Search Results (128)

Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with anti-synthetase/SD overlap syndrome and review the literature to identify published cases describing this overlap, aiming to better define its clinical, radiological, and serological features. Methods: The case description was based on a retrospective collection of clinical, laboratory, and imaging data related to the patient’s diagnostic process and clinical course. Data were anonymized and handled in accordance with the competent territorial Ethics Committee. A literature review was performed using the MEDLINE and Scopus databases by combining the keywords “Anti-Synthetase syndrome”, “Sjögren disease”, “Sjögren syndrome”, “Myositis”, and “Interstitial lung disease” (ILD). Published cases were selected if they met the 2016 EULAR/ACR criteria for SD and at least one of the currently proposed classification criteria for ASyS. Results: The described case concerns a 68-year-old woman with rapidly progressive ILD. The diagnosis of anti-synthetase/SD overlap syndrome was based on clinical, serological (anti-Ro52 and anti-PL7 antibodies), histological, and radiological findings. Despite immunosuppressive and antifibrotic treatment, the clinical course worsened, leading to a poor outcome. In addition, six relevant cases were identified in the literature. Clinical presentations, autoantibody profiles, radiological findings, and outcomes were highly heterogeneous. Among the reported cases, no standardized treatment protocols were adopted, reflecting the lack of consensus in managing this rare condition. Conclusions: In anti-synthetase/SD overlap syndrome, ILD may follow a rapidly progressive course. Early recognition can be challenging, especially in the absence of muscular involvement. This case-based review highlights the need for more standardized approaches to the diagnosis and management of this rare and complex overlap syndrome. Full article

Background/Objectives: Skin adnexal tumors (SATs) are rare neoplasms originating from sebaceous glands, hair follicles, and sweat glands, often presenting diagnostic challenges due to their histopathological diversity and clinical resemblance to other lesions. This epidemiological and clinicopathological study aimed to evaluate SATs diagnosed between January 2018 and October 2024 across two medical centers in Turkey. Methods: A total of 652 cases were analyzed based on demographic features, tumor size, anatomical localization, and histological subtypes per the 2018 WHO classification. The study also explored the predictors of malignancy, including tumor size and multifocality. Results: Among the cases, 98% were benign and 2% malignant. Sebaceous tumors were the most common (34.5%), followed by eccrine/apocrine (34.2%) and follicular tumors (31.3%). Benign tumors showed a slight female predominance (56.6%), while malignant tumors were more frequent in males (61.5%). The majority of tumors were located in the head and neck region (84.6%), and a tumor size >20 mm was significantly associated with malignancy. Conclusions: This study, one of the largest series from Turkey, highlights the importance of clinicopathological correlation in SATs. It contributes to the literature by identifying size-based cut-off values for malignancy prediction and by assessing interobserver agreement, multifocality, and tumor subtype distribution. Full article

Background: Type 2 diabetes mellitus (T2DM) is an epidemic chronic disease that affects millions of people worldwide. This study aims to explore the impact of T2DM on the tear proteome, specifically investigating whether alterations occur before the development of diabetic retinopathy. Methods: Flush tear samples were collected from healthy subjects and subjects with preDM and T2DM. Tear proteins were processed and analyzed by mass spectrometry-based shotgun proteomics using a data-independent acquisition parallel acquisition serial fragmentation (diaPASEF) approach. Machine learning algorithms, including random forest, lasso regression, and support vector machine, and statistical tools were used to identify potential biomarkers. Results: Machine learning models identified 17 proteins with high importance in classification. Among these, five proteins (cystatin-S, S100-A11, submaxillary gland androgen-regulated protein 3B, immunoglobulin lambda variable 3–25, and lambda constant 3) exhibited differential abundance across these three groups. No correlations were identified between proteins and clinical assessments of the ocular surface. Notably, the 17 important proteins showed superior prediction accuracy in distinguishing all three groups (healthy, preDM, and T2DM) compared to the five proteins that were statistically significant. Conclusions: Alterations in the tear proteome profile were observed in adults with preDM and T2DM before the clinical diagnosis of ocular abnormality, including retinopathy. Full article

