Monitoring mepolizumab treatment in chronic rhinosinusitis with nasal polyps (CRSwNP): Discontinue, change, continue therapy?

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-IL-5 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 should be monitored, what follow-up documentation is necessary, and when it should be discontinued if necessary. MATERIALS AND 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 discontinuation of therapy when using mepolizumab for the indication CRSwNP in the German healthcare system are given on the basis of a documentation sheet. CONCLUSION: 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.

[Particulars of sinogenic orbital complications in children]. / Besonderheiten der sinugenen orbitalen Komplikationen bei Kindern.

BACKGROUND: Sinogenic orbital complications in children are relatively rare but critical conditions that require accurate diagnosis and timely appropriate treatment to prevent severe sequelae. OBJECTIVE: This article concentrates on clinical, diagnostic, and therapeutic specifics of sinogenic orbital complications in children. MATERIALS AND METHODS: The work is based on a literature review (PubMed, Google Scholar) and own experience as well as data from the authors' own pediatric population. RESULTS: In children, sinogenic orbital complications are usually secondary due to acute bacterial sinusitis. Correct distinction between pre- and postseptal cellulitis is of utmost importance for correct diagnostic and therapeutic management in order to prevent long-term sequelae. Preseptal cellulitis can be treated conservatively. If there are signs of postseptal involvement, prompt cross sectional imaging will be required. Depending on the severity of the postseptal involvement, surgical treatment may be necessary. CONCLUSION: Recent literature debates three main issues: 1) developing models for different combinations of symptoms that reliably distinguish between pre- and postseptal cellulitis; 2) selection of appropriate cross-sectional imaging (MRI vs. CT); and 3) indications for surgery. All three issues will be discussed in detail in this article.

[Recommendations of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) for the granting of resident training program authorizations]. / Empfehlungen der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) für die Erteilung der fachspezifischen Weiterbildungsbefugnis.

The 2018 template for otorhinolaryngology specialist training of the German Medical Association is increasingly implemented by the federal associations. In this regard, the German Society recommended an otorhinolaryngology resident training plan for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) together with the Professional Association of German Otorhinolaryngologists as a suggested guideline for the federal medical associations. In this context, the state medical associations currently work on criteria on the basis of which otorhinolaryngologists and their training institutions can be granted authority for such a certified otorhinolaryngology resident training program.The DGHNO-KHC last made recommendations for the granting of authorizations for specialist training in otorhinolaryngology in 1999. Many contents have changed as a result of the 2018 model specialist training regulations. Therefore, a scientifically formulated proposal for the granting of continuing education authorizations is herewith provided as recommendation to the federal state medical associations.

Case report: Langerhans cell histiocytosis of the temporal bone in children: Challenging diagnosis of a rare disease with some pitfalls.

A 4-year-old girl was admitted to hospital with disturbance of balance. After being questioned, parents remembered an otitis with effusion 3 months earlier. CT-scans revealed destruction of both temporal bones. Initial biopsy showed granulomatous, necrotic inflammation, which led to comprehensive differential diagnoses. A second tissue sample confirmed Langerhans cell histiocytosis.

Multicenter Observational Study to Evaluate the Diagnostic Value of Sonography in Patients with Chronic Rhinosinusitis.

(1) Background: Computed tomography (CT) is considered mandatory for assessing the extent of pathologies in the paranasal sinuses (PNS) in chronic rhinosinusitis (CRS). However, there are few evidence-based data on the value of ultrasound (US) in CRS. This multicenter approach aimed to compare diagnostic imaging modalities in relation to findings during surgery. (2) Methods: 127 patients with CRS were included in this prospective multicenter study. Patients received preoperative US and CT scans. The sensitivity and specificity of CT and US were extrapolated from intraoperative data. (3) Results: CT scans showed the highest sensitivity (97%) and specificity (67%) in assessing CRS. Sensitivities of B-scan US were significantly lower regarding the maxillary sinus (88%), the ethmoid sinus (53%), and the frontal sinus (45%). The highest overall sensitivity was observed for assessing the pathology of the maxillary sinus. (4) Conclusions: We observed high accuracy with CT, confirming its importance in preoperative imaging in CRS. Despite the high US expertise of all investigators and a standardized examination protocol, the validity of CT was significantly higher than US. Ultrasound of the PNS sinuses is applicable in everyday clinical practice but lacks diagnostic accuracy. Nevertheless, it might serve as a complementary hands-on screening tool to directly correlate the clinical findings in patients with PNS disease.

Epithelial immune regulation of inflammatory airway diseases: Chronic rhinosinusitis with nasal polyps (CRSwNP).

