Surgical management of bilateral hip fractures in a patient with fibrodysplasia ossificans progressiva treated with the RAR-γ agonist palovarotene: a case report.

BACKGROUND: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder marked by painful, recurrent flare-ups and heterotopic ossification (HO) in soft and connective tissues, which can be idiopathic or provoked by trauma, illness, inflammation, or surgery. There are currently no effective treatments for FOP, or for patients with FOP who must undergo surgery. Palovarotene, an investigational retinoic acid receptor-γ agonist, offers a potential avenue to prevent HO formation. CASE PRESENTATION: The patient is a 32 year-old male, who at age 29 enrolled in a study evaluating palovarotene to prevent HO formation in FOP. One year after starting palovarotene, he fell resulting in a left intertrochanteric fracture. He underwent intramedullary nailing of the femur shaft with screw placement at the distal femur. After surgery, he received palovarotene at 20 mg/day for 4 weeks, then 10 mg/day for 8 weeks. Imaging 12 weeks after surgery showed new bridging HO at the site of intramedullary rod insertion and distal screw. Nine months after the left hip fracture, the patient had a second fall resulting in a subdural hematoma, left parietal bone fracture, and right intertrochanteric fracture. He underwent intramedullary nailing of the right hip, in a modified procedure which did not require distal screw placement. Palovarotene 20 mg/day was started at fracture occurrence and continued for 4 weeks, then reduced to 10 mg/day for 8 weeks. HO also formed near the insertion site of the intramedullary rod. No HO developed at the right distal intramedullary rod. After each fracture, the patient had prolonged recurrent flare-ups around the hips. CONCLUSION: Surgery is only rarely considered in FOP due to the high risks of procedural complications and potential for inducing HO. This case emphasizes the risks of increased flare activity and HO formation from injury and surgery in patients with FOP. The efficacy of HO prevention by palovarotene could not be assessed; however, our observation that palovarotene can be administered in an individual with FOP following surgery with no negative impact on clinical fracture healing, osteointegration, or skin healing will help facilitate future trials testing the role of palovarotene as a therapy for HO.

Patient Reported Outcome Measures for Salivary Function: A Systematic Review.

OBJECTIVE: A number of patient-reported outcome measures (PROMs) assess quality of life and symptom severity in patients with salivary gland dysfunction, but many vary in the extent of validation and domain types addressed. We identified PROMs validated to measure salivary gland function and analyzed key properties. DATA SOURCES: PubMed, Web of Science, Embase, PsycInfo, and CINAHL. REVIEW METHODS: A systematic review was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Validated instruments with >1 item to assess salivary gland-related symptoms were included. PROMs were evaluated for developmental methodology, structure, validity, and reliability using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) criteria. RESULTS: A total of 2059 abstracts were retrieved, and 133 full-text articles were reviewed. Sixteen PROMs assessing xerostomia (n = 7), sialadenitis (n = 4), Sjogren's syndrome (n = 2), Parkinson's-associated sialorrhea (n = 2), and oral systemic sclerosis (n = 1) were identified. Most (n = 15) were developed de novo, one was adapted from a pre-existing questionnaire. Eleven PROMs demonstrated "very good" analysis of internal consistency per COSMIN criteria, and 10 included test-retest data. Regarding content validity, four PROMs were developed with both patient and physician input, but none were rated as "adequate." All included comparisons against other questionnaires (n = 7), salivary flow rate (n = 9), and/or healthy controls (n = 3). The most rigorously developed PROM, the Xerostomia Inventory, was rated adequate in 6 out of 7 domains. CONCLUSIONS: Several PROMs evaluate salivary function. The abilties of these PROMs to meet design and validation standards were variable, with notable limitations in content validity for all tools. New and updated PROMs assessing obstructive and inflammatory salivary symptoms should  utilize patient and provider input. LEVEL OF EVIDENCE: N/A Laryngoscope, 133:1796-1805, 2023.

An Ex Vivo Investigation of Tactile Aesthesiometer Force in Laryngopharyngeal Sensory Testing.

