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.

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.

Outcome after elective neck dissection and observation for the treatment of the clinically node-negative neck (cN0) in squamous cell carcinoma of the oropharynx.

Optimal elective neck treatment in node-negative (cN0) oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversially discussed. Retrospective chart review of 49 cT1-3 cN0 cM0 OPSCC patients, who had undergone surgical resection of the primary and either elective neck dissection (END) (n = 32) or observation (OBS) (n = 17) of the neck was performed. For systematic review of literature, Pubmed and EMBASE were searched for clinical studies including data on both END and OBS of the neck in cN0 OPSCC patients. Estimated 5-year overall survival (OS) rate was 82 % for END and 76 % for OBS [hazard ratio (HR) = 1.01]. Estimated 5-year disease-free survival (DFS) rate was 78 % for END and 67 % for OBS (HR = 1.79); 5-year DSS rate was 97 % (END) and 81 % (OBS) (HR = 2.22). None of the primary outcome variables (OS, DFS, DSS) revealed statistically significant effects for the treatment assignments. Hazard ratios implied an advantage for END. Systematic review of literature yielded only retrospective chart reviews and no data meeting our selection criteria for further data analysis. Due to lack of high-level evidence, the decision for END in cN0 OPSCC remains a diagnostic and therapeutic challenge. The demonstrated clinical equipoise would provide a solid basis for a multicentric, randomized trial.

[Public awareness of human papilloma virus infection in the head and neck area: an appeal for precision in diagnostics and for public health awareness]. / Humane Papillomvirusinfektionen im Kopf-Hals-Bereich im öffentlichen Bewusstsein: Mahnung zu Präzision in Diagnostik und Öffentlichkeitsarbeit.

Infection with human papilloma virus (HPV) has been associated with head and neck carcinomas. Experts in HPV-positive carcinomas consider these carcinomas to be a new entity, because it has been shown that treatment outcome is excellent with significantly longer overall survival dependent of therapy. Despite this, in Germany public awareness of this development is rather low. A strategy for prophylactic vaccination against HPV-associated diseases has been available since 2007 but only to reduce the incidence of cervical cancer for girls between 12 and 17 years of age. There is an ongoing debate in Germany about the efficacy and safety of HPV vaccination. The results of epidemiological research in the USA which show that vaccination in young males is valuable are still not accepted in Germany. This article discusses the scientific and public awareness regarding this topic and calls for precision in diagnostics and public health awareness in order to establish a fertile ground for prevention and optimal treatment of HPV-associated diseases.

Binding properties and esterase activity of monoclonal antibodies elicited against sucrose 6-heptylphosphonate.

Various sugar phosphonates were prepared by a Mitsunobu condensation between phosphonic diacids and properly protected carbohydrates. 6'-O-p-Aminophenylsucrose 6-heptylphosphonate was coupled to Bovine Serum Albumin (BSA) and Keyhole Limpet Hemocyanin (KLH) and the KLH conjugate was used for generation of monoclonal antibodies. Binding properties of these antibodies were screened by competitive enzyme-linked immunosorbent assay (ELISA) using the BSA conjugate. A monoclonal antibody with good binding properties showed a regioselective esterase activity toward 6-octanoylsucrose compared with 6'-octanoylsucrose.

Marked resistance of RAR gamma-deficient mice to the toxic effects of retinoic acid.

Excessive intake of retinol or of retinoic acid causes a syndrome of characteristic toxic effects known as hypervitaminosis A. To test the role of the nuclear retinoic acid receptor (RAR gamma) in this process we produced mice with a targeted disruption of the RAR gamma gene and examined toxic effects of repeated doses of retinoic acid and two other synthetic retinoids, Ro 15-1570 and Ro 40-6055. Surprisingly, homozygous mutant mice were resistant to fourfold higher doses of retinoic acid than wild-type mice as well as to elevated doses of the synthetic retinoids, indicating that RAR gamma may have a major role in mediating retinoid toxicity, a finding that possibly has practical implications for reducing the toxicity of synthetic retinoids in clinical use.