versus private insurance (OR = 0.63, 95% CI = 0.53-0.74) had reduced odds of treatment at a high-volume facility. Further sensitivity analyses in which facility volume was operationalized continuously reinforced direction and significance of these associations., Conclusions: Socioeconomic disparities exist in the propensity for VS patients to be treated at a high-volume facility. Further work is needed to understand the nature of these associations and whether interventions can be designed to mitigate them., Competing Interests: Conflict of interest: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Objective: Evaluate for differences in postoperative hearing in patients who undergo immediate versus delayed hearing preservation microsurgical resection of vestibular schwannomas (VS)., Study Design: Retrospective single-institution cohort study spanning November 2017 to November 2021., Setting: Single-institution tertiary care hospital., Patients: Sporadic VS in patients with American Academy of Otolaryngology-Head and Neck Surgery hearing classification A or B, with tumor size less than or equal to 2 cm and undergoing hearing preservation microsurgical resection., Interventions: Delayed surgical intervention defined by time from first diagnostic MRI to date of surgery being greater than 3 months., Main Outcome Measures: Preoperative and postoperative audiometric performance., Results: In total, 193 patients met inclusion criteria. Within the cohort, 70 (36%) proceeded with surgery within 3 months of diagnostic MRI with a mean observation time of 62 days, whereas 123 (63%) underwent surgery after 3 months with a mean observation time of 301 days. There was no difference in preoperative hearing between the two groups with word recognition score 99% in early intervention group and 100% in delayed intervention group ( p = 0.6). However, 64% of those who proceeded with immediate surgery had successful hearing preservation, compared to a 42% of those who had delayed intervention ( p < 0.01). In a multivariable logistic regression accounting for preoperative word recognition score, tumor size, and age at diagnosis, the odds of hearing preservation were lower in those who delayed surgery compared to immediate surgery (odds ratio, 0.31; 95% confidence interval, 0.15-0.61)., Conclusions: Patients who underwent microsurgical resection within 3 months of diagnosis demonstrated a hearing preservation advantage compared to those who did not. Findings of this study highlight the counseling challenges associated with the timing of surgical treatment of VS in patients presenting with good preoperative hearing and small tumors., Competing Interests: Conflict of interest: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome caused by a mutation in the NF2 suppressor gene and is characterized by the development of multiple benign tumors throughout the central nervous system. Bilateral vestibular schwannomas (VSs) are pathognomonic for NF2 and are associated with progressive hearing loss and eventual deafness in most patients. This review presents current management options for NF-2-associated VSs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: High-volume hospitals are associated with improved surgical outcomes for acoustic neuromas (ANs). Due to the benign and slow-growing nature of ANs, many patients travel to geographically distant cities, states, or countries for their treatment. However, the impact of travel burden to high-volume centers, as well as its relative benefit are poorly understood. We compared post-operative outcomes between AN patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals., Methods: The National Cancer Database was used to analyze AN patients that underwent surgery (2004-2015). Patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) were compared to patients in the highest quartile of travel distance and volume (Long-travel/High-Volume: LTHV). Only STLV and LTHV cases were included for analysis., Results: Of 13,370 cases, 2,408 met inclusion criteria. STLV patients (n = 1,305) traveled a median of 6 miles (Interquartile range [IQR] 3-9) to low-volume centers (median 2, IQR 1-3 annual cases) and LTHV patients (n = 1,103) traveled a median of 143 miles [IQR 103-230, maximum 4,797] to high-volume centers (median 34, IQR 28-42 annual cases). LTHV patients had lower Charlson/Deyo scores (p = 0.001), mostly received care at academic centers (81.7% vs. 39.4%, p < 0.001), and were less likely to be minorities (7.0% vs. 24.2%, p < 0.001) or underinsured (4.2% vs. 13.8%, p < 0.001). There was no difference in average tumor size. On multivariable analysis, LTHV predicted increased likelihood of gross total resection (odds ratio [OR] 5.6, 95% confidence interval [CI] 3.8-8.4, p < 0.001), longer duration between diagnosis and surgery (OR 1.3, 95% CI 1.0-1.6, p = 0.040), decreased length of hospital stay (OR 0.5, 95% CI 