Differences in velopharyngeal pressures during speech sound production in patients with unilateral cleft lip and palate (UCLP) and healthy individuals.

Background: During articulation the velopharynx needs to be opened and closed rapidly and a tight closure is needed. Based on the hypothesis that patients with cleft lip and palate (CLP) produce lower pressures in the velopharynx than healthy individuals, this study compared pressure profiles of the velopharyngeal closure during articulation of different sounds between healthy participants and patients with surgically closed unilateral CLP (UCLP) using high resolution manometry (HRM). Materials and methods: Ten healthy adult volunteers (group 1: 20-25.5 years) and ten patients with a non-syndromic surgically reconstructed UCLP (group 2: 19.1-26.9 years) were included in this study. Pressure profiles during the articulation of four sounds (/i:/, /s/, /ʃ/ and /n/) were measured by HRM. Maximum, minimum and average pressures, time intervals as well as detection of a previously described 3-phase-model were compared. Results: Both groups presented with similar pressure curves for each phoneme with regards to the phases described and pressure peaks, but differed in total pressures. An exception was noted for the sound /i:/, where a 3-phase-model could not be seen for most patients with UCLP. Differences in velopharynx pressures of 50% and more were found between the two groups. Maximum and average pressures in the production of the alveolar fricative reached statistical significance. Conclusions: It can be concluded that velopharyngeal pressures of patients with UCLP are not sufficient to eliminate nasal resonance or turbulence during articulation, especially for more complex sounds. These results support a general understanding of hypernasality during speech implying a (relative) velopharyngeal insufficiency.

Modification of velopharyngeal closure pressures during phonation by neuromuscular electrical stimulation in healthy individuals.

Introduction: Rhinophonia aperta may result from velopharyngeal insufficiency. Neuromuscular electrical stimulation (NMES) has been discussed in the context of muscle strengthening. The aim of this study was to evaluate in healthy subjects whether NMES can change the velopharyngeal closure pattern during phonation and increase muscle strength. Method: Eleven healthy adult volunteers (21-57 years) were included. Pressure profiles were measured by high resolution manometry (HRM): isolated sustained articulation of /a/ over 5 s (protocol 1), isolated NMES applied to soft palate above motor threshold (protocol 2) and combined articulation with NMES (protocol 3). Mean activation pressures (MeanAct), maximum pressures (Max), Area under curve (AUC) and type of velum reactions were compared. A statistical comparison of mean values of protocol 1 versus protocol 3 was carried out using the Wilcoxon signed rank test. Ordinally scaled parameters were analyzed by cross table. Results: MeanAct values measured: 17.15±20.69 mmHg (protocol 1), 34.59±25.75 mmHg (protocol 3) on average, Max: 37.86±49.17 mmHg (protocol 1), 87.24±59.53 mmHg (protocol 3) and AUC: 17.06±20.70 mmHg.s (protocol 1), 33.76±23.81 mmHg.s (protocol 3). Protocol 2 produced velum reactions on 32 occasions. These presented with MeanAct values of 13.58±12.40 mmHg, Max values of 56.14±53.14 mmHg and AUC values of 13.84±12.78 mmHg.s on average. Statistical analysis comparing protocol 1 and 3 showed more positive ranks for MeanAct, Max and AUC. This difference reached statistical significance (p=0.026) for maximum pressure values. Conclusions: NMES in combination with articulation results in a change of the velopharyngeal closure pattern with a pressure increase of around 200% in healthy individuals. This might be of therapeutic benefit for patients with velopharyngeal insufficiency.

Study protocol of the OrkA project: orofacial and communicative activation in old age- a cluster randomized prevention study in long-term care facilities in Lower Saxony, Germany.

