Faculty Bibliography

PURPOSE/OBJECTIVE:Bevacizumab treatment is associated with imaging and hearing responses in progressive vestibular schwannoma (VS) caused by NF2-related schwannomatosis (NF2-SWN). However, its effect on co-existing intracranial non-vestibular schwannomas (NVS) and meningiomas is unclear. METHODS:We retrospectively analyzed tumor volumes of non-target intracranial NVS and meningiomas in patients with NF2-SWN and progressive VS who were prospectively treated with bevacizumab for two years on the Neurofibromatosis Clinical Trials Consortium (NFCTC) trial NF104 (NCT01767792). Radiographic response (RR) or progression (PD) were defined as ≥ 20% decrease or ≥ 20% increase in tumor volume compared to baseline, respectively. All other responses were defined as stable disease. RESULTS:A total of 40 meningiomas in eight patients and 12 NVS in six patients were evaluated across 22 enrolled trial participants. On best response analysis, RR occurred in 13% (5/40) of meningiomas and in 42% (5/12) of NVS. On a per-patient basis, RR for meningioma occurred in 38% (3/8) of patients and for NVS in 67% (4/6) of patients. RR in two NVS were durable throughout the study period. During two years of treatment, PD occurred in 55% (22/40) of meningiomas and in 8% (1/12) of NVS. Median time to tumor progression was 15 months for meningiomas and was not reached for NVS. CONCLUSIONS:We observed greater activity of bevacizumab against intracranial NVS compared to meningioma, evidenced by more favorable RR rates, durability of response, and rates of PD. Potential biological differences between meningiomas and schwannomas that underlie this differential response to bevacizumab warrant further investigation.

Most offspring are born helpless, requiring intense caregiving from parents especially during the first few days of neonatal life. For many species, infant cries are a primary signal used by parents to provide caregiving. Previously we and others documented how maternal left auditory cortex rapidly becomes sensitized to pup calls over hours of parental experience, enabled by oxytocin. The speed and robustness of this maternal plasticity suggests cortical pre-tuning or initial bias for pup call stimulus features. Here we examine the circuit basis of left-lateralized tuning to vocalization features with whole-cell recordings in brain slices. We found that layer 2/3 pyramidal cells of female left auditory cortex show selective suppression of inhibitory inputs with repeated stimulation at the fundamental pup call rate (inter-stimulus interval ∼150 msec) in pup-naïve females and expanded with maternal experience. However, optogenetic stimulation of cortical inhibitory cells showed that inputs from somatostatin-positive and oxytocin-receptor-expressing interneurons were less suppressed at these rates. This suggested that disynaptic inhibition rather than monosynaptic depression was a major mechanism underlying pre-tuning of cortical excitatory neurons, confirmed with simulations. Thus cortical interneuron specializations can augment neuroplasticity mechanisms to ensure fast appropriate caregiving in response to infant cries.

Diagnostic adjuncts for oral potentially malignant disorders such as leukoplakia or erythroplakia can aid the clinician in triaging abnormal lesions and facilitate both biopsy site selection and surgical management. No adjuncts replace gold standard biopsy and histopathological examination, and their optimal use requires training and experience. This article covers the potential applications, both in primary and expert settings, of adjuncts, such as tissue autofluorescence, toluidine blues staining, and cytopathology. It covers new and emerging adjuncts such as confocal microscopy, liquid biopsy, oral microbiome testing, and the role of artificial intelligence. Incisional biopsy site selection and techniques will also be discussed.

OBJECTIVE:The videofluoroscopic swallow study (VFSS) is an evaluation of the anatomy and physiology of swallowing, and often includes a screening evaluation of the esophagus. How the esophageal screen translates to esophageal pathology remains unknown. The purpose of this study was to determine if abnormal esophageal clearance (EC) on VFSS correlates with esophageal function on high-resolution esophageal manometry (HREM). MATERIALS AND METHODS/METHODS:This is a retrospective review of 115 adult patients who underwent both VFSS with esophageal screen and HRM. EC on VFSS was scored with the modified barium swallow impairment profile (MBSImP) component 17. Motility was characterized using HRM metrics according to the Chicago Classification Version 4.0 (CCv4.0). Predictive metrics were calculated for the esophageal screen. RESULTS:An EC score o greater than or equal to 1 had a sensitivity of 66%, specificity of 57%, PPV of 52%, NPV of 70%, and OR of 2.55 (p = 0.027). EC weakly correlated with incomplete bolus clearance (rho = 0.331, p = 0.0004) and did not correlate with bolus transit time (rho = 0.17, p = 0.105). CONCLUSIONS:The esophageal screen as characterized by the MBSImP is not an effective predictor of esophageal function on HREM as defined by the CCv4.0. Future work may focus on a defining a standardized VFSS protocol for the esophageal screen and potentially a more nuanced assessment of esophageal findings on VFSS that may enhance the sensitivity of the modality to motility disorders.

