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.

[Unilateral diseases of the maxillary sinus]. / Einseitige Erkrankungen der Kieferhöhle.

Unilateral diseases of the maxillary sinus are among the most common rhinologic diagnoses. The diversity of these diseases can represent a challenge for the treating physician. The spectrum ranges from harmless maxillary sinus cysts that seldom require treatment, to highly aggressive malignant tumors. Special attention should be given to the management of inverted papilloma. These benign tumors are characterized by high recurrence rates and the potential for malignant transformation. The key to minimizing recurrence is precise surgical intervention. Other unilateral maxillary sinus diseases such as the antrochoanal polyp and the fungus ball (aspergilloma) are also discussed in depth.

[Rare diseases of the maxillary sinus]. / Seltene Erkrankungen der Kieferhöhle.

BACKGROUND: Silent sinus syndrome (SSS), organized hematoma (OH), and pneumosinus dilatans (PD) are rare, usually unilateral diseases of the maxillary sinus. Due to misinterpretation, excessive diagnostics and unnecessarily aggressive surgery or a delay in diagnostics and treatment are common. OBJECTIVE: The objective of this study was to develop reasonable and comprehensible diagnostic criteria to improve diagnosis and treatment of these rare diseases. METHODS: In this retrospective study, all patients treated for SSS, OH, and PD from 2012 to 2019 were identified. Patient history, diagnostic tests and results, and postoperative course were analyzed and compared with the available literature. RESULTS: During the study period, 7 patients with SSS, 3 patients with PD, and 2 patients with OH were treated and available for follow-up. Comparison of these patients with the literature allowed us to develop diagnostic criteria. CONCLUSION: Medical history combined with endoscopic and radiologic criteria should improve preoperative diagnosis of these three rare diseases of the maxillary sinus and help to distinguish them from other differential diagnoses. This approach should minimize morbidity for the patients.

[Anteromedial maxillectomy for improvement of nasal breathing : Advanced procedure in surgery of the lateral nasal wall]. / Anteriomediale Maxillektomie zur Verbesserung der Nasenatmung : Erweiterte Verfahren in der Chirurgie der lateralen Nasenwand.

The aim of classical surgical correction for nasal breathing impairment is to harmonically extend the physiological space in the nose by an operation of the nasal septum and inferior nasal turbinate. In this way the airflow character should be maintained and the mucosa protected in order not to endanger the respiratory function of the nose. This article presents an operative approach developed stepwise a few years ago in which the different operative steps are carried out depending on the individual anatomical situation and the underlying mucosal disease. The focus is on partial anteromedial maxillectomy.

[Comprehensive review on endonasal endoscopic sinus surgery]. / Aktueller Stand der endonasalen Nasennebenhöhlenchirurgie.

Endonasal endoscopic sinus surgery is the standard procedure for surgery of most paranasal sinus diseases.Appropriate frame conditions provided, the respective procedures are safe and successful.These prerequisites encompass appropriate technical equipment, anatomical oriented surgical technique, proper patient selection, and individually adapted extent of surgery.The range of endonasal sinus operations has dramatically increased during the last 20 years and reaches from partial uncinectomy to pansinusoperation with extended surgery of the frontal (Draf type III), maxillary (grade 3-4, medial maxillectomy, prelacrimal approach) and sphenoid sinus.In addition there are operations outside and beyond the paranasal sinuses. The development of surgical technique is still constantly evolving.This article gives a comprehensive review on the most recent state of the art in endoscopic sinus surgery according to the literature with the following aspects: principles and fundamentals, surgical techniques, indications, outcome, postoperative care, nasal packing and stents, technical equipment.

[Nasal packing after FESS--time is over?]. / Nasentamponade nach FESS--ein Auslaufmodell?

National and international tendencies to avoid nasal packing after FESS are closed related to the surgical surgery (atraumatic endoscopic surgery, avoidance of resection of turbinates, meticulose coagulation). At the end of each operation a benefit-risk-analysis should be performed, whether nasal packing is indicated and which one. In endonasal surgery only those conventional nasal packing materials should be used - if necessary - which have a smooth surface and minimize mucosal damage, potential worsening of wound healing and negative impact on patient comfort. So called hemostatic/resorbable materials are a first step to these direction. But they are critical, because these materials cause increased synechiae and sometimes foreign body reactions because of incorporation into the mucosa. Occlusion of the nose via simple taping of the nasal entrance is a simple and very effective method to create a moist environment to optimize endonasal wound healing or management of a dry nose.

