Epistaxis first-aid: a multi-center knowledge assessment study among medical workers.

PURPOSE: To assess the knowledge and confidence level regarding the basic first-aid for treating epistaxis among medical staff, including nurses and physicians across various medical disciplines. The study focused three aspects of first aid management: location of digital pressure, head position and duration of pressure. METHODS: The study involved 597 participants, categorized into five groups according to their specialties: emergency medicine, internal medicine, surgery, pediatrics, and community-based healthcare. A paper-based multiple-choice questionnaire assessed knowledge of managing epistaxis. Correct answers were determined from literature review and expert consensus. RESULTS: Most medical staff showed poor knowledge regarding the preferred site for applying digital pressure in epistaxis management. For head position, pediatricians and internal medicine physicians were most accurate (79.4% and 64.8%, respectively, p < 0.01), and nurses from the emergency department outperformed nurses from other disciplines; internal medicine, surgery, pediatrics, and community-based healthcare (61.1%, 41.5%, 43.5%, 60%, 45.6%, respectively, p < 0.05). While most medical staff were unfamiliar with the recommended duration for applying pressure on the nose, pediatricians and community clinic physicians were most accurate (47.1% and 46.0%, respectively, p < 0.01), while ER physicians were least accurate (14.9%, p < 0.01). Interestingly, a negative correlation was found between years of work experience and reported confidence level in managing epistaxis. CONCLUSIONS: Our findings indicate a significant lack of knowledge concerning epistaxis first-aid among medical staff, particularly physicians in emergency departments. This finding highlights the pressing need for education and training to enhance healthcare workers' knowledge in managing epistaxis.

Salivary Gland Secretory Carcinoma; Review of 13 Years World-Wide Experience and Meta-Analysis.

OBJECTIVES: Secretory Carcinoma is a malignant salivary gland tumor, initially described in 2010. This rare tumor is associated with the translocation t(12;15) (p13;q25), resulting in the fusion gene ETV6-NTRK3. Since this tumor is quite rare, most publications describe only small cohorts of patients. We aimed to investigate the clinical, pathological, and prognostic features of this newly defined malignant entity. DATA SOURCES: Pubmed, Google Scholar, and Web of Science databases. REVIEW METHODS: All published articles between 2010 and 2023 were reviewed. Search terms included the terms "Mammary Analogue Secretory Carcinoma" and "Secretory Carcinoma". All articles published in English reporting on Secretory Carcinoma of salivary glands were retrieved. RESULTS: One-hundred and 12 retrospective articles reporting a total of 674 patients were included, with 52% males and a mean age of 44.9 ± 18.9. The event rate for patients with advanced-stage disease (Stage 3/4) at presentation was 24.1% (95% CI 17.6%-31.9%, I2 = 9.2%), 14.6% for regional metastases (95% CI 10.5%-20%, I2 = 12%), and the event rate of distant metastasis was 8.4% (95% CI 5.5%-12.7%, I2 = 4.2%). Adjuvant radiotherapy was administered for 30.3% of patients (95% CI 24.1%-37.2%, I2 = 21.5%). The recurrence rate was 19% (95% CI 15.1%-23.8%, I2 = 5%). Survival outcomes showed a 17.2% death of disease rate for Secretory Carcinoma patients (95% CI 13.5%-21.8%, I2 = 7.3%). CONCLUSIONS: Secretory Carcinoma is a rare and relatively newly defined entity arising in the parotid gland most commonly. Characterized as a low-grade tumor, the majority of patients are diagnosed at an early stage, without regional or distant disease, and the prognosis is relatively good. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1716-1724, 2024.

The Predictors of Persistent Posttracheostomy Tracheocutaneous Fistula and Successful Surgical Closure.

OBJECTIVE: Persistent tracheocutaneous fistula is a well-described complication of prolonged tracheostomy, with a prevalence of about 70% when decannulation is performed after more than 16 weeks. Predictors of its occurrence and outcome of treatment in adults remain unclear. The aim of the study was to describe our experience with the treatment of persistent posttracheostomy tracheocutaneous fistula in adults and to investigate factors associated with its formation and with the success of surgical closure. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary medical center. METHODS: Patients who underwent open-approach tracheostomy between 2000 and 2020 were identified by database review. Data on background, need for surgical closure, and the surgical outcome was collected from the medical files and analyzed statistically between groups. RESULTS: Of 516 patients identified, 127 with sufficient long-term follow-up data were included in the study. Compared to patients whose fistula closed spontaneously (n = 85), patients who required surgical closure (n = 42) had significantly higher rates of smoking, laryngeal or thyroid malignancy, and airway obstruction as the indication for tracheostomy, on both univariate and multivariate analysis. In a comparison of patients with successful (n = 29) or failed (n = 11) surgical closure, factors significantly associated with failure were prior radiotherapy and lower preoperative albumin level, on univariate analysis. CONCLUSION: Smoking, thyroid or laryngeal malignancy, and airway obstruction indication are risk factors for persistent posttracheostomy tracheocutaneous fistula. Patients should be closely followed after tracheostomy and referred for surgery if the fistula fails to close. Before surgery, careful evaluation of the patient's nutritional status and consideration of prior radiation treatment is mandatory.

Accuracy, predictability and prognostic implications of fine-needle aspiration biopsy for parotid gland tumours: A retrospective case series.

