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Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin. By single nucleus RNA-seq, salivary gland cells were stratified into four clusters: acinar cells, ductal cells 1, ductal cells 2 and myoepithelial cells/stromal cells. The localization of each cell group was verified by IHC of each cluster marker gene, and one group of ductal cells was found to represent intercalated ductal cells labeled with HES1. Furthermore, in comparison with SGC RNA-seq data, acinar cell markers were upregulated in AciCC, but downregulated in ACC and ductal cell markers were upregulated in SDC but downregulated in MECA, suggesting that markers of origin are highly expressed in some SGC. Cell type expressions in specific SGC histology are similar to those found in normal salivary gland populations, indicating a potential etiologic relationship.

OBJECTIVES: The Salivary Gland Committee of the American Academy of Otolaryngology-Head and Neck Surgery seeks to standardize terminology and technique for ultrasonograpy used in the evaluation and treatment of salivary gland disorders. METHODS: Development of expert opinion obtained through interaction with international practitioners representing multiple specialties. This committee work includes a comprehensive literature review with presentation of case examples to propose a standardized protocol for the language used in ultrasound salivary gland assessment. RESULTS: A multiple segment proposal is initiated with this focus on the submandibular gland. We provide a concise rationale for recommended descriptive language highlighted by a more extensive supplement that includes an extensive literature review with additional case examples. CONCLUSION: Recommendations are provided to improve consistency both in performing and reporting submandibular gland ultrasound.

Background and aims: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy with multiple morphological subtypes. Primary salivary squamous cell carcinoma (SCC) requires exclusion of high‐grade salivary malignancies and metastatic disease and is considered exceptionally rare. We report six cases of SDC with resemblance to SCC on account of variable, but often extensive, squamous differentiation. Methods and results: A retrospective review (2009–2023) at two institutions of SDC with histological and immunophenotypical evidence of squamous differentiation identified six cases. Medical charts and available glass slides were reviewed. There were five males and one female with a median age of 63 years, with tumours involving the parotid (five of six) and submandibular (one of six) glands. All six tumours showed a conventional SDC component comprising < 5–90% of viable tumour. Squamous differentiation comprised 10–95%+ (> 75% in three of six cases) of total viable tumour, and demonstrated CK5/6, p63 and/or p40 immunoexpression in all cases. A sarcomatoid component, comprising 10–60% of viable tumour, was present in three of six (50%) cases. All tumours were androgen receptor (AR)‐positive, but only two of six (33.3%) retained AR immunoreactivity in the squamous component. Metastatic SDC to regional lymph nodes exhibited exclusive squamous differentiation in two of six (33.3%) cases. Conclusion: Squamous differentiation, histologically and immunophenotypically, can be extensive in SDC. AR expression may be lost in the squamous component and metastases may demonstrate only squamous differentiation. These findings cast further doubt on the existence of primary salivary SCC. SDC should be considered whenever encountering a carcinoma with squamous differentiation in major salivary glands or within cervical lymph nodes in the setting of a salivary mass. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose Methods Results Conclusion Sialocele or salivary fistula formation is common after parotidectomy. This study aims to evaluate the predictive value of the prognostic nutritional index in the development of salivary fistulas and sialoceles after parotidectomy.Patients who underwent parotidectomy at our clinic and were diagnosed with benign salivary gland masses were included in the study. Patients who developed postoperative sialoceles or salivary fistulas were identified. Various factors were assessed, including surgical technique, tumour size, gender, age, prognostic nutritional index, and the volume of the excised mass. Variables associated with sialocele or salivary fistula were later included in a multiple logistic regression model. Possible factors related to the formation of sialocele or salivary fistulas were analysed.The study comprised 158 patients (95 male and 63 female). The frequency of sialocele or salivary fistula development was 13.9% (n = 22). The multiple logistic regression model found that the prognostic nutritional index(PNI) was linked to the occurrence of sialocele or salivary fistula (ORs = 0.9, 95% CI = [0.9], p = 0.003). Warthin tumour was associated with an elevated risk of sialocele or salivary fistula (ORs = 0.38, 95% CI = [0.184, 0.79], p = 0.009). ROC analysis demonstrated that the PNI had a specificity of 90% and a sensitivity of 68%. No significant associations were observed between the excised tumour size, surgical technique with the development of sialocele or salivary fistula.Prognostic nutritional index can be utilised as an independent risk factor for the development of sialocele, or salivary fistula. [ABSTRACT FROM AUTHOR]

Background: While statistically rare in comparison to other head and neck tumours, parotid gland swellings are often encountered in clinical practice where one of the primary goals of examination becomes distinction between benign and malignant lesions. Hallmarks of malignancy are characterized by a female preponderance, history of radiation exposure, a positive family history, and clinical features like heterogenous consistency, fixity to skin/underlying tissues and involvement of facial nerve. Case presentation: Here we present a case of parotid swelling in a 72-year old gentleman from south India that had a curious amalgamation of both benign and malignant features. Conclusions: While benign, the risk of malignant transformation and rare multicentric occurrence indicates a need to keep basal cell adenoma in mind in case of parotid swellings and their surgical management. [ABSTRACT FROM AUTHOR]

Background: Plasmodium knowlesi, identified as the fifth human malaria parasite, has rapidly spread across various Southeast Asian countries, yet uncertainties persist regarding its human-mosquito-human transmission. Therefore, this study aims to explore the transmission potential of P. knowlesi from human blood to mosquitoes. Methods: A direct membrane-feeding assay was conducted by infecting laboratory-reared female Anopheles dirus mosquitoes with P. knowlesi-infected human blood from a single patient presenting with febrile malaria. Mosquitoes were dissected 7 days post-infection under a stereomicroscope to detect oocysts in the midgut, stained with mercurochrome. Salivary glands were examined 14 days post-infection for the presence of sporozoites. Malaria diagnosis employed microscopy by expert microscopists and nested PCR assays. Results: Upon dissecting 745 out of 1439 blood-fed An. dirus mosquitoes on day 7 post-infection, two oocysts were identified in the midguts of two mosquitoes (0.27%). An additional 694 mosquitoes were dissected for salivary glands on day 14 post-infection, with three mosquitoes (0.43%) exhibiting sporozoites. Further confirmation by nested-PCR assay verified these sporozoites as belonging to the P. knowlesi species. Conclusions: The findings underscore the potential transmission of P. knowlesi from human blood to mosquitoes. The significance of these findings necessitates further investigation, such as repeating similar experiments among natural vectors, to gain deeper insights into the transmission dynamics of P. knowlesi in Southeast Asia. [ABSTRACT FROM AUTHOR]

Background: 'Kimura's disease (KD) is a rare chronic inflammatory disorder of unknown etiology and is difficult to diagnose due to poor clinical presentation and imaging features. Few studies on characteristics of 18F-FDG PET/CT of KD have been reported. This study aimed to observe the reliable characteristics and usefulness of 18F-FDG PET/CT for the evaluation of consecutive patients with KD. Methods: The clinical data and 18F-FDG PET/CT imaging findings of 8 patients with pathologically confirmed KD were reviewed retrospectively.18F-FDG PET/CT images were evaluated visually and semiquantitatively by measuring the maximum standardized uptake value (SUVmax). The correlations between clinical data and 18F-FDG PET/CT features were analyzed by simple linear regression. Results: This study included 7 males and one female ranging in age from 17 to 79 years. The longest diameter of lesions ranged from 0.8 cm to 4.8 cm, and regional or generalized lymphadenopathy was found in all 8 patients with eosinophilia, while subcutaneous masses and salivary gland involvement concurrently were found in 4 patients. 18F-FDG PET/CT revealed that these involved lesions had high 18F-FDG uptake with SUVmax > 2.5 (2.6 to 6.3). Moreover, the margin of the lesions was well defined in 6 cases and ill defined in 2 cases, and homogeneous density and 18F-FDG uptake were both found in all these lesions. There was negative correlation between eosinophils and SUVmax (R2 = 0.538). Conclusions: Kimura's disease should be considered when 18F-FDG PET/CT is characterized by homogeneous lesions of regional or generalized lymphadenopathy, accompanied with subcutaneous masses and salivary gland involvement concurrently, especially in patients with eosinophilia. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan, fibro-inflammatory condition that presents with painless organ swelling, lymphoplasmacytic infiltration, and obliterative phlebitis, often showing a favorable response to corticosteroid therapy. The most affected organs include the pancreas, kidneys, retroperitoneum, lacrimal glands, and salivary glands. Diagnosis relies on serological, imaging, and histopathological findings, with glucocorticoids as the primary treatment. Despite its reversible nature and good prognosis in many cases, long-term complications such as organ dysfunction or malignancy can still occur. International collaborative efforts have enhanced the understanding, diagnosis, and management of IgG4-RD, emphasizing the importance of comprehensive diagnostic criteria and appropriate therapeutic strategies. Herein, we present an interesting case of a geriatric male who was referred to our clinic because of concern for pancreatic cancer. We diagnosed the patient with autoimmune pancreatitis, a manifestation of IgG4-RD. The patient experienced a dramatic response to steroid therapy and is currently on maintenance therapy. [ABSTRACT FROM AUTHOR]

