Impact of Head and Neck Cancer Diagnosis and Treatment on Patient-Partner Intimacy.

OBJECTIVE: To determine the effects of head and neck squamous cell carcinoma diagnosis and treatment on patient- and partner-perceived intimacy and to understand if a diagnosis of HPV-related head and neck squamous cell carcinoma influences patient-partner intimacy. STUDY DESIGN: Prospective observational. SETTING: Single tertiary care center. METHODS: An investigator-developed questionnaire was used to prospectively survey patients and partners in 2 groups based on human papillomavirus (HPV) status: HPV+ and HPV- at diagnosis (visit 1) and after treatment (visit 2). Surveys were scored on a 60-point scale, and results were categorized as follows: loss of intimacy (0-30), stable relationship (31-41), or improvement in intimacy (42-60). Responses of couples who participated together were assessed for concordance. Responses were considered discordant if patient and partner scores equated to different levels of perceived intimacy. Median patient and partner scores were compared via Mann-Whitney U test, and concordance was assessed with a chi-square test. RESULTS: Thirty-four patients and 28 partners completed surveys at visit 1 and 28 patients and 15 partners at visit 2. Median scores among patients and partners were similar at the first time point (HPV+, 45 vs 45, P = .64; HPV-, 42.6 vs 40.8, P = .29) and the second (HPV+, 44.5 vs 44, P = .87; HPV-, 40.2 vs 39.6, P = .90). Concordance rates between HPV+ and HPV- couples were 63% vs 44% (P = .43) for the first time point and 89% vs 50% (P = .24) for the second. CONCLUSION: Patients and partners reported stable or improved intimacy at both time points, and most couples tended to agree on their levels of perceived intimacy. A diagnosis of HPV did not appear to significantly affect intimacy scores.

Total Intravenous Anesthesia Versus Inhaled Sevoflurane in Obstructive Sleep Apnea Surgery: A Randomized Controlled Trial.

OBJECTIVE: Specific guidelines regarding an optimal general anesthesia (GA) approach to obstructive sleep apnea (OSA) patients remain undefined. Literature comparing the efficacy of total intravenous anesthesia (TIVA) and inhalational anesthesia in this population is sparse. We hypothesize that OSA patients receiving TIVA will experience reduced recovery times and other improved post-surgical outcomes. STUDY DESIGN: Randomized controlled trial. METHODS: Adult OSA patients undergoing upper airway surgery (hypoglossal nerve stimulation [HNS], nasal, or palate surgery) from February 2020-December 2020 were included. A post-anesthesia care unit (PACU) nursing survey documented patients' alertness, pain, oxygen supplementation, and postoperative nausea and vomiting from PACU arrival to 2 hours. Perioperative timepoints from the electronic medical record (EMR) and a nurse-estimated Phase I recovery time were collected. RESULTS: One hundred eleven patients were included (46 TIVA and 65 inhalational anesthesia). Per EMR-recorded timepoints, TIVA patients undergoing HNS and palate surgery experienced Phase I Time reductions of 12.5 min (p = 0.042) and 27.5 min (p = 0.016), respectively. Per the PACU survey, TIVA patients undergoing any surgery, HNS, or palate surgery experienced nurse-estimated Phase I Time reductions of 16.5 min (p = 0.004), 12.5 min (p = 0.031), and 38.5 min (p = 0.024), respectively. Overall, TIVA patients experienced higher alertness and pain ratings, and lower oxygen supplementation requirements from PACU arrival to 30 min (p < 0.05). CONCLUSION: Patients with OSA receiving TIVA for GA maintenance during upper airway procedures experienced reduced recovery times and oxygen supplementation requirements, and a more rapid return to alertness. Future work toward developing optimized anesthetic guidelines for OSA patients is merited. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:984-992, 2023.

Effects of Prior Tracheostomy on Total Laryngectomy Outcomes.

OBJECTIVE: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital between 2007 and 2020. METHODS: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. RESULTS: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). CONCLUSION: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.

CD8+ and FoxP3+ T-Cell Cellular Density and Spatial Distribution After Programmed Death-Ligand 1 Check Point Inhibition.

