Transorbital ultrasound in the diagnosis of giant cell arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß = -1.91; P = 0.029; EDV: ß = -0.57; P = 0.032) and significantly elevated OND (ß = 0.79; P = 0.003) compared with controls. RI did not significantly differ from controls (ß = -0.06, P = 0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (P = 0.048) and EDV (P = 0.040). No association was found with RI (P = 0.249), while a positive significant association was noted with OND (P < 0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Exploring pulmonary involvement in newly diagnosed rheumatoid arthritis, and psoriatic arthritis: a single center study.

OBJECTIVES: This cross-sectional study aimed to determine the prevalence, manifestation, and risk factors of pulmonary involvement in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to evaluate the efficacy of various diagnostic tools in screening for pulmonary involvement. METHODS: Untreated, newly diagnosed patients with RA and PsA underwent an extensive multimodal diagnostic approach including clinical and laboratory assessment, pulmonary function tests, and chest radiography. RESULTS: We recruited 50 arthritis patients (26 RA, 24 PsA) and 26 control subjects. Respiratory symptoms were found in 36.0 % of arthritis patients and 11.5 % of controls (p = 0.031). Pathologically reduced breathing width (< 3.0 cm) was significantly more common in arthritis patients (64.0 %) than in controls (23.1 %) (p < 0.001). Pulmonary function test results did not differ significantly between groups. Chest radiography revealed pulmonary involvement in 37.0 % of arthritis patients, higher in RA (50.0 %) than in PsA (22.7 %). Notably, only 35.3 % of arthritis patients with radiographic pulmonary involvement were symptomatic, with 64.7 % being asymptomatic. Radiographic pulmonary involvement was associated with advanced age (p = 0.002) and increased rheumatoid factor levels (p = 0.024). CONCLUSION: Our research underscores the significant prevalence of largely asymptomatic pulmonary involvement in newly diagnosed RA and PsA patients. These findings highlight the importance of an early, multidisciplinary screening approach, particularly for high-risk individuals. Further large-scale studies are needed to develop comprehensive screening protocols to improve early detection and treatment of pulmonary involvement in arthritis.

Assessing sleep-related breathing disorders among newly diagnosed rheumatoid and psoriatic arthritis patients: a cross-sectional study.

OBJECTIVES: This cross-sectional study aimed to determine the prevalence and risk factors for sleep-related breathing disorders (SRBD) in newly diagnosed, untreated rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, and to develop a screening algorithm for early detection. METHODS: We evaluated newly diagnosed RA or PsA patients using the Epworth Sleepiness Scale (ESS) questionnaire, cardiorespiratory polygraphy (RPG), and clinical and laboratory assessments. Sleep apnea syndrome (SAS) was diagnosed based on pathological RPG findings excessive daytime sleepiness, defined as ESS score above 10. RESULTS: The study included 39 patients (22 RA, 17 PsA) and 23 controls. In RPG, SRBD was identified in 38.5% of arthritis patients compared to 39.1% of controls (p = 1.00), with male gender (p = .004) and age (p < .001) identified as risk factors. Excessive daytime sleepiness was noted in 36.4% of RA patients, 17.6% of PsA patients, and 21.7% of controls. Of the 24 patients diagnosed with SRBD, 41.6% met the criteria for SAS. SAS prevalence was 31.8% among RA patients, 0% in PsA patients, and 13% in controls. A significant association was observed between excessive daytime sleepiness and SRBD (p = .036). CONCLUSION: Our findings reveal a high prevalence of SRBD in newly diagnosed, untreated RA and PsA patients in ESS and RPG, with excessive daytime sleepiness being a reliable predictor of SRBD. Patients with RA exhibited a higher predisposition to SAS. We therefore suggest incorporating ESS and RPG as screening tools in RA or PsA for early detection and management of SRBD.

First insights of integrating the Bonn Internship Curriculum for Point-of-Care Ultrasound (BI-POCUS): progress and educational aspects.

