Effect of hypoglossal nerve stimulation on snoring: an evaluation using objective acoustic parameters.

STUDY OBJECTIVES: Hypoglossal nerve stimulation is an established therapy for sleep apnea syndrome. Whether or not this therapy on snoring and nighttime noise exposure is effective and how strong this effect may be has not been objectively investigated thus far and was the aim of this study. METHODS: In 15 participants (14 males; age: 30-72 years; mean: 51.7 years), polysomnography and acoustic measurements were performed before and after hypoglossal nerve stimulation. RESULTS: The therapy led to a significant improvement in sleep apnea (apnea-hypopnea index from 35.8 events/h to 11.2 events/h, P < .001). Acoustic parameters showed a highly significant reduction in the average sound pressure level (42.9 db[A] to 36.4 db[A], P < .001), averaged sound energy, A-weighted (LAeq; 33.1 db[A] to 28.7 db[A], P < .001), snoring index (1,068 to 506, P < .001), percentage snoring time (29.7-14.1%, P < .001), and psychoacoustic snore score, the latter being a measure of annoyance due to snoring (47.9 to 24.5, P < .001). CONCLUSIONS: This study was able to show for the first time by means of objective acoustic and psychoacoustic parameters that hypoglossal nerve stimulation can not only cause a significant improvement in sleep apnea but also has a positive effect on snoring and thus noise annoyance experienced by the bed partner. CLINICAL TRIAL REGISTRATION: Registry: German Clinical Trials Register; Name: Effect of Hypoglossal Nerve Stimulation on Snoring: An Evaluation Using Objective Acoustic Parameters; URL: https://drks.de/search/de/trial/DRKS00032354; Identifier: DRKS00032354. CITATION: Fischer R, Vielsmeier V, Kuehnel TS, et al. Effect of hypoglossal nerve stimulation on snoring: an evaluation using objective acoustic parameters. J Clin Sleep Med. 2024;20(3):363-370.

[Use of Contrast enhanced Ultrasound (CEUS) in the Head and Neck Area: Update]. / Anwendung der Kontrastmittelsonografie im Kopf-Hals-Bereich: Update.

With the help of contrast enhanced ultrasound, the diagnostic accuracy of conventional sonography can be increased in many areas of otorhinolaryngology. Vascularisation and tissue perfusion can be objectified through the examination. This offers promising approaches for example to monitor the therapy of metastatic cervical lymph nodes or in the treatment of vascular malformations. Contrast Enhanced Ultrasound (CEUS) also offers great potential for differential diagnosis, for example of thyroid nodules. Valid threshold values for the quantitative time intensity curve (TIC) analysis of cervical pathologies are currently still not available. Further studies are necessary. As there is currently no license for the use of contrast enhanced ultrasound in otorhinolaryngology patients must be informed about its off-label use before the examination. This article is intended to provide an overview of the current possibilities and to serve as an introduction to the topic.

Statin Use Ameliorates Survival in Oral Squamous Cell Carcinoma-Data from a Population-Based Cohort Study Applying Propensity Score Matching.

The anti-cancer properties of statins have attracted much attention recently, but little is known about the prognostic role of statins in oral squamous cell carcinoma (OSCC). In a retrospective approach, we analyzed a population-based cohort of 602 OSCC patients with primary curative tumor resection to negative margins and concomitant neck dissection between 2005-2017. Long-term medication with statins was correlated with overall survival (OAS) as well as recurrence-free survival (RFS) using uni- and multivariable Cox regression. Additionally, propensity score matching was applied to adjust for confounders. Statin use was present in 96 patients (15.9%) at a median age of 65.7 years. Statin treatment correlated with ameliorated survival in multivariable Cox regression in the complete cohort (OAS: HR 0.664; 95% CI 0.467-0.945, p = 0.023; RFS: HR 0.662; 95% CI 0.476-0.920, p = 0.014) as well as matched-pair cohort of OSCC patients (OAS: HR 0.691; 95% CI 0.479-0.997, p = 0.048; RFS: HR 0.694; 95% CI 0.493-0.976, p = 0.036) when compared to patients not taking statins at time of diagnosis. These findings were even more pronounced by sub-group analysis in the matched-pair cohort (age < 70 years). These data indicate that statin use might ameliorate the oncological outcome in primarily resected OSCC patients, but prospective clinical trials are highly recommended.

