Survey of Danish Head and Neck Cancer Patients' Positions on Personalized Medicine, Gene Tests, and Personalized Follow-Up.

The field of personalized medicine (PM) has grown rapidly because of the "omics revolution", but PM may be difficult for patients to comprehend. This study sought to explore head and neck cancer (HNC) patients' positions and knowledge of PM, gene tests, and follow-up and to compare HNC patients' positions to a sample from a national Danish questionnaire. To do this, patients with prior HNC were invited to participate in a questionnaire. Initial interviews revealed a heterogenic understanding of PM between patients. A total of 226 patients were included in the survey and 177 patients with complete data were included for analysis. Most patients were more positive than negative towards gene tests and gene research (83% and 93%, respectively), but 72% had little or no knowledge of the subject. Almost all patients, 98%, were satisfied with their follow-up. Significantly more patients with HNC were positive towards gene research compared to a sample from a national Danish questionnaire (p < 0.001). Patients with HNC were positive towards gene tests and PM, but patients may not understand or comprehend the information given, and it is important to inform and educate patients and health professionals to establish common ground in PM.

Validating the virtual: a deep dive into ultrasound simulator metrics in otorhinolaryngology.

PURPOSE: This study aimed to assess the validity of simulation-based assessment of ultrasound skills for thyroid ultrasound. METHODS: The study collected validity evidence for simulation-based ultrasound assessment of thyroid ultrasound skills. Experts (n = 8) and novices (n = 21) completed a test containing two tasks and four cases on a virtual reality ultrasound simulator (U/S Mentor's Neck Ultrasound Module). Validity evidence was collected and structured according to Messick's validity framework. The assessments being evaluated included built-in simulator metrics and expert-based evaluations using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale. RESULTS: Out of 64 built-in simulator metrics, 9 (14.1%) exhibited validity evidence. The internal consistency of these metrics was strong (Cronbach's α = 0.805) with high test-retest reliability (intraclass correlation coefficient = 0.911). Novices achieved an average score of 41.9% (SD = 24.3) of the maximum, contrasting with experts at 81.9% (SD = 16.7). Time comparisons indicated minor differences between experts (median: 359 s) and novices (median: 376.5 s). All OSAUS items differed significantly between the two groups. The correlation between correctly entered clinical findings and the OSAUS scores was 0.748 (p < 0.001). The correlation between correctly entered clinical findings and the metric scores was 0.801 (p < 0.001). CONCLUSION: While simulation-based training is promising, only 14% of built-in simulator metrics could discriminate between novices and ultrasound experts. Already-established competency frameworks such as OSAUS provided strong validity evidence for the assessment of otorhinolaryngology ultrasound competence.

Bacterial findings in patients referred to hospital for the treatment of acute tonsillitis with or without peritonsillar phlegmon.

BACKGROUND: The vast majority of patients with acute tonsillitis (AT) are managed in general practice. However, occasionally patients are referred to hospital for specialized management because of aggravated symptoms and/or findings suggestive of peritonsillar involvement. No prospective studies have been conducted aiming to investigate the prevalent and significant microorganisms in this highly selected group of patients. We aimed to describe the microbiological findings of acute tonsillitis with or without peritonsillar phlegmon (PP) in patients referred for hospital treatment and to point out potential pathogens using the following principles to suggest pathogenic significance: (1) higher prevalence in patients compared to healthy controls, (2) higher abundance in patients compared to controls, and (3) higher prevalence at time of infection compared to time of follow up. METHODS: Meticulous and comprehensive cultures were performed on tonsillar swabs from 64 patients with AT with (n = 25) or without (n = 39) PP and 55 healthy controls, who were prospectively enrolled at two Danish Ear-Nose-Throat Departments between June 2016 and December 2019. RESULTS: Streptococcus pyogenes was significantly more prevalent in patients (27%) compared to controls (4%) (p < 0.001). Higher abundance was found in patients compared to controls for Fusobacterium necrophorum (mean 2.4 vs. 1.4, p = 0.017) and S. pyogenes (mean 3.1 vs. 2.0, p = 0.045) in semi-quantitative cultures. S. pyogenes, Streptococcus dysgalactiae, and Prevotella species were significantly more prevalent at time of infection compared to follow up (p = 0.016, p = 0.016, and p = 0.039, respectively). A number of species were detected significantly less frequently in patients compared to controls and the mean number of species was significantly lower in patients compared to controls (6.5 vs. 8.3, p < 0.001). CONCLUSIONS: Disregarding Prevotella spp. because of the prevalence in healthy controls (100%), our findings suggest that S. pyogenes, F. necrophorum, and S. dysgalactiae are significant pathogens in severe AT with or without PP. In addition, infections were associated with reduced diversity (dysbacteriosis). TRIAL REGISTRATION: The study is registered in the ClinicalTrials.gov protocol database (# 52,683). The study was approved by the Ethical Committee at Aarhus County (# 1-10-72-71-16) and by the Danish Data Protection Agency (# 1-16-02-65-16).

