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.

[Epistaxis-overview and current aspects]. / Epistaxis ­ Übersicht und aktuelle Aspekte.

Nosebleeds (epistaxis) are usually minor. Medical intervention is only necessary in about 6% of cases. The source of bleeding is frequently located in the anterior region of the nose (Kiesselbach's plexus). The estimated lifetime prevalence of epistaxis is 60%. Diffuse epistaxis is often a manifestation of systemic disease. Epistaxis is the leading symptom of Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia, HHT). If intervention is required, the first-choice of treatment is bidigital compression for several minutes. Common therapeutic measures include local hemostasis using electrocoagulation or chemical agents, e.g., silver nitrate. Resorbable anterior nasal tampons or tampons with a smooth surface are also frequently employed. In case of failed surgical closure of the sphenopalatine artery, angiographic embolization is the method of choice.

Restless Leg Syndrome Is Underdiagnosed in Hereditary Hemorrhagic Telangiectasia-Results of an Online Survey.

BACKGROUND: Recurrent bleeding in patients with hereditary hemorrhagic telangiectasia (HHT) can lead to chronic iron deficiency anemia (CIDA). Existing research points to CIDA as a contributing factor in restless leg syndrome (RLS). The association between HHT-related symptoms and the prevalence of RLS was analyzed. METHODS: An online survey was conducted whereby the standardized RLS-Diagnostic Index questionnaire (RLS-DI) was supplemented with 82 additional questions relating to HHT. RESULTS: A total of 474 persons responded to the survey and completed responses for questions pertaining to RLS (mean age: 56 years, 68% females). Per RLS-DI criteria, 48 patients (48/322, 15%; 95% confidence interval (CI): 11-19%) self-identified as having RLS. An analysis of physician-diagnosed RLS and the RLS-DI revealed a relative frequency of RLS in HHT patients of 22% (95% CI: 18-27%). In fact, 8% (25/322; 95% CI: 5-11%) of the HHT patients had RLS which had not been diagnosed before. This equals 35% of the total amount of patients diagnosed with RLS (25/72; 95% CI: 25-46%). HHT patients with a history of gastrointestinal bleeding (prevalence ratio (PR) = 2.70, 95% CI: 1.53-4.77), blood transfusions (PR = 1.90, 95% CI: 1.27-2.86), or iron intake (PR = 2.05, 95% CI: 0.99-4.26) had an increased prevalence of RLS. CONCLUSIONS: Our data suggest that RLS is underdiagnosed in HHT. In addition, physicians should assess CIDA parameters for possible iron supplementation.

[Hereditary hemorrhagic telangiectasia: symptoms and diagnostic latency]. / Hereditäre hämorrhagische Teleangiektasie: Symptome und diagnostische Latenz.

OBJECTIVE: Patients with hereditary hemorrhagic Telangiectasia (HHT) suffer from a rare and systemic disease which is characterized by vascular malformations leading to a variety of different symptoms. MATERIAL AND METHODS: A retrospective review of patients who were referred to our new HHT Center of Excellence (HHT COE) for evaluation and treatment between April 2014 and August 2019 was performed. RESULTS: 235 patients were treated at the West German HHT Center. 83 % of these were diagnosed with definite HHT (235/282, 83 %) and 9 % with possible HHT (26/282). The average latency between first manifestation and definite diagnosis of HHT was 18 years. Several initial symptoms were direct or indirect signs of bleeding (224/241, 93 %). In 83 % of the patients HHT was reported having caused their degree of disability. Older, female patients and those with severe epistaxis suffered from chronic iron deficiency anemia, took iron preparations (148/261, 57 %) and received 9 blood transfusions on average (± standard deviation: 41, minimum - maximum: 0-400, number of patients: 218). 10 % of all patients tolerated anticoagulant or antiplatelet agents. 74 % of patients with HHT used nasal creams/sprays/oils (177/238) and reported fewer bleedings compared to patients without nasal care (ESS: T-Test: 3.193; p = 0.003; anemia: Chi-square: 5.173; p = 0.023). CONCLUSIONS: The diagnostic latency of HHT was almost two decades. Patients with HHT particularly suffered from recurrent epistaxis, which was mostly treated with nasal care and coagulative therapies. Antiplatelet or anticoagulant agents can be used in patients with HHT with caution if indicated.

[Implementation and development of a center for hereditary hemorrhagic telangiectasia]. / Aufbau und Entwicklung eines interdisziplinären Zentrums für hereditäre hämorrhagische Teleangiektasie.