Digital patient twins for personalized therapeutics and pharmaceutical manufacturing.

Digital twins are virtual models of physical artefacts that may or may not be synchronously connected, and that can be used to simulate their behavior. They are widely used in several domains such as manufacturing and automotive to enable achieving specific quality goals. In the health domain, so-called digital patient twins have been understood as virtual models of patients generated from population data and/or patient data, including, for example, real-time feedback from wearables. Along with the growing impact of data science technologies like artificial intelligence, novel health data ecosystems centered around digital patient twins could be developed. This paves the way for improved health monitoring and facilitation of personalized therapeutics based on management, analysis, and interpretation of medical data via digital patient twins. The utility and feasibility of digital patient twins in routine medical processes are still limited, despite practical endeavors to create digital twins of physiological functions, single organs, or holistic models. Moreover, reliable simulations for the prediction of individual drug responses are still missing. However, these simulations would be one important milestone for truly personalized therapeutics. Another prerequisite for this would be individualized pharmaceutical manufacturing with subsequent obstacles, such as low automation, scalability, and therefore high costs. Additionally, regulatory challenges must be met thus calling for more digitalization in this area. Therefore, this narrative mini-review provides a discussion on the potentials and limitations of digital patient twins, focusing on their potential bridging function for personalized therapeutics and an individualized pharmaceutical manufacturing while also looking at the regulatory impacts.

Prognostic Relevance of Type 2 Diabetes and Metformin Treatment in Head and Neck Melanoma: Results from a Population-Based Cohort Study.

BACKGROUND: Type 2 Diabetes (DM2) and the consecutively daily use of antidiabetic medication are characterized by a frequent prevalence worldwide and were shown to impact the initiation and progression of malignant diseases. While these effects were observed in a variety of malignancies, comprehensive data about the role of DM2 and antidiabetic drugs in the outcome of head and neck melanoma (HNM) patients are missing. METHODS: This retrospective population-based cohort study included 382 HNM patients from Eastern Bavaria having received tumor resection to negative margins between 2010 and 2017. Recurrence-free survival (RFS) was evaluated with regard to DM2 and routine metformin intake. Statistical analysis was performed by uni- and multivariate analyses. The median follow-up time was 5.6 years. RESULTS: DM2 was diagnosed in 68 patients (17.8%), routine metformin intake was found in 39 cases (10.2%). The univariate survival analysis revealed impaired 5-year RFS in HNM patients with DM2 compared to non-diabetic controls (p = 0.016; 64.0% and 74.5%, respectively). The multivariate Cox regression substantiated this effect (HR = 1.980, 95% CI = 1.108-3.538, p = 0.021). In detail, the cumulative locoregional recurrence rate displayed the most far-reaching negative effect on the RFS of diabetic HNM patients (HR = 4.173, 95% CI = 1.628-10.697, p = 0.003). For metformin intake, a profound positive effect on the RFS in multivariate statistics was observed, both in the complete cohort (HR = 0.396, 95% CI = 0.177-0.884, p = 0.024) as well as in the cohort of diabetic HNM patients (HR = 0.352, 95% CI = 0.135-0.913, p = 0.032). CONCLUSIONS: This study emphasizes that DM2 is a relevant comorbid condition in HNM patients, impairing patient survival. Metformin intake was associated with a favorable outcome in HNM patients, providing possible therapeutic implications for future adjuvant treatment regimes.

TIMolol Nasal Spray as a Treatment for Epistaxis in Hereditary Hemorrhagic Telangiectasia (TIM-HHT)-A Prospective, Randomized, Double-Blind, Controlled, Cross-Over Trial.

