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Dysphagia is a watershed symptom that localises poorly. Dividing causes of dysphagia into oropharyngeal and oesophageal does not always best serve the patient. We report the case of a patient whose diagnosis and treatment required three separate specialist referrals to two specialties, with 18 months passing between initial referral and definitive treatment. The predominant pathology was isolated upper oesophageal sphincter dysfunction that responded well to laser cricopharyngeal myotomy. Following surgery, patient symptoms resolved and lost weight was regained. High-resolution manometry showed that the upper sphincter resting pressure had fallen from 117±45 to 21±11mmHg, but the lower sphincter resting pressure had risen, albeit without symptoms, from 16±8 to 44±17mmHg (p<0.001 in both cases). Surgery on upper oesophageal sphincter in the presence of lower oesophageal sphincter incompetence is known to lead to intractable regurgitation and pneumonia, and this novel physiological observation further emphasises the need to holistically consider the patient and to systematically evaluate the entire swallowing system before undertaking invasive interventions. [ABSTRACT FROM AUTHOR]

Background: Assessing the internal condition of swallowing‐related muscles and muscle strength and size is important because their deterioration may lead to dysphagia. However, there are few reports on stiffness of swallowing‐related muscles measured using shear‐wave elastography (SWE) and their qualitative characteristics. Objectives: We measured stiffness of swallowing‐related muscles using SWE to investigate the relationship between muscle stiffness and body composition as well as other relevant variables in healthy adults. Methods: Thirty healthy adults were included in this cross‐sectional study. We evaluated stiffness of the genioglossus muscle (GGM) and geniohyoid muscle (GHM) using SWE. Skeletal muscle mass index, body mass index (BMI), handgrip strength, tongue pressure, and cross‐sectional areas of the muscles were measured, and we determined their relationship with muscle stiffness. Results: For muscle stiffness, the mean value for the middle GGM was 7.08 ± 1.92 kPa, that for the posterior GGM was 9.31 ± 2.68 kPa, and that for the GHM was 8.84 ± 2.15 kPa. In multiple regression analysis, with stiffness of the posterior GGM as the dependent variable, BMI (β = −.473, p =.039) was a significant negative explanatory variable. However, with the GHM stiffness as the dependent variable, BMI (β =.419, p =.033) was a significant positive explanatory variable. Conclusion: Stiffness of the posterior GGM was positively correlated with BMI and that of the GHM was negatively correlated with BMI. Stiffness, as measured using SWE, has the potential to capture the intramuscular characteristics of swallowing‐related muscles, particularly the posterior GGM. [ABSTRACT FROM AUTHOR]

Improved genetically encoded calcium indicators (GECIs) are essential for capturing intracellular dynamics of both muscle and neurons. A novel set of GECIs with ultrafast kinetics and high sensitivity was recently reported by Zhang et al. (2023). While these indicators, called jGCaMP8, were demonstrated to work in Drosophila and mice, data for Caenorhabditis elegans were not reported. Here, we present an optimized construct for C. elegans and use this to generate several strains expressing GCaMP8f (fast variant of the indicator). Utilizing the myo-2 promoter, we compare pharyngeal muscle activity measured with GCaMP7f and GCaMP8f and find that GCaMP8f is brighter upon binding to calcium, shows faster kinetics, and is not disruptive to the intrinsic contraction dynamics of the pharynx. Additionally, we validate its application for detecting neuronal activity in touch receptor neurons which reveals robust calcium transients even at small stimulus amplitudes. As such, we establish GCaMP8f as a potent tool for C. elegans research which is capable of extracting fast calcium dynamics at very low magnifications across multiple cell types. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate the relationship between perceptual ratings of hypernasality made during connected speech and velopharyngeal (VP) gap size measured in millimeters in the sagittal plane during sustained vowel production using magnetic resonance imaging (MRI). Method: A retrospective cross-sectional analysis was completed. A subgroup of 110 participants from another study with an Mage of 10.1 years presenting for management of VP insufficiency was included. Perceptual ratings of hypernasality during connected speech and measurement of gap size during sustained /i/ production on MRI were performed by raters blinded to the participants' medical and surgical history. Results: There was a moderate-to-strong, positive correlation (r = .61; p < .001) between hypernasality ratings and VP gap size measured on MRI using sustained /i/. The odds of a higher hypernasality rating increased as the gap size increased (odds ratio = 1.34; 95% CI [1.20, 1.49]; p < .001). The predicted probability for hypernasality ratings of none/minimal/mild steadily decreased as the gap size increased indicating that lower ratings of hypernasality were associated with smaller gap sizes. For the rating of "moderate" hypernasality, the predicted probability of the rating steadily increased up to 8 mm and then decreased as the gap size continued to increase. The predicted probability for a hypernasality rating of "severe" consistently increased as the gap size increased. Conclusions: Hypernasality ratings made at the connected speech level were significantly associated with VP gap size as measured during sustained vowel production. These findings suggest sustained vowel production elicited on MRI may adequately characterize VP gap size in the evaluation of VP insufficiency. [ABSTRACT FROM AUTHOR]

Purpose: Cricopharyngeus muscle dysfunction (CPMD) is a common clinical occurrence with very few clear diagnostic criteria and multiple pathways for treatment. Incidence of CPMD is not known, but some data suggest around 25% of people with dysphagia experience some degree of CPMD, which negatively impacts swallowing safety and efficiency. Workup and treatment of CPMD can require multidisciplinary collaboration across laryngologists, speech-language pathologists with training in dysphagia management, and gastroenterologists. The purpose of this paper is to review what is known about CPMD and identify areas of future research in CPMD diagnosis and treatment. Methods: An overview of CPMD, relative treatments and disorders, and a discussion of future areas of research needed to improve clinical care of CPMD. Results: Details regarding historical background, pathophysiology and treatment practiced for CPMD are included. Conclusion: In summary, CPMD is a poorly defined disease due to a lack of understanding of its pathophysiology and the lack of consensus diagnostic criteria. Well-designed, prospective clinical trials are necessary to develop a better understanding of clinical incidence of CPMD, impact of the disorder on oropharyngeal swallowing, and how to approach treatment of the disorder surgically or in conjunction with therapy directed by a specialized speech-language pathologist. [ABSTRACT FROM AUTHOR]

Background: High‐density surface electromyography (HD‐sEMG) has enabled non‐invasive analysis of motor unit (MU) activity and recruitment, but its application to swallowing‐related muscles is limited. Objective: We aimed to investigate the utility of HD‐sEMG for quantitatively evaluating the MU recruitment characteristics of the suprahyoid muscles during tongue elevation. Methods: We measured the sEMG activity of the suprahyoid muscles of healthy participants during tongue elevation using HD‐sEMG. Maximum voluntary contraction (MVC) was measured, followed by data collection during sustained and ramp‐up tasks to capture suprahyoid muscle activity. Changes in the temporal/spatial MU recruitment patterns within individual suprahyoid muscles were analysed. Results: This study enrolled 16 healthy young adults (mean age: 27.8 ± 5.3 years; eight males and eight females). Increasing muscle force corresponded to a decrease in modified entropy and correlation coefficient and an increase in the coefficient of variation. No significant differences were observed between male and female participants. Conclusion: The results of this study, consistent with those observed in other muscles, such as the vastus lateralis muscle, suggest that HD‐sEMG is a valuable and reliable tool for quantitatively evaluating MU recruitment in the suprahyoid muscles. This measurement technique holds promise for novel assessments of swallowing function. [ABSTRACT FROM AUTHOR]

The automatic segmentation of the pharyngeal airway space has many potential medical use, one of which is to help facilitate the creation of the Tubingen Palatal Plate. Therefore, it is of great importance to understand which methods are suitable for this task. Here, neural network based solutions available in the literature are compared to find the best methods. Neural network models were chosen to encompass a diverse landscape. Some models were taken from the general semantic segmentation literature, while others were taken from the medical or pharyngeal airway space segmentation literature. Some models are convolutional neural networks, while others are transformer-based model or a mix of both convolutional and transformer-based model. These models include 2d/3d U-Net, Deeplabv3, YOLOv8, Swinv2 UNETR, SegFormer, and 3D MRU-Net. Furthermore, additional strategies to enhance performance were also considered. These strategies consisted of training two separate networks in multiple stages as well leveraging unlabeled data to pretrain the neural networks before fine-tuning them on the labeled data. It was found that out of all the models considered here, the 2d U-Net performed the best achieving an average dice score of 0.9180 ± 0.0111. Out of all the strategies to enhance performance, only two strategies improve the actual results but only by a small margin. Therefore, these strategies can be consider if a small increase in performance is desired from the 2d U-Net at the expense of computational resource. [ABSTRACT FROM AUTHOR]

