Background Interleukin 23 is a critical cytokine in the pathogenesis of multiple sclerosis. But the local impact of interleukin 23 on the course of neuroinflammation is still not well defined. To further characterize the effect of interleukin 23 on CNS inflammation, we recently described a transgenic mouse model with astrocyte-specific expression of interleukin 23 (GF-IL23 mice). The GF-IL23 mice spontaneously develop a progressive ataxic phenotype with cerebellar tissue destruction and inflammatory infiltrates with high amounts of B cells most prominent in the subarachnoid and perivascular space. Methods To further elucidate the local impact of the CNS-specific interleukin 23 synthesis in autoimmune neuroinflammation, we induced a MOG35-55 experimental autoimmune encephalomyelitis (EAE) in GF-IL23 mice and WT mice and analyzed the mice by histology, flow cytometry, and transcriptome analysis. Results We were able to demonstrate that local interleukin 23 production in the CNS leads to aggravation and chronification of the EAE course with a severe paraparesis and an ataxic phenotype. Moreover, enhanced multilocular neuroinflammation was present not only in the spinal cord, but also in the forebrain, brainstem, and predominantly in the cerebellum accompanied by persisting demyelination. Thereby, interleukin 23 creates a pronounced proinflammatory response with accumulation of leukocytes, in particular B cells, CD4+ cells, but also γδ T cells and activated microglia/macrophages. Furthermore, transcriptome analysis revealed an enhanced proinflammatory cytokine milieu with upregulation of lymphocyte activation markers, co-stimulatory markers, chemokines, and components of the complement system. Conclusion Taken together, the GF-IL23 model allowed a further breakdown of the different mechanisms how IL-23 drives neuroinflammation in the EAE model and proved to be a useful tool to further dissect the impact of interleukin 23 on neuroinflammatory models.
Although IL-23 and downstream signal transduction play essential roles in neuroinflammation, the local impact of IL-23 in multiple sclerosis is still not fully understood. Our previous study revealed that the central nervous system (CNS)-restricted expression of IL-23 in a mouse model with astrocyte-specific expression of IL-23, called GF-IL23 mice, leads to spontaneous formation of infiltrates in the brain, especially in the cerebellum. To further investigate the impact of CNS-specific IL-23-expression on neuroinflammation, we studied the GF-IL23 model in mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor (GF23-2D2 mice). The GF23-2D2 mice developed a chronic progressive experimental autoimmune encephalomyelitis with myelitis and ataxia without requiring additional immunization. CNS-production of IL-23 alone induced pronounced neuroinflammation in the transgenic MOG-specific T cell receptor model. The GF23-2D2 mice spontaneously developed multilocular infiltrates with a high number of B cells, demyelination and a proinflammatory cytokine milieu indicating that the interaction of encephalitogenic T cells and B cells via co-stimulatory factors seemed to be crucial.
BackgroundPoint-of-care ultrasound (POCUS) is rapidly gaining ground within different areas of applications. Despite the high and increasing relevance of ultrasound, the availability of structured training programs in medical schools is still limited. Therefore, many doctors keep acquiring all their ultrasound skills throughout their postgraduate training. As a result, new residents lack theoretical and practical ultrasound abilities that are critical in everyday clinical practice. In order to improve this, we created and implemented a complete ultrasound curriculum for all medical students throughout their internship year that focuses on hands-on abilities in ultrasound imaging.MethodsWe used Kern‘s six-step model of curricular development comprising (1) problem identification and general needs assessment, (2) needs assessment of the targeted learners, (3) goals and objectives, (4) educational strategies, (5) implementation, and (6) evaluation and feedback by board-certified ultrasound experts. A two rounds Delphi process with multilevel, self-completed questionnaires and individual using a 9-point Likert scale and free text comments was used to identify learning objectives and reach agreement on the content of the curriculum.ResultsThe curriculum developed is aimed at students with no or little experience in their internship year and will be taught as part of their weekly-based internship training courses consisting of 2 hours of theory and 3 hours of practical training. The training will be conducted within a modular framework focusing on the key requirements of POCUS with increasing levels of complexity in accordance with the recommendations of the German Society for Ultrasound in Medicine (DEGUM), the European Federation of Societies for ultrasound in Medicine and Biology (EFSUMB) and the World Federation for ultrasound in Medicine and Biology (WFUMB). A longitudinal e-learning system will be implemented in addition to the practical and theoretical teaching units to track and examine the progress of the students.ConclusionEarly integration of ultrasound training into medical education as part of a structured and standardized broad ultrasound curriculum enables medical students to acquire basic skills and apply them practically. Fundamental scanning skills are acquired by hands-on exercises in small, supervised groups as part of BI-POCUS. BI-POCUS therefore provides an excellent opportunity to improve the clinical skills of future physicians. More research is needed to analyze the learning outcomes for medical students and the improvement of the patient’s outcome by establishing such an ultrasound curriculum.