To date, there is no approved local therapeutic agent for the treatment of epistaxis due to hereditary hemorrhagic telangiectasia (HHT). Several case reports suggest the topical use of timolol. This monocentric, prospective, randomized, placebo-controlled, double-blinded, cross-over study investigated whether the effectiveness of the standard treatment with a pulsed diode laser can be increased by also using timolol nasal spray. The primary outcome was severity of epistaxis after three months, while the main secondary outcome was severity of epistaxis and subjective satisfaction after one month. Twenty patients were allocated and treated, of which 18 patients completed both 3-month treatment sequences. Timolol was well tolerated by all patients. Epistaxis Severity Score after three months, the primary outcome measure, showed a beneficial, but statistically nonsignificant (p = 0.084), effect of additional timolol application. Epistaxis Severity Score (p = 0.010) and patients' satisfaction with their nosebleeds after one month (p = 0.050) showed statistically significant benefits. This placebo-controlled, randomized trial provides some evidence that timolol nasal spray positively impacts epistaxis severity and subjective satisfaction in HHT patients when additively applied to standard laser therapy after one month. However, the effect of timolol was observed to diminish over time. Trials with larger sample sizes are warranted to confirm these findings.

Clinical significance of panendoscopy in initial staging of oral squamous cell carcinoma and detection of synchronous second malignancies of the upper aerodigestive tract - Insights from a retrospective population-based cohort study.

The aim of this study was to examine the prevalence of synchronous upper aerodigestive tract (UAT) tumors within oral squamous cell carcinoma (OSCC) patients, and to specify distinct risk groups who benefit from panendoscopy. Definite clinical and pathohistological characteristics, as well as overall and recurrence-free survival (OAS and RFS, respectively) of OSCC patients with and without synchronous second UAT tumors, carcinomas in situ, or higher-grade dysplasia/metaplasia, were evaluated based on a retrospective population-based cohort study, including alignment with cancer registry data. Out of 727 included OSCC patients, 465 cases (64.0%) received panendoscopy. Among these, 18 UAT tumors were detected, all of which were linked to patients with a positive history of nicotine abuse. Every synchronous UAT tumor was revealed by panendoscopy, which, analyzed as an independent staging procedure, was accompanied by a low complication rate (1.7%). When illuminating the impact of a second UAT tumor in OSCC patients, survival analysis revealed reduced 5-year OAS (63.9% vs 43.5%, p = 0.010) and RFS (57.1% vs 32.4%, p = 0.016) for patients with a second oncology diagnosis of the UAT. Within the limitations of the study, it seems that panendoscopy should be performed in the majority of patients suffering from OSCC, because most of them have a history of smoking and drinking, which correlates with an increased risk of developing synchronous UAT tumors.

Prognostic Value of Perineural Invasion on Survival and Recurrence in Oral Squamous Cell Carcinoma.

A diagnosis of perineural invasion (PNI) is widely accepted as an unfavorable prognostic factor in various solid malignancies. Although PNI has been described as a high-risk parameter in oral squamous cell carcinoma (OSCC), its role in the current staging manuals of the American Joint Committee on Cancer (AJCC) is rather subordinate. We analysed the prognostic value of PNI on survival and recurrence in a large, multicenter OSCC cohort and a population-based approach. A total of 493 OSCC patients with primary tumor resection to negative margins and concomitant neck dissection between 2010 and 2017 were enrolled. PNI was evaluated in relation to overall survival (OAS) and recurrence-free survival (RFS) using uni- and multi-variable Cox regression. The median follow-up time was 5.0 years and PNI was diagnosed in 48 patients (9.7%). A pathohistological verification of PNI correlated significantly with a deteriorated OAS in uni- (HR 2.312; 95% CI 2.312-3.493, p = 0.001) and multivariable Cox regression (HR 1.820; 95% CI 1.164-2.847, p = 0.009). Additionally, a diagnosis of PNI correlated with increased cumulative, as well as distant, metastasis 5-year-recurrence rates (p = 0.027 and p = 0.011, respectively). The application of adjuvant radiotherapy (RT) or radiochemotherapy (RCT) in patients with PNI did not alter OAS or RFS in survival analysis when compared to patients without PNI. The results underline the adverse impact of PNI on the survival and recurrence of surgically treated OSCC patients. Based on our findings, we highly recommend an emphasis on PNI in the TNM staging concept.

HHT-Related Epistaxis and Pregnancy-A Retrospective Survey and Recommendations for Management from an Otorhinolaryngology Perspective.