Frequency and malignancy rate of incidental focal salivary gland lesions identified by 18F-fluorodeoxyglucose-positron emission tomography.

PURPOSE: We aimed to evaluate the frequency and malignancy rate of incidental salivary gland lesions (ISGLs) in patients undergoing 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT). METHODS: Using a predefined algorithm, all descriptions of FDG-PET/CT scans performed in the North Denmark Region at the Department of Nuclear Medicine, Aalborg University Hospital from 1.12 2009 to 31.12 2019 were electronically searched for focal uptake in one or more salivary glands. RESULTS: In total, 28,362 FDG-PET/CT scans were performed in the study period. ISGLs were found in 197 (0.7%). A total of 193 (98%) had parotid gland ISGL, and four (2%) had submandibular ISGL. No sublingual lesions were found. Ultimately, 117 patients (60%) were referred to the Department of Otorhinolaryngology-Head and Neck Surgery for evaluation. Fine needle aspiration biopsy was performed in 97 patients, and the most frequent cytopathology was Warthin's tumour (n = 62). Two patients had verified malignancy: one with histopathologically proven acinic cell carcinoma and one with cytopathologically proven metastasis from an oral squamous cell carcinoma. CONCLUSIONS: Incidental salivary gland findings on FDG-PET/CT are rare, and the risk of malignancy is low. Patients with ISGL may be evaluated secondary to the primary disease, but special attention should be given to patients with prior or known head-and-neck malignancies and patients with symptoms from the salivary glands, including swelling.

Simulation-based surgical training needs in otorhinolaryngology.

INTRODUCTION: This study aimed to conduct a targeted needs assessment to identify and prioritise technical skills and procedures suited for simulation-based training (SBT) in private otorhinolaryngology (ORL) practice in Denmark, including mapping the learning environment related to implementation of SBT. METHODS: A panel of trainers and trainees in private ORL practice was recruited. Using the Delphi method, three rounds of surveys were conducted. Round one consisted of a survey of the learning environment and a brainstorming phase. Round two quantified the frequency of procedures, ranked the importance of procedural competency, impact on patient safety and feasibility for SBT. In round three, panelists eliminated and ranked procedures for final prioritisation. RESULTS: A total of 26 of 57 invited trainers and trainees accepted participation. The educational environment was described and 136 skills were suggested in the brainstorming phase. "Non-technical" skills were removed, and the remaining 46 technical skills were grouped for appraisal in round two. In round three, panelists reduced these to eight technical skills and procedures which were maintained for final prioritisation for SBT with myringotomy with ventilation tube insertion ranking highest. Trainees and trainers indicated that close supervision and dedicated time for training were major strengths of the learning environment. CONCLUSIONS: Our findings extend the results obtained in a previous general needs assessment and may inform curricular implementation of SBT in private ORL practice. A structured "package" with SBT and assessment for the identified procedures are desired by trainers. This work is already in progress and implementation is facilitated by a positive attitude towards SBT among trainers and trainees alike. FUNDING: none. TRIAL REGISTRATION: not relevant.

Clinical evaluation of antibiotic regimens in patients with surgically verified parapharyngeal abscess: a prospective observational study.

PURPOSE: We aimed to evaluate the effectiveness of different antibiotic regimens for the treatment of parapharyngeal abscess (PPA) and characterize patients, who suffered potentially preventable complications (defined as death, abscess recurrence, spread of infection, or altered antibiotic treatment because of insufficient progress). METHODS: Sixty adult patients with surgically verified PPA were prospectively enrolled at five Danish Ear-nose-throat departments. RESULTS: Surgical treatment included internal incision (100%), external incision (13%), and tonsillectomy (88%). Patients were treated with penicillin G ± metronidazole (n = 39), cefuroxime ± metronidazole (n = 16), or other antibiotics (n = 5). Compared to penicillin-treated patients, cefuroxime-treated patients were hospitalized for longer (4.5 vs 3.0 days, p = 0.007), were more frequently admitted to intensive care (56 vs 15%, p = 0.006), underwent external incision more frequently (31 vs 5%, p = 0.018), and suffered more complications (50 vs 18%, p = 0.022), including re-operation because of abscess recurrence (44 vs 3%, p < 0.001). Nine patients suffered potentially preventable complications. These patients displayed significantly higher C-reactive protein levels, received antibiotics prior to admission more frequently, underwent external incision more commonly, and were admitted to intensive care more frequently compared to other patients. CONCLUSION: The majority of patients with PPA were effectively managed by abscess incision, tonsillectomy, and penicillin G ± metronidazole. Cefuroxime-treated patients were more severely ill at time of admission and had worse outcome compared to penicillin-treated patients. We recommend penicillin G + metronidazole as standard treatment for patients with PPA, but in cases with more risk factors for potentially preventable complications, we recommend aggressive surgical and broadened antibiotic therapy, e.g. piperacillin-tazobactam.

