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OBJECTIVES: The aim of the current study was to further collect evidence that would confirm the hypothesis that vestibular drop attacks (VDAs) could cause syncope in patients with Meniere's disease (MD). MATERIALS and METHODS: A cross-sectional survey design was employed in the present study. An Internet-based survey was administered on 602 individuals with MD. The mean age of the participants was 56.7 (25-75) years, and the mean duration of the disease was 12.4 (0.5-35) years. RESULTS: VDAs with varying severity were present among 307 (50.7%) patients and led to fall in 92 patients, and syncope occurred in 45 patients with VDA. The overall percentage of syncope due to MD was 4.7%. Factors, such as duration of disease, age, and gender of the patient, did not explain attacks of syncope. Migraine and headache were not associated with syncope. Syncope was witnessed in 23 and self-reported by 22 patients. Syncope was associated with frequent VDA, duration of VDA, and falls that occurred during VDA. Patients with syncope reported the experience as frightening, had reduced general health-related quality of life, had higher anxiousness scores, and suffered more from fatigue. They also experienced problems with work, employment, and social restrictions. CONCLUSION: Approximately 5% of patients with MD suffer from syncope, and syncope occurs among patients with VDA. In vestibular syncope, the sympathetic tone is lost, and baroreflex feedback is inhibited leading to fall and syncope. The consequences of vestibular syncope are severe, and patients face injuries and a significantly reduced quality of life.

Objectives: The COVID-19 pandemic has globally affected healthcare workers’ (HCWs) health and wellbeing. Most studies on COVID-19 have focused on tertiary healthcare. The aim of this study was to increase the knowledge on the effects of the pandemic on working conditions in tertiary and primary healthcare. Material and Methods: The comparative cross-sectional study consisted of an online questionnaire sent to HCWs of the City of Helsinki (primary healthcare) and Helsinki University Hospital (tertiary healthcare). Altogether 1580 HCWs with direct patient contact participated in the study: 895 from tertiary and 685 from primary healthcare. Statistical analysis used SPSS 25 from IBM. The tests used were the χ2 test, Fisher’s exact test, and binary logistic regression analysis. Results: Primary HCWs were less likely to treat COVID-19 patients (OR = 0.45, 95% CI: 0.37–0.56). However, both groups reported a similar number of COVID-19 infections, primary HCWs 4.9% and tertiary HCWs 5.0%, and work-related quarantine was significantly more prevalent (OR = 1.96, 95% CI: 1.38–2.79) among primary HCWs. In addition, work-related wellbeing was poorer among primary HCWs than tertiary HCWs in terms of feeling more stressed at work (OR = 3.20, 95% CI: 2.55–4.02), not recovering from work (OR = 0.49, 95% CI: 0.39–0.62), reported mental wellbeing below normal levels (OR: 1.59, 95% CI: 1.26–2.00), and increased working hours (OR = 1.63, 95% CI: 1.25–2.12). Conclusions: The study demonstrates how the pandemic has affected the wellbeing and working conditions of not only tertiary but also less studied primary HCWs. The authors’ findings suggest that the challenges identified during the COVID-19 pandemic in the health and wellbeing of healthcare workers are even greater in primary care than in tertiary care.

Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P –9) associated with medication use. Fine-mapping revealed 494 95% credible sets associated with the total number of medication purchases, changes in medication combinations or treatment discontinuation, including 46 credible sets in 40 loci not associated with the underlying treatment targets. The polygenic risk scores (PRS) for cardiometabolic risk factors were strongly associated with the medication-use behavior. A medication-use enhanced multitrait PRS for coronary artery disease matched the performance of a risk factor-based multitrait coronary artery disease PRS in an independent sample (UK Biobank, n = 343,676). In summary, we demonstrate medication-based strategies for identifying cardiometabolic risk loci and provide genome-wide tools for preventing cardiovascular diseases.

Deep learning algorithms can be used to classify medical images. In distal radius fracture treatment, fracture detection and radiographic assessment of fracture displacement are critical steps. The aim of this study was to use pixel-level annotations of fractures to develop a deep learning model for precise distal radius fracture detection. We randomly divided 3785 consecutive emergency wrist radiograph examinations from six hospitals to a training set (3399 examinations) and test set (386 examinations). The training set was used to develop the deep learning model and the test set to assess its validity. The consensus of three hand surgeons was used as the gold standard for the test set. The area under the ROC curve was 0.97 (CI 0.95–0.98) and 0.95 (CI 0.92–0.98) for examinations without a cast. Fractures were identified with higher accuracy in the postero-anterior radiographs than in the lateral radiographs. Our deep learning model performed well in our multi-hospital and multi-radiograph system manufacturer settings. Thus, segmentation-based deep learning models may provide additional benefit. Further research is needed with algorithm comparison and external validation.

Objectives The aims of this national register-based study were to examine patient injury claims related to tonsil and adenoid surgery injuries and to compare the frequency of claims between tonsillectomies and tonsillotomies in Finland. Methods We analyzed the complaints related to tonsil and adenoid surgery received by the Finnish Patient Insurance Center (PIC) between the years 2000 and 2019. One hundred seventy-two cases were included in the analysis. The annual surgery rates between the years 2000 and 2018 were acquired from the Finnish Institute for Health and Welfare. Results During the years 2000 to 2018, a total of 292,679 patients had tonsil and/or adenoid surgery nationwide. For tonsil or adenoid surgeries, the national average was 5.3 cases and 1.8 cases per 10,000, respectively, resulting in patient injury claims and compensations. A total of 33.1% of the claims regarding tonsil or adenoid surgery processed by the PIC were compensated. Most of the claims were made after a tonsillectomy (87.8%), and few were made after a tonsillotomy (1.7%). Seven deaths were recorded. Conclusion Patient injuries from tonsil and adenoid surgeries were mostly related to traditional extracapsular tonsillectomies. Most surgeries, along with most complications, involved specialists, who performed routine operations in high-volume centers. Surgeries for acute or recurrent infections resulted in more claims. Severe complications arising from tonsil and adenoid surgeries were rare. Level of Evidence 4.

