[Neuro-otological manifestations in Fabry disease-a retrospective single center study]. / Neurootologische Manifestationen bei Morbus Fabry ­ eine retrospektive Analyse.

BACKGROUND: Fabry disease (FD) is one of the X­linked lysosomal storage diseases that can affect any organ. They have a specific lysosomal dysfunction in common, which results in substrate accumulation in lysosomes instead of metabolite degradation. Due to the deficiency/absence of α­galactosidase, globotriaosylceramides (Gb3) are deposited in lysosomes of the organs. In addition to acroparesthesia, angiokeratomas, autonomic dysfunction, vortex keratopathies, ischemic cerebral or cardiac complications and chronic renal failure, also vestibulocochlear dysfunctions with sudden or progressive asymmetric hearing loss, tinnitus and vertigo may be observed. PATIENTS AND METHODS: In this retrospective study, 33 patients (men = 16 and women = 17) with FD were evaluated. All patients presented to us in interdisciplinary cooperation as part of routine examinations by the specialized center for lysosomal storage diseases of the in-house department of nephrology. This presentation is carried out as a screening examination independent of neuro-otological symptoms. RESULTS: The mean age at diagnosis was 34.76 (±11.55) years. The first presentation in our ENT department was at 40.45 (±11.71) years. We were able to demonstrate a significant correlation between neurological symptoms or apoplexy and hearing loss (p = 0.001) and between cardiac manifestations and hearing loss (p = 0.024). CONCLUSION: Hearing loss is a potential symptom of Fabry disease and is not limited to the classic male phenotype. Due to possible positive correlations with neurological and cardiological manifestations of the disease, routine ENT screening examinations should be carried out to be able to identify and treat neuro-otological deficits at an early stage. In addition, FD should also be considered and tested as a differential diagnosis, especially in younger patients with sudden unilateral or bilateral hearing loss and a family history.

The influence of antibiotic administration on the outcomes of head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiation.

PURPOSE: Effects of antibiotic administration on patients' microbiome may negatively influence cancer outcomes, and adverse prognoses after antibiotic application have been demonstrated for cancer patients receiving immune checkpoint inhibitors. While the microbiome may play an important role also in head-and-neck squamous cell carcinoma (HNSCC), the prognostic value of antibiotic treatment here is largely unknown. We therefore analyzed whether antibiotic prescription is associated with impaired oncological outcomes of HNSCC patients undergoing definitive (chemo)radiation. METHODS: A cohort of 220 HNSCC patients undergoing definitive (chemo)radiation between 2010 and 2019 was analyzed. The influence of antibiotic administration on locoregional control, progression-free survival (PFS) and overall survival (OS) was determined using Kaplan-Meier and Cox analyses. RESULTS: A total of 154 patients were treated with antibiotics within 30 days before (chemo)radiation (pretherapeutic) or during (chemo)radiation (peritherapeutic). While antibiotic prescription was not associated with age, ECOG, tumor localization or radiotherapy characteristics, patients treated with antibiotics had significantly higher tumor stages. Peritherapeutic antibiotic administration diminished PFS (HR = 1.397, p < 0.05, log-rank test) and OS (HR = 1.407, p < 0.05), whereas pretherapeutic administration did not. Antibiotic application was an independent prognosticator for OS (HR = 1.703, p < 0.05) and PFS (HR = 1.550, p < 0.05) in the multivariate Cox analysis within the subgroup of patients aged < 75 years. CONCLUSION: Peritherapeutic antibiotic usage was associated with impaired oncological outcomes in HNSCC patients undergoing (chemo)radiation. Further studies including microbiome analyses are required to elucidate underlying mechanisms.

Human Mesenchymal Stromal Cells Do Not Cause Radioprotection of Head-and-Neck Squamous Cell Carcinoma.