Severe deep neck space infection caused by Eggerthia catenaformis.

A 64-year-old woman was acutely referred to the Department of Otorhinolaryngology, Head and Neck Surgery, Aalborg University Hospital due to rapidly progressing neck swelling, fever and dysphagia. Clinical examination revealed submental swelling, trismus and laryngeal inflammation. A contrast-enhanced CT scan showed infection in the deep neck spaces with multiple abscesses. The patient underwent acute surgery and antimicrobial therapy was initiated and she was transferred to an intensive care unit. Three additional surgical procedures were needed before sufficient drainage was achieved. There was growth of different oral commensals from four separate pus aspirates, while Eggerthia catenaformis was cultured in all samples. Due to the extent of the infection, the patient stayed in the intensive care unit for 16 days, but recovered completely due to adequate surgery and antimicrobial therapy for 4 weeks. Here we present the third reported case of a severe deep neck space infection with multiple abscesses due to E. catenaformis.

Microbiology of parapharyngeal abscesses in adults: in search of the significant pathogens.

We aimed to describe the microbiology of parapharyngeal abscess (PPA) and point out the likely pathogens using the following principles to suggest pathogenic significance: (1) frequent recovery, (2) abundant growth, (3) growth in relative abundance to other microorganisms, (4) percentage of the isolates recovered in both absolute and relative abundance, (5) more frequent recovery in PPA pus compared with tonsillar surface and tissue. Comprehensive bacterial cultures were performed on specimens obtained from adult patients (n = 60) with surgically verified PPA, who were prospectively enrolled at five Danish ear-nose-throat departments. The prevalent isolates (in PPA pus) were unspecified anaerobes (73%), non-hemolytic streptococci (67%), Streptococcus anginosus group (SAG) (40%), Corynebacterium spp. (25%), Neisseria spp. (23%), Fusobacterium spp. (22%), Fusobacterium necrophorum (17%), Prevotella spp. (12%), and Streptococcus pyogenes (10%). The bacteria most frequently isolated in heavy (maximum) growth were unspecified anaerobes (60%), SAG (40%), F. necrophorum (23%), and Prevotella spp. (17%). The predominant microorganisms (those found in highest relative abundance) were unspecified anaerobes (53%), SAG (28%), non-hemolytic streptococci (25%), F. necrophorum (15%), S. pyogenes (10%), and Prevotella spp. (10%). Four potential pathogens were found in both heavy growth and highest relative abundance in at least 50% of cases: F. necrophorum, Prevotella spp., SAG, and S. pyogenes. SAG, Prevotella spp., F. necrophorum, S. pyogenes, and Bacteroides spp. were recovered with the same or higher frequency from PPA pus compared with tonsillar tissue and surface. Our findings suggest that SAG, F. necrophorum, Prevotella, and S. pyogenes are significant pathogens in PPA development.

DNA methylation biomarkers in peripheral blood of patients with head and neck squamous cell carcinomas. A systematic review.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) are often diagnosed in advanced stages. In search of new diagnostic tools, focus has shifted towards the biological properties of the HNSCC, and the number of different biomarkers under investigation is rapidly growing. OBJECTIVES: The objective was to review the current literature regarding aberrantly methylated DNA found in peripheral blood plasma or serum in patients with HNSCC and to evaluate the diagnostic accuracy of these changes. METHODS: The inclusion criteria were clinical studies involving patients with verified HNSCC that reported findings of aberrantly methylated DNA in peripheral blood serum or plasma. We systematically searched PubMed, OVID Embase and Cochrane Library. In addition to the search, we performed forward and backward chaining in references and Web of Science. The protocol was registered in PROSPERO: CRD42019135406. Two authors independently extracted data. The quality and the risk of bias of the included studies were assessed by the QUADAS-2 tool. RESULTS: A total of 1,743 studies were found eligible for screening, while ultimately seven studies were included. All studies were found to have methodological weaknesses, mainly concerning patient selection bias. The best individual marker of HNSCC was Septin 9 in plasma with a sensitivity of 57% and a specificity of 95%. CONCLUSIONS: None of the aberrantly methylated genes found in the retrieved studies are applicable as single diagnostic markers for HNSCC and the best gene-panels still lack diagnostic accuracy. Future studies may benefit from newer sequencing techniques but validation studies with well-designed cohorts are also needed in the process of developing epigenetic based diagnostic tests for HNSCC.