The aim of the study is to expound the effect of psoriasis on salivary glands by evaluating the secretion of saliva and salivary cytokine biomarkers in patients with psoriasis. This study was conducted by recruiting 120 subjects that included 60 patients diagnosed clinically with active psoriasis and 60 healthy controls who were age and gender matched to psoriatic subjects. Unstimulated whole saliva was collected from all the subjects by spitting method, and levels of tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), interleukin‐2 (IL‐2), and IL‐10 (IL‐10) were determined via enzyme‐linked immunosorbent assay (BT Lab, Shanghai, China). Secretion of saliva in psoriasis patients was considerably reduced than in healthy controls. The concentrations of pro‐inflammatory cytokines (TNF‐α, IFN‐γ, and IL‐2) were significantly increased, whereas level of anti‐inflammatory cytokine (IL‐10) was markedly decreased in the saliva of psoriasis patients with hyposalivation compared to healthy subjects. Our results demonstrated significant negative correlation of salivary flow rates with the disease severity. No significant correlations were obtained between salivary levels of tested cytokines and salivary flow rates in our study. Findings of the study reflect inflammation of salivary glands with reduced salivary flow rates in psoriasis patients. The inflammatory responses in salivary gland tissues by virtue of increased pro‐inflammatory cytokines concentrations together with lower anti‐inflammatory cytokine levels may have a role in affecting the saliva secretion in psoriasis patients. Secretion of unstimulated saliva in psoriasis patients decreases with the severity and duration of the disease. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion To evaluate the influence of MMR proteins on clinicopathological characteristics and prognosis of salivary gland adenoid cystic carcinoma (ACC).The solid pattern of ACC showed lower expression for MSH2 (p = 0.039). Significant imbalance in MSH2/MSH6 immunostaining was observed in all histological patterns (p < 0.001), and imbalance in PMS2/MLH1 immunostaining was observed in the cribriform pattern (p = 0.011). The presence of capsule was associated with high expression of MSH6 (p = 0.019), MLH1 (p = 0.045) and PMS2 (p = 0.009). The absence of cribriform pattern (p = 0.002) and capsule pattern (p = 0.025), as well as low expression for MSH6 (p = 0.006) and PMS2 (p = 0.037) were associated with lower overall survival. In multivariate analysis, loss of MSH2 (p = 0.039) and MLH1 (p = 0.017) were significantly associated with worse overall survival.Twenty‐four ACC were clinical‐pathologically evaluated and we perform immunohistochemistry for MSH2, MSH6, PMS2 and MLH1. Percentage counting of positive cells was performed in 10 fields of each histological pattern (cribriform, tubular and solid) and the averages of the 30 fields were considered for evaluation with other clinical‐pathological variables (Kruskal‐Wallis/Dunn, Friedman/Dunn, chi‐square, Log‐Rank Mantel‐Cox tests and Cox regression; SPSS v20.0, p < 0.05).Salivary glands' ACC shows imbalance of the MMR complex and loss of expression of its components is associated with the overall survival of these patients. [ABSTRACT FROM AUTHOR]

The effect of beta-adrenergic stimulation on human labial minor salivary gland epithelial cells (LMSGEC) on IL-6 production and its dependency on endoplasmic reticulum (ER) stress were investigated. Primary LMSGEC from Sjögren's syndrome (SS) patients and controls in culture were stimulated with epinephrine and IL-6 expression was evaluated by qPCR and ELISA. The expression of β-ARs in cultured LMSGEC was tested by qPCR, while adrenoceptors and cAMP levels were examined in LMSGs by immunofluorescence. ER evaluation was performed by transmission electron microscopy (TEM) and ER stress by western blot. Epinephrine-induced IL-6 production by cultured LMSGEC was evaluated after alleviation of the ER stress by applying tauroursodeoxycholic acid (TUDCA) and silencing of PKR-like ER kinase (PERK) and activating transcription factor 4 (ATF4) RNAs. Expression of IL-6 by LMSGEC was upregulated after β-adrenergic stimulation, while the silencing of adrenoreceptors downregulated IL-6. The amelioration of ER stress, as well as the silencing of PERK/ATF4, prevented epinephrine-induced upregulation of IL-6. Adrenergic stimulation led to higher and sustained IL-6 levels secreted by LMSGEC of SS patients compared to controls. Adrenergic signaling was endogenously enhanced in LMSGEC of SS patients (expression of β-ARs in situ, intracellular cAMP in cultured LMSGEC). In parallel, SS-LMSGEC expressed dilated ER (TEM) and higher levels of GRP78/BiP. PERK/ATF4 pathway of the ER stress emerged as a considerable mediator of adrenergic stimulation for IL-6 production by the LMSGEC. An enhanced endogenous adrenergic activation and a stressed ER observed in SS-LMSGEC may contribute to a sustained IL-6 production by these cells after adrenergic stimulation. This paper investigates the effect of beta-adrenergic stimulation on human labial minor salivary gland epithelial cells (LMSGEC) on IL-6 production, and its dependency on endoplasmic reticulum (ER) stress. Primary LMSGEC from Sjögren's syndrome (SS) patients and controls in culture were stimulated with epinephrine and IL-6 expression was evaluated by qPCR and ELISA. Graphical Abstract [ABSTRACT FROM AUTHOR]

Objective: Until now, the clinically relevant improvement for the Xerostomia Inventory (XI) has not been defined. Therefore, our aim was to determine the Minimally Important Difference (MID) of the XI for improvement in dry‐mouth symptoms in SjD patients. Method: The study recruited 34 SjD patients who underwent sialendoscopy of major salivary glands and 15 SjD patients in a nonintervention control group. XI scores were assessed at several time points. The MID was determined from the mean difference in XI scores between the groups with and without improvement. Results: In the control group, no significant XI score changes were seen. In the sialendoscopy group, a clinically relevant XI score change of four scale points was identified after 1 week. For a prolonged duration (≥16 weeks), a minimum reduction of seven scale points in the XI score was required to indicate clinically relevant improvement. Conclusion: In SjD patients, a minimum change of four points in the XI score indicates a clinically relevant improvement for evaluating short‐term effects. For prolonged effects, a clinically relevant improvement requires a MID of seven points. The determination of the MID in XI could assist in future studies that evaluate changes in xerostomia. [ABSTRACT FROM AUTHOR]

