Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study.

BACKGROUND: Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] with or without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus the EXTREME regimen in patients with R/M HNSCC. PATIENTS AND METHODS: Patients with HNSCC who had not received prior systemic treatment for R/M disease were randomized (2 : 1 : 1) to receive durvalumab 1500 mg every 4 weeks (Q4W) plus tremelimumab 75 mg Q4W (up to four doses), durvalumab monotherapy 1500 mg Q4W, or the EXTREME regimen (platinum, 5-fluorouracil, and cetuximab) until disease progression. Durvalumab efficacy, with or without tremelimumab, versus the EXTREME regimen in patients with PD-L1-high tumors and in all randomized patients was assessed. Safety was also assessed. RESULTS: Durvalumab and durvalumab plus tremelimumab were not superior to EXTREME for overall survival (OS) in patients with PD-L1-high expression [median, 10.9 and 11.2 versus 10.9 months, respectively; hazard ratio (HR) = 0.96; 95% confidence interval (CI) 0.69-1.32; P = 0.787 and HR = 1.05; 95% CI 0.80-1.39, respectively]. Durvalumab and durvalumab plus tremelimumab prolonged duration of response versus EXTREME (49.3% and 48.1% versus 9.8% of patients remaining in response at 12 months), correlating with long-term OS for responding patients; however, median progression-free survival was longer with EXTREME (2.8 and 2.8 versus 5.4 months). Exploratory analyses suggested that subsequent immunotherapy use by 24.3% of patients in the EXTREME regimen arm contributed to the similar OS outcomes between arms. Grade 3/4 treatment-related adverse events (TRAEs) for durvalumab, durvalumab plus tremelimumab, and EXTREME were 8.9%, 19.1%, and 53.1%, respectively. CONCLUSIONS: In patients with PD-L1-high expression, OS was comparable between durvalumab and the EXTREME regimen. Durvalumab alone, and with tremelimumab, demonstrated durable responses and reduced TRAEs versus the EXTREME regimen in R/M HNSCC.

[Influence of exogenic factors on age-related hearing impairment]. / Einfluss exogener Faktoren auf Altersschwerhörigkeit

BACKGROUND: Age-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role. METHODS: A total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors. RESULTS: Significant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.

[Chronic polypous rhinosinusitis: Genesis, clinical picture, therapy and relapse rate--a retrospective study]. / Chronisch polypöse Rhinosinusitis: Genese, Klinik, Therapie und Rezidivrate--eine retrospektive Studie.

BACKGROUND: The prevalence of chronic polypous rhinosinusitis is high at 1-2%. In the present study, the predisposing factors for this condition, the clinical symptomatology, results of surgical interventions, significance of computed tomography diagnosis, as well as histology and post-operative therapy with steroids were investigated. METHODS AND RESULTS: A 15% stratified sample, made up of 194 post-paranasal sinus surgery patients of 5 surgical years was investigated. Above all, the eosinophil dominated type led to the formation of polyps. In the diagnosis of chronic polypous rhinosinusitis computed tomography is only sufficiently sensitive for the ethmoid bone. The complication rate was, with 4.6%, in the lower range of comparable pre-examinations. In addition, the 18% relapse rate in the patient population, of whom 49% had already been operated on once or several times, corresponds to a good result when compared at an international level. CONCLUSIONS: These data confirm that surgical experience and a consistent post-surgical treatment can reduce the relapse frequency of chronic polypous rhinosinusitis. This is indicated by the on average late occurrence of a relapse.

[The influence of the Tübingen soft palate plate and early cleft closure on swallowing and Eustachian tube function in children with Pierre Robin sequence]. / Früher Gaumenspaltverschluss und Tübinger Atmungsgaumenplatte : Mögliche Einflüsse auf die Tubenfunktion bei der Pierre-Robin-Sequenz.

CURRENT KNOWLEDGE: Children with Pierre Robin sequence (PRS) typically have difficulty with bolus transport and swallowing. Due to velopharyngeal insufficiency caused by the cleft palate, a high percentage of the children affected also have impaired Eustachian tube function. AIMS OF THE STUDY: In the literature, substantial information may be obtained on conductive hearing loss in PRS patients; however, no study has yet been performed to investigate whether wearing a soft palate plate and relatively early surgical cleft palate closure positively influence Eustachian tube function. In the present study this question was investigated. METHODS AND RESULTS: A total of 41 PRS children, 27 girls and 14 boys, were included in the study and were examined for hearing ability prior to and after surgical cleft palate closure. All of the children had been wearing a Tübingen soft palate plate until surgical cleft palate closure, which occurred at an age of 3-13 months (mean age 7.3 months). Based on data obtained prior to surgery by BERA, otoacoustic emissions and tympanometry, a hearing loss of more than 30 dB was diagnosed in 68.4% of the children. After 3-6 months, normal hearing ability was found in 70%. CONCLUSIONS: Wearing the Tübingen soft palate plate, and the improved swallowing function resulting from this, as well as early surgical cleft palate closure had a very positive impact on the hearing ability of the children included in the study.

