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1.
Laryngoscope ; 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38587169

OBJECTIVES: To use portable colorimetry to quantify color differences between facial skin and potential three head and neck microvascular free tissue transfer (MFTT) donor sites-radial forearm (RF), anterolateral thigh (ALT), and fibula (FF)-and compare these differences by pigmentation of the donor site skin and self-identified race. METHODS: In this cross-sectional cohort study, healthy volunteers consented to handheld colorimeter measurements at the three potential MFTT donor sites (RF, ALT, FF) to quantify color match to the facial skin using the CIE color space (DeltaE). The comparison of ipsilateral to contralateral cheek served as control for measurements. Cross-sectional measurements in healthy volunteers were then compared to measurements obtained in postoperative head and neck MFTT patients. RESULTS: DeltaE measurements were obtained for 128 healthy controls and 24 postoperative patients (N = 152). With increasing lightness (decreased pigmentation) of the skin at the donor site, the color match significantly worsened (higher DeltaE) across all potential MFTT donor sites (all p < 0.05). DeltaE from healthy controls closely approximated postoperative color match measurements in patients who underwent cervicofacial MFTT (DeltaE RF: 5.3 vs. 6.0, p = 0.432; DeltaE ALT: 6.2 vs. 6.4, p = 0.822; DeltaE FF: 6.0 vs. 6.4, p = 0.806). CONCLUSION: Patients with decreased skin pigmentation who are undergoing head and neck MFTT may experience worse color discrepancy between cervicofacial skin and the transferred skin paddle than those with more pigmented skin. Portable colorimetry may identify patients who could benefit from interventions such as dermis-resected free tissue reconstruction with skin grafting to improve postoperative appearance. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

2.
Head Neck ; 2024 Feb 27.
Article En | MEDLINE | ID: mdl-38411290

OBJECTIVES: To describe the clinicopathologic presentation of buccal squamous cell carcinoma and identify risks factors for recurrence and overall survival. METHODS: This is a retrospective case-control study of patients with oral cavity squamous cell carcinoma (OCSCC) treated at a single tertiary care center between 2010 and 2022. All patients with buccal subsite OCSCC treated during this time frame were included and paired with a randomly selected age and gender matched patient with non-buccal OCSCC. Relevant data was collected via chart review. RESULTS: Seventy-seven patients with buccal SCC were matched with 77 non-buccal OCSCC controls. The median follow-up time was 27 months (IQR 14-61). Median age was 67 years (IQR 57-75) and 53% of the cohort was female. Twenty (26%) buccal SCC patients experienced a recurrence versus 19 (25%) in the controls. Age ≥65-years-old increased odds of all-cause mortality in the buccal SCC group, but not in the control group. Perineural invasion and positive margins increased odds of recurrence in the buccal group only. Overall survival and progression-free survival did not differ between the groups, despite a greater number of T2 buccal tumors and T1 non-buccal tumors. CONCLUSIONS: Buccal SCC presents at a higher T stage than other oral cavity SCC subsite and may exhibit variance in the pathologic risk factors that predict poor outcomes versus non-buccal OCSCC. Despite these relatively minor differences, however, oncologic outcomes between these groups were similar.

3.
Otolaryngol Head Neck Surg ; 170(2): 544-551, 2024 Feb.
Article En | MEDLINE | ID: mdl-37747036

OBJECTIVE: Examine the association between sociodemographic factors and Individualized Education Program (IEP) establishment. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. METHODS: Participants included deaf or hard-of-hearing children who were eligible for an IEP with "deafness" or "hard of hearing" as a primary or secondary disability. Primary outcome measures were time intervals between initial referral for services and parental consent; parental consent to determination of eligibility; and initial referral to eligibility (the sum of the previous 2 intervals). Student's t tests and linear regression were used to examine the association between sociodemographic factors and the primary outcome variables. RESULTS: Of the 88 participants, 51 (58%) were male, 45 (51%) were from underrepresented minority (URM) groups, 35 (40%) spoke a primary language other than English, and 53 (60%) utilized public insurance. IEP establishment was significantly delayed in participants who required an English-language interpreter. Most of the delay occurred in the time between the initial referral and parental consent (mean: 115 vs 37 days, P = .02). There were also significant delays from the time of referral for services to eligibility in URM participants (mean: 159 vs 85 days, P = .04). Significant delays were also associated with Minority Status and Language within social vulnerability index percentile rankings. CONCLUSION: This study found that IEP establishment was delayed in both URM participants and those who required an English-language interpreter. These results highlight the importance of clear communication between the school system and caregivers in the IEP establishment process, particularly with families who require an English-language interpreter or identify as URM.


