Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear.

OBJECTIVE: To investigate the impact of sound exposure, with the resultant windows vibration on perilymphatic concentrations following intratympanic (IT) dexamethasone and gentamicin in an animal model. STUDY DESIGN: Animal model blinded study. SETTING: Animal facility of a tertiary medical center. METHODS: Bilateral IT dexamethasone or gentamicin was applied to 15 tested rats. Following injections, each rat was exposed for 3 minutes to free field 30 dB sound pressure level (SPL), 512 vHz noise, with 1 external auditory canal plugged (contralateral control). Following noise exposure, perilymph was obtained from both ears. Drug concentrations were measured using ultrahigh-performance liquid chromatography-mass spectrometer. RESULTS: For dexamethasone, the average (±SD) perilymphatic steroidal concentration was 0.417 µg/mL (±0.549) in the control ears versus 0.487 µg/mL (±0.636) in the sound-exposed ears (P = .008). The average (±SD) gentamicin perilymphatic concentration was 8.628 µg/mL (±2.549) in the sound-exposed ears, compared to 4.930 µg/mL (±0.668) in the contralateral control (nonsound exposed) ears. Sound exposure promoted steroidal and gentamicin diffusion to the inner ear by an averaged (±SD) factor of 1.431 and 1.730 (±0.291 and 0.339), respectively. CONCLUSION: Low-intensity noise (30 dB SPL) was found to enhance dexamethasone phosphate and gentamicin diffusion to the inner ear (by an averaged factor of ∼1.4 and 1.7, respectively) in a murine model.

Spatially Resolved Microglia/Macrophages in Recurrent Glioblastomas Overexpress Fatty Acid Metabolism and Phagocytic Genes.

BACKGROUND: Glioblastoma (GBM) tumors are rich in tumor-associated microglia/macrophages. Changes associated with treatment in this specific cell population are poorly understood. Therefore, we studied changes in gene expression of tumor-associated microglia/macrophages (Iba1+) cells in de novo versus recurrent GBMs. METHODS: NanoString GeoMx® Digital Spatial Transcriptomic Profiling of microglia/macrophages (Iba1+) and glial cells (Gfap+) cells identified on tumor sections was performed on paired de novo and recurrent samples obtained from three IDH-wildtype GBM patients. The impact of differentially expressed genes on patient survival was evaluated using publicly available data. RESULTS: Unsupervised analyses of the NanoString GeoMx® Digital Spatial Profiling data revealed clustering based on the transcriptomic data from Iba1+ and Gfap+ cells. As expected, conventional differential gene expression and enrichment analyses revealed upregulation of immune-function-related genes in Iba1+ cells compared to Gfap+ cells. A focused differential gene expression analysis revealed upregulation of phagocytosis and fatty acid/lipid metabolism genes in Iba1+ cells in recurrent GBM samples compared to de novo GBM samples. Importantly, of these genes, the lipid metabolism gene PLD3 consistently correlated with survival in multiple different publicly available datasets. CONCLUSION: Tumor-associated microglia/macrophages in recurrent GBM overexpress genes involved in fatty acid/lipid metabolism. Further investigation is needed to fully delineate the role of PLD phospholipases in GBM progression.

Balloon dilation of the eustachian tube using endovascular balloon under local anesthesia-a case series and systematic literature review.

Objective: To report a novel technique in Balloon Dilation of Eustachian Tube (BDET) using an endovascular balloon (EVB), in a prospective cohort. The results are compared with reported outcomes using standard balloons. Methods: Demographic information and clinical parameters were collected prospectively fora series of patients with obstructive eustachian tube dysfunction (OETD). Balloon dilation Eustachian tuboplasty was performed under local anesthesia in a tertiary referral center, using the EVB. Systematic literature review was used for comparison, using Medline via "PubMed", "Embase", and "Web of Science". Results: Eight OETD candidates (12 ears) were enrolled; 5 males and 3 females. Average age was 48 (range -23 to 63) years. The most common presenting symptom was aural fullness (9/12), followed by ear pressure (7/12), hearing loss (5/12) and tinnitus (4/12). Otoscopically, tympanic membrane retraction was evident in 10/12 ears, the majority of which was class II-Sade classification. Pre-operative tympanogram was type B and C in 7 and 5 ears, respectively. All BDETs were performed without complications. Post-operative tympanometry was A in 8/12 ears. Post-operatively, Eustachian Tube Dysfunction Questionnaire-7 results reduced to within normal limits (average score ≤3) in 11/12 ears (p = 0.0014). The systematic literature review included 6 papers (193 patients, 262 ETs) with comparable results, most also with little adverse effects. Conclusion: BDET using an EVB is a safe and effective option for OETD. It is well tolerated under local anesthesia in properly selected individuals. The reduced procedural cost may be an important factor in certain healthcare jurisdictions.

