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Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs ∼US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age ≤40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care. [Cancer Res 2009;69(8):3650–6]

Supplementary Table 1 Legends and References from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Supplementary Table 1 from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Other Supporting Colleagues from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Supplementary Table 2 from Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Zusammenfassung Anamnese Eine 21-jährige Patientin erlitt im Rahmen eines Unfalls ein schweres Strangulationstrauma. Stridor und Dyspnoe setzten erst mit Verzögerung ein und führten zur Notfallintubation. Befund Im Rahmen der klinischen Untersuchung zeigten sich Strangulationsmarken und ein Emphysem der Halsweichteile. Die Computertomographie erhärtete den Verdacht auf einen Abriss der Trachea vom Kehlkopf und ergab eine Fehllage des Beatmungstubus. Diagnose Bei der weiteren chirurgischen Exploration zeigte sich eine komplette laryngotracheale (krikotracheale) Separation. Therapie und Verlauf Nach initialer Nottracheotomie wurden in einem zweizeitigen operativen Verfahren die krikotracheale Reanastomosierung und die Retracheostomie durchgeführt. Schlussfolgerung Laryngotracheale Separationen stellen den höchsten Schweregrad der Kehlkopfverletzungen dar und sind mit einer hohen Mortalität behaftet. Im geschilderten Fall überlebte die Patientin und konnte, trotz beidseitiger Rekurrensparese, dekanüliert entlassen werden.

ZusammenfassungDieser Übersichtsartikel stellt eine Zusammenstellung seltener Erkrankungen der Orbita dar. Es werden angeborene Fehlbildungen und strukturelle Läsionen, entzündliche Erkrankungen, gutartige und bösartige epitheliale sowie nicht epitheliale Tumoren erörtert. Da in der Orbita zahlreiche Gewebetypen auf engstem Raum beieinanderliegen, kommen dort besonders viele Erkrankungen vor, sodass der Vollständigkeit und dem Tiefgang bei den einzelnen Abhandlungen natürliche Grenzen gesetzt sind. Die Kapitel beinhalten eine Übersicht über das jeweilige klinische Erscheinungsbild, wichtige Stichpunkte zur Diagnostik, Therapie und gegebenenfalls zur Prognose der Erkrankung. Dabei wurde versucht, die besonders charakteristischen Merkmale der einzelnen Erkrankungen herauszuarbeiten, sodass trotz der kurzen Darstellung die relevanten Aspekte enthalten sind.

Most orbital diseases are rarely diagnosed in the clinic. Because the consequences for the eye can be severe, it is important to recognize the signs of orbital disease early in order to initiate the correct diagnostic and therapeutic steps in good time. This article presents the basics of the systematics, diagnostics and therapy of orbital diseases in preparation for the specialist examination for ENT medicine. Some orbital diseases are typical manifestations of systemic diseases (e. g. Graves' disease) or typical complications of diseases in the vicinity of the orbit (e. g. orbital complications from inflammatory or tumorous sinus diseases). The diseases of the lacrimal system and the eyelids as well as their therapy are closely related to the diseases of the orbit. Basically, it can be said that the diagnosis and therapy of orbital diseases should always be carried out on an interdisciplinary basis, whereby the involvement of the ophthalmologist is of particular importance.

The tearing eye (epiphora) is deemed to be the leading symptome of efferent tear duct stenosis. Nevertheless, epiphora might be caused by ocular surface pathologies or even intraocular diseases. A distinguished anamnesis and sufficient clinical examination is most meaningful for the differential diagnostic distinction. Therapy is based on pathologic changes. In case of ocular surface disease, a suitable tear substitution and antiinflammatory approach is mandatory. Multifarious triggers have to be considered as well. Addressing tear film distribution, suitable oculoplastic surgery is required. Efferent tear duct stenosis necessitates surgical treatment as the level of suffering is often very high and acute exacerbations may develop. Besides recanalization, anastomosing techniques represent the available therapeutic principles. Possible surgical approaches offer a great variety and many influencing factors navigate therapy decisions. This part of the review comments on the most important therapeutic approaches for lacrimal apparatus diseases.

The lacrimal apparatus is a part of the ocular adnexa preserving ocular surface homoeostasis and therefore enabling sufficiant visual functioning. Tear producting tissues, eyelids and efferent tear ducts operate as one functional unit. Pathologic changes consist of inflammatory diseases, congenital disorders, degenerations and neoplasia. Common to all these conditions is a potential impairment of the ocular integrity as well as a substantial degree of suffering for the affected patients. This review reflects basics of the anatomy, physiology, and diagnostics of the lacrimal apparatus.

