Maximum standardized uptake value for parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis using salivary gland SPECT/CT.

Recently, SPECT/CT plays an important role in assessing patients with head and neck lesions. The aim of this study was performed to investigate the maximum standardized uptake value (SUVmax) for parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis using salivary gland SPECT/CT. A prospective study was performed in 45 patients with 32 Sjögren's syndrome and 13 submandibular sialolithiasis who underwent salivary gland SPECT/CT. The SUVmax of parotid and submandibular glands was obtained using a workstation and software. The salivary secretion function of parotid and submandibular glands was defined as ratio of pre- to post-stimulation on SUVmax. A p value lower than 0.05 was considered as statistically significant. The SUVmax for parotid glands in patients with Sjögren's syndrome at pre-stimulation (18.0 ± 14.3), post-stimulation (12.0 ± 9.4), and ratio of pre- to post-stimulation (1.46 ± 0.52) were significantly lower than those of submandibular sialolithiasis (44.9 ± 8.4 (p < 0.001), 17.8 ± 6.5 (p < 0.001), and 2.75 ± 0.79 (p < 0.001), respectively). The SUVmax for submandibular glands in patients with Sjögren's syndrome at pre-stimulation (16.9 ± 18.7) were significantly lower than those with sialolithiasis (36.7 ± 27.8, p = 0.004) and without sialolithiasis (39.7 ± 16.0, p = 0.001) in patients with submandibular sialolithiasis. The salivary gland SPECT/CT SUVmax can be useful in clinical practice for the quantitative management of parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis.

Dysphagia and Dysphonia After Head and Neck Cancer.

OBJECTIVE: The purpose of this work is to synthesize the latest developments in diagnosis and management of acute and late dysphagia and dysphonia in oral cavity cancer. METHODS: A literature search was conducted using PubMed, Web of Science, Embase and Google Scholar in May 2024 of articles published between 2021 and 2024. Keywords in the search terms included oral cavity cancer, dysphagia, dysphonia, deglutition, swallowing, voice, oral cavity cancer treatment, oral cavity radiation, chemotherapy, dysgeusia, xerostomia, swallow preservation. RESULTS: Twenty-seven pertinent studies fit the inclusion criteria. The most common dysphagic complaints following head and neck cancer are trismus, xerostomia, mucositis and dysphagia. Dysphonia, change in voice is reported by half of head and neck cancer survivors. Fibrosis and neuropathy following radiation therapy to the oral cavity, tongue, oropharynx and its surrounding structures is the most common etiology of post-treatment dysphonia. CONCLUSIONS: Oral cavity cancers cause speech and swallowing dysfunction due to both anatomic and post-treatment changes. These sequalae can be detrimental to the quality of life of the head and neck cancer survivor. For both dysphagia and dysphonia after head and neck cancer early speech and swallow therapy with a Speech Language Pathologist are essential to restoring and maintaining function.

Can unstimulated whole salivary flow objectively classify salivary gland secretory function in Sjögren's syndrome?

