Exploring CT pixel and voxel size effect on anatomic modeling in mandibular reconstruction.

BACKGROUND: Computer-aided modeling and design (CAM/CAD) of patient anatomy from computed tomography (CT) imaging and 3D printing technology enable the creation of tangible, patient-specific anatomic models that can be used for surgical guidance. These models have been associated with better patient outcomes; however, a lack of CT imaging guidelines risks the capture of unsuitable imaging for patient-specific modeling. This study aims to investigate how CT image pixel size (X-Y) and slice thickness (Z) impact the accuracy of mandibular models. METHODS: Six cadaver heads were CT scanned at varying slice thicknesses and pixel sizes and turned into CAD models of the mandible for each scan. The cadaveric mandibles were then dissected and surface scanned, producing a CAD model of the true anatomy to be used as the gold standard for digital comparison. The root mean square (RMS) value of these comparisons, and the percentage of points that deviated from the true cadaveric anatomy by over 2.00 mm were used to evaluate accuracy. Two-way ANOVA and Tukey-Kramer post-hoc tests were used to determine significant differences in accuracy. RESULTS: Two-way ANOVA demonstrated significant difference in RMS for slice thickness but not pixel size while post-hoc testing showed a significant difference in pixel size only between pixels of 0.32 mm and 1.32 mm. For slice thickness, post-hoc testing revealed significantly smaller RMS values for scans with slice thicknesses of 0.67 mm, 1.25 mm, and 3.00 mm compared to those with a slice thickness of 5.00 mm. No significant differences were found between 0.67 mm, 1.25 mm, and 3.00 mm slice thicknesses. Results for the percentage of points deviating from cadaveric anatomy greater than 2.00 mm agreed with those for RMS except when comparing pixel sizes of 0.75 mm and 0.818 mm against 1.32 mm in post-hoc testing, which showed a significant difference as well. CONCLUSION: This study suggests that slice thickness has a more significant impact on 3D model accuracy than pixel size, providing objective validation for guidelines favoring rigorous standards for slice thickness while recommending isotropic voxels. Additionally, our results indicate that CT scans up to 3.00 mm in slice thickness may provide an adequate 3D model for facial bony anatomy, such as the mandible, depending on the clinical indication.

Evaluating Listening Effort in Unilateral, Bimodal, and Bilateral Cochlear Implant Users.

OBJECTIVE: Evaluate listening effort (LE) in unilateral, bilateral, and bimodal cochlear implant (CI) users. Establish an easy-to-implement task of LE that could be useful for clinical decision making. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary neurotology center. METHODS: The Sentence Final Word Identification and Recall Task, an established measure of LE, was modified to include challenging listening conditions (multitalker babble, gender, and emotional variation; test), in addition to single-talker sentences (control). Participants listened to lists of sentences in each condition and recalled the last word of each sentence. LE was quantified by percentage of words correctly recalled and was compared across conditions, across CI groups, and within subjects (best aided vs monaural). RESULTS: A total of 24 adults between the ages of 37 and 82 years enrolled, including 4 unilateral CI users (CI), 10 bilateral CI users (CICI), and 10 bimodal CI users (CIHA). Task condition impacted LE (P < .001), but hearing configuration and listener group did not (P = .90). Working memory capacity and contralateral hearing contributed to individual performance. CONCLUSION: This study adds to the growing body of literature on LE in challenging listening conditions for CI users and demonstrates feasibility of a simple behavioral task that could be implemented clinically to assess LE. This study also highlights the potential benefits of bimodal hearing and individual hearing and cognitive factors in understanding individual differences in performance, which will be evaluated through further research.