Radiotherapy of head-and-neck squamous cell carcinoma (HNSCC) can cause considerable normal tissue injuries, and mesenchymal stromal cells (MSCs) have been shown to aid regeneration of irradiation-damaged normal tissues. However, utilization of MSC-based treatments for HNSCC patients undergoing radiotherapy is hampered by concerns regarding potential radioprotective effects. We therefore investigated the influence of MSCs on the radiosensitivity of HNSCCs. Several human papillomavirus (HPV)-negative and HPV-positive HNSCCs were co-cultured with human bone marrow-derived MSCs using two-dimensional and three-dimensional assays. Clonogenic survival, proliferation, and viability of HNSCCs after radiotherapy were assessed depending on MSC co-culture. Flow cytometry analyses were conducted to examine the influence of MSCs on irradiation-induced cell cycle distribution and apoptosis induction in HNSCCs. Immunofluorescence stainings of γH2AX were conducted to determine the levels of residual irradiation-induced DNA double-strand breaks. Levels of connective tissue growth factor (CTGF), a multifunctional pro-tumorigenic cytokine, were analyzed using enzyme-linked immunosorbent assays. Neither direct MSC co-culture nor MSC-conditioned medium exerted radioprotective effects on HNSCCs as determined by clonogenic survival, proliferation, and viability assays. Consistently, three-dimensional microwell arrays revealed no radioprotective effects of MSCs. Irradiation resulted in a G2/M arrest of HNSCCs at 96 h independently of MSC co-culture. HNSCCs' apoptosis rates were increased by irradiation irrespective of MSCs. Numbers of residual γH2AX foci after irradiation with 2 or 8 Gy were comparable between mono- and co-cultures. MSC mono-cultures and HNSCC-MSC co-cultures exhibited comparable CTGF levels. We did not detect radioprotective effects of human MSCs on HNSCCs. Our results suggest that the usage of MSC-based therapies for radiotherapy-related toxicities in HNSCC patients may be safe in the context of absent radioprotection.

[Risk profile analysis of stationary epistaxis patients]. / Analyse des Risikoprofils stationärer Epistaxis-Patienten.

BACKGROUND: Epistaxis is a disease well known to general practitioners and ENT specialists in the outpatient sector as well as in hospitals. The aim of this study was to analyze data of patients that were treated as inpatients at the ENT university hospital Freiburg between 2014-2018. MATERIALS AND METHODS: This retrospective study analyzes data of admitted patients with epistaxis regarding age, medication, bleeding site, underlying health conditions, radiological imaging and treatment. Risk factors for longer inpatient length of stay and readmission were identified. RESULTS: Median length of stay was 3.5 days. 55 % of the patients suffered from posterior epistaxis. 72.3 % of patients were treated with anticoagulants at the time of admission. The most prevalent medical conditions were hypertension (66 %) and arrhythmia due to atrial fibrillation (36.1 %). 63.5 % of the patients were treated by nasal packing. 97 patients (14.6 %) had to be treated surgically. Surgical treatment, transfusion, posterior epistaxis and anticoagulant treatment were risk factors for longer length of inpatient stay. Preexisting hypertension, posterior bleeding and single anticoagulant treatment increased the risk of readmission. CONCLUSIONS: Determination and consideration of risk factors allow identification of patients at risk of longer inpatient length of stay and readmission. Adequate management accounting for risk profiles of patients could help reduce morbidity.

[Establishing an ORL virtual outpatient Dept. during the COVID-19 pandemic]. / Erstellung einer virtuellen HNO-Ambulanz in der Lehre während der COVID-19-Pandemie.

INTRODUCTION: The COVID-19 pandemic changed medical education: teaching has been mostly converted to online mode. Our aim is to offer a complete high-quality curriculum despite the fact of worldwide cutbacks in education. METHODS: The department of otorhinolaryngology introduced case-based learning (CBL). CBL is a learning and teaching approach that prepares students for clinical practice through the use of authentic clinical cases and places them in the role of decision maker. CBL combines theory and practice to prepare students as good as possible without intern shadowing. The students were asked to evaluate CBL as a digital format and as a teaching tool for future clinical work and preparation for the ORL exam. RESULTS: The majority of students (>90%) rated the CBL as a successful digital format. Most students also strongly agreed or agreed that CBL is a good preparation for their future clinical work (>90%) and the ORL exam (>80%). 100% of students CBL confirmed, that they learned something new. CONCLUSION: Following successful introduction of CBL we will implement a new teaching format. The "ORL virtual outpatient Dept." will include information from virtual, anonymized case studies. We choose diagnosis included in the "ORL virtual outpatient Dept." according to the most common ORL disorders encountered by primary care physicians. The "ORL virtual outpatient Dept." can only bridge the absence of practical training, and, in the future, serve as an additional preparation.