BACKGROUND: The process of aging involves numerous changes in the body, influencing physical, mental, and emotional well-being. Age-related changes and degradation can impact various functions of the swallowing process and lead to delayed word retrieval. Individuals with limited linguistic stimulation may experience a more rapid decline in cognitive performance. Thus, this project explores a preventive training program targeting swallowing and linguistic-communicative skills, aimed at preserving the social participation of older individuals residing in nursing homes. METHODS: A preventive intervention program, combining orofaciopharyngeal and linguistic-communicative components, will be offered twice weekly over 12 weeks in long-term care facilities in the greater Hanover area. The program will aim at: (a) activating sensitive and motor skills in the orofaciopharyngeal area to counter age-related swallowing disorders, and (b) enhancing communicative abilities through semantic-lexical activation. A cluster randomized controlled trial will be conducted to investigate whether the intervention program improves swallowing skills in older adults. Additionally, a secondary analysis will explore the impact on language skills and social participation, as well as program acceptance. DISCUSSION: The results will provide valuable insight into the effectiveness of preventive measures addressing swallowing and speech issues in older individuals. TRIAL REGISTRATION: The trial was registered with DRKS (German register for clinical trials) in June 2023 (study ID: DRKS00031594) and the WHO International Clinical Trail Registry Platform (secondary register).

[Prevalence of mucosal injuries during flexible endoscopic evaluation of swallowing in the presence of a nasogastric tube]. / Prävalenz von Schleimhautläsionen bei Durchführung der transnasalen endoskopischen Dysphagiediagnostik und angelegter Nasogastralsonde.

BACKGROUND: The flexible endoscopic evaluation of swallowing (FEES) is an established low-risk examination method to assess the risk of penetration or aspiration in patients with dysphagia. FEES might be more difficult or of higher-risk when a nasogastric tube is in place. OBJECTIVE: This study aims to identify whether the prevalence of mucosal lesions is higher when the endoscopy is carried out with a nasogastric tube in place. Pre-existing mucosal lesions were also documented. METHODS: In a retrospective, monocentric study, a total of 918 FEES procedures routinely performed in hospitalized patients of a university hospital from January 2014 to March 2019 were evaluated. Mucosal lesions were identified and characterized for descriptive statistics. RESULTS: In the video material analysed here, no endoscopy-related injuries were identified. However, pre-existing mucosal lesions, which often occurred as multiple lesions, were detected in 48.6% of the endoscopies. Further analysis showed that these pre-existing lesions were not worsened by the endoscopy performed. CONCLUSION: The results demonstrate that transnasal flexible endoscopy is a safe, low-risk examination method, even in patients with a nasogastric tube. A very high number of pre-existing mucosal lesions were found, which is probably related to the previous insertion of the nasogastric tube. Due to the high number of pre-existing lesions, strategies should be developed to minimize injuries when placing nasogastric tubes.

A systematic review and metanalysis of questionnaires used for auditory processing screening and evaluation.

The recognition of Auditory Processing Disorder (APD) as a distinct clinical condition that impacts hearing capacity and mental health has gained attention. Although pure tone audiometry is the gold standard for assessing hearing, it inadequately reflects everyday hearing abilities, especially in challenging acoustic environments. Deficits in speech perception in noise, a key aspect of APD, have been linked to an increased risk of dementia. The World Health Organization emphasizes the need for evaluating central auditory function in cases of mild hearing loss and normal audiometry results. Specific questionnaires play a crucial role in documenting and quantifying the difficulties faced by individuals with APD. Validated questionnaires such as the Children's Auditory Processing Performance Scale, the Fisher's Auditory Problems Checklist, and the Auditory Processing Domains Questionnaire are available for children, while questionnaires for adults include items related to auditory functions associated with APD. This systematic review and meta-analysis identified six questionnaires used for screening and evaluating APD with a total of 783 participants across 12 studies. The questionnaires exhibited differences in domains evaluated, scoring methods, and evaluation of listening in quiet and noise. Meta-analysis results demonstrated that individuals with APD consistently exhibited worse scores compared to healthy controls across all questionnaires. Additionally, comparisons with clinical control groups showed varying results. The study highlights (i) the importance of standardized questionnaires in identifying and assessing APD, aiding in its diagnosis and management, and (ii) the need to use sub-scores as well as overall scores of questionnaires to elaborate on specific hearing and listening situations. There is a need to develop more APD specific questionnaires for the adult population as well as for more focused research on APD diagnosed individuals to further establish the validity and reliability of these questionnaires.

