Oral conditions are associated with salt taste disability among American adults.

AIM: To explore the association between oral conditions and their interaction with salt taste disability among American adults. METHODS: Data from the 2013-2014 NHANES cycle were used (n = 2373). The exposures were periodontitis, defined by the 2017 EFP-AAP classification, dental caries, missing teeth, and edentulism, as per the DMF-T index, and xerostomia. The outcome was salt taste disability, objectively assessed. Covariates included sex, age, educational level, poverty index, obesity, diabetes, smoking, alcohol consumption, and medications related to mouth dryness. Weighted multivariable logistic regression modeling was used to evaluate the relationship between oral conditions and their interaction and salt taste disability. RESULTS: Participants who reported xerostomia were more likely to have salt taste disability (OR 2.42; 95%CI 1.44-4.07), especially those older than 60 years (OR 3.63; 95%CI 1.72-7.63). Among participants aged 40-59, xerostomia increased the chance of salt taste disability; however, the confidence interval included the null value. The interactions between xerostomia and edentulism increased the chance of salt taste disability. CONCLUSION: Oral conditions seem to influence the ability to taste salt. Dental professionals may help identify individuals with taste alterations and raise their awareness of the risk of systemic diseases that require the reduction of salt intake.

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Zebras in Adult Dysphagia Workup: Where to Look When You Think You Have Looked Everywhere.

While many patients who present with dysphagia have a clinically identifiable cause of dysphagia, the etiology of swallowing difficulty is oftentimes a diagnostic enigma. The aim of this article is to review possible etiologies of dysphagia when objective evidence of dysphagia is lacking. Included in this discussion are cricopharyngeal spasm, retrograde cricopharyngeal dysfunction, muscle tension dysphagia, dysphagia secondary to medications, and functional dysphagia.

Efficacy of natural enzymes mouthwash: a randomised controlled trial.

OBJECTIVES: Natural enzymes mouthwash has been proposed as salivary substitutes to treat xerostomia. This study aims to evaluate the efficacy of the mouthwash to treat xerostomia. MATERIALS AND METHODS: A double-blind, parallel group randomised control clinical trial involving N = 49 adult participants with xerostomia was carried out. Intervention group received natural enzymes moisturising mouthwash (with active ingredients lactoferrin, lysozyme, lactoperoxidase and glucose oxidase); while control group received benzydamine mouthwash. Mouthwashes were repacked, labelled with specific code, and were given to participants by third-party. Subjects were instructed to rinse with the mouthwash 4 times per day at a specific period, for 2 weeks. Symptoms of xerostomia were assessed using Xerostomia Inventory at day 0 and 14; together with the assessment of Clinical Oral Dryness Score (CODS), and measurement of resting and stimulated salivary flow rate. RESULTS: 48 participants completed the clinical follow-up, and n = 1 had lost of follow-up. From the 48 participants, n = 23 received natural enzymes mouthwash, while n = 25 received benzydamine mouthwash. Intervention group achieved reduction in symptoms of xerostomia from baseline. Intervention group also showed significantly better improvements in the cognitive perception of dry mouth and oromotor function such as chewing, swallowing and speech of the participants; and reduction in waking up at night to drink water (p < 0.05). The CODS and resting salivary flow rate were also significantly improved in intervention group (p < 0.05). CONCLUSION: Use of natural enzymes mouthwash improved signs and symptoms of xerostomia. CLINICAL RELEVANCE: Natural enzymes mouthwash is potentially effective to treat xerostomia, well-tolerated and safe to be used by xerostomia patients. CLINICAL TRIAL REGISTRATION NUMBER: This study was retrospectively registered in ClinicalTrials.gov ID NCT05640362 on 7 December 2022.

Does lower dose pilocarpine have a role in radiation-induced xerostomia in the modern radiotherapy era? A single-center experience based on patient-reported outcome measures.

