Raphael Micheroli’s research while affiliated with University Hospital Zürich and other places

Purpose To provide an overview of the normal anatomy of the knee using high-resolution ultrasonography. Materials and methods Normal ultrasound images were obtained from a healthy subject, and corresponding images of human anatomy and histology were acquired from body donors. Results Several high-resolution ultrasound, anatomical, and histological images were created to illustrate and comprehensively describe the basic standard scans in compliance with international standards. This atlas summarizes a selection of typical normal findings. Conclusions This overview explains the normal anatomy of the knee as seen by ultrasonography. High-resolution knee musculoskeletal ultrasonography aims to provide an accurate structural evaluation, which requires comprehensive knowledge of sonoanatomy. When used appropriately, contemporary high-resolution musculoskeletal ultrasonography enhances knee imaging by connecting anatomical cross-sections and intricate histology to specific anatomical features.

Single-cell RNA sequencing (scRNAseq) of human tissues has expanded our understanding of the complexity of cellular subsets and their changes in disease. The availability of scRNAseq data in different tissues and disease states provides an opportunity to compare cellular subsets and identify common and unique cellular activation. In this study, we aimed to characterize shared and tissue-specific myeloid and stromal phenotypes and uncover key cellular subtypes involved in pathogenic tissue activation. We analyzed scRNAseq data from 14 public datasets, comprising heart, lung, skin, and synovium in both healthy and diseased states. Our analysis identified distinct and overlapping myeloid and stromal cell populations in these tissues. Despite significant inter-individual variability, we were able to identify both shared and disease-specific changes in these cell populations. These findings provide insights into the conserved and tissue-specific roles of myeloid and stromal cells in health and disease and contribute to a better understanding of tissue pathology and potential therapeutic targets.

Background Patient research partners (PRPs) are people living with a relevant disease who actively contribute to research. Their contribution is beneficial for any research project. Although the inclusion of PRPs in rheumatology research is increasingly recommended, its practical implementation, particularly in translational research, remains limited . Enhancing PRP engagement requires a clear understanding of the necessary steps. Objective This study aims to show steps to achieve successful collaboration between PRPs and researchers in clinical and transitional research in rheumatology. Methods We established a PRP network by following five main steps: setting up infrastructure, recruitment, training, PRP involvement at an early stage, and ongoing support. We adhered to overall principles of openness, feedback, and regular evaluations to create a respectful and collaborative environment. The initiative was qualitatively assessed via an online questionnaire developed by each six researchers and PRPs. Results Communicating our initiative at laboratory open days and to patient associations has enabled to create a network of 66 PRPs. A match-making tool was introduced to allocate interested PRPs with a project request. This led to PRP involvement in 15 projects, including 9 in translational research. Two PRP-coordinators provided support including glossaries and educational courses . Conclusion Our initiative outlines five essential steps for establishing PRP collaboration in rheumatology research, including translational research. This approach benefited both PRPs and researchers and might serve as a guide for other centres.

Real-world data on gender differences in quality of life among psoriasis patients before and during treatment are scarce. This study analysed data of 748 adults with moderate-to-severe psoriasis enrolled in the Swiss Dermatology Network of Targeted Therapy registry between 2011 and 2023. Quality of life was assessed using the Dermatological Life Quality Index at baseline and at 3, 6, 12, 18, and 24 months. At baseline, women reported significantly lower quality of life than men, with higher Dermatological Life Quality Index scores in the IL-17 inhibitor group (15.0 vs 11.0, p = 0.027), IL-12/23 inhibitor group (7.5 vs 7.0, p = 0.049), and non-biologic therapy group (13.0 vs 9.0, p < 0.001). Although quality of life improved across all subgroups during the follow-up period, women treated with IL-12/23 inhibitors continued to report worse quality of life compared with men after 2 years (p < 0.05), while no significant differences were observed with other therapies. These findings emphasize that women with psoriasis experience lower quality of life at treatment initiation and throughout non-biologic and biologic therapies, underlining the importance of addressing gender-specific differences in the management of psoriasis.