Despite swallowing being a frequently performed daily function, it is highly complex. For a safe swallow to occur, muscles within the head, neck, and thorax need to contract in a concerted pattern, controlled by several swallowing centers at multiple levels of the central nervous system, including the midbrain, cerebral cortex, and cerebellum in addition to five cranial nerves. Dysphagia, or difficulty swallowing, is caused by a long list of pathologic processes and diseases, which can interfere with various stages along the swallowing sensorimotor pathway. When present, dysphagia leads to increased mortality, morbidity, hospital length of stay, and reduced quality of life. Current dysphagia management approaches, such as altering the texture and consistency of foods and fluids and teaching patients rehabilitative exercises, have been broadly unchanged for many years and, in the case of texture modification, are of uncertain effectiveness. However, evidence is emerging in support of new medication-based and neuromodulatory treatment approaches. Regarding medication-based therapies, most research has focused on capsaicinoids, which studies have shown are able to improve swallowing in patients with post-stroke dysphagia. Separately, albeit convergently, in the field of neuromodulation, there is a growing and positive evidential base behind three non-invasive brain stimulation techniques: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (TDCS), and pharyngeal electrical stimulation (PES). Should some or all of these emerging therapies fulfill their promise, dysphagia-related patient outcomes may be improved. This paper describes the current state of our understanding regarding new medication and neuromodulation-based neurogenic oropharyngeal dysphagia treatments. [ABSTRACT FROM AUTHOR]

Background: Cervical posture affects swallowing function through contractile and non‐contractile structures. Craniocervical flexor endurance training (CCFET), which focuses on the activation of deep cervical muscles, is used to ensure cervical posture stability. Objective: The aim of this study was to investigate the effect of CCFET on the suprahyoid muscles (SH), which play an important role in swallowing function. Methods: Eighty healthy individuals (52 female and 28 male, mean age 21.77 ± 1.81 years) were recruited and randomly assigned to groups that underwent either deep cervical flexor (DCF) training with a pressure biofeedback unit (CCFET group, n = 41) or no intervention (control group, n = 39). The intervention was applied for 4 weeks (five sessions per week). Static endurance and activation of DCF muscles (Craniocervical Flexion Test, CCFT), tragus–wall distance (TWD) for forward head posture and surface electromyographic (sEMG) activation of suprahyoid muscles were evaluated. Results: The endurance and activation of the DCF muscles were significantly increased in the CCFET group (p = <.001). In the CCFET group, TWD significantly lower than the control group (p = <.001) Peak SH amplitude and mean SH amplitude were lower in the CCFET group compared to the control group (p =.013, p =.003). Conclusion: The study shows that 4 weeks of CCFET reduced SH muscle activation, allowing the same work to be done with fewer motor units. CCFET can be included in rehabilitation programs as an additional method that has an effect on the muscles involved in swallowing by providing cervical motor control. [ABSTRACT FROM AUTHOR]

Introduction Adenoidectomy is one of the most common procedures performed by otolaryngologists. Traditional adenoid curettage is performed blindly, which can result in inadequate removal of the adenoid and injury to the surrounding structures. Objective To perform transnasal endoscopic examinations to assess the nasopharynx after conventional curettage adenoidectomy. Methods The present prospective study included 100 children with a mean age of 4.2 ± 3.07 years. It is composed of two steps: conventional curettage adenoidectomy by a resident trainee; and endoscopic evaluation of the nasopharynx through a 0° telescope to assess adenoidal remnants, injury to the surgical field or adjacent structures, and bleeding points. Results Adenoid remnants were observed in 42% of the cases after conventional adenoid curettage in multiple locations, such as the roof of the nasopharynx over the choana (24%), the tubal tonsil (12%), the posterior pharyngeal wall (4%), and the posterior end of the nasal septum (2%). Injury to the surgical field and adjacent structures was observed in 46% of the cases (posterior pharyngeal wall: 23%; lateral pharyngeal wall: 11%; Passavant ridge: 10%; and the Eustachian tube orifice: 2%). Endoscopic bleeding was observed in 29% of the cases; 13% of the cases were from adenoid remnants, 10%, from the mucosa, and 6%, from the pharyngeal muscles. Bleeding was mild in 19% of the cases, moderate in 9%, and severe in 1%. Conclusion Endoscopic evaluation of the nasopharynx following conventional adenoid curettage provides important data regarding adenoid remnants, injury to the surgical field or nearby structures, and bleeding points, which aids in the provision of optimal care and in the achievement of a better outcome. [ABSTRACT FROM AUTHOR]

Our purpose was to compare robust intensity modulated proton therapy (IMPT) plans, automatically generated with wish-list–based multicriterial optimization as implemented in Erasmus-iCycle, with manually created robust clinical IMPT plans for patients with head and neck cancer. Thirty-three patients with head and neck cancer were retrospectively included. All patients were previously treated with a manually created IMPT plan with 7000 cGy dose prescription to the primary tumor (clinical target volume [CTV]7000) and 5425 cGy dose prescription to the bilateral elective volumes (CTV5425). Plans had a 4-beam field configuration and were generated with scenario-based robust optimization (21 scenarios, 3-mm setup error, and ±3% density uncertainty for the CTVs). Three clinical plans were used to configure the Erasmus-iCycle wish-list for automated generation of robust IMPT plans for the other 30 included patients, in line with clinical planning requirements. Automatically and manually generated IMPT plans were compared for (robust) target coverage, organ-at-risk (OAR) doses, and normal tissue complication probabilities (NTCP). No manual fine-tuning of automatically generated plans was performed. For all automatically generated plans, voxel-wise minimum D 98% values for the CTVs were within clinical constraints and similar to manual plans. All investigated OAR parameters were favorable in the automatically generated plans (all P <.001). Median reductions in mean dose to OARs went up to 667 cGy for the inferior pharyngeal constrictor muscle, and median reductions in D 0.03cm3 in serial OARs ranged up to 1795 cGy for the spinal cord surface. The observed lower mean dose in parallel OARs resulted in statistically significant lower NTCP for xerostomia (grade ≥2: 34.4% vs 38.0%; grade ≥3: 9.0% vs 10.2%) and dysphagia (grade ≥2: 11.8% vs 15.0%; grade ≥3: 1.8% vs 2.8%). Erasmus-iCycle was able to produce IMPT dose distributions fully automatically with similar (robust) target coverage and improved OAR doses and NTCPs compared with clinical manual planning, with negligible hands-on planning workload. [ABSTRACT FROM AUTHOR]

Botulinum neurotoxin (BNT) injection into the cricopharyngeus muscle (CPM) under ultrasound (US) guidance is a minimally invasive technique performed to relieve cricopharyngeal dysphagia by reducing CPM spasticity. This technique is basically accessible only to both lateral sides of the CPM. This cadaveric study aimed to evaluate whether US-guided injection could effectively deliver BNT to abundant areas of gross nerve endings within the CPM. We utilized a newly modified Sihler's staining method to identify regions with abundant neural endings within the CPM while preserving the three-dimensional morphology of the muscle in 10 sides of 5 fresh cadavers. A mixture of 0.2 mL dye was injected into the 16 sides of CPM under US guidance in 8 cadavers. Nerve endings were abundant in posterolateral areas of the CPM; the injected dye was identified at the posterolateral area on 12 sides (12/16 side, 75%) without diffusion into the posterior cricoarytenoid muscle. The injection failed on four sides (two sides of the prevertebral fascia and two sides of the esophagus below the CPM). These results suggest that US-guided injection could be a feasible technique as it can deliver BNT to the most abundant nerve distribution areas within the CPM in most cases. [ABSTRACT FROM AUTHOR]

