Faculty Bibliography

INTRODUCTION/BACKGROUND:Neonates with severe Pierre Robin sequence (PRS) can be treated by mandibular distraction osteogenesis (MDO), tongue-lip adhesion, or tracheostomy; however, there is an active debate regarding the indications of MDO in this patient population. Published algorithms identify tracheomalacia, bronchomalacia, laryngomalacia, hypotonic syndromes, and central sleep apnea as contraindications for MDO and indications for tracheostomy, but these comorbidities may exist along a spectrum of severity. The authors propose that appropriately selected neonates with PRS who concurrently express 1 or more of these traditional contraindications may be successfully treated with MDO. METHODS:The authors performed a 5-year retrospective chart review of all neonates who underwent MDO for treatment of severe PRS. All patients expressed a comorbidity previously identified as an indication for tracheostomy. Pre- and postoperative characteristics were recorded. Apnea/hypopnea index (AHI) before and after MDO were compared using 2-tailed repeated measures t-test. RESULTS:The authors identified 12 patients with severe PRS and conditions associated with contraindications to MDO: 9 (75.0%) patients had laryngomalacia, 6 (50.0%) patients had tracheomalacia, 2 (16.6%) patients had bronchomalacia, 1 (8.3%) patient had central sleep apnea, and 3 (25.0%) patients had hypotonia. Five (41.7%) patients underwent concurrent gastrostomy tube placement due to feeding insufficiency. Average birthweight was 3.0 kg. Average pre-op AHI was 34.8. Average post-op AHI was 7.3. All patients successfully underwent MDO with avoidance of tracheostomy. CONCLUSIONS:By employing an interdisciplinary evaluation of patient candidacy, MDO can safely and effectively treat upper airway obstruction and avoid tracheostomy in higher-risk neonatal patients with traditional indications for tracheostomy.

BACKGROUND:The goal of this study was to evaluate hard tissue response following guided bone regeneration using commercially available bovine bone grafts and collagen membranes; bilayer collagen membrane and porcine pericardium-based membrane, by means of a non-destructive three-dimensional (3D) computerized volumetric analysis following microtomography reconstruction. MATERIAL AND METHODS/METHODS:Bone regenerative properties of various bovine bone graft materials were evaluated in the Göttingen minipig model. Two standardized intraosseous defects (15mm x 8mm x 8mm) were created bilaterally of the mandible of eighteen animals (n=72 defects). Groups were nested within the same subject and randomly distributed among the sites: (i) negative control (no graft and membrane), (ii) bovine bone graft/bilayer collagen membrane (BOB) (iii) Bio-Oss® bone graft/porcine pericardium-based membrane (BOJ) and (iv) cerabone® bone graft/porcine pericardium-based membrane (CJ). Samples were harvested at 4, 8, and 12-week time points (n=6 animal/time point). Segments were scanned using computerized microtomography (μCT) and three dimensionally reconstructed utilizing volumetric reconstruction software. Statistical analyses were performed using IBM SPSS with a significance level of 5%. RESULTS:From a temporal perspective, tridimensional evaluation revealed gradual bone ingrowth with the presence of particulate bone grafts bridging the defect walls, and mandibular architecture preservation over time. Volumetric analysis demonstrated no significant difference between all groups at 4 weeks (p>0.127). At 8 and 12 weeks there was a higher percentage of new bone formation for control and CJ groups when compared to BOB and BOJ groups (p<0.039). The natural bovine bone graft group showed more potential for graft resorption over time relative to bovine bone graft, significantly different between 4 and 8 weeks (p<0.003). CONCLUSIONS:Volumetric analysis yielded a favorable mandible shape with respect to time through the beneficial balance between graft resorption/bone regenerative capacity for the natural bovine bone graft.

BACKGROUND:The demand for facial feminization surgery (FFS) amongst transgender women is on the rise, and requests for a single-stage full FFS (F-FFS) are becoming more frequent. The specific aim of this article is to present our institutional experience with both partial-FFS (P-FFS) and F-FFS with a specific emphasis on safety of each approach. METHODS:We examined the electronic medical record of all patients with the diagnosis of gender dysphoria that were referred to the senior author for FFS consultation at our institution, between June 2017 and October 2020. Patients were sub-grouped into those who underwent F-FFS (upper, middle, and lower facial thirds in a single anesthetic event) and those who underwent P-FFS. Univariate analysis was used to assess for difference in postoperative complications. RESULTS:We identified 77 patients who underwent 382 total procedures. The mean follow-up time was 7.5 months (Sd = 7.3) (interquartile range 1.75-12.0 months). Fifty-one (71.4%) patients underwent F-FFS and 21 (28.6%) patients underwent P-FFS. Compared to P-FFS, F-FFS was not associated with an increase in postoperative complication (1 out of 21 [4.8%] versus 4 out of 51 [7.8%]) ( P < 0.556). When comparing characteristics of patients with postoperative complications to patients with no postoperative complications, the average body mass index was significantly higher (30.9 versus 25.4, respectively). ( P < 0.029). CONCLUSIONS:Full-FFS is a set of procedures that has gained increased popularity among male-to-female transgender patients. Our results support the understanding that F-FFS is a safe and reliable approach, which may be preferable to patients and providers alike.