National Trends in 30-Day Readmission Following Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

Importance: As the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise in the US, an increasing number of patients are being treated with transoral robotic surgery (TORS). Readmission following surgery can potentially delay initiation of adjuvant treatment and affect survival outcomes. Objective: To identify risk factors for 30-day postoperative readmission in patients undergoing TORS for OPSCC. Design, Setting, and Participants: This retrospective, population-based cohort study used data from the Nationwide Readmissions Database from 2010 to 2017. All patients undergoing TORS for OPSCC were identified using International Classification of Diseases codes and included. Exclusion criteria were age younger than 18 years or incomplete information regarding index admission or readmission. The analysis was performed from April to October 2023. Exposure: TORS for OPSCC. Main Outcomes and Measures: Univariate and multivariate analyses were performed to determine factors associated with 30-day readmission. Covariates included demographics and medical comorbidities, socioeconomic factors, hospital characteristics, and surgical details. Trends in readmission over time, reasons for readmission, and characteristics of the readmission were also examined. Results: A weighted total of 5544 patients (mean [SD] age, 60.7 [0.25] years; 4475 [80.7%] male) underwent TORS for OPSCC. The overall readmission rate was 17.5% (n = 971), and these rates decreased over the study period (50 of 211 patients [23.7%] in 2010 vs 58 of 633 patients [9.1%] in 2017). Risk factors associated with readmission included male sex (adjusted odds ratio [AOR], 1.54; 95% CI, 1.07-2.20) and a diagnosis of congestive heart failure (AOR, 2.42; 95% CI, 1.28-4.58). Factors associated with decreased rate of readmission included undergoing concurrent selective neck dissection (AOR, 0.30; 95% CI, 0.22-0.41). Among the 971 readmissions, the most common readmission diagnoses were bleeding (151 [15.6%]), electrolyte and digestive problems (44 [4.5%]), pneumonia (44 [4.5%]), and sepsis (26 [2.7%]). Conclusions and Relevance: In this cohort study, readmission rates following TORS for oropharynx cancer decreased over time; however, a subset of patients required readmission most commonly related to bleeding, infection, and electrolyte imbalance. Concurrent neck dissection may be protective against readmission. Elucidation of risk factors for readmission after TORS for OPSCC offers opportunities for evidence-based shared decision-making, quality improvement initiatives, and improved patient counseling.

Partial decellularization eliminates immunogenicity in tracheal allografts.

There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long-segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial formation while preserving mechanical properties. However, the ability of partial decellularization to eliminate graft immunogenicity remains unknown, and understanding the immunogenic properties of partially decellularized tracheal grafts (PDTG) is a critical step toward clinical translation. Here, we determined that tracheal allograft immunogenicity results in epithelial cell sloughing and replacement with dysplastic columnar epithelium and that partial decellularization creates grafts that are able to support an epithelium without histologic signs of rejection. Moreover, allograft implantation elicits CD8+ T-cell infiltration, a mediator of rejection, while PDTG did not. Hence, we establish that partial decellularization eliminates allograft immunogenicity while creating a scaffold for implantation that can support spatially appropriate airway regeneration.

Higher Computed Tomography (CT) Scan Resolution Improves Accuracy of Patient-specific Mandibular Models When Compared to Cadaveric Gold Standard.

BACKGROUND: 3D-printed patient-specific anatomical models are becoming an increasingly popular tool for planning reconstructive surgeries to treat oral cancer. Currently there is a lack of information regarding model accuracy, and how the resolution of the computed tomography (CT) scan affects the accuracy of the final model. PURPOSE: The primary objective of this study was to determine the CT z-axis resolution necessary in creating a patient specific mandibular model with clinically acceptable accuracy for global bony reconstruction. This study also sought to evaluate the effect of the digital sculpting and 3D printing process on model accuracy. STUDY DESIGN: This was a cross-sectional study using cadaveric heads obtained from the Ohio State University Body Donation Program. INDEPENDENT VARIABLES: The first independent variable is CT scan slice thickness of either 0.675 , 1.25, 3.00, or 5.00 mm. The second independent variable is the three produced models for analysis (unsculpted, digitally sculpted, 3D printed). MAIN OUTCOME VARIABLE: The degree of accuracy of a model as defined by the root mean square (RMS) value, a measure of a model's discrepancy from its respective cadaveric anatomy. ANALYSES: All models were digitally compared to their cadaveric bony anatomy using a metrology surface scan of the dissected mandible. The RMS value of each comparison evaluates the level of discrepancy. One-way ANOVA tests (P < .05) were used to determine statistically significant differences between CT scan resolutions. Two-way ANOVA tests (P < .05) were used to determine statistically significant differences between groups. RESULTS: CT scans acquired for 8 formalin-fixed cadaver heads were processed and analyzed. The RMS for digitally sculpted models decreased as slice thickness decreased, confirming that higher resolution CT scans resulted in statistically more accurate model production when compared to the cadaveric gold standard. Furthermore, digitally sculpted models were significantly more accurate than unsculpted models (P < .05) at each slice thickness. CONCLUSIONS: Our study demonstrated that CT scans with slice thicknesses of 3.00 mm or smaller created statistically significantly more accurate models than models created from slice thicknesses of 5.00 mm. The digital sculpting process statistically significantly increased the accuracy of models and no loss of accuracy through the 3D printing process was observed.