Primary Sjögren’s syndrome (pSS) exhibits considerable clinical and immunological heterogeneity, complicating personalized management. We aimed to delineate the demographic, functional, serological, histopathological, and therapeutic features of a Romanian pSS cohort and to identify biomarker–treatment correlations that could inform patient-oriented strategies. Thirty-two patients meeting the 2016 ACR/EULAR classification criteria for pSS were retrospectively analyzed. Data collected included demographics, autoantibody profiles (Anti-Ro/SSA, Anti-La/SSB, ANA, RF, Anti-CCP), immunoglobulin levels, complement consumption (C3/C4), minor salivary gland biopsy (focus score), salivary flow tests, and systemic inflammation markers (CRP). Pearson correlation matrices were constructed to explore the associations between serological markers and prescribed therapies. The cohort was predominantly female (87.5%) with a mean age of 52.8 ± 9.9 years. Seropositivity rates were 50% for Anti-Ro/SSA, 77% for Anti-La/SSB, and 40% for ANA. Clinically significant glandular dysfunction was evident in 65% of patients (unstimulated flow ≤ 0.1 mL/min), and all biopsies demonstrated focus scores > 1. Methotrexate use correlated strongly with Anti-Ro/SSA and Anti-La/SSB positivity (p ≤ 0.05), indicating its targeted application in seropositive sub-phenotypes. Conclusion: These findings underscore the immunologic and clinical diversity of pSS and support a biomarker-driven, multidisciplinary framework for personalized treatment. Larger prospective and multicenter studies are warranted to validate these correlations and to refine precision medicine approaches in pSS. Full article

Background/Objectives: The purpose of this study was to determine the incidence of salivary gland tumors based on age, gender, histological type, and localization over an eleven-year period at the University Hospital of Split. Methods: The medical records of the Department of Otorhinolaryngology with Head and Neck Surgery and the Department of Maxillofacial Surgery at the University Hospital of Split regarding salivary gland tumors were searched from January 2012 to December 2022. The current fifth World Health Organization (WHO) Classification of Head and Neck Tumors and its criteria were considered during that process. Results: Out of 404 patients, 211 (52.20%) were female and 193 (47.77%) male. The mean age was 60. There were four pediatric patients. Six patients had a combination of two different histological types of salivary gland tumors present simultaneously at the exact localization. Therefore, there were 410 histological types in total, 214 related to females and 196 to males. A total of 361 (88.05%) benign and 49 (11.95%) malignant primary salivary gland tumors were detected. The parotid gland was the predominant location (N = 361, 87.8%). There were no cases affecting the sublingual gland. Pleomorphic adenoma was the most common benign histological type (N = 169, 41.2%). The most common malignant histological types were adenoid cystic carcinoma (N = 9, 2.2%) and mucoepidermoid carcinoma (N = 9, 2.2%). The average incidences of salivary gland tumors in the 11 years for the four Dalmatian counties and the Republic of Croatia were 4.45/100,000 and 0.9/100,000, respectively. Conclusions: The results of this study, primarily the ones concerning histological types and localization, do not deviate from general knowledge about salivary gland tumors. Simultaneous and ipsilateral occurrence of different histological types is a rare and extremely valuable finding. The average incidence for Dalmatian counties and the Republic of Croatia is within the range of the International Agency for Research on Cancer estimates. Full article

