Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020.

INTRODUCTION: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings. METHODS: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences. RESULTS: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals. CONCLUSIONS: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery.

Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival.

Fasting mimicking diets (FMDs) are effective in the treatment of many solid tumors in mouse models, but their effect on hematologic malignancies is poorly understood, particularly in combination with standard therapies. Here we show that cycles of a 3-day FMD given to high-fat-diet-fed mice once a week increased the efficacy of vincristine to improve survival from BCR-ABL B acute lymphoblastic leukemia (ALL). In mice fed a standard diet, FMD cycles in combination with vincristine promoted cancer-free survival. RNA seq and protein assays revealed a vincristine-dependent decrease in the expression of multiple autophagy markers, which was exacerbated by the fasting/FMD conditions. The autophagy inhibitor chloroquine could substitute for fasting/FMD to promote cancer-free survival in combination with vincristine. In vitro, targeted inhibition of autophagy genes ULK1 and ATG9a strongly potentiated vincristine's toxicity. Moreover, anti-CD8 antibodies reversed the effects of vincristine plus fasting/FMD in promoting leukemia-free survival in mice, indicating a central role of the immune system in this response. Thus, the inhibition of autophagy and enhancement of immune responses appear to be mediators of the fasting/FMD-dependent cancer-free survival in ALL mice.

Proton Therapy for Skull Base Chondrosarcoma.

Chondrosarcoma is a type of an endochondral bone malignancy that is primarily treated surgically with radiation therapy used in the adjuvant setting or in cases of unresectable disease. Proton therapy has potential advantages compared with traditional photon therapy for the treatment of tumors in close proximity to critical structures due to the theoretic lower exit dose. Studies have shown improved survival in patients with skull base chondrosarcoma who undergo proton therapy. However, there is a lack of randomized data. Further studies are needed to define the role of proton therapy in the treatment of skull base chondrosarcoma.

Neomycin-induced deafness in neonatal mice.

BACKGROUND: Hearing impairment is a rising public health issue, and current therapeutics fail to restore normal auditory sensation. Animal models are essential to a better understanding of the pathophysiology of deafness and developing therapeutics to restore hearing. NEW METHODS: Wild-type CBA/CaJ neonatal mice P2-5 were used in this study. Neomycin suspension (500 nl of 50 or 100 mg/ml) was micro-injected into the endolymphatic space. Cochlear morphology was examined 3 and 7 days after injection; hair cell (HC) loss, supporting cell morphology, and neurite denervation pattern were assessed with whole-mounts. At 2 and 4 weeks post-injection, the spiral ganglion neuron (SGN) density was analyzed with cryostat sections. Audiometric responses were measured with auditory brain response (ABR) at 4 weeks. RESULTS: Rapid and complete degeneration of the inner and outer HCs occurred as early as 3 days post-injection. Subsequently, time- and dose-dependent degeneration patterns were observed along the axis of the cochlear membranous labyrinth forming a flat epithelium. Likewise, the SGN histology demonstrated significant cell density reduction at 2 and 4 weeks. The ABR threshold measurements confirmed profound deafness at 4 weeks. COMPARISON WITH EXISTING METHODS: Compared to previously described local and systemic aminoglycoside injections, this method provides a reliable, robust, and rapid deafening model with a single infusion of neomycin in neonatal mice. This model also allows for investigating the effects of inner ear damage during auditory maturation. CONCLUSIONS: A single injection of neomycin into the endolymphatic space induces robust HC loss and denervation in neonatal mice.

Incidence of Postoperative CSF Leaks in Class III Obese Patients Undergoing Middle Cranial Fossa Approach for Spontaneous CSF Leak Repair.

