Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD.

BACKGROUND AND OBJECTIVE: The effectiveness of biologics in chronic rhinosinusitis with nasal polyps (CRSwNP) is well-established. However, real-world experience on the effectiveness of transitioning between two monoclonal antibodies is scarce. Therefore, we aimed to analyze the safety and efficacy of antibody switching in treatment of chronic rhinosinusitis. METHODS: All patients with CRSwNP or nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease (N-ERD) requiring a switch between biologics were retrospectively studied. Analysis included changes in polyp size, quality of life parameters, asthma control, and side effects. RESULTS: Out of 195 patients treated with biologics for CRSwNP or N-ERD in our center, 23 (11.8%) required transition to a different monoclonal antibody. The majority switched from omalizumab to dupilumab (17/23, 73.9%), mostly due to inadequate symptom control. Nine out of these 17 patients (52.9%) were switched without a washout period. All patients showed significant improvement in nasal polyp score, asthma control test and sino-nasal outcome test-22 after changing to dupilumab. Keratoconjunctivitis sicca was the side-effect (4.3%) reported after the switch from omalizumab to dupilumab, which lead to termination of therapy in one patient. Due to limited sample size, other antibody transitions were reported in a descriptive manner. CONCLUSION: The transition to dupilumab is an effective option in patients with inadequate treatment response or side-effects of omalizumab in nasal polyposis. Our preliminary results indicate that a wash-out period may not be necessary when switching between biologics, however, these findings require further investigations. Other monoclonal antibody transitions also show promising results, but warrant validations in larger cohorts due to small patient samples in our study.

Management and outcome of vagus nerve stimulator implantation: experience of an otolaryngeal/neuropediatric cooperation.

OBJECTIVE: Vagus nerve stimulator (VNS) implantation is an established therapy for pharmacoresistant epilepsy that is not amenable to curative epilepsy surgery. Historically, VNS implantation has been performed by neurosurgeons, but otolaryngologist involvement is increasingly common. In this retrospective study, we aimed to evaluate the efficacy and safety of VNS implantation in children and adolescents from the otolaryngologists' perspective. METHODS: This study included children and adolescents who had undergone VNS implantation at the study center between 2014 and 2018. Patient files were analyzed with regards to the durations of device implantation and hospitalization, postoperative complications, and clinical outcome, including seizure frequency, clinical global impression of improvement (CGI-I) score, and quality of life (QoL). RESULTS: A total of 73 children underwent VNS surgery. The median age at implantation was 9.3 ± 4.6 years, and median epilepsy duration before VNS surgery was 6 ± 4 years. Lennox-Gastaut syndrome was the most common syndrome diagnosis (62.3%), and structural abnormalities (49.3%) the most frequent etiology. Operation times ranged from 30 to 200 min, and median postoperative hospitalization length was 2 ± 0.9 days. No complications occurred, except for four revisions and two explantations due to local infections (2.7%). Among our patients, 76.7% were responders (≥ 50% reduction in seizure frequency), 72.1% showed improved CGI-I scores, and 18.6-60.5% exhibited considerable improvements in the QoL categories energy, emotional health, and cognitive functions. CONCLUSION: Our results indicate that VNS implantation is a highly effective and safe treatment option for children and adolescents with AED-refractory epilepsies who are not candidates for curative epilepsy surgery.

A connection between neurovascular conflicts within the cerebellopontine angle and vestibular neuritis, a case controlled cohort study.

This retrospective, observer blinded case-control study aims to compare the prevalence of neurovascular conflicts (NVCs) of the vestibulocochlear nerve and the anterior inferior cerebellar artery (AICA) in patients presenting with clinical signs of acute vestibular neuritis with and without subsequent objective vestibular function loss (VFL). 58 acute cases of clinically suspected acute vestibular neuritis were investigated with same day cranial MRI at a tertiary referral centre and compared to 61 asymptomatic controls. The prevalence of NVCs in cases with objective VFL were also compared to cases without VFL. Radiologists described the NVC as "no contact" (Grade 0), "contact < 2 mm" (Grade 1), "contact > 2 mm" (Grade 2) and "vascular loop presence" (Grade 3) without knowledge of neurotological data. Neurotological data was collected without knowledge of MRI findings. Vestibular function was tested by bithermic caloric irrigation. 26 cases (45%) showed caloric VFL (Group A), whereas 32 (55%) exhibited no VFL (Group B). Group A included 13 cases with NVCs (50%), Group B included 26 NVC cases (82%) (p = 0.012) and the control group included 16 individuals (26%) (p < 0.001 for comparison of all 3 groups). Group B had a significantly higher NVC-Grading than Group A (p = 0.009). There was no statistically significant association between NVCs and either SNHL or tinnitus (p > 0.05). Our results suggest that patients presenting with clinical signs of acute vestibular neuritis who show symmetrical caloric vestibular function test results have a significantly higher NVC prevalence in the cerebellopontine angle.

Transtemporal ultrasound application potentially elevates brain temperature: results of an anthropomorphic skull model.