PURPOSE: This study aims to investigate the efficacy of lower dose pilocarpine in alleviating late dry mouth symptoms in head and neck cancer patients received radiotherapy. METHODS: Eighteen head and neck cancer patients experiencing persistent dry mouth were enrolled in this study. All participants started pilocarpine treatment a median of 6 months post-radiotherapy. Initially, patients received pilocarpine at 5 mg/day, with a gradual increase to the recommended dose of 15 mg/day. A Patient-Reported Outcome Measurement (PROMs) questionnaire assessed symptoms' severity related to hyposalivation. RESULTS: All patients reported symptomatic dry mouth above grade 2 before starting the medication. Pilocarpine treatment continued based on patients' self-assessment, with a median duration of 12 months (range, 3-36 months). The median daily maintenance dose was 10 mg (range, 5 to 20 mg). Total PROMs scores significantly decreased following medication, from 13 points (range 7-18 points) to 7 points (range 4-13 points) (p = 0.001). Significant improvements were observed in questions related to dry mouth (p < 0.001), water intake during eating (p = 0.01), carrying water (p = 0.01), taste (p < 0.001), and water intake during speech (p < 0.001). Initial and maintenance doses of pilocarpine were lower, and the duration of pilocarpine usage was shorter in patients treated with intensity-modulated radiation therapy compared to conformal radiotherapy (12 months vs. 25 months, p = 0.04). CONCLUSION: Pilocarpine may be considered at doses lower for late-term dry mouth. With modern radiotherapy techniques effectively preserving the parotid gland, short-term use may be recommended in these patients. Future studies may enhance the development of a more robust patient selection criteria model.

Long-Term Outcome Following Treatment With Allogeneic Mesenchymal Stem/Stromal Cells for Radiation-Induced Hyposalivation and Xerostomia.

BACKGROUND: Adipose-derived mesenchymal stem/stromal cells (ASCs) are proposed as a new xerostomia treatment. The study evaluated the long-term safety and effectiveness of allogeneic ASCs in radiation-induced xerostomia among patients with previous oropharyngeal cancer. METHODS: This study constitutes 3-year follow-up on the original 10 patients who received allogeneic ASCs injections to the submandibular and parotid glands as part of the MESRIX-II trial. The MESRIX-II trial included the preliminary 4-month follow-up. The primary endpoint was long-term safety. Secondary endpoints were effectiveness evaluated by changes in salivary flow rate and patient-reported outcomes (PROs). Immune response was evaluated by assessing the development of donor-specific antibodies (DSA). FINDINGS: All 10 MESRIX-II patients completed the long-term follow-up (ie, no missing data). During the long-term follow-up, 2 patients encountered a significant adverse event, which was determined to be unrelated to the treatment. No DSAs were detectable at 3 years. The stimulated salivary flow rate increased significantly from an average of 0.66 mL/minute at baseline to 0.86 mL/minute at follow-up, corresponding to an increase of 0.20 [95% CI 0.08 to 0.30] mL/minute, or approximately 30%. Among the PROs, sticky saliva symptoms were reduced, with a -20.0 [95% CI -37.3 to -2.7] units. INTERPRETATION: In conclusion, this study is the first to present long-term follow-up outcomes of allogeneic ASC treatment as a therapeutic option for radiation-induced xerostomia. The study found that ASC treatment appears safe, and there were no indications of adverse immune responses at the 3-year follow-up. Further studies are warranted to evaluate the findings in larger settings.

Dysregulated Ca2+ signaling, fluid secretion, and mitochondrial function in a mouse model of early Sjögren's syndrome.