Adenomyosis is a benign gynecologic disease that mainly affects women aged 30–50 years old. Background: This pathology is characterized by glands and stroma of the endometrium that enter the myometrium and is confirmed through histopathological examination after hysterectomy. Transvaginal ultrasound is the most accepted imaging approach for the diagnosis and classification of adenomyosis. Existing medical treatments are not curative and are associated with several side effects. Uterine artery embolization is an alternative treatment for controlling the symptoms of adenomyosis with less trauma while preserving the uterus. Methods: The aim of our study was to observe the utility of uterine artery embolization (UAE) compared to hysterectomy in specific cases of adenomyosis. A retrospective cohort study was carried out between February 2024 and April 2025. We included 52 patients in our study: 27 opted for hysterectomy, while the other 25 chose to receive uterine artery embolization between January 2017 and December 2018. Clinical follow-up was assessed using a questionnaire regarding symptomatic changes in menorrhagia, pelvic pain, and quality of life before and after the surgical procedure. Statistical analyses were performed. Results: Patients opted for hysterectomy in cases of severe abnormal uterine bleeding before surgery that severely affected quality of life (p < 0.03 and p < 0.001). After surgery, pelvic pain improved for women who underwent UAE, but patients also reported no pelvic pain after hysterectomy. Furthermore, mild to moderate abnormal uterine bleeding was reported in cases of UAE, and bleeding stopped completely for women who had their uterus removed (p < 0.001). Quality of life improved for both groups and was reported as being good after the interventions. Conclusions: Embolization remains an alternative therapeutic option in adenomyosis but not a substitute for hysterectomy. This was concluded based on a case-by-case evaluation, depending on the desire for pregnancy, with a focus on improved clinical outcomes. Full article

Super-enhancers (SEs) are large clusters of highly active enhancers that play key regulatory roles in cell identity, development, and disease. While conventional methods classify SEs in a binary fashion—super-enhancer or not—this threshold-based approach can overlook significant intermediate states of enhancer activity. Here, we present a dataset and accompanying framework that facilitate a more nuanced, non-binary examination of SE activation across mouse tissue types (mammary gland, lung tissue, and NMuMG cells) and various experimental conditions (normal, tumor, and drug-treated samples). By consolidating overlapping SE intervals and capturing continuous enhancer activity metrics (e.g., ChIP-seq signal intensities), our dataset reveals gradual transitions between moderate and high enhancer activity levels that are not captured by strictly binary classification. Additionally, the data include extensive functional annotations, linking SE loci to nearby genes and enabling immediate downstream analyses such as clustering and gene ontology enrichment. The flexible approach supports broader investigations of enhancer landscapes, offering a comprehensive platform for understanding how SE activation underpins disease mechanisms, therapeutic response, and developmental processes. Full article

Thyroid disease is a health concern related to the thyroid gland, which is vital for controlling the metabolism of the human body. Predominantly affecting women in their fourth or fifth decades of life, thyroid disease can result in physical and mental issues. This research focuses on improving the diagnostic process by creating a classification model that utilises various machine learning models and a deeplearning model to categorise three types of thyroid disease conditions. This research developed an automated system capable of classifying three thyroid conditions using five machine learning models and a deep learning model. Resampling techniques, such as SMOTE oversampling and Random undersampling, are utilised to correct the issue of class imbalance in the dataset. Finally, a web-based application is developed utilising the most effective model, GBC, which facilitates easy classification of thyroid diseases. The experimental analysis showed that the Gradient Boosting Classifier (GBC), using oversampling techniques, achieved the highest level of performance in classifying thyroid diseases, obtaining an accuracy and F1-Score of 99.76%. This study demonstrated that TSH was the most indicative biomarker for thyroid disease classification. The experimental results proved that the Gradient Boosting Classifier (GBC) utilising the oversampling technique achieved a superior performance compared to other classifier models, with an accuracy and F1-Score of 99.76%. This research presented insights that can assist healthcare practitioners in promptly diagnosing thyroid diseases. Full article

Objective: This study introduces a novel method for the automated detection and quantification of meibomian gland morphology using gray value distribution profiles. The approach addresses limitations in traditional manual and deep learning-based meibography analysis, which are often time-consuming and prone to variability. Methods: This study enrolled 100 volunteers (mean age 40 ± 16 years, range 18–85) who suffered from dry eye and responded to the Ocular Surface Disease Index questionnaire for scoring ocular discomfort symptoms and infrared meibography for capturing imaging of meibomian glands. By leveraging pixel brightness variations, the algorithm provides real-time detection and classification of long, medium, and short meibomian glands, offering a quantitative assessment of gland atrophy. Results: A novel parameter, namely “atrophy index”, a quantitative measure of gland degeneration, is introduced. Atrophy index is the first instrumental measurement to assess single- and multiple-gland morphology. Conclusions: This tool provides a robust, scalable metric for integrating quantitative meibography into clinical practice, making it suitable for real-time screening and advancing the management of dry eyes owing to meibomian gland dysfunction. Full article