BACKGROUND: The epithelial immune regulation is an essential and protective feature of the barrier function of the mucous membranes of the airways. Damage to the epithelial barrier can result in chronic inflammatory diseases, such as chronic rhinosinusitis (CRS) or bronchial asthma. Thymic stromal lymphopoietin (TSLP) is a central regulator in the epithelial barrier function and is associated with type 2 (T2) and non-T2 inflammation. MATERIALS AND METHODS: The immunology of chronic rhinosinusitis with polyposis nasi (CRSwNP) was analyzed in a literature search, and the existing evidence was determined through searches in Medline, Pubmed as well as the national and international study and guideline registers and the Cochrane Library. Human studies or studies on human cells that were published between 2010 and 2020 and in which the immune mechanisms of TSLP in T2 and non-T2 inflammation were examined were considered. RESULTS: TSLP is an epithelial cytokine (alarmin) and a central regulator of the immune reaction, especially in the case of chronic airway inflammation. Induction of TSLP is implicated in the pathogenesis of many diseases like CRS and triggers a cascade of subsequent inflammatory reactions. CONCLUSION: Treatment with TSLP-blocking monoclonal antibodies could therefore open up interesting therapeutic options. The long-term safety and effectiveness of TSLP blockade has yet to be investigated.

[Results of vagus nerve stimulator implantation in children and adolescents with treatment-refractory epilepsy]. / Ergebnisse der Vagusnervstimulatorimplantation bei Kindern und Jugendlichen mit therapierefraktärer Epilepsie.

Vagus nerve stimulation (VNS) is a therapeutic procedure that can be applied in a palliative setting in patients with treatment-refractory epilepsy who are not suitable for epilepsy surgery. The mechanism of action of VNS is currently not completely understood but appears to depend on a modification of neurotransmitter metabolism. Data of 25 patients with treatment-refractory epilepsy who underwent implantation of a vagus nerve stimulator were retrospectively analyzed in a monocentric study. A reduction in epileptic seizure rate of 28% was observed 3 months after initial activation and of 32.9% after 6-12 months. The responder rate (reduction in seizure rate of more than 50% compared to before implantation) was 40% 6-12 months after initial activation. In one third of patients, a reduction in epileptic seizure rate of at least 75% occurred. Adverse effects of surgery or the stimulation were rare.

[Skull and skull base injuries in children and adolescents : Results of a monocentric analysis]. / Schädel- und Schädelbasisverletzungen bei Kindern und Jugendlichen : Ergebnisse einer monozentrischen Auswertung.

BACKGROUND: The present study comprises a retrospective analysis of skull, skull base, and midface fractures in children, to provide clinical orientation for their management. To date, only few data are available on these injuries in this patient group. METHODS: Data from inpatient cases diagnosed with a midface, skull, or skull base fracture in the Children's Hospital Auf der Bult from 2015 to 2020 were evaluated. Age, gender, fracture mechanism, diagnosis, treatment, and possible complications were analyzed. Data of 224 children were grouped into 107 cases with nose fractures, 104 cases with skull fractures, 9 patients with temporal bone fractures, 4 patients with rhinobasal fractures, and 2 cases with fractures of the orbital floor. RESULTS: Among patients with nose fractures, the average age was 10.9 years (64% males), among patients with skull fractures 1.0 year (64% males), and in children with skull base fractures 6.0 years (85% males). Falls were the most frequent genesis (63%), followed by car accidents, collisions (25%), and violence (10%). Patients with skull fractures underwent sonography in 94% of cases; in 87% the fracture was verified. Patients with nose fractures underwent x­ray in 92% of cases, or sonography only in 8%; 95% of patients with nose fractures underwent operative repositioning. Typical fracture signs (i.e., hemotympanum, ophthalmic symptoms) or signs of central nervous system involvement (i.e., nausea, amnesia) occurred in 12 of 13 children with skull base fractures, and CT was performed in all these cases (none of whom developed a cerebrospinal fluid leak). CONCLUSION: The imaging modality should be selected based on the clinically suspected diagnosis and the course. Most fractures can be sufficiently treated without any permanent sequelae, except for nose fractures, which frequently require operative repositioning.

[Perfusion analysis in parotid gland tumors using contrast-enhanced ultrasound (CEUS)]. / Perfusionsanalyse von Parotistumoren mittels kontrastverstärkter Sonographie (CEUS).