Appropriate management of hereditary hemorrhagic telangiectasia (HHT) is of particular importance in females, as HHT-mediated modifications of the vascular bed and circulation are known to increase the risk of complications during pregnancy and delivery. This study was undertaken to evaluate female HHT patients' awareness of and experience with HHT during pregnancy and delivery, with a focus on epistaxis. In this retrospective study, 46 females (median age: 60 years) with confirmed HHT completed a 17-item questionnaire assessing knowledge of HHT and its pregnancy-associated complications, the severity of epistaxis during past pregnancies and deliveries, and the desire for better education and counselling regarding HHT and pregnancy. Results revealed that 85% of participants were unaware of their disease status prior to the completion of all pregnancies. Further, 91% reported no knowledge of increased pregnancy-related risk due to HHT. In regard to epistaxis, 61% of respondents reported experiencing nosebleeds during pregnancy. Finally, approximately a third of respondents suggested that receiving counseling on the risks of HHT in pregnancy could have been helpful. Findings suggest that awareness of HHT and its potential for increasing pregnancy-related risk is poor. Best practices in HHT management should be followed to minimize negative effects of the disorder.

Persisting olfactory dysfunction in post-COVID-19 is associated with gustatory impairment: Results from chemosensitive testing eight months after the acute infection.

Olfactory and gustatory disorders are prominent symptoms of acute COVID-19. Although both senses recover in many patients within weeks to months, persistency has been described in up to 60%. However up to now most reports on the course of chemosensitive disorders after COVID-19 are not based on psychophysical testing but only on subjective patients' ratings. In this study we assessed both olfaction and gustation using psychophysical tests eight months after COVID-19. Validated psychophysical testing revealed hyposmia in 18% and hypogeusia in even 32% of 303 included patients. This shows that olfactory and especially gustatory disorders have to be seen as important chronic symptoms post-COVID-19. The high prevalence of gustatory dysfunction indicates that gustatory function does not recover or might even deteriorate in the months following the acute infection.

A third hand to the surgeon: the use of an endoscope holding arm in endonasal sinus surgery and well beyond.

BACKGROUND: Extended endoscopic endonasal operations of the sinuses and the frontal skull base require a bimanual action of the surgeon in many cases. Thus, typically an assistant guides the endoscope and centers the field of view. In this study, we investigate in which cases an endoscope holding arm can be used alternatively. MATERIALS AND METHODS: The electromagnetic system ENDOFIXexo was used in different surgical interventions of the paranasal sinuses and beyond questioning ergonomics and geometrical limitations. The realized degrees of freedom were documented, and a topography of possible applications compiled. RESULTS: The presented system is limited by the anatomy of the anterior ethmoid and dynamic working conditions in the sagittal direction. Especially in extended interventions in the posterior ethmoid, in which parts of the nasal septum have been resected and a static position of the endoscope is desired the surgeon can greatly benefit from the robotic arm. Moreover, through the high flexibility of the endoscopic arm surgeries of the pharynx and larynx were performed, questioning the current gold standard of microscope-assisted surgical procedures. CONCLUSION: Under the impression of an urging staff shortage and due to its unlimited patience, the ENDOFIXexo arm seems promising. Taking into account the complex anatomy and the limited access, we especially see a favorable field of application in the surgery of the pituitary gland and skull base tumors.

Hereditary Hemorrhagic Telangiectasia: Success of the Osler Calendar for Documentation of Treatment and Course of Disease.

Hereditary hemorrhagic telangiectasia (HHT; Rendu-Osler-Weber syndrome) affects the capillary and larger vessels, leading to arteriovenous shunts. Epistaxis is the main symptom impairing quality of life. The aim of the Osler Calendar is to offer information about the extent of the systemic disease and the current state of treatment. A care plan with information on the rare disease and self-treatment of epistaxis was created. Organ examinations and ongoing treatments were recorded. A questionnaire documents the treatment success, including patient satisfaction, frequency of hemorrhage and hemoglobin levels. The patients using the Osler Calendar for at least one year (n = 54) were surveyed. Eighty-five percent of patients (n = 46) used the calendar to gain information about HHT. Seventy-two percent (n = 39) used the Osler Calendar for instructions on the self-treatment of nosebleeds. The calendar increased patients' understanding for the need for organ screenings from 48% (n = 26) to 81% (n = 44). Seventy-nine percent (n = 43) of patients confirmed that the Osler Calendar documented their therapeutic process either well or very well. Fifty-two percent (n = 28) saw an improvement in the therapeutic process due to the documentation. The Osler Calendar records the individual intensity of the disease and facilitates the communication between attending physicians. It is a tool for specialists to review treatment strategies. Furthermore, the calendar enhances patients' comprehension of their condition.