[Nasal packing and stenting]. / Nasentamponaden und Stents.

Despite nasal packing is not necessary after functional endoscopic sinus surgery according to modern surgical techniques, nasal packing is a necessary tool in ENT. Therefore the state of the art regarding indications, benefit and risk of nasal packing and stents are given. In endonasal surgery only those conventional nasal packing materials should be used--if necessary--which have a smooth surface and minimize mucosal damage, potential worsening of wound healing and negative impact on patient comfort. Modern FESS implicates modern types of nasal packing, which leave the old concept of performing pressure and occupying space. So called hemostatic/resorbable materials are a first step in this direction. But they are critical, because these materials cause increased synechiae and sometimes foreign body reactions because of incorporation into the mucosa. Occlusion of the nose via simple taping of the nasal entrance is a simple and very effective method to create a moist environment to optimize endonasal wound healing or management of a dry nose. Stenting of the frontal sinus is only recommended if it is not possible to realize a sufficiently wide, physiologically formed and in large areas with mucosa covered frontal sinus outflow tract.

Posterior translacrimal approach to the maxillary sinus.

BACKGROUND: This study aimed to compare the view into the maxillary sinus using the posterior translacrimal approach compared with grade 3 antrostomy. METHODS: Grade 3 antrostomy followed by a posterior translacrimal approach was performed on four cadavers. The maximum intramaxillary view was documented endoscopically guided by electromagnetic navigation. Representative screenshots were evaluated in a blinded manner by three independent sinus surgeons. In addition, a prospective investigation of specific complications in the post-operative course of consecutive patients was performed. RESULTS: In the cadaver study, the posterior translacrimal approach provided a significantly better view into the maxillary sinus compared with grade 3 antrostomy. In the clinical study, only 1 out of 20 patients reported on a minor problem with lacrimal drainage at 6 months. CONCLUSION: The posterior translacrimal approach to visualising the maxillary sinus should be considered a strong alternative to more radical techniques.

[Persistant chronic rhinosinusitis after endonasal sinus surgery]. / Persistierende chronische Sinusitis nach Nasennebenhöhlenoperation.

Reasons for recurrent or persistent chronic rhinosinusitis could be the operation technique of the primary surgery, postoperative scarring, persistent inflammation or pathophysiologic agent or local factors. The management should be individualized and demands precise analysis of the clinical problem of the patient, nasal endoscopy and CT examination. Dependent on the results conservative or surgical therapy is mandatory. Medical and operative approaches are discussed in detail.

[Is packing of the nose up-to-date ?]. / Ist die Nasentamponade noch zeitgemäss?

BACKGROUND: Generally accepted standards regarding the materials which should be used for packing, how long the packing should be left in place or the indications for nasal packing are lacking. Nasal packing is used primarily to control bleeding in endonasal surgery, to stabilize the cartilaginous and bony skeleton and to prevent synechiae or restenosis. For the latter some authors recommend to pack the nose for several days. We want to prove the acceptance according to time, particularly wether there is an increase in discomfort. PATIENTS: Prospective study in 60 patients who underwent septoplasty and submucosal resection of inferior turbinates (n = 30) or endonasal sinus surgery (n = 30, in 15 cases septoplasty was performed too). The nose was packed for 4 or 5 days. Using a visual analog scale (0 - 10) the patient's condition was examined regarding: stuffy nose, headache, sleeping disorders, overall judgement. RESULTS: In two patients the packing had to be removed early (once because of the development of swelling of the lower lid and cheek; once because of lacking acceptance). The average condition of the remaining 58 patients showed no worsening during time for all 4 features. Analyzing the individual, only two patients (3.5 %) showed continuous increasing of complaints. CONCLUSIONS: According to this investigation, nasal packing for 4 or 5 days is well accepted by most of the patients, if you be able to make clear its sense to the patient. Nevertheless, looking for alternative operative techniques or nasal packing materials is mandatory to improve the patient's comfort postoperatively.

[First experiences in endonasal duraplasty without antibiotics]. / Erste Erfahrungen mit der endonasalen Duraplastik ohne die routinemässige Gabe von Antibiotika.