A multitask approach for automated detection and segmentation of thyroid nodules in ultrasound images.

An increase in the incidence and diagnosis of thyroid nodules and thyroid cancer underscores the need for a better approach to nodule detection and risk stratification in ultrasound (US) images that can reduce healthcare costs, patient discomfort, and unnecessary invasive procedures. However, variability in ultrasound technique and interpretation makes the diagnostic process partially subjective. Therefore, an automated approach that detects and segments nodules could improve performance on downstream tasks, such as risk stratification. Ultrasound studies were acquired from 280 patients at UCLA Health, totaling 9888 images, and annotated by collaborating radiologists. Current deep learning architectures for segmentation are typically semi-automated because they are evaluated solely on images known to have nodules and do not assess ability to identify suspicious images. However, the proposed multitask approach both detects suspicious images and segments potential nodules; this allows for a clinically translatable model that aptly parallels the workflow for thyroid nodule assessment. The multitask approach is centered on an anomaly detection (AD) module that can be integrated with any UNet architecture variant to improve image-level nodule detection. Of the evaluated multitask models, a UNet with a ImageNet pretrained encoder and AD achieved the highest F1 score of 0.839 and image-wide Dice similarity coefficient of 0.808 on the hold-out test set. Furthermore, models were evaluated on two external validations datasets to demonstrate generalizability and robustness to data variability. Ultimately, the proposed architecture is an automated multitask method that expands on previous methods by successfully both detecting and segmenting nodules in ultrasound.

Biophysical Control of the Glioblastoma Immunosuppressive Microenvironment: Opportunities for Immunotherapy.

GBM is the most aggressive and common form of primary brain cancer with a dismal prognosis. Current GBM treatments have not improved patient survival, due to the propensity for tumor cell adaptation and immune evasion, leading to a persistent progression of the disease. In recent years, the tumor microenvironment (TME) has been identified as a critical regulator of these pro-tumorigenic changes, providing a complex array of biomolecular and biophysical signals that facilitate evasion strategies by modulating tumor cells, stromal cells, and immune populations. Efforts to unravel these complex TME interactions are necessary to improve GBM therapy. Immunotherapy is a promising treatment strategy that utilizes a patient's own immune system for tumor eradication and has exhibited exciting results in many cancer types; however, the highly immunosuppressive interactions between the immune cell populations and the GBM TME continue to present challenges. In order to elucidate these interactions, novel bioengineering models are being employed to decipher the mechanisms of immunologically "cold" GBMs. Additionally, these data are being leveraged to develop cell engineering strategies to bolster immunotherapy efficacy. This review presents an in-depth analysis of the biophysical interactions of the GBM TME and immune cell populations as well as the systems used to elucidate the underlying immunosuppressive mechanisms for improving current therapies.

MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis.

PURPOSE: Lumbar spinal stenosis (LSS) is the most common reason for spinal surgery in patients over the age of 65, and there are few effective non-surgical treatments. Therefore, the development of novel treatment or preventative modalities to decrease overall cost and morbidity associated with LSS is an urgent matter. The cause of LSS is multifactorial; however, a significant contributor is ligamentum flavum hypertrophy (LFH) which causes mechanical compression of the cauda equina or nerve roots. We assessed the role of a novel target, microRNA-29a (miR-29a), in LFH and investigated the potential for using miR-29a as a therapeutic means to combat LSS. METHODS: Ligamentum flavum (LF) tissue was collected from patients undergoing decompressive surgery for LSS and assessed for levels of miR-29a and pro-fibrotic protein expression. LF cell cultures were then transfected with either miR-29a over-expressor (agonist) or inhibitor (antagonist). The effects of over-expression and under-expression of miR-29a on expression of pro-fibrotic proteins was assessed. RESULTS: We demonstrated that LF at stenotic levels had a loss of miR-29a expression. This was associated with greater LF tissue thickness and higher mRNA levels of collagen I and III. We also demonstrated that miR29-a plays a direct role in the regulation of collagen gene expression in ligamentum flavum. Specifically, agents that increase miR-29a may attenuate LFH, while those that decrease miR-29a promote fibrosis and LFH. CONCLUSION: This study demonstrates that miR-29a may potentially be used to treat LFH and provides groundwork to initiate the development of a therapeutic product for LSS.

