Faculty Bibliography

OBJECTIVE:This study aimed to assess the impact of oral medicine (OM) practitioners on the literature regarding oral potentially malignant disorders (OPMDs), focusing on oral leukoplakia. STUDY DESIGN/METHODS:Using a bibliometric approach on the Scopus database until September 1, 2022, the top 100 cited articles were analyzed for article type, subtopic, specialty contributions, author metrics, and keywords. The Bibliometrix package for R and VOSviewer were used to evaluate interactions and generate science maps. RESULTS:OM practitioners, comprising 39% of contributors, played a significant role in studies related to nomenclature and screening of OPMDs. Notably, 4 OM specialists ranked among the most prolific authors, demonstrating denser collaboration with OM co-authors compared to other cancer specialists. However, there was a scarcity of OPMD management studies authored by OM practitioners. CONCLUSIONS:Despite the paucity of OM practitioners, the findings underscored the substantial contribution of OM practitioners in developing OPMD nomenclature and classification, emphasizing the need for increased collaboration with cancer specialists to conduct comprehensive clinical trials for OPMD management. The study highlights the importance of standardized criteria in OPMDs research for better data comparison and encourages further efforts from the OM scientific community.

BACKGROUND:Myocardial infarction and heart failure are major cardiovascular diseases that affect millions of people in the US with the morbidity and mortality being highest among patients who develop cardiogenic shock. Early recognition of cardiogenic shock allows prompt implementation of treatment measures. Our objective is to develop a new dynamic risk score, called CShock, to improve early detection of cardiogenic shock in cardiac intensive care unit (ICU). METHODS:We developed and externally validated a deep learning-based risk stratification tool, called CShock, for patients admitted into the cardiac ICU with acute decompensated heart failure and/or myocardial infarction to predict onset of cardiogenic shock. We prepared a cardiac ICU dataset using MIMIC-III database by annotating with physician adjudicated outcomes. This dataset that consisted of 1500 patients with 204 having cardiogenic/mixed shock was then used to train CShock. The features used to train the model for CShock included patient demographics, cardiac ICU admission diagnoses, routinely measured laboratory values and vital signs, and relevant features manually extracted from echocardiogram and left heart catheterization reports. We externally validated the risk model on the New York University (NYU) Langone Health cardiac ICU database that was also annotated with physician adjudicated outcomes. The external validation cohort consisted of 131 patients with 25 patients experiencing cardiogenic/mixed shock. RESULTS:CShock achieved an area under the receiver operator characteristic curve (AUROC) of 0.821 (95% CI 0.792-0.850). CShock was externally validated in the more contemporary NYU cohort and achieved an AUROC of 0.800 (95% CI 0.717-0.884), demonstrating its generalizability in other cardiac ICUs. Having an elevated heart rate is most predictive of cardiogenic shock development based on Shapley values. The other top ten predictors are having an admission diagnosis of myocardial infarction with ST-segment elevation, having an admission diagnosis of acute decompensated heart failure, Braden Scale, Glasgow Coma Scale, Blood urea nitrogen, Systolic blood pressure, Serum chloride, Serum sodium, and Arterial blood pH. CONCLUSIONS:The novel CShock score has the potential to provide automated detection and early warning for cardiogenic shock and improve the outcomes for the millions of patients who suffer from myocardial infarction and heart failure.

Turn-taking is a central feature of conversation across languages and cultures.¹

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABA_A and metabotropic GABA_B receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABA_A receptors. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABA_A, Gabra1; GABA_B, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABA_B receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABA_B receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.

BACKGROUND:Isocitrate dehydrogenase (IDH) mutant astrocytoma grading, until recently, has been entirely based on morphology. The 5th edition of the Central Nervous System World Health Organization (WHO) introduces CDKN2A/B homozygous deletion as a biomarker of grade 4. We sought to investigate the prognostic impact of DNA methylation-derived molecular biomarkers for IDH mutant astrocytoma. METHODS:We analyzed 98 IDH mutant astrocytomas diagnosed at NYU Langone Health between 2014 and 2022. We reviewed DNA methylation subclass, CDKN2A/B homozygous deletion, and ploidy and correlated molecular biomarkers with histological grade, progression free (PFS), and overall (OS) survival. Findings were confirmed using 2 independent validation cohorts. RESULTS:There was no significant difference in OS or PFS when stratified by histologic WHO grade alone, copy number complexity, or extent of resection. OS was significantly different when patients were stratified either by CDKN2A/B homozygous deletion or by DNA methylation subclass (P value = .0286 and .0016, respectively). None of the molecular biomarkers were associated with significantly better PFS, although DNA methylation classification showed a trend (P value = .0534). CONCLUSIONS:The current WHO recognized grading criteria for IDH mutant astrocytomas show limited prognostic value. Stratification based on DNA methylation shows superior prognostic value for OS.