Alston's singing mice (Scotinomys teguina) are highly vocal Central American rodents that produce structured "songs" (duration: 5-10 s),¹

BACKGROUND:Accurate intraoperative diagnosis is crucial for differentiating between primary CNS lymphoma (PCNSL) and other CNS entities, guiding surgical decision-making, but represents significant challenges due to overlapping histomorphological features, time constraints, and differing treatment strategies. We combined stimulated Raman histology (SRH) with deep learning to address this challenge. METHODS:We imaged unprocessed, label-free tissue samples intraoperatively using a portable Raman scattering microscope, generating virtual H&E-like images within less than three minutes. We developed a deep learning pipeline called RapidLymphoma based on a self-supervised learning strategy to (1) detect PCNSL, (2) differentiate from other CNS entities, and (3) test the diagnostic performance in a prospective international multicenter cohort and two additional independent test cohorts. We trained on 54,000 SRH patch images sourced from surgical resections and stereotactic-guided biopsies, including various CNS neoplastic/non-neoplastic lesions. Training and test data were collected from four tertiary international medical centers. The final histopathological diagnosis served as ground-truth. RESULTS:In the prospective test cohort of PCNSL and non-PCNSL entities (n=160), RapidLymphoma achieved an overall balanced accuracy of 97.81% ±0.91, non-inferior to frozen section analysis in detecting PCNSL (100% vs. 77.77%). The additional test cohorts (n=420, n=59) reached balanced accuracy rates of 95.44% ±0.74 and 95.57% ±2.47 in differentiating IDH-wildtype diffuse gliomas and various brain metastasis from PCNSL. Visual heatmaps revealed RapidLymphoma's capabilities to detect class-specific histomorphological key features. CONCLUSIONS:RapidLymphoma proves reliable and valid for intraoperative PCNSL detection and differentiation from other CNS entities. It provides visual feedback within three minutes, enabling fast clinical decision-making and subsequent treatment strategy planning.

Animals need daily intakes of three macronutrients: sugar, protein, and fat. Under fasted conditions, however, animals prioritize sugar as a primary source of energy. They must detect ingested sugar-specifically D-glucose-and quickly report its presence to the brain. Hypothalamic neurons that can respond to the caloric content in the gut regardless of the identity of macronutrient have been identified, but until now, the existence of neurons that can encode the specific macronutrients remained unknown. We found that a subset of corticotropin-releasing factor (CRF)-expressing neurons in the hypothalamic paraventricular nucleus (CRF^PVN) respond specifically to D-glucose in the gut, separately from other macronutrients or sugars. CRF^PVN neuronal activity is essential for fasted mice to develop a preference for D-glucose. These responses of CRF^PVN neurons to intestinal D-glucose require a specific spinal gut-brain pathway including the dorsal lateral parabrachial nuclei. These findings reveal the neural circuit that encodes the identity of D-glucose.

OBJECTIVE:Post-tonsillectomy hemorrhage is a highly studied outcome of tonsillectomy with serious consequences. The off-label use of tranexamic acid (TXA) is of growing interest to control post-tonsillectomy hemorrhage but has not been incorporated in management guidelines. STUDY DESIGN/METHODS:Scoping review on the use of tranexamic acid for post-tonsillectomy hemorrhage. SETTING/METHODS:N/A. METHODS:A comprehensive literature search was performed across the following research databases: PubMed, Embase, CINAHL, and Web of Science. The search was limited to English-language studies and patients without prior diagnosis of bleeding disorders. The articles were screened for relevance based on inclusion and exclusion criteria. Our initial search generated 131 articles. RESULTS:A total of 24 articles were identified, published in mostly otolaryngology journals. Over 96 000 tonsillectomy cases were included. There was variability in administration routes: intravenous, nebulized, oral, and topical. Intravenous was most used, particularly as prophylaxis for post-tonsillectomy hemorrhage, and nebulized administration was more common in therapeutic settings. Dosing regimens ranged between 5 and 15 mg/kg. We found mixed results across studies regarding peri-operative and post-operative bleeding outcomes, though multiple studies demonstrated decreased intraoperative bleeding. Many studies concurred that TXA was safe to use for post-tonsillectomy hemorrhage. CONCLUSION/CONCLUSIONS:The existing literature indicates TXA shows promising results in safety and reducing intraoperative blood volume loss. Further prospective and randomized controlled trials are needed to ensure the clinical benefits of TXA in tonsillectomy surgery prior to the inclusion in clinical practice guidelines.

Developed by the Center for Robust Speech Systems at the University of Texas at Dallas, in collaboration with New York University and the University of Wisconsin-Madison, CCi-MOBILE addresses a critical challenge in optimizing cochlear implant (CI) fitting and enhancing sound coding strategies. Existing clinical CI processors and research tools often lack either the necessary computational power and flexibility or the portability required for real-world testing. CCi-MOBILE bridges this gap by enabling the implementation and evaluation of diverse real-time sound coding algorithms in both laboratory and real-world settings, including those requiring synchronized bilateral stimulation. Building upon previous publications, this paper provides new detailed discussion on parameter setting for stimulus generation with CCi-MOBILE and serves as a comprehensive resource for scientists and engineers developing novel real-time sound coding and signal processing strategies with this platform. As part of an ongoing development effort, future generations of CCi-MOBILE may offer additional functionalities beyond those described here.