Background/Aim: The oral bacteria involved in the development of periodontitis alter the tissue conditions and modify immune responses in a way that may also influence tumor development. We investigated the prevalence of R gingipain (Rgp), a key virulence factor of the oral pathobiont Porphyromonas gingivalis, and the tissue-destructive enzymes matrix metalloproteinase 8 (MMP-8) and 9 (MMP-9) in 202 unselected consecutive oropharyngeal squamous cell carcinoma

Chronic sclerosing sialadenitis is commonly regarded as a manifestation of IgG4-related disease. We previously found that a high IgG4 expression or IgG4-related disease could accompany nonspecific sialadenitis, whereas chronic sclerosing sialadenitis was not directly associated with IgG4-related disease. Our previous findings lead us to hypothesize that these inflammatory conditions of the submandibular gland signify a continuous progression of disease rather than different disease entities. We, therefore, aimed to determine the presence of IgG4-positivity and genuine IgG4-related disease in a cohort of 165 submandibular gland specimens from patients who underwent surgery due to chronic nonspecific sialadenitis or sialolithiasis. To do so, we re-evaluated histopathological features and divided samples into three groups: (A) nonspecific sialadenitis without known sialolithiasis, (B) sialadenitis with sialolithiasis, and (C) sialolithiasis without sialadenitis. We performed immunohistochemical staining for IgG4, IgG, and CD31, and assessed the Boston consensus statement criteria for IgG4-related disease in IgG4-positive samples. We also reviewed patient records and supplemented follow-up data with a questionnaire among patients with IgG4-positive samples. IgG4-positive plasma cells (range 1-344) were found in 131 samples. Among these, 19 samples were classified as IgG4-positive (>= 70 IgG4-positive plasma cells/high-power field). Two IgG4-positive samples were histologically highly suggestive of IgG4-related disease, but only one had a clinically confirmed diagnosis of IgG4-related disease. Our results indicate that patients with sialadenitis and sialolithiasis often present with IgG4-positive lymphoplasmacytic infiltrates, but exceedingly rarely present with genuine IgG4-related disease. In sialolithiasis without sialadenitis, IgG4-positive plasma cells are often absent or appear in small numbers. These results support our hypothesis of a continuum of disease, and indicate that progressive inflammation of the submandibular gland leads to the development of more specific pathological features over time.

Purpose Congenital cytomegalovirus infection (cCMV) is the most frequent nonhereditary cause for sensorineural hearing loss (SNHL) in children. Data on vestibular function in children with cCMV are, however, scarce, although some evidence for cCMV-associated vestibular dysfunction exists. In this prospective cohort study, we evaluated long-term vestibular function and hearing outcomes in a cohort of children with cCMV. Methods Participants were 6–7-year-old children with cCMV from a large population-based screening study. Controls were age and gender matched healthy children, who were CMV-negative at birth. Hearing was examined with pure tone audiometry. Definition of hearing loss was pure-tone average > 20 dB. Vestibular function was assessed using the video head impulse test that provides a measure of semicircular canal function. Definition of vestibular dysfunction was lateral semicircular canal gain Results Vestibular dysfunction occurred in 7/36 (19.4%) of children with cCMV and in 1/31 (3.2%) of controls (p = 0.060). SNHL was recorded in 4/38 (10.5%) of children with cCMV and in 0/33 of controls (p = 0.118). Hearing loss was unilateral in all cases. In cCMV group, the two children with bilateral vestibular dysfunction also had SNHL, whereas those with unilateral vestibular dysfunction (n = 5) had normal hearing. Conclusions In this cohort of children with cCMV identified using newborn screening, vestibular dysfunction was more common than SNHL at 6 years of age. Vestibular dysfunction occurred both in children with and without SNHL. Based on these data, inclusion of vestibular tests in follow-up protocol of cCMV should be considered.

Background Although needle biopsy is widely used in work-up of lymphadenopathy, lymph node excision (LNE) is often required especially in lymphoma diagnostics. LNE is an invasive procedure, which carries a potential risk of complications. However, comprehensive studies evaluating the spectrum and occurrence of complications are lacking. Aims/Objectives This study addresses the role of preoperative needle biopsies in patients who underwent LNE. Furthermore, surgical complications related to LNE are analyzed. Materials and methods Altogether 321 patients, who underwent LNE in two-year period in 2018-19, and fulfilled our study criteria, were included. Patients' data were retrieved from the electronic patient records. Results The surgical complication rate was 5.9%. Most of the complications (n = 16; 84.2%) were categorized as minor (I-II) according to the Clavien-Dindo scale. The remaining three (15.8%), all hemorrhages, were categorized as major complications and required intervention. Preoperative needle biopsy might have avoided the need for LNE in some patients, which we discuss in this study. Conclusions and significance Surgical complications after LNE in the head and neck area are rare and mostly minor. Needle biopsy is often recommended preoperatively to avoid unnecessary operations and to refrain performing LNE for patients with non-lymphatic malignancy.

Background During the COVID-19 pandemic, health care had to find new ways to care for patients while reducing infection transmission. The role of telemedicine role has grown exponentially. Methods A questionnaire on experiences and satisfaction was sent to the staff of the Head and Neck Center of Helsinki University Hospital and to otorhinolaryngology patients treated remotely between March and June 2020. Additionally, patient safety incident reports were examined for incidents involving virtual visits. Results Staff (response rate 30.6%, (n = 116)) opinions seemed to be quite polarized. In general, staff felt virtual visits were useful for select groups of patients and certain situations, and beneficial in addition to face-to-face visits, not instead of them. Patients (response rate 11.7%, (n = 77)) gave positive feedback on virtual visits, with savings in time (average 89 min), distance travelled (average 31.4 km) and travel expenses (average 13.84€). Conclusions While telemedicine was implemented during the COVID-19 pandemic to ensure patient treatment, its usefulness after the pandemic must be examined. Evaluation of treatment pathways is critical to ensure that quality of care is upheld while new treatment protocols are introduced. Telemedicine offers the opportunity to save environmental, temporal, and monetary resources. Nonetheless, the appropriate use of telemedicine is essential, and clinicians must be offered the option to examine and treat patients face-to-face.

