Targeting the microenvironment in the treatment of arteriovenous malformations.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology. AVM cells were isolated from three patients and exposed to cyclic mechanical stretching for 24 h. Thalidomide and bevacizumab, both VEGF inhibitors, were tested for their ability to prevent the formation of circular networks and proliferation of CD31+ endothelial AVM cells. Furthermore, the effect of thalidomide and bevacizumab on stretched endothelial AVM cells was evaluated. In response to mechanical stress, VEGF gene and protein expression increased in patient AVM endothelial cells. Thalidomide and bevacizumab reduced endothelial AVM cell proliferation. Bevacizumab inhibited circular network formation of endothelial AVM cells and lowered VEGF gene and protein expression, even though the cells were exposed to mechanical stress. With promising in vitro results, bevacizumab was used to treat three patients with unresectable AVMs or to prevent regrowth after incomplete resection. Bevacizumab controlled bleeding, pulsation, and pain over the follow up of eight months with no patient-reported side effects. Overall, mechanical stress increases VEGF expression in the microenvironment of AVM cells. The monoclonal VEGF antibody bevacizumab alleviates this effect, prevents circular network formation and proliferation of AVM endothelial cells in vitro. The clinical application of bevacizumab in AVM treatment demonstrates effective symptom control with no side effects.

A database for oncological research and quality assurance: implementation and first experiences with the University Clinical Cancer Registry Regensburg.

Legal requirements, certification specifications, as well as the demand for real world data on cancer research and treatment led to the decision to establish the University Clinical Cancer Registry Regensburg. The first organizational step in the implementation process of this oncological data registry was the evaluation and acquisition of suitable tumor documentation and database software. For this purpose, an evaluation matrix comprising required database software criteria was designed and consented by a multidisciplinary group of experts. Next, a yearly report of the Institute for Cancer Center Certification (OnkoZert 2019) was considered to identify database software already in use. The identified systems were rated according to the established criteria matrix and other relevant aspects. Onkostar was the system considered most suited for building up an oncological data repository. In the second step, the central IT department implemented Onkostar on-premise and migrated digitally available data after an adaptation and verification process. In parallel, a uniformed process for handling emerging oncological research questions was established. For research requirements, a data analysis concept was established comprising a proposal for data extraction, procedural instructions, and statistical training materials. In the final step, the implemented software and the process for handling research requirements in practice were evaluated by using two exemplary use cases with the focus on clinic-wide analyses and currently relevant scientific topics. A 2-month test phase conducted by various user groups showed a preference for Onkostar tumor documentation software from IT-Choice, mainly because of its adjustability to support research and treatment. Newly added and migrated data can be used for certification and research purposes. This software also provides support in current tumor documentation by displaying the course of cancer disease for individual patients over time. Such oncological data registries can be a powerful tool for legally required cancer registration, the certification of medical centers, as well as for additional oncological research. Tumor databases can be helpful in projects on cancer treatment and scientific aims. The experiences made at the University Hospital Regensburg may be used as a guidance for implementing clinical databases in similar settings with interdisciplinary responsibilities.

[Management of pediatric vascular malformations]. / Management vaskulärer Malformationen im Kindesalter.

BACKGROUND: Vascular malformations belong to the group of vascular anomalies. They are rare congenital diseases resulting from abnormal development of vessels and can arise in any location, often in the head and neck region. Clinical symptoms are variable, functional handicaps and esthetic problems may result. MATERIALS AND METHODS: One differentiates between arteriovenous, lymphatic, venous, and capillary malformations and combinations thereof. Their classification, symptoms, diagnostics, and treatment options are discussed. RESULTS: The different types of vascular malformations as well as their clinical presentation, diagnostic workup, and therapeutic options are presented, supported by clinical examples. CONCLUSION: Interdisciplinary care of pediatric patients with vascular malformations is essential in order to generate a treatment concept after correct diagnosis and improve symptoms and quality of life.

Lateral neck cyst surgery without ipsilateral tonsillectomy: a retrospective analysis.