Saliva is essential for oral health. The molecular mechanisms leading to physiological fluid secretion are established, but factors that underlie secretory hypofunction, specifically related to the autoimmune disease Sjögren's syndrome (SS) are not fully understood. SS-like disease was induced by the treatment with 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA), an activator of the stimulator of the interferon gene (STING) pathway. This mouse model mimics exposure to foreign cytoplasmic ribonucleotides occurring following viral and bacterial infection and thought to be an initiating event in SS. Neurotransmitter-stimulated increases in cytoplasmic [Ca2+] are central to stimulating fluid secretion, primarily by increasing the activity of the Ca2+-activated Cl- channel, TMEM16a. Paradoxically, in DMXAA-treated mice in vivo imaging demonstrated that neural-stimulation resulted in greatly enhanced Ca2+ levels when a significant reduction in fluid secretion was observed. Notably, in the disease model, the spatiotemporal characteristics of the Ca2+ signals were altered to result in global rather than largely apically confined Ca2+ rises observed physiologically. Notwithstanding the augmented Ca2+ signals, muscarinic stimulation resulted in reduced activation of TMEM16a, although there were no changes in channel abundance or absolute sensitivity to Ca2+. However, super-resolution microscopy revealed a disruption in the localization of Inositol 1,4,5-trisphosphate receptor Ca2+ release channels in relation to TMEM16a. Appropriate Ca2+ signaling is also pivotal for mitochondrial morphology and bioenergetics and secretion is an energetically expensive process. Disrupted mitochondrial morphology, a depolarized mitochondrial membrane potential, and reduced oxygen consumption rate were observed in DMXAA-treated animals compared to control animals. We report that early in SS disease, dysregulated Ca2+ signals lead to decreased fluid secretion and disrupted mitochondrial function contributing to salivary gland hypofunction and likely the progression of SS disease.

Oral health status, related behaviours and perceived stress in xerostomia, Sicca and Sjögren's syndromes patients - a cross-sectional study.

BACKGROUND: Mouth dryness increases the risk of some oral health-related conditions. Furthermore, it is unclear if patients with dry mouth engage in appropriate oral health-related behaviours. The study examined oral health, related behaviours, and perceived stress in dry-mouth patients and compared them to matched controls without mouth dryness. METHODS: Information about 182 dry-mouth patients and 302 age- and sex-matched subjects was retrieved. Three dry mouth groups: xerostomia, Sicca syndrome and Sjögren's syndrome, were formed based on patient self-reported and objectively assessed symptoms. The World Health Organization's Oral Health for Adults and Perceived Stress Scale (PSS-10) questionnaires inquired about sociodemographic characteristics, oral health-related behaviours, and self-perceived stress. Clinical oral health assessments included: caries experience measured as total numbers of decayed (DS), missing (MS), filled surfaces (FS), number of remaining teeth, erosive tooth wear and extent of periodontal pocketing. Data were analyzed using bivariate and multivariable tests. RESULTS: The dry-mouth participants had higher mean (SD) DMFS scores than their matched controls: xerostomia patients vs. controls: 74.6 (34.4) and 66.3 (35.4), Sicca syndrome patients vs. controls: 88.3 (34.0) and 70.1 (33.9), and Sjögren's syndrome patients vs. controls: 95.7 (31.5) and 74 (33.2). In comparison to controls, individuals with Sicca and patients with Sjögren's syndromes had lower mean (SD) number of remaining teeth, 15.9 (10.1) vs. 21.7 (8.4) and 13.8 (10.0) vs. 20.1 (9.2), and a lower mean (SD) extent of periodontal pocketing, 20.7 (28.6) vs. 41.1 (31.0), and 21.2 (24.1) vs. 34.8 (34.2), respectively. Xerostomia, Sicca syndrome and Sjögren's syndrome patients had higher odds of using fluoridated toothpaste; OR 1.8 (95%CI 1.1-2.9), OR 5.6 (95%CI 1.7-18.3) and OR 6.9 (95%CI 2.2-21.3), respectively. Participants with Sjögren's syndrome had lower odds of the last dental visit being within the last year; OR 0.2 (95%CI 0.1-0.8). CONCLUSIONS: Dry-mouth patients had higher caries experience and fewer teeth than comparison groups but a lower extent of periodontal pocketing. Even though more participants with dry mouth used fluoridated toothpastes, their oral health-related behaviours were not optimal.

Radiation-induced xerostomia is related to stem cell dose-dependent reduction of saliva production.