Mono-institutional retrospective cohort analysis of the insurance status dependent access to ENT-professionals and survival in head and neck squamous cell carcinoma.

BACKGROUND: To access the influence of insurance status on time of diagnosis, quality of treatment and survival in head and neck squamous cell carcinoma (HNSCC). METHODS: This mono-institutional retrospective cohort analysis included all HNSCC patients (n = 1,054) treated between 2001 and 2011, and subdivided the cohort according to the insurance status. Differences between the groups were analyzed using the Chi square and the unpaired student's t-test. Survival rates were calculated by Kaplan-Meier and Cox regression for forward selection. RESULTS: Nine hundred twenty-five patients showed general, 129 private insurance. The 2 groups were equal regarding age, gender, tumor localization, therapy, and N/M/G/R-status. The T-status differed significantly between the groups showing more advanced tumors in patients with general insurance (p = 0.002). While recurrence-free survival was comparable in both groups, overall survival was significantly better in private patients (p = 0.009). The time frame between first symptom and diagnosis was equal in both groups. CONCLUSIONS: The time frame between subjective percipience of first symptom and final therapy did not differ between the groups. In our cohort, access to otorhinolaryngological specialists is favorable in both, patients with general and private insurance. Recurrence-free survival was comparable in both groups, indicating successful HNSCC treatment both groups. However, overall survival was significantly better in patients with private insurance suggesting other socioeconomic factors influencing survival.

Collateral damage of the COVID-19 pandemic: an alarming decline in critical procedures in otorhinolaryngology in a German university hospital.

PURPOSE: The COVID-19 pandemic has a major impact on the diagnosis and treatment of ENT patients. The aim of this study was to analyze the influence of the pandemic on the number of otolaryngological procedures, particularly for critical diagnoses with potential negative effects due to prolonged symptom duration. METHODS: We evaluated 10,716 surgical procedures between January 1, 2018 and May 31, 2020, focusing on the 16-week period around March 16, 2020, which includes 1080 observations. We further analyzed subsets of critical procedures. RESULTS: We found a decline in critical procedures by 43% although no critical procedures were postponed by the hospital. Meanwhile, the share of critical procedures increased up to 90% caused by the cancellation of elective surgery. Especially worrisome was that diagnostic procedures for suspected malignancies decreased by 41% during the pandemic. CONCLUSION: The decline in critical procedures in otorhinolaryngology as collateral damage of the COVID-19 pandemic is considerable and therefore alarming.

Review of surgical techniques and guide for decision making in the treatment of benign parotid tumors.

PURPOSE: Surgical treatment of benign parotid tumors has developed in the direction of less invasive procedures in recent years and has raised great debate about the best surgical approach. Aim of this article is to analyse anatomical and other factors that are important in selection of the appropriate surgical technique in treatment of benign parotid tumors. Furthermore, to discuss the risk of complications and recurrent disease according to selected operation. Finally, to define patient selection criteria to facilitate decision making in parotid surgery and become a guide for younger surgeons. METHODS: Literature review and authors' personal opinions based on their surgical experience. RESULTS: All possible surgical techniques for benign parotid surgery with advantages and disadvantages are being described. An algorithm with anatomical and other criteria influencing decision making in benign parotid surgery is presented. CONCLUSION: Surgeons nowadays have many options to choose from for benign parotid surgery. ECD is one of the many surgical techniques available in parotid surgery and can achieve excellent results with proper training and if used for proper indications. PSP is mainly indicated in large tumors of the caudal part of the PG (ESGS level II). SP represents a universal solution in parotid surgery and should be the first technique young surgeons learn. TP has only few but important indications in benign parotid surgery. Surgeons need to carefully consider the patient and his/her preoperative imaging as well as her or his own special expertise to select the most appropriate surgical technique.