INTRODUCTION: The aim of this study is to investigate whether the testing time for unstimulated whole salivary flow (UWSF) can be shortened to 5 min in patients with suspected Sjögren's syndrome (SjS); and which SjS patients can use UWSF to evaluate salivary gland (SG) secretory function. METHOD: A diagnostic cohort comprising suspected SjS patients was conducted to investigate the correlation between UWSF measurements taken at 10 min (UWSF_10 min) and those taken at 5 min (UWSF_5 min). A group of SjS patients was enrolled for a comparison between UWSF and stimulated whole salivary flow (SWSF). RESULTS: In 734 suspected SjS patients, there was a remarkably high concordance between UWSF_10 min and UWSF_5 min (ICC 0.970, P < 0.001; r 0.973, P < 0.001). Reducing the testing time for UWSF to 5 min resulted in a high PPV of 83.8% and an exceptionally high NPV of 98.7%. In 408 SjS patients, the cut-off values of UWSF_10 min were investigated to classify SG secretory function. Using a threshold of > 0.2 mL/min (36.8%, 150/408) instead of SWSF > 0.7 mL/min (indicating mild secretory hypofunction), the specificity and PPV were found to be 94.2% and 94.0%, respectively; and using a threshold of < 0.05 mL/min (16.9%, 69/408) instead of SWSF ≤ 0.7 mL/min (indicating moderate to severe secretory hypofunction), the specificity was remarkably high at 97.6%, accompanied by a high PPV of 91.3%. CONCLUSIONS: This study supports the possibility of reducing UWSF testing time to 5 min; and the SWSF test may be skipped for SjS patients with USWF > 0.2 mL/min, indicating mild secretory hypofunction, or < 0.05 mL/min, indicating moderate to severe secretory hypofunction. Key Points •A diagnostic cohort of 734 patients with clinical suspicion of SjS provides compelling evidence for the potential to reduce the testing time for UWSF from 10 to 5 min. •Our finding challenges the 2019 treatment recommendation for SjS, which does not require SWSF measurement in SjS patients with UWSF ≥ 0.1 mL/min. •We propose that it may be feasible to consider utilizing UWSF instead of SWSF test for objective classification of SG secretory function in over half of SjS patients.

The efficacy of occlusal appliance with a moisturizing gel pocket on sleep quality in patients with nocturnal xerostomia: A case series.

PATIENTS: A case series of five patients (mean age, 77.0 years) with complaints of nocturnal xerostomia were subjected to occlusal appliance treatment with a reservoir of moisturizing gel during the night. An occlusal appliance covers the dental arch and hard palate, providing space in the midline of the hard palate to hold the moisturizing gel. Sleepiness was assessed using the Epworth Sleepiness Scale (ESS), and sleep quality was assessed using the Japanese version of the Pittsburgh Sleep Questionnaire (PSQI-J) before and after treatment. The total PSQI-J scores decreased in all patients after treatment. The ESS score, sleep time, and sleep efficiency improved or remained unchanged and none of the patients' symptoms worsened. DISCUSSION: This study demonstrated the efficacy of occlusal appliance treatment in patients with dry mouth in improving self-reported sleep quality. Patients included those with nocturnal xerostomia and poor sleep quality on the PSQI-J. Treatment with xerostomia resulted in improved sleep quality, as assessed by the decrease in PSQI-J scores. CONCLUSIONS: This case series suggests that sleep quality may be worse in patients with xerostomia, and that treatment for nocturnal xerostomia using occlusal appliances may improve sleep quality.

Adipose derived or bone-marrow derived mesenchymal stem cell treatment for hyposalivation: protocol for a systematic review and network meta-analysis.

BACKGROUND: Salivary hypofunction leads to debilitating oral symptoms and has major complications for overall quality of life. Two of the most frequent causes of xerostomia are radiotherapy in the head and neck and Sjögren's syndrome. Only symptomatic treatment is available today. An increasing number of both preclinical and clinical studies have suggested that mesenchymal stem cell (MSC) transplantation treatment can increase the salivary flow rate and ameliorate symptoms of xerostomia. However, both adipose-derived and bone marrow-derived MSCs are used, although they differ in important ways. The primary objective of this study is an indirect comparison of the change in the unstimulated salivary flow rate after intervention between patients treated with adipose-derived or bone marrow-derived MSCs. METHODS: This systematic review and network meta-analysis will search for eligible studies in the MEDLINE, EMBASE, and Cochrane CENTRAL register of Controlled Trials. Eligible studies are as follows: clinical studies including human patients with salivary hypofunction due to either radiotherapy or Sjogren's syndrome who were subsequently treated with either adipose-derived MSCs or bone marrow-derived MSCs. Studies with no control group will be excluded. The search phrase has been peer-reviewed following the PRESS guidelines. The primary outcome is the change in the unstimulated salivary flow rate after treatment with either adipose-derived or bone marrow-derived MSCs. Secondary outcomes are as follows: change in patient reported outcomes, methods of intervention administration, number of injected MSCs, and safety. Data from included studies will be pooled and compared with a fixed-effects or random effects model dependent on signs of heterogeneity, presented with a forest plot, and indirectly compared with a meta-regression in a network meta-analysis. Risk of bias will be assessed with the tools ROBINS-I or RoB-2 depending on type of study. DISCUSSION: Both adipose-derived and bone marrow-derived MSCs are used today for experimental treatment of salivary hypofunction in humans as no direct or indirect comparisons have been made. Therefore, an evaluation of the effect of adipose-derived vs bone marrow-derived MSC treatment is needed to support future decision-making on the type of MSC used in a clinical trial. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ID CRD42024527183.