BACKGROUND AND PURPOSE: Previous studies have shown that the mean dose to the parotid gland stem cell rich regions (Dmean,SCR) is the strongest dosimetric predictor for the risk of patient-reported daytime xerostomia. This study aimed to test whether the relationship between patient-reported xerostomia and Dmean,SCR is explained by a dose-dependent reduction of saliva production. MATERIAL/METHODS: In 570 head and neck cancer patients treated with definitive radiation therapy (RT), flow from the parotid (FLOWPAR) and submandibular/sublingual glands (FLOWSMSL) and patient-reported daytime (XERDAY) and nighttime xerostomia (XERNIGHT) were prospectively measured before, and at 6 and 12 months after RT. Using linear mixed effect models, the relations of mean dose to the parotid glands (Dmean,par), Dmean,SCR, non-SCR parotid gland tissue (Dmean,non-SCR), submandibular glands (Dmean,sub) and oral cavity (Dmean,oral) with salivary flow and xerostomia were analyzed while correcting for known confounders. RESULTS: Dmean,SCR proved to be responsible for the effect of Dmean,par on FLOWPAR (p≤0.03), while Dmean,non-SCR did not affect FLOWPAR (p≥0.11). To illustrate, increasing Dmean,SCR by 10 Gy at fixed Dmean,non-SCR, reduced FLOWPAR by 0.02 (25%) after RT. However, if the opposite happened, no change in FLOWPAR was observed (0.00 ml/min [4%]). As expected, Dmean,sub was significantly associated with FLOWSMSL (p<0.001). For example, increasing Dmean,sub by 10 Gy, reduced FLOWSMSL with 0.07 ml/min (26%) after RT. Xerostomia scores were also affected by dose to the salivary glands. Dmean,SCR and Dmean,oral were associated with higher XERDAY scores (p≤0.05), while Dmean,sub increased XERNIGHT scores (p=0.01). For example, an increase of 10 Gy in Dmean,SCR raised XERDAY scores with 2.13 (5%) points after RT, while an additional 10 Gy in Dmean,subs increased XERNIGHT scores with 2.20 points (6%) after RT. Salivary flow was not only associated with radiation dose, but also with xerostomia scores in line with the salivary glands' functions, i.e., FLOWPAR only influenced XERDAY (p<0.001, 10.92 points lower XERDAY per 1 ml/min saliva), while FLOWSMSL affected XERDAY and XERNIGHT (p≤0.004, 6.69 and 5.74 points lower XERDAY and XERNIGHT, respectively, per 1 ml/min saliva). Therefore, the observed relations between dose and xerostomia were corrected for salivary flow. As hypothesized, Dmean,SCR only increased XERDAY scores via reducing FLOWPAR; whereas the effects of Dmean,oral on XERDAY and of Dmean,sub on XERNIGHT were independent of salivary flow. CONCLUSION: Higher SCR region dose reduced parotid gland saliva production, subsequently resulting in higher daytime xerostomia scores. Consequently, this study supports the clinical implementation of stem cell sparing RT to preserve salivary flow with the aim of reducing the risk of xerostomia.

Evaluation of the Effect of Photobiomodulation on Radiation-Induced Xerostomia in Head and Neck Cancer Patients: A Randomized Clinical Trial.

