Cervical Fibrosis as a Predictor of Dysphagia.

OBJECTIVE: Radiotherapy of head and neck cancer (HNCA) causes dysfunction through radiation-induced fibrosis (RIF). We hypothesize that the degree of cervical fibrosis is associated with swallowing dysfunction. This study evaluated the association between cervical fibrosis and swallowing dysfunction in patients after radiation therapy for HNCA. STUDY DESIGN: Cross sectional study. METHODOLOGY: A convenience sample of patients with dysphagia who were at least 1 year post radiation therapy for HNCA underwent simultaneous cervical ultrasound (US) and video-fluroscopic swallow study (VFSS). US determinants of fibrosis were measurements of sternocleidomastoid fascia (SCMF) thickness bilaterally at the level of the cricoid. Primary and secondary outcome variables on VFSS were pharyngeal constriction ratio, a validated measure of pharyngeal contractility, and penetration aspiration scale (PAS). A qualitative assessment of lateral neck rotation was performed as a functional measure of neck fibrosis. RESULTS: Simultaneous cervical US and VFSS examinations were performed on 18 patients with a history of radiotherapy for HNCA and on eight controls. The mean (±SD) age of the entire cohort (N = 26) was 66 (±10) years. Individuals with a history of radiation had significantly thinner mean SCMF (0.26 [±0.04 mm]) compared to controls (0.48 [±0.06 mm]; P < .05). Individuals with thinner SCMF were more likely to have moderate to severe restriction in lateral neck rotation, a higher PCR, and a higher PAS (P < .05). CONCLUSION: Thinner sternocleidomastoid fascia on ultrasound in patients having undergone radiotherapy for head and neck cancer was associated with reduced lateral neck movement, poorer pharyngeal constriction and greater penetration/aspiration scale. The data suggest that cervical fibrosis is associated with swallowing dysfunction in head and neck cancer survivors and support the notion that, "As the neck goes, so does the swallow." LEVEL OF EVIDENCE: 3. Laryngoscope, 131:548-552, 2021.

Eustachian tube dysfunction in children with cleft palate: A tympanometric time-to-event analysis.

OBJECTIVES: To characterize the duration of Eustachian tube dysfunction in children with cleft palate compared to those without cleft palate by performing time-to-event analysis on tympanometric data. To determine predictive characteristics of earlier achievement of normal tympanograms in children with cleft palate. METHODS: Longitudinal tympanometric data from a minimum of 10 years at a single center were reviewed for children with cleft palate born in the years 2003 through 2007. Children with cleft lip without cleft palate born in the same years were used as a reference group to compare children with similar length of follow-up. The association between time to sustained normal (type A) tympanograms with patient demographics, clinical characteristics, and otologic history was evaluated using time-to-event analysis and compared with log rank tests. Adjusted and unadjusted hazard ratios were estimated using Cox proportional hazard models. RESULTS: The median age of achieving a type A tympanogram in children with cleft palate was 9.9 years for one and 12.1 years for both ears, compared to 7.1 and 7.4 years in children with cleft lip only (P < 0.0001). On multivariate analysis, clinical characteristics such as the severity of palatal clefting or the presence of a cleft-associated syndrome/sequence were not predictors of a longer time to a type A tympanogram. CONCLUSION: Our results help characterize the observation that there is delayed time to normal Eustachian tube function in children with cleft palate, which is not associated with the degree of palatal clefting. LEVEL OF EVIDENCE: 3b Laryngoscope, 130:1044-1050, 2020.

Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation.

HYPOTHESIS: Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). BACKGROUND: Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. METHODS: Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7-P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. RESULTS: Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. CONCLUSION: Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.

Operant psychostimulant self-administration in a rat model of depression.

Depression and psychostimulant addiction are co-morbid conditions; depression is a significant risk factor for psychostimulant abuse, and the rate of depression in drug addicts is higher than in the general population. Despite the prevalence of this comorbidity, there are few animal models examining psychostimulant abuse behaviors in depression. We have shown previously that while rats selectively bred for depression-like phenotypes (SwLo) have blunted mesolimbic dopamine (DA) signaling and locomotor responses to dopaminergic drugs, they voluntarily administer excessive amounts of psychostimulants compared to normal or depression-resistant (SwHi) rats in oral consumption paradigms. To determine whether this increased drug intake by depression-sensitive rats extends to operant self-administration, we assessed fixed ratio-1, progressive ratio, extinction, and reinstatement responding for cocaine and amphetamine in SwLo and SwHi rats. Contrary to the oral consumption results, we found that the SwHi rats generally responded more for both cocaine and amphetamine than the SwLo rats in several instances, most notably in the progressive ratio and reinstatement tests. Food-primed reinstatement of food seeking was also elevated in SwHi rats. These results provide further insight into the neurobiology of depression and addiction comorbidity and caution that oral and operant psychostimulant self-administration paradigms can yield different, and this case, opposite results.

Seizure susceptibility and epileptogenesis in a rat model of epilepsy and depression co-morbidity.

Although a strong co-morbidity exists clinically between epilepsy and depression, the cause of this co-morbidity remains unknown, and a valid animal model is crucial for the identification of underlying mechanisms and the development of a screening tool for novel therapies. Although some rodent models of epilepsy have been reported to display behaviors relevant to affective disorders, the seizure susceptibility of animals prone to depression-like behavior has not been characterized. Toward this end, we assessed several forms of seizure sensitivity and epileptogenesis in rats selectively bred for vulnerability (Swim Lo-Active; SwLo) or resilience (Swim High-Active; SwHi) to depression-like phenotypes. The SwLo rats exhibit decreased motor activity in a swim test and other depression-like phenotypes, whereas the SwHi rats display increased motor activity in a swim test. SwLo rats exhibited a decreased latency to limbic motor seizures following acute pilocarpine administration in the absence of differences in pilocarpine pharmacokinetics, and also had a decreased threshold to tonic seizures induced by electroshock. Approximately half of the SwLo rats, but none of the SwHi rats, had spontaneous limbic motor seizures 5 weeks following pilocarpine-induced status epilepticus. While the number of stimulations required to achieve full amygdala and hippocampal electrical kindling were similar in the two rat lines, SwLo rats had a lower final hippocampal kindling threshold and more wet dog shakes during both amygdala and hippocampal kindling. Combined, these results indicate that SwLo rats are a model of epilepsy and depression co-morbidity that can be used for investigating underlying neurobiological and genetic mechanisms and screening novel therapeutics.