PURPOSE: Transtemporal sonothrombolysis is a tool for a more effective treatment in acute stroke patients. However, some reports revealed side effects, which might be potentially connected to temperature elevation. To gain better insight into cerebral temperature changes during transtemporal sonication, diagnostic and therapeutic ultrasound (US) applications were evaluated using an anthropomorphic skull model. MATERIALS AND METHODS: The impact of diagnostic (PW-Doppler, 1.8-MHz, 0.11 W/cm², TIC 1.2) and therapeutic (1-MHz and 3-MHz, 0.07 - 0.71 W/cm², continuous and pulsed mode) US application on temperature changes was evaluated at the level of muscle/temporal bone (TB), TB/brain, brain and at the middle cerebral artery (MCA) using 4 miniature thermocouples along the US beam. Sonication lasted 120 minutes. RESULTS: Diagnostic ultrasound revealed a maximum temperature increase of 1.45°/0.60°/0.39°/0.41°C (muscle/TB, TB/brain, brain, MCA) after 120 minutes. Therapeutic-1-MHz ultrasound raised temperature by 4.33°/2.02°/1.05 °C/0.81°C (pulsed 1:20) and by 10.38°/4.95°/2.43°/2.08°C (pulsed 1:5) over 120 minutes. Therapeutic-3-MHz US raised temperature by 4.89°/2.56°/1.24/1.25°C (pulsed 1:20) and by 14.77°/6.59°/3.56°/2.86°C (pulsed 1:5) over 120 minutes, respectively. Continuous application of therapeutic US (1-MHz and 3-MHz) led to a temperature increase of 13.86°/3.63°/1.66°/1.48°C and 17.09°/4.28°/1.38/0.99°C within 3 minutes. CONCLUSION: Diagnostic PW-Doppler showed only a moderate temperature increase and can be considered as safe. Therapeutic sonication is very powerful in delivering energy so that even pulsed application modes resulted in significant and potentially harmful temperature increases.

Thermal effects of diagnostic ultrasound in an anthropomorphic skull model.

PURPOSE: Exposure to diagnostic ultrasound (US) can significantly heat biological tissue although conventional routine examinations are regarded as safe. The risk of unwanted thermal effects increases with a high absorption coefficient and extended insonation time. Certain applications of transcranial diagnostic US (TC-US) require prolonged exposure. An anthropomorphic skull model (ASM) was developed to evaluate thermal effects induced by TC-US of different modalities. The objective was to determine whether prolonged continuous TC-US application results in potentially harmful temperature increases. MATERIALS AND METHODS: The ASM consists of a human skull with tissue mimicking material and exhibits acoustic and anatomical characteristics of the human skull and brain. Experiments are performed with a diagnostic US device testing four different US modalities: Duplex PW (pulsed wave) Doppler, PW Doppler, color flow Doppler and B-mode. Temperature changes are recorded during 180 minutes of insonation. RESULTS: All measurements revealed significant temperature increases during insonation independent of the US modality. The maximum temperature elevation of + 5.25° C (p < 0.001) was observed on the surface of the skull exposed to duplex PW Doppler. At the bone-brain border a maximum temperature increae of + 2.01 °C (p < 0.001) was noted. Temperature increases within the brain were < 1.23 °C (p = 0.001). The highest values were registered using the duplex PW Doppler modality. CONCLUSION: TC-US induces significant local heating effects in an ASM. An application duration that extends routine clinical periods causes potentially harmful heating especially in tissue close to bone. TC-US elevates the temperature in the brain mimicking tissue but is not capable of producing harmful temperature increases during routine examinations. However, the risk of thermal injury in brain tissue increases significantly after an exposure time of > 2 hours.

The inflammatory mediator oncostatin M induces angiopoietin 2 expression in endothelial cells in vitro and in vivo.

OBJECTIVES: Members of the glycoprotein 130 (gp130) receptor-gp130 ligand family play a role in angiogenesis in different tissues. We tested the effect of this cytokine family on the angiopoietin (Ang)-Tie system, which is involved in blood vessel maturation, stabilization, and regression. RESULTS: Oncostatin M (OSM) increased Ang2 expression in human umbilical vein endothelial cells via Janus kinase/signal transducer and activator of transcription (JAK/STAT) and mitogen-activated protein (MAP) kinase activation. Furthermore, OSM induced Ang2 expression in macrovascular endothelial cells isolated from the human aorta and in microvascular endothelial cells isolated from human heart. Our in vivo experiments revealed that mRNA expression of Ang2 in hearts of mice injected with OSM increased significantly, and levels of OSM mRNA significantly correlated with mRNA levels of Ang2 in human hearts. In addition, OSM increased the expression of its own receptors, gp130 and OSM receptor, in endothelial cells in vitro and in mice in vivo, and levels of OSM mRNA significantly correlated with mRNA levels of gp130 and OSM receptor in human hearts. CONCLUSION: Our data, showing the effects of OSM on the Ang-Tie system in endothelial cells, in hearts of mice, and in human heart tissue, provide yet another link between inflammation and angiogenesis.