PURPOSE: Several theories have been proposed regarding the origin of lateral neck cysts (LNC). Besides complete surgical resection ipsilateral tonsillectomy and dissection of a tract or its remnants is sometimes recommended. In this retrospective trial we wanted to evaluate if patients, who received LNC resection only, develop complications or recurrence to justify this surgical strategy. METHODS: Patients who received LNC resection between 2004 and 2017 at the Ear Nose and Throat Department of a university hospital were included. Data was collected from the clinic database and through a structured telephone interview. RESULTS: A total of 126 patients met the inclusion criteria. In this collective, the diagnosis of a lateral neck cyst was confirmed histologically. Mean age at time of operation was 38 years (± 14.6). The median follow-up time was 7 years (range 3-18). None of the participants experienced recurrent unilateral pharyngitis or tonsillitis during follow-up. Furthermore, there was no case of postoperative peritonsillar, neck phlegmon or neck abscess. No patient reported recurrence of LNC. CONCLUSIONS: Sole complete resection of LNCs is sufficient to avoid postoperative infections and recurrences. Therefore, ipsilateral tonsillectomy and tract dissection is not necessary in routine cases of LNC surgery.

[Somatosensory tinnitus]. / Somatosensorischer Tinnitus.

BACKGROUND: Somatosensory tinnitus represents a clinically significant subgroup of chronic tinnitus. Although not completely understood, increasing evidence suggests interactivity between the somatosensory and auditory systems is responsible for both the development and maintenance of tinnitus. OBJECTIVES: The aim of this study is to provide an overview of the evaluation of somatosensory tinnitus and to propose an examination protocol to support the diagnosis and treatment of this patient group. MATERIALS AND METHODS: In addition to patient history, various clinical examination maneuvers are presented to establish the diagnosis of somatosensory tinnitus. RESULTS: The maneuvers can be divided into examinations of the cervical spine, temporomandibular joint, and soft tissue near the jaw. The maneuvers should be performed in a quiet environment and usually in comparison between sides. CONCLUSION: Accurate and efficient diagnosis of somatosensory tinnitus is essential to initiate appropriate treatment. The clinical maneuvers presented here are well suited for this purpose.

Prevalence of acute olfactory dysfunction differs between variants of SARS-CoV-2-results from chemosensitive testing in wild type, VOC alpha (B.1.1.7) and VOC delta (B.1617.2).

BACKGROUND: Olfactory dysfunction is one of the leading symptoms of COVID-19. Previous data suggest a different prevalence between the wild type virus and its subsequent variants. Here, we report on a prospective study to psychophysically compare olfactory function in acute SARS-CoV-2 infection between wild type, VOC alpha and VOC delta. METHODS: SARS-CoV-2 was confirmed by reverse-transcription quantitative real-time PCR and virus variants were differentiated by high-sensitive next-generation sequencing. Home-quarantined were sent a validated and blinded smell identification test. A detailed instruction ensured correct self-administration. RESULTS: A total of 125 patients were included in study. Patients with the wild type of SARS-CoV-2 self-evaluated their olfactory function significant lower on the visual analog score compared patients with the VOCs alpha or delta (4.1 ± 1.5 vs. 6.8 ± 2.9 and 7.3 ± 0.9; p < 0.001). Likewise, a significant difference of the prevalence of psychophysically confirmed hyposmia (wild type: 73%; alpha: 41%; delta 48%; p < 0.01) and smell test score (48 ± 25% vs. 70 ± 23% and 67 ± 18%; p < 0.01) could be seen between wild type on one side and VOCs alpha and delta on the other side. CONCLUSION: In this study, both self-reports and psychophysical testing revealed a significant higher prevalence of olfactory impairment in the wild type of SARS-CoV-2 compared to the VOCs alpha and delta.

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.

[Evaluation of oesophagoscopy for staging and restaging of head and neck squamous cell carcinoma]. / Evaluation der Ösophagoskopie im Staging und Restaging von Kopf-Hals-Plattenepithelkarzinomen.