Introduction: Thyroidectomy is commonly performed in otolaryngology. Complications such as recurrent laryngeal nerve (RLN) injury and severe hypocalcemia have reported incidences in national studies as high as 3% and 8%, respectively. Narcotic pain medications are commonly used for postoperative pain management. Here, we present the long-term results of a thyroidectomy quality and safety improvement program, with an emphasis on reducing narcotic use.
Method(s): All surgeons who perform thyroidectomy established standards for antibiotic administration, postoperative calcium management, and narcotics use. The program was established in 2018 and data on adverse events, length of stay, antibiotic and narcotic use were recorded prospectively from June 2018 to January 2021. Data trends were analyzed throughout the course of the study.
Result(s): During the study period, 542 thyroidectomies were performed by 14 surgeons. The average length of stay was less than 24 hours. Five (0.9%) adverse events were recorded: 1 (0.2%) temporary RLN dysfunction, 3 (0.6%) hematomas, 1 (0.2%) surgical site infection, and 1 (0.2%) temporary hypocalcemia. The average number of narcotics prescribed declined from 18 doses (95%CI: 16.8-18.5) in 2019 to 9 in 2020 (95%CI: 8.5-9.6) (p<0.0001), without an increase in need for refills. No instances of permanent hypocalcemia or permanent RLN injury were identified.
Conclusion(s): By implementing a thyroidectomy quality improvement program, we achieved extremely low rates of adverse events and significantly reduced the use of narcotics without adverse effects. These data can inform practitioners and the public about expected outcomes of thyroid surgery, and establish benchmarks for quality and safety.
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Introduction: Diabetic neuropathy (DN) is a debilitating disorder characterized by sensory loss and pain. Although common, DN has no effective treatment. A notable pathologic finding of DN is loss of sensory apparatus in the skin, causing sensory abnormalities and pain. Given that diabetic patients frequently develop skin complications, we hypothesize that skin microenvironment is important for the pathogenesis of DN.
Method(s): Our investigation focused on a skin molecule epidermal sirtuin 1 (SIRT1), which is an NAD + -dependent deacetylase known to regulate metabolism and senescence. To address the role of epidermal SIRT1 in neuroprotection against DN, we created a tamoxifeninducible epidermal SIRT1 knockout (KO) and a doxycycline-inducible epidermal SIRT1 overexpression (OE) mouse model. The KO and control mice were placed on high-fat diets (HFDs), and were subsequently assessed by behavioral, morphologic and transcriptome analyses. SIRT1 overexpression was induced in mice after three months of HFDs.
Result(s): The DN phenotype was greatly exacerbated by depletion of epidermal SIRT1, as mice developed extreme mechanical allodynia after HFD. There was also evidence of large-fiber neuropathy, including loss of Meissner corpuscles, tail sensory nerve conduction defects and degeneration of large-diameter axons, while small nerve fibers and the corresponding nociception were largely intact. The phenotype could not be rescued by treatment with the NAD+ precursor nicotinamide riboside. In comparison, induction of epidermal SIRT1 overexpression alleviated the diabetic mechanical allodynia in mice. One potential mechanism of achieving epidermal SIRT1-mediated neuroprotection is increasing the expression of epidermal brainderived neurotrophic factor (BDNF), which could preserve the morphologic and functional integrity of Meissner corpuscles.
Conclusion(s): Our data suggest an important role of epidermal SIRT1 in maintaining skin sensory apparatus and preventing mechanical allodynia in the setting of diabetes. The findings also highlight epidermal SIRT1 as a promising therapeutic target for DN due to easy accessibility of SIRT1 in skin keratinocytes