Radiation-induced toxicities and outcomes after radiotherapy are independent of patient age in elderly salivary gland cancer patients: results from a matched-pair analysis of a rare disease.

PURPOSE: This study analyzed survival and toxicity after (chemo)radiotherapy for primary salivary gland cancer patients aged ≥ 65 years and compared these results with younger patients using a matched-pair analysis. METHODS: Twenty-nine elderly patients with primary salivary gland carcinomas treated with (chemo)radiotherapy from 2008 to 2020 at University of Freiburg Medical Center were analyzed for oncological outcomes and therapy-associated toxicities. Local/locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and the influence of clinical parameters on patient outcomes was assessed. A matched-pair analysis was performed after matching with patients < 65 years. RESULTS: Nine patients (31.0%) received definitive (chemo)radiotherapy, and 20 patients (69.0%) were treated in the adjuvant setting. 2-year LRC, PFS and OS ranged at 82.4%, 53.7% and 71.8%, respectively. Smoking (HR 3.980, p = 0.020), reduced performance status (HR 3.735, p = 0.016) and higher comorbidity burden (HR 4.601, p = 0.005) correlated with inferior OS. Using a matched-pair analysis with younger patients, elderly patients exhibited a trend towards reduced OS (HR 3.015, p = 0.065), but not PFS (HR 1.474, p = 0.371) or LRC (HR 1.324, p = 0.633). Acute and chronic grade 3 toxicities occurred in 31.0% and 12.5% of elderly patients, respectively, and the matched-pair analysis revealed no significant differences between age groups regarding treatment-related toxicities. CONCLUSION: Treatment-related toxicities as well as LRC and PFS were comparable for salivary gland cancer patients undergoing radiotherapy. Therefore, concerns for more pronounced toxicities or reduced local/locoregional response rates should not guide treatment decisions in affected elderly patients.

[Digitalization in curricular teaching: Experiences with the Freiburg ENT Learning Program]. / Digitalisierung in der curricularen Lehre: Erfahrungen mit dem Freiburger HNO-Lernprogramm.

BACKGROUND: The relevance of undergraduate Online Teaching increases - on one hand to diversify (ENT) teaching, on the other to continue medical training even in times of crisis like the SARS-CoV-2 pandemic. Therefore, at the university hospital of Freiburg we build and launched the ENT Learning Program, an online learning platform for medical students. OBJECTIVES: This study will give an insight into structure and functions of the learning program. Furthermore, its use and usefulness will be subjectively and objectively evaluated. MATERIALS AND METHODS: The ENT Learning Program is a web application, that can be used by any Internet-enabled device. ENT content is presented by text, images, video tutorials and interactive features like multiple-choice questions and feedback functions. To evaluate students' use and benefits of the program we first conducted a questionnaire survey with 116 medical students. To objectify the results, we then counted the actual visits to the program and carried out a randomised learning-control-study (n = 47). RESULTS: The learning program was used by 97 % of the interrogated students. Over 80 % said that the program improved their exam preparation, motivated them to study and enhanced their interest in ENT. In one year, we counted almost 90.000 visits to the website. Furthermore, the learning-control-study showed a significant better test outcome in students, who used the LP in addition. CONCLUSIONS: The ENT Learning Program is a promising tool in online teaching, that did not yet exist in Germany that way. Through academic collaborations it could be optimized further and integrated into ENT courses at other universities.

Bilateral versus ipsilateral neck dissection in oral and oropharyngeal cancer with contralateral cN0 neck.