Evaluation of the Effect of Lorlatinib on CYP2B6, CYP2C9, UGT, and P-Glycoprotein Substrates in Patients with Advanced Non-Small Cell Lung Cancer.

BACKGROUND AND OBJECTIVE: Lorlatinib is a tyrosine kinase inhibitor approved for the treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. This study assessed the effect of steady-state lorlatinib on the metabolic enzymes cytochrome P450 (CYP) 2B6, CYP2C9, and uridine 5'-diphospho-glucuronosyltransferase (UGT) and the P-glycoprotein (P-gp) transporter. METHODS: Thirty-two patients received a single oral dose of a probe drug on Day - 2 to determine the pharmacokinetics of the probe drug alone. Starting on Day 1, patients received 100 mg oral lorlatinib daily. On Day 15, a single oral dose of the probe drug was administered concurrently with lorlatinib. Pharmacokinetic parameters for these probe substrates were assessed. RESULTS: Plasma exposures of all probe substrates were reduced by lorlatinib compared with the probe alone. The greatest reduction in area under the plasma concentration-time curve from time zero to infinity (AUC∞) and maximum (peak) plasma drug concentration (Cmax) (67% and 63% decrease, respectively) was observed with the P-gp probe substrate fexofenadine. Lorlatinib coadministration also decreased the AUC∞ and Cmax of bupropion (CYP2B6 probe substrate) by 25% and 27%, tolbutamide (CYP2C9 probe substrate) by 43% and 15%, and acetaminophen (UGT probe substrate) by 45% and 28%, respectively. CONCLUSIONS: Lorlatinib is a net moderate inducer of P-gp and a weak inducer of CYP2B6, CYP2C9, and UGT after steady state is achieved with daily dosing. Medications that are P-gp substrates with a narrow therapeutic window should be avoided in patients taking lorlatinib; no dose modifications are needed with substrates of CYP2B6, CYP2C9, or UGT. CLINICALTRIALS: gov: NCT01970865.

Virtual Reality Simulation for the Middle Cranial Fossa Approach: A Validation Study.

BACKGROUND AND OBJECTIVES: Virtual reality (VR) surgical rehearsal is an educational tool that exists in a safe environment. Validation is necessary to establish the educational value of this platform. The middle cranial fossa (MCF) is ideal for simulation because trainees have limited exposure to this approach and it has considerable complication risk. Our objectives were to assess the face, content, and construct validities of an MCF VR simulation, as well as the change in performance across serial simulations. METHODS: Using high-resolution volumetric data sets of human cadavers, the authors generated a high-fidelity visual and haptic rendering of the MCF approach using CardinalSim software. Trainees from Neurosurgery and Otolaryngology-Head and Neck Surgery at two Canadian academic centers performed MCF dissections on this VR platform. Randomization was used to assess the effect of enhanced VR interaction. Likert scales were used to assess the face and content validities. Performance metrics and pre- and postsimulation test scores were evaluated. Construct validity was evaluated by examining the effect of the training level on simulation performance. RESULTS: Twenty trainees were enrolled. Face and content validities were achieved in all domains. Construct validity, however, was not demonstrated. Postsimulation test scores were significantly higher than presimulation test scores ( P < .001 ). Trainees demonstrated statistically significant improvement in the time to complete dissections ( P < .001 ), internal auditory canal skeletonization ( P < .001 ), completeness of the anterior petrosectomy ( P < .001 ), and reduced number of injuries to critical structures ( P = .001 ). CONCLUSION: This MCF VR simulation created using CardinalSim demonstrated face and content validities. Construct validity was not established because no trainee included in the study had previous MCF approach experience, which further emphasizes the importance of simulation. When used as a formative educational adjunct in both Neurosurgery and Otolaryngology-Head and Neck Surgery, this simulation has the potential to enhance understanding of the complex anatomic relationships of critical neurovascular structures.

The Effect of Timing Between Traumatic Flexor Tendon Injury of the Hand and Surgical Intervention on Repair Failure Rates.