Introduction: Radiotherapy-induced xerostomia is an important side effect of head and neck cancer (HNC) treatment. Photobiomodulation (PBM) is one of the new emerging methods for preventing or reducing this problem. The aim of this study is to evaluate the effect of PBM on radiation-induced xerostomia in HNC patients. Methods: Thirty-seven patients with HNC who were referred for radiotherapy to Mashhad cancer center. In the case group, an infrared diode laser was used in contact mode on 16 points (covering minor and major salivary glands). The device emitted a wavelength of 810 nm and operated at the power of 200 mW and continuous wave mode. Each area was irradiated for 4 seconds in contact mode with gentle pressure, and the laser energy was 0.8 J with an energy density of 2.85 J/cm2 at the surface of the probe (spot size, 0.28 cm2 ). The total dose was 45.6 J/cm2. The power density was 714.2 w/cm2. In the control group, the sham laser device was used. Subjective xerostomia was evaluated through the LENT SOMA scale (LSS). Stimulated and unstimulated saliva was also assessed. Data were analyzed with SPSS ver22 statistical software. Results: The study included 26 men and 11 women with a mean age of 55.6±15.3 years. In the sixth week, the case group produced more stimulated saliva than the control group (P=0.006). They also had less subjective xerostomia than the control group in weeks four to six. Conclusion: In the present study, PBM had a preventive effect on stimulated saliva and subjective xerostomia and can be recommended as an adjunctive treatment. Further studies with a higher sample size and the use of a low-level laser in more sessions are needed for definitive comment.

Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients.

OBJECTIVE: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. METHODS: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. RESULTS: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p=0.013) and use of other antipsychotics (p=0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p=0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p=0.029). CONCLUSION: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

Manifestaciones orales del COVID-19 en Paraguay: resultados de una encuesta en línea

Introducción: Estudios previos han reportado que pacientes infectados con el virus del COVID-19, podrían manifestar sintomatologías a nivel de la cavidad oral. Objetivo: Evaluar la frecuencia de manifestaciones orales asociadas a COVID-19 en un segmento de la población paraguaya y determinar cuáles son las más prevalentes. Metodología: Estudio descriptivo de corte transversal. Fue realizada una encuesta electrónica de enero a marzo del 2022. Los datos fueron presentados como frecuencias y porcentajes y analizados mediante la prueba de chi-cuadrado. El análisis estadístico se realizó con el software R versión 4.0.3. Resultados: La muestra estuvo compuesta por 478 personas. El 79,50 % correspondió al sexo femenino y el 45,19 % tenía entre 25 y 34 años. El 65,48 % informó haber experimentado al menos 1 síntoma o signo oral durante el curso de COVID-19. La pérdida de la sensación de sabores amargos, seguida de la alteración del sabor de los alimentos y la pérdida de la percepción dulce, fueron los síntomas más comunes. Se encontró una proporción significativamente mayor de manifestaciones orales en el rango de 18-24 años (χ²; p= 0,003). Entre las personas que desarrollaron COVID-19 de forma moderada a severa hubo mayor número de manifestaciones de síntomas orales (χ²; p= 0,044). Discusión: Se identificó una alta frecuencia de manifestaciones orales en pacientes con casos de moderados a severos de COVID-19, destacándose los trastornos del gusto como los más predominantes. Los individuos más jóvenes fueron los más afectados.

Introduction: Previous studies have reported that patients infected with the COVID-19 virus could manifest symptoms in the oral cavity. Objective: To evaluate the frequency of oral manifestations associated with COVID-19 in a segment of the Paraguayan population and determine the most prevalent ones. Methods: Descriptive cross-sectional study. An electronic survey was conducted from January to March 2022. The data were presented as frequencies and percentages and analyzed using the chi-square test. Statistical analysis was performed with R software version 4.0.3. Results: The sample consisted of 478 individuals. 79.50% were female, and 45.19% were between 25 and 34 years old. 65.48% reported having experienced at least 1 oral symptom or sign during the course of COVID-19. The loss of the sensation of bitter tastes, followed by the alteration of the taste of foods and the loss of sweetness perception, were the most common symptoms. A significantly higher proportion of oral manifestations was found in the 18-24 age range (χ²; p= 0.003). Among people who developed COVID-19 in a moderate to severe form, a greater number of oral symptom manifestations were observed (χ²; p= 0.044). Discussion: A high frequency of oral manifestations was identified in patients with moderate to severe cases of COVID-19, with taste disorders standing out as the most predominant. Younger individuals were the most affected.

Age related impairments in ingestion from a large population based-sample.