OBJECTIVE: Contralateral elective neck dissection (cEND) in oral and oropharyngeal squamous cell cancer (OC/OPC) is still a matter of debate. The current study analyzed the outcome in OC/OPC patients with/without cEND. METHODS: OC/OPC patients (n = 471) were diagnosed with contralateral N0 after CT/MRI-scan combined with neck ultrasound. Clinico-pathological features were analyzed using Chi-square/Fisher exact/Student's t test. Survival rates were calculated using Kaplan-Meier and log-rank test. Prognostic variables were evaluated by Cox regression. Primary/secondary endpoints were overall/recurrence-free survival (OS/RFS). RESULTS: Pre-therapeutic imaging revealed a significantly over-staged N-status (p = 0.01), while occult contra-lateral N + was diagnosed in one patient only (0.4%). OC patients did not show differences in OS/RFS between the groups (ipsi- vs. bi-lateral). There was a strong tendency towards a better OS in OPC patients who underwent ipsi-lateral ND (p = 0.07). Cox-regression demonstrated that only tumor recurrence was associated with a fivefold increased risk of recurrence-associated death (p < 0.0001) that referred to a significant higher recurrence rate at primary tumor site (rT +) and increased distant metastatic outgrowth in OPC who underwent bi-lateral neck dissection (p = 0.03). While RFS of any cause (rT + /rN + /rM +) was significantly better in OPC with ipsi-lateral ND (p < 0.05), RFS of contralateral lymph node recurrence (rN2c) was comparable in both groups. CONCLUSION: END of the contralateral cN0 neck is not correlated by an increased RFS or OS. Standard imaging techniques including CT/MRI scan and neck ultrasound warrant watchful waiting for neck dissection of the contralateral cN0 neck.

[Telemedicine in the fight against SARS-COV-2-opportunities and possible applications in otorhinolaryngology : Narrative review]. / Chancen und Einsatzmöglichkeiten von Telemedizin in der Hals­, Nasen- und Ohrenheilkunde bei der Bekämpfung von SARS-COV-2 : Narratives Review.

INTRODUCTION: The COVID-19 pandemic is bringing healthcare systems worldwide to the brink of collapse. One reason for this is the rapidly increasing number of new infections. On the other hand, the high sickness rates of doctors and nurses, particularly in ENT medicine, are aggravating the situation. Telemedicine can be a useful tool to reduce the number of physician-patient contacts. This could break infection chains and minimize the risk of infection for physicians. METHODS: To prepare the review, a selective literature search was conducted at www.pubmed.com using the relevant English technical terms for telemedicine and ENT. In addition, research was conducted at www.news.google.com on current developments of the COVID-19 pandemic with the search terms "telemedicine" and "COVID-19." RESULTS: Telemedicine can be helpful in direct contact with patients as well as in the conciliar support of general practitioners. The available studies show that, on average, more than 50% of medical consultations could be carried out telemedically. Both physicians and patients rate the use of telemedicine positively. Neither image quality nor the handling of the technology are relevant obstacles to a reliable diagnosis. Patients indicated that the telemedical consultation did not last longer than a traditional consultation. Patients also highlighted the faster and better availability of medical care through telemedicine. CONCLUSION: Telemedicine can make a decisive contribution to coping with the current COVID-19 pandemic. Furthermore, the establishment of telemedicine can help us to become better prepared for future pandemics.

[Sinus surgery at German ENT departments - a regional survey]. / Nasennebenhöhlenchirurgie an deutschen HNO-Kliniken ­ eine Bestandsaufnahme.