Head and neck melanoma: outcome and predictors in a population-based cohort study.

BACKGROUND: To evaluate predictive clinico-pathological characteristics on outcome in head and neck melanoma (HNM) in a population-based study with particular emphasis on the prognostic effect of sentinel lymph node biopsy (SLNB), Charlson comorbidity index (CCI) and distinct tumor localisations. METHODS: Here we primarily describe a retrospective multicenter population-based cohort study with 402 patients having undergone resection with curative intent of HNM between 2010 and 2017. SLNB was used in the diagnosis of 79 HNM patients. Outcome was analyzed, focusing on SLNB, CCI as well as tumor localisation. Overall survival (OAS) und recurrence free survival (RFS) was examined by uni- and multivariate analysis. RESULTS: Histopathologically verified lymph node metastasis according to SLNB was associated with impaired RFS in HNM patients (p = 0.004). Especially in higher tumor stages, the sole implementation of SLNB improved survival significantly in the present cohort (p = 0.042). With most of the HNM being located in the face, melanoma of the scalp and neck could be linked to deteriorated patient's outcome in uni- as well as multivariate analysis (p = 0.021, p = 0.004). CONCLUSIONS: SLNB is a useful tool in predicting development of distant metastasis after HNM resection with curative intent. Especially in higher tumor stages, performing a SLNB ameliorated survival of HNM patients. Additionally, CCI as well as a distinct tumor localisations in HNM were identified as important risk factors in our population-based cohort study.

Lymph node ratio as a predictor for outcome in oral squamous cell carcinoma: a multicenter population-based cohort study.

OBJECTIVES: Recently, multiple studies addressed the importance of lymph node ratio (LNR) in specifying patients' risk of disease recurrence in various malignancies. The present study examines the prognostic significance of LNR in predicting outcome of oral squamous cell carcinoma (OSCC) patients after surgical treatment with curative intent. METHODS: Here, we describe a retrospective population-based cohort with 717 patients previously diagnosed with OSCC. Histopathologically verified lymph node metastasis was diagnosed in 290 patients. Among these patients, we evaluated the impact of LNR on overall survival (OAS) and recurrence-free survival (RFS) in uni- as well as multivariate analysis. RESULTS: A median cutoff (0.055) in LNR was found to significantly predict outcome in OSCC patients. Five-year OAS was 54.1% in patients with a low LNR, whereas a high LNR was associated with a 5-year OAS of 33.3% (p < 0.001). Similar results were detected for RFS with a 5-year survival rate of 49.8% (LNR low) and 30.3% (LNR high) (p = 0.002). Results were confirmed in multivariate Cox regression which substantiated the importance of LNR in predicting survival in OSCC patients. CONCLUSIONS: LNR was shown to be an independent prognostic factor for outcome of OSCC in a population-based cohort in uni- as well as multivariate analysis. Hereby, a LNR ≥ 0.055 predicted a shorter OAS and RFS in our cohort. CLINICAL RELEVANCE: Besides established histopathological factors, LNR can be used as a reliable predictor of outcome in OSCC and might therefore be further applied in evaluating adjuvant treatment after resection in curative intention.

Are annoyance scores based on sound pressure levels suitable for snoring assessment in the home environment?