Background/Objectives: Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the minor salivary glands, often affecting the hard palate. Preoperative diagnosis and surgical planning are challenging due to anatomical complexity and limitations in sampling, generally obtained by fine-needle aspiration (FNA). This study retrospectively evaluated the diagnostic and therapeutic performance of a high-definition ultrasound (HDUS)-guided fine-needle aspiration cytology/biopsy (FNAC/FNAB) protocol in diagnosing intraoral MEC, based on the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), with the relative clinical outcomes. Methods: A cohort of 64 patients with histologically confirmed MEC of the minor salivary glands, treated between 2000 and 2022, was retrospectively analyzed. All patients underwent HDUS-guided FNAC/FNAB, imaging (CT, MRI, and panoramic X-ray), and subsequent surgical treatment. The cytological specimens were classified using the MSRSGC. Surgical margins, histopathological findings, lymph node status, and follow-up outcomes were recorded. Results: Of 64 MECs, 42 cases were finally diagnosed as low-grade (LG)/intermediate grade (IG) and 22 as high-grade (HG) carcinomas, using a two-tier histological classification system. HDUS accurately delineated the lesion size, infiltration depth, and bone proximity, with excellent correlation with surgical specimens (difference ≤ 0.6 mm). MSRSGC classification distributed the cases across all categories, with 28 classified as malignant (category VI). Repeat FNAC improved the diagnostic yield in non-diagnostic and atypical cases. FNAB confirmed the cytological findings in all cases, with immunohistochemistry investigation with Ki-67 supporting tumor grading. Surgical margins were clear in all resections. Lymph node metastases were identified in all patients who underwent neck dissection (n = 18), all with HG-MEC. No recurrences occurred among the LG/IG-MEC patients during a median 2-year follow-up. Conclusions: The combined use of HDUS and FNAC/FNAB, interpreted through the MSRSGC framework, offers a highly accurate, minimally invasive approach for preoperative diagnosis and surgical planning in intraoral MEC. HDUS-guided cytology significantly improves diagnostic reliability, particularly in LG/IG and cystic variants, facilitating tailored surgical management. Also, the clinical outcomes may support the possibility of using a simplified grading classification for two histopathological types. Full article

Background/Objectives: Salivary gland tumors (SGTs) are a rare and histologically heterogeneous group of neoplasms that are challenging to diagnose due to phenotypic heterogeneity and overlapping histomorphological markers. Accurate diagnosis is required for clinical management, particularly in unusual subtypes. The objective of this study was to ascertain whether attenuated total reflectance–Fourier transform infrared (ATR-FTIR) spectroscopy, in combination with enzymatic deglycosylation, would be useful in SGT classification by detecting glycosylation-related metabolic variations. Methods: 155 tissue sections, consisting of 80 SGTs and 75 controls, were analyzed. ATR-FTIR spectroscopy was used to record the mid-infrared (MIR) spectra (4000–400 cm⁻¹) of enzymatically untreated and deglycosylated samples. Spectral data were preprocessed and analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). Enzymatic deglycosylation focused on sialic acid and fucose residues with α2-3,6,8 neuraminidase, α1-2,4,6 fucosidase O, and α1-3,4 fucosidase. Results: Tumor and control samples were discriminated with an OPLS-DA model, achieving an accuracy of 81.9% (78.7% for controls and 85.0% for tumors), especially in the glycosylation-relevant spectral range (850–1250 cm⁻¹). Classification between benign and malignant tumors was more challenging, with an accuracy of 70.0% (72.5% for benign and 67.5% for malignant cases). Enzymatic deglycosylation resulted in detectable changes in the MIR spectra, confirming the contribution of glycosylation to tumor-specific signatures. Benign vs. malignant tumor discrimination was still poor and was not much enhanced in the sense of incorporating glycosylation-specific regions. Conclusions: ATR-FTIR spectroscopy coupled with enzymatic deglycosylation can distinguish tumor and control tissues based on glycan-associated spectral differences. Application of the technique to benign/malignant SGT discrimination is hampered by spectral overlap and tumor heterogeneity. Further research will be necessary to explore other clustering algorithms and larger and more homogeneous datasets for improved diagnostic accuracy. Full article