Flexor tendon injuries of the hand, especially in zone II, pose a challenge for hand surgeons because of the region's intricate pulley mechanism and local avascularity, and post-surgical complications such as repair failure are not uncommon. One proposed predictor of outcomes following flexor tendon repair has been timing of surgery from initial injury. However, the effect of the timing of flexor tendon repair on failure rates remains controversial and understudied. The purpose of this study was to compare the failure rates of zone II flexor tendon repairs in patients at various time intervals from onset of injury. A retrospective chart review was conducted using data from hand surgery specialists at our level 1 trauma center from January 1, 2010, through May 31, 2020. This retrospective review included 407 zone II flexor tendon repairs. The primary outcome was failure of repair. Among 407 flexor tendon repairs, there were 12 reported repair failures. The failure rate was 2.9%. In the non-failure group, the mean number of days between the date of injury and the date of surgery was 7±13 days. For the failure group, this value was 14±17 days. Repairs occurring within 14 days had a failure rate of 2.3%, while repairs occurring beyond 14 days had a failure rate of 7.7%. This study demonstrates that there is a benefit to repairing the tendon within a 14-day window, as evidenced by a lower failure rate. More research is required to determine if other complications and overall health of the hand are also improved when a repair is performed in a more expedient manner. [Orthopedics. 2024;47(2):113-117.].

How standardised are antibiotic regimens in otologic surgery?

BACKGROUND: Within otologic surgery, a paucity of well-controlled studies assessing the use of systemic antibiotic to reduce surgical site infections exists. Moreover, discrepancies in wound classification of procedures challenge consensus in antimicrobial prescribing patterns. We sought to compare surgeons from two different health systems to examine how surgeons' prescribing habits compared to practice guidelines for numerous otologic procedures. METHODS: An online questionnaire was distributed to 33 Canadian and 32 Austrian surgeons who regularly perform otologic surgery. Current systemic antibiotic prescribing habits for cochlear implantation, cholesteatoma surgery, stapes surgery, and tympanoplasty ± ossiculoplasty were collected. RESULTS: Eighteen of 33 (54.5%) Canadian surgeons provided responses, while 18 of 32 (56.3%) of Austrian surgeons answered. Clear consistency with clinical practice guidelines exists for pre-operative antibiotics use in cochlear implant surgery and infected cholesteatoma surgery. However, for stapes surgery and tympanoplasty ± ossiculoplasty, consensus is lacking for both pre- and post-operative antibiotic prescribing habits. Notable differences between the two countries include post-operative antibiotics for cochlear implant surgery (Austria: 36.4%, Canada: 71.4%) and uninfected cholesteatoma surgery (Austria: 33.3%, Canada: 77.8%). Across all procedures, both induction and post-operative antibiotic administration was not significantly associated with surgeon seniority when stratified by five-year increments. CONCLUSION: The lack of consensus among each country's otologic surgeons underscores the uncertainty in wound classification and thus, adherence to clinical practice guidelines.

Gene mutations as a non-invasive measure of adult cochlear implant performance: Variable outcomes in patients with select TMPRSS3 mutations.

BACKGROUND: The cochlear implant (CI) has proven to be a successful treatment for patients with severe-to-profound sensorineural hearing loss, however outcome variance exists. We sought to evaluate particular mutations discovered in previously established sensory and neural partition genes and compare post-operative CI outcomes. MATERIALS AND METHODS: Utilizing a prospective cohort study design, blood samples collected from adult patients with non-syndromic hearing loss undergoing CI were tested for 54 genes of interest with high-throughput sequencing. Patients were categorized as having a pathogenic variant in the sensory partition, pathogenic variant in the neural partition, pathogenic variant in both sensory and neural partition, or with no variant identified. Speech perception performance was assessed pre- and 12 months post-operatively. Performance measures were compared to genetic mutation and variant status utilizing a Wilcoxon rank sum test, with P<0.05 considered statistically significant. RESULTS: Thirty-six cochlear implant patients underwent genetic testing and speech understanding measurements. Of the 54 genes that were interrogated, three patients (8.3%) demonstrated a pathogenic mutation in the neural partition (within TMPRSS3 genes), one patient (2.8%) demonstrated a pathogenic mutation in the sensory partition (within the POU4F3 genes). In addition, 3 patients (8.3%) had an isolated neural partition variance of unknown significance (VUS), 5 patients (13.9%) had an isolated sensory partition VUS, 1 patient (2.8%) had a variant in both neural and sensory partition, and 23 patients (63.9%) had no mutation or variant identified. There was no statistically significant difference in speech perception scores between patients with sensory or neural partition pathogenic mutations or VUS. Variable performance was found within patients with TMPRSS3 gene mutations. CONCLUSION: The impact of genetic mutations on post-operative outcomes in CI patients was heterogenous. Future research and dissemination of mutations and subsequent CI performance is warranted to elucidate exact mutations within target genes providing the best non-invasive prognostic capability.