Background Multi slice computed tomography (MSCT) is the most common used method in middle ear imaging. However, MSCT lacks the ability to distinguish the ossicular chain microstructures in detail resulting in poorer diagnostic outcomes. Novel cone beam computed tomography (CBCT) devices’ image resolution is, on the other hand, better than MSCT resolution. The aim of this study was to optimize imaging parameters of a novel full body CBCT device to obtain optimal contrast to noise ratio (CNR) with low effective dose, and to optimize its clinical usability. Methods Imaging of five anonymous excised human cadaver temporal bones, the acquisition of the effective doses and the CNR measurements were performed for images acquired on using Planmed XFI® full body CBCT device (Planmed Oy, Helsinki, Finland) with a voxel size of 75 µm. All images acquired from the specimens using 10 different imaging protocols varying from their tube current exposure time product (mAs) and tube voltage (kVp) were analyzed for eight anatomical landmarks and evaluated by three evaluators. Results With the exception of protocol with 90 kVp 100 mAs, all other protocols used are competent to image the finest structures. With a moderate effective dose (86.5 µSv), protocol with 90 kV 450 mAs was chosen the best protocol used in this study. A significant correlation between CNR and clinical image quality of the protocols was observed in linear regression model. Using the optimized imaging parameters, we were able to distinguish even the most delicate middle ear structures in 2D images and produce accurate 3D reconstructions. Conclusions In this ex vivo experiment, the new Planmed XFI® full body CBCT device produced excellent 2D resolution and easily created 3D reconstructions in middle ear imaging with moderate effective doses. This device would be suitable for middle ear diagnostics and for e.g., preoperative planning. Furthermore, the results of this study can be used to optimize the effective dose by selecting appropriate exposure parameters depending on the diagnostic task.

With computed tomography (CT), the delicate structures of the inner ear may be hard to visualise, which a cochlear implant (CI) electrode array can further complicate. The usefulness of a novel cone-beam CT device in CI recipient’s inner ear imaging was evaluated and the exposure parameters were optimised to attain adequate clinical image quality at the lowest effective dose (ED). Six temporal bones were implanted with a Cochlear Slim Straight electrode array and imaged with six different imaging protocols. Contrast-to-noise ratio was calculated for each imaging protocol, and three observers evaluated independently the image quality of each imaging protocol and temporal bone. The overall image quality of the inner ear structures did not differ between the imaging protocols and the most relevant inner ear structures of CI recipient’s inner ear can be visualised with a low ED. To visualise the most delicate structures in the inner ear, imaging protocols with higher radiation exposure may be required.

Objective Survival of patients with advanced laryngeal squamous cell carcinoma (LSCC) remains poor and management protocols warrant further development. We thus investigated treatment and outcome-related factors for LSCC in Stockholm, Sweden.Methods In a retrospective setting, 520 patients with LSCC diagnosed during 2000-2014, were included. Data on stage, treatment, and outcome were correlated with recurrence-free and overall survival (RFS and OS, respectively).Results Five-year OS for all patients was 65%. Five-year RFS for T1a, T1b, T2, T3, and T4 glottic LSCC was 90%, 91%, 77%, 47%, and 80%, respectively. The corresponding figures for T1, T2, T3, and T4 supraglottic LSCC were 64%, 66%, 64%, and 86%.Conclusion Patients with a T3 glottic LSCC had unexpectedly poor survival, especially when compared with patients with a T4 tumor. Patients with T4 disease were primarily treated with laryngectomy and postoperative radiotherapy (RT)/chemoradiotherapy (CRT), while most patients with T3 LSCC were treated with RT/CRT.

Publisher Copyright: © 2023 International Federation of Clinical Neurophysiology Objective: To study if interictal epileptiform discharges (IEDs) are associated with language performance or pre-/perinatal factors in children with developmental language disorder (DLD). Methods: We recorded routine EEG in wake and sleep in 205 children aged 2.9–7.1 years with DLD, without neurologic diseases or intellectual disability. We examined the language performance of the children and collected data on pre-/perinatal factors. Results: Interictal epileptiform discharges were not associated with lower language performance. Children with so-called “rolandic”, i.e. centrotemporoparietal, IEDs had better language skills, but age explained this association. Most pre-/perinatal factors evaluated did not increase the risk of rolandic IEDs, except for maternal smoking (OR 4.4, 95% CI 1.4–14). We did not find electrical status epilepticus during slow-wave sleep (ESES)/spike-and-wave activation in sleep (SWAS) in any children. Conclusions: Interictal epileptiform discharges are not associated with lower language performance, and ESES/SWAS is not common in children with DLD. Significance: Routine EEGs do not bring additional information about language performance in children with DLD who do not have any neurologic diseases, seizures, intellectual disability, or regression of language development.