Introduction: To assess the usage of contralateral infrahyoid muscles as onlay flap in prevention of pharyngo‐cutaneous fistula (PCF) in total laryngectomy (TL) patients with high risk factors of PCF development. Methods: This study included 10 patients who suffered from advanced laryngeal carcinoma with presence of risk factors for development of PCF. We added an enforcement muscular layer during neo‐pharynx wall repair, the infrahyoid muscle flap of the contralateral side of the tumour origin as an onlay muscular flap to cover the anastomotic site for healing augmentation. Patients were followed up for PCF development where the PCF incidence was calculated. Results: One patient died from congestive heart failure in the 21th post‐operative day so, the actual PCF rate in TL patients with high risk factors of PCF development in our study was 11.11% (1 out of 9 cases). Conclusions: Infrahyoid muscle flap may have a role in preventing PCF after TL in patients with high risk factors of PCF development in this case series study to be further assessed in other studies to justify its role. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Objectives: The author discusses current otolaryngological procedures employing the palatopharyngeus muscle, based on the surgical anatomy of the muscle and its neural supply. These techniques should be deeply revised for more conservative, anatomically-based maneuvers. Methods: Revision of anatomical and surgical research and comments with the provision of a primary concept. Results: The palatopharyngeus muscle is innervated by the pharyngeal plexus (the vagus and the accessory nerves) with additional fibers from the lesser palatine nerves. The innervation enters the muscle mainly through its lateral border. Conclusions: The palatopharyngeus muscle has a fundamental role in swallowing and speech. The muscle helps other dilators to maintain upper airway patency. Sphincter pharyngoplasty should be revised as regards its role as a sphincter. Palatopharyngeal procedures for OSA employing the palatopharyngeus muscle should follow the conservative, anatomically-based, and non-neural ablation concept. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Introduction: Swallowing impairment is a crucial issue that can lead to aspiration, pneumonia, and malnutrition. Animal models are useful to reveal pathophysiology and to facilitate development of new treatments for dysphagia caused by many diseases. The present study aimed to develop a new dysphagia model with reduced pharyngeal constriction during pharyngeal swallowing. Methods: We analyzed the dynamics of pharyngeal swallowing over time with the pharyngeal branches of the vagus nerve (Ph-X) bilaterally or unilaterally transected, using videofluoroscopic assessment of swallowing in guinea pigs. We also evaluated the detailed anatomy of the pharyngeal constrictor muscles after the denervation. Results: Videofluoroscopic examination of swallowing showed a significant increase in the pharyngeal area during swallowing after bilateral and unilateral sectioning of the Ph-X. The videofluoroscopy also showed significantly higher pharyngeal transit duration for bilateral and unilateral section groups. The thyropharyngeal muscle on the sectioned side was significantly thinner than that on the intact side. In contrast, the thickness of the cricopharyngeal muscles on the sectioned and intact sides were not significantly different. The mean thickness of the bilateral thyropharyngeal muscles showed a linear correlation to the pharyngeal area and pharyngeal transit duration. Discussion: Data obtained in this study suggest that denervation of the Ph-X could influence the strength of pharyngeal contraction during pharyngeal swallowing in relation to thickness of the pharyngeal constrictor muscles, resulting in a decrease in bolus speed. This experimental model may provide essential information (1) for the development of treatments for pharyngeal dysphagia and (2) on the mechanisms related to the recovery process, reinnervation, and nerve regeneration following injury and swallowing impairment possibly caused by medullary stroke, neuromuscular disease, or surgical damage from head and neck cancer. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this research was to compare two treatment techniques for oropharyngeal cancers: conventional linac-based static intensity-modulated radiotherapy (sIMRT) and helical tomotherapy (HT). The study examined several parameters, including target coverage, organs at risk, integral dose, and beam on time. Additionally, the study evaluated the doses to the parotid, temporomandibular joint, and pharyngeal constrictor muscles, which are important for swallowing. Method: The present study retrospectively analyzed the data of 13 patients with oropharyngeal cancer who underwent radiotherapy between 2019 and 2021. The treatment plans for each patient were regenerated using both sIMRT and HT treatment planning systems with the sequential boost method. The techniques were evaluated and compared based on dose-volume histogram, homogeneity index, and conformity index parameters. The target coverage and organs at risk were statistically compared for two techniques. Additionally, the doses received by the healthy tissue volume were obtained for integral dose evaluation. The beam on time for each technique was assessed. Results: When considering planning target volume evaluation, there was no difference in Dmeans between the two techniques and sIMRT demonstrated higher D2% values compared to the HT. The HT technique had better results for all organs at risk, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle. As for integral dose, it has been shown that the sIMRT technique provides better protection compared to HT. In addition, the beam on time was also longer with the HT technique. Conclusion: Both techniques may provide optimal target coverage for patients with oropharyngeal cancer. HT conferred notable advantages, especially with regard to critical structures implicated in swallowing, such as the parotid, temporomandibular joint, and pharyngeal constrictor muscle, in comparison to sIMRT. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). Methods: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan–Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. Results: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. Conclusions: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival. [ABSTRACT FROM AUTHOR]

In the Adriatic Sea, a female common bottlenose dolphin named "Boa" was observed on 19 occasions between 2009 and 2019, inhaling via her mouth for every observed respiration. We provide some explanations for the potential cause of this behaviour using existing evidence. Boa appeared to be in good physical shape and displayed behaviour similar to other individuals. She mothered three calves, raising at least one to independence successfully. Because she lived a normal life, we believe she could vocalise and echolocate. Boa may have been forced to breathe through her mouth to deal with internal injuries, occlusion, or disease. Of the potential causes, an occlusion of the upper respiratory tract seems more likely than a perforation or permanent dislocation of the larynx. An occlusion could result from disease, a congenital disorder, and/or wrongly ingested or inhaled food items or foreign materials. To breathe via the mouth, Boa must have been able to circumvent the separation of the respiratory tract from the oral cavity. By relaxing the respiratory muscles, particularly the palatopharyngeus, she could have used the negative pressure of the lungs to pull in air from the oropharynx into the upper respiratory tract. The true cause of Boa's condition will probably never be discovered. [ABSTRACT FROM AUTHOR]

Purpose: This study determined the contributions of the anterior and posterior tongue regions in tongue pressure generation during regular saliva swallows (SSs) and effortful swallows (ESs) completed under two different instructions. The association between tongue pressure and perceived effort to swallow was also examined. Method: Forty healthy adults without swallowing disorders participated in this study, divided into two age groups: 20 younger (Mage = 21.95 years, SD = 4.43) and 20 older (Mage = 70.10 years, SD = 4.30). Simultaneous data acquisition involved submental surface electromyography, tongue manometry, and a visual analog scale across swallowing conditions (SS, ES with tongue emphasis, and ES with pharyngeal squeezing). The main outcome measures were tongue pressure during swallowing and perceived effort to swallow. Results: Overall tongue pressure during ESs with tongue emphasis and with pharyngeal squeezing was greater than that during SSs (R² = .78, p < .001). Moreover, tongue pressure during the ES with tongue emphasis was greater than that during the ES with pharyngeal squeezing (t = 25.63, p < .001). The posterior tongue region generated more pressure during SSs (R² = .64, p < .001) and the ES with tongue emphasis (R² = .55, p < .001) than the anterior tongue. Finally, a positive correlation was found between perceived effort and tongue pressure during swallowing (r = .75, 95% CI [0.72, 0.77]). Conclusions: Tongue pressure generation was affected by the type of instruction used to elicit ESs, and the posterior tongue showed relatively greater pressure contributions than the anterior tongue for ESs with tongue emphasis and SSs. Furthermore, age-related declines in pressure generation during swallowing were not evidenced in this study, underscoring the ability of healthy older individuals to appropriately modulate lingual pressure during ESs. Last, our results showed that the visual analog scale is a simple tool for rating swallowing effort during ESs, supporting its potential clinical use to train ESs. [ABSTRACT FROM AUTHOR]

Salt (NaCl), is an essential nutrient for survival, while excessive salt can be detrimental. In the fruit fly, Drosophila melanogaster, internal taste organs in the pharynx are critical gatekeepers impacting the decision to accept or reject a food. Currently, our understanding of the mechanism through which pharyngeal gustatory receptor neurons (GRNs) sense high salt are rudimentary. Here, we found that a member of the ionotropic receptor family, Ir60b, is expressed exclusively in a pair of GRNs activated by high salt. Using a two- way choice assay (DrosoX) to measure ingestion volume, we demonstrate that IR60b and two co- receptors IR25a and IR76b are required to prevent high salt consumption. Mutants lacking external taste organs but retaining the internal taste organs in the pharynx exhibit much higher salt avoidance than flies with all taste organs but missing the three IRs. Our findings highlight the vital role for IRs in a pharyngeal GRN to control ingestion of high salt. [ABSTRACT FROM AUTHOR]