Objectives: To establish an inflammation grading system for radioactive iodine‐induced sialadenitis (RAIS) based on spiral computed tomography (CT), ultrasonography and sialography. Methods: In all, 120 RAIS patients (18 males and 102 females) were retrospectively included. Spiral CT, ultrasonography and sialography appearances were analysed and categorized as follows: grade I, approximately normal or mild sialadenitis; grade II, moderate sialadenitis; and grade III, severe sialadenitis. Adenitis severity was analysed relative to sex, age, RAI treatment sessions and cumulative doses. Results: Spiral CT showed heterogeneous (78.9%) and atrophic changes (36.8%) in the parotid glands (PGs) and duct ectasia (24.8%) in the submandibular glands (SMGs). Ultrasonography showed heterogeneous echogenicity (54.3%) and diminished gland size (30.2%) in PGs and duct ectasia in SMGs (34.7%). Sialography showed duct obliteration in 25.3% PGs and 3.2% SMGs. Statistical analysis showed good consistency among the three imaging grading results. The incidence and severity of PG lesions were significantly higher than that of SMGs (p < 0.001). As for PGs, adenitis severity was associated with both treatment sessions and cumulative doses; but in SMGs, disease severity was only related to treatment sessions. Conclusions: A grading system for severity of RAIS was established based on spiral CT, ultrasonography and sialography appearances. [ABSTRACT FROM AUTHOR]

New technologies are increasingly widespread in medical practice. Particularly, the 3D view is considered among the most useful innovations for surgery. It allows the operator to reconstruct the patient's anatomy in his own mind, going beyond his personal imagination. In the last few years, a new facility has been experienced, it's the Exoscopy. Exoscopy is a magnified vision system, similar to Microscopy, but which also allows a tridimensional vision of the surgical anatomy. Despite Exoscopy having been used for years in Neurosurgery, it has been just rarely described in parotid surgery. We intend to report our experience with Exoscope Aesculap AEOS used to remove benign tumors of the parotid gland. We treated 14 patients with benign tumors of the parotid gland, since September 2023 to November 2023. Each surgery was conducted by the same expert surgeon which also reported his experience about intra-operative complications (as bleeding) in comparison to the traditional procedure without Exoscope. We evaluated the learning curve of Exoscope-Assisted Parotid Surgery comparing, among them, the operative times of the same procedures performed in chronological order. Each patient underwent the same follow-up which included three checks at one month, three months and six months. The follow-up was especially about the evaluation of palsy of the VII C.N. which was assessed through House-Brackmann score (H-B score). The results of our experience reports that the Exoscope is a useful tool for parotid gland surgery. It allows an excellent visualization of the facial nerve main trunk and its branches. Although the first procedures presented longer times in comparison to traditional surgery, the progressive reduction of the operative times demonstrates that the learning curve of Exoscopy is very fast. Certainly, more experience is required for the full introduction of Exoscopy in surgery practice of parotid gland but, now, its potentialities are highly exciting. [ABSTRACT FROM AUTHOR]

Central mucoepidermoid carcinoma is a relatively rare salivary gland tumour of the jawbone. Glandular odontogenic cyst is another unique odontogenic developmental cyst characterised by glandular differentiation. Both entities share several histological characteristics, and a pre-existing Glandular odontogenic cyst can evolve into Central mucoepidermoid carcinoma. Case 1: A 56-year-old male presented with chief complaint of swelling in lower left facial region since 1 year. Histopathology revealed multicystic compartments resembling mucoepidermoid carcinoma, but strong positive expression of Cytokeratin 13 upon immunohistochemistry helped us in rendering the final diagnosis as Glandular odontogenic cyst Case 2: A 34-year-old female presented with a lesion on right side of face. Histologically, the biopsy specimen revealed both typical findings of a Glandular odontogenic cyst component and a recognizable component of Mucoepidermoid carcinoma. The results from cytokeratin profiling demonstrated that, while both Mucoepidermoid carcinoma and Glandular odontogenic cyst expressed Cyokeratins 7, 18, and 19. Cytokeratin 13 was interestingly exclusively expressed in Glandular odontogenic cyst. Present case findings showed that central mucoepidermoid carcinoma and Glandular odontogenic cyst may be part of the same disease spectrum. However, because the expression profile of Cytokeratin13 in mucoepidermoid carcinoma and Glandular odontogenic cyst was so diverse, it can be used to differentiate both. [ABSTRACT FROM AUTHOR]

Mucoepidermoid carcinoma (MEC) is a malignant locally invasive tumour of salivary glands, presumed to arise from reserve cells of salivary gland ducts. It accounts approximately 35% of all malignancies of major and minor salivary glands [1]. MEC arising in minor salivary glands can be located in different areas such as palate, retromolar trigone, floor of mouth, buccal mucosa, lips and tongue. MEC of tongue base are not common but they constitute around 50% of malignant lesions of salivary glands in this region. It presents in fifth and sixth decades of life mostly [1]. We present a rare case of 29 year old woman with low grade mucoepidermoid carcinoma of base of tongue operated by the Trotter procedure with harmonic scalpel – median labio-mandibular glossotomy approach. It's an interesting approach first described by William Trotter in 1920s. It's used by head and neck surgeons for accessing tongue base lesions, pharyngeal wall and cervical spine. [ABSTRACT FROM AUTHOR]

Objective: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands. Methods: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2. Results: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months. Conclusion: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes. [ABSTRACT FROM AUTHOR]

Choristomas are aggregates of microscopically normal tissues in aberrant locations. They can be cartilage, bone, glial tissue, salivary gland, and thyroid tissue. Cartilaginous choristomas of the oral cavity are rare and occur most commonly on the tongue and less often in sites such as the soft palate and gingiva. We report two cases of cartilaginous choristoma in young females presenting with recurrent tonsillitis. Histopathological examination showed the presence of mature island of hyaline cartilage surrounded by lymphoid hyperplasia. Level of Evidence: Level 4 [ABSTRACT FROM AUTHOR]

Mumps, caused by the mumps virus, is a contagious disease primarily affecting children and young adults. While typically presenting with salivary gland swelling and systemic symptoms, mumps can lead to various complications including SNHL, orchitis/ oophoritis, aseptic meningitis. Recent observations suggest atypical features in mumps cases, raising concerns of a potential outbreak in India. To discuss the etiopathogenesis and clinical presentation in cases of atypical mumps with increasing number of cases, a prospective multicentric study was conducted across five major centers - SMS Medical College Jaipur, RDBP Jaipuria Hospital, Jaipur, Shri Ashwini Saxena ENT Hospital Rewari, AIIMS Bhubaneswar and SP Medical College Bikaner, in India to evaluate patients with acute salivary gland swellings. Clinical and laboratory data were collected, including demographics, presenting symptoms, history of vaccination, imaging findings, and treatment outcomes. Patients were followed for four weeks post-treatment to monitor for delayed complications. Among 53 patients, a bimodal age distribution was observed, with peaks in early adolescents and middle-aged individuals. Vaccination status was recorded based on recall. Fever and salivary gland swelling were predominant symptoms, with a significant proportion experiencing submandibular gland involvement. Elevated serum amylase and CRP levels correlated with disease severity and prolonged symptomatic resolution. Notably, cases of sensorineural hearing loss (SNHL) and airway complications emerged as significant concerns. The study highlights a shift in mumps demographics, with higher age groups affected and increased incidence of complications like SNHL and airway compromise. International trends also suggest periodic outbreaks and evolving clinical manifestations post-COVID-19 pandemic. Factors contributing to mumps resurgence include lack of vaccination or vaccine efficacy, population immunity, and seasonal variations. India appears to be facing a potential mumps outbreak, characterized by atypical features and increased risk of complications like SNHL and airway compromise. Serum amylase and CRP serve as valuable markers for disease severity. Early recognition and management of complications are crucial, emphasizing the importance of mumps immunization to mitigate the impact of the disease. ENT specialists should remain vigilant for emerging complications, particularly SNHL, advocating for comprehensive immunization strategies. [ABSTRACT FROM AUTHOR]

Salivary gland canalicular adenoma is rare yet benign. It accounts for fewer than 1% of salivary tumors and is the third most common non-cancerous mass in the small salivary glands. A 45-year-old presented to the outpatient department with complaints of swelling in the left parotid region for the past 3 years. Examination revealed a firm swelling in the left parotid region. USG and MRI revealed features suggestive of pleomorphic adenoma. Superficial parotidectomy was planned but intra-operatively, the mass was seen between the two lobes of the parotid, which was removed, and on histopathological examination, it was diagnosed as canalicular adenoma. Post-operatively, the patient's condition is excellent. [ABSTRACT FROM AUTHOR]

Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour that primarily affects the liver, lungs and bone. It is very rarely described in the head and neck region, and is exceptionally uncommon within the submandibular region. We report a very rare case of EHE originating in a lymph node within the submandibular salivary gland of a 54-year-old female patient. The tumour was resected and the patient was regularly followed up, with no recurrence of disease at 24 months postoperatively. A review of existing literature, clinical and immunohistopathological features are discussed, which highlight the diagnostic dilemma, absence of consensus for management and appropriate surveillance method associated with EHE. [ABSTRACT FROM AUTHOR]

[Display omitted] • Lipidomics identified 23 lipid classes low in glycolipids in tick salivary glands. • Phosphatidylcholine (PC; 26.66%) was the lipid class with the highest representation. • Tick salivary glycolipids were mostly represented by diacylglycerol (DG; 0.48%). • Individuals bitten by ticks produced more phosphatidylcholine-IgG antibodies. • DG levels were higher in tick salivary glands than in tick saliva. Ticks, as hematophagous ectoparasites, can manipulate host immune and metabolic processes, causing tick-borne allergies such as α-Gal syndrome (AGS). Glycolipids with bound galactose-alpha-1–3-galactose (α-Gal) are potential allergenic molecules associated with AGS. Nevertheless, proteins and lipids lacking α-Gal modifications may contribute to tick salivary allergies and be linked to AGS. In this study, we characterized the effect of deglycosylated tick salivary proteins without lipids on treated zebrafish fed with dog food formulated with mammalian (beef, lamb, pork) meat by quantitative proteomics analysis of intestinal samples. The characterization and functional annotations of tick salivary lipids with low representation of glycolipids was conducted using a lipidomics approach. Results showed a significant effect of treatment with saliva and saliva deglycosylated protein fraction on zebrafish abnormal or no feeding (p < 0.005). Treatment with this fraction affected multiple metabolic pathways, defense responses to pathogens and protein metabolism, which correlated with abnormal or no feeding. Lipidomics analysis identified 23 lipid classes with low representation of glycolipids (0.70% of identified lipids). The lipid class with highest representation was phosphatidylcholine (PC; 26.66%) and for glycolipids it corresponded to diacylglycerol (DG; 0.48%). Qualitative analysis of PC antibodies revealed that individuals bitten by ticks were more likely to produce PC-IgG antibodies (p < 0.001). DG levels were significantly higher in tick salivary glands (p < 0.05) compared with tick saliva and salivary fractions. The α-Gal content was higher in tick saliva than in deglycosylated saliva and lipid fractions. These results support a possible role for tick salivary proteins and lipids without α-Gal modifications in AGS. [ABSTRACT FROM AUTHOR]

Introduction: Stem cells from various sources including major salivary glands have been used to establish pancreatic differentiation in an attempt to provide new treatment options for patients with diabetes mellitus. In contrast, the potential of using the more easily accessible intraoral minor salivary glands has not been evaluated so far. Materials and Methods: Salivary stem cells were isolated from normal labial minor salivary glands that were removed during the excision of a mucocele and were attempted to differentiate into pancreatic cell lines using a culture medium enriched with activin A, retinoic acid and GLP-1.Real time RT-PCR was used to evaluate the expression of the genes of pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx. Complementary, 22 labial minor salivary gland paraffin-embedded specimens were examined using immunohistochemistry for the presence of the relevant gene products of the pancreatic transcription factors Arx, MafA, Ptf1a and Pdx1. Results: The differentiated salivary stem cells(cells of passage 3) expressed the genes of the pancreatic transcription factors MafA, Ptf1a, Hb9 and Arx even on the first day of the experiment while immunohistochemistry also confirmed the presence of the protein products of Arx, MafA, Ptf1a as well as Pdx1[> 50% of the specimens for Arx(5/8) and MafA(7/8), < 50% for Ptf1a(5/11) and Pdx1(5/11)] in ducts, mesenchymal connective tissue and acinar cells. Conclusions: Labial minor salivary glands may share gene and protein characteristics with pancreas suggesting a possible usefulness for pancreatic regeneration or substitution in cases of deficiency. [ABSTRACT FROM AUTHOR]

Objectives To compare focus score and other histopathological features between paired labial and parotid salivary gland biopsies in a diagnostic cohort of suspected Sjögren's disease (SjD) patients. Methods Labial and parotid salivary gland biopsies were simultaneously obtained from patients with sicca complaints, suspected of having SjD. Biopsies were formalin fixed and paraffin embedded. Sections were stained with haematoxylin & eosin, and for CD3, CD20, CD45, cytokeratin, CD21, Bcl6, activation-induced deaminase (AID) and IgA/IgG. Focus score and other histopathological features characteristic for SjD were analysed. Results Based on the expert opinion of three experienced rheumatologists, 36 patients were diagnosed as SjD and 63 as non-SjD sicca patients. When taking all patients together, absolute agreement of various histopathological features between labial and parotid biopsies was high and varied between 80% (focus score) and 93% [(pre-)lymphoepithelial lesions (LELs)]. More labial gland biopsies had a focus score ≥1 compared with their parotid counterpart. Accordingly, the area of infiltrate was larger in labial gland biopsies. When considering only SjD patients, labial glands contained significantly fewer B-lymphocytes and germinal centres/mm2, and less severe LELs compared with parotid glands. Conclusion Labial and parotid glands from SjD patients contain similar histopathological key features, and thus both glands can be used for diagnosis and classification of SjD. However, parotid salivary glands reveal more evident B-lymphocyte-related features, while labial glands exhibit more inflammation, which may be partially unrelated to SjD. [ABSTRACT FROM AUTHOR]

Aims Methods and Results Conclusion Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with HMGA2 fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context.A retro‐ and prospective review (2013–2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty‐one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next‐generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma‐like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well‐demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S‐100, and SOX‐10 and variable expression of p63 but negative p40. HMGA2 alterations were detected in 16 of 18 cases (89%). Follow‐up was available on two carcinomas, with one being locally recurrent.While most HMGA2‐positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) poses clinical challenges due to its heterogeneous ocular and systemic manifestations. We aim to report the systemic involvement and the clinical, serological and radiological associations of a cohort of Chinese patients. Methods: A territory-wide, biopsy-proven, Chinese cohort. A retrospective, masked chart review of medical records, orbital images, and histopathology reports. Results: A total of 122 (65 male) patients with a follow-up of 81 ± 49 (24 to 84) months were reviewed. Ninety (74%) patients presented bilaterally. Subacute upper eyelid swelling was the commonest presentation (82/122, 67%). During follow-up, 91/122 patients (75%) underwent extra-orbital imaging including computer tomography (692 films), ultrasonography (182 films), magnetic resonance imaging (76 films) and whole body FDG-PET scan (33 films). Eighty-six (95%) of these 91 patients had extra-orbital involvement radiologically (2.7 ± 1.6 regions, range: 0 to 9). Lymph node was the most prevalent (N = 60,66%), followed by salivary gland (N = 51,56%), lung (N = 49,54%), kidney (N = 22, 24%), hepatobiliary tree (N = 18, 20%) and pancreas (N = 17, 19%). Other organs include thyroid, aorta, meninges/brain and skin. Twenty-eight (23%) patients had allergic diseases (19 asthma, 16 allergic rhinitis, and 6 eczemas). Fifty-seven (48%) patients had paranasal sinusitis. Serum eosinophilia was associated with a higher number (3.24 versus 2.52, P = 0.0304) of organ involvement. Patients with deep organ involvement was associated with a higher age of IgG4-ROD onset (70 ± 12 versus 56 ± 13, P < 0.0001). Conclusions: 95% of the patients who underwent systemic imaging in our cohort had systemic organ involvement. An early physicians' assessment and radiological imaging are recommended after the diagnosis of IgG4-ROD. [ABSTRACT FROM AUTHOR]