Background and Aims: We systematically evaluated the impact of the coronavirus 2019 (COVID-19) pandemic on stroke care across the world.
Method(s): Observational studies comparing characteristics, acute treatment delivery or hospitalization outcomes between stroke patients admitted during the COVID-19 pandemic and those admitted prior to the pandemic were identified by Medline, Scopus and Embase databases search. Random-effects meta-analyses were conducted for all outcomes.
Result(s): We identified 46 studies including 129, 494 patients. Patients admitted with stroke during the COVID-19 pandemic were found to be younger [mean difference (MD)= -1.19, 95%CI: -2.05, -0.32; I²=70%] and more frequently male (OR=1.11, 95%CI:1.01, 1.22; I²=54%) compared to stroke patients admitted in the pre-pandemic era. Stroke patients admitted during the COVID-19 pandemic, also, had higher baseline NIH Stroke Scale (NIHSS) scores (MD=0.55, 95%CI:0.12, 0.98; I²=90%), higher probability for large vessel occlusion presence (OR=1.63, 95%CI: 1.07, 2.48; I²=49%) and higher risk for in-hospital mortality (OR=1.26, 95%CI:1.05, 1.52; I²=55%). Acute ischemic stroke patients admitted during the COVID-19 pandemic had higher probability of receiving endovascular thrombectomy (EVT) treatment (OR=1.24, 95%CI:1.05, 1.47; I²=40%). No difference in the rates of intravenous thrombolysis administration or difference in time metrics regarding onset to treatment time for intravenous thrombolysis and onset to groin puncture time for EVT were detected.
Conclusion(s): Increased prevalence of younger patients, more severe strokes attributed to large vessel occlusion, and higher endovascular treatment rates were observed during the COVID-19 pandemic. Stroke patients admitted during the COVID-19 pandemic had higher in-hospital mortality. These findings need to be interpreted with caution in view of discrepant reports and heterogeneity being present across studies

OBJECTIVE:Evaluate the effect of aging using two different methods on the three-dimensional fit of zirconia abutments at the implant-abutment connection and estimate the probability of survival of anterior crowns supported by straight and 17-degree angled abutments. MATERIALS AND METHODS/METHODS:Two different zirconia abutment designs, straight and 17-degree angled abutments (n = 63/group), were evaluated in the current study. The abutments were randomly allocated into three experimental groups according to laboratory aging condition (134°C, 2.2 bar, 20 h): (i) control, (ii) autoclave aging, and (iii) hydrothermal reactor aging. Crystalline content was determined by X-Ray diffraction (XRD) and Raman spectroscopy, and microstructure was analyzed using field-emission gun scanning electron microscope (FEG-SEM). Implant-abutment volume misfit was determined in the straight abutments by micro-computed tomography using the silicone replica technique. For fatigue testing, abutments were torqued to the implants and connected to standardized maxillary incisor zirconia crowns. The assemblies were subjected to step-stress accelerated life testing (SSALT) in water until fracture or suspension. The use level probability Weibull curves and probability of survival for a mission of 50,000 cycles at 50, 100, 150 and 200 N were calculated and plotted. Fractured samples were analyzed using a stereomicroscope and scanning electron microscope. RESULTS:). The beta (β) values indicated that failures were predominantly controlled by material strength rather than fatigue damage accumulation for all groups, except for straight control abutments. Irrespective of aging, the probability of survival of straight and angled zirconia abutments was up to 95% (95-100%) at 50 and 100 N. A 50N-increase in the load resulted in wider range of survival estimate, with straight autoclave abutments percentage significantly lower probability of survival (77%) than angled hydrothermal reactor abutments (99%). At 200N, angled hydrothermal reactor (97%) or autoclave (82%) aged abutments demonstrated the highest probability of survival, angled control (71%) and straight hydrothermal reactor (69%) abutments intermediate values, and straight autoclave (23%) and control (7%) abutments the lowest estimate. The failure mode predominantly involved abutment and/or abutment screw fracture for both straight and angled abutments. CONCLUSIONS:Hydrothermal aging significantly influenced volume misfit, as well as the probability of survival of zirconia abutments at higher loads for both angled and straight abutments.

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR₂) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR₂. We report here a role for cathepsin S in PAR₂-dependent cancer pain. We report that cathepsin S was more active in human oral SCC than matched normal tissue, and in an orthotopic xenograft tongue cancer model than normal tongue. The multiplex immunolocalization of cathepsin S in human oral cancers suggests that carcinoma and macrophages generate cathepsin S in the oral cancer microenvironment. After cheek or paw injection, cathepsin S evoked nociception in wild-type mice but not in mice lacking PAR₂ in Na_v1.8-positive neurons (Par₂Na_v1.8), nor in mice treated with LY3000328 or an endogenous cathepsin S inhibitor (cystatin C). The human oral SCC cell line (HSC-3) with homozygous deletion of the gene for cathepsin S (CTSS) with CRISPR/Cas9 provoked significantly less mechanical allodynia and thermal hyperalgesia, as did those treated with LY3000328, compared to the control cancer mice. Our results indicate that cathepsin S is activated in oral SCC, and that cathepsin S contributes to cancer pain through PAR₂ on neurons.