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105 result(s) for "Sudhoff, Holger"
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Round Window Reinforcement for Semicircular Canal Dehiscence Syndrome
BACKGROUND: To evaluate the clinical outcomes and safety profile of round window reinforcement (RWR) as a minimally invasive surgical treatment for patients with semicircular canal dehiscence syndrome (SCDS). METHODS: This retrospective case series analyzed 7 patients (mean age: 59 years) diagnosed with SCDS who underwent transcanal RWR between June 2024 and June 2025 at the Kopfzentrum Bielefeld. Inclusion criteria followed the Barany Society consensus diagnostic standards. Clinical symptoms, audiometric findings, and vestibular test results–including Dizziness Handicap Inventory (DHI) scores–were assessed pre-and postoperatively. In 2 patients, endolymphatic hydrops was diagnosed via delayed contrast-enhanced magnetic resonance imaging and monitored postoperatively. RESULTS: All patients completed follow-up (mean: 35 months). Improvement in auditory symptoms was observed in 5 of 7 patients (71.4%), including tinnitus relief in 83.3% and hyperacusis relief in 75%. Vertigo improved in 50% of symptomatic cases. No postoperative deterioration in symptoms, DHI score, or hearing was observed. Audiometric outcomes showed a non-significant mean change in air-bone gap ([+ or -]2.5 dB). No intra- or postoperative complications occurred. In patients with concomitant hydrops, auditory improvement was noted, though vertigo persisted. CONCLUSION: Round window reinforcement appears to be a safe and effective therapeutic option for selected patients with SCDS, particularly those presenting predominantly auditory symptoms or contraindications to more invasive procedures. Further prospective studies are needed to validate these findings and define the role of RWR in the broader surgical management of third window syndromes. KEYWORDS: Auditory symptoms, endolymphatic hydrops, round window reinforcement, superior semicircular canal dehiscence, third window syndrome, transcanal surgery, vertigo
Review of potential medical treatments for middle ear cholesteatoma
Middle ear cholesteatoma (MEC), is a destructive, and locally invasive lesion in the middle ear driven by inflammation with an annual incidence of 10 per 100,000. Surgical extraction/excision remains the only treatment strategy available and recurrence is high (up to 40%), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review was targeted at connecting the dysregulated inflammatory network of MEC to pathogenesis and identification of pharmaceutical targets. We summarized the numerous basic research endeavors undertaken over the last 30+ years to identify the key targets in the dysregulated inflammatory pathways and judged the level of evidence for a given target if it was generated by in vitro, in vivo or clinical experiments. MEC pathogenesis was found to be connected to cytokines characteristic for Th1, Th17 and M1 cells. In addition, we found that the inflammation created damage associated molecular patterns (DAMPs), which further promoted inflammation. Similar positive feedback loops have already been described for other Th1/Th17 driven inflammatory diseases (arthritis, Crohn’s disease or multiple sclerosis). A wide-ranging search for molecular targeted therapies (MTT) led to the discovery of over a hundred clinically approved drugs already applied in precision medicine. Based on exclusion criteria designed to enable fast translation as well as efficacy, we condensed the numerous MTTs down to 13 top drugs. The review should serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history. 9oEnHnw4b3NC5oSfFmj_8G Video Abstract Plain English summary Middle ear cholesteatoma (MEC) is a destructive and locally invasive ulcerated lesion in the middle ear driven by inflammation which occurs in 10 out of 100,000 people annually. Surgical extraction/excision is the only treatment strategy available and recurrence is high (up to 40% after ten years), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review is focused on the connections between inflammation and MEC pathogenesis. These connections can be used as attack points for pharmaceuticals. For this we summarized the results of research undertaken over the last 30 + years. MEC pathogenesis can be described by specific inflammatory dysregulation already known from arthritis, Crohn’s disease or multiple sclerosis. A hallmark of this dysregulation are positive feedback loops of the inflammation further amplifying itself in a vicious circle-like manner. We have identified over one hundred drugs which are already used in clinic to treat other inflammatory diseases, and could potentially be repurposed to treat MEC. To improve and expedite clinical success rates, we applied certain criteria based on our literature searches and condensed these drugs down to the 13 top drugs. We hope the review will serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history.