OBJECTIVES: Epidemiological data regarding the evolution of problems related to mastication and swallowing with age are lacking. This study aims to (i) describe changes in oral function with age, using data from a large French population, (ii) validate online, self-report uses of an ICF questionnaire in older persons, and (iii) assess whether impairment is related to avoidance of certain foods, xerostomia, body mass index (BMI) and oral health related quality of life (OHRQoL). METHODS: Volunteers aged ≥18 years with internet access completed a series of questionnaires on sociodemographic, anthropometric and oral health characteristics (oral function, Xerostomia Index (XI), OHRQoL, reasons for avoidance of certain food). Oral function was assessed using items derived from the International Classification of Functioning (ICF). Five ICF items related to ingestion function and six items related to activities and participation were used. A validation study was undertaken to identify those with poor chewing ability and low salivary flow amongst older participants reporting impairment. FINDINGS: 39 597 individuals were included. The prevalence of individuals with impairment for ICF items related to ingestion function and oral activity (eating, drinking and speaking), and the percentage of participants with poor OHRQoL increased significantly with age (p < 0.001). Each ICF item was significantly associated with OHRQoL (p < 0.001), XI (p < 0.001), BMI (p < 0.001) and avoidance of certain food due to chewing or swallowing difficulties. CONCLUSION: Overall, 21.5% and 13.5% of the study population had chewing and/or biting impairments respectively, which might affect food selection and consumption. These findings raise individual and population-based issues. Further studies are needed to assess whether impairment in oral function might increase frailty in older individuals, and also to compare data with those from other countries.

The Validity and Reliability of the Persian Version of the Xerostomia Inventory Questionnaire.

Statement of the Problem: Reduced saliva production or changes in the quality of saliva are major causes of xerostomia as a perceptual disease. Purpose: This study aimed to measure validity and reliability of the Persian version of the xerostomia inventory (XI) questionnaire. Materials and Method: This cross-sectional study was performed in Kerman in 2021. The sample size for this study was 100 people. To test the discriminant validity of XI, 50 healthy people (control group) and 50 people undergoing or recovering from laryngeal radiation (xerostomia group) were chosen. Cronbach's alpha coefficient was used to determine internal consistency, and the intra-cluster correlation (ICC) coefficient was used to determine test-retest reliability after two weeks. To evaluate the concurrent validity, the relationship between the total score of the questionnaire and the golden question, which was defined as "How often do you have dry mouth?" was measured. Results: Cronbach's alpha and ICC coefficient for the total XI score were 0.84 and 0.95, respectively. The mean ages of patients in the radiotherapy group and the healthy participants were 59±7.5 and 41.1±6.6 years, respectively. Participants who were having or had had laryngeal radiotherapy had a significantly higher mean total XI score than healthy individuals (p< 0.001). Conclusion: The Persian version of the Xerostomia Inventory is a valid and reliable tool for assessing xerostomia.

Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies. METHODS: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336. RESULTS: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors. CONCLUSION: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting.

A 16-year-old boy presented with triple-A syndrome associated with neuromuscular disorders: a case report.

Introduction and importance: Allgrove syndrome (AS) (AAA syndrome) is a rare autosomal recessive disease caused by mutations in the AAAS gene located on chromosome 12q13. The AAAS gene encodes for the ALADIN protein (alacrima, achalasia, adrenal insufficiency, neurologic disorder). AS can manifest with a plethora of symptoms. Early recognition of the syndrome remains challenging due to its rarity and progressive nature. This report presents an unusual case of triple-A syndrome (TAS) with concurrent neuromuscular manifestations. Understanding the atypical presentation of this syndrome is vital for early diagnosis and appropriate management. Case presentation: We report a 16-year-old boy with severe malnutrition presented with painful swallowing, fatigue, and bilateral congenital ptosis. Barium swallow, upper gastrointestinal endoscopy, and Shimmer test were performed, which led to the diagnosis of TAS. Treatment included laparoscopic Heller's procedure, artificial tears, hydrocortisone. Clinical discussion: TAS, also known as AS, is a rare multisystem disorder characterized by achalasia, Addison's disease, and alacrima. This syndrome is occasionally referred to as 4A syndrome due to the inclusion of autonomic dysfunction. There is no treatment for AS. Management includes artificial tears for alacrima, glucocorticoid replacement therapy to treat adrenal insufficiency, and treatment of achalasia. Conclusion: This case emphasizes the importance of considering atypical presentations of TAS. Early diagnosis and treatment are paramount in addressing the varied components of this rare disorder. Understanding the clinical complexities of this syndrome aids in improved patient care and underscores the necessity for comprehensive evaluation and management in similar cases.