Katarzyna Ewa Nowik,1 Kamil Nowik,1 Piotr Kanclerz,2,3 Jacek Paweł Szaflik1 1Department of Ophthalmology, Public Ophthalmic Clinical Hospital (SPKSO), Medical University of Warsaw, Warsaw, Poland; 2Department of Ophthalmology, Hygeia Clinic, Gdańsk, Poland; 3Helsinki Retina Research Group, University of Helsinki, Helsinki, FinlandCorrespondence: Katarzyna Ewa Nowik, Tel +48 509 873 680, Email lek.katarzynaolejnik@onet.euPurpose: Extended depth of focus intraocular (EDOF) IOLs form a bridge between single- and multifocal IOL design. This study aimed to compare clinical outcomes obtained after implanting two different optical designs of EDOF IOLs: the Mini Well Ready (SIFI Medtech, Catania, Italy) and Tecnis Symfony (Abbott Laboratories, Illinois, USA).Methods: The retrospective observational study included 61 patients (122 eyes) who underwent bilateral implantation of the Mini Well Ready IOL (32 patients) or the Tecnis Symfony IOL (29 patients). The following preoperative and postoperative parameters were evaluated: spherical equivalent, anterior astigmatism, pupil size, monocular and binocular uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), monocular and binocular uncorrected intermediate visual acuity (UIVA) and distance-corrected intermediate visual acuity (DCIVA), monocular and binocular uncorrected near visual acuity (UNVA) and distance-corrected near visual acuity (DCNVA). In the 6 months postoperative period, defocus curve, contrast sensitivity, photopic phenomena, and posterior capsule opacification were assessed.Results: The patients receiving the Tecnis Symfony had slightly better monocular and binocular UDVA and CDVA than with the Mini Well Ready IOL, the differences were not statistically significant. Whereas the UIVA, DCIVA, UNVA, DCNVA, UNVA and DCNVA values were higher in the Mini Well Ready group, the differences were not significant. There were no significant between-group differences regarding the defocus curve for the vast majority of tested vergences. Dysphotopsias postoperatively were assessed at 6 months.Conclusion: Patients receiving both the Mini Well Ready and Symfony IOLs had excellent visual acuity outcomes and spectacle independence.Keywords: cataract, extended depth of focus, defocus curve, intraocular lens

Purpose: The prognosis of glottic T1a laryngeal squamous cell carcinoma (LSCC) is excellent with both transoral laser surgery (TLS) and radiation therapy (RT). Our aim was to compare TLS and RT treatment results in a randomized study. Methods and Materials: Of 56 male patients with glottic T1a LSCC, 31 were randomized for TLS and 25 for RT. Survival and larynx preservation data were collected from medical records. Results: Five-year overall survival (OS) was 87%, disease-specific survival (DSS) was 97%, and recurrence-free survival (RFS) was 81% in patients treated with TLS. Five-year OS was 92%, DSS was 100%, and RFS was 88% in patients treated with RT. The primary treatment method was not associated with OS, RFS, or DSS in a log-rank test. The larynx preservation rate was similar in both groups (TLS, 97%; RT, 92%; P = .575). Conclusions: In a prospective randomized setting oncological outcomes of both treatment modalities (TLS or RT) for T1a LSCC were similar. (C) 2022 Elsevier Inc. All rights reserved.

Background Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. Aims/objectives To review the management and outcome of ear canal and middle ear tumors at an academic referral center. Materials and methods Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. Results Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. Conclusions and significance EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.

Background Different bacterial infections of the oro-naso-pharyngeal (ONP) region may progress and require hospital care. The present study clarified differences in infection characteristics between hospitalized patients with odontogenic infections (OIs) and other bacterial ONP infections. The specific aim was to evaluate clinical infection variables and infection severity according to infection aetiology, particularly regarding features of OIs compared with other ONPs. Methods Records of patients aged ≥16 years requiring hospital care for an acute bacterial ONP infection in the emergency units of Otorhinolaryngology or Oral and Maxillofacial Surgery at the Helsinki University Hospital (Helsinki, Finland) during 2019 were evaluated retrospectively. The main outcome variables were need for intensive care unit (ICU) treatment and length of hospital stay. The primary predictor variable was infection category, defined as OI or other ONP. The secondary predictor variable was specific ONP infection group. Additional predictor variables were primary clinical infection signs, infection parameters at hospital admission, and delay from beginning of symptoms to hospitalization. Explanatory variables were sex, age, current smoking, heavy alcohol use or substance abuse, and immunosuppressive disease, immunosuppressive medication, or both. Comparison of study groups was performed using Fisher’s exact test, student’s t-test, and Mann-Whitney U. Results A total of 415 patients with bacterial ONPs fulfilled the inclusion criteria. The most common infections were oropharyngeal (including peritonsillar, tonsillar, and parapharyngeal infections; 51%) followed by infections from the odontogenic origin (24%). Clinical features of OIs differed from other ONPs. Restricted mouth opening, skin redness, or facial or neck swelling (or both) were found significantly more often in OIs (p p p = 0.017). Conclusions Infections originating from the tonsillary and dental origin had the greatest need for hospitalization. Clinical features of OIs differed; the need for ICU treatment was more common and hospital stay was longer compared with other ONPs. Preventive care should be emphasized regarding OIs, and typical infection characteristics of ONP infection subgroups should be highlighted to achieve early and prompt diagnosis and treatment and to reduce hospitalization time.

All treatment modalities for head and neck cancer carry with them a risk of adverse events. Head and neck surgeons are faced with significant challenges to minimize associated morbidity and manage its sequelae. Recognizing situations in which a surgical complication is an adverse event inherent to the procedure can alleviate the psychologic impact a complication might have on the treatment team and minimize external and internal pressures. Focusing on the complications that can be effectively modified, future complications can be avoided. Also, some surgical morbidities may not be preventable, necessitating the option to reconsider whether the incidents should be labeled toxic reactions rather than a complication. This discussion highlights some of the areas in which additional research is needed to achieve the goal of minimizing the impact of surgical morbidity.