Untangling the web of glioblastoma treatment resistance using a multi-omic and multidisciplinary approach.

Glioblastoma (GBM), the most common human brain tumor, has been notoriously resistant to treatment. As a result, the dismal overall survival of GBM patients has not changed over the past three decades. GBM has been stubbornly resistant to checkpoint inhibitor immunotherapies, which have been remarkably effective in the treatment of other tumors. It is clear that GBM resistance to therapy is multifactorial. Although therapeutic transport into brain tumors is inhibited by the blood brain barrier, there is evolving evidence that overcoming this barrier is not the predominant factor. GBMs generally have a low mutation burden, exist in an immunosuppressed environment and they are inherently resistant to immune stimulation, all of which contribute to treatment resistance. In this review, we evaluate the contribution of multi-omic approaches (genomic and metabolomic) along with analyzing immune cell populations and tumor biophysical characteristics to better understand and overcome GBM multifactorial resistance to treatment.

Metabolomic differentiation of tumor core versus edge in glioma.

OBJECTIVE: Gliomas exhibit high intratumor and interpatient heterogeneity. Recently, it has been shown that the microenvironment and phenotype differ significantly between the glioma core (inner) and edge (infiltrating) regions. This proof-of-concept study differentiates metabolic signatures associated with these regions, with the potential for prognosis and targeted therapy that could improve surgical outcomes. METHODS: Paired glioma core and infiltrating edge samples were obtained from 27 patients after craniotomy. Liquid-liquid metabolite extraction was performed on the samples and metabolomic data were obtained via 2D liquid chromatography-mass spectrometry/mass spectrometry. To gauge the potential of metabolomics to identify clinically relevant predictors of survival from tumor core versus edge tissues, a boosted generalized linear machine learning model was used to predict metabolomic profiles associated with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. RESULTS: A panel of 66 (of 168) metabolites was found to significantly differ between glioma core and edge regions (p ≤ 0.05). Top metabolites with significantly different relative abundances included DL-alanine, creatine, cystathionine, nicotinamide, and D-pantothenic acid. Significant metabolic pathways identified by quantitative enrichment analysis included glycerophospholipid metabolism; butanoate metabolism; cysteine and methionine metabolism; glycine, serine, alanine, and threonine metabolism; purine metabolism; nicotinate and nicotinamide metabolism; and pantothenate and coenzyme A biosynthesis. The machine learning model using 4 key metabolites each within core and edge tissue specimens predicted MGMT promoter methylation status, with AUROCEdge = 0.960 and AUROCCore = 0.941. Top metabolites associated with MGMT status in the core samples included hydroxyhexanoycarnitine, spermine, succinic anhydride, and pantothenic acid, and in the edge samples metabolites included 5-cytidine monophosphate, pantothenic acid, itaconic acid, and uridine. CONCLUSIONS: Key metabolic differences are identified between core and edge tissue in glioma and, furthermore, demonstrate the potential for machine learning to provide insight into potential prognostic and therapeutic targets.

Using augmented reality to guide bone conduction device implantation.

Exact placement of bone conduction implants requires avoidance of critical structures. Existing guidance technologies for intraoperative placement have lacked widespread adoption given accessibility challenges and significant cognitive loading. The purpose of this study is to examine the application of augmented reality (AR) guided surgery on accuracy, duration, and ease on bone conduction implantation. Five surgeons surgically implanted two different types of conduction implants on cadaveric specimens with and without AR projection. Pre- and postoperative computer tomography scans were superimposed to calculate centre-to-centre distances and angular accuracies. Wilcoxon signed-rank testing was used to compare centre-to-centre (C-C) and angular accuracies between the control and experimental arms. Additionally, projection accuracy was derived from the distance between the bony fiducials and the projected fiducials using image guidance coordinates. Both operative time (4.3 ± 1.2 min. vs. 6.6 ± 3.5 min., p = 0.030) and centre-to-centre distances surgery (1.9 ± 1.6 mm vs. 9.0 ± 5.3 mm, p < 0.001) were significantly less in augmented reality guided surgery. The difference in angular accuracy, however, was not significantly different. The overall average distance between the bony fiducial markings and the AR projected fiducials was 1.7 ± 0.6 mm. With direct intraoperative reference, AR-guided surgery enhances bone conduction implant placement while reduces operative time when compared to conventional surgical planning.

