Serological Cross-Reactivity of Various Aspergillus spp. with Aspergillus fumigatus: A Diagnostic Blind Spot.

INTRODUCTION: Aspergillus fumigatus is the most common airborne allergen of the Aspergillus family. However, allergies to Aspergillus spp. are increasing, and subsequently, allergies to Aspergillus species other than fumigatus are also on the rise. Commercial diagnostic tools are still limited to Aspergillus fumigatus. Hence, there is a need for improved tests. We decided to investigate the correlation between serological sensitization to A. fumigatus and other Aspergillus species. METHODS: Hundred and seven patients with positive skin prick tests to A. fumigatus were included in this study. Immunoglobulin E (IgE) concentrations against A. fumigatus, A. terreus, A. niger, A. flavus, and A. versicolor were measured from specimens by fluorescent enzyme-linked immunoassays. RESULTS: Patients showed considerably higher IgE concentrations against A. fumigatus (6.00 ± 15.05 kUA/L) than A. versicolor (0.30 ± 1.01 kUA/L), A. niger (0.62 ± 1.59 kUA/L), A. terreus (0.45 ± 1.12 kUA/L), or A. flavus (0.41 ± 0.97 kUA/L). Regression analysis yielded weak positive correlations for all Aspergillus spp., but low r2 values and heteroscedastic distribution indicate an overall poor fit of the calculated models. CONCLUSION: Serological sensitization against A. fumigatus does not correlate with sensitization against other Aspergillus spp. To detect sensitization against these, other diagnostic tools like a skin prick test solution of different Aspergillus spp. are needed.

[High interaction potential of online-only courses with breakout sessions-results of a pilot study]. / Hohes Interaktionspotenzial volldigitaler Lehrveranstaltungen mit Breakout-Sessions ­ Ergebnisse einer Pilotstudie.

BACKGROUND: The flipped classroom (FC) is nowadays a popular principle of blended student-centered learning. Students first prepare basic knowledge at home and subsequently meet for consolidation and a more in-depth look at a certain topic. During the COVID-19 pandemic, several groups developed approaches to also transform the characteristic FC second session into an online-only format. OBJECTIVE: Herein, we present a pilot study on establishing an online-only FC format with elements of collaborative learning and its evaluation by medical students. MATERIALS AND METHODS: The FC design related to diseases of the salivary glands was transformed into an online-only event. After studying the basic information online, supported by self-made interactive videos and/or lecture recordings, students met in a video conference enriched by breakout sessions, interactive demonstration of the related clinical examination including ultrasound, and a formative assessment. A questionnaire with 27 items was answered by participants to evaluate the concept and the event. RESULTS: Use of common hard- and software systems led to a technically stable video conference. A total of 55 students completed the questionnaire and were included into data analysis. During the breakout sessions, lively interaction between participants was observed. The evaluation of both the event itself and the related learning progress showed good results despite the lack of preparation beforehand in 27% of participants. CONCLUSION: Online-only FC designs can result in high satisfaction. High quality of online preparation, a solid technical platform, accurate time management, and a reasonable selection of topics are the main parameters contributing to successful course design. Nowadays, embedding medical imaging can be realized in appropriate quality for educational purposes. The implementation of breakout sessions and voting tools enables collaborative online learning with high levels of interaction and satisfaction for both teachers and students.

[Providing practical skills in curricular teaching-effect of SkillsLab and flipped classroom]. / Vermittlung praktischer Fähigkeiten in der curricularen Lehre ­ Effekt von SkillsLab und "flipped classroom".

BACKGROUND: In the course of the restructuring of medical studies, practical competencies are clearly defined as learning objectives for the first time. In order to make most effective use of the short attendance time available in otolaryngology, the aim of this study was to teach practical skills with the help of flipped classroom, digital teaching, and a newly established SkillsLab. MATERIALS AND METHODS: During their ENT internship, two groups of students-group A = 93 students (male n = 42, female n = 51) and group B = 113 students (male n = 42, female n = 71)-first worked through material provided online, which explained the individual examinations. This was followed by face-to-face teaching, which consisted of observation and practical exercise of the different examination techniques. While group A practiced on each other or on dummies, group B used structured workstations in the ENT SkillsLab, which was newly built for this purpose. The effects on motivation and subjective competence were measured using a questionnaire developed for this study. RESULTS: After working through the online material, both groups showed a high level of motivation and competence. On the day of face-to-face teaching, there was a gain in motivation and competence, which was statistically significant only in the SkillsLab group (p < 0.001). Although the SkillsLab group was inferior in terms of its subjective competence at the beginning, it was superior to the other group after the face-to-face teaching. CONCLUSION: Combination of digitized teaching in the flipped classroom with structured workstations in the setting of a SkillsLab enables more effective teaching of practical skills, which was reflected by increases in motivation and subjective competence in group B. In particular, the presentation of all collected findings on monitors allows verification of learning success and stimulates discussion.