BACKGROUND/OBJECTIVE: Cheung-Bearelly aesthesiometers can deliver buckling-force stimuli to the laryngopharynx and objectively evaluate sensation. Ambiguity surrounds the transformation of stimuli in the laryngopharyngeal environment. This study aims to evaluate the effect of aesthesiometer size, saliva, successive compressions, and angles of tissue contact on stimulus force delivered. METHODS: An ex vivo stimulus delivery device was constructed to measure the buckling force of aesthesiometers. Dry and saliva-saturated aesthesiometers (6-0, 5-0, 4.5-0, and 4-0) were each compressed six times on cadaveric buccal mucosa on an electronic balance. The force for each compression was recorded at 0, 15, 30, 45, and 60° from the vertical plane. 240 compressions were analyzed utilizing a mixed-effects statistical model. RESULTS: The mean force delivered by the 6-0, 5-0, 4.5-0, and 4-0 aesthesiometers were 0.017, 0.082, 0.120, and 0.268 g respectively (p < 0.001). Mean force significantly reduced for the 4-0 aesthesiometer at 30° (p = 0.003) and 60° (p = 0.001). Force decreased by the 4th compression for the 5-0 aesthesiometer (p = 0.004) and after one compression for the 4.5-0 (p = 0.004) and 4-0 (p < 0.001) aesthesiometer. By the 4th compression, the 4.5-0 aesthesiometer was indistinguishable (p > 0.05) from the 5-0 aesthesiometer. The effect of saliva was insignificant (p = 0.83). CONCLUSION: Aesthesiometers can deliver discrete buckling-force stimuli to evaluate laryngopharynx sensory function. Up to 60° (15° for 4-0 aesthesiometer) deviation from orthogonal tissue contact and salivary forces do not significantly alter force delivered. 4.5-0 aesthesiometers should be exchanged after three compressions. For all other aesthesiometers, force reduction after six compressions is likely clinically insignificant given current laryngopharyngeal sensory testing protocols. LEVEL OF EVIDENCE: N/A Ex Vivo Laboratory Design Laryngoscope, 133:1933-1937, 2023.

Abnormal Laryngopharyngeal Sensation in Adductor Laryngeal Dystonia Compared to Healthy Controls.

BACKGROUND/OBJECTIVES: Laryngeal sensory abnormality has been implicated as a component of adductor laryngeal dystonia (AdLD). The study objective was to assess laryngopharyngeal sensation in AdLD utilizing a calibrated, tactile aesthesiometer to deliver differential stimuli to lateral pyriform sinus (LPS), aryepiglottic fold (AEF), and false vocal fold (FVF). METHODS: Patients with known Botox-responsive AdLD underwent sensory testing using a previously-validated methodology involving calibrated tactile stimuli (6-0, 5-0, 4.5-0, 4-0 nylon monofilaments). Laryngeal adductor reflex (LAR) and participant-rated perceptual strength of stimulI were evaluated. Responses were compared to normative controls (n = 33). Two-samples, Mann-Whitney and Fisher exact tests compared mean strength ratings and LAR between AdLD and control groups. Mixed-effects logistic regression and linear models assessed association of filament size, stimulus site, age, sex, and LD status on LAR and perceptual strength rating respectively. RESULTS: Thirteen AdLD patients (nine women, mean age 60+/-15 years) completed testing. Average LAR response rates were higher amongst all filament sizes in AdLD versus controls at LPS (56.3% vs. 35.7%) and AEF (96.1% vs. 70.2%) with comparable rates at FVF (90.2% vs. 91.7%). AdLD had 3.3 times the odds of observed LAR compared to controls (p = 0.005), but differences in subjective detection of stimuli, perceptual strength ratings, and cough/gag rates were insignificant on multivariate modeling (p > 0.05). CONCLUSIONS: This is the first study to objectively assess laryngopharyngeal sensation in AdLD. Findings demonstrated increased laryngopharyngeal sensation in AdLD compared to controls. The identification of increased laryngeal hypersensitivity in these patients may improve understanding of AdLD pathophysiology and identify future targets for intervention. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:2271-2278, 2023.

Assessment of Laryngeal Sensory Function using a Tactile Aesthesiometer in Healthy Adults.

INTRODUCTION: Laryngeal sensory function in healthy adults was assessed through the delivery of tactile stimuli using Cheung-Bearelly monofilaments. METHODS: 37 healthy adults were recruited with 340 tactile stimuli analyzed. Four calibrated tactile stimuli were delivered to three laryngeal sites: false vocal fold (FVF), aryepiglottic fold (AEF), and lateral pyriform sinus (LPS). Primary outcome was the elicitation of laryngeal adductor reflex (LAR). Secondary outcomes were gag, patient-reported laryngeal sensation (PRLS), and perceptual strength. Analysis was performed with mixed effects logistic regression modeling. RESULTS: Positive LAR was observed in 35.7%, 70.2%, and 91.2% of stimuli at LPS, AEF, and FVF respectively. LAR rates were significantly associated with laryngopharyngeal subsite (p < 0.001), tactile force (p = 0.001), age (p = 0.022) and sex (p = 0.022). LAR, gag, PRLS, and perceptual strength significantly increased as a more medial laryngeal subsite was stimulated and as stimulus force increased. Each of the ten years of age increase was associated with 19% reduction in odds of LAR (aOR = 0.81, 95% CI [0.68, 0.97]; p = 0.022). Male gender was associated with a 55% reduction in odds of LAR (aOR = 0.45, 95% CI [0.23, 0.89]; p = 0.022). CONCLUSION: LAR elicitation capability decreases in the male gender, aging, and a more lateral subsite. This study provides insight into the pathophysiology of hypo- and hyper-sensitive laryngeal disorders and is paramount to making accurate diagnostic assessments and finding novel treatment options for various laryngological disorders. Laryngoscope, 133:2525-2532, 2023.