OBJECTIVES: To analyze CD8+ and FoxP3+ T-cell cellular density (CD) and intercellular distances (ID) in head and neck squamous cell carcinoma (HNSCC) samples from a neoadjuvant trial of durvalumab +/- metformin. METHODS: Paired pre- and post-treatment primary HNSCC tumor samples were stained for CD8+ and FoxP3+. Digital image analysis was used to determine estimated mean CD8+ and FoxP3+ CDs and CD8+-FoxP3+ IDs in the leading tumor edge (LTE) and tumor adjacent stroma (TAS) stratified by treatment arm, human papillomavirus (HPV) status, and pathologic treatment response. A subset of samples was characterized for T-cell related signatures using digital spatial genomic profiling. RESULTS: Post-treatment analysis revealed a significant decrease in FoxP3+ CD and an increase in CD8+ CDs in the TAS between patients receiving durvalumab and metformin versus durvlaumab alone. Both treatment arms demonstrated significant post-treatment increases in ID. Although HPV+ and HPV- had similar immune cell CDs in the tumor microenvironment, HPV+ pre-treatment samples had 1.60 times greater ID compared with HPV- samples, trending toward significance (p = 0.05). At baseline, pathologic responders demonstrated a 1.16-fold greater CD8+ CDs in the LTE (p = 0.045) and 2.28-fold greater ID (p = 0.001) than non-responders. Digital spatial profiling revealed upregulation of FoxP3+ and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in the TAS (p = 0.006, p = 0.026) in samples from pathologic responders. CONCLUSIONS: Analysis of CD8+ and FoxP3+ detected population differences according to HPV status, pathologic response, and treatment. Greater CD8+-FoxP3+ ID was associated with pathologic response. CD8+ and FoxP3+ T-cell distributions may be predictive of response to immune checkpoint inhibition. CLINICALTRIALS: gov (Identifier NCT03618654). LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1875-1884, 2023.

Migraine-Associated Otalgia: An Underappreciated Entity.

BACKGROUND AND OBJECTIVES: Otalgia can be primary/otogenic or secondary as a referred pain from another site, which can be difficult to establish owing to various causes and the complex innervation of the ear. In our center, we observed a large group of patients with unexplained otalgia that had a higher prevalence of migraine. We hypothesized that migraine may cause secondary otalgia. This study then aimed to determine the prevalence of migraine-associated otalgia and evaluate the efficacy of migraine treatment. SUBJECTS AND METHODS: This 2-year retrospective study was conducted at a busy otology clinic. Patients were identified using diagnostic codes corresponding to otalgia. The prevalence of migraine-associated otalgia was determined, and the efficacy of migraine treatment was evaluated in these patients. The interventions included prophylactic and abortive migraine treatments. Statistical analysis was conducted to compare between the pre- and post-treatment symptoms. RESULTS: A total of 208 patients with otalgia were identified. Sixty-four out of ninety patients with unexplained otalgia met the criteria for migraine; of them, 30 patients had an adequate follow-up and were thus included in the evaluation of treatment efficacy. Otalgia improved in 87% of the patients who received migraine treatment. After treatment, the mean pain score and headache frequency significantly decreased from 7 to 2 and from 27 to 9 days per month, respectively (p<0.001). CONCLUSIONS: Migraine should be considered as a source of secondary otalgia, and patients should receive treatment as they often respond to migraine treatment.

A randomized control trial employing infraorbital nerve stimulation as a neural distractor during nasopharyngeal swab.

INTRODUCTION: With the global COVID-19 pandemic, nasopharyngeal swabbing has become commonplace and can occasionally cause discomfort, tearing, and anxiety. OBJECTIVE: To evaluate whether using a neural distraction device during nasopharyngeal swabbing can mitigate patient discomfort. METHODS: Participants were randomized into nasal swab with vibration first (treatment-control or Tc) or nasal swab without vibration first (control-treatment or Ct). Then the swab was repeated with the opposite technique. The vibration device was used to stimulate the infraorbital nerve at the midpupillary line, while a nasopharyngeal swab was performed according to CDC protocol. After each swab, participants filled out a survey to assess pain, discomfort, and tearing. This procedure was replicated on the contralateral nostril for a total of 4 swabs and 4 surveys. RESULTS: Thirty-four subjects were included in the analysis. In the Ct group, there was a median 1.0-point decrease in pain with the use of vibration (95% CI [-1.8, -0.3], P = 0.0117), 2.5-point decrease (95% CI [-3.0, -0.8], P = 00039) in discomfort, and a 1.0-point decrease (95% CI [-2.6, -0.2] P = 0.0303) in tearing when the vibratory device was used. In the Tc group, there was a median 2.0-point decrease in pain with vibration (95% CI [ -2.7, -1.1], P < 0.0001), 2.3-point decrease in discomfort (95% CI [-3.1, -1.5], P < 0.0001), and a 1.5-point decrease in tearing (95% CI [-2.5, -0.5], P = 0.0037) when vibration was used. CONCLUSION: Vibratory stimulation of the infraorbital nerve is safe and effectively reduced pain, discomfort, and tearing during nasopharyngeal swab. Vibration is a reasonable option to minimize patient discomfort during COVID-19 or other microbiological testing.