Background/Aims: Retrograde cricopharyngeus dysfunction (R-CPD) is a new clinical entity characterized by inability to belch and associated symptoms of loud gurgling noises, chest and/or abdominal pressure, abdominal bloating, and excessive flatulence. R-CPD can be treated with botulinum toxin (BT) injection in the upper esophageal sphincter. We hereby report patient demographics, symptomatology, and treatment results of a series of consecutive patients who presented at our center. Methods: Data on 50 consecutive patients presenting with R-CPD were prospectively collected using a standardized questionnaire prior to, 1 month after treatment and at the end of follow-up. All patients were diagnosed using a set of clinical symptoms. Results: Fifty patients (26 females) were included, median age was 27.5 years (range, 17-65). Median body mass index was 22.7 kg/m2 (range, 16.6-37.5). Inability to belch was present in all patients, > 90% of patients experienced gurgling noises and abdominal/chest discomfort as result of their condition. One month after injection of BT, 40.8% of patients experienced complete relief of symptoms, 24.5% good symptom improvement, 24.5% some symptom improvement and 10.2% no improvement. At median follow-up of 29 months (range, 3-50) post-treatment, 51.3% (n = 20/39) of patients reported persistent complete relief of symptoms, 12.8% good improvement of symptoms (n = 5/39), in 15.4% some improvement (6/39) and 20.5% loss of or no response (n = 8/39). Only minor and transient side effects were reported. Conclusions: Our case series of 50 patients with R-CPD shows very good short-term and good long-term improvement of symptoms after injection of BT. These results are in line with previous studies. [ABSTRACT FROM AUTHOR]

The upper airway experiences mechanical loads during breathing. Obstructive sleep apnea is a very common sleep disorder, in which the normal function of the airway is compromised, enabling its collapse. Its treatment remains unsatisfactory with variable efficacy in the case of many surgeries. Finite element models of the upper airway to simulate the effects of various anatomic and physiologic manipulations on its mechanics could be helpful in predicting surgical success. Partial 3D finite element models based on patient-specific CT-scans were undertaken in a pilot study of 5 OSA patients. Upper airway soft tissues including the soft palate, hard palate, tongue, and pharyngeal wall were segmented around the midsagittal plane up to a width of 2.5 cm in the lateral direction. Simulations of surgical interventions such as Uvulopalatopharyngoplasty (UPPP), maxillo-mandibular advancement (MMA), palatal implants, and tongue implants have been performed. Our results showed that maxillo-mandibular advancement (MMA) surgery of 1 cm improved the critical closing pressure by at least 212.2%. Following MMA, the best improvement was seen via uvulopalatopharyngoplasty (UPPP), with an improvement of at least 19.12%. Palatal and tongue implants also offered a certain degree of improvement. Further, we observed possible interacting mechanisms that suggested simultaneous implementation of UPPP and tongue stiffening; and palatal and tongue stiffening could be beneficial. Our results suggest that computational modeling is a useful tool for analyzing the influence of anatomic and physiological manipulations on upper airway mechanics. The goal of personalized treatment in the case of OSA could be achieved with the use of computational modeling. [ABSTRACT FROM AUTHOR]

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Division of labor within a honey bee colony creates a codependence between bees performing different tasks. The most obvious example of this is between the reproductive queen and worker bees. Queen bees lay 1,000 or more eggs a day, while young worker bees tend and feed queens. Young workers and queens can be exposed to pesticides when foragers return to the hive with contaminated resources. Previous research has found negative effects of larval exposure to insect-growth disruptors (IGD) methoxyfenozide and pyriproxyfen, on adult responsiveness to artificial queen pheromone. The present work investigates potential physiological and molecular mechanisms underpinning this behavioral change by examining the development of hypopharyngeal glands and ovaries as well as the expression of genes related to reproduction and worker endocrine signaling in the brain and hypopharyngeal gland tissues. Though hypopharyngeal gland and ovary development were not altered by developmental exposure to IGDs, gene expression differed. Specifically, in the brain tissue, ilp1 was downregulated in bees exposed to pyriproxyfen during development, and Kr-h1 was downregulated in both methoxyfenozide- and pyriproxyfen-exposed bees. In the hypopharyngeal glands, Kr-h1 , EcR-A , EcR-B , and E75 were upregulated in honey bees exposed to methoxyfenozide compared to those in the pyriproxyfen or control treatments. Here we discuss these results and their potential implications for the health and performance of honey bee colonies. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the effects of Class III correction appliances including the Facemask (FM), and the new non-compliance fixed functional appliances such as the Reversed Forsus Fatigue Resistant Device (FRD), as well as the CS-2000 (CS), on the sagittal pharyngeal airway dimension (SPAD). Pre-treatment and post-treatment lateral cephalograms of 45 patients who underwent Class III appliance treatment, using either FM, Reversed FRD, or CS were collected from the files of treated patients. SPAD changes were evaluated in each group, and comparisons were conducted between the three study groups. Additionally, sagittal and vertical skeletal measurements were conducted. The FM, the Reversed FRD, and the CS, were found to generate a significant increase in the SPAD, with the Reversed FRD contributing to the most significant change at the OPAA (116.80 ± 26.36 mm2). All three appliances elicited significant antero-posterior changes in the SNA°, SNB°, and ANB°, also with the greatest intermaxillary change documented with the employment of the Reversed FRD (ANB° = 3.33 ± 0.82°). As for the vertical dimension, the FM, the Reversed FRD, and the CS elicited significant FMA° increases, with the greatest change attributed to the FM (FMA° = 2.32 ± 0.97°). Therefore, the three tested Class III corrective appliances generated significant SPAD, antero-posterior, and vertical changes. However, the Revered FRD showed a superior impact in increasing the SPAD at the OPAA level and in eliciting significant intermaxillary changes. [ABSTRACT FROM AUTHOR]

The PEARL study is a phase 2 multi-centre trial for good prognosis HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, currently open in the UK. PEARL is investigating the dosimetric impact of re-planning a radical radiotherapy plan midway through a course of treatment, based upon the biological response of the primary GTV on 18 FDG PET-CT. With the wider availability of proton beam therapy in the form of Intensity Modulated Proton Therapy (IMPT) as a potential option for radiotherapy in the management of OPSCC, in addition to substantial cost implications, improving methods to determine the patients who will benefit most from IMPT is required. The organ sparing benefits of IMPT are well documented. This modelling planning study investigated whether the benefits of proton therapy can be improved by applying biological response-based adaptation as per the PEARL study planning method. Objectives: 1. Investigate the dosimetric impact of IMPT by comparing mean dose received by swallowing OARs (SWOARs) between non-adaptive VMAT and non-adapted IMPT plans 2. Investigate the dosimetric impact of adaptation by comparing dose received by SWOARs between non-adaptive IMPT and adapted IMPT plans 3. Investigate the relative dosimetric impact of adaptation by comparing dose received by SWOARs between adaptive VMAT and IMPT plans 4. Identify whether adaptation as per the PEARL Study protocol would influence the delta normal tissue complication probability (ΔNTCP) threshold for proton beam therapy funding in The Netherlands Anonymized patient datasets were used to model VMAT and IMPT plans using RayStation and optimised for SWOARs. The following plans were generated: 1. 'NON-ADAPTIVE': Manually planned non-adapted VMAT 2. 'ADAPTIVE': Manually planned adapted VMAT 3. 'NON-ADAPTIVE_PROTON': Manually planned non-adapted IMPT 4. 'ADAPTIVE_PROTON': Manually planned adapted IMPT NTCP calculations for dysphagia risk we performed using the validated dysphagia model described by Christianen et al (1). Individual calculations were performed on each case comparing adapted and non-adapted VMAT plans to non-adapted IMPT plans to explore whether they reached the threshold for proton beam treatment funding as per The Netherlands scheme. Mean dose to the superior pharyngeal constrictor muscle and the supraglottis was entered into the following calculation: 1/NTCP = (1+ e)– s where s = -6.09 + (mean dose to the superior pharyngeal constrictor muscle x 0.057) + (mean dose to the supraglottis × 0.037) All cases had a reduction in their total mean dose to SWOARs, adapted as per PEARL, and planned with IMPT. The magnitude of impact was ranked in the same order for all cases, with optimisation reducing the total mean dose the least, and adapted IMPT the most. Cases 1 and 2, and Cases 3 and 4, demonstrated similar total mean dose reductions despite having different degrees of biological GTV reduction on the iPET-CT. Adaptation had the greatest impact on Cases 2 and 3 for both VMAT and IMPT plans. [Display omitted] The NTCP differences between non-adaptive VMAT plans and non-adaptive IMPT plans were >10% suggesting these cases would be candidates for IMPT funding as as per the National Indication Protocol Proton therapy (NIPP) - head and neck cancer criteria in The Netherlands. Whilst primarily limited by the small number of cases, we have demonstrated that IMPT markedly reduces doses to SWOARs compared to VMAT planning in line with widely published studies. We have also demonstrated that adaptation based on the biological response to the tumour after 2 weeks of chemoradiotherapy can further improve the tissue sparing already achieved with IMPT. This is the first study to demonstrate that SWOAR sparing by IMPT can be improved with biological response guided adaptive radiotherapy. Our results are in line with published data that IMPT can spare many head and neck SWOARs to a greater extent than VMAT in the treatment of oropharyngeal cancers. In the cases studied here, the impact of IMPT on the mean dose to SWOARs was greater than the impact of adaptation, when compared to standard VMAT planning. However, there may be additional dosimetric benefit when IMPT is adapted to tumour response during a course of radiotherapy treatment, particularly dose to more caudal SWOARs. In this small cohort, adaptation on VMAT plans was unlikely to have affected a decision for IMPT treatment as per the Netherlands NTCP-based algorithm. Further work with a larger cohort of patients, as well as real-time studies to collect prospective clinical data on xerostomia and dysphagia rates, is required to properly investigate the clinical advantages of adaptive IMPT. [ABSTRACT FROM AUTHOR]