Funding Information: This work was supported by the National Institutes of Health (NIH)/National Cancer Institute (NCI) through a Cancer Center Support Grant (CCSG; P30CA016672-44). MN is supported by an NIH grant (R01DE028290-01). KW is supported by a training fellowship from The University of Texas Health Science Center at Houston Center for Clinical and Translational Sciences TL1 Program (TL1TR003169), the American Legion Auxiliary Fellowship in Cancer Research, and an NIH/National Institute for Dental and Craniofacial Research (NIDCR) F31 fellowship (1 F31DE031502-01). CF received funding from the NIH/NIDCR (1R01DE025248-01/R56DE025248); an NIH/NIDCR Academic-Industrial Partnership Award (R01DE028290); the National Science Foundation (NSF), Division of Mathematical Sciences, Joint NIH/NSF Initiative on Quantitative Approaches to Biomedical Big Data (QuBBD) Grant (NSF 1557679); the NIH Big Data to Knowledge (BD2K) Program of the NCI Early Stage Development of Technologies in Biomedical Computing, Informatics, and Big Data Science Award (1R01CA214825); the NCI Early Phase Clinical Trials in Imaging and Image-Guided Interventions Program (1R01CA218148); an NIH/NCI Pilot Research Program Award from the UT MD Anderson CCSG Radiation Oncology and Cancer Imaging Program (P30CA016672); an NIH/NCI Head and Neck Specialized Programs of Research Excellence (SPORE) Developmental Research Program Award (P50CA097007); and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Research Education Program (R25EB025787). Publisher Copyright: Copyright © 2023 Sahlsten, Wahid, Glerean, Jaskari, Naser, He, Kann, Mäkitie, Fuller and Kaski. Background: Demand for head and neck cancer (HNC) radiotherapy data in algorithmic development has prompted increased image dataset sharing. Medical images must comply with data protection requirements so that re-use is enabled without disclosing patient identifiers. Defacing, i.e., the removal of facial features from images, is often considered a reasonable compromise between data protection and re-usability for neuroimaging data. While defacing tools have been developed by the neuroimaging community, their acceptability for radiotherapy applications have not been explored. Therefore, this study systematically investigated the impact of available defacing algorithms on HNC organs at risk (OARs). Methods: A publicly available dataset of magnetic resonance imaging scans for 55 HNC patients with eight segmented OARs (bilateral submandibular glands, parotid glands, level II neck lymph nodes, level III neck lymph nodes) was utilized. Eight publicly available defacing algorithms were investigated: afni_refacer, DeepDefacer, defacer, fsl_deface, mask_face, mri_deface, pydeface, and quickshear. Using a subset of scans where defacing succeeded (N=29), a 5-fold cross-validation 3D U-net based OAR auto-segmentation model was utilized to perform two main experiments: 1.) comparing original and defaced data for training when evaluated on original data; 2.) using original data for training and comparing the model evaluation on original and defaced data. Models were primarily assessed using the Dice similarity coefficient (DSC). Results: Most defacing methods were unable to produce any usable images for evaluation, while mask_face, fsl_deface, and pydeface were unable to remove the face for 29%, 18%, and 24% of subjects, respectively. When using the original data for evaluation, the composite OAR DSC was statistically higher (p ≤ 0.05) for the model trained with the original data with a DSC of 0.760 compared to the mask_face, fsl_deface, and pydeface models with DSCs of 0.742, 0.736, and 0.449, respectively. Moreover, the model trained with original data had decreased performance (p ≤ 0.05) when evaluated on the defaced data with DSCs of 0.673, 0.693, and 0.406 for mask_face, fsl_deface, and pydeface, respectively. Conclusion: Defacing algorithms may have a significant impact on HNC OAR auto-segmentation model training and testing. This work highlights the need for further development of HNC-specific image anonymization methods.

Introduction: 3D printing has quickly found many applications in medicine. However, as with any new technology the regulatory landscape is struggling to stay abreast. Unclear legislation or lack of legislation has been suggested as being one hindrance for wide-scale adoption.Methods: A scoping review was performed in PubMed, Web of Science, SCOPUS and Westlaw International to identify articles dealing with legal issues in medical 3D printing.Results: Thirty-four articles fulfilling inclusion criteria were identified in medical/technical databases and fifteen in the legal database. The majority of articles dealt with the USA, while the EU was also prominently represented. Some common unresolved legal issues were identified, among them terminological confusion between custom-made and patient-matched devices, lack of specific legislation for patient-matched products, and the undefined legal role of CAD files both from a liability and from an intellectual property standpoint. Data protection was mentioned only in two papers and seems an underexplored topic.Conclusion: In this scoping review, several relevant articles and several common unresolved legal issues were identified including a need for terminological uniformity in medical 3D printing. The results of this work are planned to inform our own deeper legal analysis of these issues in the future.

IntroductionImmune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, but preclinical testing of hypotheses such as combination therapies has been complicated, in part due to species incompatibility issues. For example, one of few known permissive animal models for oncolytic adenoviruses is the Syrian hamster, for which an ICI, mainly an anti-PD-L1 monoclonal antibody (mAb) was not previously available. In this study, we developed an anti-Syrian hamster PD-L1 mAb to enable the evaluation of safety and efficacy, when combining anti-PD-L1 with an oncolytic adenovirus encoding tumour necrosis factor alpha (TNFα) and interleukin-2 (IL-2) (Ad5/3-E2F-D24-hTNFα-IRES-hIL-2 or TILT-123).MethodsRecombinant Syrian hamster PD-L1 was expressed and mice immunized for mAb formation using hybridoma technology. Clonal selection through binding and functional studies in vitro, in silico and in vivo identified anti-PD-L1 clone 11B12-1 as the primary mAb candidate for immunotherapy modelling. The oncolytic virus (OV) and ICI combination approach was then evaluated using 11B12-1 and TILT-123 in a Syrian hamster model of pancreatic ductal adenocarcinoma (PDAC).ResultsSupernatants from hybridoma parent subclone 11B12B4 provided the highest positive PD-L1 signal, on Syrian hamster PBMCs and three cancer cell lines (HT100, HapT1 and HCPC1). In vitro co-cultures revealed superior immune modulated profiles of cell line matched HT100 tumour infiltrating lymphocytes when using subclones of 7G2, 11B12 and 12F1. Epitope binning and epitope prediction using AlphaFold2 and ColabFold revealed two distinct functional epitopes for clone 11B12-1 and 12F1-1. Treatment of Syrian hamsters bearing HapT1 tumours, with 11B12-1 induced significantly better (pConclusionsNovel Syrian hamster anti-PD-L1 clone 11B12-1 induces tumour growth control in a hamster model of PDAC. Combining 11B12-1 with oncolytic adenovirus TILT-123 improves tumour growth control further and demonstrates good safety and toxicity profiles.