PURPOSE: An objective statement about the annoyance of snoring can be made with the Psychoacoustic Snore Score (PSS). The PSS was developed based on subjective assessments and is strongly influenced by observed sound pressure levels. Robustness against day-to-day interfering noises is a fundamental requirement for use at home. This study investigated whether or not the PSS is suitable for use in the home environment. METHODS: Thirty-six interfering noises, which commonly occur at night, were played in the acoustic laboratory in parallel with 5 snoring sounds. The interfering noises were each presented at sound pressure levels ranging from 25 to 55 dB(A), resulting in 3255 distinct recordings. Annoyance was then assessed using the PSS. RESULTS: In the case of minimally annoying snoring sounds, interfering noises with a sound pressure level of 25 dB(A) caused significant PSS changes from 40 to 55 dB(A) for annoying snoring sounds. If the interfering noise was another snoring sound, the PSS was more robust depending on the sound pressure level of the interfering noise up to 10 dB(A). Steady (no-peak) interfering noises influenced the PSS more strongly than peak noises. CONCLUSIONS: The PSS is significantly distorted by quiet interfering noises. Its meaningfulness therefore depends strongly on the acoustic environment. It may therefore be assumed that scores dependent on sound pressure level are suitable for measurements when there is minimal ambient noise, as in the sleep laboratory. However, for measurements where noise is incalculable, as in the home environment, interfering noises may distort the results.

Lymphatic and vascular invasion in oral squamous cell carcinoma: Implications for recurrence and survival in a population-based cohort study.

OBJECTIVE: Numerous studies analyzed lymphovascular invasion (LVI) in various malignant diseases, however, little is known about the role of lymphatic invasion (LI) as well as vascular invasion (VI) in oral squamous cell carcinoma (OSCC). The aim of this study is to illuminate the role of LI and VI in a population-based cohort study. METHODS: We retrospectively analyzed 745 primarily resected OSCC patients in Eastern Bavaria for histopathologically verified LI and VI. Overall survival (OS) and recurrence-free survival (RFS) were calculated, whereas analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.4 years. RESULTS: LI was found in 115 patients (15.4%), VI was diagnosed in 23 cases (3.1%). LI correlated significantly with distinct anatomical sites (p = 0.004), increasing pT-classification (p < 0.001), lymph node involvement (p < 0.001), higher grading (p < 0.001), advanced UICC-stages (p < 0.001) and adjuvant therapies (p < 0.001). Similar results were found for VI. Survival analysis resulted in a significantly decreased five-year OS and RFS in patients with diagnosed LI (OS: 41.1%, RFS: 38.3%) in contrast to LI-negative cases (OS: 66.8%, RFS: 59.7.7%, p < 0.001). Analogous outcomes were seen for patients with VI. Additionally, LI was identified as a predictive parameter, indicating individual patients' response to adjuvant therapies. CONCLUSION: This population-based cohort study underlines the unfavorable aspect of LI and VI on outcome in OSCC. Including LI and VI in existing staging systems could help to stratify patients' risk for adverse outcome and consecutively determine adjuvant treatment in malignant disease.

Prognostic value of perioperative red blood cell transfusion and anemia on survival and recurrence in oral squamous cell carcinoma.

OBJECTIVE: To evaluate the prognostic effect of allogenic red blood cell transfusion (RBT) and preoperative anemia in patients with oral squamous cell carcinoma (OSCC) undergoing primary tumor resection. METHODS: We retrospectively analyzed a cohort of 621 patients, diagnosed with OSCC receiving tumor resection in curative intention. Preoperative anemia and perioperative RBT were evaluated according to WHO definition. Overall survival (OAS) as well as recurrence-free survival (RFS) was evaluated in transfused and non-transfused as well as in anemic and non-anemic patients. In addition, outcome parameters were calculated for distinct amounts of perioperatively administered RBTs. Data analysis was performed by uni- and multivariate statistics. Mean follow-up time was 7.3 years. RESULTS: Preoperative anemia was diagnosed in 29% of OSCC patients. Anemic patients displayed a significantly decreased five-year OAS (44%) in comparison to non-anemic equivalents (69%). 70% of non-transfused OSCC patients were alive after five years, whereas in case of RBT five-year OAS was 41%. These findings were substantiated by subgroup analysis in patients without preoperative anemia. For anemic patients however, no deleterious effect on survival in case of perioperative RBT was seen. Increasing numbers of received RBTs were shown to worsen outcome of OSCC patients in a dose-dependent manner. CONCLUSION: Preoperative anemia and RBT are significantly associated with impaired long-term outcome of patients suffering from OSCC. Future studies are needed to evaluate differentiated effects of RBTs in anemic and non-anemic OSCC patients and accordingly providing individual transfusion strategies to ameliorate outcome of patients suffering from OSCC.