Objectives: Among the complications of parotid surgery, facial palsy is frequent and burdened by high functional and social impact for the patient. There are few data on the efficacy of facial neuromuscular retraining (FNR) in patients with facial palsy after parotid surgery, and no data exist on its impact in timing and extent of recovery. Material and methods: A retrospective study was conducted on patients undergoing FN sparing parotid surgery and suffering from postoperative facial palsy. Among 400 patients undergoing surgery between July 2016 and May 2023, those with the preservation of the FN and onset of facial palsy were selected. Nerve function was evaluated during 2 years follow up using the House-Brackman (H&Bs) and Sunnybrook scales (SBs). Results: A total of 46 patients undergoing partial or total parotidectomy were included. At discharge 18 patients (39,1%) had IV to VI grade paralysis according to the H&Bs and the mean SBs value was 54. At 2 and 6 months after surgery, the average value of Sunnybrook increased to 76.5 and 95.4 respectively. After 12 months no patients with IV to VI grade paralysis were represent in our cohort. Two years after surgery, only five patients (10.9%) had persistent grade II paralysis according to HBs. Conclusions: Our study supports the efficacy of FNR in the rehabilitation of facial paralysis after nerve-sparing parotidectomy. The greater functional improvement is achieved within the first 6 months of rehabilitation. A significant improvement is detected still after 18 months, supporting the importance of long rehabilitation for patients without complete recovery after the first year. [ABSTRACT FROM AUTHOR]

Sjӧgren's syndrome (SS), also known as Sjögren's disease, is a chronic autoimmune condition predominantly affecting the salivary and lacrimal glands. The disease is driven by autoimmune responses involving the activation and actions of major innate- and adaptive immune cell subsets. However, the specific characteristics and roles of regulatory T cells (Tregs) in SS remain elusive. This study seeks to clarify the main phenotypic and functional attributes of Tregs in the salivary glands and their draining lymph nodes in murine models of SS. Our flow cytometric analysis revealed that Tregs in the salivary gland-draining lymph nodes of female non-obese diabetic (NOD) mice, a spontaneous model of SS, exhibited a greater proportion of activated Tregs and fewer resting Tregs compared to Balb/c mice. Furthermore, Tregs from the salivary gland-draining lymph nodes of female C57BL/6.NOD-Aec1Aec2 (B6.NOD-Aec) mice, a model for primary SS, demonstrated significantly lower IL-10 production but markedly higher IFNγ- and IL-17 production than their C57BL/6 counterparts. Additionally, treatment of C57BL/6 Tregs with IL-7, a cytokine critical for SS pathogenesis, resulted in diminished IL-10 production and enhanced IFNγ and IL-17 production in these cells. Notably, the alterations in B6.NOD-Aec Tregs also included an increased expression of the immune-inhibitory molecule CTLA-4 compared to the C57BL/6 Tregs. Intriguingly, in vitro co-cultures of Tregs with conventional CD4 T cells and other key immune populations from lymph nodes indicated that Tregs from salivary gland-draining lymph nodes of both B6.NOD-Aec and C57BL/6 strains exhibited comparable and limited immunosuppressive effects on the proliferation and function of conventional CD4 T cells. The ability of B6.NOD-Aec Tregs to directly inflict damages to salivary gland epithelial tissues and contribute to SS pathologies through IFNγ and IL-17 that they produce warrants further investigations. In addition, enhancing the relatively weak immunosuppressive capacities of these Tregs may also serve as a viable strategy to alleviate the SS phenotype in the mouse models and potentially in patients. 1. Tregs in SS murine models exhibit distinct features compared to those in control mice 2. Tregs in target tissues of B6.NOD-Aec model of SS display aberrant cytokine profiles 3. IL-7 treatment increases IFNγ and IL-17 production and reduces IL-10 output in Tregs 4. B6.NOD-Aec Tregs and C57BL/6 Tregs show similarly weak suppressive functions in vitro [ABSTRACT FROM AUTHOR]

The study aimed to determine the influencing factors, reference range, the changes of salivary gland secretion function and repeatability of measurements taken from ultrasound (US) viscoelastic imaging in the salivary glands of healthy adults. From August 2023 to October 2023, 206 healthy adults were recruited. In November 2023, 50 healthy adults were recruited for acid stimulation testing. All volunteers underwent conventional and viscoelastic US of the salivary glands. The viscoelasticity values in different regions of interest (ROI), observers, genders, ages, body mass index (BMI) groups and before and after acid stimulation were compared separately. A two-sided 95% reference range was estimated accordingly. There was no difference in the E-mean and V-mean values among different ROIs (p > 0.05). The intra-group correlation coefficient values between the different observers were all >0.908. Except for the influence of age on the E-mean value of the parotid gland, the V-mean of the parotid gland, the E-mean and V-mean of the submandibular gland were not affected by age, gender or BMI. Finally, differences were detected in the E-means and V-means of the parotid and submandibular glands before and after acid stimulation (p < 0.05). US viscoelastic imaging is a simple and reliable technique for evaluating the stiffness and viscosity of salivary glands in healthy adults. It also can be used to dynamically evaluate the changes of salivary gland secretion function. [ABSTRACT FROM AUTHOR]

Tertiary lymphoid structures (TLSs) are formed in tissues targeted by chronic inflammation processes, such as infection and autoimmunity. In Sjögren's disease, the organization of immune cells into TLS is an important part of disease progression. Here, we investigated the dynamics of tissue resident macrophages in the induction and expansion of salivary gland TLS. We induced Sjögren's disease by cannulation of the submandibular glands of C57BL/6J mice with LucAdV5. In salivary gland tissues from these mice, we analyzed the different macrophage populations prior to cannulation on day 0 and on day 2, 5, 8,16 and 23 post-infection using multicolored flow cytometry, mRNA gene analysis, and histological evaluation of tissue specific macrophages. The histological localization of macrophages in the LucAdV5 induced inflamed salivary glands was compared to salivary glands of NZBW/F1 lupus prone mice, a spontaneous mouse model of Sjögren's disease. The evaluation of the dynamics and changes in macrophage phenotype revealed that the podoplanin (PDPN) expressing CX3CR1+ macrophage population was increased in the salivary gland tissue during LucAdV5 induced inflammation. This PDPN+ CX3CR1+ macrophage population was, together with PDPN+CD206+ macrophages, observed to be localized in the parenchyma during the acute inflammation phase as well as surrounding the TLS structure in the later stages of inflammation. This suggests a dual role of tissue resident macrophages, contributing to both proinflammatory and anti-inflammatory processes, as well as their possible interactions with other immune cells within the inflamed tissue. These macrophages may be involved with lymphoid neogenesis, which is associated with disease severity and progression. In conclusion, our study substantiates the involvement of proinflammatory and regulatory macrophages in autoimmune pathology and underlines the possible multifaceted functions of macrophages in lymphoid cell organization. [ABSTRACT FROM AUTHOR]

Introduction and aim: Adenoma pleomorphum (multiform adenoma) is the most popular bening tumor, that originates from the salivary glands. Neoplasm develops mainly from large salivary glands and its occurrence in the nasal cavity is rare and falls mainly in the 3-6 decade of life. Only 1% of all pleomorphic adenomas develop in the nasal and sinus cavities. Despite being a benign tumor, malignant transformation can occur in 2-10% of cases. Description of the case: We report a case of a 21-year-old female ethnically Polish patient with nasal multiform adenoma with initial diagnosis, which indicated a polyp. The final diagnosis was based on the histopathological examination of the resected lesion. The tumor was removed by an endoscopic method with no tissue margins, which may increase the risk of recurrence. Conclusions: Our case demonstrates that despite pleomorphic adenomas typically occurs in the 3rd to 6th decade of life, clinical symptoms are nondistinctive with a polyp and nasal cavity is a very rare location there should be always be increased vigilance leading to choosing best diagnostic measures to form right diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The complex nature of Sjögren's Disease (SjD) necessitates a comprehensive and patient-centered approach in both diagnosis and management. This narrative review emphasizes the need for a holistic understanding of the connection between salivary gland inflammation and oral symptoms in SjD. Areas covered: The intricate relationship between salivary gland inflammation and dry mouth is explored, highlighting the variability in associations reported in studies. The association of the severity of xerostomia and degree of inflammation is also discussed. The frequent presence of recurrent sialadenitis in SjD further accentuates the connection of compromised salivary gland function and inflammation. The review additionally discusses local inflammatory factors assessed through salivary gland biopsies, which could potentially serve as predictors for lymphoma development in SjD. Insights into compromised quality of life and hypercoagulable state and their association with salivary gland inflammations are provided. Advancements in noninvasive imaging techniques, particularly salivary gland ultrasonography and color Doppler ultrasound, offer promising avenues for noninvasive assessment of inflammation. Expert opinion: There is a need for longitudinal studies to unravel the connections between salivary gland inflammation and oral symptoms. This will enhance management strategies and optimize treatment outcomes for SjD patients. [ABSTRACT FROM AUTHOR]