A 21-year-old female was injured by accidental strangulation. Dyspnea and stridor occurred with delay, and led to emergency intubation.Physical examination showed strangulation marks and neck emphysema. Computed tomography confirmed laryngotracheal separation and revealed misplacement of the ventilation tube.Further surgical exploration revealed complete laryngotracheal (cricotracheal) separation.After initial emergency tracheotomy, cricotracheal reanastomosis was achieved by a two-stage surgical approach.Laryngotracheal separation is associated with high mortality. In the case presented herein, the patient survived and was discharged from hospital without a tracheostomy tube despite bilateral recurrent laryngeal nerve palsy.ANAMNESE: Eine 21-jährige Patientin erlitt im Rahmen eines Unfalls ein schweres Strangulationstrauma. Stridor und Dyspnoe setzten erst mit Verzögerung ein und führten zur Notfallintubation.Im Rahmen der klinischen Untersuchung zeigten sich Strangulationsmarken und ein Emphysem der Halsweichteile. Die Computertomographie erhärtete den Verdacht auf einen Abriss der Trachea vom Kehlkopf und ergab eine Fehllage des Beatmungstubus.Bei der weiteren chirurgischen Exploration zeigte sich eine komplette laryngotracheale (krikotracheale) Separation.Nach initialer Nottracheotomie wurden in einem zweizeitigen operativen Verfahren die krikotracheale Reanastomosierung und die Retracheostomie durchgeführt.Laryngotracheale Separationen stellen den höchsten Schweregrad der Kehlkopfverletzungen dar und sind mit einer hohen Mortalität behaftet. Im geschilderten Fall überlebte die Patientin und konnte, trotz beidseitiger Rekurrensparese, dekanüliert entlassen werden.

Most orbital diseases are rarely diagnosed in the clinic. Because the consequences for the eye can be severe, it is important to recognize the signs of orbital disease early in order to initiate the correct diagnostic and therapeutic steps in good time. This article presents the basics of the systematics, diagnostics and therapy of orbital diseases in preparation for the specialist examination for ENT medicine. Some orbital diseases are typical manifestations of systemic diseases (e. g. Graves' disease) or typical complications of diseases in the vicinity of the orbit (e. g. orbital complications from inflammatory or tumorous sinus diseases). The diseases of the lacrimal system and the eyelids as well as their therapy are closely related to the diseases of the orbit. Basically, it can be said that the diagnosis and therapy of orbital diseases should always be carried out on an interdisciplinary basis, whereby the involvement of the ophthalmologist is of particular importance.

The tearing eye (epiphora) is deemed to be the leading symptome of efferent tear duct stenosis. Nevertheless, epiphora might be caused by ocular surface pathologies or even intraocular diseases. A distinguished anamnesis and sufficient clinical examination is most meaningful for the differential diagnostic distinction. Therapy is based on pathologic changes. In case of ocular surface disease, a suitable tear substitution and antiinflammatory approach is mandatory. Multifarious triggers have to be considered as well. Addressing tear film distribution, suitable oculoplastic surgery is required. Efferent tear duct stenosis necessitates surgical treatment as the level of suffering is often very high and acute exacerbations may develop. Besides recanalization, anastomosing techniques represent the available therapeutic principles. Possible surgical approaches offer a great variety and many influencing factors navigate therapy decisions. This part of the review comments on the most important therapeutic approaches for lacrimal apparatus diseases.

The lacrimal apparatus is a part of the ocular adnexa preserving ocular surface homoeostasis and therefore enabling sufficiant visual functioning. Tear producting tissues, eyelids and efferent tear ducts operate as one functional unit. Pathologic changes consist of inflammatory diseases, congenital disorders, degenerations and neoplasia. Common to all these conditions is a potential impairment of the ocular integrity as well as a substantial degree of suffering for the affected patients. This review reflects basics of the anatomy, physiology, and diagnostics of the lacrimal apparatus.

Background The cardinal symptom of lacrimal stenosis is epiphora and a subjective high level of discomfort due to continuous dacryorrhea. Objective The aim of the current paper is to present a structured review of common diagnostic and therapeutic strategies for lacrimal stenosis. Materials and methods The most important diagnostic and therapeutic approaches are analysed using the existing literature and by reporting the authors' own experiences. Results A detailed patient history is crucial for diagnosis of lacrimal disorders. Precise inspection and palpation of the lacrimal and lid region may confirm lacrimal stenosis. Examinations of tear production, tear quality and the properties of the ocular surface are helpful. The most important diagnostic tool is lacrimal duct probing and syringing. Therapy is guided by underlying pathologies. Treatment of congenital lacrimal stenosis follows a staged concept. Epiphora in adults without signs of dacryocystitis should be treated with dacryoendoscopy. Dacryoendoscopy is also a therapeutic option for chronic dacryocystitis, but dacryocystorhinostomy may also be required. Lacrimal trauma should be reconstructed rapidly after the incident by lacrimal intubation. Neoplasia of the lacrimal excretory system requires histological classification to enable multidisciplinary management. Conclusion Basic ophthalmologic diagnostics are complemented by special symptom-based examinations. Due to ongoing improvement of available diagnostic and therapeutic options, patients' care is becoming increasingly individualised.