OBJECTIVE: The diagnosis of parotid gland tumors is challenging due to their rarity and heterogenity. Neither conventional ultrasound nor magnetic resonance imaging (MRI) nor computed tomography (CT) allow a reliable pretherapeutic diagnosis. In addition to conventional ultrasound, contrast-enhanced ultrasound (CEUS) enables a more detailed assessment of perfusion in parotid gland tumors, thereby improving evaluation of this tumor entity. Extensive studies with analysis of perfusion characteristics in different regions of interest (ROI) in parotid gland tumors are currently lacking. This study analysed and compared perfusion parameters in different intratumoral areas of malignant and benign parotid gland tumors using CEUS. MATERIALS AND METHODS: A total of 100 patients with tumors in the parotid gland were examined using B­mode sonography, colour Doppler sonography and CEUS. The parameters magnitude, echogenicity, demarcation, vascularisation and in particular perfusion characteristics were measured and analysed. Analysis of quantitative CEUS parameters was performed using a specific method for perfusion analysis with certain ROI, which were allocated in a standardized manner in the entire parotid gland tumors. The perfusion parameters were compared between intratumoral ROI in the tumors and between particular tumor entities. Qualitative CEUS analysis with an estimation of perfusion patterns was additionally performed. RESULTS: Histologically benign tumors were found in 92 cases, and malignant tumors in eight cases. CEUS analysis of perfusion patterns revealed a centripetal perfusion pattern in malignant tumors significantly more frequently than in benign tumors. In the perfusion analysis of quantitative CEUS parameters, all tumors showed higher perfusion intensities in the peripheral ROI. In benign tumors, more differences in perfusion intensity between the intratumoral ROIs were detected compared to malignant tumors. CONCLUSION: The perfusion parameters (centripetal perfusion pattern; area under the curve) evaluated in this study have the potential to improve pretherapeutic diagnostics of parotid gland tumors in terms of differentiation of tumor entity. Further studies with larger patient cohorts are required for subsequent investigation and validation of the diagnostic accuracy of particular parameters to detect perfusion patterns potentially specific to particular tumor entities.

[Granulomatosis with polyangiitis - manifestations in the head and neck area]. / Granulomatose mit Polyangiitis ­ Manifestationen im Kopf-Hals-Bereich.

Granulomatosis with polyangiitis is a rare chronic rheumatologic systemic disease with a vasculitis of small- and medium-size vessels. Mostly the upper airways, lung and kidneys are affected. Symptoms are unspecific. Patients complain about stuffy nose, crustiness of nasal secretions, ulcera of the oral mucosa or epistaxis. The otorhinolaryngologist may be the first one to evaluate the patient's health condition. Long term complications may be cardial, renal or pulmonal failure. To this day the aetiology is still unknown. Severe disease is treated with a combination of immunosuppressive medications. Clinic examinations and laboratory tests should be carried out for life-time.

[Follow-up care of sinonasal papillomas - risk factors for recurrence and malignant progression]. / Tumornachsorge sinunasaler Papillome ­ Risikofaktoren für Rezidiv-Entwicklung und maligne Entartung.

OBJECTIVE: Sinonasal papillomas are tumors of the nasal cavity and paranasal sinuses. They are treated through complete resection under oncologic conditions. Two characteristics complicate follow-up: 1) frequent tumor recurrences (even many years after initial diagnosis), 2) possibility for malignant progression. This review elucidates risk factors for these two characteristics to depict "high-risk patients" for whom a closer follow-up is mandatory. MATERIALS AND METHODS: Literature was searched in Pubmed (NCBI). RESULTS: The most important risk factor for recurrence is incomplete tumor resection. This comprises several more factors: inappropriate surgical procedure, large tumors, difficult surgical conditions due to tumor localization or to prior surgery. Young age and tobacco smoking are risk factors for frequent recurrences. In regard to malignant progression, extended tumors, smoking, senior age, female sex, bone invasion, and lack of inflammatory polyps have been identified as risk factors. Histopathological factors for both - recurrences and malignant progression - are epithelial dysplasia, hyperkeratosis, squamous hyperplasia, as well as (if known) increased proliferation, aneuploidy, and infection with human papillomaviruses. CONCLUSIONS: Complete resection of sinunasal papillomas under oncologic conditions is of utmost importance. A careful postoperative follow-up is mandatory. Most authors suggest at least a five-year, some a lifelong follow-up. Patients with one or more risk factors should be monitored more closely.

Rare Differential Diagnosis of Dyspnea: Extramedullary Plasmocytoma (EMP) of the Larynx-Case Report and Review of the Latest Literature of Laryngeal EMP and Laryngeal Involvement of Multiple Myeloma.