Valproic acid-associated sialadenosis of the parotid and submandibular glands: diagnostic and therapeutic aspects.

Sialadenosis has been defined as a non-inflammatory, parenchymatous salivary gland disease causing recurrent, bilateral swelling of the salivary glands. As an adverse drug reaction of valproic acid, sialadenosis is very rare. To our knowledge, it has been reported only once in the world literature to date. We present herein the case of a patient with valproic acid-associated sialadenosis of both the parotid and submandibular glands. This appears to be the first published case of a patient who received surgical treatment. On light and electron microscopy of all the affected salivary glands, granular sialadenosis with predominantly moderate electron-dense secretory cytoplasmatic granules was observed. No relevant degenerative alterations were seen. There was no histological evidence of peripheral neuropathy of the nerve supply, leading to disordered activity of acinar cells by loss of neurosecretory granules. Lateral parotidectomy, performed under neuromonitoring control for safety reasons, is the treatment of choice for chronic recurrent parotitis that does not respond to conservative therapy, particularly if the cosmetic deformity is unacceptable to the patient. If the submandibular glands are involved, partial removal is recommended.

Complications of ultrasound guided percutaneous ethanol injection therapy of the thyroid and parathyroid glands.

OBJECTIVES: Since 1990 percutaneous ethanol injection therapy (PEIT) has been applied clinically as a treatment strategy for focal and diffuse autonomy of the thyroid, for cystic lesions and for ablation of parathyroid hyperplasia (PEA). There are some additional indications currently under consideration as for example inoperable advanced cancer of the thyroid. Since its inception PEIT and PEA have been regarded as an effective, inexpensive and low risk procedure. MATERIAL AND METHODS: We discuss mild and severe complications of these methods reported in literature and the first case so far of a severe ethyl toxic necrosis of the larynx and adjacent skin in a patient treated with PEIT by a radiologist. RESULTS: To date, no serious side effects have been reported in connection with these therapies. Some authors conclude that the side effects are in no way negligible and caution and routine should be exercised when using PEIT or PEA. Most complications have been transient in nature. The complication of ethyl toxic necrosis of the larynx was serious and the patient was admitted to hospital, treated conservatively and ten month later microsurgically. Voice thus could be restored to almost normal. CONCLUSIONS: PEIT for focal and diffuse autonomy, for cystic lesions of the thyroid, for thyroid hyperplasia and PEA for parathyroid hyperplasia are methods which are inexpensive and can be performed on an ambulatory base. These are the methods of choice if surgical intervention or radioiodine therapies are not practicable out of medical reasons or by refusal of the patient. The patient must be informed about possible severe complications. The examiner should have substantial experience in these methods. If complications an early opinion of a specialist is required.

[Quality control of audiologic results in a university phoniatric/pediatric institution. An example of expert assessment of occupational noise induced hearing loss]. / Qualitätskontrolle audiologischer Befunde einer universitären phoniatrisch/pädaudiologischen Einrichtung. Am Beispiel der Begutachtung der beruflichen Lärmschwerhörigkeit.

AIM: An investigation was made to reveal whether suspicion of occupational hearing loss can be satisfactorily determined by an otolaryngologist or workplace audiological measurement. These were compared with a formal audiometrical assessment at a university clinic. METHODS AND RESULTS: A retrospective study was made of 95 cases of noise induced hearing loss. A total of 78 individuals were investigated by an otolaryngologist and 70 by workplace audiometry. Using workplace audiometry, 27% of the tests showed a reduction in working capacity of at least 20%. In only five of these was a specialist opinion sought within a year. In 50%, this took longer than 5 years. A comparison of audiometric data from expert opinion revealed that there was conformity in only 47% with workplace audiometry and 48% with otolaryngologist testing. In some cases (27% workplace and 33% ENT practice), the measured hearing loss and calculation of disability exceeded that determined by the experts. CONCLUSIONS: The results of workplace audiometry demonstrated that hearing loss was frequently reported only after the workers had received a disability of at least 20%. Possible reasons for discrepancies in audiological testing might be the exaggeration of hearing loss by the worker, insufficient recovery time after noise exposure, or inexperienced audiologists. Our data show that audiometric testing in workplace audiometry, as well as in ENT practice, often reveal a higher disability rating compared to formal audiological (university) assessment, even if these discrepancies do not reach statistical significance.