Metabolomic insights into idiopathic xerostomia: The central role of caffeine metabolism in salivary biochemistry.

OBJECTIVE: This study aims to delineate the salivary metabolomic profile of patients with idiopathic xerostomia using untargeted metabolomics techniques, with the goal of addressing the lack of clear diagnostic markers and providing insights into the pathophysiological mechanisms of the condition. DESIGN: In this observational, cross-sectional study, saliva samples from 33 patients with idiopathic xerostomia and 34 healthy controls were analyzed using Ultra Performance Liquid Chromatography Quadrupole Time of Flight Mass Spectrometry (UPLC-QTOF MS). Metabolomic profiling was complemented by multivariate statistical analysis to differentiate between affected individuals and controls. RESULTS: Metabolomic analysis delineated a pronounced differentiation between patients with idiopathic xerostomia and healthy controls. A total of 195 metabolites displayed significant differential expression, each with a variable importance in projection (VIP) greater than 1 and a P-value less than 0.05. Pathway enrichment analysis, according to the Kyoto Encyclopedia of Genes and Genomes (KEGG), identified 22 metabolites that participated in 18 distinct metabolic pathways. Among these, the caffeine metabolism pathway, characterized by notable alterations in impact values (VIP, P-value, Log2-fold change, Rich factor), emerged as the most significantly disrupted, underscoring its potential role in the pathophysiology of idiopathic xerostomia (P = 0.0000395). CONCLUSIONS: The salivary metabolomic profiling revealed distinct alterations in idiopathic xerostomia, with a significant reduction in caffeine metabolism pathways, underscoring potential neuropathic involvement. This study advances our understanding of the metabolic alterations in xerostomia, suggesting that salivary metabolomics may offer viable biomarkers for diagnosing and understanding the etiology of idiopathic xerostomia. Future research should focus on therapeutic targeting of these metabolic disturbances and evaluating their reversibility with treatment.

Oral Chronic Graft-versus-Host Disease and Oral Health after Allogeneic Hematopoietic Cell Transplantation - What the Care Team Needs to Know.

Oral chronic graft-versus-host disease (cGVHD) can present with a multitude of clinical signs and is associated with morbidity and lower quality of life. Oral cGVHC may affect the oral mucosa (reticular white striae, erythema, and/or ulcerations), the salivary glands (hyposalivation and/or xerostomia) and the peri-oral soft tissues (fibrosis and trismus). This review provides a practical and concise approach to the diagnosis and management of oral health needs in pediatric and adult alloHCT recipients within the first 2 years post-transplantation.

Salivary flow rate, subjective oral dryness and dental caries 5 years after haematopoietic cell transplantation.