Introduction: Almost one-quarter of immune checkpoint inhibitor (ICI) recipients experience sicca syndrome, while Sjögren's disease (SjD) is estimated at 0.3–2.5%, possibly underreported. Areas covered: This narrative review (Medline/Embase until January/31/2024) addresses the pathophysiology, incidence, demographic/clinical features, biomarkers, labial salivary gland biopsy (LSGB), fulfillment of the idiopathic SjD (iSjD) classificatory criteria, differential diagnosis, and management of sicca syndrome/SjD associated with ICIs. Expert opinion: SjD associated with ICIs is underdiagnosed, since studies that performed the mandatory SjD investigation identified that 40–60% of patients with sicca syndrome associated with ICIs meet the iSjD classificatory criteria. LSGB played a fundamental role in recognizing these cases, as most of them had negative anti-Ro/SS-A antibody. Despite the finding of focal lymphocytic sialoadenitis in LSGB samples mimicking iSjD, immunohistochemical analysis provided novel evidence of a distinct pattern for sicca syndrome/SjD associated with ICIs compared to iSjD. The former has scarcity of B lymphocytes, which are a hallmark of iSjD. Additionally, patients with sicca syndrome/SjD associated with ICIs have demographical/clinical/serological and treatment response dissimilarities compared to iSjD. Dryness symptoms are more acute in the former than in iSjD, with predominance of xerostomia over xerophthalmia, and partial/complete response to glucocorticoids. Dryness symptoms in ICI-treated patients warrant prompt SjD investigation. [ABSTRACT FROM AUTHOR]

Introduction: Primary Sjögren's syndrome (pSS) is an autoimmune disorder primarily affecting salivary and lacrimal glands, although about 40% of patients experience systemic complications. In this setting, the identification of patient phenotypes characterized by increased risk of extra-glandular involvement still represents an unmet need. Areas covered: The aim of this paper is to review the scientific evidence on the utility of salivary gland biopsies in pSS, emphasizing their role in defining prognosis. In latest years, research focused on disease-specific clinical, serological, or histological features able to categorize patient prognosis. Among histopathological features, focus score and ectopic germinal centers exhibit associations with glandular and extraglandular manifestations, including higher rates of lymphomagenesis. Expert Opinion: Pathological characterization of salivary glands provides information that go beyond a mere diagnostic or classification utility, providing insights for a stratification of disease severity and for predicting systemic manifestations. Thus, a salivary gland biopsy should be offered to all patients and included in routine practice, even when not strictly required for diagnostic purposes. More advanced analysis techniques of the tissue, including immunohistochemistry and 'omics' should be further explored in longitudinal studies to boost the ability to further stratify and predict disease evolution. [ABSTRACT FROM AUTHOR]

Proton therapy gives less dose to healthy tissue compared to conventional X-ray therapy, but systematic comparisons of normal tissue responses are lacking. The aim of this study was to investigate late tissue responses in the salivary glands following proton- or X-irradiation of the head and neck in mice. Moreover, we aimed at investigating molecular responses by monitoring the cytokine levels in serum and saliva. Female C57BL/6J mice underwent local fractionated irradiation with protons or X-rays to the maximally tolerated acute level. Saliva and serum were collected before and at different time points after irradiation to assess salivary gland function and cytokine expression. To study late responses in the major salivary glands, histological analyses were performed on tissues collected at day 105 after onset of irradiation. Saliva volume after proton and X-irradiation was significantly lower than for controls and remained reduced at all time points after irradiation. Protons caused reduced saliva production and fewer acinar cells in the submandibular glands compared to X-rays at day 105. X-rays induced a stronger inflammatory cytokine response in saliva compared to protons. This work supports previous preclinical findings and indicate that the relative biological effectiveness of protons in normal tissue might be higher than the commonly used value of 1.1. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the salivary gland ultrasonography(SGUS) findings in patients with primary Sjögren's Syndrome (pSS) and diabetes mellitus(DM) patients with sicca symptoms and to examine the relationship between salivary gland ultrasonography (SGUS) findings with clinical and laboratory parameters. Methods: In this study, 34 patients with pSS and 34 DM patients with sicca symptoms were included. In all patients, bilateral parotid, and submandibular gland ultrasonography (totally 272 glands) was performed by blinded rheumatologist, using the Hocevar and the Outcome Measures in Rheumatology (OMERACT) scoring system. Clinic and ultrasonographic variables were compared between groups. The association between SGUS score and disease duration was analyzed by correlation analysis. Results: Patients with pSS presented significantly higher SGUS scores than patients with DM (the Hocevar score; 20.93(± 9.65) vs. 3.82(± 3.71); p < 0.05, the OMERACT score; 5.96(± 2.30) vs. 2.07(± 1.65); p < 0.05, respectively). In patients with pSS, the submandibular gland scores were significantly higher than the parotid gland scores (right; p < 0.05 vs. left; p < 0.01) while DM patients showed significantly higher parotid gland scores (right; p < 0.05 vs. left; p < 0.05). In pSS patients, the SGUS scores were associated with disease duration (r = 0.57; r = 0.50; p < 0.05), symptom duration (r = 50; r = 0.47; p < 0.05), and the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI)-dryness score (r = 0.35, r = 0.36; p < 0.05). However, in DM patients, the SGUS scores are highly correlated with the ESSPRI-dryness (r = 0.74, r = 0.72; p < 0.05) and HbA1C level (r = 0.91, r = 0.86; p < 0.05). Conclusions: This study demonstrated that major salivary gland involvement was more severe and correlated with disease duration, and submandibular gland was dominantly affected in pSS. Contrarily, in DM patients, salivary gland involvement was milder, parotid dominant and related to level of dryness and HbA1C, rather than disease duration when compared to pSS, [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Conclusions Oral and maxillofacial tissue defects resulting from factors such as trauma or infection, can significantly impact both facial function and aesthetics. Additionally, the complex anatomical structure of the face often increases the difficulty of treatment. With the advantages of controlled release, targeted delivery, and enhanced mechanical properties, injectable hydrogels have been investigated for the treatment of oral and maxillofacial diseases. In the field of regeneration, injectable hydrogels have a structure similar to the extracellular matrix (ECM) and are biocompatible, which can be used as scaffolds for tissue regeneration.This review aims to summarize the literature on the current status and limitations of injectable hydrogels in the field of oral tissue regeneration.We searched Pubmed and Web of Science databases to find and summarize the articles on the application of injectable hydrogels in tissue regeneration.This review focuses on the current status and limitations of injectable hydrogels in the field of tissue regeneration (periodontal tissue, dentin‐pulp complex, bone and cartilage, salivary gland regeneration, and mucosal repair). Although fully studied in animal models, there are still challenges in clinical transformation of injectable hydrogels in promoting tissue regeneration. [ABSTRACT FROM AUTHOR]

