Increased Risk for Infections and Allergic Disease in Hereditary Hemorrhagic Telangiectasia.

Background/Objectives: Hereditary hemorrhagic telangiectasia (HHT) is a rare disorder characterized by dilated blood vessels. Different immunological changes have been described in these patients. In this study, the predisposition of patients with HHT to infections and allergic diseases was assessed. Methods: Patients with HHT completed an online survey in English or German. Their data were compared to non-affected partners or friends. Results: A total of 430 out of 588 respondents with HHT answered our questions about infections and allergies. Patients with HHT suffered significantly more often from various types of allergies than their partners, especially type I allergies (n = 226/276, 82%), and had a higher risk for sinusitis, urinary tract infections, pulmonary infections, and abscesses. A total of 38% of the patients took antibiotics prior to dental or surgical procedures (n = 57/152), and, in 10% of these patients, pulmonary arteriovenous malformations (PAVMs) were not detected. On the other hand, 51% of patients with PAVM did not report a prophylactic antibiotic intake (n = 40/79). The patients who needed iron supplementations suffered more often from sepsis (OR: 9.00, 95%CI: 0.92-88.16). Conclusions: Compared to their non-affected controls, patients with HHT showed an increased risk for infections in different organs and allergic diseases. There is a need for campaigns raising greater awareness recommending prophylactic antibiotic intake in patients with PAVM.

Detection of Reduced Diameter of the Cochlear Nerve in Long-term Deaf Patients Quantified With Semiautomatic Measurement of Nerve Cross-sectional Area Using 3T MRI Data.

Hypothesis: High-resolution parallel transmit T2 sampling perfection with application optimized contrast using different flip angle evolution sequence with improved edge discrimination and semiautomatic determination of nerve cross-sectional area (CSA) can be used to evaluate nerve degeneration in the inner auditory canal (IAC) in long-term deaf patients. Background: In patients with hearing loss, temporal bone MRI is routinely acquired to evaluate the morphology of the nerves within the IAC. Earlier studies have shown that the diameter of the cochlear nerve can be used as prognostic marker for the auditory performance after cochlear implantation in postlingually deaf patients. Methods: Eighty-two consecutive MRI scans were analyzed using a semiautomatic tool to measure CSA of cranial nerves in the IAC. Results were correlated with patient history and audiology testing as well as with age and gender. Results: There was a significant reduced CSA of the cochlear nerve in ears with moderate-to-profound hearing loss and deafness compared with ears with normal hearing, but no significant difference in ears with mild-to-moderate hearing loss compared with normal hearing. In detail, normal hearing ears had a CSA of 1.23 ± 0.11 mm2, whereas ears with pantonal hearing loss of more than 40 dB had 1.02 ± 0.05 mm2 (P = 0.026). Maximal CSA of the facial nerve was not different among all groups (average, 1.04 mm2 ± 0.03; linear regression, P = 0.001) and stable with age. However, vestibular nerve CSA decreased significantly with age (average, 1.78 ± 0.05 mm2; linear regression, P = 0.128). Conclusions: In long-term deaf patients, smaller the diameter of cochlear nerve is the more severe the hearing loss is. The new semiautomatic tool can primarily be used to assess nerve diameter and possibly determine ears with nerve degeneration.

Role of prior intratympanic gentamicin and corticosteroids therapy on speech understanding in patients with Menière's disease after cochlear implantation.

AIM: Intratympanic injection of corticosteroids (ITC) and gentamicin therapy (ITG) are widely used treatments for vertigo in Meniere's disease (MD). Even though studies show good results after cochlea implantation (CI) in MD patients when compared to non-MD groups, there is no indication on the effect of ITC and ITG prior to CI on hearing after CI. This study compares the post-operative hearing of CI patients with and without MD and patients who have received ITG or ITC prior to CI. METHODS: In a retrospective case control study, adult patients with MD who received CI from 2002 till 2021 were compared to a matched control group of CI patients without MD. Patients with prior ITC/ITG were extracted from MD group. Pre-operative audiological results were measured and trends across post-operative monosyllabic word recognition score at 65 decibels (WRS65CI) at switch-on, 3-6 months, 1 year and last yearly value were analyzed across all groups. RESULTS: 28 MD ears were compared with 33 control ears. From MD ears 9 had received ITG and 6 ITC prior to CI. WRS65CI increased significantly with time within MD and control groups, but no difference in WRS65CI was found between these 2 groups. ITG ears showed fluctuating WRS65CI after CI with no change across time, while ITC ears showed significant increase in trend of WRS65CI values across time. CONCLUSION: MD and non-MD patients showed comparable hearing results after CI. Prior ITC might positively influence hearing preservation after CI in MD patients whereas ITG group showed fluctuating hearing.

Auditory capacity of the better-hearing ear in asymmetric hearing loss.