Head and neck radiotherapy long-term survival continues to improve and the management of long-term side-effects is moving to the forefront of patient care. Dysphagia is associated with dose to the pharyngeal constrictors and can be measured using patient-reported outcomes to evaluate its effect on quality of life. The aim of the present study was to relate pharyngeal constrictor dose–volume parameters with patient-reported outcomes to identify prognostic dose constraints. A 64-patient training cohort and a 24-patient testing cohort of oropharynx and nasopharynx cancer patients treated with curative-intent chemoradiotherapy were retrospectively examined. These patients completed the MD Anderson Dysphagia Inventory outcome survey at 12 months post-radiotherapy to evaluate late dysphagia: a composite score lower than 60 indicated dysphagia. The pharyngeal constrictor muscles were subdivided into four substructures: superior, middle, inferior and cricopharyngeal. Dose–volume histogram (DVH) metrics for each of the structure combinations were extracted. A decision tree classifier was run for each DVH metric to identify dose constraints optimising the accuracy and sensitivity of the cohort. A 60% accuracy threshold and feature selection method were used to ensure statistically significant DVH metrics were identified. These dose constraints were then validated on the 24-patient testing cohort. Existing literature dose constraints only had two dose constraints performing above 60% accuracy and sensitivity when evaluated on our training cohort. We identified two well-performing dose constraints: the pharyngeal constrictor muscle D63% < 55 Gy and the superior–middle pharyngeal constrictor combination structure V31Gy < 100%. Both dose constraints resulted in ≥73% mean accuracy and ≥80% mean sensitivity on the training and testing patient cohorts. In addition, a pharyngeal constrictor muscle mean dose <57 Gy resulted in a mean accuracy ≥74% and mean sensitivity ≥60%. Mid-dose pharyngeal constrictor muscle and substructure combination dose constraints should be used in the treatment planning process to reduce late patient-reported dysphagia. • Current treatment planning methods constrain pharyngeal constrictor mean dose. • Literature constraints classify patient-reported dysphagia below 60% accuracy. • Decision tree and feature selection method identified new clinical constraints. • Combination and mid-dose pharyngeal constraints perform better than literature. [ABSTRACT FROM AUTHOR]

Objective: To determine whether method of maxillary advancement in adolescents with cleft palate with or without cleft lip (CP ± L) influences post-operative velopharyngeal function. Design: Retrospective cohort. Setting: Pediatric Tertiary Care Hospital. Participants: One hundred and ninety-nine patients with CP ± L after LeFort I osteotomy for maxillary advancement at our institution between January 2007 and June 2019. Interventions: LeFort I osteotomy via distraction osteogenesis (DO) or conventional osteotomy (CO). Main Outcome Measures: Patients who underwent DO or CO were compared for the presence of new velopharyngeal insufficiency (VPI), as measured by perceptual rating by a craniofacial speech-language pathologist. Results : Of the 199 patients who underwent maxillary advancement, 126 were available for analysis. The DO group was younger, male, and had more severe maxillary hypoplasia. Following surgery, 17/41 (41.5%) of the DO group had new VPI, compared to just 23/85 (27.1%) of the CO group. After adjusting for cleft type and predicted maxillary advancement, however, there was not sufficient evidence to reject the null hypothesis of no difference in risk of post-operative VPI between the two surgical groups (prevalence ratio [PR] 1.40, 95% CI 0.68-2.90). Increased prevalence of VPI after DO versus CO was primarily observed among patients with a pre-operative velopharyngeal need ratio < 0.8 (PR = 2.01, 95% CI 0.79-5.10) and patients with normal velopharyngeal function pre-operatively (PR = 2.86, 95% CI 0.96-8.50). Conclusion : Our results suggest an increased rather than decreased risk of VPI following DO relative to CO. This association is primarily seen among those with a smaller velopharyngeal ratio or perceptually normal velopharyngeal function pre-operatively. [ABSTRACT FROM AUTHOR]

Laryngopharyngeal reflux disease (LPRD) is a condition characterized by the regurgitation of stomach and duodenal contents into the laryngopharynx, with variable and non-specific symptoms. Therefore, developing an accurate symptom scale for different regions is essential. Notably, the symptoms of "dryness and burning sensation in the laryngopharynx or mouth" are prevalent among the Chinese population but are often omitted from conventional symptom assessment scales, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) scales. To address this gap, our study incorporated the symptoms into the RSI and RSS-12 scales, developing the RSI-10/RSS-13 scales. Afterward, we assessed the role of the new scale's reliability (Cronbach's α and test–retest reliability), construct validity (confirmatory factor analysis and confirmatory factor analysis), and diagnostic efficiency. Our study encompassed 479 participants (average = 39.5 ± 13.4 years, 242 female) and 91 (average = 34.01 ± 13.50 years, 44 female) completed 24 h MII-pH monitoring. The Cronbach's α values of 0.80 and 0.82 for the RSI-10 and RSS-13 scales, respectively. RSI-10 and RSS-13 exhibited strong test–retest reliability (ICCs = 0.82–0.96) and diagnostic efficacy (AUC = 0.84–0.85). Furthermore, the factor analysis identified the RSS-13 and its three sub-scales (ear-nose-throat, digestive tract, respiratory tract) exhibited good to excellent structural validity (χ2/df = 1.95, P < 0.01; CFI = 0.95, RMSEA = 0.06, SRMR = 0.05). The AUC optimal thresholds for the RSI-10 and RSS-13 in the Chinese population were 13 and 36, respectively. Besides, the inclusion of the new item significantly improved the diagnostic efficiency of the RSI scale (P = 0.04), suggesting that RSI-10 holds promise as a more effective screening tool for LPRD, and global validation is needed to demonstrate the impact of this new symptom on the diagnosis of LPRD. [ABSTRACT FROM AUTHOR]

Background: Retrograde cricopharyngeus dysfunction (R‐CPD), a condition first detailed in 1987 and termed in 2019, refers to the cricopharyngeal muscle's inability to relax to allow the retrograde passage of gas. Limited research exists on the fundamental characteristics of this condition, including its impact on one's life. The purpose of this study is to characterize R‐CPD and how the inability to burp affects the social lives of people who suffer from it. Methods: A Qualtrics survey was distributed on the subreddit "r/noburp," a community of 26,000 individuals sharing information about R‐CPD. Adults aged 18–89 experiencing R‐CPD symptoms were invited to participate. Participants reported on their experiences with R‐CPD and its effects on social life on a 4‐point Likert scale (1 = strongly disagree to 4 = strongly agree). Data was analyzed using descriptive statistics. Key Results: Among the 199 respondents, the mean age was 30.9, and gender identity was 74%/25% female/male. 99% reported inability to burp, 98% reported abdominal bloating, 93% reported socially awkward gurgling noises, 89% reported excessive flatulence, and 55% reported difficulty vomiting. Only half discussed their symptoms with their primary care provider (PCP), and 90% disagreed with receiving adequate help. Average Likert scores indicated embarrassment (3.4), anxiety/depression (3.1), negative impact on relationships (2.6), and work disruption (2.7) due to R‐CPD. Conclusions & Inferences: R‐CPD is unfamiliar to many healthcare providers, leaving patients underserved. It not only affects daily life but also personal and professional relationships. Raising awareness by understanding disease basic features may increase diagnosis and treatment rates, improving quality of life. [ABSTRACT FROM AUTHOR]