In the pathogenesis and progression of Sjögren's syndrome (SS), hematopoietic cells in the peripheral circulation, tissue-resident immune cells, and parenchymal cells of salivary gland tissues (such as epithelial cells, endothelial cells, fibroblasts, etc.) all play crucial roles. These diverse cells form intricate networks and interact with each other, leading to tissue destruction and persistent chronic inflammation, ultimately causing irreversible damage in glandular function. Among these, salivary gland epithelial cells (SGECs) consistently hold a key position, characterized by their functions in expressing co-stimulatory and antigen-presenting molecules and secreting pro-inflammatory cytokines and chemokines. Moreover, SGECs actively engage in and facilitate the development of specific pathological structures within the salivary gland, such as lymphoepithelial lesions (LELs) and tertiary lymphoid structures (TLSs), thereby substantially elevating the risk of mucosa-associated lymphoid tissue (MALT) lymphoma. Overall, SGECs are recognized for their essential and irreplaceable contributions to the pathogenesis of SS. This review article initially delves into the anatomical composition of salivary gland epithelial cells, subsequently focusing on elucidating the different cytokines derived from SGECs, encompassing chemokines, pro-inflammatory cytokines, anti-inflammatory cytokines, prosurvival cytokines, and damage-associated molecular patterns (DAMPs), to explore their key roles in the pathogenesis of SS. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 74-year-old female patient with rheumatoid arthritis who developed adenosquamous carcinoma within a long-standing intrapulmonary bronchogenic cyst. The patient was asymptomatic for 43 years before experiencing dropping serum sodium levels, which led to the discovery of the malignancy. The article emphasizes the importance of surgical excision for bronchogenic cysts due to the risk of malignant transformation, even after a long period of time. It also discusses the molecular characteristics of adenosquamous carcinomas and potential targeted therapies. [Extracted from the article]

Simple Summary: This study investigates the influence of various pharmacokinetic parameters on 177Lu-PSMA therapies via physical, biological, and statistical measures. Employing a clinically validated physiologically based pharmacokinetic (PBPK) model, realistic time–activity curves (TACs) in tumors, salivary glands, and kidneys are generated, allowing for the calculation of metrics such as AUC, dose, BED, and fBED. The results demonstrate the significant impact of multiple parameters on the measured outcomes. In addition to the great impact of administered ligand amount, tumor volume, and receptor density, other pharmacokinetic parameters such as rates of radiopharmaceutical association, internalization, and release were identified as key influencers. Notably, alterations in the parameters induced distinct modifications in TAC features, affecting radiobiological, pharmacokinetic, and statistical aspects. These insights contribute to advancing personalized treatment regimens by understanding the key contributions of various parameters towards improving therapeutic efficacy while minimizing radiation-related toxicities. Purpose: To investigate the impact of physiologically based pharmacokinetic (PBPK) parameters on physical, biological, and statistical measures in lutetium-177-labeled radiopharmaceutical therapies (RPTs) targeting the prostate-specific membrane antigen (PSMA). Methods: Using a clinically validated PBPK model, realistic time–activity curves (TACs) for tumors, salivary glands, and kidneys were generated based on various model parameters. These TACs were used to calculate the area-under-the-TAC (AUC), dose, biologically effective dose (BED), and figure-of-merit BED (fBED). The effects of these parameters on radiobiological, pharmacokinetic, time, and statistical features were assessed. Results: Manipulating PBPK parameters significantly influenced AUC, dose, BED, and fBED outcomes across four different BED models. Higher association rates increased AUC, dose, and BED values for tumors, with minimal impact on non-target organs. Increased internalization rates reduced AUC and dose for tumors and kidneys. Higher serum protein-binding rates decreased AUC and dose for all tissues. Elevated tumor receptor density and ligand amounts enhanced uptake and effectiveness in tumors. Larger tumor volumes required dosimetry adjustments to maintain efficacy. Setting the tumor release rate to zero intensified the impact of association and internalization rates, enhancing tumor targeting while minimizing the effects on salivary glands and kidneys. Conclusions: Optimizing PBPK parameters can enhance the efficacy of lutetium-177-labeled RPTs targeting PSMA, providing insights for personalized and effective treatment regimens to minimize toxicity and improve therapeutic outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate salivary gland involvement in patients with anti-centromere antibody (ACA)-positive primary Sjögren's syndrome (pSS). We retrospectively evaluated 134 patients with pSS. Patients were divided into four groups based on the results of ACA and SSA antibodies. We compared clinical manifestations, laboratory findings, salivary gland shear wave elastography, minor salivary gland biopsy results, and EULAR Sjögren's syndrome disease activity index (ESSDAI) scores among the four groups. A total of 134 patients were classified as having pSS and divided into three groups based on serum ACA and anti-SSA antibody status: ACA + SSA + , ACA + SSA-, ACA-SSA + , and seronegative. The primary analysis focused on comparing the clinical and SWE findings between the ACA + SSA + and ACA + SSA- groups. In the double-positive group, SWE revealed fewer minor salivary glands along with higher mean (Emean) and maximum (Emax) values of Young's moduli than those in the ACA-negative group. Patients in the positive group had increased occurrence of Raynaud's phenomenon, liver involvement, and a higher incidence of malignancy (P < 0.05). ACA-positive pSS patients are a subgroup with different clinical manifestations and more pronounced involvement of the minor salivary glands. SWE findings revealed that ACA-positive patients exhibit significantly higher mean and maximum stiffness values compared to ACA-negative patients, indicating more extensive glandular fibrosis and involvement. These results underscore the utility of SWE as a valuable method for evaluating salivary gland pathology and supporting the stratification of pSS patients. [ABSTRACT FROM AUTHOR]

Summary: Catalase (CAT) is the main reactive oxygen species (ROS)‐scavenging enzyme in plants and insects. However, it remains elusive whether and how insect saliva CAT suppresses ROS‐mediated plant defense, thereby promoting initial virus transmission by insect vectors.Here, we investigated how leafhopper Recilia dorsalis catalase (RdCAT) was secreted from insect salivary glands into rice phloem, and how it was perceived by rice chaperone NO CATALASE ACTIVITY1 (OsNCA1) to scavenge excessive H2O2 during insect‐to‐plant virus transmission.We found that the interaction of OsNCA1 with RdCAT activated its enzymatic activity to decompose H2O2 in rice plants during leafhopper feeding. However, initial insect feeding did not significantly change rice CATs transcripts. Knockout of OsNCA1 in transgenic lines decreased leafhopper feeding‐activated CAT activity and caused higher H2O2 accumulation. A devastating rice reovirus activated RdCAT expression and promoted the cosecretion of virions and RdCAT into leafhopper salivary cavities and ultimately into the phloem. Virus‐mediated increase of RdCAT secretion suppressed excessive H2O2, thereby promoting host attractiveness to insect vectors and initial virus transmission.Our findings provide insights into how insect saliva CAT is secreted and perceived by plant chaperones to suppress the early H2O2 burst during insect feeding, thereby facilitating viral transmission. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Positronium is abundantly produced within the molecular voids of a patient's body during positron emission tomography (PET). Its properties dynamically respond to the submolecular architecture of the tissue and the partial pressure of oxygen. Current PET systems record only two annihilation photons and cannot provide information about the positronium lifetime. This study presents the in vivo images of positronium lifetime in a human, for a patient with a glioblastoma brain tumor, by using the dedicated Jagiellonian PET system enabling simultaneous detection of annihilation photons and prompt gamma emitted by a radionuclide. The prompt gamma provides information on the time of positronium formation. The photons from positronium annihilation are used to reconstruct the place and time of its decay. In the presented case study, the determined positron and positronium lifetimes in glioblastoma cells are shorter than those in salivary glands and those in healthy brain tissues, indicating that positronium imaging could be used to diagnose disease in vivo. [ABSTRACT FROM AUTHOR]