OBJECTIVE: To determine the safety and effectiveness of the middle cranial fossa (MCF) approach for spontaneous cerebrospinal fluid leak (sCSF-L) repair in class III obese patients. To also assess the need for prophylactic lumbar drain (LD) placement in this patient population. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary Academic Center. PATIENTS: All patients older than 18 years undergoing sCSF-L repair with an MCF approach. INTERVENTION: An MCF craniotomy for sCSF-L repair. MAIN OUTCOME MEASURE: Rate of complications and postoperative leaks. RESULTS: There were no perioperative complications in 78.9% (56/71) of cases. The surgical complication rate was 12.5% (2/16), 10% (2/20), and 22.2% (6/27) in class I, class II, and class III obese patients. There was no statistically significant difference in complications among these three groups. The most common postoperative complication was a persistent CSF leak in the acute postoperative period with an overall rate of 9.9% (7/71) with six of the seven patients requiring postoperative LD placement. The percentage of postoperative CSF leaks in nonobese, class I, class II, and class III patients were 25% (2/8), 12.5% (2/16), 0% (0/20), and 11.1% (3/27), respectively. There was no statistically significant difference in the rate of postoperative CSF leaks among the four groups (chi-square, p = 0.48). In all cases, the acute postoperative CSF leaks resolved in the long term and did not require further surgical repair. CONCLUSIONS: We determine that MCF craniotomy repair for sCSF-Ls is safe in patients with class III obesity, and the incidence of postoperative CSF leaks did not vary among other obesity classes. We also find that prophylactic placement of LDs is not routinely needed in this population.

Long-term outcomes with the pulmonary autograft inclusion technique in adults with bicuspid aortic valves undergoing the Ross procedure.

OBJECTIVE: To compare outcomes with wrapped (pulmonary autograft inclusion) versus unwrapped techniques in adults with bicuspid aortic valves undergoing the Ross procedure. METHODS: Between 1992 and 2019, 129 adults with bicuspid aortic valves (aged ≥18 years) underwent the Ross procedure by a single surgeon. Patients were divided into those without autograft inclusion (unwrapped, n = 71) and those with autograft inclusion (wrapped, n = 58). Median follow-up was 10.3 years (interquartile range, 3.0-16.8 years). Need for autograft reintervention was analyzed using competing risks. RESULTS: Pre- and intraoperative characteristics as well as 30-day morbidity or mortality did not differ between cohorts. Survival at 1, 5, and 10 years, respectively, was 97.2%, 97.2%, and 95.6% in the unwrapped cohort and 100%, 100%, and 100% in the wrapped cohort (P = .15). Autograft valve failure occurred in 25 (35.2%) of the unwrapped and 3 (5.2%) of the wrapped patients. Competing risks analysis demonstrated the wrapped cohort to have a lower need for autograft reintervention (subhazard ratio, 0.28, 95% confidence interval, 0.08-0.91; P = .035). The cumulative incidence of autograft reintervention (death as a competing outcome) at 1, 5, and 10 years, respectively, was 10.2%, 14.9%, and 26.8% in the unwrapped cohort and 4.0%, 4.0%, and 4.0% in the wrapped cohort. CONCLUSIONS: In adults with bicuspid aortic valves, the Ross procedure with pulmonary autograft inclusion stabilizes the aortic root preventing dilatation and reduces the need for reoperation. The autograft inclusion technique allows the Ross procedure to be performed in this population with excellent long-term outcomes.

Neuralgia and Atypical Facial, Ear, and Head Pain.

Though there have been considerable strides in the diagnosis and care of orofacial pain disorders, facial neuralgias, and myofascial pain dysfunction syndrome remain incredibly cumbersome for patients and difficult to manage for providers. Cranial neuralgias, myofascial pain syndromes, temporomandibular dysfunction (TMD), dental pain, tumors, neurovascular pain, and psychiatric diseases can all present with similar symptoms. As a result, a patient's quest for the treatment of their orofacial pain often begins on the wrong foot, with a misdiagnosis or unnecessary procedure, which makes it all the more frustrating for them. Understanding the natural history, clinical presentation, and management of facial neuralgias and myofascial pain dysfunction syndrome can help clinicians better recognize and treat these conditions. In this article, we review updated knowledge on the pathophysiology, incidence, clinical features, diagnostic criteria, and medical management of TN, GPN, GN, and MPDS.