OBJECTIVE: Sinus surgery has evolved dramatically over the last decades towards endonasal endoscopic techniques for the treatment of benign and malignant diseases of the paranasal sinuses. The aim of this survey was to capture the current state of sinus surgery in German ENT departments. MATERIAL AND METHODS: A questionnaire with questions regarding number of surgeries, surgical technique, interdisciplinary cooperation, postoperative care, CT-checklists, surgical training and quality of life was sent to all ENT departments in Germany. RESULTS: 79.5 % of questionnaires were answered and returned. 89.1 % of ENT departments state that they conduct 200-400 or more than 400 sinus surgeries per year for benign diseases of the paranasal sinuses. The number of sinus surgeries for malignancies of the paranasal sinuses is much smaller. Not all of the departments who take part in interdisciplinary tumor boards work in interdisciplinary surgical teams. Most of the departments declare that they use video endoscopy and surgical navigation systems for their surgeries. Surgical training for sinus surgery usually starts in year 2 to 4 and almost all trainees visit dissection courses during their training. In more than half of the departments CT checklists are used for preoperative analyses of CT scans. Quality of life before and after surgery is evaluated in only a few departments. CONCLUSION: Our investigation is a representative survey of current practice in sinus surgery in ENT departments in Germany.

[Drug-induced sleep endoscopy]. / Medikamentös induzierte Schlafendoskopie.

Drug-induced sleep endoscopy (DISE) is a procedure for the assessment of the upper airways in patients with obstructive sleep apnea (OSA) and was first described by Croft and Pringle in 1991 1. So far, it has not been clarified to what extent the DISE can be compared to natural sleep. Eastwood and colleagues ultimately described a correlation in terms of the tendency to collapse in sedation and during natural sleep. It was shown, that DISE is useful in individual therapeutic descisions 2. In recent years, efforts to standardize the procedure have been made in order to make the results more comparable and reproducible. With the introduction and increasing use of stimulation therapy of the hypoglossal nerve, DISE has been used more and more in hospitals in recent years. This article is intended to present the procedure based on the European position paper on DISE 3 4.

Patient experience with upper airway stimulation in the treatment of obstructive sleep apnea.

OBJECTIVE: Selective upper airway stimulation (sUAS) is a new treatment modality for patients with obstructive sleep apnea (OSA) and continuous positive airway pressure (CPAP) failure. The aim of this study was to analyze therapy adherence and to structure patient experience reports. METHODS: Patients from two German implantation centers were included. Besides demographic and OSA characteristics of that cohort, patients answered a questionnaire on subjective sensation of the stimulation, use of different functions, side effects, and an inventory for the description of the attitude towards sUAS. The use of the sUAS was evaluated as a read-out of the implanted system. RESULTS: The overall apnea-hypopnea-index (AHI) of that 102 assessed patients reduced from initially 32.8/h to 12.6/h at the last available assessment. The responder rate was 75%. There was an objective therapy usage of 5.7 h and subjective reports of 6.8 nights per week. The attitude resulted in strong agreement towards the statement "UAS reduces the problems caused by my sleep apnea". Information on sensing the stimulation and usage habits could be gathered such as that stimulation is only sensed by 67.9% of the patients upon waking in the morning and that 73.6% of the patients do not change the voltage in general. CONCLUSION: This investigation on the sUAS therapy revealed a high adherence to the therapy. The AHI or daytime sleepiness do not have obvious influence on adherence. Patients expressed a positive attitude towards sUAS. These patient reports upon stimulation experiences are of great help to consult candidates for sUAS in future.

[Differentiation of ultrasonographic hypoechoic head and neck lesions]. / Differentialdiagnostik sonographisch echoarmer Kopf-Halsläsionen.

AIM: To evaluate ultrasonographic hypoechoic lesions (HEL) of the head and neck region to predict their entity and plan surgery. METHODS: Patients with HEL were included that were further analysed by B-mode ultrasound (US), colour-coded duplex sonography (CDS), contrast enhanced US (CEUS), and strain elastography (SE). RESULTS: 184 patients were included. Level VIII, II, and I were affected frequently with 103, 40, and 21 HEL. The cohort comprised 40 lymph node disorders, 101 salivary gland diseases, 31 cystic lesions, and 12 other rarer entities. HEL in level II were significantly larger than in level I and VIII (p < 0.001). HEL in level VI showed less vascularisation than in level VIII in CDS (p < 0.01). There were no differences in B-mode criteria, SE, or CEUS between HEL in the different neck levels. Patients with cystic lesions were significantly younger than patients with metastases or Warthin's tumours (p = 0.026, 0.028). Pleomorphic adenomas were significantly smaller than cystic lesions (p < 0.0006), lymphomas (p = 0.026), metastases (p = 0.0003), or Warthin's tumours (p = 0.034). In CDS and CEUS, cystic lesions showed significantly less vascularisation and perfusion than lymphomas (p = 0.014) and Warthin's tumours (p < 0.0001), while pleomorphic adenomas were stiffer than cystic lesions in SE (p = 0.0006). CONCLUSION: Predicting lesion's entity is still challenging. The combination of different ultrasonographic criteria helped selecting patients that needed intraoperative fresh frozen section with possible extended surgery and profited from intraoperative nerve monitoring.

