Presbycusis and Hearing Preservation in Observed Vestibular Schwannomas.

OBJECTIVE: We reviewed a cohort of patients with untreated sporadic vestibular schwannoma (VS) and examined the relationship between high-frequency hearing loss (HFHL) in the non-VS ear and long-term hearing outcomes in the VS-affected ear. We hypothesized that the progression of HFHL is associated with accelerated hearing decline in sporadic VS. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary center. PATIENTS: We studied 102 patients with sporadic VS diagnosed from 1999 to 2015 with ≥5 years of observation (median, 6.92; interquartile range, 5.85-9.29). Sixty-six patients had AAO-HNS class A/B hearing at presentation and were included in analysis. INTERVENTIONS: Audiometry, serial magnetic resonance imaging for observation of VS. MAIN OUTCOME MEASURES: Four-frequency pure tone average (PTA) and word recognition scores (WRS) in the VS-affected ear. Decline in high-frequency PTA (average of thresholds at 4000, 6000, and 8,000 Hz) was defined as ≥10 dB during the study period. Decline in WRS was defined as ≥10%. RESULTS: Compared with those without, patients with progressive HFHL in the non-VS ear were more likely to experience a decline in WRS in the VS ear (80% vs. 54%, p = 0.031). However, the same group showed no difference (52% vs. 41%, p = 0.40) in decline in PTA of the VS ear. CONCLUSIONS: Patients with observed VS who experience progressive HFHL in the non-VS ear are more likely to experience significant declines in speech understanding in the VS-affected ear over time. Patients with a history of presbycusis may have an increased risk of losing serviceable hearing because of sporadic VS.

First Report of the Bat Tick Carios kelleyi (Acari: Ixodida: Argasidae) From Vermont, United States.

The soft tick Carios kelleyi (Cooley and Kohls, 1941) is an ectoparasite of bats that can harbor bacteria known to cause disease in humans, such as Rickettsia spp., Bartonella spp., and relapsing fever Borrelia spp. Human-tick encounters may occur when bats occupy attics or similar dwellings with access points to human-inhabited areas. During May 2021, a partially engorged adult female C. kelleyi was collected from a Vermont home with an attic that was being used as a roost by big brown bats, Eptesicus fuscus (Chiroptera: Vespertilionidae). The source of the blood in the tick was the domestic dog, Canis lupus familiaris. Subsequently, eight C. kelleyi larvae were collected from a rescued E. fuscus adult. This is the first report of a soft tick species from Vermont and it is unknown how long C. kelleyi has been present in this state. Reports of C. kelleyi are on the rise across the northeastern United States but the implications for the health of humans, domestic animals, and bats in northern New England remain unclear. Bat management plans should consider the importance of bat exclusion in preventing tick encounters with members of the household and should include a tick monitoring component if bats are evicted.

Comparative hologenomics of two Ixodes scapularis tick populations in New Jersey.

Tick-borne diseases, such as those transmitted by the blacklegged tick Ixodes scapularis, are a significant and growing public health problem in the US. There is mounting evidence that co-occurring non-pathogenic microbes can also impact tick-borne disease transmission. Shotgun metagenome sequencing enables sampling of the complete tick hologenome-the collective genomes of the tick and all of the microbial species contained therein, whether pathogenic, commensal or symbiotic. This approach simultaneously uncovers taxonomic composition and allows the detection of intraspecific genetic variation, making it a useful tool to compare spatial differences across tick populations. We evaluated this approach by comparing hologenome data from two tick samples (N = 6 ticks per location) collected at a relatively fine spatial scale, approximately 23 km apart, within a single US county. Several intriguing variants in the data between the two sites were detected, including polymorphisms in both in the tick's own mitochondrial DNA and that of a rickettsial endosymbiont. The two samples were broadly similar in terms of the microbial species present, including multiple known tick-borne pathogens (Borrelia burgdorferi, Babesia microti, and Anaplasma phagocytophilum), filarial nematodes, and Wolbachia and Babesia species. We assembled the complete genome of the rickettsial endosymbiont (most likely Rickettsia buchneri) from both populations. Our results provide further evidence for the use of shotgun metagenome sequencing as a tool to compare tick hologenomes and differentiate tick populations across localized spatial scales.

Preclinical assessment of clinically streamlined, 3D-printed, biocompatible single- and two-stage tissue scaffolds for ear reconstruction.

Auricular reconstruction is a technically demanding procedure requiring significant surgical expertise, as the current gold standard involves hand carving of the costal cartilage into an auricular framework and re-implantation of the tissue. 3D-printing presents a powerful tool that can reduce technical demands associated with the procedure. Our group compared clinical, radiological, histological, and biomechanical outcomes in single- and two-stage 3D-printed auricular tissue scaffolds in an athymic rodent model. Briefly, an external anatomic envelope of a human auricle was created using DICOM computed tomography (CT) images and modified in design to create a two-stage, lock-in-key base and elevating platform. Single- and two-stage scaffolds were 3D-printed by laser sintering poly-L-caprolactone (PCL) then implanted subcutaneously in five athymic rats each. Rats were monitored for ulcer formation, site infection, and scaffold distortion weekly, and scaffolds were explanted at 8 weeks with analysis using microCT and histologic staining. Nonlinear finite element analysis was performed to determine areas of high strain in relation to ulcer formation. Scaffolds demonstrated precise anatomic appearance and maintenance of integrity of both anterior and posterior auricular surfaces and scaffold projection, with no statistically significant differences in complications noted between the single- and two-staged implantation. While minor superficial ulcers occurred most commonly at the lateral and superior helix coincident with finite element predictions of high skin strains, evidence of robust tissue ingrowth and angiogenesis was visible grossly and histologically. This promising preclinical small animal model supports future initiatives for making clinically viable options for an ear tissue scaffold.