PURPOSE: Our aim was to investigate the course of the hearing capacity of the better-hearing ear in single-sided deafness (SSD) and asymmetric hearing loss (AHL) over time, in a multicenter study. METHODS: We included 2086 pure-tone audiograms from 323 patients with SSD and AHL from four hospitals and 156 private practice otorhinolaryngologists. We collected: age, gender, etiology, duration of deafness, treatment with CI, number and monosyllabic speech recognition, numerical rating scale (NRS) of tinnitus intensity, and the tinnitus questionnaire according to Goebel and Hiller. We compared the pure tone audiogram of the better-hearing ear in patients with SSD with age- and gender-controlled hearing thresholds from ISO 7029:2017. RESULTS: First, individuals with SSD showed a significantly higher hearing threshold from 0.125 to 8 kHz in the better-hearing ear compared to the ISO 7029:2017. The duration of deafness of the poorer-hearing ear showed no relationship with the hearing threshold of the better-hearing ear. The hearing threshold was significantly higher in typically bilaterally presenting etiologies (chronic otitis media, otosclerosis, and congenital hearing loss), except for Menière's disease. Second, subjects that developed AHL did so in 5.19 ± 5.91 years and showed significant reduction in monosyllabic word and number recognition. CONCLUSIONS: Individuals with SSD show significantly poorer hearing in the better-hearing ear than individuals with NH from the ISO 7029:2017. In clinical practice, we should, therefore, inform our SSD patients that their disease is accompanied by a reduced hearing capacity on the contralateral side, especially in certain etiologies.

Universal Newborn Hearing Screening Program: 10-Year Outcome and Follow-Up from a Screening Center in Germany.

Regular reporting of quality control is important in newborn hearing screening, ensuring early diagnosis and intervention. This study reports on a population-based newborn hearing screening program in North-Rhine, Germany and a hospital-based screening at a University Hospital for 2007-2016. The two-staged 'screening' and 'follow-up' program involving TEOAE and AABR recruited newborns through participating birth facilities. Results were sent to the regional tracking center, and the data were analyzed based on recommended benchmarks. The percentage of newborns from the participating birth facilities in the region increased from 1.4% in 2007 to 57.5% in 2016. The 10-year coverage rate for these newborns was 98.7%, the referral rate after a failed two-step screening was 3.4%, and the lost-to-follow-up rate was 1%. At the hospital, >95% of the screened newborns completed screening within 30 days, the 10-year referral rate was 5%, and 64% were referred within 3 months of age. The median time for screening completion was 6 days after birth, for referral it was 74 days after birth, and for diagnosis it was 55 days after birth. Regional-centralized tracking centers with uniform structure are necessary for proper quality control. Obligatory participation of birthing facilities and quality reports may improve performance, but the recommended quality criteria need considerable financial and infrastructural expenditure.

Referral rate and false-positive rates in a hearing screening program among high-risk newborns.

AIM: More studies exploring referral rates and false-positive rates are needed to make hearing screening programs in newborns better and cost-effective. Our aim was to study the referral and false-positivity rates among high-risk newborns in our hearing screening program and to analyze the factors potentially associated with false-positive hearing screening test results. METHODS: A retrospective cohort study was done among the newborns hospitalized at a university hospital from January 2009 to December 2014 that underwent hearing screening with a two-staged AABR screening protocol. Referral rates and false-positivity rates were calculated and possible risk factors for false-positivity were analyzed. RESULTS: 4512 newborns were screened for hearing loss in the neonatology department. The referral rate for the two-staged AABR-only screening was 3.8% with false-positivity being 2.9%. Our study showed that the higher the birthweight or gestational age of the newborn, the lower the odds of the hearing screening results being false-positive, and the higher the chronological age of the infant at the time of screening, the higher the odds of the results being false-positive. Our study did not show a clear association between the mode of delivery or gender and false-positivity. CONCLUSION: Among high-risk infants, prematurity and low-birthweight increased the rate of false-positivity in the hearing screening, and the chronological age at the time of the test seems to be significantly associated with false-positivity.

Role of cochlear reserve in adults with cochlear implants following post-lingual hearing loss.

INTRODUCTION: Pre-operative assessments before cochlear implantation (CI) includes the examination of both tone hearing, and the level of the cochlear reserve indicated by speech understanding. The goal of this study was to explore the predictive influence of tone hearing and cochlear reserve in CI. METHODS: We did a retrospective cohort study, which included adult patients who had undergone CI between January 2012 and December 2019 in a tertiary care center. The pre-operative tone hearing, unaided maximum monosyllabic word recognition score (WRSmax), aided hearing gain, aided monosyllabic word recognition score at 65 dB (WRS65(HA)), and speech perception gap (SPG) were measured. The duration of unaided hearing loss (UHL) was also assessed. These variables were compared with post-operative monosyllabic word recognition score after CI at 65 dB (WRS65(CI)). RESULTS: 103 patients and 128 ears were included in this study. Regardless of tone hearing, patients with better pre-operative WRSmax and WRS65(HA) performed better post-operatively. WRSmax was found to be the most important factor that was statistically significantly associated with WRS65(CI). SPG was statistically significantly associated with WRSmax and SPG ≥ 20% group performed better post-operatively. Any duration of unaided hearing loss was statistically significantly inversely associated with WRSmax above 0%. CONCLUSION: Cochlear reserve represented by WRSmax may play the most important role as a predictive factor in outcomes after CI. SPG should be considered for indicating CI in patients, when WRS65(HA) does not reach WRSmax. Early rehabilitation with hearing aids and duration of hearing aid usage might play an important role in preserving cochlear reserve in adults.