Successful Early Neovascularization in Composite Tracheal Grafts.

OBJECTIVE: Long-segment tracheal defects require tissue replacement for successful reconstruction. Rapid revascularization is imperative to maintain graft function. We previously showed that partially decellularized tracheal grafts (PDTG) and composite tracheal grafts (CTG; PDTG supported by a 3-dimensionally printed external splint) regenerate respiratory epithelium and may support the regeneration of endothelial cells (CD31+). However, the capability of graft endothelial cells to organize or contribute to tracheal revascularization remains unclear. In this study, we quantified endothelial cells (CD31+) and neovessel formation in PDTG and CTG. We hypothesize that PDTG and CTG support tracheal neovascularization to a similar extent as surgical (syngeneic tracheal graft [STG]) and native trachea (NT) controls. STUDY DESIGN: The animal study, a randomized control trial. SETTING: Center for Regenerative Medicine, Nationwide Children's Hospital. METHODS: PDTG was created via an established decellularization protocol. Segmental tracheal reconstruction was performed with STG, PDTG, or CTG using a mouse microsurgical model. NT was used as a nonsurgical control. At 1 month, mice were euthanized, grafts harvested, sectioned, and stained with CD31 and hematoxylin and eosin. Neovessel formation was quantified by the number of formed blood vessels in the lamina propria and vessel size (vessel/graft area, mm2 ). RESULTS: Decellularization eliminated all endothelial cells and there were no perfused vessels at implantation. At 1 month, PDTG and CTG supported neovessel formation with tubular vessels lined with endothelial cells. There was no difference in the number or size of vessels compared to controls. CONCLUSION: PDTG and CTG support tracheal endothelial cell regeneration and neovessel formation. Future directions to assess the function, kinetics, and distribution of graft neovessels are needed.

Association of Vibrotactile Biofeedback With Reduced Ergonomic Risk for Surgeons During Tonsillectomy.

Importance: Work-related musculoskeletal disorders are common among otolaryngologists and can be associated with decreased productivity, missed workdays, and reduced quality of life. Ergonomic risk for surgeons is elevated during common otolaryngology procedures; current ergonomic interventions lack the ability to provide real-time feedback. The ability to quantify and mitigate ergonomic risk during surgery may reduce work-related musculoskeletal disorders. Objective: To quantify the association of vibrotactile biofeedback with intraoperative ergonomic risk to surgeons during tonsillectomy. Design, Setting, and Participants: This cross-sectional study was conducted between June 2021 and October 2021 at a freestanding tertiary care children's hospital and included 11 attending pediatric otolaryngologists. Data analysis was conducted from August to October 2021. Interventions: Real-time quantification of ergonomic risk during tonsillectomy and the use of a vibrotactile biofeedback posture monitor. Main Outcomes and Measures: Association of vibrotactile biofeedback with objective measures of ergonomic risk. Assessment tools included the Rapid Upper Limb Assessment, craniovertebral angle, and time spent in an at-risk posture. Results: Eleven surgeons (mean [SD] age 42 [7] years; 2 women [18%]) performed 126 procedures with continuous posture monitoring in the presence (80 [63%]) and absence (46 [37%]) of vibrotactile biofeedback. No complications or delays associated with the device were reported. Intraoperative vibrotactile biofeedback was associated with improved Rapid Upper Limit Assessment neck, trunk, and leg scores by 0.15 (95% CI, 0.05-0.25), improved craniovertebral angle by 1.9 (95% CI, 0.32-3.40), and decreased overall time spent in an at-risk posture by 30% (95% CI, 22%-39%). Conclusions and Relevance: The results of this cross-sectional study suggest that use of a vibrotactile biofeedback device to quantify and mitigate ergonomic risk for surgeons is feasible and safe while performing surgery. Vibrotactile biofeedback was associated with reduced ergonomic risk during tonsillectomy and may have a role in improving surgical ergonomics and preventing work-related musculoskeletal disorders.