Intraoperative Fluorescent Angiography Predicts Pharyngocutaneous Fistula After Salvage Laryngectomy.

BACKGROUND: Technology to assess tissue perfusion is exciting with translational potential, although data supporting its clinical applications have been lagging. Patients who have undergone radiation are at particular risk of poor tissue perfusion and would benefit from this expanding technology. We designed a prospective clinical trial using intraoperative indocyanine green angiography to evaluate for wound-healing complications in patients undergoing salvage laryngectomy after radiation failure. PATIENTS AND METHODS: This prospective trial included patients undergoing salvage laryngectomy at a National Cancer Institute-designated tertiary cancer center between 2016 and 2018. After tumor extirpation and prior to reconstruction, 10 mg indocyanine green dye was infused and the fluorescence (FHYPO) and ingress rate of the pharyngeal mucosa recorded. The primary outcome measure was formation of a pharyngocutaneous fistula (PCF). RESULTS: Patients who developed a PCF had significantly lower FHYPO (87 vs 172, p < 0.001) and ingress rates (6.7 vs 15.8, p = 0.043) compared with those who did not develop a fistula. There were no fistulas in patients with FHYPO > 150 (n = 21) or ingress > 15 (n = 15). There was a 50% fistula rate in patients with FHYPO ≤ 103 (n = 10) and ingress rate ≤ 6 (n = 6). CONCLUSIONS: Intraoperative indocyanine green angiography can assess hypoperfusion in patients and predict risk of PCFs after salvage laryngectomy, and can thus intraoperatively risk-stratify patients for postoperative wound-healing complications.

Head and Neck Squamous Cell Carcinoma Detection and Surveillance: Advances of Liquid Biomarkers.

Head and neck squamous cell carcinomas are aggressive tumors that often present at advanced stage in difficult-to-biopsy regions of the head and neck. With the rapid move to analyze circulating tumor DNA (ctDNA) to either detect cancer or monitor disease progression and response to therapy, we have designed this article as a primer to understand the recent studies that support a transition to use these circulating biomarkers as a part of routine clinical care. Whereas some technical challenges still need to be overcome, the utility of ctDNA in cancer care is already evident from these early studies. Therefore, it is critical to understand recent advances in this area as well as emerging questions that need to be addressed as these biomarkers move closer to enhancing routine clinical care paradigms. Laryngoscope, 129:1836-1843, 2019.

Pore architecture effects on chondrogenic potential of patient-specific 3-dimensionally printed porous tissue bioscaffolds for auricular tissue engineering.

OBJECTIVE: This study aims to determine the effect of auricular scaffold microarchitecture on chondrogenic potential in an in vivo animal model. METHODS: DICOM computed tomography (CT) images of a human auricle were segmented to create an external anatomic envelope. Image-based design was used to generate 1) orthogonally interconnected spherical pores and 2) randomly interspersed pores, and each were repeated in three dimensions to fill the external auricular envelope. These auricular scaffolds were then 3D printed by laser sintering poly-l-caprolactone, seeded with primary porcine auricular chondrocytes in a hyaluronic acid/collagen hydrogel and cultured in a pro-chondrogenic medium. The auricular scaffolds were then implanted subcutaneously in rats and explanted after 4 weeks for analysis with Safranin O and Hematoxylin and Eosin staining. RESULTS: Auricular constructs with two micropore architectures were rapidly manufactured with high fidelity anatomic appearance. Subcutaneous implantation of the scaffolds resulted in excellent external appearance of both anterior and posterior auricular surfaces. Analysis on explantation showed that the defined, spherical micropore architecture yielded histologic evidence of more robust chondrogenic tissue formation as demonstrated by Safranin O and Hematoxylin and Eosin staining. CONCLUSIONS: Image-based computer-aided design and 3D printing offers an exciting new avenue for the tissue-engineered auricle. In early pilot work, creation of spherical micropores within the scaffold architecture appears to impart greater chondrogenicity of the bioscaffold. This advantage could be related to differences in permeability allowing greater cell migration and nutrient flow, differences in surface area allowing different cell aggregation, or a combination of both factors. The ability to design an anatomically correct scaffold that maintains its structural integrity while also promoting auricular cartilage growth represents an important step towards clinical applicability of this new technology.

REV1 and polymerase ζ facilitate homologous recombination repair.

REV1 and DNA Polymerase ζ (REV3 and REV7) play important roles in translesion DNA synthesis (TLS) in which DNA replication bypasses blocking lesions. REV1 and Polζ have also been implicated in promoting repair of DNA double-stranded breaks (DSBs). However, the mechanism by which these two TLS polymerases increase tolerance to DSBs is poorly understood. Here we demonstrate that full-length human REV1, REV3 and REV7 interact in vivo (as determined by co-immunoprecipitation studies) and together, promote homologous recombination repair. Cells lacking REV3 were hypersensitive to agents that cause DSBs including the PARP inhibitor, olaparib. REV1, REV3 or REV7-depleted cells displayed increased chromosomal aberrations, residual DSBs and sites of HR repair following exposure to ionizing radiation. Notably, cells depleted of DNA polymerase η (Polη) or the E3 ubiquitin ligase RAD18 were proficient in DSB repair following exposure to IR indicating that Polη-dependent lesion bypass or RAD18-dependent monoubiquitination of PCNA are not necessary to promote REV1 and Polζ-dependent DNA repair. Thus, the REV1/Polζ complex maintains genomic stability by directly participating in DSB repair in addition to the canonical TLS pathway.