Background: We evaluated clinical and dosimetric outcomes of radiotherapy using two anterior oblique portals (AOP), to reduce the dose to the bilateral internal carotid arteries (CAs) and pharyngeal constrictor muscle (PCM) during early‐stage glottic cancer (ESGC) treatment. Methods: We identified patients with ESGC who underwent definitive radiotherapy between June 2014 and May 2020. Results: Among the 66 patients, 32 (48%) underwent radiotherapy using AOP, and the remaining underwent typical radiotherapy using parallel opposed lateral portals (POLP). The median follow‐up duration was 53 months. No significant differences were observed in the 5‐year local failure (0%/9.4%), progression‐free survival (90.6%/90.8%), and overall survival (90.6%/91.0%) rates between the two groups. The grade ≥2 acute mucositis incidence rate was significantly lower in the AOP group (44%/85%). Radiotherapy using AOP maintained an adequate dose coverage to the target while markedly reducing the CAs and PCM doses. Conclusion: Radiotherapy with AOP resulted in favorable clinical and dosimetric outcomes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a framework for 3D subject-specific computational models capable of simulating velopharyngeal biomechanics for anatomic changes that occur following pharyngoplasty and to gain insight into biomechanical factors that may lead to different speech/surgical outcomes. Patient-specific models for two, matched participants with differing speech/surgical outcomes were developed: one with a successful pharyngoplasty outcome and one with a failed pharyngoplasty outcome. Surgical scenarios were simulated to model pharyngoplasty location, identify LVP muscle biomechanics, and identify an optimal pharyngoplasty location for each participant. These simulations illustrate the potential for optimizing pharyngoplasties based on patient-specific geometry. [ABSTRACT FROM AUTHOR]

Retrograde cricopharyngeal dysfunction (RCPD), also referred to as retrograde cricopharyngeus dysfunction, is a condition characterized by the inability to burp. The pathophysiology of this condition is thought to result from failure of cricopharyngeal sphincter relaxation during periods of esophageal distension, which leads to patients' bothersome symptoms. RCPD negatively impacts patients' quality of life and is associated with bloating, gurgling, avoidance of carbonation, self-imposed dietary and lifestyle changes designed to minimize discomfort, and flatulence. Complaints often start during adolescence, and many patients search for a diagnosis for years before obtaining treatment. A recent increase in awareness through patient-led social media discussion boards describing the 'no burp' syndrome is leading to an increasing incidence of presentations, often with patients making a self-diagnosis. The increased incidence of RCPD is fueling a larger case series investigating treatment options and outcomes. In this review, we discuss what is known about the pathophysiology of this condition, the otolaryngologic perspective on diagnosis and treatment, the patients' lived experience of this condition, and the influence of social media on RCPD. [ABSTRACT FROM AUTHOR]

Changes in pharyngeal and upper-esophageal-sphincter (UES) motor dynamics contribute to swallowing dysfunction. Children with type 1 laryngeal clefts can present with swallowing dysfunction and associated symptoms which may persist even after the initial endoscopic intervention. This study sought to characterize pharyngeal and esophageal motor function in children with type 1 laryngeal clefts who had persistent presenting symptoms after their initial therapeutic intervention. We retrospectively analyzed high-resolution esophageal manometry studies of children ≤ 18 years old with type 1 laryngeal clefts who had an esophageal manometry study performed for persistent symptoms after an initial repair. A total of 16 children were found to have significantly increased UES resting pressure, UES pre- and post-swallow maximum pressures, and duration of UES contraction during swallows in comparison to nine age-matched controls of children without pharyngeal anatomical abnormalities. There was no difference between UES residual pressures or pharyngeal dynamics between the two groups. UES resting and residual pressures did not correlate with VFFS in penetration and aspiration scores of children with type 1 laryngeal clefts status post repair. Our study is the first to identify specific changes in UES motor function in patients with type 1 laryngeal cleft post initial repair. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the impact of the involvement of the superior pharyngeal constrictor muscle (SPCM) evaluated by magnetic resonance imaging (MRI) on outcome in oropharyngeal squamous cell carcinomas (OPSCCs). Methods: A retrospective study including consecutive patients with OPSCC treated with curative intent. Results: A total of 82 consecutive patients with OPSCC met inclusion criteria. At multivariate analysis, patients with SPCM infiltration were at significantly higher risk of death (HR: 3.37, CI: 1.21–9.38) and progression (HR: 3.39, CI: 1.38–8.32). In a multivariate model conditioned on HPV status, a significantly higher risk of death and progression was observed by combining both SPCM and HPV status with patients harboring an HPV‐negative OPSCC with SPCM infiltration showing the poorest outcome. Conclusion: MRI evidence of SPCM involvement significantly and independently increases the risk of death and progression in subjects with OPSCC. Considering both MRI‐assessed SPCM infiltration and HPV status significantly improved risk stratification in these malignancies. [ABSTRACT FROM AUTHOR]

PurposeThe purpose of this study was to evaluate if HPV status serves as an independent predictor of early and late dysphagia outcomes when considered alongside standard patient characteristics and dose metrics for head and neck cancer patients treated with radiotherapy.Methods and materialsThe age, sex, smoking history, cancer type (oropharyngeal vs non-oropharyngeal), HPV status, and early and late dysphagia outcomes were obtained for 99 retrospective head and neck cancer patients treated at our clinic with radiotherapy. Additionally for each patient, the mean radiation dose to the pharynx, superior/middle/inferior pharyngeal constrictor muscles, and cricopharyngeus was calculated. The predictive power of these clinical characteristics and radiation metrics was evaluated using chi-square tests for categorical variables and t-tests for continuous variables. Then multi-variate logistic models were built for each outcome using a single dose metric at a time, and either HPV status, cancer type, or both. Multi-variate models were built using both top-down and bottom-up technique to establish the most predictive independent covariates.ResultsIn the univariate analysis for early dysphagia, cancer type (p = 0.04) and four dose metrics (p ≤ 0.02) were significantly associated with outcome, while for late dysphagia, only cancer type (p = 0.04) was associated with outcome. In the multivariate analysis for early dysphagia, cancer type, smoking history, and mean dose to the five structures were consistently selected as covariates. For late dysphagia, either HPV status or cancer type was selected in each model and the mean dose to the cricopharyngeus was selected in one model.ConclusionWhile HPV is a known contributing factor for tumor prognosis in oropharyngeal cancers, its role in normal tissue toxicities for head and neck cancers has not previously been evaluated. Our results indicate having an oropharyngeal cancer may increase a patient's risk of high-grade early and late dysphagia while HPV status was seldom selected.