Response to induction chemotherapy in sinonasal malignancies: A single-institutional experience.

BACKGROUND: Sinonasal malignancy (SNM) is a heterogeneous group of diseases for which induction chemotherapy (IC) may reduce tumor burden. The purpose of this study was to characterize the response to IC in SNM as a prognostic factor through its effect on survival. METHODS: Retrospective cohort of patients undergoing IC for SNM between 2010 and 2019 at our quaternary referral center. RESULTS: Forty-two patients with advanced SNM were included in the analysis. Patients with a favorable response to IC had higher survival rates than those who had an unfavorable response (5-year OS: 66.8% vs. 9.7%; p < 0.001; PFS: 56.8% vs. 0%; p < 0.001). CONCLUSIONS: Response to IC in our patient cohort was a prognostic indicator of overall response to treatment. Further elucidation of predictors of response is needed for appropriate patient selection.

Hypothyroidism as an Independent Predictor of 30-day Readmission in Head and Neck Cancer Patients.

OBJECTIVES: To define the role of hypothyroidism and other risk factors for unplanned readmissions after surgery for head and neck cancer. STUDY DESIGN: Retrospective cohort study. METHODS: The Nationwide Readmission Database (NRD) was used to identify patients who underwent surgery for mucosal head and neck cancer (oral cavity, oropharynx, larynx, and hypopharynx) between 2010 and 2017. Univariate and multivariate logistic regression were performed to determine patient, tumor, and hospital related risk factors for 30-day readmission. Readmitted patients were stratified by preoperative diagnosis of hypothyroidism to compare readmission characteristics. RESULTS: For the 131,013 patients who met inclusion criteria, the readmission rate was 15.9%. Overall, 11.91% of patients had a preoperative diagnosis of hypothyroidism. After controlling for other variables, patients with a preoperative diagnosis of hypothyroidism had 12.2% higher odds of readmission compared to those without hypothyroidism (OR: 1.12, 1.03-1.22, p = 0.008). Patients with hypothyroidism had different reasons for readmission, including higher rates of wound dehiscence, fistula, infection, and electrolyte imbalance. Among readmitted patients, the length of stay for index admission (mean 10.5 days vs. 9.2 days, p < 0.001), readmission (mean 7.0 vs. 6.6 days, p = 0.05), and total hospital charge were higher for hypothyroid patients ($137,742 vs. $119,831, p < 0.001). CONCLUSION: Hypothyroidism is an independent risk factor for 30-day readmission following head and neck cancer resection. Furthermore, hypothyroid patients are more likely to be readmitted for wound complications, infection, and electrolyte imbalance. Targeted interventions should be considered for hypothyroid patients to decrease readmission rates and associated patient morbidity, potentially leading to earlier initiation of adjuvant treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2988-2998, 2023.

The Larry Tube: Customized 3D Printed Laryngectomy Tubes Following Total Laryngectomy.

OBJECTIVE: To determine whether a custom laryngectomy tube can improve airway symptoms in total laryngectomy patients with atypical anatomy who are unable to use commercial laryngectomy tubes. Furthermore, to exemplify the power of customizable 3D printed medical devices when combined with the expanded access pathway through the FDA. METHODS: A custom-fabricated laryngectomy tube, manufactured at in-house clinical engineering labs, was utilized for each patient following typical laryngectomy tube protocols. All participants had previously undergone a total laryngectomy. Patients were selected based on critical airway obstruction posing potentially life-threatening scenarios while using commercially available laryngectomy tubes. RESULTS: For all patients involved, there were no further airway obstruction complications or events, and they reported a subjective, significant improvement in comfort after placement of the custom laryngectomy tube. CONCLUSION: Custom laryngectomy tubes can provide patients with atypical anatomy relief from airway obstructions and improve comfort when commercial options fail to address the anatomic restriction. The process used to develop custom laryngectomy tubes may be relevant for other diseases and patients with atypical anatomies through the expanded access pathway.