Hearing Loss , Child , Humans , Male , Female , Retrospective Studies , Language , Communication , Hearing
5.
JCI Insight ; 8(24)2023 Dec 22.
Article En | MEDLINE | ID: mdl-37943620

Transmembrane and tetratricopeptide repeat 4 (Tmtc4) is a deafness gene in mice. Tmtc4-KO mice have rapidly progressive postnatal hearing loss due to overactivation of the unfolded protein response (UPR); however, the cellular basis and human relevance of Tmtc4-associated hearing loss in the cochlea was not heretofore appreciated. We created a hair cell-specific conditional KO mouse that phenocopies the constitutive KO with postnatal onset deafness, demonstrating that Tmtc4 is a hair cell-specific deafness gene. Furthermore, we identified a human family in which Tmtc4 variants segregate with adult-onset progressive hearing loss. Lymphoblastoid cells derived from multiple affected and unaffected family members, as well as human embryonic kidney cells engineered to harbor each of the variants, demonstrated that the human Tmtc4 variants confer hypersensitivity of the UPR toward apoptosis. These findings provide evidence that TMTC4 is a deafness gene in humans and further implicate the UPR in progressive hearing loss.


Deafness , Hearing Loss , Animals , Humans , Mice , Cochlea/metabolism , Deafness/genetics , Hair , Hair Cells, Auditory/metabolism , Hearing Loss/genetics , Hearing Loss/metabolism
6.
Mol Ther Methods Clin Dev ; 30: 413-428, 2023 Sep 14.
Article En | MEDLINE | ID: mdl-37663645

Adeno-associated virus (AAV)-mediated gene transfer has shown promise in rescuing mouse models of genetic hearing loss, but how viral capsid and promoter selection affects efficacy is poorly characterized. Here, we tested combinations of AAVs and promoters to deliver Tmprss3, mutations in which are associated with hearing loss in humans. Tmprss3tm1/tm1 mice display severe cochlear hair cell degeneration, loss of auditory brainstem responses, and delayed loss of spiral ganglion neurons. Under the ubiquitous CAG promoter and AAV-KP1 capsid, Tmprss3 overexpression caused striking cytotoxicity in vitro and in vivo and failed to rescue degeneration or dysfunction of the Tmprss3tm1/tm1 cochlea. Reducing the dosage or using AAV-DJ-CAG-Tmprss3 diminished cytotoxicity without rescue of the Tmprss3tm1/tm1 cochlea. Finally, the combination of AAV-KP1 capsid and the EF1α promoter prevented cytotoxicity and reduced hair cell degeneration, loss of spiral ganglion neurons, and improved hearing thresholds in Tmprss3tm1/tm1 mice. Together, our study illustrates toxicity of exogenous genes and factors governing rescue efficiency, and suggests that cochlear gene therapy likely requires precisely targeted transgene expression.

7.
Otolaryngol Head Neck Surg ; 169(6): 1436-1444, 2023 Dec.
Article En | MEDLINE | ID: mdl-37555241

OBJECTIVE: Otolaryngologists take on various leadership roles throughout their daily practice, but specific training focused on leadership development during otolaryngology-head and neck surgery (OHNS) residency is not well-defined. This project explores the current state of leadership curricula for OHNS residents. DATA SOURCES: Google Scholar, Embase, PubMed, and MedEdPORTAL. REVIEW METHODS: A scoping review was performed on English-language, full-text, peer-reviewed articles that describe leadership curricula for OHNS residents. Investigators reviewed curriculum settings, content, delivery methods, and assessment; curriculum effectiveness was evaluated using Kirkpatrick effectiveness scores and article quality was assessed using the Best Evidence in Medical Education (BEME) index. CONCLUSION: Three thousand four hundred sixteen articles met search criteria, 198 articles were included for full-text review, and 4 articles met inclusion criteria. Curriculum content and delivery methods were diverse. Curriculum cadence ranged from 2-day immersion trainings to year-long longitudinal programs. Only one of the included studies utilized a needs assessment to inform curriculum development. Two articles achieved Kirkpatrick effectiveness scores of 2, indicating changes in the attitudes or perceptions among participants and a quality measure of 3, indicating clear conclusions drawn from the results. IMPLICATIONS FOR PRACTICE: The current state of leadership training in OHNS residency is limited and nonuniform. These data align with descriptions of leadership training in other surgical residencies which are reported as heterogenous and lacking in effectiveness. This review highlights the need for standardized leadership training for OHNS residents. The high-quality leadership development initiatives within graduate medical education are reviewed to inform future directions for effective curriculum development and assessment.