OBJECTIVE:To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN/METHODS:Multi-institutional historical cohort study. SETTING/METHODS:Five tertiary care referral centers. PATIENTS/METHODS:Adults ≥18 years old with sporadic VS. INTERVENTION/METHODS:Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE/METHODS:Microsurgery-free survival after repeat SRS. RESULTS:Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION/CONCLUSIONS:Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

OBJECTIVE(S)/OBJECTIVE:Previous literature has established a high prevalence of upper airway obstruction in children with craniofacial abnormalities. This study aims to perform quantitative airway volume measurements in patients with craniofacial abnormalities and compare them to age and sex-matched controls. METHODS:We performed a retrospective review of the records of all children with craniofacial abnormalities who underwent head-and-neck computed tomography (CT) imaging at a single tertiary-care center between 1/1/13 and 12/31/20 using the ICD-10 codes Q75.1, Q75.4, and Q87.0. These patients were then matched by age and sex to patients with isolated craniosynostosis (Q75.0). CT scans were imported into Dolphin Imaging software, and airway volumes were measured for the nasal cavity, nasopharynx, oropharynx, and hypopharynx. The primary outcome was the total airway volume, defined as the sum of these measurements. RESULTS:Thirty subjects with craniofacial syndromes were matched to 30 patients with isolated craniosynostosis (controls). In both groups, 18 subjects (60%) were male (p = 0.99). The average ages for syndromic patients and controls were 12.1 and 12.9 months, respectively (p = 0.84). On average, the total airway volumes of syndromic patients were 25% lower than those of controls (p = 0.02). Syndromic patients had 39% smaller nasal cavity volumes (p < 0.001) and 32% smaller nasopharyngeal volumes (p < 0.01). Significant volume differences were not observed for the oropharynx or hypopharynx. CONCLUSION/CONCLUSIONS:We present a unique technique to measure airway volumes in patients with craniofacial abnormalities. These findings will help practitioners to further understand the anatomy and pathophysiology of disturbed breathing in children with craniofacial syndromes. LEVEL OF EVIDENCE/METHODS:III Laryngoscope, 2023.

OBJECTIVES/OBJECTIVE:Despite performing well in standard clinical assessments of speech perception, many cochlear implant (CI) users report experiencing significant difficulties when listening in real-world environments. We hypothesize that this disconnect may be related, in part, to the limited ecological validity of tests that are currently used clinically and in research laboratories. The challenges that arise from degraded auditory information provided by a CI, combined with the listener's finite cognitive resources, may lead to difficulties when processing speech material that is more demanding than the single words or single sentences that are used in clinical tests. DESIGN/METHODS:Here, we investigate whether speech identification performance and processing effort (indexed by pupil dilation measures) are affected when CI users or normal-hearing control subjects are asked to repeat two sentences presented sequentially instead of just one sentence. RESULTS:Response accuracy was minimally affected in normal-hearing listeners, but CI users showed a wide range of outcomes, from no change to decrements of up to 45 percentage points. The amount of decrement was not predictable from the CI users' performance in standard clinical tests. Pupillometry measures tracked closely with task difficulty in both the CI group and the normal-hearing group, even though the latter had speech perception scores near ceiling levels for all conditions. CONCLUSIONS:Speech identification performance is significantly degraded in many (but not all) CI users in response to input that is only slightly more challenging than standard clinical tests; specifically, when two sentences are presented sequentially before requesting a response, instead of presenting just a single sentence at a time. This potential "2-sentence problem" represents one of the simplest possible scenarios that go beyond presentation of the single words or sentences used in most clinical tests of speech perception, and it raises the possibility that even good performers in single-sentence tests may be seriously impaired by other ecologically relevant manipulations. The present findings also raise the possibility that a clinical version of a 2-sentence test may provide actionable information for counseling and rehabilitating CI users, and for people who interact with them closely.

The most widely used fluorophore in glioma-resection surgery, 5-aminolevulinic acid (5-ALA), is thought to cause the selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumour cells. Here we show that the clinical detection of PpIX can be improved via a microscope that performs paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF). We validated the technique in fresh tumour specimens from 115 patients with high-grade gliomas across four medical institutions. We found a weak negative correlation between tissue cellularity and the fluorescence intensity of PpIX across all imaged specimens. Semi-supervised clustering of the TPEF images revealed five distinct patterns of PpIX fluorescence, and spatial transcriptomic analyses of the imaged tissue showed that myeloid cells predominate in areas where PpIX accumulates in the intracellular space. Further analysis of external spatially resolved metabolomics, transcriptomics and RNA-sequencing datasets from glioblastoma specimens confirmed that myeloid cells preferentially accumulate and metabolize PpIX. Our findings question 5-ALA-induced fluorescence in glioma cells and show how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of gliomas.