Phonation-induced Upper Esophageal Sphincter Contraction Caused by Different Phonation Types.

INTRODUCTION: The upper esophageal sphincter (UES) has been reported to show activity during phonation. As it is still unknown whether the phonation-induced UES contraction represents a reflex or a simultaneous activation phenomenon, i.e. co-innervation, this study aims to investigate and characterize the phonation-induced contraction of the UES in healthy individuals by analyzing the influence of various phonation tasks on pressure parameters of the UES. METHODS: Twenty-five healthy volunteers produced the German neutral vowel [ə] in five different phonation tasks (modal voice, whispering, voiceless speech, creaky voice, and whispery voice). Simultaneously, they underwent high resolution manometry and electroglottography for measurement of pressure parameters in the region of the UES and latencies between larynx and UES activation. RESULTS: During all types of phonation, the maximum pressures of the UES increased significantly (maximum pressure increases of 72%-132%). With regard to mean pressures this was valid for modal voice and whispering (mean pressure increases of 20%-25%). Differences concerning total pressure changes reached statistical significance when comparing whispering and voiceless speech as well as whispery voice. However, differences concerning the total pressure change between modal voices on the one hand and voiceless speech and whispery voice on the other hand turned out to be small. The averaged time delay between larynx and UES activation ranged from approximately -15 ms (whispery voice) to +15 ms (whispering). CONCLUSION: A phonation induced pressure increase of the UES was confirmed in this study and did exist for different types of phonation. The extent of total pressure changes in the UES increases in relation with laryngeal muscle activity necessary for the phonation type. Next to varying effects of different types of phonation on UES activation, very short latencies indicate that a phonation induced contraction of the UES exists most likely due to co-innervation of UES and laryngeal muscles by the vagus nerve.

Review of the effectiveness of neuromuscular electrical stimulation in the treatment of dysphagia - an update.

Background: Neuromuscular electrical stimulation (NMES) has been used as a treatment option in the therapy of dysphagia for several years. In a previous review of the literature, it was concluded that NMES might be a valuable adjunct in patients with dysphagia and in patients with vocal fold paresis. However, due to different stimulation protocols, electrode positioning and various underlying pathological conditions, it was difficult to compare the studies which were identified and it was concluded that more empirical data is needed to fully understand the benefits provided by NMES. The purpose of this systematic review is, therefore, to evaluate recent studies regarding a potential effectiveness of transcutaneous NMES applied to the anterior neck as a treatment for dysphagia considering these different aspects. Method: For this systematic review, a selective literature research in PubMed has been carried out on 5th May 2021 using the terms electrical stimulation AND dysphagia and screened for inclusion criteria by two reviewers in Rayyan. The search resulted in 62 hits. Results: Studies were excluded due to their publication language; because they did not meet inclusion criteria; because the topical focus was a different one; or because they did not qualify as level 2 studies. Eighteen studies were identified with varying patient groups, stimulation protocols, electrode placement and therapy settings. However, 16 studies have reported of beneficial outcomes in relation with NMES. Discussion: The purpose of this systematic review was to evaluate the most recent studies regarding a potential effectiveness of NMES as a treatment for oropharyngeal dysphagia considering different aspects. It could generally be concluded that there is a considerable amount of level 2 studies which suggest that NMES is an effective treatment option, especially when combined with TDT for patients with dysphagia after stroke and patients with Parkinson's disease, or with different kinds of brain injuries. Further research is still necessary in order to clarify which stimulation protocols, parameters and therapy settings are most beneficial for certain patient groups and degrees of impairment.