OBJECTIVE: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare and systemic disorder which is characterized by recurrent epistaxis, mucocutaneous telangiectases, and visceral arteriovenous malformations (AVM). An interdisciplinary concept is recommended. MATERIAL AND METHODS: We performed a retrospective review of consecutive patients who were referred to our newly established HHT Center of Excellence (HHT COE) for evaluation and treatment between April 2014 and August 2019. RESULTS: A network of over 20 departments was established at the University Hospital Essen. In 261 of the 282 patients (93 %), who were referred to the hospital's COE, the HHT diagnosis was at least possible. Most patients suffered from several symptoms (epistaxis and / or telangiectasia: > 80 %, visceral involvement: 65 %) and received a variety of treatments, often in a multidisciplinary setting. Alongside this direct treatment, the COE leader manages the coordination of the center and its public relations, which involves more than 900 e-mails per year. International collaboration and exchanges of expertise within the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN) can improve the treatment of patients with HHT particularly where these cases are complex. CONCLUSIONS: An HHT COE provides an interdisciplinary network where highly specialized diagnostic and therapeutic processes can be updated and optimized continuously.

UV light-based reprocessing of flexible endoscopes without working channel in Oto-Rhino-Laryngology: an effective method?

BACKGROUND: Reprocessing of flexible endoscopes (FEs) is often expensive, time consuming, and becomes increasingly complex, due to rising demands of hygiene. After beneficial results in reprocessing of rigid endoscopes using Impelux™ UV-C light technology, we tested the same method for reprocessing of FEs without working channel. MATERIALS AND METHODS: Testing was performed on FEs without working channel after routine clinical use (transnasal flexible endoscopy). Disinfection consisted of mechanical precleaning and 60 s exposure to Impelux™ UV-C light technology. Bacterial contamination was tested on 50 FEs before and after disinfection. Further 50 FEs regarding protein residuals. The absolute effectiveness of the D60 was tested on 50 test bodies (RAMS) with a standardized contamination of 107 colony-forming units (CFU) of Enterococcus faecium. RESULTS: The FEs were contaminated with a high average value of 916.7 CFU (± 1057 CFU) after clinical usage. After reprocessing, an average contamination of 2.8 CFU (± 1.6) on 14% (n = 7) of the FEs was detected consisting of non-pathogenic species, the remaining FE were sterile. After reprocessing, all FEs were protein-free (< 1 µg). The artificially contaminated test bodies showed no remaining bacterial contamination after disinfection, resulting in an average absolute germ reduction of about 107 CFU. CONCLUSION: Impelux™ UV-C light technology efficiently reduces bacterial contamination of FEs and might be useful in daily practice.

Trauma Can Induce Telangiectases in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease of the fibrovascular tissue resulting in visceral vascular malformations and (muco-) cutaneous telangiectases with recurrent bleedings. The mechanism behind the disease is not fully understood; however, observations from HHT mouse models suggest that mechanical trauma may induce the formation of abnormal vessels. To assess the influence of environmental trauma (mechanical or light induced) on the number of telangiectases in patients with HHT, the number of telangiectases on the hands, face, and lips were counted on 103 HHT patients possessing at least three out of four Curaçao criteria. They were then surveyed for information concerning their dominant hand, exposure to sunlight, and types of regular manual work. Patients developed more telangiectases on their dominant hand and lower lip (Wilcoxon rank sum test: p < 0.001). Mechanical stress induced by manual work led to an increased number of telangiectases on patients' hands (Mann-Whitney U test: p < 0.001). There was also a positive correlation between sun exposure and the number of telangiectases on the lips (Mann-Whitney U test: 0.027). This study shows that mechanical and UV-induced trauma strongly influence the formation of telangiectases in HHT patients. This result has potential implications in preventive measures and on therapeutic approaches for HHT.

UV light-based decontamination: an effective and fast way for disinfection of endoscopes in otorhinolaryngology?

BACKGROUND: Reprocessing of endoscopes becomes increasingly complex, due to rising demands of hygiene. Established methods are often expensive/time-consuming. Recent studies suggest beneficial aspects of disinfection by UV light. In this study we analyzed the efficiency of UV light disinfection of rigid otorhinolaryngological endoscopes. MATERIALS AND METHODS: After mechanical pre-cleaning, the endoscopes were decontaminated for 25 s in the D25 using Impelux™ UV C light technology (UV Smart B.V., Delft, The Netherlands). First, the surface contact samples were taken from 50 used endoscopes to evaluate the bacterial load. Additionally, surface contact samples were taken from further 50 used endoscopes after reprocessing with the D25. Another 50 endoscopes were tested on protein residuals. Furthermore, the absolute effectiveness of the D25 was tested on 50 test bodies (RAMS) with a standardized contamination of 107 colony-forming units (CFU) of Enterococcus faecium. RESULTS: The used endoscopes showed a high bacterial contamination with an average value of 66.908 (± 239.215) CFU. After reprocessing, only a minimal contamination on 10% (n = 5) of the endoscopes with a mean value of 0.12 CFU (± 0.39) was found, resulting in a log-5 reduction in a clinical environment. The documented bacteria were components of the normal skin flora. All tested endoscopes were practically protein-free (< 1 µg). Furthermore, the average absolute germ reduction of the D25 was about 106 CFU on the tested RAMS. CONCLUSION: The D25 UV light system seems to be an effective device for the reprocessing of rigid ORL endoscopes, and therefore, might be suitable for the usage in clinical practice on site.