BACKGROUND: Available evidence does not support the use of prophylactic antibiotics in patients with CSF fistulae. The question arises whether an antibiotic prophylaxis or therapy is mandatory planning an operative closure of frontobasal dural lesions. PATIENTS: In a retrospective survey a consecutive sample of 7 patients who had undergone endonasal ENT-department of two universities and an university teaching hospital was taken. The hospital course was evaluated and all patients were interviewed after a postoperative period between 6 and 36 months. Endonasal duraplasty by underlay or onlay technique without pre- or intraoperative application of antibiotics was performed. Hospital course, development of meningitis, need for antibiotic therapy later on, subjective complaints, history of meningitis, cerebrospinal fluid rhinorrhea, fluoresceine test (intrathecal administration of fluoresceine sodium and subsequent nasal endoscopy) were evaluated. RESULTS: 6 patients had an uneventful postoperative hospital course without any sign of inflammatory complications. In one patient with a larger resection of dura antibiotics were administered at the second postoperative day because of recurrent fever. There occurred no meningitis in any patient. All duraplasties were successfully closed. 5 patients showed a negative fluoresceine test, 2 patients denied it having no special problems. CONCLUSIONS: Duraplasty can be performed satisfactorily by endonasal approach. In small lesions and in the absence of special risk factors (diabetes, acute sinusitis, immunodeficient patients) endonasal duraplasty don't seem to inevitably need an antibiotic cover. A larger patient population is necessary to confirm these results.

General anesthesia in Eisenmenger's syndrome.

The anesthetic management of a woman with Eisenmenger's syndrome undergoing abdominal hysterectomy with general anesthesia is described. Proper anesthetic management of patients with this syndrome depends on a knowledge of the pathophysiologic process and associated complications. The potential problems of systemic hypotension, pulmonary embolism and infective endocarditis are outlined. Sudden death is a common and pregnancy is a major hazard.

[Gastroesophageal reflux disease and chronic sinusitis]. / Gastroösophageale Refluxkrankheit und chronische Sinusitis.

BACKGROUND: It is increasingly suggested that there may be a connection between gastrooesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR) and chronic sinusitis. We therefore wished to establish whether the literature contains sufficient evidence to support this assumption. MATERIAL AND METHODS: We performed a search in Medline (PubMed) and EMBASE with the key words "GERD, GER, reflux, sinusitis, chronic sinusitis". The literature obtained was assessed with regard to the reported results and their evidence levels. The level of evidence was classified according to the usual levels I - IV, only levels Ia or Ib being considered sufficient evidence for a knowledge gain confirmed by therapeutic trials. RESULTS: A total of 77 references were found in Medline and 142 in EMBASE. A large number of these were narrative review articles addressing the connection between GERD or sinusitis and asthma or GERD or sinusitis and chronic cough. Only 12 papers and one case report dealt more or less directly with the question of a connection between chronic sinusitis and reflux. None of the studies could be classed as evidence level I (randomised controlled trials), ten were classed as level III studies, one as level IIb and one as level IV. DISCUSSION AND CONCLUSIONS: The existing studies do not allow us to pinpoint LPR (and even less so GERD) as a clear-cut factor in the aetiopathogenesis of chronic sinusitis. However, despite all their deficiencies and limitations the studies nevertheless do show that reflux into the pharynx and nasopharynx is possible. This reflux (= LPR) can lead to chronic inflammation which can be successfully treated with antireflux therapy with proton pump inhibitors. Quantification of the association is not currently possible. An above-average proportion of the patients with chronic rhinosinusitis appear to have GERD/LPR. However the prevalence of GERD in the population is generally high. It has not yet been established with sufficient certainty whether the LPR must be regarded as a causative factor, whether it exacerbates or chronifies the disease or whether it is merely an epi-phenomenon which does not require specific treatment. To answer this important question we need prospective randomised controlled studies which will provide evidence of sufficient quality. These should be conducted with the help of standardised documentation.

[Review: pathophysiology and methodology of nasal packing]. / Ubersicht: Art und Wirkung geläufiger Nasentamponaden.