Inconsistent Skin Prick Tests for Allergy to Birch Homologous Trees May Result from Cross-Reacting Allergens or Technical Errors.

INTRODUCTION: Skin prick tests (SPTs) are the gold standard for diagnosis of allergic rhinitis (AR). A decrease in the number of allergens included in standard SPT panels has recently been debated - particularly regarding the cross-reacting homologous pollen from birch, alder, and hazel trees - but has not yet been implemented in clinical guidelines. METHODS: A subgroup of patients with AR (n = 69) who showed inconsistent SPT results among birch, alder, and hazel was investigated in detail. Beyond SPT, patient workup included assessment of clinical relevance and various serological parameters (total IgE, and specific IgE to birch, alder, and hazel and to Bet v 1, Bet v 2, and Bet v 4). RESULTS: More than half the study group had negative SPT results for birch but positive results for alder and/or hazel, and 87% of the study group was polysensitized, showing at least one more positive SPT result for other plants. Whereas 30.4% of patients showed serological sensitization to birch pollen extract, only 18.8% displayed positive specific IgE to Bet v 1. Clinical assessment revealed that most patients with AR were polysensitized and had perennial symptoms or symptoms also occurring during times other than tree flowering times. If the SPT panel is limited to testing birch only, 52.2% of patients in this subgroup would have been overlooked. CONCLUSION: Inconsistent SPT results in the birch homologous group may result from cross-reacting allergens or technical errors. If patients report convincing clinical symptoms despite negative results from a reduced SPT panel or inconsistent results for homologous allergens, SPT should be repeated, and molecular markers should be added to achieve a correct diagnosis.

Ultrafast optogenetic stimulation of the auditory pathway by targeting-optimized Chronos.

Optogenetic tools, providing non-invasive control over selected cells, have the potential to revolutionize sensory prostheses for humans. Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in cochlear implants. However, most channelrhodopsins do not support the high temporal fidelity pertinent to auditory coding because they require milliseconds to close after light-off. Here, we biophysically characterized the fast channelrhodopsin Chronos and revealed a deactivation time constant of less than a millisecond at body temperature. In order to enhance neural expression, we improved its trafficking to the plasma membrane (Chronos-ES/TS). Following efficient transduction of SGNs using early postnatal injection of the adeno-associated virus AAV-PHPB into the mouse cochlea, fiber-based optical stimulation elicited optical auditory brainstem responses (oABR) with minimal latencies of 1 ms, thresholds of 5 µJ and 100 µs per pulse, and sizable amplitudes even at 1,000 Hz of stimulation. Recordings from single SGNs demonstrated good temporal precision of light-evoked spiking. In conclusion, efficient virus-mediated expression of targeting-optimized Chronos-ES/TS achieves ultrafast optogenetic control of neurons.

[New interdisciplinary teaching concept for the cross-sectional subject of allergology in human medicine studies]. / Interdisziplinäre Neukonzeption der Lehre im Querschnittsfach "Allergologie" im Studiengang Humanmedizin.

BACKGROUND: Although allergic diseases are among the most important health disorders, allergology is not anchored as an independent subject in the clinical part of medical studies in Germany. OBJECTIVE: As all universities and institutes face the same challenge, the aim of our project was to establish exemplary coordination and networking of education in allergology at one location in agreement with all involved departments and institutes. Particularly, Comprehensive Allergy Centers (CAC) offer an established infrastructure via which the revised allergology education program can be transferred to other universities. MATERIALS AND METHODS: After an extensive inventory of the current allergological curriculum at the University Medical Center Göttingen, a new teaching concept was developed in interdisciplinary consensus, supplemented by first-time provision of additional digital contents ("blended learning"), and finally evaluated. RESULTS: Initially, we observed a high level of fragmentation in the teaching of allergology in the clinical study sections of human medicine, with no coordination between the 12 clinical departments/institutes involved and no coherent framework for the specific learning content. Within the established structure of the interdisciplinary CAC, we revised, coordinated, and defined key areas for improved student education in clinical allergology. The allocation of new interactive learning elements as well as supplementary materials for self-studies was welcomed by the students and positively evaluated. A survey among students after completing the former vs. current curricula showed significant improvements in achieving the desired educational objectives.

Fast-track flipping: flipped classroom framework development with open-source H5P interactive tools.