Surrogate viruses theoretically provide an opportunity to study the viral spread in an indoor environment, a highly needed understanding during the pandemic, in a safe manner to humans and the environment. However, the safety of surrogate viruses for humans as an aerosol at concentrations has not been established. In this study, Phi6 surrogate was aerosolized at concentration (Particulate matter(2.5): similar to 1018 mu g m(-3)) in the studied indoor space. Participants were closely followed for any symptoms. We measured the bacterial endotoxin concentration the virus solution used for aerosolization as well as the concentration in the room air containing the aerosolized viruses. In addition, we measured how the bacterial endotoxin concentration the sample was affected by different traditional virus purification procedures. Despite the puri-fication, bacterial endotoxin concentration of the Phi6 was high (350 EU/ml in solution used aerosols) with both (two) purification protocols. Bacterial endotoxins were also detected aerosolized form, but below the occupational exposure limit of 90 EU/m(3). Despite these concerns, no symptoms were observed in exposed humans when they were using personal protective equipment. In the future, purification protocols should be developed to reduce associated terial endotoxin levels in enveloped bacterial virus specimens to ensure even safer research use surrogate viruses.

Objectives: To investigate tympanostomy tube (TT) treatment in young children, with special interest in bloodless surgical methods (laser and radiofrequency), myringosclerosis formation and tympanometric testing.Methods: This prospective study includes 76 children whose 121 ears with middle ear effusion were treated with tympanostomy tubes. Myringotomy was performed with CO2 laser in 37, radiofrequency in 40 and myringotomy knife in 44 ears. The ears were evaluated with otomicroscopy and tympanometry preoperatively and post-operatively every 3-4 months until spontaneous tube extrusion.Results: All tubes extruded spontaneously (mean 12.8 months, range 3-36 months), with no persistent perfora-tions or cholesteatomas. CO2 laser and radiofrequency inserted tympanostomy tubes extruded faster (mean 11 months) compared to incisional myringotomy (mean 15 months, p = 0.002). Myringosclerosis was noted in 25 (21%) ears after treatment. There was a tendency to less myringosclerosis with bloodless techniques, but the difference was not significant. Flat tympanograms on the day of procedure predicted continuation of ventilation problems also after TT treatment (p = 0.003). Ears with preoperative type B tympanogram had significantly more myringosclerosis 21/75 (28%) compared with type A and C tympanograms 4/41 (10%) (p = 0.032).Conclusions: While all myringotomy methods were effective and safe, the traditional incisional myringotomy with a tympanostomy knife is still a good, feasible and cost-effective myringotomy method. No surgical removal of tympanostomy tubes is needed before 3 years of uncomplicated tympanostomy treatment. Tympanometry turned out to be a useful tool in prediction of post TT treatment ventilation problems of the middle ear.

Non

Background Bacterial meningitis (BM) causes significant morbidity and mortality. We investigated predisposing factors, clinical characteristics, spectrum of etiological bacteria, and clinical outcome of community-acquired and nosocomial BM. Methods In this retrospective study we analyzed data of 148 adults (age > 16 years) with BM treated in Turku University Hospital, Southwestern Finland, from 2011 to 2018. Besides culture- or polymerase chain reaction (PCR)-positive cases we also included culture-negative cases with laboratory parameters strongly suggestive of BM and those with meningitis-related findings in imaging. We used Glasgow Outcome Scale (GOS) score 1–4 to determine unfavorable outcome. Results The median age of patients was 57 years and 48.6% were male. Cerebrospinal fluid (CSF) culture for bacteria showed positivity in 50 (33.8%) cases, although pre-diagnostic antibiotic use was frequent (85, 57.4%). The most common pathogens in CSF culture were Streptococcus pneumoniae (11, 7.4%), Staphylococcus epidermidis (7, 4.7%), Staphylococcus aureus (6, 4.1%) and Neisseria meningitidis (6, 4.1%). Thirty-nine patients (26.4%) presented with the triad of fever, headache, and neck stiffness. A neurosurgical procedure or an acute cerebral incident prior BM was recorded in 74 patients (50%). Most of the patients had nosocomial BM (82, 55.4%) and the rest (66, 44.6%) community-acquired BM. Ceftriaxone and vancomycin were the most used antibiotics. Causative pathogens had resistances against the following antibiotics: cefuroxime with a frequency of 6.8%, ampicillin (6.1%), and tetracycline (6.1%). The case fatality rate was 8.8% and the additional likelihood of unfavorable outcome 40.5%. Headache, decreased general condition, head computed tomography (CT) and magnetic resonance imaging (MRI), hypertension, altered mental status, confusion, operative treatment, neurological symptoms, pre-diagnostic antibiotic use and oral antibiotics on discharge were associated with unfavorable outcome. Conclusions The number of cases with nosocomial BM was surprisingly high and should be further investigated. The usage of pre-diagnostic antibiotics was also quite high. Headache was associated with unfavorable outcome. The frequency of unfavorable outcome of BM was 40.5%, although mortality in our patients was lower than in most previous studies.

Purpose Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990–1999. Methods We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. Results The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. Conclusions The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.

