[Does aspirin therapy after desensitization still have a role in treatment of chronic rhinosinusitis with nasal polyposis in the era of biologics?] / Hat die ASS-Desaktivierung in Zeiten von Biologika noch einen Stellenwert bei chronischer Rhinosinusitis mit nasaler Polyposis?

The prevalence of analgesic intolerance syndrome (AIS), internationally known as NSAID-exacerbated respiratory disease (NERD), is reported to be 0.5-5.7% in the general population. The disease often begins with nasal symptoms, which are later joined by chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and respiratory hypersensitivity reactions following use of nonsteroidal anti-inflammatory drugs (NSAIDs). In the setting of chronic respiratory disease, the type 2 inflammatory endotype is predominant in approximately 80% of patients with CRSwNP, rendering biologics directed against interleukin (IL)-4, IL­5, IL-13, and IgE of high clinical interest, particularly in patients with severe CRSwNP and NERD. NERD is often associated with CRSwNP and asthma. Patients with CRSwNP and NERD have been treated, among other therapies, with aspirin therapy after desensitization (ATAD). With the approval of monoclonal antibodies for CRSwNP and asthma, the question arises as to what extent ATAD, which is associated with undesirable side effects, is still useful in the treatment of CRSwNP. In this manuscript, the use of ATAD in CRSwNP patients is discussed from different medical and socioeconomic points of view, both alternatively to or in combination with monoclonal antibodies. Accordingly, both ATAD and biologics continue to play a supporting role in modern treatment of CRSwNP in NERD patients, and should be used judiciously to complement each other.

[Neuroimmunology of allergic rhinitis part 2 : Interactions of neurons and immune cells and neuroimmunological units]. / Neuroimmunologie der allergischen Rhinitis Teil 2 : Interaktionen von Neuronen und Immunzellen und neuroimmunologische Einheiten.

Allergic rhinitis is an IgE-mediated, type­2 inflammatory disease. neuropeptides are released by neurons and interact with immune cells. Via colocalization, neuroimmune cell units such as nerve-mast cell units, nerve-type 2 innate lymphoid cell (ILC2) units, nerve-eosinophil units, and nerve-basophil units are formed. Markedly elevated tryptase levels were found in nasal lavage fluid and were strongly associated with neuropeptide levels. A close anatomical connection allows bidirectional communication between immune and neuronal cells. Transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin repeat 1 (TRPA1) are critically involved in immunological reactions in the setting of allergic rhinitis. Neuroimmunological communication plays an important role in the inflammatory process, so that allergic rhinitis can no longer be considered a purely immunological disease, but rather a combined neuroimmunological disease.

[Neuroimmunology of allergic rhinitis : Part 1: Cellular and humoral basic principles]. / Neuroimmunologie der allergischen Rhinitis : Teil 1: Zelluläre und humorale Grundlagen.

Allergic rhinitis (AR) is a very common disease with a high prevalence worldwide. It is an IgE-mediated type 2 inflammatory disease following exposure to inhalant allergens. A multitude of different neuropeptides including substance P, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), and neuromedin U (NMU) can be released via peripheral axon or central reflexes, interact with immune cells, and thus contribute to neurogenic inflammation which causes the nasal hyperreactivity (NHR) characteristic of AR. Independent production of neuroendocrine hormones and neuropeptides by immune cells has also been demonstrated. Neuro-immune cell units arise when immune and neuronal cells colocalize, for which typical anatomic regions are, e.g., the mast cell-nerve functional unit. The focus of this review is the elucidation of neuroimmune communication mechanisms in AR.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[Allergic reactions to COVID-19 vaccines: evidence and practice-oriented approach]. / Allergische Reaktionen auf COVID-19-Impfstoffe ­ Evidenz und praxisorientiertes Vorgehen.