Snoring: is a reliable assessment possible?

PURPOSE: It is not easy to assess how severe and annoying a patient's snoring is. Solid parameters are lacking; snorers cannot deliver a reliable self-assessment and it is uncertain whether bed partners' statements can be relied upon. The purpose of the present study was therefore to investigate whether and how well snoring assessment based on acoustic parameters and bed partners' reporting agree. METHODS: In a double-blind, placebo-controlled study on snoring treatment, several acoustic parameters [snoring index (SI), percentage snoring time (ST), sound pressure level, sound energy, loudness, psychoacoustic annoyance and psychoacoustic snore score (PSS)] were measured in 18 subjects during 24 polysomnographies. Bed partners also assessed snoring annoyance and loudness as well as treatment outcome. RESULTS: No correlation was found between the subjective annoyance caused by snoring and the acoustic parameters. Regarding perceived loudness, there was a moderate, significant correlation with loudness (N5) and PSS over the hour with the highest SI. SI, ST, LAeq and maximum sound pressure level dB(A)max showed no significant correlation. After the intervention only mean sound energy LAeq over the entire night showed a significant correlation (rs = 0.782; p = 0.022) with bed partners' assessments. However, this result was not confirmed in the second control night. CONCLUSIONS: The non-existent or only weak correlation between bed partners' ratings and objective parameters indicate that snoring severity should be evaluated with caution. Neither acoustic parameters, at least for one measurement over just one night, nor bed partners' ratings should be used as the sole basis for snoring assessment.

Rheumatoid Arthritis-Associated Autoimmunity Due to Aggregatibacter actinomycetemcomitans and Its Resolution With Antibiotic Therapy.

Background:Aggregatibacter actinomycetemcomitans (Aa) is a Gram-negative coccobacillus recognized as a pathogen in periodontitis and infective endocarditis. By producing a toxin (leukotoxin A, LtxA) that triggers global hypercitrullination in neutrophils, Aa has been recently linked to rheumatoid arthritis (RA) pathogenesis. Although mechanistic and clinical association studies implicate Aa infection in the initiation of autoimmunity in RA, direct evidence in humans is lacking. Case:We describe a 59-year-old man with anti-citrullinated protein antibody (ACPA)-positive RA who presented for evaluation of refractory disease. He was found to have Aa endocarditis. Following antibiotic treatment, joint symptoms resolved and ACPAs normalized. Given the implications for RA immunopathogenesis, we further investigated the bacterial, genetic and immune factors that may have contributed to the patient's clinical and autoimmune phenotypes. Methods:DNA was extracted from serum and used to amplify the Aa leukotoxin (ltx) promoter region by PCR, which was further analyzed by Sanger sequencing. High-resolution identification of HLA alleles was performed by sequenced based typing (SBT). TNF-α, IFN-γ, GM-CSF, IL-1ß, IL-6, IL-8, IL-17A, IL-18, IL-21, and IL-22 were quantified in serum by a multiplex immunoassay. IgG and IgA antibodies to Aa LtxA were assayed by ELISA. Results:Aa genotyping confirmed infection with a highly leukotoxic strain carrying a 530-bp ltx promoter deletion, shown to result in 10- to 20-fold higher bacterial expression of LtxA. Immuno-phenotyping showed high anti-LtxA antibodies, elevated cytokines implicated in RA pathogenesis (Th1/Th17), and specific host susceptibility conferred by three HLA alleles strongly linked to ACPAs and RA (DRB1*04:04, DRB1*15:01, and DPB1*04:01). One year after eradication of Aa, the patient remained free of arthritis and anti-CCP antibodies. Conclusion: In the context of genetic risk for RA, systemic subacute infection with a leukotoxic strain of Aa can drive ACPA production and a clinical phenotype similar to RA.