A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

AIMS: To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). METHODS: Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. RESULTS: Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. CONCLUSIONS: Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

Chronic oral diseases secondary to COVID-19 infection or vaccination: clinical cases and a narrative review.

OBJECTIVES: Autoimmune activation by COVID-19 infection/vaccination has been postulated to be responsible for initiating or reactivating multiple types of oral mucosal immune disorders. These include oral lichen planus (OLP); oral pemphigoid, either bullous pemphigoid (BP) or mucous membrane pemphigoid (MMP) with oral involvement; pemphigus vulgaris (PV) with oral involvement; or Sjögren's disease. In addition, chronic conditions such as oral burning, xerostomia or changes in taste and/or smell have also been linked to COVID-19 infection/vaccination. DATA SOURCES: Part 1 (mucosal conditions): an English-language literature review of Pubmed, Web of Science, Scopus, and Embase was performed searching cases of OLP, oral BP, MMP, PV and COVID-19 infection/vaccination, with additional cases from the authors' clinical practice presented. Part 2 (non-mucosal conditions): Cases of initiated or flared Sjögren's disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination from the authors' clinical practice were aggregated. Our literature review discovered 29 cases of OLP following COVID-19 infection/vaccination. For BP, 10 cases were identified after infection/vaccination. The number of PV cases following infection/vaccination were 28. The majority of mucosal cases were reported after vaccination. Most reported initial disease, but a substantial amount included recurrences of existing diseases. Non-mucosal disease: Sjögren's disease, chronic oral burning, or xerostomia after COVID-19 infection/vaccination cases totaled 12 cases identified from the authors' clinical practice, with the majority occurring after infection. CONCLUSIONS: Chronic conditions after infection with COVID-19 or vaccination remain relatively rare and self-limited, yet reinforce the importance of comprehensive history taking involving COVID-19 to differentiate potential etiologic factors for these conditions.

Use of the modified Schirmer test to measure salivary gland hypofunction/hyposalivation: Systematic review and meta-analysis.

Although dry mouth is a relatively common condition, salivary flow is not routinely measured in dental clinical practice. Moreover, existing data regarding the use of the modified Schirmer test (MST) for the screening of dry mouth has not been summarized. This systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, aimed to determine whether the modified Schirmer test can be used to identify dry mouth. The databases of PubMed, Scopus, ScienceDirect, and CENTRAL (CRD42023393843) were systematically searched to retrieve articles published until 9th November 2023. Among the 343 original articles retrieved, six met the inclusion criteria. A total of 1150 patients, comprising 710 (61.7%) women and 440 (38.3%) men (mean age, 47.1 ± 7.3 years), were included. The meta-analysis revealed a weak correlation coefficient of r ¯ $\bar{r}$  = 0.42 (95% Cl: 0.29-0.55) between MST and the unstimulated salivary flow rate. Therefore, while the MST might offer a simple and accessible alternative for initial screening in the future, especially in non-specialized settings, its variability in sensitivity and specificity, along with an actual lack of standardization, necessitates cautious interpretation. Further studies are necessary before recommending the test in clinical routine.

Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy.

OBJECTIVES: We sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). MATERIALS AND METHODS: Patients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. RESULTS: Median follow-up was 12.9 months (1.3 - 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was -3.8 kg (-14.1 - 5.1) for VMAT and -3 kg (-16.8 - 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. CONCLUSIONS: Cutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.