BACKGROUND: The aim of this study was to describe salivary flow rate, subjective oral dryness and dental caries 5 years post haematopoietic cell transplantation (HCT). METHODS: HCT survivors of a previous longitudinal observational cohort study in the Netherlands (the H-OME study) were invited to participate in this additional follow-up after 5 years (the HOME2 study). During the additional follow-up appointment, stimulated (SWS) and unstimulated whole saliva (UWS) was collected, participants rated subjective oral dryness on a 0 - 10 scale, and caries lesions were assessed. Furthermore, dental records, including treatments and radiographs, were requested for the 5 years preceding and the 5 years following transplantation. Paired t-tests were performed to determine changes in UWS and SWS flow rates and subjective oral dryness from pre-HCT, and to compare the number of caries-related dental treatments (restorations, endodontic treatments or extractions) before and after HCT. Hyposalivation of UWS (< 0.2 mL/min) and SWS (< 0.7 mL/min) at 3 and 12 months, was used to explore the predictive potential of hyposalivation on a high dental treatment need (> 3 treatments) over the 5 years post-HCT. RESULTS: Five years post-HCT, 39 HCT survivors were included. The mean UWS flow rate was 0.36 mL/min (SD 0.26) and the mean SWS flow rate 1.02 (SD 0.57); survivors were diagnosed with a median of 0 dentine lesions (range 0 - 12) and 73% reported a subjective oral dryness score ≥ 1. Survivors underwent a median of 3 (range 0 - 20) dental treatments during the 5 years following transplantation. The mean difference in UWS 5 years post-HCT compared to pre-HCT was 0.03 (95% CI: -0.07 - 10.12), the mean difference for SWS was -0.18 (95% CI: -0.45 - 0.08) and for subjective oral dryness 1.2 (95% CI: 0.2 - 2.1). In the 5 years post-HCT, non-significantly more treatments were performed compared to the 5 years pre-HCT (mean difference: 0.5, 95%CI: -1.2 - 2.2). Seventy eight percent of patients with hyposalivation of SWS at 12 months had a high dental treatment need, compared with 38% with no hyposalivation. CONCLUSIONS: Five years post-HCT, mean UWS and SWS flow rates were not significantly different from pre-HCT levels but subjective oral dryness scores were elevated.

Clinical outcomes of NBF gel application in managing mucositis associated with xerostomia.

BACKGROUND: Xerostomia, or dry mouth, can be a temporary or persistent symptom resulting from various factors, such as medication use, therapeutic radiation, chemotherapy, autoimmune conditions (e.g., Sjögren's syndrome), and hormonal imbalances. Xerostomia often leads to associated mucositis, which significantly impacts patients' quality of life. The nano-bio-fusion (NBF) gingival gel, a gel-type functional toothpaste containing vitamins C, E, propolis, and herbal extracts in a nano-emulsion state, has shown potential in accelerating the healing of oral mucosal lesions. METHODS: A total of 127 patients (102 females, 25 males) with persistent xerostomia were treated from 2018 to 2023. Of these, 32 patients were treated exclusively with NBF Gel, while 95 patients received NBF Gel in combination with other medications, such as pilocarpine. The underlying causes of xerostomia included irradiation and chemotherapy (12 patients), medication (40 patients), hormonal imbalance (28 patients), and Sjögren's syndrome (47 patients). NBF Gel was applied 2-3 times daily to the tongue and oral mucosa. Treatment effectiveness was evaluated through physical examinations and a patient-reported scale ranging from 1 (no improvement) to 10 (complete improvement), focusing on the healing of mucosal lesions rather than saliva production. RESULTS: Both treatment groups showed significant improvements in the healing of xerostomia-associated mucositis, particularly in severe cases with visible lesions. Patients treated with NBF Gel reported improved symptoms related to mucosal health, while those who received combination therapy also experienced reduced side effects of pilocarpine due to dose reduction. The most substantial improvements were observed in patients with drug-induced and hormonally-caused xerostomia-related mucositis. No adverse side effects from NBF Gel were reported during the study. CONCLUSION: NBF gingival gel proved to be beneficial in accelerating the healing of mucositis associated with xerostomia, regardless of the underlying cause, including medication use, radiotherapy, chemotherapy, hormonal imbalances, and Sjögren's syndrome. It presents a promising adjunctive treatment to improve mucosal health and quality of life for patients suffering from xerostomia-associated mucositis.

Imipramine Increases Norepinephrine and Serotonin in the Salivary Glands of Rats.