Use of 3-dimensional printing at the point-of-care to manage a complex wound in hemifacial necrotizing fasciitis: a case report.

BACKGROUND: Complex facial wounds can be difficult to stabilize due to proximity of vital structures. We present a case in which a patient-specific wound splint was manufactured using computer assisted design and three-dimensional printing at the point-of-care to allow for wound stabilization in the setting of hemifacial necrotizing fasciitis. We also describe the process and implementation of the United States Food and Drug Administration Expanded Access for Medical Devices Emergency Use mechanism. CASE PRESENTATION: A 58-year-old female presented with necrotizing fasciitis of the neck and hemiface. After multiple debridements, she remained critically ill with poor vascularity of tissue in the wound bed and no evidence of healthy granulation tissue and concern for additional breakdown towards the right orbit, mediastinum, and pretracheal soft tissues, precluding tracheostomy placement despite prolonged intubation. A negative pressure wound vacuum was considered for improved healing, but proximity to the eye raised concern for vision loss due to traction injury. As a solution, under the Food and Drug Administration's Expanded Access for Medical Devices Emergency Use mechanism, we designed a three-dimensional printed, patient-specific silicone wound splint from a CT scan, allowing the wound vacuum to be secured to the splint rather than the eyelid. After 5 days of splint-assisted vacuum therapy, the wound bed stabilized with no residual purulence and developed healthy granulation tissue, without injury to the eye or lower lid. With continued vacuum therapy, the wound contracted to allow for safe tracheostomy placement, ventilator liberation, oral intake, and hemifacial reconstruction with a myofascial pectoralis muscle flap and a paramedian forehead flap 1 month later. She was eventually decannulated and at six-month follow-up has excellent wound healing and periorbital function. CONCLUSIONS: Patient-specific, three-dimensional printing is an innovative solution that can facilitate safe placement of negative pressure wound therapy adjacent to delicate structures. This report also demonstrates feasibility of point-of-care manufacturing of customized devices for optimizing complex wound management in the head and neck, and describes successful use of the United States Food and Drug Administration's Expanded Access for Medical Devices Emergency Use mechanism.

Superior Laryngeal Nerve Block Response Rates in 54 Neurogenic Cough Patients.

OBJECTIVE: Neurogenic cough related to hypersensitivity of the internal branch of the superior laryngeal nerve (SLN) is often treated with neuromodulating medications, which can cause considerable side effects. An alternative therapy is steroid and local anesthetic injection of the SLN ("SLN block"), initially proposed to benefit those with lateralizing symptoms (tenderness over the thyrohyoid membrane or unilateral cough source). Our objectives are to determine if SLN block produces subjective symptomatic improvements and if repeat injections further improve symptoms, and evaluate clinical factors potentially predictive of response. METHODS: Retrospective chart review of 54 patients receiving SLN blocks at a tertiary medical academic center from January 2010 to June 2020. Medical history and anticipated predictors of positive response, including stigmata of laryngeal hypersensitivity, were recorded. Outcomes included symptomatic response, number of injections required, and side effects. Response was defined subjectively by asking patients whether the injection was beneficial and objectively by using CSI scores. RESULTS: Fifty-four patients met the inclusion criteria. Thirty-eight patients (70.4%) endorsed improvement. No variables were identified as positive predictors of response. Thirty-two of the 38 (84.2%) endorsed improvement after one injection. Six of 15 (40%) patients who failed the first injection had positive response to the second. No significant side effects were reported. CONCLUSION: No localizing symptoms, specific cough features, or aspects of the medical history helped predict response, suggesting that a broader range of patients may be offered the intervention. The majority of patients reported symptomatic improvement and repeat injections may benefit patients with initial nonresponse. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2647-2653, 2023.

Modifiable risk factors for oral cavity cancer in non-smokers: A systematic review and meta-analysis.