Developmental stage of transplanted neural progenitor cells influences anatomical and functional outcomes after spinal cord injury in mice.

Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery of motor and sensory functions after SCI, is poorly understood. We transplanted developmentally-restricted spinal cord NPCs, isolated from E11.5-E13.5 mouse embryos, into sites of adult mouse SCI and analyzed graft axon outgrowth, cellular composition, host axon regeneration, and behavior. Earlier-stage grafts exhibited greater axon outgrowth, enrichment for ventral spinal cord interneurons and Group-Z spinal interneurons, and enhanced host 5-HT+ axon regeneration. Later-stage grafts were enriched for late-born dorsal horn interneuronal subtypes and Group-N spinal interneurons, supported more extensive host CGRP+ axon ingrowth, and exacerbated thermal hypersensitivity. Locomotor function was not affected by any type of NPC graft. These findings showcase the role of spinal cord graft cellular composition in determining anatomical and functional outcomes following SCI.

Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: phase 1 trial results.

Neuroblastomas harbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-generation ALK inhibitor lorlatinib. We conducted a first-in-child study evaluating lorlatinib with and without chemotherapy in children and adults with relapsed or refractory ALK-driven neuroblastoma. The trial is ongoing, and we report here on three cohorts that have met pre-specified primary endpoints: lorlatinib as a single agent in children (12 months to <18 years); lorlatinib as a single agent in adults (≥18 years); and lorlatinib in combination with topotecan/cyclophosphamide in children (<18 years). Primary endpoints were safety, pharmacokinetics and recommended phase 2 dose (RP2D). Secondary endpoints were response rate and 123I-metaiodobenzylguanidine (MIBG) response. Lorlatinib was evaluated at 45-115 mg/m2/dose in children and 100-150 mg in adults. Common adverse events (AEs) were hypertriglyceridemia (90%), hypercholesterolemia (79%) and weight gain (87%). Neurobehavioral AEs occurred mainly in adults and resolved with dose hold/reduction. The RP2D of lorlatinib with and without chemotherapy in children was 115 mg/m2. The single-agent adult RP2D was 150 mg. The single-agent response rate (complete/partial/minor) for <18 years was 30%; for ≥18 years, 67%; and for chemotherapy combination in <18 years, 63%; and 13 of 27 (48%) responders achieved MIBG complete responses, supporting lorlatinib's rapid translation into active phase 3 trials for patients with newly diagnosed high-risk, ALK-driven neuroblastoma. ClinicalTrials.gov registration: NCT03107988 .

The feasibility and safety of eustachian tube dilation with a standard endovascular balloon: a clinical pilot study.

BACKGROUND: Obstructive eustachian tube dysfunction is a common pathology, generally accepted as the underlying cause for chronic ear diseases. Eustachian tube dilation has shown promising results in randomized controlled trials, but is a costly procedure. The aim of the current study was to assess the feasibility of transnasal balloon dilatation of the eustachian tube with an endovascular balloon in the context of ease of use, maneuverability, and safety. METHODS: Clinical pilot study carried out at a university tertiary care facility. In total, twelve patients, were included over a period of 6 months. All patients underwent tympanoplasty or tympanomastoidectomy surgeries. Eustachian tube dilation was carried out transnasal using an endovascular balloon. A computed tomography was carried out after surgery to assess for any potential damages and compared to preoperative imaging studies. Postoperative endoscopy was performed intraoperatively and at follow up to assess for any potential damages. RESULTS: All eustachian tube dilations were carried out successfully. No severe adverse events were noted during the procedure, in the postoperative period, or on imaging studies. Minor adverse events such as mild intraoperative bleeding was managed in a routine fashion. CONCLUSIONS: Balloon dilation of the eustachian tube with the endovascular balloon was feasible and safe in all cases. It is likely a more cost-effective alternative to commercially available balloons with similar designs and specifications. Trial registration The study was registered at clinicaltrials.gov; NCT04809753, initial release February 24th, 2021.