ObjectiveTo explore predictive factors of postoperative outcome of frontal sinus balloon dilation. Study DesignRetrospective questionnaire study. SettingDepartment of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Finland. MethodsWe reviewed electronic records of all patients who underwent frontal sinus balloon dilatation (successful or attempted) in our clinic from 2008 to 2019. We documented patient characteristics, preoperative imaging results, intraoperative factors, possible complications, and reoperations. Those who underwent frontal sinus balloon sinuplasty were sent a questionnaire regarding their current symptoms and long-term satisfaction with surgery. ResultsIn total, 258 operations (404 frontal sinuses) were reviewed, with a technical success rate of 93.6% (n = 378). The revision rate was 15.7% (n = 38). Previous sinonasal surgery predicted a higher revision rate (p = .004, odds ratio [OR] = 3.03, 95% confidence interval [CI] 1.40-6.56). Patients with hybrid surgery had significantly fewer reoperations compared to the balloon only group (p = .002, OR = 0.33, 95% CI 0.16-0.67). The response rate of the questionnaire was 64.5% (n = 156), of which 88.5% (n = 138) reported a long-term benefit from the balloon sinuplasty. Patient satisfaction was higher (p = .02, OR = 8.26, 95% CI 1.06-64.24) among patients using nasal corticosteroids. ConclusionTechnical success rate and patient satisfaction after frontal sinus balloon sinuplasty are high. Balloon sinuplasty seems insufficient in reoperations. A hybrid approach appears to result in fewer reoperations than a balloon only approach.

Plexiform variants of neurofibromas and schwannomas are rare and typically arise in superficial soft tissues in the head and neck region. The treatment of these tumors is challenging and no generally accepted guidelines exist for their optimal management. The purpose of this study was to review the management and longterm prognosis of head and neck plexiform neurofibromas and schwannomas at 2 tertiary care academic hospitals in Finland over a 31-year period. The pathology files were searched for plexiform neurofibromas and schwannomas between the years 1990 and 2020. The case notes were reviewed for full management details. Two plexiform schwannomas and 6 plexiform neurofibromas were identified. Five of the 6 plexiform neurofibromas were managed operatively. All patients with a surgically managed plexiform neurofibroma underwent multiple operations. Sclerotherapy abolished 1 patient's cutaneous plexiform neurofibromas. The management of plexiform neurofibromas and plexiform schwannomas remains challenging. Sclerotherapy may offer a promising management option for cutaneous plexiform neurofibromas.

Publisher Copyright: © 2021 John Wiley & Sons Ltd Objectives Postoperative infection is the most common complication after septoplasty. Pre- or postoperative prophylactic antibiotics are commonly used, although no official guidelines exist. Design We retrospectively collected data on postoperative infections from 772 septoplasties performed in 2015, 2016 and 2018, and classified the infections according to surgical site infection (SSI) criteria by the Centers for Disease Control and Prevention (CDC). We evaluated the infections according to antibiotic use (preoperative or postoperative, both, or none) and accounted for patient and surgical confounding factors. We compared the results with three previous studies from our department to find out the trend in the occurrence of postoperative infections and in the use of antibiotics. Results Twenty-nine cases (3.8%) fulfilled CDC infection criteria. Any kind of antibiotic prophylaxis reduced the risk of SSI (p = .018). One dose of intravenous cefuroxime before incision was the most effective preventive measure (p = .045). We found no significant effect of postoperative antibiotics. However, postoperative antibiotics lowered the infection rate to 1.8% compared to 6.1% among those not treated with any antibiotics. The only other factor reducing the risk of SSI was local anaesthesia compared with general anaesthesia. Conclusion Preoperative antibiotic prophylaxis effectively reduced postoperative infection rate after septoplasty.

Background Insufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common. Methods This retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival. Results The lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS. Conclusions Diagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.

BACKGROUND: Sinus barotraumas are a common condition in aviation medicine, sometimes compromising flight safety and even permanently grounding aircrew. Considering this and the ever-increasing amount of commercial aviation, a thorough examination is required.METHODS: In this survey study, an anonymous, electronic questionnaire was distributed to commercial aircrew of the three major commercial airlines operating in Finland (N = 3799), covering 93% of the target population (i.e., all commercial aircrew operating in Finland, N = 4083). Primary outcomes were self-reported prevalence, clinical characteristics, and health and occupational effects of sinus barotraumas in flight. Secondary outcomes were adjusted odds ratios (OR) for frequency of sinus barotraumas with respect to possible risk factors.RESULTS: Response rate was 47% (N = 1789/3799), with 61% (N = 1088) of the respondents having experienced sinus barotraumas in flight. Of those affected, 59% had used medications, 18% had undergone surgical procedures, and 53% had been on sick leave due to sinus barotraumas (38% during the last year) in flight. Factors associated with sinus barotraumas were female sex [OR, 2.47; 95% confidence interval (CI) 1.35–4.50] and a high number of upper respiratory tract infections (≥3 vs. CONCLUSION: Sinus barotraumas were reported by 61% of commercial aircrew. They caused an increased need for medications, otorhinolaryngology-related surgical procedures, and sickness absence from flight duty. The possible risk factors were female sex and a high number of URTIs/yr.Lindfors OH, Ketola KS, Klockars TK, Leino TK, Sinkkonen ST. Sinus barotraumas in commercial aircrew. Aerosp Med Hum Perform. 2021; 92(11):857–863.