Updates and Knowledge Gaps in Cholesteatoma Research
The existence of acquired cholesteatoma has been recognized for more than three centuries; however, the nature of the disorder has yet to be determined. Without timely detection and intervention, cholesteatomas can become dangerously large and invade intratemporal structures, resulting in numerous intra- and extracranial complications. Due to its aggressive growth, invasive nature, and the potentially fatal consequences of intracranial complications, acquired cholesteatoma remains a cause of morbidity and death for those who lack access to advanced medical care. Currently, no viable nonsurgical therapies are available. Developing an effective management strategy for this disorder will require a comprehensive understanding of past progress and recent advances. This paper presents a brief review of background issues related to acquired middle ear cholesteatoma and deals with practical considerations regarding the history and etymology of the disorder. We also consider issues related to the classification, epidemiology, histopathology, clinical presentation, and complications of acquired cholesteatoma and examine current diagnosis and management strategies in detail.
Mouthrinses against SARS-CoV-2: anti-inflammatory effectivity and a clinical pilot study
Purpose The scope of this research endeavor was the determination of the applicability of over the counter mouthwash solutions in reducing the viral load in the saliva of COVID-19 patients and hence decreasing their infectivity. Beyond that, new experimental mouthwashes were investigated in terms of a possible positive immune modulation, which might offer an additional opportunity for a positive pharmaceutical effect. Methods The effectivity of the mouth washing solution was determined on 34 hospitalized COVID-19 patients by measuring the viral load by RT-qPCR in pharyngeal swabs, which were taken before and after rinsing. The inflammatory modulation thru the experimental solutions was assayed in an in vitro model of virus infected nasopharyngeal epithelium cells. Results The clinical pilot study demonstrated that the mouth rinsing solution was able to reduce the viral load by about 90% in the saliva of most patients. This reduction was determined to persist for about 6 h. In the experimental solutions, the ingredients dexpanthenol and zinc were able to reduce the expression of proinflammatory cytokines in the cell culture model, while the antiviral response was not altered significantly. Conclusion We recommend the application of mouth wash solutions to COVID-19 patients, since our results indicate a reduction in infectivity and might govern the protection of health care professionals. Further improvement to the over the counter formulation can be made by utilizing zinc and dexpanthenol, as they which might be beneficial for the patients’ health.
EAONO/JOS Joint Consensus Statements on the Definitions, Classification and Staging of Middle Ear Cholesteatoma
The European Academy of Otology and Neurotology (EAONO) has previously published a consensus document on the definitions and classification of cholesteatoma. It was based on the Delphi consensus methodology involving the broad EAONO membership. At the same time, the Japanese Otological Society (JOS) had been working independently on the \"Classification and Staging of Cholesteatoma.\" EAONO and JOS then decided to collaborate and produce a joint consensus document. The EAONO/JOS joint consensus on \"Definitions, Classification and Staging of Middle Ear Cholesteatoma\" was formally presented at the 10th International Conference on Cholesteatoma and Ear Surgery in Edinburgh, June 5-8, 2016. The international otology community who attended the consensus session was given the chance to debate and give their support or disapproval. The statements on the \"Definitions of Cholesteatoma\" received 89% approval. The \"Classification of Cholesteatoma\" received almost universal approval (98%). The \"EAONO/JOS Staging System on Middle Ear Cholesteatoma\" had a majority of approval (75%). Some international otologists wanted to see more prognostic factors being incorporated in the staging system. In response to this, the EAONO/JOS steering group plans to set up an \"International Otology Outcome Working Group\" to work on a minimum common otology data set that the international otology community can use to evaluate their surgical outcome. This will generate a large database and help identify relevant prognostic factors that can be incorporated into the staging system in future revisions.
Deregulation of SYCP2 predicts early stage human papillomavirus‐positive oropharyngeal carcinoma: A prospective whole transcriptome analysis
This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)‐positive and HPV‐negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty‐four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT–quantitative real‐time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin‐fixed, paraffin‐embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high‐risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV‐associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV‐associated cancer development. If further corroborated, this data may contribute to the development of a non‐invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945). This study was designed to identify significant differences in the gene expression profiles of HPV‐positive and HPV‐negative oropharyngeal squamous cell carcinomas (OPSCC). Our objective was to better understand the functional and biological effects of HPV infection in the pre‐malignant pathway.
