ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

[Statement on the lower age limit for outpatient adenotomies and tonsillotomies]. / Stellungnahme zur Altersuntergrenze bei der ambulanten Durchführung von Adenotomien und Tonsillotomien.

At the beginning of 2023, there have been significant changes to the regulations for outpatient surgery in Germany, which were set out in a trilateral self-administration agreement between the umbrella association of statutory health insurance companies, the German Hospital Association and the Federal Association of Statutory Health Insurance Physicians. Among other things, a catalog stated circumstances under which an operation should not be carried out on an outpatient basis or should only be carried out with doubt. This catalog explains the patient's age: up to the first year of life, inpatient performance of a service can be justified. This formulation in itself means that children from one year of age on should regularly undergo outpatient surgery.In the german scientific societies for otolaryngology, head and neck surgery as well as for anesthesiology and intensive care medicine, doubts arose as to whether this age limit could also be scientifically justified for operations in the throat such as adenotomy or tonsillotomy.A search was carried out in international guidelines and in the international literature and the statements were evaluated. The results of this literature search were discussed with representatives of the Pediatric Otorhinolaryngology Working Group (AG PädHNO) of the German Society for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) and the scientific working group for pediatric anesthesia (WAKKA) of the German Society for Anesthesiology and Intensive Care Medicine (DGAI) in conferences.The consensus revealed that a strict age limit of the first year of life is not appropriate for the outpatient performance of adenotomies and tonsillotomies. First of all, specifying a strict age limit is questionable because, regardless of age, a number of other medical and social factors influence the responsible performance of outpatient operations. Furthermore, the age limit of one year is not considered appropriate in view of literature, guidelines and practical experience in the international area. The assessment of the literature and the consideration of the implementation in the international area make an age limit in the range of 2-3 years seem more appropriate.This review provides the responsible doctors with a variety of insights, aspects and arguments so that they can make their decision to carry out these operations on an outpatient or inpatient basis appropriately and responsibly.

[Management of Primary Ciliary Dyskinesia]. / Management der Primären Ciliären Dyskinesie.

Primary Ciliary Dyskinesia (PCD, MIM 242650) is a rare, hereditary multiorgan disease characterized by malfunction of motile cilia. Hallmark symptom is a chronic airway infection due to mucostasis leading to irreversible lung damage that may progress to respiratory failure. There is no cure for this genetic disease and evidence-based treatment is limited. Until recently, there were no randomized controlled trials performed in PCD, but this year, data of the first placebo-controlled trial on pharmacotherapy in PCD were published. This cornerstone in the management of PCD was decisive for reviewing currently used treatment strategies. This article is a consensus of patient representatives and clinicians, which are highly experienced in care of PCD-patients and provides an overview of the management of PCD. Treatments are mainly based on expert opinions, personal experiences, or are deduced from other lung diseases, notably cystic fibrosis (CF), COPD or bronchiectasis. Most strategies focus on routine airway clearance and treatment of recurrent respiratory tract infections. Non-respiratory symptoms are treated organ specific. To generate further evidence-based knowledge, other projects are under way, e. g. the International PCD-Registry. Participating in patient registries facilitates access to clinical and research studies and strengthens networks between centers. In addition, knowledge of genotype-specific course of the disease will offer the opportunity to further improve and individualize patient care.

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

[Diagnostics and management of choanal atresia]. / Diagnostik und Management der Choanalatresie.

Choanal atresia is a rare malformation that represents a special challenge. While bilateral choanal atresia usually needs to be surgically treated within a few days of birth, the intervention for one-sided choanal atresia can be postponed for years. Treatment planning requires adequate imaging (CT or MRI), which also serves to exclude other skull base malformities. Surgical treatment currently focuses on transnasal endoscopic techniques. Simultaneous resection of the parts of the vomer involved in the atresia seems to be important surgical success. Postoperative stenting is still controversially discussed. Postoperative application of corticosteroid nasal sprays and saline nasal rinsing for several weeks is of great importance. Due to the rarity of the diagnosis, the absence of prospective randomized controlled trials does not allow definitive statements regarding the optimal surgical technique or stenting.