OBJECTIVE: To evaluate the precision and utility of fine-needle aspiration (FNA) in differentiating between benign and malignant parotid tumours, and the implications of FNA results on management and outcomes. DESIGN: Retrospective case series. SETTING: Tertiary medical centre. PARTICIPANTS: All adults who underwent preoperative FNA, followed by postoperative histological examination, between 1986 and 2014. MAIN OUTCOME MEASURES: Differences in clinical management and outcomes of patients with parotid masses in light of FNA results. RESULTS: We analysed 505 samples from 485 patients. According to histopathological results, preoperative FNA successfully identified benign tumours in 89% of the cases (362/405) and only 59% of malignant tumours (59/100). Overall sensitivity and specificity of FNA in distinguishing between different subtypes of benign lesions were 80% and 99%, respectively, whereas positive predictive value (PPV) and negative predictive value (NPV) were 85% and 98%. Moreover, malignant lesions subtyping had high false-positive and false-negative rates with sensitivity, specificity, PPV and NPV of 44%, 100%, 75% and 99%, respectively. Additionally, when FNA falsely classified malignant tumours as benign, surgeries were inappropriately delayed and the durations of surgeries and hospitalisations were shorter, compared to true malignant FNA results. Interestingly, survival was not affected in falsely benign lesions that were mostly low-grade, conversely non-diagnostic FNA for malignant tumours resulted in decreased survival. CONCLUSIONS: Our findings highlight the limitations of FNA as a decision-making tool in preoperative evaluation of parotid masses. Clinicians should take into account that FNA is inaccurate for identifying specific subtypes of malignant lesions, which may eventually delay treatment and influence outcome.

R269C variant of ESR1: high prevalence and differential function in a subset of pancreatic cancers.

BACKGROUND: Estrogen receptor α (ESR1) plays a critical role in promoting growth of various cancers. Yet, its role in the development of pancreatic cancer is not well-defined. A less studied region of ESR1 is the hinge region, connecting the ligand binding and DNA domains. rs142712646 is a rare SNP in ESR1, which leads to a substitution of arginine to cysteine at amino acid 269 (R269C). The mutation is positioned in the hinge region of ESR1, hence may affect the receptor structure and function. We aimed to characterize the activity of R269C-ESR1 and study its role in the development of pancreatic cancer. METHODS: Transcriptional activity was evaluated by E2-response element (ERE) and AP1 -luciferase reporter assays and qRT-PCR. Proliferation and migration were assessed using MTT and wound healing assays. Gene-expression analysis was performed using RNAseq. RESULTS: We examined the presence of this SNP in various malignancies, using the entire database of FoundationOne and noted enrichment of it in a subset of pancreatic non-ductal adenocarcinoma (n = 2800) compared to pancreatic ductal adenocarcinoma (PDAC) as well as other tumor types (0.53% vs 0.29%, p = 0.02). Studies in breast and pancreatic cancer cells indicated cell type-dependent activity of ESR1 harboring R269C. Thus, expression of R269C-ESR1 enhanced proliferation and migration of PANC-1 and COLO-357 pancreatic cancer cells but not of MCF-7 breast cancer cells. Moreover, R269C-ESR1 enhanced E2-response elements (ERE) and AP1-dependent transcriptional activity and increased mRNA levels of ERE and AP1-regulated genes in pancreatic cancer cell lines, but had a modest effect on MCF-7 breast cancer cells. Accordingly, whole transcriptome analysis indicated alterations of genes associated with tumorigenicity in pancreatic cancer cells and upregulation of genes associated with cell metabolism and hormone biosynthesis in breast cancer cells. CONCLUSIONS: Our study shed new light on the role of the hinge region in regulating transcriptional activity of the ER and indicates cell-type specific activity, namely increased activity in pancreatic cancer cells but reduced activity in breast cancer cells. While rare, the presence of rs142712646 may serve as a novel genetic risk factor, and a possible target for therapy in a subset of non-ductal pancreatic cancers.

Ligand-binding Domain-activating Mutations of ESR1 Rewire Cellular Metabolism of Breast Cancer Cells.

PURPOSE: Mutations in the ligand-binding domain (LBD) of estrogen receptor α (ER) confer constitutive transcriptional activity and resistance to endocrine therapies in patients with breast cancer. Accumulating clinical data suggest adverse outcome for patients harboring tumors expressing these mutations. We aimed to elucidate mechanisms conferring this aggressive phenotype. EXPERIMENTAL DESIGN: Cells constitutively expressing physiologic levels of ER-harboring activating LBD mutations were generated and characterized for viability, invasiveness, and tumor formation in vivo. Gene expression profile was studied using microarray and RNAseq technologies. Metabolic properties of the cells were assessed using global metabolite screen and direct measurement of metabolic activity. RESULTS: Cells expressing mutated ER showed increased proliferation, migration, and in vivo tumorigenicity compared with cells expressing the wild-type ER (WT-ER), even in the presence of estrogen. Expression of the mutated ER was associated with upregulation of genes involved in invasion and metastases, as well as elevation of genes associated with tumor cell metabolism. Indeed, a metabolic examination revealed four distinct metabolic profiles: WT-ER-expressing cells either untreated or estrogen treated and mutated ER-expressing cells either untreated or estrogen treated. Pathway analyses indicated elevated tricarboxylic acid cycle activity of 537S-ER-expressing cells. Thus, while WT-ER cells were mostly glucose-dependent, 537S-ER were not addicted to glucose and were able to utilize glutamine as an alternative carbon source. CONCLUSIONS: Taken together, these data indicate estrogen-independent rewiring of breast cancer cell metabolism by LBD-activating mutations. These unique metabolic activities may serve as a potential vulnerability and aid in the development of novel treatment strategies to overcome endocrine resistance.