BACKGROUND: The availability and popularity of laptops, tablet PCs and smartphones in private and work environments offers considerable potential for reasonably integrating blended learning formats into structured medical learning environments. The promising educational principle of the flipped classroom (FC) provides the opportunity to effectively combine e-learning and face-to-face teaching within a single framework. However, similar to most blended learning formats, the FC requires a solid groundwork of structured digitized learning content. As rearranging a whole curriculum is intense and time consuming, physicians occupied simultaneously in clinical practice and teaching may be confronted with a lack of time during this process. METHODS: We developed two straightforward approaches to transforming a pre-existing, lecture-based otolaryngology curriculum into interactive videos within a Moodle learning management system. Special attention was given to reducing individual working time for medical professionals. Thus, while one approach was mainly guided by a medical professional to control the content-related quality of video processing, we investigated an alternative approach outsourcing work to a technician. Afterwards, the working time was analysed and compared. The resulting videos were revised with the H5P plugin for moodle to adjust the content where necessary. RESULTS: We identified a fast-track approach for creating structured e-learning content suitable for flipped-classroom-based lectures, other blended learning formats, or even providing a whole curriculum online. The alternative approach significantly reduced working time for medical professionals but did not impair the content-related quality significantly. CONCLUSIONS: The use of H5P interactive tools via Moodle LMS provides a major procedural benefit by allowing the easy adjustment of pre-existing video material into suitable online content. Reasonably outsourcing work to technicians can significantly reduce the working time of medical professionals without decreasing the quality of learning content. The presented workflow can be used as a flexible approach for flipped classroom frameworks or other blended learning strategies where interactive videos are applicable.

Strategies of Digitized Learning. / Digitale Strategien in der Lehre.

The development of digital strategies in teaching is based on the technological progress of the last decades, but also on the strong motivation to focus a didactic concept on the learning individuals. The available data of German medical faculties indicate that digital teaching concepts currently play a subordinate role in medicine in general and specifically in otorhinolaryngology. By assessing data of our own institution, we could demonstrate that the majority of medical students refer mainly to material handed out by the lecturers as single source of information for learning Otorhinolaryngology. Therefore, the application of sound digital teaching strategies provides special chances, in particular in otorhinolaryngology to cope with the excessive amount of online information from partly unclear sources.Currently, the possible degree of digital teaching reaches from digital service supply via punctual provision of classic teaching concepts and blended learning up to completely digital curricula. The attractiveness of curricular integration of digital teaching strategies is less based on the utilization of merely technological progress, but rather on the variety of applying innovative curricula and new didactic concepts. Depending on the intended teaching purpose, the flipped classroom and the virtual reality seem to have a particularly high potential, while mobile learning is already established in individual practice. Testing and evaluating digital teaching innovations for concrete scenarios currently belongs to the most important scientific challenges of digital teaching concepts.Today, the nationwide implementation of digital teaching in Germany is less impeded by technical conditions, but by missing financing because sponsoring is currently mainly performed with reference to concrete projects; in the context of permanent implementation, however, regular costs arise. To support these promising teaching concepts, the sponsoring of institutions for digital teaching with provision of hard- and software solutions at universities could contribute significantly. Establishing cooperation to use such digital platforms might lead to a high efficiency regarding the distribution with simultaneously profiting of savings potential.

Flipped classroom frameworks improve efficacy in undergraduate practical courses - a quasi-randomized pilot study in otorhinolaryngology.

BACKGROUND: Curriculum design and specific topic selection for on-site practical courses in clinical disciplines with limited teaching time is challenging. An electronic learning supported curriculum based on the flipped classroom principle has a high potential to effectively gain knowledge and education along with improving practical experience. Here, we demonstrate the introduction of a flipped classroom curriculum for practical courses in Otorhinolaryngology (ORL) in real world practice to improve the on-site time management and students' experience. METHODS: Educational aims of our practical curriculum were analysed and rearranged into a flipped classroom (FC) framework. Core knowledge was taught preliminary based on a moodle platform in predominantly interactive formats. Two quasi-randomized groups were formed with 212 participants either receiving or not receiving access to the e-learning program to reduce a potential allocation bias to the e-learning group. All students completed a questionnaire with learning related items. Focusing the study on the intervention group, we investigated if students using the flipped classroom more often felt better prepared for the practical course. RESULTS: The online learning platform was highly accepted and frequently used by 66% of participating students in the e-learning group. Students with frequent use of our e-learning platform significantly felt better prepared for the practical course (p = 0.001). The far majority of all students supports the idea of further development of e-learning. More than 70% were generally interested in ORL. Handouts were the overall most important learning resource and more than 50% relied solely on them. CONCLUSIONS: Flipped classroom curricula can save time and help improving the on-site experience in practical courses especially in smaller surgical disciplines. The acceptance of digital learning is high, and most students rely on handouts for learning ORL, emphasizing the need for guidance by the teacher e.g. through electronic learning. Our results underline the high potential of FC to address teaching challenges for smaller medical disciplines with limited teaching time like ORL.