The DARS trial is a phase 3, multicentre, randomised controlled trial published by Nutting et al in 2023 (1). Within the trial, patients with oropharyngeal or hypopharyngeal cancer were randomised to dysphagia optimised intensity-modulated radiotherapy (DO-IMRT) or standard IMRT. The trial demonstrated that patients in the DO-IMRT group had significantly higher MD Anderson Dysphagia Inventory (MDADI) composite scores at 12 months than patients in the standard IMRT group. The DARS protocol for the delineation of the primary tumour clinical target volumes (CTVp) included an anatomical approach. A 10 mm margin was added to the Gross tumour volume (GTV) to construct a high-dose clinical target volume, which was to receive 65Gy in 30 fractions. The remaining primary tumour subsite was then delineated to form a low dose CTV to receive 54Gy in 30 fractions (2). In 2017 the consensus guidelines on delineation of the primary tumour CTV were published by Gregoire et al (3). These guidelines recommend two CTVs for the primary tumour. A 5mm margin is added to the GTV to construct the high-dose CTV, and an additional 5mm rim of tissue is added to form the lower dose CTV. Our centre has adopted these guidelines, and their use is recommended in RCR consensus statements. (4) Given the differences in the delineation of the high and low dose CTVs between consensus guidelines and the approach used in the DARS trial, one could question how applicable the results of the DARS trial are to wider practice as doses to OARs are likely to be different. [Display omitted] We aimed to assess the validity of the DARS trial findings by comparing average mean dose to the pharyngeal constrictor muscles when CTVs were delineated according to the consensus guidelines (3) and compare these to the standard IMRT and DO-IMRT groups within the DARS trial (2). Patients treated at our institution between March 2020 and March 2023 were screened for eligibility, mirroring the criteria used in the DARS trial. Patients had to have been treated for oropharyngeal or hypopharyngeal cancer, with radical radiotherapy and bilateral neck treatment. Patients with a primary tumour involving the posterior pharyngeal wall or the post cricoid oesophagus were excluded. Patients had their primary contoured with a 5+5 expansion, as per the consensus guidelines (3) and received 3 dose levels. The high dose CTV received 65Gy in 30 fractions, as per DARS, but the lower dose CTV around the primary received 60Gy in 30 fractions. The nodal high dose CTV was between 5 and 10mm around the nodal GTV and received 65Gy in 30 fractions. The elective lymph node CTV received 54Gy in 30 fractions. PTV margins were 3-5mm. The IMRT treatment was planned using Pinnacle, using 2 full VMAT arcs. The pharyngeal constrictor muscles were delineated on the CT planning scans, either by a radiation oncologist, or by the LIMBUS AI outlining software and edited appropriately. As per the DARS protocol, the superior and middle pharyngeal constrictor muscles (SMPCM) were defined as a single structure with the inferior pharyngeal constrictor muscle (IPCM) defined separately. No dose constraints had been applied to the constrictors when planning, and PTV coverage had not been compromised for them. The mean dose to each structure, not overlapping with CTV65Gy or CTV60Gy, (Plan_SMPCM and Plan_IPCM) was calculated. 22 eligible patients were identified. 3 (14%) were female and 19 (86%) were male with a median age of 59. 21 patients (95%) had P16 positive oropharyngeal SCC and 1 patient (5%) had hypopharyngeal SCC. In our cohort, the median of the mean dose to the Plan_SMPCM was 55.3Gy (IQR 53.6-57.1). The median of the mean dose to the Plan_IPCM was 45.6Gy (IQR 42.6-48.0). (See table for comparison) [Display omitted] The average dose to the pharyngeal constructor muscles in our cohort was lower than in the standard arm of DARS, likely reflecting the difference in high and low dose CTV volumes. The average dose, particularly to the IPCM, was significantly higher in our patient group, than in the DARS cohort planned with DO-IMRT. These data support the observation in the DARS trial that DO_IMRT is associated with significantly lower radiation doses to the pharyngeal constrictor muscles, even when accounting for differences in target volume delineation. 83% of patients in the DARs trial had HPV positive OPC, and we conclude DO_IMRT should be considered a standard of care in these good prognosis patients. [ABSTRACT FROM AUTHOR]

Sustained pharyngeal inflation (SPI) with pharyngeal oxygen flow and nasal closure (PhO2-NC) technique create positive inflation pressure in the airway. This study measured the peak inflation pressure (PIP) levels and image changes with SPI-assisted flexible bronchoscopy (SPI-FB) and compared the effects in the pharyngeal space and mid-tracheal lumen. This prospective study enrolled 20 participants aged 6 months to 3 years. Each participant underwent sequential SPI-FB of four different durations (0, 1s, 3s, and 5s) for three cycles. We used a 3.8 mm OD flexible bronchoscope to measure and analyze PIP levels, images, and lumen dimension scores. A total of 480 data were collected. The mean (SD) age and body weight were 12.0 (11.5) months and 7.8 (7.5) kg, respectively. The mean (IQR) PIPs were 4.2 (2.0), 18.5 (6.1), 30.6 (13.5), and 46.1 (25.0) cmH2O in the pharynx and 5.0 (1.6), 17.5 (6.5), 28.0 (12.3), 46.0 (28.5) cmH2O in the mid-trachea at SPI durations of 0, 1s, 3s, and 5s, respectively. The PIP levels had a positive correlation (p <0.001) with different SPI durations in both pharynx and trachea, and were nearly identical (p = 0.695, 0.787, and 0.725 at 1s, 3s, and 5s, respectively) at the same duration except the 0 s (p = 0.015). Lumen dimension scores also significantly increased with increasing SPI durations (p <0.05) in both locations. The identified lesions significantly increased as PIP levels increased (p <0.001). Conclusion: SPI-FB using PhO2-NC with durations up to 3s is safe and informative technique that provides controllable PIP, dilates airway lumens, and benefits lesion detection in the pharyngeal space and mid-tracheal lumen. [ABSTRACT FROM AUTHOR]

Even slight imbalance between the growth rate of different organs can accumulate to a large deviation from their appropriate size during development. Here, we use live imaging of the pharynx of C. elegans to ask if and how organ size scaling nevertheless remains uniform among individuals. Growth trajectories of hundreds of individuals reveal that pharynxes grow by a near constant volume per larval stage that is independent of their initial size, such that undersized pharynxes catch-up in size during development. Tissue-specific depletion of RAGA-1, an activator of mTOR and growth, shows that maintaining correct pharynx-to-body size proportions involves a bi-directional coupling between pharynx size and body growth. In simulations, this coupling cannot be explained by limitation of food uptake alone, and genetic experiments reveal an involvement of the mechanotransducing transcriptional co-regulator yap-1. Our data suggests that mechanotransduction coordinates pharynx growth with other tissues, ensuring body plan uniformity among individuals. Imbalance in the growth rate of two organs can perturb their appropriate scaling. Here, Stojanovski et al., identify a mechanism involving the mechanotransducer YAP-1 which ensures proper proportions of the pharynx and the body length of C. elegans. [ABSTRACT FROM AUTHOR]

Dysphagia is a common toxicity after head and neck (HN) radiation therapy that negatively affects quality of life. We explored the relationship between radiation therapy dose to normal HN structures and dysphagia 1 year after treatment using image-based datamining (IBDM), a voxel-based analysis technique. We used data from 104 patients with oropharyngeal cancer treated with definitive (chemo)radiation therapy. Swallow function was assessed pretreatment and 1 year posttreatment using 3 validated measures: MD Anderson Dysphagia Inventory (MDADI), performance status scale for normalcy of diet (PSS-HN), and water swallowing test (WST). For IBDM, we spatially normalized all patients' planning dose matrices to 3 reference anatomies. Regions where the dose was associated with dysphagia measures at 1 year were found by performing voxel-wise statistics and permutation testing. Clinical factors, treatment variables, and pretreatment measures were used in multivariable analysis to predict each dysphagia measure at 1 year. Clinical baseline models were found using backward stepwise selection. Improvement in model discrimination after adding the mean dose to the identified region was quantified using the Akaike information criterion. We also compared the prediction performance of the identified region with a well-established association: mean doses to the pharyngeal constrictor muscles. IBDM revealed highly significant associations between dose to distinct regions and the 3 outcomes. These regions overlapped around the inferior section of the brain stem. All clinical models were significantly improved by including mean dose to the overlap region (P ≤.006). Including pharyngeal dosimetry significantly improved WST (P =.04) but not PSS-HN or MDADI (P ≥.06). In this hypothesis-generating study, we found that mean dose to the inferior section of the brain stem is strongly associated with dysphagia 1 year posttreatment. The identified region includes the swallowing centers in the medulla oblongata, providing a possible mechanistic explanation. Further work including validation in an independent cohort is required. [ABSTRACT FROM AUTHOR]

Background: Oculopharyngodistal myopathy (OPDM) is an autosomal dominant adult-onset degenerative muscle disorder characterized by ptosis, ophthalmoplegia and weakness of the facial, pharyngeal and limb muscles. Trinucleotide repeat expansions in non-coding regions of LRP12, G1PC1, NOTCH2NLC and RILPL1 were reported to be the etiologies for OPDM. Results: In this study, we performed long-read whole-genome sequencing in a large five-generation family of 156 individuals, including 21 patients diagnosed with typical OPDM. We identified CGG repeat expansions in 5'UTR of RILPL1 gene in all patients we tested while no CGG expansion in unaffected family members. Repeat-primed PCR and fluorescence amplicon length analysis PCR were further confirmed the segregation of CGG expansions in other family members and 1000 normal Chinese controls. Methylation analysis indicated that methylation levels of the RILPL1 gene were unaltered in OPDM patients, which was consistent with previous studies. Our findings provide evidence that RILPL1 is associated OPDM in this large pedigree. Conclusions: Our results identified RILPL1 is the associated the disease in this large pedigree. [ABSTRACT FROM AUTHOR]