Impaired Release of Neutrophil Extracellular Traps and Anemia-Associated T Cell Deficiency in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by mucocutaneous telangiectases and visceral vascular malformations. Individuals suffering from HHT have a significantly increased risk of bacterial infections, but the mechanisms involved in this are not clear. White blood cell subpopulations were estimated with flow cytometry in 79 patients with HHT and 45 healthy individuals, and association with clinicopathological status was assessed. A prominent decrease in absolute numbers of T cells in HHT was revealed (0.7 (0.5-1.1) vs. 1.3 (0.8-1.6), 106/mL, p < 0.05), and in multivariate regression analysis, hemoglobin level was associated with lymphopenia (OR = 0.625, 95% CI: 0.417-0.937, p < 0.05). Although no changes in absolute numbers of neutrophils and monocytes were observed, we revealed a significant impairment of neutrophil antibacterial functions in HHT (n = 9), compared to healthy individuals (n = 7), in vitro. The release of neutrophil extracellular traps (NETs) against Pseudomonas aeruginosa MOI10 was significantly suppressed in HHT (mean area per cell, mm2: 76 (70-92) vs. 121 (97-128), p < 0.05), due to impaired filamentous actin organization (% of positive cells: 69 (59-77) vs. 92 (88-94), p < 0.05). To conclude, this study reveals the categories of patients with HHT that are prone to immunosuppression and require careful monitoring, and suggests a potential therapeutic strategy based on the functional activation of neutrophils.

Prevalence and risk factors for hearing loss in high-risk neonates in Germany.

AIM: Hearing loss in infants is often diagnosed late, despite universal screening programmes. Risk factors of hearing impairment in high-risk neonates, identified from population-based studies, can inform policy around targeted screening. Our aim was to determine the prevalence and the risk factors of hearing loss in a high-risk neonatal population. METHODS: This was a retrospective cohort study of neonates hospitalised at the University Hospital Cologne, Germany from January 2009 to December 2014 and were part of the newborn hearing screening programme. Multivariable regression analyses using the lasso approach was performed. RESULTS: Data were available for 4512 (43% female) neonates with a mean gestational age at birth of 35.5 weeks. The prevalence of hearing loss was 1.6%, and 42 (0.9%) neonates had permanent hearing loss. Craniofacial anomalies, hyperbilirubinaemia requiring exchange transfusion, oxygen supplementation after 36 weeks of gestation and hydrops fetalis showed associations with permanent hearing loss. CONCLUSION: Our findings of risk factors for hearing loss were consistent with other studies. However, some commonly demonstrated risk factors such as perinatal infections, meningitis, sepsis and ototoxic drugs did not show significant associations in our cohort. Targeted screening based on risk factors may help early identification of hearing loss in neonates.

Childhood Vaccination Against Seasonal Influenza to Reduce the Overall Burden of Disease: Ethical Perspectives.

INTRODUCTION: Childhood immunisation against seasonal influenza promises to reduce the burden of disease through herd immunity. The option of intranasal vaccination seemed to offer a more acceptable vaccination for children, as they are perceived to be less invasive. Yet, intranasal vaccines have been recently proven not to be as effective as presumed. In Germany, contradictory recommendations of the Standing Committee on Vaccination (STIKO) first, to use and then, in October 2016, not use these vaccines have been issued for the 2016-2017 season, whereas recommendations not to use them were already issued in the USA (CDC, ACIP). This controversy spurs the discussion of immunisation programmes for children again. Despite studies discussing the effectiveness of a comprehensive immunisation programme targeting children also in the German and wider European context, an accompanying ethical discussion is missing. METHODOLOGY: We discuss several policy options from different key ethical perspectives that are widely used in public health: if seasonal influenza vaccination should be intensively offered to or even made mandatory for children to decrease the societal burden of the disease. RESULTS: Various ethical perspectives reflect the question how to balance individual autonomy, personal benefit and population benefit differently. DISCUSSION: A convincing justification for suggestions on immunisation policies has to balance norms anchored in different ethical theories. There are good reasons to offer immunisation programmes against seasonal influenza to children, using a voluntary, possibly incentive-based approach.