BACKGROUND: Point-of-care ultrasound (POCUS) is rapidly gaining prominence in various clinical settings. As its use becomes more widespread, there is a growing need for comprehensive ultrasound training in medical education to ensure that future healthcare professionals are proficient in this essential diagnostic tool. OBJECTIVE: This study is the first attempt by the University of Bonn to seamlessly integrate ultrasound courses and the use of ultrasound devices into the regular activities of final year medical students and to evaluate the usage of these devices. METHODS: A total of forty students in their practical year were provided with a hendheld ultrasound device for a period of four months. During this time, they were invited to take part in eight optional ultrasound courses in which they acquired images and those images were rated using a specially developed rating system. At the end of the tertial, students were able to take part in a voluntary survey on the use of the equipment. RESULTS: Participation in the optional ultrasound courses was well received, with the Introduction and FAST module drawing the largest number of participants (29). Among the ultrasound images acquired by students, those of the lungs obtaining the highest rating, with 18.82 (SD ± 4.30) points out of 23 points, while the aorta and vena cava images scored lowest, with an average of 16.62 (SD ± 1.55) points. The overall mean score for all images was 17.47 (SD ± 2.74). Only 21 students responded to the survey. Of the participating students, 67% used the device independently four times or fewer during the tertial. CONCLUSION: The study aimed to enhance the BI-POCUS curriculum by improving students' ultrasound skills during their practical year. However, device usage was lower than expected, with most students using it only once a month or less. This raises concerns about the justification of the effort and resources. Future initiatives will focus on technical improvements, better login data provision, and closer monitoring of usage and progress, emphasizing the need for practical ultrasound training in medical education.

[News on the imaging of large vessel vasculitis]. / Neues in der Bildgebung von Großgefäßvaskulitiden.

Large vessel vasculitis, including giant cell arteritis (GCA) and Takayasu arteritis (TAK), are autoimmune diseases primarily affecting the aorta and its branches. GCA is the most common primary vasculitis. Inflammatory changes in the vessel walls can cause serious complications such as amaurosis, stroke, and aortic dissection and rupture. Imaging techniques have become an integral part for the diagnosis and monitoring of large vessel vasculitis, allowing for effective disease monitoring. GCA and TAK exhibit similar patterns of vascular distribution. However, the temporal arteries are never involved in TAK, and axillary arteritis occurs more frequently in GCA. In most centers, ultrasound of the temporal and axillary arteries has replaced temporal artery biopsy as the primary diagnostic tool for GCA. In addition to ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and [18F]-FDG (fluorodeoxyglucose) positron emission tomography-computed tomography (PET) are important, particularly for visualizing the aorta. Moreover, PET-CT is now also capable of assessing the temporal arteries, although it is not yet widely available. In polymyalgia rheumatica (PMR), ultrasound of the shoulder and hip regions is part of the ACR/EULAR classification criteria. MRI allows detailed visualization of additional inflammatory extraarticular manifestations, showing characteristic inflammatory lesions in entheses, tendons, and ligaments. [18F]-FDG-PET-CT also enables the visualization of musculoskeletal inflammation, especially in the shoulder and hip regions, as well as paravertebral areas. Ultrasound can detect subclinical GCA in up to 23% of patients with PMR, which should be treated like GCA. Technological innovations such as new radiotracers and improved MRI imaging could further enhance the diagnosis and monitoring of large vessel vasculitis and PMR, thus playing a crucial role in improving the prognosis through faster initiation of therapy.

Astrocyte-specific expression of interleukin 23 leads to an aggravated phenotype and enhanced inflammatory response with B cell accumulation in the EAE model.

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.

Vascular-adhesion protein 1 in giant cell arteritis and polymyalgia rheumatica.

Vascular adhesion protein-1 (VAP-1) is a type 2 transmembrane sialoglycoprotein with oxidative deamination functionality, encoded by the amine oxidase copper-containing 3 (AOC3) gene. VAP-1 is widely expressed across various tissues, particularly in highly vascularized tissues and organs essential for lymphocyte circulation. In the vascular system, VAP-1 is predominantly found in vascular smooth muscle cells and endothelial cells, with higher expression levels in vascular smooth muscle cells. Under inflammatory conditions, VAP-1 rapidly translocates to the endothelial cell surface, facilitating leukocyte adhesion and migration through interactions with specific ligands, such as sialic acid-binding immunoglobulin-type lectins (Siglec)-9 on neutrophils and monocytes, and Siglec-10 on B cells, monocytes, and eosinophils. This interaction is crucial for leukocyte transmigration into inflamed tissues. Furthermore, VAP-1's enzymatic activity generates hydrogen peroxide and advanced glycation end-products, contributing to cytotoxic damage and vascular inflammation. In this context, the soluble form of VAP-1 (sVAP-1), produced by matrix metalloproteinase cleavage from its membrane-bound counterpart, also significantly influences leukocyte migration. This review aims to elucidate the multifaceted pathophysiological roles of VAP-1 in vascular inflammation, particularly in giant cell arteritis (GCA) and associated polymyalgia rheumatica (PMR). By exploring its involvement in immune cell adhesion, migration, and its enzymatic contributions to oxidative stress and tissue damage, we investigate the importance of VAP-1 in GCA. Additionally, we discuss recent advancements in imaging techniques targeting VAP-1, such as [68Ga]Ga-DOTA-Siglec-9 PET/CT, which have provided new insights into VAP-1's role in GCA and PMR. Overall, understanding VAP-1's comprehensive roles could pave the way for improved strategies in managing these conditions.