Clinical presentation and microbiology of acute salivary gland infections.

INTRODUCTION: Acute salivary gland infections (ASI) have been associated with poor outcome in elderly and postoperative patients. Perioperative care and treatment of co-morbidities have improved considerably, but most of our knowledge regarding ASI dates back several decades. The aim of this study was to describe the microbiology and treatment of ASI in a large post-millennial cohort. METHODS: All patients with ASI admitted to the Department of Otorhinolaryngology - Head and Neck Surgery, Aarhus University Hospital in the period from 2001 to 2017 were included. RESULTS: In total, 157 patients with ASI were included. The parotid gland (PG) was affected in 89 (57%) cases and the submandibular gland (SMG) in 68 (43%) cases. The most prevalent bacterial findings were viridans streptococci (25 isolates) and Staphylococcus aureus (19 isolates). S. aureus was almost exclusively found in PG (17/19 cases). S. aureus-positive cases showed a significantly higher inflammatory response than other bacteria (C-reactive protein, p = 0.008 and absolute neutrophil count, p = 0.0108). CONCLUSIONS: S. aureus is a significant pathogen in ASI and especially in PG cases. Other pathogens may play a role in the development of SMG infections. Based on the bacterial findings in this study, we recommend penicillinase-resistant penicillin as first-line treatment in ASI. FUNDING: none Trial registration: not relevant. The Danish Data Protection Agency approved the project.

Tonic-clonic seizures as first symptom of a disseminated supraglottic laryngeal cancer.

A 60-year-old man was found unconscious at work, without any signs of trauma. At the site, he presented with tonic-clonic seizures, central facial palsy and eye deviation. A CT scan of the cerebrum did not find bleeding or thrombosis, but contrast enhancement at the superior sagittal sinus and pathological cervical lymph nodes. The MRI demonstrated multiple intracerebral metastases, while a supplementary fluoro-deoxy-glucose positron emission tomography scan revealed metastatic lesions above and below the diaphragm, without signs of a primary tumour. An ear, nose and throat examination found a small supraglottic tumour and cervical lymph node metastases. Following a multidisciplinary team discussion, biopsies from the duodenal mucosa and an inguinal lymph node were performed, showing squamous cell carcinoma with its origin in the head and neck. The patient was diagnosed with a T1N2cM1 supraglottic laryngeal cancer, receiving palliative whole brain radiation therapy but died 11 weeks after the debut of symptoms.

Low rate of co-infection in complicated infectious mononucleosis.

INTRODUCTION: It remains unclarified if bacterial co-infection is common in patients with infectious mononucleosis (IM) and acute tonsillitis and/or peritonsillar abscess (PTA). Recent studies suggest that Fusobacterium necrophorum is a prevalent pathogen in acute tonsillitis and PTA. We hypothesised that this anaerobe may play a significant role for the aggravated infection and the development of PTA among teenagers and young adults with IM. METHODS: All patients with IM and clinical findings of acute tonsillitis or PTA admitted to our department in the 2001-2015 period were included in the study. RESULTS: In total, 257 patients with IM and acute tonsillitis (n = 220) or PTA (n = 37) were included. Positive bacterial cultures were obtained in 28% of patients with AT and in 50% with PTA. The most prevalent bacterial findings were Group C/G streptococci (14%) among patients with acute tonsillitis and Staphylococcus aureus (22%) in patients with PTA. F. necrophorum was recovered in 9% and 2% of patients with acute tonsillitis and PTA, respectively. CONCLUSIONS: We were unable to substantiate a prevalent role for F. necrophorum in patients with IM and acute tonsillitis/PTA. S. aureus may play a role in PTA development in patients IM. The majority of our findings did not support the use of antibiotics in patients with IM, even in this selected group of patients with severe symptoms and a high risk of PTA. FUNDING: This work was funded by the Lundbeck Foundation (Grant number R185-2014-2482). TRIAL REGISTRATION: The Danish Data protection Agency approved the project.