Longitudinal Analysis of Swallowing Displacement Kinematics After Oropharyngeal Cancer Treatment.

BACKGROUND/OBJECTIVE: Quantitative swallowing displacement kinematics evolve in patients treated for oropharyngeal squamous cell carcinoma (OPSCC). We aimed to longitudinally assess these measurements and correlate them with functional swallowing outcomes. METHOD: A retrospective review was conducted on patients with OPSCC treated with definitive (chemo)radiation ([C]RT) or surgery with adjuvant (chemo)radiation (S-[C]RT) who completed at least two videofluoroscopic swallow studies (VFSS). Longitudinal analysis was accomplished via mixed-effects logistic regression for the Functional Oral Intake Scale (FOIS), and Penetration Aspiration Scale (PAS), and mixed-effects linear regression for kinematic measures. Spearman's correlation was conducted between changes in FOIS/PAS and kinematic measures. RESULTS: Ninety-seven patients (76 males; mean age 61) completed 245 VFSS studies. A total of 94% had human papillomavirus (HPV)/p16 positive OPSCC and 74% were T0-T2. Sixty-four patients underwent [C]RT while 33 patients underwent S-[C]RT. After treatment, posterior pharyngeal wall at hold (PPWhold) increased 3.2 standard deviation (SD) between 0 and 6 months (p < 0.001), then decreased 2.2 SD between 6 and 12 months (p < 0.001) and did not return to baseline. Hyoid-to-larynx (HL) (p = 0.046) and maximal hyoid displacement (Hmax) + HL (p = 0.042) increased between 6 and 12 months. Hmax (p = 0.020) and Hmax + HL (p < 0.001) decreased between 12-24 months beyond baseline values. The decrease in HL and increase in PPWhold (p < 0.05) correlated with an increase in PAS. From baseline, increased pharyngeal constriction ratio correlated with decreased FOIS and PPWhold (p < 0.05). CONCLUSIONS: Quantitative swallowing kinematic measures can effectively track changes in swallowing physiology. Increased PPWhold and restricted hyolaryngeal movement were seen in patients with OPSCC after treatment and correlated with a change in swallowing outcome, emphasizing the need for serial VFSS monitoring and targeted intervention. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1339-1348, 2023.

Identification of Risk Factors in the Development of Heterotopic Ossification After Primary Total Hip Arthroplasty.

PURPOSE: Heterotopic ossification (HO) is a process by which bone forms abnormally in soft tissues. Known risk factors for developing HO include male sex, spinal cord injury, trauma, and surgery. We investigated additional risk factors in the development of HO after hip arthroplasty. METHODS: We performed a retrospective review of electronic medical records of 4070 individuals who underwent hip arthroplasty from September 2010 to October 2019 at the University of California, San Francisco Hospital. Demographics, anthropometrics, medications, and comorbid conditions were used in logistic regression analysis to identify factors associated with the development of HO. RESULTS: A total of 2541 patients underwent primary hip arthroplasty in the analyzed timeframe (46.04% men, mean age at procedure: 62.13 ±â€…13.29 years). The incidence of postsurgical HO was 3% (n = 80). A larger proportion of individuals who developed HO had underlying osteoporosis (P < 0.001), vitamin D deficiency (P < 0.001), spine disease (P < 0.001), type 1 or 2 diabetes (P < 0.001), amenorrhea (P = 0.037), postmenopausal status (P < 0.001), parathyroid disorders (P = 0.011), and history of pathologic fracture (P = 0.005). Significant predictors for HO development were Black/African American race [odds ratio (OR) 2.97, P = 0.005], preexisting osteoporosis (OR 2.72, P = 0.001), spine disease (OR 2.04, P = 0.036), and low estrogen states (OR 1.99, P = 0.025). In the overall group, 75.64% received perioperative nonsteroidal anti-inflammatory drugs (NSAIDs), which negatively correlated with HO formation (OR 0.39, P = 0.001). CONCLUSIONS: We identified new factors potentially associated with an increased risk of developing HO after primary hip arthroplasty, including African American race, osteoporosis, and low estrogen states. These patients may benefit from HO prophylaxis, such as perioperative NSAIDs.