Xerostomia induced by antidepressants such as imipramine has long been thought to be due to their anticholinergic effects. However, even antidepressants with low anticholinergic effects may have a high incidence of xerostomia. In salivary glands, norepinephrine activates alpha-adrenergic receptors in blood vessels and beta-adrenergic receptors in acinar cells, respectively, causing a decrease in the blood flow and an increase in the protein secretion, resulting in the secretion of viscous saliva with low water content and high protein content. A previous study demonstrated that perfusion of the submandibular glands of rats with serotonin significantly decreased saliva secretion. The results of the present study revealed the following: (1) that norepinephrine and serotonin, but not epinephrine nor dopamine, were detected in the interstitial fluids in rat submandibular glands; (2) that norepinephrine and serotonin concentrations in the dialysate was 4.3 ± 2.8 nM and 32.3 ± 19.6 nM at stable level, respectively; (3) that infusion with imipramine, a reuptake inhibitor of norepinephrine and serotonin, significantly and dose-dependently increased both norepinephrine and serotonin concentrations in the dialysate; and (4) that intraperitoneal administration of imipramine significantly increased both norepinephrine and serotonin concentrations in the dialysate. These results suggested that one of the mechanisms of xerostomia induced by reuptake inhibitors of norepinephrine and serotonin involves the activation of adrenergic and serotonin receptors in the salivary glands, respectively.

Xerostomia and Salivary Dysfunction in Patients With Diabetes Mellitus. A Cross-Sectional Study.

BACKGROUND: Diabetes mellitus (DM) has been associated with salivary disorders such as xerostomia and hyposalivation. The aim of this study was to determine the prevalence of these disorders and their risk factors in DM patients. METHODS: DM patients from two health centers were included. Epidemiological and DM control-related variables were collected. Xerostomia Inventory was filled out by the patients and unstimulated whole salivary flow was collected. Logistic regression tests were performed. RESULTS: A total of 168 patients were included (46.4% men, 53.6% women, mean age 72.54 [SD 11.03 years]). Thirteen patients had Type 1 DM and 155 had Type 2 DM. 52.4% experienced xerostomia and 41.1% had unstimulated whole salivary flow hyposalivation. Women were more likely to suffer hyposalivation than men (OR 2.5, 95% CI 1.32-4.73; p = 0.005). Patients with T2DM were less likely to suffer UWS hyposalivation than T1DM patients (OR 0.28, 95% CI 0.08-0.95; p = 0.04). Glycemic control was not significantly worse in patients with xerostomia and hyposalivation. The drugs for the treatment of DM were not associated with salivary disorders. However, some drugs to treat other comorbidities such hypertension and neurological diseases were associated with xerostomia and hyposalivation. CONCLUSIONS: The prevalence of xerostomia and unstimulated whole salivary flow hyposalivation in patients with DM is high. Female sex, T1DM, and the use of certain non-antidiabetic drugs increased the risk of suffering these disorders. The possible association between DM, xerostomia, and/or hyposalivation is complex and may be influenced by multiple factors. Therefore, further studies are needed to evaluate whether DM influences these salivary disorders.

Self-perceived oral health in hemato-oncological patients and the relation to quality of life.

PURPOSE: To assess the self-reported oral health and oral health-related quality of life of patients diagnosed with hemato-oncological disease. PATIENTS AND METHODS: Data was collected through a digital questionnaire in collaboration with the Dutch patient organization Hematon. The questionnaires EORTC-QLQ-C30, EORTC-QLQ-OH15, shortened Xerostomia Inventory (XI), and the OHIP-14 were used. RESULTS: Seven hundred five patients were included (52.5% female, mean age 63.2 ± 10.1). The majority was diagnosed more than 2 years ago (86%) and had received treatment (81%) for their disease. Lymphoma, leukemia, and multiple myeloma were the most frequent malignancies. Chemotherapy alone, chemotherapy in combination with targeted therapy or immunotherapy, and myeloablative chemotherapy followed by autologous stem cell transplantation were the most common treatment modalities. The XI identified that 40.5% met the criteria for xerostomia. Other complaints included mouth soreness and sensitivity, gingival pain and bleeding, problems with teeth or with an ill-fitting denture. Despite reporting oral complaints, most patients experienced a rather good OH-QoL. A high xerostomia score led to a significantly lower OH-QoL. Female gender, history of stem cell transplantation, radiation to head and neck, and multiple daily medication use were significant predictors of xerostomia. CONCLUSION: Patients with hematologic malignancies frequently reported a dry mouth and other oral complaints including mouth soreness and sensitivity, gingival pain and bleeding, and problems with teeth. Despite these oral complaints, most patients experienced a relatively good OH-QoL. Future longitudinal studies are needed, and health professionals should have an active role in providing oral supportive care based on patients' individual needs.

Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome.

Some forms of Sjögren's syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging.

Xerostomia prediction in patients with nasopharyngeal carcinoma during radiotherapy using segmental dose distribution in dosiomics and radiomics models.

OBJECTIVES: This study aimed to integrate radiomics and dosiomics features to develop a predictive model for xerostomia (XM) in nasopharyngeal carcinoma after radiotherapy. It explores the influence of distinct feature extraction methods and dose ranges on the performance. MATERIALS AND METHODS: Data from 363 patients with nasopharyngeal carcinoma were retrospectively analyzed. We pioneered a dose-segmentation strategy, where the overall dose distribution (OD) was divided into four segmental dose distributions (SDs) at intervals of 15 Gy. Features were extracted using manual definition and deep learning, applying OD or SD and integrating radiomics and dosiomics, yielding corresponding feature scores (manually defined radiomics, MDR; manually defined dosiomics, MDD; deep learning-based radiomics, DLR; deep learning-based dosiomics, DLD). Subsequently, 18 models were developed by combining features and model types (random forest and support vector machine). RESULTS AND CONCLUSION: Under OD, O(DLR_DLD) demonstrated exceptional performance, with an optimal area under the curve (AUC) of 0.81 and an average AUC of 0.71. Within SD, S(DLR_DLD) surpassed the other models, achieving an optimal AUC of 0.90 and an average AUC of 0.85. Therefore, the integration of dosiomics into radiomics can augment predictive efficacy. The dose-segmentation strategy can facilitate the extraction of more profound information. This indicates that ScoreDLR and ScoreMDR were negatively associated with XM, whereas ScoreDLD, derived from SD exceeding 15 Gy, displayed a positive association with XM. For feature extraction, deep learning was superior to manual definition.

Submandibular Gland Preservation in Oral Cavity Squamous Cell Carcinomas: Our Analysis at A Tertiary Care Hospital.

Introduction: Surgical excision forms the principal treatment of oral cavity squamous cell carcinomas. The comprehensive surgical management consists of Wide Local Excision of the tumor and Neck Dissection with removal of Submandibular gland. The submandibular gland accounts for 70-90 % of unstimulated salivary volume. Its excision as a part of neck dissection has been found to cause high Incidence (21% vs 7%) of postoperative xerostomia. Recent studies have highlighted that the preservation of the SMG is possible and oncologically safe in early-grade OCSCC with N0 neck as the involvement of SMG in such cases is low and its preservation decreases the chances of xerostomia. Materials and Methods: 80 subjects were included in the study to estimate the prevalence of metastatic submandibular gland involvement in oral cavity squamous cell carcinomas. The presence of metastasis into the salivary gland was studied and the mechanism/route of involvement was analysed. The comparison was made between the early and advanced tumors for SMG metastasis irrespective of the primary subsite involvement. Results: In the current study low prevalence (6.2 %) of metastasis to SMG was seen. It was seen in high-grade tumors only. None of the early-grade tumors showed any evidence of SMG metastasis. The most common pattern (80%) of glandular involvement was a direct extension from the primary tumor. Conclusions: Our study concludes that SMG preservation neck dissections can be carried out in early-grade OCSCC irrespective of primary tumor site involvement. The advantages of preserving the SMG are multiple. Furthermore, the morbidity is markedly decreased with its preservation without any compromise on oncological safety.

Identifying dose constraints for the parotid ducts to minimize patient-reported xerostomia: Is conventional mean dose sparing of the parotid glands sufficient?