Nasal packing is a frequent procedure to control spontaneous nasal bleeding or postoperative oozing following different types of nasal surgery. It strives for internal stabilization of the nasal framework and for optimizing wound healing by prevention of stenosis or synechia. A lot of different materials is used and there is no accepted standard concerning the type and application. A review on pathophysiology of the packed nose is given together with a survey on customary packing materials focussing on the specific merits, demerits and side-effects including economical aspects.

Prolongation of life span in hypertensive rats by dietary interventions. Effects of garlic and linseed oil.

The effects of long-term dietary application of garlic (dried powder, 0.5% in weight of standard chow; G group) or linseed oil (2.5%; L group) as well as a combination of both interventions (L + G group) on the life span of hypertensive rats (SHR SP) was investigated. A further group fed with standard chow served as control (C). The dietary interventions were started at the age of three weeks. Besides regular measurements of the systolic arterial blood pressure (oscillometrically at the tail artery) as well as of heart rate and body weight, autopsy and histological investigations were performed. Both diets, and particularly their combination, prolonged life span significantly (mean values (days) C: 434.5 +/- 23.5; G: 453.2 +/- 16.2; L: 470.0 +/- 26.2; L + G: 494.8 +/- 39.2). There was no significant interaction of the factors garlic and linseed oil. Systolic blood pressure as measured during the compensatory stage (data used until the 39th week of life) was significantly lowered by both garlic (mean -5.8 mm Hg), linseed oil (mean -6.3 mm Hg), and their combination (mean -11.3 mm Hg). The animals died as a consequence of congestive left and right ventricular failure with ventricular hypertrophy, dilatation, myocardial fibrosis and cellular infiltration, left ventricular atrial thrombosis (in most cases), and terminal pneumonia. On the other hand, arteriosclerotic plaques and signs of cerebral stroke could not be detected. Except for the degree of hypertrophy, which was lower in the treated groups, no differences were obvious regarding the morphological findings at the time of death. There was a significant positive correlation between mean blood pressure and the degree of left ventricular hypertrophy. Furthermore, a significant negative correlation between mean blood pressure and ventricular hypertrophy on the one hand and survival on the other hand was obvious provided the total number of animals was considered, however, not within the individual groups. The same applies to the relation between the reduction of left ventricular hypertrophy and life span. The relatively slight hypotensive effect of both dietary interventions as well as the results of previous investigations speaks in favor of a substantial influence of factors independent of blood pressure. In view of controversial results and interpretations in international literature, the mechanisms involved need further study.

[Complications of lumbar administration of 5% sodium fluorescein solution for detection of cerebrospinal fluid fistula]. / Komplikationen bei intrathekaler Applikation einer 5 %igen Natriumfluoresceinlösung zum Nachweis von Liquorfisteln.

BACKGROUND: The detection of cerebrospinal fluid fistulas in the region of the anterior or lateral skull base can be difficult. The fluorescein test with lumbar administration of 5% sodium fluorescein solution can be used to detect cerebrospinal fluid leakage, identify weak points in the dura, achieve precise localisation of cerebrospinal fluid fistulas and to check intraoperatively that watertight dural closure has been achieved. However, use of the test is problematic as the fluorescein solution used is not licensed for this indication in Germany and severe neurological complications are described in the literature. In order to clarify the legal situation regarding use of the test, we therefore analysed the complications occurring in a sizeable patient sample. METHOD: The records of all patients in whom a fluorescein test had been performed between 1979 and June 2000 were analysed retrospectively for the occurrence of complications. RESULTS: The most frequent complication in the 368 fluorescein tests performed was headache, followed by nausea and vomiting, temperature elevation, dizziness and nuchal pain. These side-effects were no more frequent than described for lumbar puncture alone. Twenty-six patients experienced side-effects on the day of the operation, 65 on the first postoperative day, 36 on the second day, 34 on the third day and 13 patients after the third day. There were two cases of grand mal seizures following concomitant intrathecal contrast medium administration. None of the patients had side effects persisting longer than 4 weeks. CONCLUSIONS: Intrathecal administration of a 5 % fluorescein solution is a safe procedure provided that the maximum dosages are not exceeded and the solution is prepared and administered correctly and in accordance with the specified indications and contraindications. In view of its great diagnostic benefit and low risk when properly used, the dictates of therapeutic freedom allow use of this drug despite the fact that it is not licensed for this purpose in Germany. It is necessary to obtain written informed consent from the patient.