[Supraglottoplasty for pediatric laryngomalacia : Results from 71 cases]. / Supraglottoplastik bei kindlicher Laryngomalazie : Ergebnisse aus 71 Fällen.

Laryngomalacia is the most common cause of stridor in infants. The stridor is caused by an inward collapse of supraglottic structures during inspiration resulting in an inspiratory stridor. The exact etiology still remains unclear. The surgical procedure of choice for laryngomalacia is supraglottoplasty. From 2009 to 2016 a total of 71 children were treated by supraglottoplasty in the department for pediatric otorhinolaryngology of the Stuttgart Hospital. The indications for supraglottoplasty were laryngomalacia with severe inspiratory stridor, oxygen desaturation, suprasternal or chest retraction, feeding difficulties and/or failure to thrive. The overall success rate was 86 % but there was a clear difference between children with isolated laryngomalacia and the group with associated comorbidities. The success rate for patients with isolated laryngomalacia was 98 % and for patients with associated comorbidities 57 %. Supraglottoplasty is therefore an effective and safe treatment for symptomatic laryngomalacia and a reduction in the success rate showed a clear correlation with the presence of congenital comorbidities.

[Rhinosinusitis in cystic fibrosis]. / Rhinosinusitis bei Mukoviszidose

In cystic fibrosis (CF) mucociliary clearance of the entire respiratory system is impaired. This allows pathogens, such as Pseudomonas aeruginosa to persist and proliferate, which by progressive pulmonary destruction causes 90 % of premature deaths due to this inherited disease. The dramatic improvement in life expectation of patients due to intensive therapy has resulted in the inevitable but variably expressed sinonasal involvement coming into the clinical and scientific focus. Thereby, almost all CF patients reveal sinonasal pathology and many suffer from chronic rhinosinusitis. Recently, the sinonasal niche has been recognized as a site of initial and persistent colonization by pathogens. This article presents the pathophysiological background of this multiorgan disease as well as general diagnostic and therapeutic standards. The focus of this article is on sinonasal involvement and conservative and surgical options for treatment. Prevention of pathogen acquisition is an essential issue in the otorhinolaryngological treatment of CF patients.

[Pediatric radiology in oto-rhino-laryngology]. / Pädiatrische Radiologie in der Hals-Nasen-Ohren-Heilkunde.

Head and neck diseases in children and adolescents pose special diagnostic and differential diagnostic challenges to ENT surgeons as well as to radiologists. Both disciplines have to adapt the latest radiological and interventional technologies to the needs of the paediatric patient in order to enable a minimally invasive but successful diagnostic procedure. High quality sonography by an experienced examiner often is the only imaging technique that is required in children and adolescents. Radiographs are rarely indicated in paediatric head and neck diseases. MRI, compared to computed tomography, has the advantage of the lack of radiation exposure. Additionally, because of current advances in high resolution techniques to delineate very small details or in visualization of different tissue characteristics it has become an integral part of the pre-and post-operative imaging. However, children should not be denied an adequate diagnostic procedure even if it includes a sedation, an intervention or an exposure to radiation. The responsible use of the diagnostic options under consideration of the therapeutic consequences is essential. It is most likely to be successful in a close interdisciplinary cooperation of paediatric ENT specialists and radiologists as well as paediatric anaesthesiologists in selected cases. Although benign diseases predominate in children and adolescents, the possibility of a malignancy has to be considered in case of atypical clinical and radiological findings. In many of these young patients the outcome and the probability of survival are directly connected to the initial diagnostic and therapeutic strategies, which should therefore be in accordance with the current guidelines in oncological therapy studies. Our collection of clinical cases consists of representative examples of useful diagnostic approaches in common and age specific diagnoses as well as in rare diseases and malformations. It shows the significance of a special knowledge in embryology and normal postnatal development for the differentiation of normal variants from pathological findings. Only in considering the results of imaging studies in their clinical context, we may succeed in detecting a syndrome behind a single malformation or in adequately caring for a patient with a chronic disease such as cystic fibrosis.

[Middle ear salivary gland choristoma related to branchio-oto-renal syndrome diagnosed by array-CGH]. / Speicheldrüsenchoristom im Mittelohr bei mittels Array-CGH diagnostiziertem branchiootorenalem Syndrom.