Less than a year after the first detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccines have been approved for routine use in numerous countries and have already been used in mass vaccination programs. Vaccines include the mRNA BNT162b2 and mRNA 1273. Allergic reactions and anaphylaxis account for a substantial proportion of the adverse reactions to these vaccines observed to date, but overall they are rare. The incidence of anaphylaxis in the context of SARS-CoV­2 vaccination with the mRNA vaccines appears to be approximately 10-fold higher than with previous vaccines, at approximately 1 per 100,000 vaccine injections. One focus of the present article is a systematic review of the components of mRNA vaccines against " coronavirus disease 2019 " (COVID-19). Differences from established vaccines are addressed and the allergic potential of liposomes, polyethylene glycol, tromethamine/trometamol, and mRNA are discussed. Another focus is on the clinical presentation and course of allergic reactions to the COVID-19 vaccines. This is followed by a discussion of the therapeutic approach to anaphylactic reactions, as well as the drugs and medical supplies required to treat them. It is important to note that any vaccinee may be affected by anaphylaxis, regardless of whether or not allergic diseases are already known. Therefore, every vaccination site and every vaccinator must be prepared to recognize and treat severe allergic reactions.

The toll of noninfected CRS patients to the COVID-19 pandemic.

Social distancing with the aim of avoiding infections and pre-serve critical care capacities during the COVID-19 pandemic has been implemented in Germany according to World Health Organization (WHO) recommendations from early March onwards. Limitations of physical contacts to reduce exposure to SARS-CoV-2 infected individuals were handled strictly, particularly in medical centers dealing with airway diseases, like rhinology and pneumology clinics. Such measures and reluctance to visit out- and inpatient services resulted in a 82% decrease in consultations to the 12 German oto-rhino-laryngological (ORL) centres forming our database during the 50 days following March 09 in 2020 if compared to the same period in 2019. Our data on CRS care underline reports on undertreatment of non-COVID-19 individuals with several different diseases during the current pandemic. We should try to reduce the toll these patients have to pay as much as possible. We established telemedicine, e-Health and artificial intelligence-supported triage for selecting the right patients for onsite-consultations and to advise patients in several demands.

[Angiolytic laser applications for the larynx : Phonosurgical concepts for transoral laser microsurgery]. / Angiolytische Laserverfahren am Kehlkopf : Phonochirurgische Aspekte bei transoraler Lasermikrochirurgie.

Transoral laser microsurgery (TLM) for treatment of laryngeal cancer has reduced temporary tracheotomies, increased organ preservation rates, and improved functional results. Gold standard for laser-based transoral resection of laryngeal cancer is the application of CO2 lasers. Oncologically safe radical resection and postoperative voice outcome must be weighed up individually. Angiolytic laser effects enable modification of the tumor micromilieu by targeted obliteration of microvessels and antagonization of angiogenesis with preservation of vibrating laryngeal tissue for good voice function. Introduction of the German S3 guideline on diagnosis, treatment, and follow-up of laryngeal cancer is a critical step towards national evidence-based standardization. Internationally, the evidence for treatment of laryngeal mucosal dysplasia and T1a cancer with angiolytic potassium titanyl phosphate (KTP) lasers is increasing. Angiolytic lasers are also used for juvenile papillomatosis and suspension microlaryngoscopy under general anesthesia or local anesthesia in selected patients.

[Immunology of chronic rhinosinusitis with nasal polyps as a basis for treatment with biologicals]. / Immunologie der Polyposis nasi als Grundlage für eine Therapie mit Biologicals.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial inflammation of the nasal and paranasal mucosa. Until now, no internationally standardized classification could be developed. In most cases, CRS is phenotypically classified according to chronic rhinosinusitis with (CRScNP) and without nasal polyps (CRSsNP). However, recent studies could show that there are numerous endotypes within these phenotypes based on different inflammatory mechanisms. This review describes the important immunological mechanisms of CRScNP and highlights modern treatment options with biologicals directly addressing particular immunological processes. METHODS: Current knowledge on immunological and molecular processes of CRS, particularly CRScNP, was extracted from Medline, PubMed, national and international study- and guideline-registers, and the Cochrane library by a systematic review of the literature. RESULTS: Based on current literature, various immunological mechanisms for CRS and CRScNP could be identified. Relevant studies for the treatment of eosinophilic conditions such as asthma or CRScNP are presented and, if available, results of these studies are discussed. CONCLUSION: The growing insight into the underlying immunological mechanisms of CRScNP could pave the way for new personalized treatment options such as biologicals in the future.