BACKGROUND: Oral cavity cancer (OCC) is traditionally associated with smoking, but there is an increasing prevalence of the disease among non-smokers. This review investigates possible modifiable risk factors in the development of OCC in non-smokers (OCCNS). METHODS: PubMed, EMBASE, Web of Science, and Scopus were searched for publications prior to June 2021. Comparative studies investigating modifiable OCCNS risk factors were identified following PRISMA guidelines. Publication date, population size, and results were indexed. Study quality was assessed using MINORS (Methodological Index for Non-Randomized Studies). Factors examined by multiple studies were analyzed using random-effect meta-analysis framework. RESULTS: Literature search resulted in 1,625 unique publications. 52 records met inclusion criterion, investigating alcohol (n = 22), chewing products (n = 18), diet (n = 7), dental health (n = 11), and medical comorbidities (n = 6). CONCLUSION: This review demonstrates the paucity of large studies investigating OCCNS risk factors. Further investigation is warranted to help clinicians risk-stratify patients without traditional risk factors.

The role of computer aided design/computer assisted manufacturing (CAD/CAM) and 3- dimensional printing in head and neck oncologic surgery: A review and future directions.

Microvascular free flap reconstruction has remained the standard of care in reconstruction of large tissue defects following ablative head and neck oncologic surgery, especially for bony structures. Computer aided design/computer assisted manufacturing (CAD/CAM) and 3-dimensionally (3D) printed models and devices offer novel solutions for reconstruction of bony defects. Conventional free hand techniques have been enhanced using 3D printed anatomic models for reference and pre-bending of titanium reconstructive plates, which has dramatically improved intraoperative and microvascular ischemia times. Improvements led to current state of the art uses which include full virtual planning (VP), 3D printed osteotomy guides, and patient specific reconstructive plates, with advanced options incorporating dental rehabilitation and titanium bone replacements into the primary surgical plan through use of these tools. Limitations such as high costs and delays in device manufacturing may be mitigated with in house software and workflows. Future innovations still in development include printing custom prosthetics, 'bioprinting' of tissue engineered scaffolds, integration of therapeutic implants, and other possibilities as this technology continues to rapidly advance. This review summarizes the literature and serves as a summary guide to the historic, current, advanced, and future possibilities of 3D printing within head and neck oncologic surgery and bony reconstruction. This review serves as a summary guide to the historic, current, advanced, and future roles of CAD/CAM and 3D printing within the field of head and neck oncologic surgery and bony reconstruction.

Tissue-engineered composite tracheal grafts create mechanically stable and biocompatible airway replacements.

We tested composite tracheal grafts (CTG) composed of a partially decellularized tracheal graft (PDTG) combined with a 3-dimensional (3D)-printed airway splint for use in long-segment airway reconstruction. CTG is designed to recapitulate the 3D extracellular matrix of the trachea with stable mechanical properties imparted from the extraluminal airway splint. We performed segmental orthotopic tracheal replacement in a mouse microsurgical model. MicroCT was used to measure graft patency. Tracheal neotissue formation was quantified histologically. Airflow dynamic properties were analyzed using computational fluid dynamics. We found that CTG are easily implanted and did not result in vascular erosion, tracheal injury, or inflammation. Graft epithelialization and endothelialization were comparable with CTG to control. Tracheal collapse was absent with CTG. Composite tracheal scaffolds combine biocompatible synthetic support with PDTG, supporting the regeneration of host epithelium while maintaining graft structure.

Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis.

Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can enhance pancreatic islet function in cystic fibrosis (CF) is not known. We studied 32 adults with PI-CF and AGT randomized to receive either GLP-1 (n = 16) or GIP (n = 16) during glucose-potentiated arginine (GPA) testing of islet function on two occasions, with either incretin or placebo infused, in a randomized, double-blind, cross-over fashion. Another four adults with PI-CF and normal glucose tolerance (NGT) and four matched control participants without CF underwent similar assessment with GIP. In PI-CF with AGT, GLP-1 substantially augmented second-phase insulin secretion but without effect on the acute insulin response to GPA or the proinsulin secretory ratio (PISR), while GIP infusion did not enhance second-phase or GPA-induced insulin secretion but increased the PISR. GIP also did not enhance second-phase insulin in PI-CF with NGT but did so markedly in control participants without CF controls. These data indicate that GLP-1, but not GIP, augments glucose-dependent insulin secretion in PI-CF, supporting the likelihood that GLP-1 agonists could have therapeutic benefit in this population. Understanding loss of GIP's insulinotropic action in PI-CF may lead to novel insights into diabetes pathogenesis.