Internship and Residency , Otolaryngology , Humans , Leadership , Curriculum , Education, Medical, Graduate , Otolaryngology/education
8.
Surg Neurol Int ; 14: 222, 2023.
Article En | MEDLINE | ID: mdl-37404522

Background: Unruptured intracranial aneurysms (UIAs) have an estimated global prevalence of 2.8% in the adult population; however, UIA was identified among more than 10% of ischemic stroke patients. Many epidemiological studies and reviews have pointed to the presence of UIA among patients with ischemic stroke; yet, the extent of this association is not fully known. We performed a systematic review and meta-analysis to determine the prevalence of UIA in patients admitted to hospitals with ischemic stroke and transient ischemic attack (TIA) at both global and continental levels and evaluate factors associated with UIA in this population. Methods: We identified, in five databases, all studies describing UIA in ischemic stroke and TIA patients between January 1, 2000, and December 20, 2021. Included studies were of observational and experimental design. Results: Our search yielded 3581 articles of which 23 were included, with a total of 25,420 patients. The pooled prevalence of UIA was 5% (95% confidence interval [CI] = 4-6%) with stratified results showing 6% (95% CI = 4-9%), 6% (95% CI = 5-7%), and 4% (95% CI = 2-5%) in North America, Asia, and Europe, respectively. Significant risk factors were large vessel occlusion (odds ratios [OR] = 1.22, 95% CI = 1.01-1.47) and hypertension (OR = 1.45, 95% CI = 1.24-1.69), while protective factors were male sex (OR = 0.60, 95% CI = 0.53-0.68) and diabetes (OR = 0.82, 95% CI = 0.72-0.95). Conclusion: The prevalence of UIA is notably higher in ischemic stroke patients than the general population. Physicians should be aware of common risk factors in stroke and aneurysm formation for appropriate prevention.

9.
Cell Rep ; 36(2): 109358, 2021 07 13.
Article En | MEDLINE | ID: mdl-34260939

The utricle is a vestibular sensory organ that requires mechanosensitive hair cells to detect linear acceleration. In neonatal mice, new hair cells are derived from non-sensory supporting cells, yet cell type diversity and mechanisms of cell addition remain poorly characterized. Here, we perform computational analyses on single-cell transcriptomes to categorize cell types and resolve 14 individual sensory and non-sensory subtypes. Along the periphery of the sensory epithelium, we uncover distinct groups of transitional epithelial cells, marked by Islr, Cnmd, and Enpep expression. By reconstructing de novo trajectories and gene dynamics, we show that as the utricle expands, Islr+ transitional epithelial cells exhibit a dynamic and proliferative phase to generate new supporting cells, followed by coordinated differentiation into hair cells. Taken together, our study reveals a sequential and coordinated process by which non-sensory epithelial cells contribute to growth of the postnatal mouse sensory epithelium.


Ear, Inner/cytology , Sensation/genetics , Single-Cell Analysis , Transcriptome/genetics , Animals , Animals, Newborn , Cell Differentiation , Cell Lineage , Epithelial Cells/cytology , Hair Cells, Auditory/cytology , Mice , Reproducibility of Results , Saccule and Utricle/cytology , Transcription, Genetic
10.
Cureus ; 13(12): e20517, 2021 Dec.
Article En | MEDLINE | ID: mdl-35070552

Fournier's gangrene (FG) is an atypical, life-threatening polymicrobial infection characterized by the rapid destruction of soft tissue, predominantly in the perineal region. Retroperitoneal spread of FG represents an uncommon condition described in a few case reports, and its presentation as the first manifestation of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is even more infrequent. Here, we present the case of a 40-year-old male who was admitted to the emergency department with a low-grade fever of 37.8°C, abdominal pain, and four-day history of sharp, bilateral testicular pain and swelling. On physical examination, the patient was hypotensive with necrotic tissue in the perineum. A computed tomography study displayed an extensive retroperitoneal spread of suspected FG. Due to the massive spread of the infection, an HIV test was requested, yielding positive results, which indicated that HIV/AIDS had first manifested as FG with retroperitoneal extension. This is an extremely rare initial presentation of HIV/AIDS. To treat the patient and address the severe necrosis, a peritoneal lavage, surgical debridement, right orchiectomy, and colostomy were performed. After the procedure, antiretroviral therapy was established with tenofovir, emtricitabine, and efavirenz.

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