Branchio-oto-renal (BOR) syndrome is characterized by ear malformations associated with sensorineural or mixed hearing loss. In addition, preauricular tags, preauricular pits, branchial cleft fistulas and cysts, as well as renal dysplasia are seen. A genetic mutation on chromosome 8, either autosomal dominantly inherited or occuring as a spontaneous mutation, is the cause in the majority of cases. Using array-based comparative genomic hybridization (CGH), it is possible to detect even the smallest genetic changes. Salivary gland choristoma in the middle ear is very rare. Surgical removal and histological clarification are required.

[Acute otitis media in children: antibiotic therapy or watchful waiting?]. / Akute Otitis media bei Kindern: Antibiose oder "watchful waiting"?

Acute otitis media is one of the most common infections in childhood and the options of therapy have been examined in numerous studies. Nevertheless, there are controversial opinions regarding the question whether antibiotic therapy makes sense. This is proved through the many different ways that the primary treatment of the middle ear infection is handled throughout the international community. This work gives an overview of the current knowledge and based on these results gives practical recommendations to assist with the diagnosis and treatment of the individual patients.

[What can blind patients see in daily life with the subretinal Alpha IMS implant? Current overview from the clinical trial in Tübingen]. / Was können blinde Patienten mit dem subretinalen Alpha-IMS-Implantat im Alltag sehen? Aktuelle Übersicht aus der Tübinger klinischen Studie.

The subretinal visual implant is a scientific research approach to restore partial vision in end-stage hereditary retinal diseases by replacing the function of the degenerated photoreceptors by microelectronic chips. In a clinical trial in Tübingen these implants were tested on voluntary blind patients. By using the implants in daily living the patients reported valuable visual information. The subretinal microchip mediates subjectively useful visual information in near as well as in distant vision.

[Laryngomalacia. When does surgery make sense?]. / Laryngomalazie. Wann ist eine Operation sinnvoll?

The most common cause of stridor in newborns is instability of the upper larynx, called laryngomalacia. In approximately 10% of children normal development is impaired. The diagnostics and therapy must follow a clear plan that is also comprehensible to the parents. The obstruction should be localized endoscopically, the anatomical characteristics determined, and the surgical possibilities evaluated. Additional pathological changes of the upper airway (e.g., vocal fold paresis) need to be excluded. Surgery for laryngomalacia, called supraglottoplasty, allows reduction of excess mucus, transectioning of aryepiglottic folds that are too short, and in some cases epiglottic fixation to the base of the tongue. In extreme cases tracheotomy is unavoidable. Surgery is only recommended for severe cases; when carried out correctly according to the medical indications, the success rate is over 90%.

Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links.

Mechano-electrical transduction (MET) in the stereocilia of outer hair cells (OHCs) was studied in newborn Wistar rats using scanning electron microscopy to investigate the stereociliar cross-links, Nomarski laser differential interferometry to investigate stereociliar stiffness and by testing the functionality of the MET channels by recording the entry of fluorescent dye, FM1-43, into stereocilia. Preparations were taken from rats on their day of birth (P0) or 1-4 days later (P1-P4). Hair bundles developed from the base to the apex and from the inner to outer OHC rows. MET channel responses were detected in apical coil OHCs on P1. To study the possible recovery of MET after disrupting the cross-links, the same investigations were performed after the application of Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and allowing the treated samples to recover in culture medium for 0-20 h. We found that the structure and function were abolished by BAPTA. In P0-P1 samples, structural recovery was complete and the open probability of MET channels reached control values. In P3-P4 samples, complete recovery only occurred in OHCs of the outermost row. Although our results demonstrate an enormous recovery potential of OHCs in the postnatal period, the structural component restricts the potential for therapy in patients.

Image quality analysis to reduce dental artifacts in head and neck imaging with dual-source computed tomography.

