Clinical Research Directory

Extracellular Vesicle Dynamics Predicting Vascular Complications and Treatment Response in Systemic Sclerosis

Systemic sclerosis is a multisystem autoimmune disease characterized by vascular dysfunction, immune dysregulation, and progressive tissue fibrosis. Cardiopulmonary complications and peripheral vascular involvement are the principal causes of disability and mortality. Extracellular vesicles (EVs) have emerged as key mediators of paracrine intercellular communication. Preclinical studies further suggest that EVs mediate long-range inter-organ communication through the circulation. However, the inability to directly track EV trafficking in vivo in humans has limited the understanding of their contribution to systemic inter-organ communication. The investigators propose that systemic sclerosis provides a unique human model for investigating circulating EV-mediated inter-organ communication in a multisystem disease. The central hypothesis is that arteriovenous differences in the molecular and cellular characteristics of circulating EVs reflect their dynamic exchange between individual organs and the bloodstream, and that these differences are associated with disease severity. Comparison of EVs across the circulation, rather than relying exclusively on peripheral blood samples, enables a more direct assessment of organ-specific EV release and uptake. Characterizing EV dynamics along the circulatory pathway has the potential to identify novel biomarkers and therapeutic targets for systemic sclerosis while providing fundamental insights into EV-mediated inter-organ communication in humans.

Prospective Exploration of Vascular Complications Associated With the Use of Immune Checkpoint Inhibitors

The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of many oncological diseases, and their use continues to increase. ICIs are monoclonal antibodies that target immune checkpoints such as PD-1 (programmed cell death protein 1, as seen in nivolumab, pembrolizumab, and cemiplimab), PD-L1 (programmed cell death protein 1 ligand, as seen in atezolizumab, avelumab, and durvalumab), CTLA-4 (cytotoxic T-lymphocyte antigen 4, as seen in ipilimumab and tremelimumab), or LAG-3 (lymphocyte-activating gene 3, as seen in relatlimab), which play a crucial role in immune tolerance to cancer cells. However, the surge in ICI prescriptions has been accompanied by the occurrence of numerous side effects, some of which are severe or even fatal. ICIs have a different toxicity spectrum than conventional chemotherapy, and most toxicities result from excessive immunity against different organs. This immune-mediated toxicity can affect various organ systems, including the heart and blood vessels. Pharmacovigilance data from clinical trials conducted by Bristol-Myers Squibb, which marketed ipilimumab (anti-CTLA-4) and nivolumab (anti-PD1), revealed 18 cases (0.09%) of myocarditis among 20,594 subjects. While cardiac complications induced by immune checkpoint inhibitors (ICIs), particularly autoimmune myocarditis, are widely described, the impact of these treatments on the vascular system remains poorly understood. However, a variety of vascular complications have been reported, ranging from vasculitis of large, medium, and small vessels to a possible increase in arterial thrombotic events, ischemic strokes, and acute coronary syndromes. The incidence of vasculitis appears to be between 1% and 2% of patients treated with immune checkpoint inhibitors (ICIs). This is emerging as a significant signal in various pharmacovigilance studies, suggesting the involvement of immune checkpoint derepression in the pathophysiology of vasculitis. A translational study demonstrated the major role of CTLA-4 in the pathophysiology of giant cell arteritis (GCA), although the precise mechanisms involved remain to be determined. Therefore, a specific immune environment could promote the development of vasculitis, a phenomenon reproduced by ICI administration. The increase in arterial thrombotic vascular events was primarily observed in a matched cohort study, which showed a threefold increased risk of arterial thrombotic vascular events following the initiation of ICI therapy. These thrombotic events would coincide with the acceleration of atherosclerosis in patients treated with ICIs. This "accelerated" atherosclerosis could be linked to inflammatory changes within the plaques, causing plaque destabilization or rupture. It is also unreasonable to rule out the possibility that the accelerated atherosclerosis is related to the development of vasculitis in these patients.

Management of Vascular Complications in Pediatric Supracondylar Humerus Fractures

* To determine the incidence and types of vascular injuries associated with pediatric supracondylar humerus fractures. * Identify outcomes of different management strategies * Identify risk factors for vascular injury

Qualitative and Quantitative Evaluation of Vascular Flows of Radial, Ulnar and Interdigital Arterial Trees Under Normal and Pathological Conditions by 3 Tesla MRI

Allotransplants of vascularized composite tissues are subject to chronic vascular rejection, which can lead to graft loss. Currently, no imaging technique allows a reproducible quantitative exploration of the arterial trees of the hand, and therefore a satisfactory monitoring of transplants. Since 2014, flow MRI has been applied to the analysis of small-calibre arteries by the Image Processing Team at the Amiens-Picardie University Hospital. Between 2015 and 2017, several acquisitions were made in 3 patients who received facial allotransplantation, and the team recently developed a flow MRI protocol dedicated to the study of arterial trees in the hand. The main objective is to measure vascular flows of radial, ulnar and interdigital arterial trees in normal (healthy volunteers) and pathological situations (patients with radial forearm flap reconstruction and patients with hand allotransplantation) using the specifically developed flow MRI protocol.