Malignant Cerebellopontine Angle Peripheral Nerve Sheath Tumor with Divergent Mesenchymal (Cartilaginous) Differentiation Presenting with Catastrophic Hemorrhage: Case Report and Review.

Malignant peripheral nerve sheath tumors of the cerebellopontine angle are rare, especially even outside of the context of neurofibromatosis or malignant transformation of previously radiated vestibular schwannomas. This case report describes a case of a presumed vestibular schwannoma without previous radiation or history of neurofibromatosis presenting with progressive hearing loss, facial weakness, growth, and ultimately catastrophic hemorrhage requiring urgent surgery. Histopathology revealed an exceptionally rare malignant peripheral nerve sheath tumor with divergent mesenchymal (chondrosarcomatous) differentiation with few rigorously interrogated cases in the literature. In retrospect, facial weakness, growth, and early intratumoral hemorrhage were harbingers of atypical malignant pathology. We advocate for a heightened index of suspicion, shorter interval follow-up, and consideration of early surgery in such cases in hopes of preventing potentially catastrophic outcomes.

Spine Fractures of Patients with Ankylosing Spondylitis and Diffuse Idiopathic Skeletal Hyperostosis: Fracture Severity and Injury-Related Mortality at a Level I Trauma Center.

STUDY DESIGN: Retrospective review of prospectively collected cohort. PURPOSE: To identify differences in treatment and mortality of spine fractures in patients with ankylosing conditions of the spine. OVERVIEW OF LITERATURE: Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are the two most common etiologies of ankylosing spinal disorder (ASD). However, studies on the treatment and outcomes of spine fractures in AS and DISH patients remain few. METHODS: Patients presenting with a spine fracture were diagnosed with AS or DISH at a single tertiary care center between 2010 and 2019. We excluded those who lacked cross-sectional imaging or fractures occurring at spinal segments affected by ankylosis, as well as polytraumatized patients. Patient demographics, injury mechanism, fracture level, neurologic status, treatment, and 1-year mortality were recorded. Computed tomography imaging was reviewed by two independent readers and graded according to the indicated AO Spine Injury Classification System. Differences in fracture severity, treatment method, and mortality were examined using Student t -tests, chi-square tests, and two-proportion Z-tests with significance set to p <0.05. RESULTS: We identified 167 patients with spine fracture diagnosed with AS or DISH. Patients with AS had more severe fractures and more commonly had surgery than patients with DISH (p <0.001). Despite these differences, 1-year mortality did not significantly differ between AS and DISH patients (p =0.14). CONCLUSIONS: Although patients with AS suffered more severe fractures compared to DISH and more frequently underwent surgery for these injuries, outcomes and 1-year mortality did not differ significantly between the two groups. For patients with ASDs and fractures, outcomes appear similar regardless of treatment modality. Consequently, there may be an opportunity for critical reappraisal of operative indications in ASD and a larger role for nonoperative management in these challenging patients.

A Multitask Approach for Automated Detection and Segmentation of Thyroid Nodules in Ultrasound Images.

An increase in the incidence and diagnosis of thyroid nodules and thyroid cancer underscores the need for a better approach to nodule detection and risk stratification in ultrasound (US) images that can reduce healthcare costs, patient discomfort, and unnecessary invasive procedures. However, variability in ultrasound technique and interpretation makes the diagnostic process partially subjective. Therefore, an automated approach that detects and segments nodules could improve performance on downstream tasks, such as risk stratification.Current deep learning architectures for segmentation are typically semi-automated because they are evaluated solely on images known to have nodules and do not assess ability to identify suspicious images. However, the proposed multitask approach both detects suspicious images and segments potential nodules; this allows for a clinically translatable model that aptly parallels the workflow for thyroid nodule assessment. The multitask approach is centered on an anomaly detection (AD) module that can be integrated with any U-Net architecture variant to improve image-level nodule detection. Ultrasound studies were acquired from 280 patients at UCLA Health, totaling 9,888 images, and annotated by collaborating radiologists. Of the evaluated models, a multi-scale UNet (MSUNet) with AD achieved the highest F1 score of 0.829 and image-wide Dice similarity coefficient of 0.782 on our hold-out test set. Furthermore, models were evaluated on two external validations datasets to demonstrate generalizability and robustness to data variability. Ultimately, the proposed architecture is an automated multitask method that expands on previous methods by successfully both detecting and segmenting nodules in ultrasound.