BACKGROUND AND AIM The lacrimal system (LS) crosses regions of ocular adnexa, the nose, and the paranasal sinuses. Surgery of disorders requires a targeted ophthalmologic and otolaryngologic examination. Since 2013, an Interdisciplinary Conference on Lacrimal System Disorders (ICLSD) has existed at the University Hospital Halle. First results of our experiences with this cooperation between ophthalmic and ENT surgeons are presented. METHODS In a retrospective study at the Department of Ophthalmology, University Hospital Halle, all patients aged 22-80 years (n = 43, 10 with bilateral manifestation; mean age 65.1 years) having had a consultation in ICLSD between February 2013 and May 2015 were analyzed. Thereby, 53 LS were included in the descriptive evaluation. RESULTS The main relevant pathology in terms of ophthalmologic manifestation was chronic dacryocystitis and its complications (n = 42), whereas nasal septum deviation (n = 11) and chronic rhinosinusitis (n = 10) were the most frequent otorhinolaryngologic pathologies. Prior to consultation, ENT (n = 34) and/or ophthalmic surgery (n = 40) had been performed. During ICLSD, an individualized therapeutic regime for each patient was developed. Surgery was required in 43 out of 53 LS. Of these, 32 were mainly ophthalmic, 11 mainly ENT interventions. At the time of evaluation (median 3 months; range 1 to 24 months), 29 out of 38 patients (76.3 %) were free of complaints. CONCLUSION Since 2013, competences of ophthalmic and ENT surgeons have been integrated in ICLSD for advanced diagnosis and therapy of lacrimal disorders at the University Hospital Halle. Encouraging functional results are shown in this study, as most patients have had a long and complicated history of lacrimal system disorders. ICLSD enables interdisciplinary patient care.

There is currently no standardized ear, nose, and throat (ENT) clinical examination for patients with sleep-disordered breathing (SDB). As a result, there are large inter-individual differences in the examinations due to an inadequate estimation of the relevance of certain anatomic sites. We aimed to identify which examinations/dynamic tests are considered most relevant by German ENT physicians. A questionnaire was designed, evaluating 23 anatomic sites/dynamic tests of the upper aero-digestive tract. The questionnaire was sent to all German ENT departments (n = 153), including universities and other tertiary or secondary referral centers, by postal mail. In addition, almost all private ENT specialists registered with the German professional association (n = 2496) were contacted via e-mail. Participants assessed how often they examined the sites/dynamic tests, subjective importance, and the impact on the therapeutic procedure. A mean score of relevance (mSOR) was generated (minimum score 1; maximum score 75) from these three items. The response rate for hospitals was 58.8 %; while, it was 4.1 % for ENT specialists in private practice. Therefore, the total response rate was 7.3 %. Of the 23 assessed items, some showed a high overall relevance, such as the tonsils (mSOR 64.75), webbing (mSOR 58.14), uvula (mSOR 55.12), or tongue base (mSOR 53.99). Other examinations, such as simulated snoring (mSOR 19.34) or the Mueller maneuver (mSOR 18.98), were estimated as less relevant. Our data reflect the assessment of German otorhinolaryngologists on the clinical examination of SDB patients. The results should be considered as a basis for compiling a standardized procedure.

Drug-induced sleep endoscopy (DISE) and simulated snoring (SimS) are performed as part of the diagnostic procedure in patients with suspected sleep-disordered breathing (SDB). Despite both techniques frequently performed, they have rarely been evaluated yet in terms of agreement of the obtained results. Both diagnostic procedures were performed consecutively in 40 patients with SDB and documented identically. The obtained data were analysed with respect to the agreement of both procedure at different levels of the oropharynx as well as different patterns of obstruction and vibration. The anterior-posterior collapsibility of the soft palate/uvula revealed a moderate agreement between SimS and DISE (κ = 0.42; 95 % CI 0.22-0.63). The dorsal shift of the tongue base agreed moderate for patients with an AHI below 10 (κ = 0.47) and above 25 (κ = 0.44) between SimS ad DISE. The lateral and circular pharyngeal collapsibility at velum and tongue base level did not agree between SimS and DISE, was higher for DISE and could be partially reversed by mandibular protrusion. Collapse patterns of the soft palate and uvula can be induced by SimS and resemble the patterns induced by DISE. The dorsalization of the tongue base can be simulated to a lower extent by SimS. Lateral and circular patterns of collapse at the upper and lower oropharynx induced by DISE do not seem to be simulated by SimS. SimS seems to be an additional method to screen the collapsibility of the soft palate and uvula prior to DISE.