Studying effects of neuromuscular electrostimulation therapy in patients with dysphagia: which pitfalls may occur? A translational phase I study.

Background: Previous results of clinical studies suggest that neuromuscular electrostimulation (NMES) therapy, especially in combination with traditional dysphagia therapy, may be helpful in patients with neurogenic swallowing disorders. In these studies, repetitive application of a rectangular current impulse was used to increase muscle strength of the anterior neck. However, according to sports physiological findings, an increase of muscle strength can be better achieved by using different NMES stimulation protocols, e.g. KOTS. The aim of the translational investigator-initiated, non-commercial pilot study presented here was to provide data and insights for the planning of subsequent phase II and III studies on the effectiveness of such stimulation protocols in dysphagia therapy. Methods: 30 post-stroke patients with oropharyngeal dysphagia were included in this prospective pilot study and randomly allocated to either neuromuscular electrostimulation (NMES) or sham stimulation in combination with traditional dysphagia therapy (TDT), a pre- and post-therapeutic fiberoptic-endoscopic evaluation of swallowing (FEES) with the Dysphagia Outcome and Severity Scale (DOSS) (primary outcome measure), Secretion Scale by Murray, Penetration and Aspiration Scale (PAS) and throat clearance (TC) abilities. Recruitment rate, interrater comparison and number of relevant adverse events were recorded as metadata. Results: Despite a recruiting time of over 24 months, only twelve patients could be included. Moreover, clinical data indicated a significant variance of clinical pictures. Significant differences in verum versus sham therapy were not observed. DOSS values in both study groups showed general improvements at the end of the trial. Interrater reliability was low. No adverse events were reported. Discussion: When planning further dysphagia therapy studies, it must be taken into account that it can be problematic to recruit sufficiently large study collectives within an appropriate study period. This is especially important since a possible additional benefit of NMES to TDT is probably rather small or may only occur in certain deficit constellations. The low interrater reliability observed here must be improved by appropriate training measures. Fortunately, no relevant undesirable side effects occurred. This could have a positive effect on the acceptance of volunteers to participate in the study.

Influence of Acid Swallows on the Dynamics of the Upper Esophageal Sphincter.

Mechanisms of the upper esophageal sphincter (UES) when exposed to acid are still incompletely understood. The presented work investigated the reaction of the UES to acid exposure during swallowing. Ten healthy individuals swallowed ten 2 ml neutral water boli of pH 7, followed by 10 swallows each of different levels of acidity (pH 1.8, pH 3 and pH 5). Effects were analyzed by high-resolution manometry (HRM) for the primary parameter Restitution Time, as well as Resting Pressures, maximal, minimal pressures and time intervals. Restitution Times measured mean values of 12.67 s (SD ± 7.03 s) for pH 1.8, pH 7 = 8.69 s (SD ± 2.72 s), pH 3 = 7.56 s (SD ± 2.23 s) and pH 5 = 7.29 s (SD ± 2.55 s), showing prolonged Restitution Times in the UES when exposed to strong bolus acidity. This difference was significant towards the neutral bolus, but also to less acidic boli (pH 5: p = 0.006, pH 3: p = 0.009, pH 7: p = 0.038). Considerable differences of mean values were found for Post-Swallow Maximum and Period of Sphincter Activity. Also, Pre-Swallow Maximum values were found to be highest with the strongest acid. Relaxation Times showed a slight trend of prolongation for the highest bolus acidity. Prolonged Restitution Times may represent a reflexive protective mechanism triggered by receptors in the pharyngeal mucosa or the UES preventing regurgitation of acid into the pharynx and larynx, besides representing ongoing attempts of acid clearance. Exposure to high levels of acidity by a swallowed bolus does influence UES functions during swallowing.

Upper Esophageal Sphincter Response to Laryngeal Adductor Reflex Elicitation in Humans.