BACKGROUND AND PURPOSE: The aim of this study was to identify dose constraints for the parotid ducts that limit patient-reported xerostomia and estimate whether these constraints are achieved during conventional parotid gland sparing radiation therapy (PGS-RT). METHODS AND MATERIALS: Thirty-eight oropharyngeal squamous cell carcinoma patients were treated prospectively on trial with MRI sialography-guided parotid duct sparing radiation therapy (PDS-RT). PDS-RT explicitly minimizes dose to the parotid ducts in addition to PGS-RT. Parotid duct dose constraints were identified that distinguished patients reporting high and low rates of xerostomia. Atlas-based parotid duct contours were generated on a retrospective cohort of similar patients where the parotid ducts were not contoured nor explicitly spared to estimate the dose received by the parotid ducts during PGS-RT. RESULTS: Patients whose intraglandular parotid ducts or total parotid ducts were planned for a mean dose < 14 Gy and < 12 Gy, respectively, reported significantly (p < 0.01) lower rates of xerostomia at 6 and 12 months post-RT. Patients receiving PDS-RT had average total and intraglandular duct doses of 11.6  and 13.6 Gy, respectively, compared to an estimated 23.8  and 22.1 Gy, for those receiving PGS-RT (p < 0.01). Only 6% (6/108) and 20% (22/108) of patients receiving PGS-RT were estimated to meet the dose constraints for the total ducts and intraglandular ducts, respectively. CONCLUSION: Parotid duct dose thresholds exist that appear to distinguish patients with and without xerostomia. The identified dose thresholds are frequently not met in PGS-RT plans. In addition to reducing the dose to the parotid gland(s), parotid duct sparing may also further reduce xerostomia.

Metformin Attenuates Partial Epithelial-Mesenchymal Transition in Salivary Gland Inflammation via PI3K/Akt/GSK3ß/Snail Signaling Axis.

Chronic inflammation in the salivary glands (SG) often triggers epithelial-mesenchymal transition (EMT), leading to the loss of acinar function and promoting fibrosis. This study explores the role of Metformin in mitigating partial EMT in SG inflammation. In vitro, human salivary gland epithelial cells (hSGECs) were treated with lipopolysaccharide (LPS) and Metformin. EMT markers and the PI3K/Akt/GSK3ß/Snail signaling axis were assessed using RNA-seq and Western blot analysis. In vivo, a Wharton's duct ligation rat model was employed to mimic chronic sialadenitis (CS). Nine Wistar rats were randomly divided into three groups: Control, Ligation and Ligation + Metformin groups, with three rats per group. After ductal ligation, the Ligation + Metformin group received 100 mg/kg of Metformin via intragastric administration, while the Control and Ligation groups received an equivalent saline every 24 h. Histological analysis, immunohistochemical and immunofluorescence staining were conducted to evaluate acinar morphology, EMT, and the PI3K/Akt/GSK3ß/Snail signaling axis. The results showed that in CS tissues, atrophied acinar cells underwent partial EMT. In vitro, Metformin reversed LPS-induced EMT in hSGECs. RNA-seq and Western blot revealed that Metformin achieved this effect by targeting the PI3K/Akt/GSK3ß/Snail signaling axis (P < 0.01). In ductal ligation models, Metformin treatment restored ligation-induced acinar damage and functional loss (P < 0.01). Further histological evidence supported that Metformin mitigated EMT by inhibiting inflammatory activation of PI3K/Akt/GSK3ß/Snail signaling axis (P < 0.01). In conclusion, Metformin alleviates partial EMT in SG inflammation by targeting the PI3K/Akt/GSK3ß/Snail signaling axis, highlighting its potential as a therapeutic strategy for SG inflammation.