Development and implementation of a comprehensive ultrasound curriculum for medical students: The Bonn internship point-of-care-ultrasound curriculum (BI-POCUS).

Background: Point-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. Methods: We 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. Results: The 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. Conclusion: Early 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.

Lung Ultrasound in Predicting Outcomes in Patients with COVID-19 Treated with Extracorporeal Membrane Oxygenation.

Pulmonary involvement due to SARS-CoV-2 infection can lead to acute respiratory distress syndrome in patients with COVID-19. Consequently, pulmonary imaging is crucial for management of COVID-19. This study aimed to evaluate the prognostic value of lung ultrasound (LUS) with a handheld ultrasound device (HHUD) in patients with COVID-19 treated with extracorporeal membrane oxygenation (ECMO). Therefore, patients underwent LUS with a HHUD every two days until they were either discharged from the intensive care unit or died. The study was conducted at the University Hospital of Bonn's anesthesiological intensive care ward from December 2020 to August 2021. A total of 33 patients (median [IQR]: 56.0 [53-60.5] years) were included. A high LUS score was associated with a decreased P/F ratio (repeated measures correlation [rmcorr]: -0.26; 95% CI: -0.34, -0.15; p < 0.001), increased extravascular lung water, defined as fluid accumulation in the pulmonary interstitium and alveoli (rmcorr: 0.11; 95% CI: 0.01, 0.20; p = 0.030), deteriorated electrolyte status (base excess: rmcorr: 0.14; 95% CI: 0.05, 0.24; p = 0.004; pH: rmcorr: 0.12; 95% CI: 0.03, 0.21; p = 0.001), and decreased pulmonary compliance (rmcorr: -0.10; 95% CI: -0.20, -0.01; p = 0.034). The maximum LUS score was lower in survivors (median difference [md]: -0.35; 95% CI: -0.55, -0.06; p = 0.006). A cutoff value for non-survival was calculated at a LUS score of 2.63. At the time of maximum LUS score, P/F ratio (md: 1.97; 95% CI: 1.12, 2.76; p < 0.001) and pulmonary compliance (md: 18.67; 95% CI: 3.33, 37.15; p = 0.018) were higher in surviving patients. In conclusion, LUS with a HHUD enables continuous evaluation of cardiopulmonary function in COVID-19 patients receiving ECMO support therapy and provides prognostic value in determining the patients' likelihood of survival.

MOG-Specific T Cells Lead to Spontaneous EAE with Multilocular B Cell Infiltration in the GF-IL23 Model.

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.

Central role of B cells in interleukin-23 dependent neuroinflammation in the GF-IL23 model.

Interleukin (IL)-23 is one of the critical cytokines in autoimmune neuroinflammation. To further clarify the local function of IL-23 on the course of neuroinflammation, we recently established a transgenic mouse model with astrocyte-specific expression of IL-23 (GF-IL23). The GF-IL23 mice spontaneously developed a progressive ataxic phenotype with cerebellar infiltration with high amounts of B cells most prominent in the subarachnoid and perivascular space. To enlighten the B cell role in GF-IL23 mice, we generated GF-IL23 mice on a B cell knockout (k.o.) background (GF-IL23 B cell k.o.). GF-IL23 B cell k.o. mice compared with GF-IL23 mice had no infiltrates or only minor infiltration, and no antibody deposition was detected in the cerebellum. Furthermore, microglia, astrocyte activation, hypervascularization and demyelination were reduced in GF-IL23 B cell k.o. mice compared with GF-IL23 mice. Cytokines and chemokine receptors like IL-12a, cerebrospinal fluid 2 and CXCR3 were downregulated. Our study indicates that B cells are essential in IL-23-dependent neuroinflammation in the GF-IL23 model.