OBJECTIVE: The laryngeal adductor reflex (LAR) is an important mechanism to secure the airways from potential foreign body aspiration. An involvement of the upper esophageal sphincter (UES) in terms of a laryngo-UES contractile reflex has been identified after laryngeal mucosa stimulation. However, the LAR-UES relationship has not yet been fully explained. This study aimed to determine the magnitude, latency, and occurrence rate of the UES pressure response when the LAR is triggered in order to elucidate the functional relationship between the larynx and the UES. METHODS: This prospective study included seven healthy volunteers (5 female, 2 male, age 22-34 years). Laryngeal penetration was simulated by eliciting the LAR 20 times in each individual by applying water-based microdroplets onto the laryngeal mucosa. UES pressures were measured simultaneously using high-resolution manometry. RESULTS: Two distinct pressure phases (P1, P2) associated with the LAR were identified. P1 corresponded with a short-term UES pressure decrease in two subjects and a pressure increase in five subjects occurring 200 to 500 ms after the stimulus. In P2, all subjects experienced an increase in UES pressure with a latency time of approximately 800 to 1700 ms and an average of 40 to 90 mmHg above the UES resting tone. CONCLUSION: Foreign bodies penetrating the laryngeal inlet lead to a reflex contraction of the UES. Phase P1 could be a result of vocal fold activity caused by the LAR, leading to pressure changes in the UES. The constriction during P2 could strengthen the barrier function of the UES in preparation to a subsequent cough that may be triggered to clear the airways. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1778-E1784, 2021.

Three-dimensional analysis of the velopharyngeal region in patients with cleft palate and healthy individuals.

PURPOSE: This study aims to attain metric data of the velopharyngeal dimensions of healthy subjects as well as patients with velopharyngeal insufficiency using the example of cleft and lip palate (CLP) in order to determine possible differences in the volumes of both groups. METHODS: Volumes and distances of velopharyngeal areas were analyzed retrospectively using cone beam computed tomography data sets (n = 60). Group 1 included healthy patients receiving dental implants (n = 31). Group 2 was represented by patients with surgically closed cleft lip and palate (n = 29). RESULTS: Biggest differences among mean values of both groups were found for: minimum axial area (p = 0.000), airway area caudal (p = 0.000), distance between posterior nasal spine and posterior pharyngeal wall (PPW) (p = 0.014), mean distance between velum and PPW (p = 0.000), length of PPW (p = 0.000) and length of anterior pharyngeal wall (p = 0.000). CONCLUSION: Differences in the shape and geometry of the velopharyngeal area in subjects with a regular velopharyngeal structure and function and patients with cleft palate do exist. The significant differences found here can be categorized into two groups: one reflects distances between the anterior and posterior pharynx, presenting longer distances for patients with CLP. The second significant difference regards values of length in cranio-caudal direction, which is longer in healthy subjects. With regards to these values, one could conclude, that even though total volumes of both groups did not differ in size, group 1 shows three-dimensional velopharyngeal shapes that are longer and narrower, whereas shapes of patients of group 2 tend to be wider and shorter in general.

Clinical predictors of adverse cardiovascular events for acute pediatric drug exposures.