During early stages of cancer, neutrophils initiate anti-tumor immune responses in tumor-draining lymph nodes.

Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner. In metastasis-free stages (N0), neutrophils develop an antigen-presenting phenotype (HLA-DR+CD80+CD86+ICAM1+PD-L1-) and stimulate T cells (CD27+Ki67highPD-1-). LN metastases release GM-CSF and via STAT3 trigger development of PD-L1+ immunosuppressive neutrophils, which repress T cell responses. The accumulation of neutrophils in T cell-rich zones of LNs in N0 constitutes a positive predictor for 5-year survival, while increased numbers of neutrophils in LNs of N1-3 stages predict poor prognosis in HNC. These results suggest a dual role of neutrophils as essential regulators of anti-cancer immunity in LNs and argue for approaches fostering immunostimulatory activity of these cells during cancer therapy.

The accuracy of clinical neck staging for p16-positive and negative oropharyngeal cancer and its therapeutic implications.

PURPOSE: Oropharyngeal squamous cell carcinoma (OPSCC) may be treated with primary surgery or primary (chemo)radiation. While surgery with concurrent neck dissection provides definitive pathological staging of the neck, non-surgical treatment relies on clinical staging for treatment planning. To assess the accuracy of clinical neck staging, we compared clinical to surgical staging after primary surgery in patients with p16-negative and p16-positive OPSCC. METHODS: Retrospective analysis of clinical, pathological, and oncologic outcome data of patients with OPSCC treated with primary surgery and bilateral neck dissection. Clinical and pathological nodal status were compared for p16-negative and p16-positive patients. Patients with occult metastatic disease were analyzed in detail. RESULTS: 95 patients were included. 60.5% of p16-negative patients and 66.6% of p16-positive patients had pathologically confirmed metastatic neck disease. p16-positive patients had improved 24-month recurrence-free survival compared to p16-negative patients at 93.3% vs. 69.6%. Pathological N-status differed from clinical N-status in 36.8% of p16-negative patients vs. 31.6% of p16-positive patients. Occult metastatic disease was more common in p16-negative patients at 18.4% vs. 8.8% for p16-positive patients. Clinical detection sensitivity for extranodal extension was low overall; sensitivity was 27.3% and specificity was 91.6% for p16-negative patients vs. 61.5% and 80.0% for p16-positive patients, respectively. CONCLUSION: Our data show a considerable degree of inaccuracy of clinical neck staging results in all OPSCC patients which needs to be taken into consideration during therapy planning. For p16-positive patients, these findings warrant attention in the context of therapy deintensification to avoid undertreatment.

Clinical Impact of CYFRA 21-1 a Marker for Treatment Failure in Patients With Oropharyngeal Cancer Treated by Radio(chemo)therapy.

BACKGROUND: Primary radio(chemo)therapy [R(C)T] is a treatment option for advanced oropharyngeal squamous cell carcinoma (OSCC). Nevertheless, early diagnostics of treatment failure is problematic. Cytokeratin fragment 19 (CYFRA 21-1), an established marker in the management of pulmonary cancer, might be helpful here. Hence, in this study the impact of CYFRA 21-1 as an indicator for treatment failure and tumor recurrence (TR) in OSCC after R(C)T was analyzed. PATIENTS AND METHODS: The data of 77 patients with advanced OSCC and R(C)T were retrospectively examined. For determination of CYFRA 21-1 at the time of diagnosis and after R(C)T, an electrochemiluminescence immunoassay was used. Tumor residuals and tumor recurrence were pathologically verified after detection by radiological imaging and endoscopy. The mean follow-up was 44.4 months. RESULTS: After R(C)T, 48 (62%) patients showed locoregional control and 29 (38%) patients experienced locoregional failure. No statistical difference in the CYFRA 21-1 level between groups both before (p=0.75) and after R(C)T (p=0.85) was found. Nevertheless, in cases of TR in follow-up, the CYFRA 21-1 level was significantly higher (p≤0.01). The occurrence of TR was significantly associated with a CYFRA 21-1 elevation at this time (p≤0.01). However, CYFRA 21-1 failed to show a suitable discriminative ability for TR (area under the curve=0.57). CONCLUSION: In OSCC, CYFRA 21-1 does not seem to be a useful marker for locoregional failure after R(C)T. Nevertheless, a higher level immediately after R(C)T and in the further course of the disease may be associated with TR in individual patients.