Background: Intraoperative facial nerve monitoring (IFNM) is becoming increasingly prevalent as an established intraoperative aid in parotid gland surgery. To date, however, there are few scientific studies on the postoperative outcomes of submandibular gland surgery, particularly on the postoperative injury of the marginalis mandibulae branch (MMB) of the facial nerve (FN). This branch represents the most frequent and feared complication of this surgery, with an incidence of 1–7% of cases. Objective: This retrospective study aims to evaluate the incidence of postoperative MMB paralysis in patients undergoing submandibular sialoadenectomy for benign conditions from 2014 to 2023, focusing on the role of IFNM. Materials and Methods: The patients were divided into two groups: the subjects of Group 1 (G1) had undergone submandibular sialoadenectomy after identification and clamped facial vessels, without the aid of IFNM (from 1 January 2014 to 31 December 2018). Conversely, subjects in Group 2 (G2) underwent IFNM procedures (from 1 January 2019 to 31 December 2023). The classification of any FN malfunctions was conducted following the House–Brackmann grading system. A descriptive analysis was performed, and univariate and multivariate logistic regressions were used to examine the impact of IFNM on surgical timing and the association between G2 deficit (vs. G1) corrected for age, sex, and smoking status. Results: The study population comprised a total of 101 patients with a mean age of 55 ± 16 years. The sample population comprised 50 subjects assigned to Group 1 (49.5%, 24 females and 26 males) and 51 subjects assigned to Group 2 (50.5%, 21 males and 30 females). Postoperative paralysis of the MMB occurred in 23 subjects (22.77%), including 12 of G1 (4 had a grade II and 8 grade III dysfunction) and 11 of G2 (8 had a grade II and 3 grade III dysfunction). A six-month evaluation revealed that only five patients in G1, previously diagnosed with grade II dysfunction, exhibited a residual deficit. The mean surgical time for the entire patient cohort was 99 ± 44 min: 110 ± 43 min for Group 1 and 92 ± 42 min for Group 2 (Beta = −19; 95% CI −37 at −0.16; p-value = 0.048). Furthermore, a longer operative time was observed in smokers than in non-smokers (p-value = 0.008), suggesting that smoking affects the length of surgery (Beta = 0.32; 95% CI −0.08 to −0.55). Discussion and Conclusions: MMB paralysis is one of the most prevalent complications that may arise in submandibular gland surgery. IFNM provides surgeons with a valuable tool for identifying MMB in submandibular sialoadenectomy. The efficacy of IFNM as an aid is contingent upon the expertise of the operating surgeon. Full article

Background/Objectives: Salivary adenoid cystic carcinoma (ACC) is a rare but aggressive neoplasm that predominantly arises from the salivary glands, accounting for a significant proportion of salivary gland cancers. The aim of this literature review is to illustrate the current insights on ACC with regards to related genes and molecular pathways by analyzing original research articles from the period 2015–2025. Methods: An electronic search of literature was performed between January and February 2025 to identify all articles investigating the current insights on salivary gland adenoid cystic carcinoma and its related genes and molecular pathways. The search was conducted using MEDLINE (National Library of Medicine)-PubMed with restrictions concerning the date of publication. In particular, we focused on the period 2015–2025 using the following keywords: Salivary gland adenoid cystic carcinoma AND genes AND molecular pathways. This was followed by a manual search, and references were used to identify relevant articles. Results: In total, 41 articles were identified through the keywords. After the implementation of the time frame 2015–2025, 31 articles remained. Subsequently, by reading the titles and abstracts and thereby excluding non-original research articles and articles written in a language other than English, 23 articles remained. Conclusions: These studies identified 23 relevant genes or pathways whose analysis yielded the most recent data regarding their function. The classification of ACC is multifaceted, encompassing distinct histological subtypes that are crucial for determining prognosis and treatment approaches. Current oncological practices classify ACC based on these histological features alongside emerging genetic and molecular markers that promise to enhance our understanding of the disease’s biology. Diagnostic strategies have evolved, leveraging techniques such as biopsy and molecular diagnostics, which have significantly improved the detection and characterization of ACC. Regarding treatment, the management of ACC remains a challenge due to its propensity for local invasion and metastasis, with surgery, radiation, and chemotherapy being the mainstays of therapy. The development of targeted therapies based on ACC’s molecular profile will allow for a better prognosis and an enhanced quality of life of patients. Full article