Context: Risk factors for adverse cardiovascular events (ACVE) from drug exposures have been well-characterized in adults but not studied in children. The objective of the present study is to describe the incidence, characteristics, and risk factors for in-hospital ACVEs among pediatric emergency department (ED) patients with acute drug exposures.Methods: This is a prospective cohort design evaluating patients in the Toxicology Investigators Consortium (ToxIC) Registry. Pediatric patients (age <18 years) who were evaluated at the bedside by a medical toxicologist for a suspected acute drug exposure were included. The primary outcome was in-hospital ACVE (myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest). The secondary outcome was in-hospital death. Multiple logistic regression analyses were performed to examine novel clinical risk factors and extrapolate adult risk factors (bicarbonate <20 mEq/L; QTc ≥500 ms), for the primary/secondary outcomes.Results: Among the 13,097 patients (58.5% female), there were 278 in-hospital ACVEs (2.1%) and 39 in-hospital deaths (0.3%). Age and drug class of exposure (specifically opioids and cardiovascular drugs) were independently associated with ACVE. Compared with adolescents, children under 2 years old (OR: 0.41, 95% CI: 0.21-0.80), ages 2-6 (OR: 0.37, 95% CI: 0.21-0.80), and ages 7-12 (OR: 0.51, 95% CI: 0.27-0.95) were significantly less likely to experience an ACVE. Serum bicarbonate concentration <20 mEq/L (OR: 2.31, 95% CI: 1.48-3.60) and QTc ≥ 500 ms (OR: 2.83, 95% CI: 1.67-4.79) were independently associated with ACVE.Conclusion: Previously derived clinical predictors of ACVE from an adult drug overdose population were successfully extrapolated to this pediatric population. Novel associations with ACVE and death included adolescent age and opioid drug exposures. In the midst of the opioid crisis, these findings urgently warrant further investigation to combat adolescent opioid overdose morbidity and mortality.

Euclidean distances of laryngopharyngeal structures obtained from CT data for preclinical development of laryngoscopic devices.

PURPOSE: This study aims to determine Euclidean distances between landmark structures in the larynx and pharynx to optimize endoscope shaft designs with regard to gentle and patient-oriented handling. METHODS: Four Euclidean distances between landmarks in the larynx and pharynx were analyzed based on CT data of 66 patients. Distance (1): labium inferius oris-posterior pharyngeal wall at the cervical vertebra C1 (atlas), anterior edge of the tuberculum anterius atlantis. Distance (2): posterior pharyngeal wall adjacent to C1-entrance of pyriform sinus. Distance (3): inferior edge of the uvula-superior edge of the epiglottis. Distance (4): base of the vallecula-posterior pharyngeal wall. The minimum angular field of view α required to observe the glottis with a rigid transoral laryngoscope was derived trigonometrically from distances (2) and (4). RESULTS: Average Euclidean distances measured: Distance (1): 90.7 mm ± 6.9 mm in men and 86.9 mm ± 5.9 mm in women. (2): 73.7 mm ± 13.4 mm and 56.2 mm ± 7.6 mm. (3): 25.2 mm ± 8.6 mm and 18.5 mm ± 6.8 mm. (4): 20.8 mm ± 4.6 mm and 16.5 mm ± 3.4 mm. α: 16.0° ± 3.9° and 16.6 ± 4.3°. CONCLUSIONS: As expected, statistically significant sex-related differences could be observed for distances (1)-(4). The results indicate that the length of transoral laryngoscopes should not be below 110 mm and that a minimum angular field of view of α = 17° is required to fully observe the laryngeal inlet.

Swallowing Function After Continuous Neuromuscular Electrical Stimulation of the Submandibular Region Evaluated by High-Resolution Manometry.

Although neuromuscular electrical stimulation (NMES) is increasingly used in dysphagia therapy, patient responses to NMES are inconsistent and conflicting results have been reported. This, together with a lack of information about the effects of NEMS on the swallowing process, has led to an ongoing debate about its impact on swallowing function. In order to address this, we set out to (i) collect baseline information on the physiological effects of NMES on the complex pharyngeal phase of swallowing and (ii) to compare two different stimulation protocols. In doing so, we provide information useful for evaluating the therapeutic effectiveness of NMES on the swallowing process. In a prospective study, 29 healthy participants performed water swallows after receiving continuous NMES for 10 min. The stimulus was applied in the submandibular region using one of two different stimulation protocols: low-frequency stimulation (LFS) and mid-frequency stimulation (MFS). Swallowing parameters of the pharynx and UES were measured using high-resolution manometry. Maximum tongue base pressure increased by 8.4% following stimulation with the MFS protocol. Changes in UES function were not found. LFS stimulation did not result in any significant changes in the parameters examined. The MFS protocol enhances tongue base retraction during swallowing in healthy volunteers. The magnitude of the effect, however, was small, possibly due to the ability of healthy subjects to compensate for external influences, such as NMES, and may actually prove to be much greater in patients with diminished tongue base retraction. Thus, further studies are needed to determine whether a similar effect is also achievable in dysphagic patients with impaired bolus propulsion, possibly allowing MFS stimulation of the tongue base region to be used as an additional treatment tool.