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

The molecular mechanisms leading to saliva secretion are largely established, but factors that underlie secretory hypofunction, specifically related to the autoimmune disease Sjögren's syndrome (SS) are not fully understood. A major conundrum is the lack of association between the severity of salivary gland immune cell infiltration and glandular hypofunction. SS-like disease was induced by treatment with DMXAA, a small molecule agonist of murine STING. We have previously shown that the extent of salivary secretion is correlated with the magnitude of intracellular Ca2+ signals (Takano et al., 2021). Contrary to our expectations, despite a significant reduction in fluid secretion, neural stimulation resulted in enhanced Ca2+ signals with altered spatiotemporal characteristics in vivo. Muscarinic stimulation resulted in reduced activation of the Ca2+-activated Cl- channel, TMEM16a, although there were no changes in channel abundance or absolute sensitivity to Ca2+. Super-resolution microscopy revealed a disruption in the colocalization of Inositol 1,4,5-trisphosphate receptor Ca2+ release channels with TMEM16a, and channel activation was reduced when intracellular Ca2+ buffering was increased. These data indicate altered local peripheral coupling between the channels. Appropriate Ca2+ signaling is also pivotal for mitochondrial morphology and bioenergetics. Disrupted mitochondrial morphology and reduced oxygen consumption rate were observed in DMXAA-treated animals. In summary, early in SS disease, dysregulated Ca2+ signals lead to decreased fluid secretion and disrupted mitochondrial function contributing to salivary gland hypofunction.

Xerostomia in a Group of Turkish Patients Using an Online Survey During the COVID-19 Pandemic.

Background Xerostomia is defined as the subjective feeling of dry mouth and affects millions of patients worldwide. Most studies are based on samples of the elderly in nursing homes. This study aimed to investigate the presence of xerostomia and the severity of self-reported xerostomia by sociodemographic variables and to evaluate xerostomia symptoms (self-reported halitosis, burning mouth, and mouth sores) in young adults. Methodology A questionnaire regarding sociodemographic data and the 11-item Xerostomia Inventory was delivered to patients aged 20-65 years who applied to the Ankara University Faculty of Dentistry for dental treatment before the COVID-19 pandemic. Statistical analyses were performed to determine the relationships between the presence of xerostomia and other variables such as age, gender, the presence of a systemic disease, medication use, smoking, alcohol consumption, and the use of removable prostheses. Results A total of 300 patients were included in the study. Xerostomia presence of 54.6% (164 patients) was identified. A significant relationship was found between age and xerostomia (p = 0.023; p = 0.001). The presence of xerostomia decreased as age increased. Xerostomia was more common in female patients (p = 0.028; p = 0.004). The presence of xerostomia was found to be high, not only in the elderly but also in younger adults. Conclusions This study sheds light on the current status, symptoms, and etiology of xerostomia presence in the young population in Turkey. Factors associated with xerostomia were age, female gender, and the number of cigarettes smoked per day. In this study, the high presence of xerostomia was due to smoking.

Salivary Gland Sonography in Patients with Primary Fibromyalgia-A Pilot Study.

Primary Sjogren's syndrome (pSS) is often concomitant with fibromyalgia (FM). Salivary gland sonography aids in the diagnosis of pSS. We aimed to discover, in primary FM patients, the presence of pSS in undiagnosed patients through salivary gland sonography. We prospectively recruited 42 primary FM patients. FM symptoms were evaluated based on the revised Fibromyalgia Impact Questionnaire (FIQR). Salivary gland sonography was performed. Patients with positive findings underwent salivary gland biopsy. Comparisons were undertaken using the Mann-Whitney U tests and Chi-squared test. In primary FM patients, the prevalence of dry eye was 83%, and dry mouth was 90%. The salivary gland sonographic score did not differ between patients with and without dry eye/mouth. One patient with a positive finding at salivary gland sonography had a positive result of salivary gland biopsy. In the other four patients who received salivary gland biopsy, despite negative findings in salivary gland sonography, only one had a positive result of salivary gland biopsy. To be noted, scores evaluated by salivary gland sonography were negatively associated with levels of pain (rho = -0.360, p= 0.023) and levels of sleep quality (rho = -0.447, p = 0.004). Our pilot study demonstrated the potential of salivary gland biopsy in detecting undiagnosed pSS in primary FM patients.