How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project).

OBJECTIVES: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren's syndrome (SjS). METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays. RESULTS: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains). CONCLUSIONS: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.

Olfactory Function is Affected in Patients with Cirrhosis Depending on the Severity of Hepatic Encephalopathy.

INTRODUCTION AND AIM: Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the "Sniffin' Sticks" test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria. MATERIAL AND METHODS: 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the "Sniffin' Stick" test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West- Haven criteria) and according to CFF, which was determined using a portable analyzer. RESULTS: Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension. CONCLUSIONS: Olfactory testing serves as a screening tool for HE and may facilitate grading of HE-severity.

Improved overall survival in head and neck cancer patients after specific therapy of distant metastases.

PURPOSE: While metastases directed therapy for oligometastatic disease is recommended in different cancer entities, the treatment of solitary metastases in head and neck squamous cell carcinoma (HNSCC) patients is not clearly defined. METHODS: A retrospective analysis was performed on data from 143 HNSCC patients treated between 2001 and 2016 in a tertiary university hospital. Clinical factors and outcome were measured using the median survival of patients receiving metastases specific therapy in comparison with matched control patients. RESULTS: In 37 patients, distant metastases were treated specifically with either surgery and/or stereotactic ablative radiotherapy and had with 23.97 months a more than three times higher median survival than 10 untreated matched controls with potentially treatable distant metastases (7.07 months). CONCLUSIONS: Our retrospective analysis demonstrates a significant survival benefit for HNSCC patients who received a specific therapy regarding distant metastasis irrespective of localization as compared to a matched control cohort.

Effects of upper-airway stimulation on sleep architecture in patients with obstructive sleep apnea.

PURPOSE: Selective upper-airway stimulation (UAS) is a novel therapy for patients with obstructive sleep apnea (OSA). The aim of this study was to compare changes in sleep architecture during the diagnostic polysomnography and the post-implantation polysomnography in UAS in patients with OSA. METHODS: Twenty-six patients who received a UAS device (Inspire Medical Systems) were included. Treatment outcome was evaluated 2 and 3 months after surgery. Data collection included demographics, body mass index (BMI), apnea hypopnea index (AHI), oxygen saturation and desaturation index (ODI), Epworth sleepiness score (ESS), arousal parameter, and sleep patterns. RESULTS: The mean age was 60.2 years, 25 patients were male, 1 patient was female. Mean BMI was 29.0 kg/m2. The mean pre-implantation AHI of 33.9/h could be reduced to 9.1/h at 2 months post-implantation (p < 0.001). The amount of time spent in N1-sleep could be reduced from 23.2% at baseline to 16.0% at month 3 post-implantation. The amount of time spent in N2- and N3-sleep did not change during the observation period. A significant increase of the amount of REM sleep at month 2 (15.7%) compared to baseline (9.5%; p = 0.010) could be observed. A reduction of the number of arousals and the arousal index could be observed. CONCLUSION: In conclusion, significant changes in sleep architecture of patients with OSA and sufficient treatment with UAS could be observed. A reduction of the amount of time spent in N1-sleep could be caused by treatment with UAS and the rebound of REM sleep, observed for the first time in a study on UAS, is also a potential marker of the efficacy of UAS on sleep architecture. TRIAL REGISTRATION: NCT02293746.