PURPOSE: Important oropharyngeal structures can be superimposed by metallic artifacts due to dental implants. The aim of this study was to compare the image quality of multiplanar reconstructions and an angulated spiral in dual-source computed tomography (DSCT) of the neck. MATERIALS AND METHODS: Sixty-two patients were included for neck imaging with DSCT. MPRs from an axial dataset and an additional short spiral parallel to the mouth floor were acquired. Leading anatomical structures were then evaluated with respect to the extent to which they were affected by dental artifacts using a visual scale, ranging from 1 (least artifacts) to 4 (most artifacts). RESULTS: In MPR, 87.1 % of anatomical structures had significant artifacts (3.12 +/- 0.86), while in angulated slices leading anatomical structures of the oropharynx showed negligible artifacts (1.28 +/- 0.46). The diagnostic growth due to primarily angulated slices concerning artifact severity was significant (p < 0.01). CONCLUSION: MPRs are not capable of reducing dental artifacts sufficiently. In patients with dental artifacts overlying the anatomical structures of the oropharynx, an additional short angulated spiral parallel to the floor of the mouth is recommended and should be applied for daily routine. As a result of the static gantry design of DSCT, the use of a flexible head holder is essential.

Comparison of imaging techniques in the diagnosis of bridging bronchus.

Bridging bronchus (BB) is a rare, congenital bronchial anomaly that is frequently associated with congenital cardiac malformations, especially left pulmonary artery sling. It represents an anomalous bronchus to the right originating from the left main bronchus. Discrimination from other bronchial anomalies is important, since BB is frequently associated with bronchial stenoses due to abnormal cartilage rings. This case study describes the findings of bronchoscopy, bronchography and multidetector computed tomography (MDCT) in three patients. Bronchoscopy was helpful in the description of the severity and length of bronchial stenoses. However, it was not possible to establish a diagnosis of BB based on this method in two patients, since it is difficult or even impossible to differentiate the bifurcation from the pseudocarina. It was not possible to establish the correct diagnosis in all patients based on bronchography or MDCT. MDCT was able to depict the relationship of bronchial and vascular structures, which is particularly important in patients with pulmonary artery sling. Multidetector computed tomography is preferable to bronchography as it is less invasive and due to its short acquisition time it can be performed in children with severe respiratory disease. In the current authors' experience, detection of cartilage rings still requires flexible bronchoscopy.

[What makes "Head-and-Neck-Cancers" recur: Tumorinvasion "revisited"]. / Gibt es tumorbiologische Besonderheiten, die ein bevorzugtes Auftreten von Rezidiven bei Kopf-Hals-Tumoren begünstigen: Tumorinvasion "revisited".

Head and neck squamous cell carcinomas (HNSCC) are common cancers with a relatively poor prognosis. Locoregionale recurrences are regularly encountered and associated with a detrimental outcome. Studies of the last few years report that not only tumor staging and grading influence locoregional control but also histologic and biological markers. One such histological marker is coined "worst pattern of invasion". It describes a histologic growth pattern consisting of invading tumor cell islands and strands that are dispatched from the invasion front (POI typ 4 and 5). Additional features of invasion are perineural invasion and extracapsular nodal extension. Besides histological markers there are molecular characteristics that include the expression of gene families involved in extracellular matrix degradation. The data suggest that head and neck cancers differ with respect to their invasive growth capacity and thus their ability to generate locoregionale recurrences. It appears that locoregionale control is a consequence of this growth pattern. This may explain, why in recent clincial studies the prognostic marker "pattern-of-invasion" outweights even such well established prognosticators such as "surgical margins".

Suprastomal tracheal stenosis after dilational and surgical tracheostomy in critically ill patients.

We have previously reported cases of severe suprastomal stenosis after tracheostomy. In this observational study we investigated the occurrence of suprastomal stenosis as a late complication. Patients with persistent tracheostomy after intensive care underwent an endoscopic examination of tracheostoma, larynx and trachea. A percutaneous dilational tracheostomy was employed in 105 (71.9%) and surgical tracheostomy in 41 (28.1%) of the cases (n = 146). The incidence of severe suprastomal stenosis (grade II > 50% of the lumen) was 23.8% (25 of 105) after dilational tracheostomy and 7.3% (3 of 41) after surgical tracheostomy (p = 0.033). Age, gender, underlying disease, ventilation time, and swallowing ability were not significantly associated with the tracheal pathology. This study suggests that dilational tracheostomy is associated with an increased risk of severe suprastomal tracheal stenosis compared to the surgical technique.