Cost of Total Intravenous Anesthesia Versus Inhalation Anesthesia in Obstructive Sleep Apnea Surgery.

OBJECTIVES: To compare cost and time spent in surgical and postoperative courses in patients with obstructive sleep apnea (OSA) undergoing surgery with either total intravenous anesthesia (TIVA) or inhalational anesthesia. STUDY DESIGN: Retrospective chart review. METHODS: Retrospective review on patients undergoing surgery for OSA under general anesthesia from January 2019 to October 2020. Cost per service was acquired for the day of surgery. RESULTS: A total of 230 patients were included: 95 received TIVA; 135 received inhalation anesthesia. Total cost was significantly higher in the TIVA nasal surgery group by $286 (P = .035). TIVA produced significantly higher pharmacy and operating room costs across all surgeries and OSA severities. These increased costs were offset by significantly lower supply costs in upper airway stimulator (UAS, -$419.50; P = .007) and uvulopalatopharyngoplasty (UPPP, -$115.16; P = .015) patients receiving TIVA. In the TIVA cohort, there was a trend toward lower recovery room costs after UAS (-$111.09; P = .063) and nasal surgery (-$64.45; P = .096) and anesthesia costs after nasal surgery (-$36.67; P = .054). Total recovery time was reduced by 18 minutes (P = .004) for nasal surgery, 25 minutes (P = .043) for UAS, and 27 minutes (P = .147) for UPPP patients receiving TIVA. CONCLUSION: When used in an outpatient setting for patients with OSA, TIVA adds to pharmacy and operating room costs, but this is usually offset by lower supply, anesthesia, and recovery room costs. We found decreased recovery times in the TIVA cohort. TIVA has proven benefits in patient outcomes and can be cost-effective in OSA surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:1487-1494, 2022.

Novel alendronate-CGS21680 conjugate reduces bone resorption and induces new bone formation in post-menopausal osteoporosis and inflammatory osteolysis mouse models.

Loss of bone is a common medical problem and, while it can be treated with available therapies, some of these therapies have critical side effects. We have previously demonstrated that CGS21680, a selective A2A adenosine receptor agonist, prevents bone loss, but its on-target toxicities (hypotension, tachycardia) and frequent dosing requirements make it unusable in the clinic. We therefore generated a novel alendronate-CGS21680 conjugate (MRS7216), to target the agonist to bone where it remains for long periods thereby diminishing the frequency of administration and curtailing side effects. MRS7216 was synthesized from CGS21680 by sequential activation of the carboxylic acid moiety and reacting with an appropriate amino acid (PEG, alendronic acid) under basic conditions. MRS7216 was tested on C57BL/6J (WT) mice with established osteoporosis (OP) and WT or A2A KO mice with wear particle-induced inflammatory osteolysis (OL). Mice were treated weekly with MRS7216 (10mg/kg). Bone formation was studied after in vivo labeling with calcein/Alizarin Red, and µCT and histology analyses were performed. In addition, human primary osteoblasts and osteoclasts were cultured using bone marrow discarded after hip replacement. Receptor binding studies demonstrate that MRS7216 efficiently binds the A2A adenosine receptor. MRS7216-treated OP and OL mice had significant new bone formation and reduced bone loss compared to vehicle or alendronate-treated mice. Histological analysis showed that MRS7216 treatment significantly reduced osteoclast number and increased osteoblast number in murine models. Interestingly, cultured human osteoclast differentiation was inhibited, and osteoblast differentiation was stimulated by the compound indicating that MRS7216 conjugates represent a novel therapeutic approach to treat osteoporosis and osteolysis.

Analysis of cost and outcomes in bony versus soft tissue midface free flap reconstruction.

BACKGROUND: Outcomes and cost of soft tissue versus bony midface free flap reconstruction (MR) with and without virtual surgical planning (VSP) were evaluated. METHODS: Retrospective review of MR including ischemic time (IT), operative duration (OD), length of stay (LOS), and total cost (TC). Eighty-one soft tissue and 76 bony MR (VSP = 23) were reviewed. RESULTS: Bony MR was used for higher complexity defects (p = 0.003) and was associated with higher IT (p < 0.001), OD (p < 0.001), LOS (p = 0.032), and TC (p < 0.001). VSP was associated with a mean 111.2 ± 37.9 minute reduction in OD (p = 0.004) compared to non-VSP bony flaps. VSP was associated with higher itemized cost, but no increase in TC (p = 0.327). CONCLUSIONS: Bony MR was used for higher complexity MR and was associated with increased TC, LOS, OD, and IT. VSP shortened OD with no significant increase in TC.