Calculation of upper esophageal sphincter restitution time from high resolution manometry data using machine learning.

OBJECTIVE: After swallowing, the upper esophageal sphincter (UES) needs a certain amount of time to return from maximum pressure to the resting condition. Disturbances of sphincter function not only during the swallowing process but also in this phase of pressure restitution may lead to globus sensation or dysphagia. Since UES pressures do not decrease in a linear or asymptotic manner, it is difficult to determine the exact time when the resting pressure is reached, even when using high resolution manometry (HRM). To overcome this problem a Machine Learning model was established to objectively determine the UES restitution time (RT) and moreover to collect physiological data on sphincter function after swallowing. METHODS AND MATERIAL: HRM-data of 15 healthy participants performing 10 swallows each were included. After manual annotation of the RT interval by two swallowing experts, data were transferred to the Machine Learning model, which applied a sequence labeling modeling approach based on logistic regression to learn and objectivize the characteristics of all swallows. Individually computed RT values were then compared with the annotated values. RESULTS: Estimates of the RT were generated by the Machine Learning model for all 150 swallows. When annotated by swallowing experts mean RT of 11.16s±5.7 (SD) and 10.04s±5.74 were determined respectively, compared to model-generated values from 8.91s±3.71 to 10.87s±4.68 depending on model selection. The correlation score for the annotated RT of both examiners was 0.76 and 0.63 to 0.68 for comparison of model predicted values. CONCLUSIONS: Restitution time represents an important physiologic swallowing parameter not previously considered in HRM-studies of the UES, especially since disturbances of UES restitution may increase the risk of aspiration. The data presented here show that it takes approximately 9 to 11s for the UES to come to rest after swallowing. Based on maximal RT values, we demonstrate that an interval of 25-30s in between swallows is necessary until the next swallow is initiated. This should be considered in any further HRM-studies designed to evaluate the characteristics of individual swallows. The calculation model enables a quick and reproducible determination of the time it takes for the UES to come to rest after swallowing (RT). The results of the calculation are partially independent of the input of the investigator. Adding more swallows and integrating additional parameters will improve the Machine Leaning model in the future. By applying similar models to other swallowing parameters of the pharynx and UES, such as the relaxation time of the UES or the activity time during swallowing, a complete automatic evaluation of HRM-data of a swallow should be possible.

Impact of neuromuscular electrical stimulation on upper esophageal sphincter dynamics: a high-resolution manometry study.

OBJECTIVES: Beside traditional dysphagia therapy, neuromuscular electrical stimulation (NMES) has been proposed to treat patients with dysphagia. Considering the complexity of the nerve-muscle interaction during swallowing, the underlying physiology of NMES remains unclear. Here, we addressed the question of whether NMES can modify upper esophageal sphincter (UES) dynamics. METHODS: In a prospective study, 26 healthy volunteers performed water swallows with and without NMES. The stimulus was applied in a participant- and operator-initiated stimulation above, near, and below the motor threshold. Swallowing parameters were measured using high-resolution manometry. RESULTS: The UES relaxation time was found to be extended by 10%, indicating a modification in UES dynamics. CONCLUSIONS: The chosen NMES paradigm influenced the involuntary swallowing phase by extending relaxation time, providing more time for bolus passage into the esophagus. Future studies will have to evaluate if this effect can be found in patients with dysphagia and whether it is beneficial for treatment.

Electrical stimulation in treatment of pharyngolaryngeal dysfunctions.