BackgroundGiant cell arteritis (GCA) is an immune-mediated, granulomatous vasculitis that primarily affects the elderly and results in local vascular changes of middle-sized and large arteries. A protracted diagnosis delaying high-dose corticosteroid therapy may result in permanent visual loss. Therefore, invasive and time-consuming biopsy of the superficial temporal artery has been replaced by high-resolution vascular ultrasound of the temporal and axillary artery to evaluate extracranial inflammation. Intracranial involvement of the ophthalmic vessels can be visualized by magnetic resonance imaging. Transorbital Ultrasound (TOS), as a simple and inexpensive diagnostic method, could be an option for assessing the optic nerve and the central retinal artery (CRA) and might improve diagnostic sensitivity in GCA, especially in anterior optic neuropathy (AION).ObjectivesThe purpose of this study was to assess the utility of TOS in patients with untreated and newly diagnosed GCA.MethodsPatients with new GCA diagnosed by a board-certified rheumatologist who also met the expanded ACR-EULAR classification criteria were enrolled in the study between October 1, 2018, and May 31, 2022. Each participant underwent TOS to assess the CRA and optic nerve diameter (OND). The eyes of the patients with GCA were categorized as eyes with or without visual impairment (VI), which was defined as transient or persistent visual field loss, diplopia, amaurosis, and blurred vision. Peak systolic velocity (PS), end diastolic velocity (ED), resistance index (RI) of the CRA and OND were recorded.ResultsA total of 54 GCA patients were prospectively enrolled in the study, 27 of whom had VI in at least one eye. To account for repeated measures within a patient, associations between TOS and VI were evaluated using linear mixed-effect models (LME). PS and ED values of the CRA were statistically significant lower in the eyes with GCA manifestation (ß=-1.93; p<0.001 for PS; ß=-0.61; p=0.003 for ED). The RI of the CRA was statistically significant reduced in the eyes with GCA associated VI (ß=-0.04; p=0.007). OND was lower in the eyes with VI, too (ß=-0.36; p=0.06) (Table 1, Figure 1).ConclusionIn TOS, eyes affected by VI exhibited significantly reduced PS, ED, and RI indicating an inflammatory process of the intracranial vessels leading to impaired blood flow to the optic nerve and contributing to ischemia-associated optic neuropathy. The shown decrease in OND is probably due to reduced blood flow and the resulting lessened vessel diameter and, in the case of a persistent depletion of blood flow, due to atrophic alterations of the optic nerve suggestive of irreversible damage. Therefore, VI in combination with decreased PS, ED, RI and OND may constitute a specific finding in the diagnosis of optic affection in GCA. Our study was the first to prospectively demonstrate the diagnostic value of TOS in untreated and new diagnosed GCA patients as a complementary diagnostic tool to assess GCA associated intracranial inflammation.Table 1.Mean values of central retinal artery flow velocity, resistance index, optic nerve diameter in patients with/ without visual impairmentGCA without VIGCA with VILME (ß)p-valuePeak systolic velocity (SD); cm/s12.95 (± 3.84)10.16 (± 4.10)- 1.93<0.001End diastolic velocity (SD); cm/s3.91 (± 0.12)3.18 (± 1.27)-0.610.003Resistance Index (SD)0.69 (± 0.10)0.64 (± 0.17)-0.040.007Optic nerve diameter (SD); mm5.3 (± 0.99)4.93 (± 1.1)-0.360.06Eyes affected by VI exhibited reduced flow velocity and resistance index of the central retinal artery and decreased optic nerve diameter. Abbrev.: GCA: Giant Cell Arteritis, VI: Visual impairment, LME: Linear mixed-effects model, SD: standard deviationFigure 1.Assessment of central retinal artery/ optic nerve diametera, b: Measurement of central retinal artery flow velocity/ optic nerve diameter; c, d: Central retinal artery flow velocity (cm/s), e: Resistance Index, f: Optic nerve diameter (mm). Abbrev.: GCA: Giant Cell Arteritis, VI: Visual impairment, PS: Peak systolic velocity, ED: End diastolic velocityREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
BackgroundMusculoskeletal ultrasound (MSUS) is increasingly gaining importance as an imaging tool in rheumatology. Most training programs currently address resident doctors. However, several studies have demonstrated that teaching MSUS to medical students improves their palpation skills and understanding of musculoskeletal anatomy. With the development of portable ultrasound devices, MSUS education is lately getting more flexible and location-independent. In addition, the COVID-19 pandemic raised awareness of telemedicine training as a powerful tool to ensure the teaching of practical skills under pandemic conditions.ObjectivesThe purpose of our study is to establish a telemedical MSUS course for medical students and to compare its effectiveness with a conventional on-campus course as a world-wide pilot study. In doing so, we aim to expand student educational opportunities in MSUS using innovative teaching options while ensuring quality maintenance of teaching.MethodsThirty medical students were randomized to either a virtual group being delivered only telemedicine instructions, or an on-campus cohort receiving the course in a conventional format. Each student was provided with a handheld ultrasound device. Prior to the start of the course, the students’ skills were assessed with an Objective Clinical Structured Examination (OSCE). During the course, a DEGUM-III-certified course instructor taught the basic physics of ultrasound and standard sections of the MUDE ultrasound protocol[1]. In order to quantify the students’ learning progress, a second OSCE was carried out after completion of the course. [1].ResultsAt the time of this analysis, data collection within the on-campus course has already been completed, whereas the virtual course is still ongoing. While the average score of the students in the PRE-course OSCE was 21,02% (SD ±6,78), the students were able to achieve an average of 90% (SD ±6,81) in the POST-course OSCE after the intervention.ConclusionWith the results obtained so far, it can be shown that an innovative course concept with hand-held ultrasound devices, originally developed for dermatologists to improve the detection of psoriatic arthritis, can be used very well in student teaching without major modifications and leads to a significant increase in MSUS skills among medical students. The TELMUS study thereby offers a successful example of extending an existing course concept to student teaching and thus promoting the next generation of rheumatologists.Reference[1]Grobelski J, Recker F, Wilsmann- Theis D,et al.Etablierung und Validierung eines didaktischen muskuloskelettalen Ultraschallkurses für Dermatologen unter Verwendung eines innovativen Hand-Ultraschallsystems – die MUDE-Studie (Muskuloskelettaler Ultraschall für Dermatologen).J Deutsche Derma Gesell2021;19:1753–60. doi:10.1111/ddg.14614_gFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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