Background Efficacy of tumour necrosis factor inhibitors (TNFi) for peripheral arthritis in patients with psoriatic arthritis (PsA) has been established in randomized clinical trials that have used improvement in summated joint counts as an outcome. Whether joints at different anatomical locations might respond differentially to TNFi remains unknown. The aim of the study was to investigate potential variations in the responsiveness to a first tumour necrosis factor inhibitor (TNFi) among joints at distinct locations in patients with psoriatic arthritis (PsA) treated in routine clinical care. Methods Bionaive PsA patients from nine European countries were included in this observational cohort study if ≥ 1 joint was swollen at the initiation of a first TNFi as monotherapy or added to methotrexate. Only the 28-joint count was available without imaging data confirming the presence of synovitis. The primary outcome was time to first resolution of joint swelling at each joint level. Hazard ratios (HR) for resolution comparing different joint locations were estimated using interval-censored mixed-effects Cox proportional hazards models, including a random effect for country and patient, adjusted for age and sex. Results A total of 1729 patients with 8397 swollen joints at the start of TNFi were included. Considering the upper extremity, a higher rate of resolution of joint swelling (HR, 95% CI) was observed for the shoulder (1.65, 1.16–2.35) and elbow (1.90, 1.38–2.61), while a lower rate was found for the wrist (0.72, 0.62–0.83) compared to the joints of digit 3. Within fingers, and using the same reference, joint swelling resolved fastest in digit 4 (1.77, 1.49–2.11) and digit 5 (1.88, 1.53–2.31). A lower rate of resolution of joint swelling was found for the knee in comparison to the elbow, the corresponding joint on the upper limb (0.56, 0.40–0.78). Conclusion The time to resolution of joint swelling upon treatment with TNFi in patients with PsA seems to depend on the localisation of the affected joints.

Objectives To investigate the pro-phagocytic phenotype of macrophages in SSc and other rheumatic diseases by examining their activation, signaling pathways, and treatment responses, with the goal of uncovering mechanisms that drive enhanced phagocytosis. Methods Single-cell RNA sequencing (scRNA-seq) datasets (GSE138669/GSE212109) from skin and lung macrophages of healthy controls and SSc patients were analyzed. Human monocyte-derived macrophages (hMDM) were differentiated from CD14+ monocytes from healthy controls, SSc, RA, PsA, and axSpA patients. In selected experiments, hMDMs were pretreated with 0.1 μM nintedanib. Phagocytic activity was quantified using pHrodo bioparticles and flow cytometry. Macrophage surface markers were evaluated by flow cytometry, NF-κB signaling by Western blot, and gene expression by RT-qPCR. Results Analysis of scRNA-seq datasets revealed a pro-phagocytic signature in SSc-affected organs. SSc macrophages, particularly the FCGR3A hi cluster in skin, exhibited elevated expression of FCGR genes and enriched FcγR-mediated phagocytosis pathways, accompanied by pro-inflammatory markers. This phenotype extended to FCN1 hi lung macrophages in SSc patients with interstitial lung disease, indicating a systemic pro-inflammatory and phagocytic profile. hMDMs from SSc, RA, and PsA patients demonstrated enhanced phagocytic activity in vitro. Elevated FcγRI and FcγRII levels were identified as key drivers of increased phagocytic activity and subsequent IL-6-driven inflammation. Nintedanib showed reduction in FcγRI expression, suggesting its potential therapeutic benefit in attenuating the phagocytic process. Conclusion This study highlights FcγR-expressing macrophages as drivers of phagocytosis and inflammatory responses in SSc. Dysregulated activation of these macrophages could lead to persistent inflammation and fibrosis in rheumatic diseases, highlighting new potential therapeutic approaches.

Real-world data on the effectiveness and safety of tildrakizumab, an interleukin 23p19 inhibitor, in Switzerland is limited. The objectives of this analysis were to assess the effectiveness and safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis in Switzerland. Twenty-eight adults from the Swiss Dermatology Network for Targeted Therapies registry (SDNTT), who were on tildrakizumab treatment and had at least 3 months’ follow-up, were enrolled in this prospective, multicentre study. No missing data imputation was performed. The median Psoriasis Area and Severity Index (PASI) decreased from 9.5 at baseline to 2.1 and 0.3 (both p < 0.001) after 3 and 18 months, respectively, of tildrakizumab treatment. After 3 months, 76.9%/30.8% patients reached an absolute PASI < 3/ < 1. These rates increased to 85.7%/57.1% after 18 months of treatment. The proportions of patients achieving PASI 90/100 responses were 47.8%/30.4% at month 6 and 42.9%/14.3% at month 18. A significant improvement in quality of life up to 18 months of follow-up was observed as measured by the Dermatology Life Quality Index. There were no treatment discontinuations due to adverse events. This real-world registry provides robust evidence supporting the long-term effectiveness and favourable safety profile of tildrakizumab in treating patients with moderate-to-severe psoriasis.

Ultrasonography is a reliable imaging technique for the accurate diagnosis and evaluation of musculoskel- etal disorders. Recent developments in ultrasound technology have significantly increased image resolu- tion, making it possible to see anatomical features at almost microscopic dimensions. Current standards for standardized shoulder ultrasonography mostly depend on outdated machine types and configurations that may not fully utilize these high-resolution imaging capabilities. In this article, we give a clear and com- prehensive introduction to high-resolution shoulder sonography, using histological and anatomical images from cadavers for comparison. Images collected using contemporary technology are shown, and interna- tional standard practices are considered. The examination and normal results are presented in a methodical manner, beginning posteriorly, moving frontally, then more anteriorly, and concluding with a lateral and optional axillary examination. This article focuses on the anterior and lateral shoulder.