Audiometric Results of Open Cavity Tympanomastoidectomy in Advanced Attic Cholesteatoma.

In this retrospective study, we evaluated the audiometric results after using the retrograde mastoidectomy technique with open mastoid cavity for the removal of extended attic cholesteatomas. The described technique was used for cholesteatoma removal in 168 adult patients with an average follow-up time of 12 months. Due to cholesteatoma extension far into the mastoid, the disease was eradicated by the canal wall down (CWD) technique with the creation of an open mastoid cavity. Primary surgery was carried out in 47% of ears, with the remaining 53% representing revision surgery. In all cases, a classical CWD with an open mastoid cavity and partial obliteration with cartilage was created. A dry ear was achieved in 94% of cases. A postoperative air-bone gap ≤ 20 dB was achieved in 42.9% of the operated ears. 9.3% (n = 15) of the operated ears showed a postoperative air-bone gap > 30 dB. Important factors leading to significantly better hearing restoration were an intact malleus, the use of alloplastic titanium prostheses and primary surgery. Although most cholesteatomas nowadays can be eradicated with the canal wall up technique, in far advanced cholesteatomas, the CWD technique can be applied with acceptable postoperative hearing results.

Subgroups in the treatment of nasal polyposis with dupilumab: A retrospective study.

Dupilumab has been shown to be safe and effective in treating chronic rhinosinusitis with polyposis (CRSwNP). There is to this date no published data whether subgroups like patients with aspirin exacerbated respiratory disease (AERD), increased histologic eosinophilia or elevated blood eosinophil or IgE-levels benefit greater from dupilumab therapy. Moreover, there is no data comparing the efficacy of functional endoscopic sinus surgery (FESS) with dupilumab therapy. We conducted a retrospective chart review of all patients that were treated at a tertiary referral center for CRswNP with dupilumab. We also contacted the patients with a questionnaire to evaluate the efficacy of previous surgeries and dupilumab therapy by visual analogue scale (VAS) and the glasgow benefit inventory (GBI) as well as report on side effects. Overall, 75 patients were included in the study at hand that reported back 138 times. While dupilumab treatment was efficient, we found no systematic evidence of greater efficacy of dupilumab in patients with AERD, histologic eosinophilia or increased blood eosinophil or IgE-levels. All patients showed a considerable decrease in subjective burden of disease, objective smell tests and endoscopic findings. From the patients point of view, dupilumab therapy showed greater efficacy both in the VAS and the GBI overall and all subcategories but "social support." Dupilumab is efficient in treating CRSwNP; this effect is independent from disease characteristics like AERD, histologic eosinophilia, serum IgE-levels or eosinophil counts. There seems to be a group of patients that benefit greater from dupilumab therapy compared to FESS.

Developing Fast, Red-Light Optogenetic Stimulation of Spiral Ganglion Neurons for Future Optical Cochlear Implants.

Optogenetic stimulation of type I spiral ganglion neurons (SGNs) promises an alternative to the electrical stimulation by current cochlear implants (CIs) for improved hearing restoration by future optical CIs (oCIs). Most of the efforts in using optogenetic stimulation in the cochlea so far used early postnatal injection of viral vectors carrying blue-light activated channelrhodopsins (ChRs) into the cochlea of mice. However, preparing clinical translation of the oCI requires (i) reliable and safe transduction of mature SGNs of further species and (ii) use of long-wavelength light to avoid phototoxicity. Here, we employed a fast variant of the red-light activated channelrhodopsin Chrimson (f-Chrimson) and different AAV variants to implement optogenetic SGN stimulation in Mongolian gerbils. We compared early postnatal (p8) and adult (>8 weeks) AAV administration, employing different protocols for injection of AAV-PHP.B and AAV2/6 into the adult cochlea. Success of the optogenetic manipulation was analyzed by optically evoked auditory brainstem response (oABR) and immunohistochemistry of mid-modiolar cryosections of the cochlea. In order to most efficiently evaluate the immunohistochemical results a semi-automatic procedure to identify transduced cells in confocal images was developed. Our results indicate that the rate of SGN transduction is significantly lower for AAV administration into the adult cochlea compared to early postnatal injection. SGN transduction upon AAV administration into the adult cochlea was largely independent of the chosen viral vector and injection approach. The higher the rate of SGN transduction, the lower were oABR thresholds and the larger were oABR amplitudes. Our results highlight the need to optimize viral vectors and virus administration for efficient optogenetic manipulation of SGNs in the adult cochlea for successful clinical translation of SGN-targeting gene therapy and of the oCI.