Faculty Bibliography

Objective: We conducted a qualitative study of patients"™ perspectives on dry mouth outcomes to explore their personal experiences and investigate which outcomes are most important to them. This work was part of the WONDER initiative (World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research) exploring Core Outcome Measures in Effectiveness Trials. Study Design: Using a study-specific topic guide, we conducted digitally recorded, semi-structured interviews of focus groups of patients with dry mouth secondary to Sjogren syndrome and head and neck radiotherapy. We conducted interviews until data saturation had been achieved and evaluated all transcripts for accuracy before we anonymized the data. Results: Two focus groups consisting of 4 participants per group identified 4 distinct themes: (1) impact on oral health and function, (2) social isolation and withdrawal, (3) frustration with dry mouth management, and (4) limited knowledge of the medical community and lack of understanding of family and friends. Conclusions: The diversity of self-reported outcomes and the complexity of patient perceptions identified in our work may represent additional barriers to successful dry mouth management that should be considered in the design of future clinical trials.

Although generally regarded as degradatory enzymes, certain proteases are also signaling molecules that specifically control cellular functions by cleaving protease-activated receptors (PARs). The four known PARs are members of the large family of G protein-coupled receptors. These transmembrane receptors control most physiological and pathological processes and are the target of a large proportion of therapeutic drugs. Signaling proteases include enzymes from the circulation, from immune, inflammatory epithelial and cancer cells, as well as from commensal and pathogenic bacteria. Advances in our understanding of the structure and function of PARs provide insights into how diverse proteases activate these receptors to regulate physiological and pathological processes in most tissues and organ systems. The realization that proteases and PARs are key mediators of disease, coupled with advances in understanding the atomic level structure of PARs and their mechanisms of signaling in subcellular microdomains, has spurred the development of antagonists, some of which have advanced to the clinic. Herein we review the discovery, structure and function of this receptor system, highlight the contribution of PARs to homeostatic control, and discuss the potential of PAR antagonists for the treatment of major diseases.

Agnathia-otocephaly complex (AOC), a first branchial arch defect, is characterized by mandibular hypoplasia or aplasia, ear abnormalities, microstomia, and macroglossia and is a rare and often fatal diagnosis. Herein, the technical considerations and details of mandibular reconstruction using virtual surgical planning (VSP) and a vascularized free fibula flap for further mandibular reconstruction in a 10-year-old boy are presented. The patient's preoperative examination was consistent with agnathia (absence of mandibular symphysis, bilateral mandibular bodies, condyles, coronoids, rami, and temporomandibular joint), severe microstomia, and a Tessier # 30 cleft (maintained to allow oral access until later in treatment). Virtual surgical planning was utilized to plan a 3-segment fibula for the reconstruction of the mandibular symphysis and bilateral body segments, and bilateral costochondral grafts were planned for the rami. To the authors' knowledge, this represents the first application of virtual surgical planning for mandibular reconstruction with a vascularized free fibula flap in a pediatric patient with severe agnathia-otocephaly complex.

BACKGROUND:The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies. METHODS:The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004-2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS:Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan-Meier analysis (HR: 0.98; 95% CI: 0.86-1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78-1.09; p = 0.34). CONCLUSIONS:Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