Treatment decision and estimation of growth of head and neck paragangliomas.

PURPOSE: Head and neck paragangliomas are slow growing tumors where observation has become more widely accepted. Tumor growth rate as well as predictors of increased tumor growth were analyzed with the goal to identify factors to better predict disease progression and counsel patients. MATERIALS AND METHODS: Multi-institutional retrospective cohort study from 2011 to 2020. RESULTS: 130 head and neck paragangliomas in 125 patients were analyzed. 38 were observed (30.4%), 16 radiated (12.8%), and 71 underwent surgery (56.8%). Surgical patients were significantly younger (p = 0.038) and with more genetically mediated paragangliomas (p = 0.026). Significantly more patients were asymptomatic in the observation group (p = 0.005). Of the 39 observed tumors, 43.6% (n = 17) grew with a tumor doubling time of 5.67 years. More than half of the observed paragangliomas had no growth. When examining symptoms postoperatively and at follow-up, the surgical cohort had significantly more worsening symptoms (p = 0.007) and new cranial neuropathies (p = 0.031). CONCLUSIONS: Head and neck paragangliomas have slow growth rates if they grow at all. Patients in the surgical cohort had more clinical symptoms at presentation and worsening postoperative symptoms.

Spontaneous Regression of Recurrent Respiratory Papillomatosis with HPV Vaccination: A Case Study.

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is characterized by recurrent laryngeal papillomas and treated with repeated surgical excision. The human papillomavirus (HPV) vaccine prevents infection with strains of HPV unrelated to RRP, and has recently been shown to increase the interval between surgeries when used as an adjuvant. The objective of this study was to report one case from our institution in which HPV vaccination was found to induce spontaneous regression of disease, absent of surgical intervention or use of other adjuvants. STUDY DESIGN: Retrospective case study. METHODS: Records of one patient with RRP receiving partial HPV vaccination was reviewed with attention to videolaryngostroboscopic findings, Derkay score, need for surgical intervention, and voice quality. RESULTS: Spontaneous regression of disease after vaccination was seen in this patient, as evidenced by reduced tumor burden and decreased voice handicap index. The patient was a 30-year old female, who had improved disease burden and voice quality after one dose and total resolution of disease following the second dose. Vaccine administration was the sole therapeutic mechanism. CONCLUSIONS: These findings suggest that HPV vaccination can treat RRP without surgical intervention. Further studies are needed to investigate the underlying mechanism of disease regression and which patients may benefit most. We believe that HPV vaccination for all patients with RRP, even over the age of 45 years, may decrease treatment costs for individuals and the healthcare system overall.

Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance.

PURPOSE: Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] concentrations augment insulin secretion and glucagon suppression and lower postprandial glycemia in PI-CF with AGT. METHODS: 26 adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT [defined by oral glucose tolerance test glucose (mg/dL): early glucose intolerance (1-h ≥ 155 and 2-h < 140), impaired glucose tolerance (2-h ≥ 140 and < 200 mg/dL), or diabetes (2-h ≥ 200)] were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched placebo; 24 completed the trial (n = 12 sitagliptin; n = 12 placebo). Main outcome measures were mixed-meal tolerance test (MMTT) responses for intact GLP-1 and GIP, insulin secretory rates (ISRs), glucagon suppression, and glycemia and glucose-potentiated arginine (GPA) test-derived measures of ß- and α-cell function. RESULTS: Following 6-months of sitagliptin vs placebo, MMTT intact GLP-1 and GIP responses increased (P < 0.001), ISR dynamics improved (P < 0.05), and glucagon suppression was modestly enhanced (P < 0.05) while GPA test responses for glucagon were lower. No improvements in glucose tolerance or ß-cell sensitivity to glucose, including for second-phase insulin response, were found. CONCLUSIONS: In glucose intolerant PI-CF, sitagliptin intervention augmented meal-related incretin responses with improved early insulin secretion and glucagon suppression without affecting postprandial glycemia.