Snoring sounds are discussed to contain acoustic information about their geneses. Nocturnal snoring can easily be recorded acoustically but it is difficult to visually verify its genesis. Contrary, snoring patterns induced by drug-induced sleep endoscopy (DISE) can be visually differentiated. The aim of the study was to classify patterns of obstructions and vibration during DISE and to evaluate acoustic characteristics between these different patterns of snoring.DISE was performed in 41 male patients with sleep-disordered breathing. The recorded video sequences (n = 108) were classified visually at a mute mode in different patterns of snoring (velar, velar obstructive, tonsillar, post-apnoeic). The sound tracks of these subgroups were analysed and compared with regard to the parameters sound pressure level, loudness, sharpness, roughness, fluctuations strength and centre frequency.Obstructive snoring patterns revealed a higher loudness than non-obstructive patterns (25 sone). Velar snoring showed more roughness (150 cAsper) than tonsillar and post-apnoeic snoring and revealed the lowest centre frequency (3000 Hz) of all patterns. Tonsillar snoring presented the highest sharpness (1.6 acum) whereas post-apnoeic snoring revealed the largest fluctuation strength (50 cVacil).Different snoring patterns induced by DISE can be classified visually, and an approach to differentiate them acoustically by means of psychoacoustic analyses is demonstrated. On the basis of these results, nocturnal snoring might also be differentiated by psychoacoustic algorithms which could be implemented in acoustic polygraphic screening devices in the future.

To evaluate the feasibility and hearing outcome of a biocompatible degradable dexamethasone releasing implant for continuous drug delivery to the round window membrane in patients with idiopathic sudden sensorineural hearing loss (ISSHL) and insufficient recovery after systemic high dose glucocorticoid therapy.Five patients with profound or moderate-to-severe hearing loss after systemic high-dose prednisolone for ISSHL received local salvage therapy with a controlled release dexamethasone implant in the middle ear.Pieces of a sterile rod shaped poly(D,L-lactide-co-glycolide) PLGA polymer matrix containing a total of 0.7 mg dexamethasone, which is approved for intravitreal use were implanted into the round window niche.Intraoperative handling and feasibility and hearing recovery as measured by change in pure tone threshold, final word recognition score, and categories of improvement were evaluated.The implants were surgically placed without major difficulties. The mean hearing threshold significantly improved at follow up by 31 ± 31 dB HL (from 94 ± 27 to 63 ± 36 dB HL; p0.05). Two of five patients recovered completely. One patient showed partial hearing recovery with serviceable hearing.Although no drugs are currently approved for local therapy of inner ear disorders, there is increasing evidence that intratympanic glucocorticoids are effective as salvage therapy in ISSHL. The present study has shown encouraging results with a biodegradable polymer delivery system, demonstrating the translation of preclinical studies with controlled drug delivery into clinical practice.

Persistent tracheopharyngeal (TPF) and tracheo-oesophageal (TEF) fistulas after laryngectomy create a therapeutic challenge. The current classification of TPFs and TEFs is based on clinical experience without detailed anatomical information. In this study, casts of TPFs/TEFs were obtained from 16 patients; these were the first steps in manufacturing customised prostheses. Fistulas were classified according to the shape and dimension of the tracheopharyngeal and tracheo-oesophageal silicone casts and prostheses as well as on epithetic requirements. Four different types of fistulas were classified: Type A, a fistula with a straight axis between the neopharynx and oesophagus; Type B, a fistula with a stenosis of the neopharynx but a straight axis; Type C, the axis between the neopharynx and oesophagus is flexed anteriorly; and Type D, neighbouring structures are absent creating a large defect. This classification system might improve the manufacturing processes of customised prostheses in individual cases with challenging tracheopharyngeal and tracheo-oesophageal fistulas.

Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes (SDHx). Mutation analysis for all 3 costs ∼US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC, and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB, 14.2% SDHC, and 51.4% SDHD. Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age ≤40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care. [Cancer Res 2009;69(8):3650–6]