[Factors influencing rehabilitation of sensorineural hearing loss with hearing aids]. / Einflussfaktoren auf die Rehabilitation der Innenohrschwerhörigkeit mit Hörgeräten.

BACKGROUND: A large proportion of older as well as younger patients do not use their hearing aids. Of the younger hearing impaired population, this occurs in the majority of those who do not benefit sufficiently from their hearing aids and, consequently, they face difficulties in their working and social life. SCIENTIFIC QUESTION: Our aim was to evaluate whether a classical hearing aid adjustment is of sufficient predictive value to determine whether adequate rehabilitation in everyday and professional life will occur. METHODS AND RESULTS: A questionnaire was returned by 197 adult hearing impaired patients. Only 108 were using their hearing aids all the time; 57 rarely and 32 never. The main reason for this low rehabilitation rate proved to be inadequate amplification. At the workplace, insufficient speech discrimination came into play. Another important factor was dysacusis induced by specific noise signals. There was an intolerable acoustic feedback in 40% which could not be sufficiently alleviated. Taking these results into account, only about a third of patients were sufficiently rehabilitated. CONCLUSIONS: Proof of effectiveness in a typical audiological testing situation is an important but not a fully reliable predictor for effectiveness in everyday life. Even when hearing aids are shown to be effective with such testing, their application in particular everyday or work situations may be insufficient of even impossible.

Acoustomechanical properties of open TTP titanium middle ear prostheses.

OBJECTIVE: The purpose of the study was to identify acoustcomechanical properties of various biostable and biocompatible materials to create a middle ear prosthesis with the following properties: (i) improved handling including a good view of the head of the stapes or footplate and adjustable length, (ii) improved acoustical characteristics that are adequate for ossiculoplastic. The identified material should serve to build CE and FDA approved prostheses for clinical use in patients. METHODS: Test models made of Teflon, polyetheretherketone, polyethylenterephtalate, polysulfone, gold, Al2O3 ceramics, carbon and titanium were investigated for their potential to fulfill the requirements. Acoustical properties were investigated by laser Doppler velocimetry (LDV) in mechanical middle ear models (MMM). Measured data were fed in to a recently created computer model of the middle ear (multibody systems approach, MBS). Using computer-aided design (CAD) measured and computed data allowed creation and fine precision of titanium prostheses (Tübingen Titanium Protheses, TTP). Their handling was tested in temporal bones. Acoustomechanical properties were investigated using the MBS and mechanical middle ear models. MAIN OUTCOME MEASURES: Input impedance, mass, stiffness, and geometry of test models and prostheses were determined. Furthermore, their influence on the intraprosthetic transfer functions and on coupling to either tympanic membrane or stapes was investigated. RESULTS: Final results were FDA- and CE-approved filigreed titanium prostheses with an open head that fulfilled the four requirements detailed above. The prostheses (TTP) were developed in defined lengths of between 1.75 and 3.5 mm (partial) and 3.0 and 6.5 mm (total) as well as in adjustable lengths (TTP-Vario). CONCLUSIONS: The results suggest acoustomechanical advantages of TTPs because they combine a significantly low mass with high stiffness. In contrast to closed prostheses, the open head and filigreed design allow an excellent view of the prosthesis foot during coupling to the head or footplate of stapes, contributing to an improved intraoperative reliability of prosthesis coupling.

[The use of disposable instruments of a high performance polymer for tonsillectomy and adenoidectomy]. / Kunststoff-Einmalinstrumente aus Hochleistungspolymer bei Tonsillektomien und Adenotomien.

Cases of the new variant Creutzfeldt-Jakob disease (vCJD) in human beings have to be anticipated in Germany. In subclinical vCJD, the accumulation of prions in lymphoid tissue has been identified prior to their manifestation in cerebral tissue. The remarkable resistance of prions to standard methods of sterilisation questions the safety of reusing metallic surgical instruments. The transmission of vCJD via such reusable surgical instruments in tonsillectomies and adenoidectomies cannot be excluded. In this study, 96 tonsillectomies and adenoidectomies were performed with disposable instruments made of a high performance polymer (Aesculap, Tuttlingen). No increase in the number of intra- or postoperative complications was evident. These disposable instruments may represent an alternative to reusable metallic surgical instruments in potentially infected patients or in patients desiring the use of disposable instruments during their operation for safety reasons.