Characterization of non-invasive oropharyngeal samples and nucleic acid isolation for molecular diagnostics
Molecular diagnostics is an increasingly important clinical tool, especially in routine sampling. We evaluated two non-invasive methods (oral swabs and mouthwashes) for sampling nucleic acids from the oral/pharyngeal area. We created a workflow from sample collection (n = 59) to RT-qPCR based analysis. The samples were further characterized in terms of their cellular composition as well as the purity, degradation and microbial content of the derived DNA/RNA. We determined the optimal housekeeping genes applicable for these types of samples. The cellular composition indicated that mouthwashes contained more immune cells and bacteria. Even though the protocol was not specifically optimized to extract bacterial RNA it was possible to derive microbial RNA, from both sampling methods. Optimizing the protocol allowed us to generate stable quantities of DNA/RNA. DNA/RNA purity parameters were not significantly different between the two sampling methods. Even though integrity analysis demonstrated a high level of degradation of RNA, corresponding parameters confirmed their sequencing potential. RT-qPCR analysis determined TATA-Box Binding Protein as the most favorable housekeeping gene. In summary, we have developed a robust method suitable for multiple downstream diagnostic techniques. This protocol can be used as a foundation for further research endeavors focusing on developing molecular diagnostics for the oropharyngeal cavity.
CRSwNP-derived cells retain native disease-relevant characteristics in vitro
Objective and design Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the paranasal sinuses, which is divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP is typically caused by type 2 inflammation, which is characterized by elevated IL-4 and IL-13 levels, impairment of the epithelial barrier, and tissue remodeling. While the involvement of immune cells is well known, it remains unclear to what extent structural cells intrinsically maintain disease-specific functional programs. The aim of this study was to determine whether epithelial cells and fibroblasts derived from CRSwNP and CRSsNP differ in their barrier properties, inflammatory reactivity, and type 2-associated functional characteristics. Methods Air–liquid interface (ALI) epithelial cultures and primary fibroblast cultures were generated from CRSwNP and CRSsNP tissue. Epithelial barrier integrity was assessed by transepithelial electrical resistance (TEER), and inflammatory responses to TLR stimulation were analyzed by qRT-PCR. Fibroblast migration was evaluated using scratch assays. Cellular responses to IL-4/IL-13 with or without Dupilumab were quantified by qRT-PCR. Results CRSwNP-derived epithelial cells exhibited delayed tight junction formation and impaired differentiation compared to CRSsNP cells. Poly(I:C) stimulation induced stronger expression of Th2-associated cytokines in CRSwNP cultures. CRSwNP fibroblasts showed reduced migratory capacity and a heightened induction of Th2 cytokines and extracellular matrix genes following IL-4/IL-13 stimulation relative to CRSsNP fibroblasts. Conclusion Epithelial cells and fibroblasts derived from CRSwNP retain disease-associated type 2 characteristics in vitro, indicating persistent disease-aligned programmed functional alterations of the polyp microenvironment. In contrast, CRSsNP-derived cells lacked comparable enhanced type 2 responsiveness. These findings support CRSwNP as a distinct, self-sustaining inflammatory endotype and underscore the value of patient-derived models for investigating disease mechanisms and targeted therapies.
Permanent occlusion of the Eustachian tube: a retrospective study on reopening procedures
Purpose This study retrospectively evaluated the efficacy and versatility of reopening procedures for the permanent occlusion of the cartilaginous Eustachian tube (POET) by analyzing four consecutive cases. Methods The study included all patients diagnosed with POET who suffered from Eustachian tube occlusion and glue ear. A combined approach of endoscopic transnasal/transoral laser surgery was utilized to reopen the POET. This was subsequently followed by balloon dilation (BET) and stenting for a duration of six weeks. In one distinct case, the Eustachian tube orifice was approached via a transtympanic method, where a balloon catheter was placed. The primary outcome measures targeted the success rate of reopening, which was quantified using audiological outcomes and Eustachian tube patency verified by a positive Valsalva maneuver. Results Four patients, with an age range of 14–62 years (mean age of 29.3 years), were subject to Eustachian tube reopening. The duration of follow-up varied between 10 and 24 months, averaging at 16.2 months. Notably, 75% of the surgically treated ears displayed no evidence of glue ear upon their last follow-up and showed restoration of Eustachian tube patency. The procedures were executed without any surgical complications. The causes for POET in these patients were heterogeneous: two were attributed to scarring post adenoidectomy, one to occlusion following orthognathic surgery and the remaining one due to prior radiotherapy treatment for squamous cell carcinoma located at the soft palate. Discussion Total occlusion of the cartilaginous Eustachian tube may be linked to persistent middle ear diseases. It is imperative to conduct nasopharyngeal endoscopy in these cases. The findings from this study suggest that the Eustachian tube reopening procedure is predominantly effective and safe for patients with POET stemming from a variety of pathologies. Future research should focus on exploring advanced stenting devices and necessitate longer follow-up periods for comprehensive understanding.