Purpose: An accurate estimation of range uncertainties is essential to exploit the potential of proton therapy. According to Paganetti's study, a value of 2.4% (1.5 standard deviation) is currently recommended for planning robust treatments with Monte Carlo dose engines. This number is based on a dominant contribution from the mean excitation energy of tissues. However, it was recently shown that expressing tissues as a mixture of water and "dry" material in the CT calibration process allowed for a significant reduction of this uncertainty. We thus propose an adapted framework for pencil beam scanning robust optimization. First, we move towards a spot‐specific range uncertainty (SSRU) determination. Second, we use the water‐based formalism to reduce range uncertainties and, potentially, to spare better the organs at risk. Methods: The stoichiometric calibration was adapted to provide a molecular decomposition (including water) of each voxel of the CT. The SSRU calculation was implemented in MCsquare, a fast Monte Carlo dose engine dedicated to proton therapy. For each spot, a ray‐tracing method was used to propagate molecular I‐values uncertainties and obtain the corresponding effective range uncertainty. These were then combined with other sources of range uncertainties, according to Paganetti's study of 2012. The method was then assessed on three head‐and‐neck patients. Two plans were optimized for each patient: the first one with the classical 2.4% flat range uncertainty (FRU), the second one with the variable range uncertainty. Both plans were then compared in terms of target coverage and OAR mean dose reduction. Robustness evaluations were also performed, using the SSRU for both plans in order to simulate errors as realistically as possible. Results: For patient 1, it was found that the median SSRU was 1.04% (1.5 standard deviation), yielding, therefore, a very large reduction from the 2.4% FRU. All three SSRU plans were found to have a very good robustness level at a 90% confidence interval while sparing OAR better than the classical plan. For instance, in nominal cases, average reductions in the mean dose of 15.7, 8.4, and 13.2% were observed in the left parotid, right parotid, and pharyngeal constrictor muscle, respectively. As expected, the classical plans showed a higher but unnecessary level of robustness. Conclusions: Promising results of the SSRU framework were observed on three head‐and‐neck cases, and more patients should now be considered. The method could also benefit to other tumor sites and, in the long run, the variable part of the range uncertainty could be generalized to other sources of uncertainty in order to move towards more and more patient‐specific treatments. [ABSTRACT FROM AUTHOR]

Objectives Dysphagia is a common debilitating clinical feature of IBM. However, the impact of dysphagia in IBM has been historically overlooked. This study aimed to identify, evaluate and summarize the evidence regarding the assessment and management of dysphagia in persons with IBM undergoing treatment. Methods A systematic review was conducted using a multiengine search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Eligible studies had to employ an intervention for persons with IBM, report a swallowing outcome and be published in English. Quality assessments of the eligible studies were performed. Results Of 239 studies found, 19 met the inclusion criteria. One study was rated as 'fair' and the rest as 'poor' quality, particularly due to the lack of published and validated swallowing assessment procedures and outcome measures. Cricopharyngeal (CP) dysfunction (12/19) was the most commonly reported swallowing abnormality. Interventions for disease management included pharmacological agents (10/19), followed by surgical (3/19), behavioral (1/19) and combined approaches (5/19). Interventions with immunosuppressants, botulinum toxin injection, balloon dilation and/or CP myotomy led to mixed and transient benefits. Few studies examining statins or behavioral therapies (primarily focused on respiratory function) showed no effects for dysphagia. Conclusion Various interventions have been reported to temporarily improve dysphagia in persons with IBM. However, these findings are based on limited and overall low-quality evidence. This study cautions against the generalization of these findings and emphasizes the need for further systematic research to improve the diagnosis and management of dysphagia in IBM. [ABSTRACT FROM AUTHOR]

Subjects with maxillary skeletal classes II and III not only express alterations in the hard and soft maxillofacial tissues, but also in the morphology and dimensions of the upper airway. A small space in the upper airway has been associated with sleep disorders, such as snoring and mainly obstructive sleep apnea/hypopnea syndrome (OSAHS). Consequently, interest has increased due to the influence of orthognathic surgery in the airway space. Although there are studies in the literature that have compared upper airway spaces, most have evaluated the changes using two-dimensional images, mainly lateral skull X-rays. The present study aimed to determine the airway volume in subjects with skeletal classes II and III who underwent bimaxillary orthognathic surgery. 80 CBCT exams from 40 subjects obtained before and 6 months after surgery were used. There were 20 class II and 20 class III subjects. For the volumetric analysis, a 3D rendering of the upper airway was made in previously established segments, and then the airway volume was calculated using the 3D Slicer® software version 4.11 (Slicer, USA). The statistical analysis by t-test of related samples revealed statistically significant volumetric increases in the nasopharynx, laryngopharynx, and total volume in class II patients. However, in class III patients, there were significant increases in the nasopharynx and total volume, while the volume was maintained in the oropharynx and laryngopharynx. [ABSTRACT FROM AUTHOR]

The pharyngeal arches are a series of bulges found on the lateral surface of the head of vertebrate embryos. In humans, and other amniotes, there are five pharyngeal arches and traditionally these have been labelled from cranial to caudal—1, 2, 3, 4 and 6. This numbering is odd—there is no '5'. Two reasons have been given for this. One is that during development, a 'fifth' arch forms transiently but is not fully realised. The second is that this numbering fits with the evolutionary history of the pharyngeal arches. Recent studies, however, have shown that neither of these justifications have basis. The traditional labelling is problematic as it causes confusion to those trying to understand the development of the pharyngeal arches. In particular, it creates difficulties in the field of congenital cardiac malformations, where it is common to find congenital cardiac lesions interpreted on the basis of persistence of the postulated arteries of the fifth arch. To resolve these problems and to take account of the recent studies that have clarified pharyngeal arch development, we propose a new terminology for the pharyngeal arches. In this revised scheme, the pharyngeal arches are to be labelled as follows—the first, most cranial, the mandibular (M), the second, the hyoid (H), the third, the carotid (C), the fourth, the aortic (A) and the last, most caudal, the pulmonary (P). [ABSTRACT FROM AUTHOR]

Objective: Velopharyngeal dysfunction (VPD) associated with 22q11.2 deletion syndrome (22q11.2DS) has a complex etiology. This study had 3 aims: (1) assess differences in velopharyngeal and levator muscle configuration during rest versus sustained speech production (2) compare differences in velopharyngeal changes between children with and without 22q11.2DS (3) examine the relationship between adenoid thickness, pharyngeal depth, and velopharyngeal changes. Design: Cross-sectional. Methods: A total of 22 participants, 11 with 22q11.2DS and 11 controls with normal speech and velopharyngeal anatomy (ages 4-12 years), underwent nonsedated MRI at rest and during sustained /i/. Differences in velar and levator muscle contraction across the 2 different conditions were analyzed, using matched paired t -tests. Mean differences across participant groups were examined. Correlation analyses were also conducted. Results: When comparing differences between rest and sustained phoneme production (aim 1), significant (P <.05) differences were noted for all velar and levator muscle variables. For differences in velopharyngeal changes between children with and without 22q11.2DS (aim 2), VP ratio and effective VP ratio were noted to be significantly different. Pharyngeal depth and adenoid thickness were correlated with velar and levator muscle change measures and ratios (aim 3). Conclusion: Results from this study provide quantitative in vivo measurements of the contracted levator muscle and velum in young children with 22q11.2DS. Results demonstrated that VP ratio and EVP ratio are significantly different between children with and without 22q11.2DS and that pharyngeal depth is a strong clinical determinant of VPD in children with 22q11.2DS. [ABSTRACT FROM AUTHOR]

During aging, proteostasis capacity declines and distinct proteins become unstable and can accumulate as protein aggregates inside and outside of cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of cytoplasmic protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of 3 core protein quality control systems, namely chaperones, the proteasome, and macroautophagy, leads to lower levels of age-dependent protein aggregation in Caenorhabditis elegans pharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism that selectively targets newly synthesized proteins to suppress their aggregation and associated proteotoxicity. The safety mechanism relies on macroautophagy-independent lysosomal degradation and involves several previously uncharacterized components of the intracellular pathogen response (IPR). We propose that this protective mechanism engages an anti-aggregation machinery targeting aggregating proteins for lysosomal degradation. This study shows that during failure of core protein quality control in C. elegans, a specialized anti-aggregation mechanism relying on intracellular pathogen response factors and lysosomal mediated degradation is triggered, promoting tissue-specific resilience to age-dependent protein aggregation and its proteotoxicity. [ABSTRACT FROM AUTHOR]