OBJECTIVE: Oesophagoscopy is important in diagnostic and follow up investigation in patients with head and neck squamous cell carcinoma (HNSCC). Second primary malignancies of the oesophagus have major impact on therapy of the primary tumour. Considering the low incidence of oesophageal second primaries and the serious complication of oesophageal perforation routine oesophagoscopy is being discussed. MATERIAL AND METHODS: Incidence of oesophageal second primaries and complication rates in oesophagoscopy were identified in a systematic review. A retrospective analysis was performed in our own patient collective. To evaluate the current practice at German ENT Clinics a survey was conducted. RESULTS: 1053 oesophagoscopies in 800 patients were analysed. In 800 patients seven (0.9 %) synchronous secondary malignancies of the oesophagus occurred. In 253 follow up oesophagoscopies five (2 %) metachronous secondary malignancies were discovered. 14 (1.3 %) complications were detected; oesophageal perforation was only detected in one case (0.1 %). There was no association of certain risk factors with the incidence of secondary malignancies. The review of literature showed an incidence of secondary malignancies for Europe/USA of 1.8 % and for Asia of 4.1 %. Incidence of oesophageal perforation was 0-0.2 %. Survey results showed routine oesophagoscopy in staging (100 %) and regularly in follow up (65.3 %). CONCLUSIONS: Oesophagoscopy is a convenient method to detect secondary malignancies of the oesophagus. To allow a selection of patients developing secondary malignancies according to risk profiles further prospective multicentre studies are required.

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.

A prospective clinical pilot study on the effects of a hydrogen peroxide mouthrinse on the intraoral viral load of SARS-CoV-2.

OBJECTIVES: SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. METHODS: Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. RESULTS: Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. CONCLUSION: A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. CLINICAL RELEVANCE: The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. TRIAL REGISTRATION: German Clinical Trials Register (ref. DRKS00022484).

Predictive value of FHIT, p27, and pERK1/ERK2 in salivary gland carcinomas: a retrospective study.

OBJECTIVES: The aim of this study was to investigate the predictive value of the biomarkers FHIT, p27, and pERK1/ERK2 in salivary gland carcinomas. MATERIAL AND METHODS: Immunohistochemical staining of FHIT, p27, and pERK1/ERK2 of 265 patients with salivary gland carcinomas was conducted, and associations with clinico-histopathological data, overall survival, and disease-specific survival were examined. RESULTS: Expression of FHIT (quick score 98.7 vs. 206.4) and p27 (QS 187.3 vs. 244.8) was significantly lower in carcinomas compared to non-tumor control tissue. Loss of FHIT frequently occurred in ACC (55.2%), SDC (68.2%), and SCC (100%). In the totality of tumors, loss of FHIT expression was found in 46.7% (106/227) and was significantly associated with advanced T stage and UICC stage, high-grade histology, loss of p27, PI3K, and survivin. FHIT positivity went along with significantly better overall and disease-specific survival. Negativity of p27 occurred in 28.7% (70/244) of tumors, particularly in SDC (54.4%) and SCC (50%). In the totality of tumors, p27 was associated with advanced patient age, high-grade histology, PI3K, survivin as well as better overall and disease-specific survival (p < 0.05). Positive pERK1/ERK2 expression correlated with positive survivin expression but did not affect overall survival in the totality of tumors. In mucoepidermoid carcinomas, pERK1/ERK2 expression was associated with low-grade malignancy, positive nuclear survivin, and better disease-specific survival. CONCLUSIONS: Loss of FHIT and p27 characterizes aggressive tumor growth and unfavorable prognosis in salivary gland cancer. CLINICAL RELEVANCE: The results may help to stratify patient-specific therapies according to individual tumor characteristics.

Technique in Cleft Rhinoplasty: The Foundation Graft.

Secondary cleft rhinoplasty represents a particular surgical challenge. The authors have identified the deficit in skeletal projection of the cleft-sided piriform rim as an important contributor to the pathology. A graft is described to augment the piriform crest on the cleft side. This foundation graft is suture fixated to the piriform crest after complete release of all soft tissue attachments to the alar base. The foundation graft is articulated with a long alar strut graft, which allows for powerful projection of the cleft-sided nasal tip. An advancement flap of vestibular skin is described to correct the vestibular stenosis. A transplant of diced cartilage in fascia is added to augment maxillary soft tissue volume. Subjective and objective measures of form and function are presented in a retrospective series of five cases, illustrating the efficacy of the techniques described.

Trauma-associated tinnitus.