Cost comparison between surgical and conservative management for pediatric sinogenic subperiosteal abscesses.

BACKGROUND: There remains variation in management of orbital complications of acute bacterial rhinosinusitis (ABRS); specifically, those subperiosteal abscesses that present without immediate surgical indication. Recent systematic reviews on management and proposed treatment algorithms are helpful but do not consider the financial implications for healthcare systems and patients. METHODS: A retrospective chart review of pediatric patients from a tertiary care children's hospital between 2002 and 2020 was performed, identifying patients via ICD coding corresponding to acute bacterial sinusitis and orbital involvement classified as Chandler 3 confirmed by contrasted computed tomography (CT). Two groups of patients were identified: intravenous (IV) antibiotics alone and IV antibiotics plus surgery. Billing records of total hospital charges and physician fees were recorded for financial analysis. Demographic, length of stay, and charges were analyzed. RESULTS: 58 patients with ABRS and Chandler 3 orbital involvement were confirmed by CT imaging. Twenty-nine (50%) were treated with IV antibiotics alone, and twenty-nine (50%) underwent surgery in addition to IV antibiotics. There were no significant differences in patient demographics. The average total hospital charges for the medically managed group were $9262 ± 4831 compared to $30,830 ± 11,397 for the surgical group (p < 0.0001). In the medically managed group, the average hospital fees were $7305 ± 4048 and the average physician fees were $1543 ± 799. In the surgical group, the average hospital and physician fees were also significantly higher at $23,071 ± 7305 (p < 0.0001) and $7763 ± 3335 (p < 0.0001), respectively. Patients who were treated medically and had a longer than average LOS still had significantly fewer charges than those treated with antibiotics plus surgery and a shorter than average length of stay [$15,311 and $27,723, respectively (p = 0.02)]. CONCLUSION: Pediatric ABRS with orbital involvement requires prompt attention and management. Controversy persists over subperiosteal abscess management that present without overt surgical indications. Surgical intervention is expensive. Our subgroup analysis demonstrates the magnitude of this cost difference. Specifically, longer inpatient stays with IV antibiotics alone appear to be significantly cheaper than shorter ones that include surgery. Not all Chandler 3 patients are candidates for non-surgical management; however, clinicians are encouraged to keep these data in mind for those patients where further medical management is safe and may yield less expensive clinical resolution.

Disease involvement in the central compartment in eosinophilic chronic rhinosinusitis.

OBJECTIVE: To evaluate disease presence in the central compartment (CC) in patients with eosinophilic chronic rhinosinusitis (CRS). METHODS: Patients with eosinophilic CRS were divided into three endotypes: aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and eosinophilic CRS with nasal polyps (eCRSwNP). CT scans were reviewed for CC involvement, defined as the area between the superior nasal septum (SNS) and middle turbinate (MT). CC involvement was measured based on the degree of opacification (0: no opacification, 1: up to 50% opacification, and 2: >50% opacification), and distance from SNS to MT (mm). Patients who had lateralized MTs from prior surgery as the cause of CC widening were excluded. Patients who underwent orbital decompression were included as a control group. RESULTS: Fifty patients in each group (AERD, AFRS, and eCRSwNP) and 50 control patients were included. Average number of surgeries was 2.5 in AERD (p = 0.05), 2 in AFRS (p = 0.4), and 1.7 in eCRSwNP. Preoperative CC distance was significantly higher in AERD versus control, AFRS, and eCRSwNP: 4.2 versus 2.8 mm (p < 0.0001), 4.2 versus 1.9 mm (p < 0.0001), and 4.2 versus 2.7 mm (p < 0.0001), respectively. Postoperatively, CC distance and degree of opacification were significantly higher in AERD versus control, AFRS, and eCRSwNP. Within the AERD group, CC distance was significantly higher postoperatively than preoperatively (6.5 vs. 4.2 mm, p = 0.002). CONCLUSION: CC involvement is more significant in AERD patients and if present, rhinologists should be suspicious of the diagnosis. This area could represent a source of inflammatory load in patients with AERD.