BACKGROUND:Although the prevalence of thyroid nodules is high, few prove to be malignant. Based on sonographic features, the American College of Radiology Thyroid Imaging Reporting and Data System categorizes malignancy risk of thyroid nodules with associated management recommendations for each category level. Malignancy rates among nodules with a highly suspicious Thyroid Imaging Reporting and Data System category 5 warrant examination in the context of additional risk stratification tools, including cytopathology and molecular testing. METHODS:All patients who underwent fine-needle aspiration biopsy for Thyroid Imaging Reporting and Data System category 5 nodules from January 2018 to September 2021 in a large integrated academic health system were reviewed. Using the Bethesda System for Reporting Thyroid Cytopathology, categories V and VI were set as malignant. Molecular testing (ThyroSeq version 3; Rye Brook, NY) yielding ≥50% risk of malignancy was deemed positive and correlated with surgical pathology. RESULTS:A total of 496 Thyroid Imaging Reporting and Data System category 5 nodules were identified. On fine-needle aspiration cytopathology, 61 (12.3%) were malignant. The breakdown included Bethesda System for Reporting Thyroid Cytopathology I, 15 (3%); II, 362 (73%); III, 52 (10.5%); IV, 5 (1%); V, 6 (1.3%); and VI, 55 (11.1%). Of Bethesda System for Reporting Thyroid Cytopathology III/IV nodules with molecular testing (n = 53), 24.5% yielded positive results. In total, 42 (8.5%) nodules underwent surgical resection, most of which were Bethesda System for Reporting Thyroid Cytopathology VI (n = 26, 61.9%). Of excised nodules, 33 (78.6%) nodules were malignant, 6 (14.3%) benign, and 3 (7.1%) noninvasive follicular thyroid neoplasm with papillary-like nuclear features. All Thyroid Imaging Reporting and Data System category 5 nodules with malignant cytology (Bethesda System for Reporting Thyroid Cytopathology V/VI) that underwent surgery were malignant on histopathology. On average, the total Thyroid Imaging Reporting and Data System points were higher in malignant nodules compared with benign (9.3 vs 7.3; P = .015). Moreover, benign nodules more frequently received Thyroid Imaging Reporting and Data System points when the radiologist was unable to determine composition or echogenicity (33% vs 3% among malignant nodules; P = .01). CONCLUSION/CONCLUSIONS:Thyroid Imaging Reporting and Data System category 5 designation in thyroid nodules is associated with a lower risk of malignancy than previously reported. Benign and malignant nodules with Thyroid Imaging Reporting and Data System category 5 designation have discrepancies in certain Thyroid Imaging Reporting and Data System characteristics and individual points assigned, which may offer an opportunity for quality improvement and standardization measures in ultrasound reporting practices.

Cochlear implants (CIs) are neuroprosthetic devices that can provide hearing to deaf people¹. Despite the benefits offered by CIs, the time taken for hearing to be restored and perceptual accuracy after long-term CI use remain highly variable^2,3. CI use is believed to require neuroplasticity in the central auditory system, and differential engagement of neuroplastic mechanisms might contribute to the variability in outcomes^4-7. Despite extensive studies on how CIs activate the auditory system^4,8-12, the understanding of CI-related neuroplasticity remains limited. One potent factor enabling plasticity is the neuromodulator noradrenaline from the brainstem locus coeruleus (LC). Here we examine behavioural responses and neural activity in LC and auditory cortex of deafened rats fitted with multi-channel CIs. The rats were trained on a reward-based auditory task, and showed considerable individual differences of learning rates and maximum performance. LC photometry predicted when CI subjects began responding to sounds and longer-term perceptual accuracy. Optogenetic LC stimulation produced faster learning and higher long-term accuracy. Auditory cortical responses to CI stimulation reflected behavioural performance, with enhanced responses to rewarded stimuli and decreased distinction between unrewarded stimuli. Adequate engagement of central neuromodulatory systems is thus a potential clinically relevant target for optimizing neuroprosthetic device use.

In situ simulation has frequently been used to improve team performance and provide an opportunity for the practice of critical skills and identify latent safety threats, which are undetected risks that may lead to adverse outcomes. However, the use of known quality improvement tools to prioritize and mitigate these safety threats is an area requiring further study. Over the course of 9 in situ simulations of a pediatric shock case, postcase debriefs were held to identify latent safety threats in an emergency department and a mixed pediatric and adult inpatient unit. Latent safety threats identified included structure-related threats such as inability to locate critical equipment, knowledge-based threats relating to rapid intravenous fluid administration, and communication-based threats such as lack of role designation. Identification of latent safety threats in the health care environment may assist clinician leaders in mitigating risk of patient harm. The protocol described may be adopted and applied to other critical event simulations, with structured debriefing used as a tool to identify and mitigate threats before they affect the patient.

BACKGROUND:There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population. METHODS:Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines. RESULTS:A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens. CONCLUSION/CONCLUSIONS:Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.