AbstractPrimary pulmonary salivary gland tumors (PSGT) constitute a rare subtype of non-small cell lung cancer (NSCLC). Currently, no established treatment guidelines exist for advanced PSGT. The efficacy of platinum-based chemotherapy for PSGT within the context of NSCLC remains uncertain. Therefore, we retrospectively collected 37 PSGT patients who underwent first-line platinum-based chemotherapy from 2010 to 2023. Survival analysis, employing the Kaplan–Meier method, and group comparisons via the log rank test were conducted. Our results show that first-line platinum-based chemotherapy demonstrates favorable efficacy and manageable safety in advanced PSGT, with the combination of Paclitaxel + Platinum emerging as a preferred option. [ABSTRACT FROM AUTHOR]

Background: Epithelial tumors of lacrimal glands are rare and primary ductal adenocarcinoma of the lacrimal gland accounts for only 2% of all epithelial lacrimal gland tumors. Considering its rarity and lack of uniform diagnostic criteria, treatment protocols are not well defined. In this study, we describe a Her‐2 positive case and review previously reported cases. Methods: In 2012, a 42‐year‐old woman affected by primary ductal adenocarcinoma of the lacrimal gland was treated with transpalpebral anterior orbitotomy and adjuvant radiotherapy. In July 2013, she presented local relapse and she underwent orbital exenteration. In November 2013, for neck nodal progression, seven cycles of chemotherapy (cisplatin and epirubicin) associated with a humanized monoclonal antibody–targeting HER 2 therapy (trastuzumab and pertuzumab) were performed, with a marked response rate. Then, she underwent total parotidectomy with right neck lymphadenectomy and adjuvant hadrontherapy. Results: Nine years later (113 months) after treatment completion, the patient was alive without disease and with acceptable toxicity. Conclusions: In primary ductal adenocarcinoma of the lacrimal gland, early diagnosis and multimodal treatments could be crucial, considering its often aggressive tendency. Considering the lack of treatment guidelines, case report recording can be useful in patient management. [ABSTRACT FROM AUTHOR]

The tomato-potato psyllid, Bactericera cockerelli (Šulc), belonging to the Hemiptera order, is an insect pest of solanaceous crops and vectors a fastidious bacterium, Candidatus Liberibacter solanacearum (CLso), the presumptive causal agent of zebra chip and vein greening diseases in potatoes and tomatoes, respectively. The genome of B. cockerelli has been sequenced recently, providing new avenues to elucidate mechanistic insights into pathogenesis in vegetable crops. In this study, we performed RNA-sequencing of the critical psyllid organs (salivary glands and ovaries) involved in CLso pathology and transmission to host plants. Transcriptome analysis revealed differentially expressed genes and organ-specific enrichment of gene ontology (GO) terms related to metabolic processes, response to stress/stimulus, phagocytosis, proteolysis, endocytosis, and provided candidate genes encoding transcription factors (TFs). To examine gene regulatory networks across the psyllid organs under CLso(-) and CLso(+) conditions, we performed weighted gene co-expression network analysis (WGCNA), and unique modules differentiating the psyllid organs were identified. A comparative GO analysis of the unique gene modules revealed functional terms enriched in response to stress, gene regulation, and cell division processes in the ovaries. In contrast, respiration, transport, and neuronal transmission-related GO terms were enriched in the salivary glands. Altogether, this study reveals new insights into tissue-specific expression of the psyllid organs in the absence or presence of CLso bacterium. This knowledge can be leveraged to develop new pest and disease management strategies by delineating the regulatory networks involved in the psyllid-CLso interaction. [ABSTRACT FROM AUTHOR]

Background: Trypanosomiasis is an infectious disease caused by parasitic protozoa of the genus Trypanosome and primarily transmitted by tsetse flies. This study aimed to determine the density of tsetse flies and the rate of trypanosome infection in the Bedele and Dabo Hana districts of the Buno Bedele Zone in Ethiopia. Results: A cross-sectional study was conducted from January to February 2023 to catch tsetse flies, determine tsetse density, and estimate the trypanosome infection rate. We used 100 traps (40 NGU, 30 pyramidal, and 30 biconical) to catch the flies. The following standard procedures were followed to identify the specific trypanosome species in the collected tsetse flies: The flies were dissected, and the salivary glands were removed. We placed the salivary glands in a drop of saline solution on a microscope slide. A coverslip was placed over the salivary glands, the slide was examined under a microscope, and the trypanosomes were identified based on their morphology. A total of 3,740 tsetse flies were captured from 100 traps, resulting in an overall apparent density of 18.7 flies per trap per day. Within the study area, only one species of tsetse fly, Glossina tachinoides, was identified. Of the 1,320 dissected Glossina tachinoides, 1.82% were found to be infected with trypanosome parasites. Among these infections, 58.33% were attributed to Trypanosoma congolense, while the remaining 41.67% were caused by Trypanosoma brucei. The infection rate of trypanosomes was significantly higher in female tsetse flies (87.5%) as compared to male flies (12.5%). Furthermore, a significantly higher infection rate was observed in flies older than 20 days (83.33%) and in hunger stage 1 flies (58.33%) compared to hunger stages 2, 3, and 4. Conclusions: This study highlights the necessity of implementing control and suppression measures targeting the vector (tsetse flies) and the parasite (trypanosomes) to effectively manage and prevent pathogenic animal trypanosomiasis. [ABSTRACT FROM AUTHOR]

Non-healing skin wounds pose significant clinical challenges, with biologic products like exosomes showing promise for wound healing. Saliva and saliva-derived exosomes, known to accelerate wound repair, yet their extraction is difficult due to the complex environment of oral cavity. In this study, as a viable alternative, we established human minor salivary gland organoids (hMSG-ORG) to produce exosomes (MsOrg-Exo). In vitro, MsOrg-Exo significantly enhanced cell proliferation, migration, and angiogenesis. When incorporated into a GelMA-based controlled-release system, MsOrg-Exo demonstrated controlled release, effectively improving wound closure, collagen synthesis, angiogenesis, and cellular proliferation in a murine skin wound model. Further molecular analyses revealed that MsOrg-Exo promotes proliferation, angiogenesis and the secretion of growth factors in wound sites. Proteomic profiling showed that MsOrg-Exo's protein composition is similar to human saliva and enriched in proteins essential for wound repair, immune modulation, and coagulation. Additionally, MsOrg-Exo was found to modulate macrophage polarization, inducing a shift towards M1 and M2 phenotypes in vitro within 48 h and predominantly towards the M2 phenotype in vivo after 15 days. In conclusion, our study successfully extracted MsOrg-Exo from hMSG-ORGs, confirmed the effectiveness of the controlled-release system combining MsOrg-Exo with GelMA in promoting skin wound healing, and explored the potential role of macrophages in this action. [ABSTRACT FROM AUTHOR]

Salivary gland branching morphogenesis is regulated by the functional integration of neuronal signaling, but the underlying mechanisms are not fully understood in aging accelerated klotho‐deficient (Kl−/−) mice. Here, we investigated whether the neuropeptides substance P (SP) and neuropeptide Y (NPY) affect the branching morphogenesis of embryonic salivary glands in aging Kl−/− mice. In the salivary glands of embryonic Kl−/− mice, morphological analysis and immunostaining revealed that epithelial bud formation, neuronal cell proliferation/differentiation, and the expression of the salivary gland functional marker ZO‐1 were decreased in embryonic ductal cells. Incubation with SP/NPY at E12‐E13d promoted branching morphogenesis, parasympathetic innervation, and epithelial proliferation in salivary glands of embryonic Kl−/− mice. The ERK inhibitor U0126 specifically inhibited neuronal substance‐induced epithelial bud formation in the embryonic salivary gland. RNA‐seq profiling analysis revealed that the expression of fibroblast growth factors/fibroblast growth factors (FGFs/FGFRs) and their receptors was significantly regulated by SP/NPY treatment in the embryonic salivary gland (E15). The FGFR inhibitor BGJ389 inhibited new branching formation induced by SP and NPY treatment and ERK1/2 expression. These results showed that aging may affect virtually the development of salivary gland by neuronal dysfunction. The neuropeptides SP/NPY induced embryonic salivary gland development through FGF/FGFR/ERK1/2‐mediated signaling. [ABSTRACT FROM AUTHOR]