Hypopituitarism is a condition characterized by the deficiency of several hormones produced by the pituitary gland. Genetic factors play an important role. Variants in the POU1F1 gene are associated with combined pituitary hormone deficiency 1 (CPHD1), which manifests as deficiencies in growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin (PRL). This study aimed to analyze the phenotype, genotype, treatment, and outcomes of Vietnamese patients with deficiency. Six patients from five unrelated families, initially diagnosed with hypopituitarism, were enrolled in this study. Data on physical characteristics, biochemical tests, treatment, outcomes, and follow-up were collected. Exome sequencing and Sanger sequencing were conducted to identify disease-causing variants in five probands and their families. All six patients exhibited anterior pituitary hypoplasia on brain magnetic resonance imaging and presented with TSH, GH, and PRL deficiencies. Exome sequencing identified three variants in the POU1F1 gene: c.428G>A p.(Arg143Gln), c.557T>G p.(Leu186Arg), and c.811C>T p.(Arg271Trp). The c.811C>T p.(Arg271Trp) variant was found in three patients, while c.557T>G p.(Leu186Arg) is a novel variant. Based on the ACMG classification, these variants were categorized as likely pathogenic or pathogenic variants. All patients were definitively diagnosed with CPHD1 caused by POU1F1 variants. All patients received levothyroxine and recombinant human growth hormone (rhGH) replacement therapy, leading to considerable growth. During the first year of treatment, all patients showed excellent growth response, with height increases ranging from 11 to 24 cm. After three years of treatment, two patients achieved normal height. One of the six patients developed scoliosis during treatment, which resolved after a one-year pause in rhGH therapy. Upon resuming treatment, no recurrence of scoliosis was observed. Our findings reveal the importance of early hormone testing and genetic analysis in improving the care and outcomes for patients with combined pituitary hormone deficiency. Full article

Background/Objectives: Endometrial hyperplasia is a uterine pathology characterized by the abnormal proliferation of endometrial glands, resulting in an increased gland-to-stroma ratio. Complex atypical hyperplasia represents the primary precursor to endometrial cancer. Given the high risk of progression to endometrial adenocarcinoma, the accurate diagnosis and classification of endometrial hyperplasia are crucial. Since the treatment for atypical endometrial hyperplasia is the same as that for early-stage endometrial cancer (i.e., total hysterectomy and bilateral salpingo-oophorectomy), researchers have questioned whether sentinel lymph node mapping could also have a prognostic role in atypical endometrial hyperplasia. Methods: A literature search was conducted in PubMed and Scopus from 2014 to 2025. Of the 65 papers found, 31 relevant articles were selected based on inclusion criteria, focusing on sentinel lymph node staging in patients with atypical endometrial hyperplasia. This review aims to assess whether sentinel lymph node mapping can be routinely used for prognostic and therapeutic purposes in clinical practice. Results: Sentinel lymph node biopsy represents a promising diagnostic technique for patients with atypical endometrial hyperplasia, reducing the need for invasive procedures and postoperative risks. However, its application requires advanced surgical skills and access to specific technologies, raising ethical and financial concerns, while future studies could improve patient selection and the reliability of the procedure through technological innovations. Conclusions: Sentinel lymph node biopsy is a safe and effective method for staging early-stage endometrial cancer and atypical hyperplasia, with low metastasis rates, but future research should focus on identifying patients who would benefit most from this procedure, considering its costs and required expertise. Full article