Adherence to antibiotic guidelines in the treatment of acute pharyngeal infections.

INTRODUCTION: We aimed to investigate doctors' ad-herence to the local antibiotic guidelines for treatment of patients admitted with acute pharyngeal infections and to identify patient-related risk factors for non-adherence. METHODS: All patients with acute tonsillitis, peritonsillar abscess (PTA), and parapharyngeal abscess admitted to the Ear-Nose-Throat Department, Aarhus University Hospital, in the 2001-2014 period were included in the study. RESULTS: In total, 2,567 patients were hospitalised with acute pharyngeal infection. In non-allergic patients, penicillin was prescribed to 81%, either alone (48%) or in combination with metronidazole (33%). Macrolides (54%) and cefuroxime (44%) were the drugs of choice in 85 (98%) patients who were allergic to penicillin. Patients were prescribed antibiotics according to guidelines in 63% of cases. The addition of metronidazole to penicillin was the main (75% of cases) reason for non-adherence. Increasing patient age and male gender were independent risk factors for non-adherence. PTA patients treated according to the guidelines had a significantly shorter hospital stay than patients treated with additional metronidazole or broad-spectrum antibiotics. CONCLUSIONS: A significant (37%) proportion of patients with acute pharyngeal infections were treated non-adherently to antibiotic guidelines, mainly because of (inappropriate) addition of metronidazole to penicillin. FUNDING: This work was supported by the Lundbeck Foundation (Grant number R185-2014-2482). TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency.

Characteristics of CI children with complicated middle ear infections.

OBJECTIVE: To describe cases of complicated middle ear infections in children with cochlear implants (CI), i.e., episodes of acute otitis media (AOM) and acute mastoiditis (AM), resulting in hospitalization. METHODS: A total of 206 children under 16 years (300 implantations) were implanted between 1 January 2008 and 31 December 2014 at the West Danish CI Center, Department of Otorhinolaryngology Head and Neck Surgery, Aarhus, Denmark. By means of two prospective local databases, episodes of AOM or AM and demographics were retrieved including biochemistry, microbiology, length of follow- up, and variable treatment modalities (intravenous (IV) antibiotics, revision mastoidectomy, and insertion of ventilation tubes). RESULTS: Overall rate of AOM and/or AM was 9.2% (AOM: 9%, AM: 1.9%). Mean age at CI was 46 months. Mean follow-up was 45 months. Mean time from CI operation to AOM or AM was 3 and 4 months, respectively. Children younger than 2 years were at highest risk of AOM and/or AM. All had antibiotics prescribed before admittance, and two- thirds of infected ears had already ventilation tubes inserted. Bacteria could not be detected in more than half of cases. The most frequently isolated strains were pneumococci and nontypable Haemophilus influenzae. The majority of patients were successfully treated with IV cefuroxime (64% of cases) and insertion of ventilation tubes. None of the children developed facial nerve paralysis, intracranial infections, or septicemia. DISCUSSION: Almost 10% of CI children required at least one hospitalization due to AOM and/or AM compared with 0.1 per thousand of non-CI children. This discrepancy can be explained by a low threshold for active treatment of otitis media in CI children and hence referral to a CI center. The results suggest that benzylpenicillin might be an appropriate initial treatment of AOM and AM. However, cephalosporin was the most preferred antibiotic. Most CI children were already treated with ventilation tubes at admission and almost all children without ventilation tubes, had a tube inserted during admission. Insertion of ventilation tubes is still much debated and more research in this field is needed. CONCLUSION: AOM and/or AM were seen in Danish children with CI as often as in other western countries. Treatment of complicated middle ear infections was sufficient with IV cephalosporin and ventilation tube insertion. Special attention should be paid to children younger than 4 years and the associated microbiology including serotyping should be monitored.

Large laryngeal vascular malformation in a 5-year-old child.

A 5-year-old boy was admitted with stridor, which was initially interpreted as subglottic laryngitis. He had a history of prolonged hoarseness and his voice was deep for his age. The stridor persisted despite treatment with epinephrine inhalations and intravenous glucocorticoids. A direct laryngoscopy and blood work up did not support the suspected diagnosis. A MRI was then carried out, followed by angiography. The latter revealed an arteriovenous malformation (AVM) involving the lingual and superior thyroid arteries bilaterally. Owing to the rareness and extent of such an AVM, the patient was referred to Paris for further treatment. This case presents the difficulties in diagnostics and emphasises the importance of diagnostics and multidisciplinary approaches with regard to treatment of AVMs.