Objective COVID-19 spreads through aerosols produced in coughing, talking, exhalation, and also in some surgical procedures. Use of CO2 laser in laryngeal surgery has been observed to generate aerosols, however, other techniques, such cold dissection and microdebrider, have not been sufficiently investigated. We aimed to assess whether aerosol generation occurs during laryngeal operations and the effect of different instruments on aerosol production. Methods We measured particle concentration generated during surgeries with an Optical Particle Sizer. Cough data collected from volunteers and aerosol concentration of an empty operating room served as references. Aerosol concentrations when using different techniques and equipment were compared with references as well as with each other. Results Thirteen laryngological surgeries were evaluated. The highest total aerosol concentrations were observed when using CO2 laser and these were significantly higher than the concentrations when using microdebrider or cold dissection (p p p p p = 0.146, p = 0.753). In comparing all three techniques, microdebrider produced the least aerosol particles. Conclusions Microdebrider and cold dissection can be regarded as aerosol-generating relative to background reference concentrations, but they should not be considered as high-risk aerosol-generating procedures, as the concentrations are low and do not exceed those of coughing. A step-down algorithm from CO2 laser to cold instruments and microdebrider is recommended to lower the risk of airborne infections among medical staff.

Objectives The study purpose was to evaluate the effects of the COVID-19 pandemic on the rate and disease profile of orofacial and respiratory infections in oral and maxillofacial surgery (OMFS) and ear, nose, and throat (ENT) emergency units. Materials and methods Records of patients with orofacial or respiratory infection, or infectious symptoms, diagnosed in the OMFS or ENT Emergency Departments of the Helsinki University Hospital, Helsinki, Finland between 1st March and 30th October 2020 and the corresponding periods in 2018 and 2019 were reviewed. The main outcome variable was the occurrence of studied infections during the evaluated periods. Other study variables were age, gender, residence area, speciality, specific cause for the emergency department visit and admission to ward. Results There was a significant 37% decrease in the number of infection patients in 2020 compared to the years 2019 and 2018 (1894 vs. 2929 and 3077, respectively, p p = .013). Conclusion A significant decrease was observed in the volume of emergency department visits for orofacial and respiratory infections during the COVID-19-pandemic in 2020 compared to the non-COVID periods. Clinical relevance It seems that social distancing, facial mask wearing, and other infection prevention precautions have changed the accustomed patient profile in orofacial and respiratory infections.

Background: The optimal management of oropharyngeal squamous cell carcinoma (OPSCC) includes both sur-gical and non-surgical, that is, (chemo)radiotherapy treatment options and their combinations. These approaches carry a risk of specific treatment-related side effects. HPV-positive OPSCC has been reported to be more sensitive to (chemo)radiotherapy-based treatment modalities. Objectives: This study aims to demonstrate how machine learning can aid in classifying OPSCC patients into risk groups (low-chance or high-chance) for overall survival. We examined the input variables using permutation feature importance. Furthermore, we provided explanations and interpretations using the Local Interpretable Model Agnostic Explanations (LIME) and SHapley Additive Explanation (SHAP) frameworks. Methods: The machine learning model for 3164 OPSCC patients was built using data obtained from the Surveillance, Epidemiology, and End Results (SEER) program database. A total of five variants of tree-based machine learning algorithms (voting ensemble, light GBM, XGBoost, Random Forest, and Extreme Random Trees) were used to divide the patients into risk groups. The developed model with the best predictive performance was temporally validated with a different cohort. Results: The voting ensemble machine learning algorithm showed an accuracy of 88.3%, Mathews' correlation coefficient of 0.72, and weighted area under curve of 0.93, when temporally validated. Human papillomavirus (HPV) status, age of the patients, T stage, marital status, N stage, and the treatment modality (surgery with postoperative radiotherapy) were found to have the most significant effects on the ability of the machine learning model to predict overall survival. Similarly, for the individual patients with SHAP framework, HPV status, gender, and treatment modality (surgery with postoperative radiotherapy) were the input features that improved the model's prediction. Conclusion: The proposed stratification of OPSCC patients into risk groups by machine learning techniques can provide accurate predictions and thus aid clinicians in administering early and personalized interventions. Clinicians could utilize the predicted risk with the explanations offered by the SHAP and LIME frameworks to understand previously undetected relationships between prognostic variables to make informed clinical decisions and effective interventions.

Background Vocal-fold augmentation is a continuously developing treatment modality for glottic insufficiency. Patients with glottic insufficiency attend the phoniatrics clinics with increasing frequency. Glottic insufficiency may be due to vocal-fold paralysis, paresis, atrophy, sulcus vocalis, scarring, and vocal-fold deficiency after laryngeal surgery. A variety of materials exist for injection augmentation. This follow-up study aimed to assess the short-term as well as long-term outcomes of vocal-fold injection with calcium hydroxyapatite (CaHA) in patients with glottic gap 1–3 mm. Method This study included 25 patients with glottic insufficiency who underwent injection augmentation with CaHA. All patients were scheduled for voice evaluation using a comprehensive subjective and objective battery of assessments. Assessments were performed before the procedure and after the procedure at 2 months and at 1 year. Results Perceptual voice quality assessed with the GRBAS scale improved and the results were stable after 1 year. Shimmer and HNR improved continuously through the follow-up sessions, while jitter and f0 showed slight improvement after CaHA injection. Conclusion Voice improvement after injection of CaHA requires a minimum of 2 months to develop and may last for a long period.

Bilateral Sensorineural Hearing Loss is a rare disease that is often associated with other complex medical conditions. Primary central nervous system lymphoma is an uncommon and aggressive variant of non-Hodgkin lymphoma that can mimic many other neurological diseases. Herein, we present a rare case of lymphoma of the CNS as the etiology for progressive SSNHL. We describe a 58-year-old male with previous IgG4-disease presentation who was diagnosed with progressive sensorineural hearing loss. The condition evolved rapidly despite proper, conventional therapy. The patient acquired vestibular symptoms and other cranial nerve deficiencies and he was diagnosed with intracranial lymphoma, mainly in the cerebellar region. This case demonstrates that rare intracranial lymphoma can present initially as sensorineural hearing loss. A higher suspicion for malignancy should be held in mind for patients with a history of IgG4-related diseases and for patients presenting with progressing bilateral SSNHL that is not responding to therapy.