BACKGROUND: Up to 53% of individuals suffering from traumatic brain injuries develop tinnitus. OBJECTIVE: To review the current literature on trauma-associated tinnitus in order to provide orientation for the clinical management of patients with trauma-associated tinnitus. MATERIALS: A systematic literature search has been conducted in PubMed database applying the search terms posttraumatic tinnitus and trauma-associated tinnitus. Results have been complemented by related studies, book chapters, and the authors' clinical experience. RESULTS: Not only mechanical, pressure-related, or noise-related head traumata but also neck injuries and emotional trauma can cause tinnitus. Exact diagnosis is essential. Disorders such as ossicular chain disruption, traumatic eardrum perforation, or perilymphatic fistula can be surgically treated. It should also be considered that pulsatile tinnitus can be a sign of life-threatening disorders such as carotid cavernous fistulas, arteriovenous malformations, and carotid dissections. Also, posttraumatic stress disorder should be taken into consideration as a potential contributing factor. CONCLUSIONS: There is an evident mismatch between the high incidence of trauma-associated tinnitus and scarce literature on the topic. A consistent and-at best-standardized assessment of tinnitus- and hearing-related sequelae of trauma is recommended both for the improvement of clinical care and for a deeper understanding of the various pathophysiological mechanisms of trauma-associated tinnitus.

Reduced variability of auditory alpha activity in chronic tinnitus.

Subjective tinnitus is characterized by the conscious perception of a phantom sound which is usually more prominent under silence. Resting state recordings without any auditory stimulation demonstrated a decrease of cortical alpha activity in temporal areas of subjects with an ongoing tinnitus perception. This is often interpreted as an indicator for enhanced excitability of the auditory cortex in tinnitus. In this study we want to further investigate this effect by analysing the moment-to-moment variability of the alpha activity in temporal areas. Magnetoencephalographic resting state recordings of 21 tinnitus subjects and 21 healthy controls were analysed with respect to the mean and the variability of spectral power in the alpha frequency band over temporal areas. A significant decrease of auditory alpha activity was detected for the low alpha frequency band (8-10 Hz) but not for the upper alpha band (10-12 Hz). Furthermore, we found a significant decrease of alpha variability for the tinnitus group. This result was significant for the lower alpha frequency range and not significant for the upper alpha frequencies. Tinnitus subjects with a longer history of tinnitus showed less variability of their auditory alpha activity which might be an indicator for reduced adaptability of the auditory cortex in chronic tinnitus.

Is there a link between tinnitus and temporomandibular disorders?

STATEMENT OF PROBLEM: The frequent concurrence of tinnitus and temporomandibular joint and masticatory muscle disorders (TMD) has led to the assumption that a possible relationship exists between these 2 conditions. PURPOSE: The present prospective clinical study was conducted to assess the possible association between tinnitus and TMD and to investigate the effect of stomatognathic therapy on tinnitus distress. MATERIAL AND METHODS: The prevalence of TMD and tinnitus was investigated in a consecutive series of 951 patients at the Department of Prosthetic Dentistry at the University Medical Center Regensburg, Germany. Patients with TMD and simultaneous tinnitus were included in the prospective clinical trial (n=25). Baseline examination comprised a detailed functional analysis, diagnosis of temporomandibular joint and masticatory muscle disorder, and a tinnitus questionnaire. All the participants received individual dental functional therapy (oral splints, physiotherapy). The effects of functional therapy on TMD and tinnitus symptoms were examined 3 to 5 months after the initiation of dental functional therapy. Means (standard deviations) were calculated, and 1-way ANOVA was used to investigate statistical differences (α=.05). The differences of the 2 binary outcomes were compared with the Pearson χ(2) test, and the relative risk was calculated. RESULTS: Prevalence of tinnitus was found to be 8 times higher in participants with TMD (30 of 82 [36.6%]) than in participants without TMD (38 of 869 [4.4%]). All the participants with unilateral TMD and unilateral tinnitus showed these conditions on the same side. Stomatognathic therapy improved tinnitus symptoms in 11 of 25 participants (44%). CONCLUSIONS: The results of this study and the prospective clinical trial showed a significant correlation between tinnitus and TMD. The observed treatment outcome suggests that dental functional therapy may have a positive effect on TMD-related tinnitus.

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.