OBJECTIVE: Neuromuscular electrical stimulation (NMES) has been proposed in the treatment of laryngopharyngeal dysfunctions (dysphonia, dyspnoea, dysphagia) for more than 40 years. Several studies have investigated possible therapeutic effects. Some researchers described favourable results, whereas others did not find relevant benefits. This article aims to review available studies to give an overview regarding the current state of knowledge. METHODS: We conducted a selective literature search using PubMed. RESULTS: In total, 356 papers were identified: 6 case reports, 11 reviews, 43 prospective clinical trials and 3 retrospective trials were found. CONCLUSION: Due to different stimulation protocols, electrode positioning and various underlying pathological conditions, summarizing the present studies appears to be difficult. However, there is evidence that NMES is a valuable adjunct in patients with dysphagia and in patients with vocal fold paresis. Nevertheless, more empirical data is needed to fully understand the benefits provided by NMES. Further research suggestions are put forward.

IFN-gamma-receptor signaling ameliorates transplant vasculopathy through attenuation of CD8+ T-cell-mediated injury of vascular endothelial cells.

Occlusive transplant vasculopathy (TV) is the major cause for chronic graft rejection. Since endothelial cells (EC) are the first graft cells encountered by activated host lymphocytes, it is important to delineate the molecular mechanisms that coordinate the interaction of EC with activated T cells. Here, the interaction of CD8(+) T cells with Ag-presenting EC in vivo was examined using a transgenic heart transplantation model with beta-galactosidase (beta-gal) expression exclusively in EC (Tie2-LacZ hearts). We found that priming with beta-gal peptide-loaded DC failed to generate a strong systemic IFN-gamma response, but elicited pronounced TV in both IFN-gamma receptor (IFNGR)-competent, and ifngr(-/-) Tie2-LacZ hearts. In contrast, stimulation of EC-specific CD8(+) T cells with beta-gal-recombinant mouse cytomegalovirus (MCMV-LacZ) in recipients of ifngr(+/+) Tie2-LacZ hearts did not precipitate significant TV. However, MCMV-LacZ infection of recipients of ifngr(-/-) Tie2-LacZ hearts led to massive activation of beta-gal-specific CD8 T cells, and led to development of fulminant TV. Further analyses revealed that the strong systemic IFN-gamma "storm" associated with MCMV infection induced upregulation of programmed death-1 ligand 1 (PD-L1) on EC, and subsequent attenuation of programmed death-1 (PD-1)-expressing EC-specific CD8(+) T cells. Thus, IFNGR signaling in ECs activates a potent peripheral negative feedback circuit that protects vascularized grafts from occlusive TV.

Immunopathological basis of lymphocytic choriomeningitis virus-induced chorioretinitis and keratitis.

The infection of humans with the rodent-borne lymphocytic choriomeningitis virus (LCMV) can lead to central nervous system disease in adults or severe neurological disease with hydrocephalus and chorioretinitis in children infected congenitally. Although LCMV-induced meningitis and encephalitis have been studied extensively, the immunopathological mechanisms underlying LCMV infection-associated ocular disease remain elusive. We report here that the intraocular administration of the neurotropic LCMV strain Armstrong (Arm) elicited pronounced chorioretinitis and keratitis and that infection with the more viscerotropic strains WE and Docile precipitated less severe immunopathological ocular disease. Time course analyses revealed that LCMV Arm infection of the uvea and neuroretina led to monophasic chorioretinitis which peaked between days 7 and 12 after infection. Analyses of T-cell-deficient mouse strains showed that LCMV-mediated ocular disease was strictly dependent on the presence of virus-specific CD8(+) T cells and that the contribution of CD4(+) T cells was negligible. Whereas the topical application of immunosuppressive agents did not prevent the development of chorioretinitis, passive immunization with hyperimmune sera partially prevented retinal and corneal damage. Likewise, mice displaying preexisting LCMV-specific T-cell responses were protected against LCMV-induced ocular disease. Thus, antibody- and/or T-cell-based vaccination protocols could be employed as preventive strategies against LCMV-mediated chorioretinitis.