Utility of telephone visits at an urban safety-net hospital during 2020: A retrospective review.

Objective: During COVID-19, otolaryngology clinics rapidly implemented telehealth programs in accordance with social distancing guidelines and institutional policies. Our objectives are to evaluate the usefulness of telephone audio visits for underserved patients seeking otolaryngological care at an urban safety-net hospital and identify patient factors associated with telephone visit attendance. Methods: In a retrospective review of all adult telephone visits in 2020, we compared the demographics and visit characteristics of patients who attended telehealth versus in-person visits and patients who attended versus missed telehealth visits. Univariable and multivariable regressions were utilized to identify predictors of missing telehealth visits. Results: We identified 318 telehealth encounters completed by 254 patients (72.8% were of racial/ethnic minority; 76.3% had low-income, need-based insurances; 43.7% had limited English proficiency). The most common chief complaints were related to head and neck oncology (n = 85, 26.7%), otology/neurotology (n = 74, 23.3%), and general otolaryngology (n = 69, 21.7%). The following actions were executed during telephone visits: behavioral and/or medication patient education (n = 152, 47.8%); sharing testing/imaging/tumor board results (n = 125, 39.3%); referrals to another department (n = 103, 32.4%); rendering a new diagnosis (n = 98, 30.8%); changing medications (n = 60, 18.9%). Less than half of telephone visits (46.2%) resulted in in-person follow-up, most commonly for in-person exams. The distribution of race/ethnicity differed between attended in-person appointments versus telephone visits (p = .01), but race and ethnicity were not significant predictors of telephone visit attendance. Conclusion: Despite limited diagnostic capabilities, telephone audio visits can be an effective and accessible tool for providing continuity and advancing care in socially disadvantaged patients. Level of evidence: IV.

Prospective, Multi-Center Study of the Anatomic Distribution of Recurrent Respiratory Papillomatosis.

OBJECTIVES/HYPOTHESIS: To create a model of the anatomic distribution, recurrence, and growth patterns of recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Prospective, multi-institutional cohort study. METHODS: Adult patients with a diagnosis of RRP evaluated between August 1, 2018 and February 1, 2021 at six participating centers were invited to enroll. At each office or operating room encounter, laryngologists recorded the location and size of RRP lesions using a 22-region schematic. A generalized linear mixed effects model was used to compare region variations in lesion prevalence and recurrence. RESULTS: The cohort comprised 121 patients: 74% were male, 81% had been diagnosed with adult-onset RRP, and a plurality (34%) had undergone 0 to 3 RRP interventions prior to enrollment. Across the study period, the odds of a lesion occurring in the glottis was significantly higher (odds ratio [OR]: 26.51; 95% confidence interval [CI]: 11.76-59.75, P < .001) compared with all other areas of the larynx and trachea. Within the true vocal folds, the membranous vocal folds had significantly higher odds (OR: 6.16; 95% CI: 2.66-14.30, P < .001) of lesion occurrence compared to the cartilaginous vocal folds. Despite these strong trends in lesion distribution, there were no differences in the odds of lesion recurrence, growth, or in the time to recurrence, between anatomic subsites. CONCLUSIONS: RRP lesions are most likely to occur in the glottis, particularly the membranous vocal folds, compared with other regions of the larynx or trachea. However, all lesions demonstrate similar behavior with respect to recurrence, growth, and time to recurrence regardless of anatomic location. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2403-2411, 2022.

Are preoperative chlorhexidine gluconate showers associated with a reduction in surgical site infection following craniotomy? A retrospective cohort analysis of 3126 surgical procedures.

OBJECTIVE: Surgical site infection (SSI) is a complication linked to increased costs and length of hospital stay. Prevention of SSI is important to reduce its burden on individual patients and the healthcare system. The authors aimed to assess the efficacy of preoperative chlorhexidine gluconate (CHG) showers on SSI rates following cranial surgery. METHODS: In November 2013, a preoperative CHG shower protocol was implemented at the authors' institution. A total of 3126 surgical procedures were analyzed, encompassing a time frame from April 2012 to April 2016. Cohorts before and after implementation of the CHG shower protocol were evaluated for differences in SSI rates. RESULTS: The overall SSI rate was 0.6%. No significant differences (p = 0.11) were observed between the rate of SSI of the 892 patients in the preimplementation cohort (0.2%) and that of the 2234 patients in the postimplementation cohort (0.8%). Following multivariable analysis, implementation of preoperative CHG showers was not associated with decreased SSI (adjusted OR 2.96, 95% CI 0.67-13.1; p = 0.15). CONCLUSIONS: This is the largest study, according to sample size, to examine the association between CHG showers and SSI following craniotomy. CHG showers did not significantly alter the risk of SSI after a cranial procedure.