[Is routine histopathologic examination of middle ear cholesteatoma necessary?] / Ist die routinemäßige histologische Untersuchung von Mittelohrcholesteatomen nötig?

BACKGROUND: In the course of restoration of the middle ear, routine histological examinations are initiated in many cases, although a middle ear cholesteatoma can be clinically diagnosed in a normal case. AIM OF THE STUDY: To determine the correlation between the surgeons' diagnosis and that of the pathologist and comparison with literature data. To check the rate of unexpected diagnoses. Analysis of the costs and survey of German ENT clinics with regard to handling of the histological examination in suspected cholesteatoma. MATERIALS AND METHODS: Retrospective evaluation of cholesteatoma cases of the ENT Department of the University Medical Center of Mainz from 2010-2015. Germany-wide postal survey of ENT clinics. RESULTS: In all, 449 operations for the rehabilitation of a middle ear cholesteatoma, of which there were 312 (69.5%) first diagnoses and 137 (30.5%) recurrences. A histological examination was conducted in 78.6%. For first diagnoses, the sensitivity of the clinical assessment was 97.9%, specificity 10%, positive predictive value 96.3%, and negative predictive value 16.7%. Recurrences showed values of 100%, 40%, 97.1% and 100%. Unexpected malignant findings did not occur. This routine histological examination was performed by 58.6% of German ENT hospitals. A total of 80% of those questioned this to be useful. A histological examination cost an average of 14.06 €. CONCLUSION: Intraoperatively, there is a high degree of accuracy in diagnosing cholesteatoma. The cost factor of the histological examination is low and should not be the basis for the decision. The ear microscopy and the experience of the ear surgeon should be decisive for the decision for histological examination.

[Immunodeficiency in chronic rhinosinusitis : An important and often underestimated cause]. / Immundefekte bei chronischer Rhinosinusitis : Eine bedeutende und oft unterschätzte Ursache.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. METHODS: A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. RESULTS: The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. CONCLUSION: Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies.

[Staging of oropharyngeal carcinomas : New TNM classification as a challenge for head and neck cancer centers]. / Staging von Oropharynxkarzinomen : Neue TNM-Klassifikation als Herausforderung für Kopf-Hals-Tumorzentren.

BACKGROUND: The TNM (tumor, nodes, metastasis) classification is updated periodically according to the literature and international recommendations. With the 8th edition, notable changes have been developed especially with regard to oropharyngeal cancer. MATERIALS AND METHODS: The modifications as well as the practicability of the classification for staging of oropharyngeal cancers are demonstrated on the basis of cases from the tumor database. RESULTS: The latest edition of the TNM classification realizes requirements to differentiate between human papilloma virus (HPV) positive and HPV-negative tumors during staging. Furthermore, the prognostic relevance of extranodal extension of lymph node metastases was integrated into the classification. While downstaging is performed regarding N category and Union Internationale Contre le Cancer (UICC) stage in many p16-positive tumors, for p16-negative tumors, extranodal spread mostly leads to a notable upstaging. Due to limited specificity of the p16 immunostaining, the relevance of false positive results has to be underlined. Missing integration of smoking behavior, limited standardization of the extranodal extension examination technique, as well as high demands on the documentation quality should be kept in mind. CONCLUSION: Clinical trials will have to show whether deescalation strategies regarding p16-positive carcinomas are supported by the changes made in the TNM staging system. A prospective multicenter study should examine the universal applicability, the appropriateness for all sublocations, as well as the prognostic significance of the current edition.