Multiple myeloma (MM) of the larynx is extremely rare. It can be either a laryngeal manifestation of a general multiple myeloma or it can occur as a primary laryngeal mass, which is then called extramedullary plasmocytoma (EMP). We present the case of an 81-year-old male patient who was admitted for dyspnea. He had a history of multiple myeloma but was in complete remission since some years. Histological and immunohistological examination of tissue samples revealed an EMP. The patient was first treated by laser surgery in order to reduce the tumor mass and secure the airway. Afterwards, he was systematically treated by radiation therapy with 60 Gy, which achieved a good response and complete remission proven by control laryngoscopy and histological examination of tissue samples taken from the former tumor area three months after laser excision. The latest literature in the field is reviewed. There were only ten cases of EMP in the larynx or laryngeal involvement of MM published within the last five years (Pubmed was searched for "larynx," "laryngeal" and "EMP," "Extramedullary Myeloma," "Multiple Myeloma," and "MM"). Due to its rarity, there are currently no evidence-based therapeutic guidelines available. For their development, multicenter studies are required.

MGMT activity in mucosal epithelium and squamous cell carcinoma of the head and neck.

UNLABELLED: Smoking and alcohol abuse cause squamous cell carcinoma of the head and neck (SCCHN) through smoke-induced mutations, which are counteracted by O(6)-methylguanine-DNA methyltransferase (MGMT). This study aimed at elucidating the role of MGMT in SCCHN and its precursor lesions (SIN). MGMT was also determined in the normal mucosa (NM) and blood lymphocytes (PBLCs). RESULTS: a) MGMT was lower in NM than in PBLCs. b) Smoking reduced MGMT in NM but had no effect in PBLCs. c) MGMT activity increased in the sequence NM

Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy.

Reports of decreased serum 25-hydroxyvitamin D (25-OHD) and altered bone metabolism associated with antiepileptic drug (AED) treatment are inconsistent and predominantly restricted to adults. In this cross-sectional observational study, the aim was to evaluate the influence of AED treatment on vitamin D status and markers of bone turnover in children with epilepsy. In 38 children taking AEDs and 44 healthy control subjects, blood samples were collected to determine the levels of serum 25-OHD, intact parathyroid hormone (iPTH), calcium (Ca), phosphate (P), bone alkaline phosphatase (BAP), osteocalcin (OC) and C terminal telopeptide of type I collagen (ICTP). More than 75% of the patients were vitamin D deficient (serum 25-OHD<20 ng/mL) and 21% of the patients had an insufficient vitamin D status (serum 25-OHD=20-30 ng/mL). In the patients, the serum levels of OC (p = 0.002) and BAP (p < 0.001) were significantly increased, but ICTP (p = 0.002) concentrations were significantly decreased compared with the control group. When patients where divided into two groups according to their medication (mono- or polytherapy), significantly lower 25-OHD (p = 0.038) and ICTP (p = 0.005) levels and elevated BAP (p = 0.023) concentrations were found in patients under polytherapy. An association between 25-OHD and the measured bone markers could not be determined. Our results indicate that the prevalence of vitamin D deficiency in epilepsy patients under AED treatment is high, especially under polytherapy, and alteration markers of bone formation and resorption suggests an accelerated skeletal turnover. The routine monitoring of serum 25-OHD and vitamin D supplementation on an individual basis should be considered.

Analysis of ploidy in hypopharyngeal cancer by laser scanning cytometry on fine needle aspirate biopsies.

AIM: To test laser scanning cytometry (LSC) for the analysis of ploidy in squamous cell carcinoma of the hypopharynx (SCCH) and to develop a routine application for minimal samples such as fine needle aspirate biopsies (FNABs). METHODS: From 11 individuals 30 FNABs of primary tumors (n=11) and lymphatic metastases of SCCH (n=11) and non-metastatic lymph nodes (n=8) are analyzed by LSC. This microscope based instrument scans the cells after immobilization on a glass slide and after double staining of cytokeratin and DNA. The location of each cell is stored with the fluorescence data. Therefore the morphology of every cell can be documented by re-staining with H & E; and re-localization on the slide. Additionally, aliquots are Feulgen-stained for image cytometry in 8 specimens. RESULTS: The diploid reference peak is identified taking leukocytes as internal standard. The DNA-index of the carcinoma cells ranges from 0.4 to 3.8. Comparison with image cytometry shows good correlation (r=0.89). CONCLUSION: LSC provides a reliable and objective way to determine the ploidy of SCCH pre-operatively. Colour figures can be viewed on http://www.esacp.org/acp/2003/25-2/gerstner.htm.