0.4-0.7, p < 0.001), and greater overall survival (Hazard Ratio [HR] 0.6, 95% CI 0.4-0.95, p = 0.029). There was no significant difference in 30-day readmission on adjusted analysis., Conclusion: Although traveling farther to high-volume centers was associated with greater time between diagnosis and treatment for AN patients, they experienced superior postoperative outcomes compared to patients who received treatment locally at low-volume centers. Enabling access and travel to high-volume centers may improve AN patient outcomes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the senescence-accelerated mouse prone 8 (SAMP8) mouse model, oxidative stress leads to premature senescence and age-related hearing impairment (ARHI). CMS121 inhibits oxytosis/ferroptosis by targeting fatty acid synthase. The aim of our study was to determine whether CMS121 is protective against ARHI in SAMP8 mice. Auditory brainstem responses (ABRs) were used to assess baseline hearing in sixteen 4-week-old female SAMP8 mice, which were divided into two cohorts. The control group was fed a vehicle diet, while the experimental group was fed a diet containing CMS121. ABRs were measured until 13 weeks of age. Cochlear immunohistochemistry was performed to analyze the number of paired ribbon-receptor synapses per inner hair cell (IHC). Descriptive statistics are provided with mean ± SEM. Two-sample t-tests were performed to compare hearing thresholds and paired synapse count across the two groups, with alpha = 0.05. Baseline hearing thresholds in the control group were statistically similar to those of the CMS121 group. At 13 weeks of age, the control group had significantly worse hearing thresholds at 12 kHz (56.5 vs. 39.8, p = 0.044) and 16 kHz (64.8 vs. 43.8, p = 0.040) compared to the CMS121 group. Immunohistochemistry showed a significantly lower synapse count per IHC in the control group (15.7) compared to the CMS121 group (18.4), p = 0.014. Our study shows a significant reduction in ABR threshold shifts and increased preservation of IHC ribbon synapses in the mid-range frequencies among mice treated with CMS121 compared to untreated mice., (© 2023. The Author(s).)

Importance: High surgical vestibular schwannoma case volume in a medical institution may decrease the risk of adverse outcomes among patients undergoing vestibular schwannoma surgery., Objective: To study the association between surgical vestibular schwannoma case volume and excess time in the hospital after vestibular schwannoma surgery., Design, Setting, and Participants: This cohort study evaluated data from the National Cancer Database from January 1, 2004, through December 31, 2019, on Commission on Cancer-accredited facilities in the US. The hospital-based sample comprised adult patients aged 18 years or older with a vestibular schwannoma treated with surgery., Exposures: Facility case volume, defined as the mean number of surgical vestibular schwannoma cases per year in the 2 years preceding the index case., Main Outcomes and Measures: The primary outcome was a composite of prolonged hospital stay (>90th percentile) or 30-day readmission. Risk-adjusted restricted cubic splines were used to model the probability of the outcome according to facility volume. The inflection point (in cases per year) when the declining risk of excess time in the hospital began to plateau was selected as the threshold to define high- and low-volume facilities. Outcomes were compared among patients treated at high- and low-volume facilities, with mixed-effects logistic regression models adjusting for patient sociodemographic characteristics, comorbidities, tumor size, and clustering within facilities. Collected data were analyzed between June 24 and August 31, 2022., Results: Among 11 524 eligible patients (mean [SD] age, 50.2 [12.8] years; 53.5% female; 46.5% male) who underwent surgical resection of vestibular schwannoma at 66 reporting facilities, the median length of stay was 4 (IQR, 3-5) days, and 655 patients (5.7%) were readmitted within 30 days. The median case volume was 16 (IQR, 9-26) cases per year. An adjusted restricted cubic spline model identified a downtrending probability of excess time in the hospital with increasing volume. The declining risk of excess time in the hospital began to plateau at a facility volume of 25 cases per year. Surgery at a facility with an annual case volume at or above this threshold was independently associated with a 42% reduction in the odds of excess time in the hospital compared with surgery at a low-volume center (odds ratio, 0.58; 95% CI, 0.44-0.77)., Conclusions and Relevance: This cohort study found that among adults undergoing vestibular schwannoma surgery, a higher facility case volume was associated with a reduced risk of prolonged hospital stay or 30-day readmission. A facility case volume of 25 cases per year may represent a risk-defining threshold.