Sensorineural correlates of failed functional recovery after natural regeneration of vestibular hair cells in adult mice.

Vestibular hair cells (HCs) are mechanoreceptors that sense head motions by modulating the firing rate of vestibular ganglion neurons (VGNs), whose central processes project to vestibular nucleus neurons (VNNs) and cerebellar neurons. We explored vestibular function after HC destruction in adult Pou4f3+/DTR (DTR) mice, in which injections of high-dose (50 ng/g) diphtheria toxin (DT) destroyed most vestibular HCs within 2 weeks. At that time, DTR mice had lost the horizontal vestibulo-ocular reflex (aVORH), and their VNNs failed to upregulate nuclear cFos expression in response to a vestibular stimulus (centrifugation). Five months later, 21 and 14% of HCs were regenerated in utricles and horizontal ampullae, respectively. The vast majority of HCs present were type II. This degree of HC regeneration did not restore the aVORH or centrifugation-evoked cFos expression in VNNs. The failure to regain vestibular pathway function was not due to degeneration of VGNs or VNNs because normal neuron numbers were maintained after HC destruction. Furthermore, sinusoidal galvanic stimulation at the mastoid process evoked cFos protein expression in VNNs, indicating that VGNs were able to regulate VNN activity after HC loss. aVORH and cFos responses in VNNs were robust after low-dose (25 ng/g) DT, which compared to high-dose DT resulted in a similar degree of type II HC death and regeneration but spared more type I HCs in both organs. These findings demonstrate that having more type I HCs is correlated with stronger responses to vestibular stimulation and suggest that regenerating type I HCs may improve vestibular function after HC loss.

Beyond Laryngeal Clefts: Interarytenoid Injection Augmentation to Predict Success of Suture Augmentation in Children.

OBJECTIVE: To assess the efficacy of interarytenoid injection augmentation (IAIA) and the ability of IAIA to predict response to interarytenoid suture augmentation (IASA) based on diet advancement on video fluoroscopic swallow studies (VFSS). METHODS: Retrospective cohort analysis of patients with persistent pharyngeal dysphagia at a tertiary children's hospital with VFSS pre- and post-IAIA were included between March 2011 and June 2019. RESULTS: Median age of the 229 patients was 2.2 years (5.8 months-19 years). Interarytenoid mucosal height (IAMH) was found to be above the false vocal folds in 112 patients (53.4%) and at true vocal folds in 10 (4.9%) patients. On VFSS post-IAIA, 95 (41.5%) patients were successfully advanced in recommended diet consistency, 115 (50.2%) were stable, and 19 (8.3%) needed thicker consistency. Paired t-tests on pre- and post-operative consistency scores showed significant improvement, p-value of <0.0001, 95% confidence interval (CI; 0.50-0.85). Poisson regression found no covariates with significant association with improvement on IAIA. For IASA patients, 35/60 (58.3%) improved on post-op VFSS. Paired t-tests on pre- and post-operative consistency scores showed significant improvement, p-value of <0.0001, 95% CI (0.63-1.33). Positive predictive value for IAIA predicting response to IASA was 77% with positive likelihood ratio of 2.3. The response to IAIA versus no response to IAIA likelihood ratios were found to have a statistically significant difference (p < 0.05). CONCLUSIONS: Our study suggests IAIA yields objective improvement in swallow function on VFSS in nearly half of our patients and may be a reliable diagnostic tool to predict response to IASA in patients with persistent pharyngeal dysphagia with or without a laryngeal cleft. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1749-1756, 2023.

Current management of type III and IV laryngotracheoesophageal clefts: the case for a revised cleft classification.

PURPOSE OF REVIEW: This review summarizes the paediatric laryngotracheoesophageal cleft (LTEC) literature, with an emphasis on recent trends, evaluation and management, surgical techniques, postoperative care of Type III and IV LTECs, and to propose a revised cleft classification system that more accurately reflects our current understanding of these anomalies. RECENT FINDINGS: There are a number of techniques described to address Type III and IV LTEC, from endoscopic to open approaches with thoracotomy. The surgical approach should be tailored to the length of the cleft and its proximity to important anatomical structures. On the basis of review of the literature, we propose a modified Benjamin-Inglis classification (MBI) with subcategories to address this issue. Postoperative complications are common, namely, tracheoesophageal fistulae and tracheomalacia, which may necessitate subsequent procedures or prolonged tracheostomy dependence. SUMMARY: The medical and surgical management of Type III and IV LTEC is challenging with a high rate of morbidity and mortality. The rarity and difficulties in management of these malformations have made large cohort studies difficult, thus generalizable recommendations have been elusive. Experience and patient selection are critical for successful endoscopic repair. Anterior cervical approach, often with complete laryngofissure, appears to be the most common and preferred method for open repairs, though some use a lateral approach. The proposed MBI classification appears to be a useful adjunct to aid in surgical decision-making for deeper LTEC.

Comparison of W-Plasty vs Traditional Straight-Line Techniques for Primary Paramedian Forehead Flap Donor Site Closure.

IMPORTANCE: The paramedian forehead flap (PMFF) donor site scar is hard to disguise and may be a source of patient dissatisfaction. OBJECTIVE: To evaluate the aesthetic outcome of W-plasty vs traditional straight-line (SL) closure techniques of the PMFF donor site. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at the University of California, San Francisco Medical Center. Clinical history and operative reports were reviewed for 31 patients who underwent a PMFF procedure performed between November 1, 2011, and May 29, 2014. Blinded photographic analysis of postoperative photographs was performed. INTERVENTIONS: The pedicled component of the PMFF was raised primarily with either a W-plasty or traditional SL design. MAIN OUTCOMES AND MEASURES: Standard photographs of the donor site, obtained at least 90 days after surgery, were reviewed and scored in a blinded fashion by 4 dermatologic surgeons using a 100-point visual analog scale (from 0 [worst possible outcome] to 100 [best possible outcome]) and a 5-point Likert scale (from very poor to excellent). Interrater reliability was assessed via Cronbach α testing. RESULTS: All 31 forehead flaps survived during this study period; 16 PMFFs were raised with the W-plasty technique and 15 were raised with the SL technique. The W-plasty and SL groups were similar in terms of age, sex, and race/ethnicity (mean [SD] age, 68.4 [12.4] vs 61.8 [11.6] years; 13 [84%] vs 9 [60%] men; and 15 [94%] vs 13 [87%] white). Patients undergoing W-plasty closure had significantly higher mean visual analog scale scores compared with those undergoing SL closure (72.8 [18.3] vs 65.6 [18.1]; P = .03). Mean Likert scale scores for W-plasty were higher than those for SL closure, but the difference was not significant (3.77 [1.02] vs 3.43 [0.98]; P = .08). Overall interrater reliability for the visual analog scale and Likert scale scores were 0.67 and 0.58, respectively. CONCLUSIONS AND RELEVANCE: Patients undergoing PMFF donor site closure using a primary W-plasty technique demonstrated better mean scar appearance of the forehead donor site compared with SL closure. The primary W-plasty technique did not result in any PMFF losses and should be considered for appropriate patients. LEVEL OF EVIDENCE: 3.

Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by osteocytes, to protect hearing. Understanding the cellular and molecular mechanisms that confer site-specific control of bone remodeling has the potential to elucidate new pathways that are deregulated in skeletal disease.