Vasculitis

The current state of knowledge on ANCA-associated vasculitis (AAV) indicates that it is a group of autoimmune diseases in which small blood vessels in various organs are affected. Disease entities included in this group are granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). These are rare diseases, with an incidence in Europe of approximately 20-25 cases per million people per year. There is a slight predominance among men, and the risk of developing the disease increases with age. ANCA antibodies play a role in the pathogenesis of the disease, and inflammation within small vessels leads to damage of the vessel walls, resulting either in rupture or occlusion of the vessel lumen. Consequently, vital organs such as the kidneys, lungs, heart, nervous system, upper respiratory tract, gastrointestinal tract, and eyes may be affected. If the disease is not diagnosed, untreated, or treated improperly, it can lead to irreversible failure of these organs and even death. Despite appropriate treatment, AAV diseases tend to relapse; therefore, therapy consists of two phases: induction therapy and maintenance therapy. Current EULAR/EDTA guidelines for induction treatment of AAV recommend the use of cyclophosphamide (CYC) or rituximab (RTX) in combination with glucocorticosteroids in cases of severe disease. If remission is achieved after induction therapy, maintenance treatment should be initiated with drugs such as azathioprine, mycophenolate mofetil, methotrexate, or rituximab, combined with a low dose of glucocorticosteroids. Maintenance therapy should last no less than two years. The study will focus on ophthalmological evaluation of patients diagnosed with ANCA-associated vasculitis. In this disease, all structures of the eye may be involved. The most common ocular manifestations include scleritis, keratitis, proptosis, inflammation of orbital tissues, nasolacrimal duct obstruction, and orbital involvement leading to proptosis, double vision, and restricted eye movement. Until recently, the disease was often fatal. However, advances in diagnostics and current pharmacological treatment options, combined with appropriately aggressive immunosuppressive therapy, have significantly improved survival, enhanced patients' quality of life, and reduced mortality. Early diagnosis and prompt initiation of appropriate therapy are crucial.

The main objective of this study is to explore the efficacy of avacopan in participants affected by AAV.

Patients harboring dolichoectactic vertebrobasilar (DVB) aneurysms are at risk of suffering SAH, ischemic stroke, and/or brainstem compression and many patients are not offered invasive treatment due to the futility of existing surgical methods. Consequently, there is demand for development of medical therapy for DVB aneurysms

This will be a pragmatic programme of research, consecutively recruiting all-comers who have been referred to secondary care for assessment of suspected Systemic Vasculitis (SV) into a longitudinal inception cohort. For patients with a pre-existing diagnosis, data on the disease onset will be collected retrospectively. All patients followed prospectively from the time of inclusion into the study will be followed at intervals corresponding to the recommended standard of care. We will invite participants to consent to the whole programme of research in order to allow their samples, as well as their data, to be used for in multiple related projects that have the same common aim. In this long-term inception cohort we will collect data on clinical features, prognostic factors and outcomes of patients diagnosed with a SV over the course of 10 years. We will examine the role of clinical features, imaging and biomarkers in the characterisation of the disease with a particular focus on risk stratification. This will be closely integrated with the other objectives of the study: analysing clinical features, imaging characteristics, outcomes, rates and predictors of relapses and remission, in order to obtain a prognostic stratification of the patients and to capture a cohort of patients at high risk of relapse and poor outcome who could inform on the potential use of more intensive treatment strategies to be assessed in future studies. The SMART programme will be guided by three main overarching themes: 1. "Theme 1": The identification of risk factors associated with poor outcome, relapse and failure to achieve remission 2. "Theme 2": The assessment of different tools to assess risk factors (imaging, biomarkers, clinical features) 3. "Theme 3": The analysis of cohorts of SV patients in observational studies The overarching aims of the study will be overlapping throughout the different investigations outlined in the following paragraphs analyzing: outcomes (including treatment-derived damage), monitoring and relapse, and remission in SV. We aim to follow patients up over a total of 10 years, in order to provide the richest and most complete set of data that has ever been collected for this patient group.

The goal of this prospective observational quality improvement study is to determine if a physician tool, MedSafer, combined with educational brochures for patients, can help to reduce the use of 'potentially inappropriate medications' (PIMs) in adults aged 60 and over with rheumatic conditions and polypharmacy (taking 5 or more regular medications). Researchers will follow participants during usual rheumatic disease care. They will compare the rate of PIM deprescribing (stopping medications or reducing the dose) before and after the introduction of the following interventions: * MedSafer reports provided to treating physicians * EMPOWER consumer brochures provided to participants Participants will complete 4 study visits over 18-20 months during which researchers will collect information on medication changes, serious adverse events (emergency visits or hospitalizations), and quality of life.

This is a pilot study to investigate serum prednisolone profiles in: * Patients on high doses of prednisolone for any inflammatory disorder, both in the acute and chronic setting. * Patients stepping up from or down to prednisolone therapy in association with a course of high dose methyl-prednisolone or dexamethasone. The study will comprise 3 groups, including those started on high doses of prednisolone acutely in an inpatient or outpatient setting, participants on chronically high doses, and those receiving a several week course of high dose methylprednisolone or dexamethasone. The study aims to measure prednisolone levels at a number of time points to investigate serum profile differences in those receiving prednisolone acutely compared with longer term steroid use. Further samples will be taken to characterise additional metabolic changes.

The aim of this project is to start a biological and clinical collection of patients presenting systemic autoimmune disease. This collection will provide appropriate biological samples to identify new biomarkers and to be accessible to the medical, scientific and industrial communities for the identification of new therapeutic strategies

Primary central nervous system vasculitis (CNSV) is a potentially fatal, single-organ vasculitis that often involves a spectrum of neurologic complications, including strokes, cognitive and speech impairment, visual loss, dementia, and encephalopathy. The purpose of this study is to establish a research cohort to investigate the disease process, treatments, and patient outcomes in CNSV.

Relapsing polychondritis (RP) is a rare systemic inflammatory disease characterized by recurrent inflammation of cartilage including ears, nose, tracheobronchial tree, chest wall and joints. Less commonly, it can cause inflammation of eyes, vasculature, nervous system, skin and inner ear. The purpose of this study is to study the pathogenesis of RP.

Multi-center observational study to evaluate the histopathology and transcriptome of cutaneous lesions in patients with several different types of vasculitis.

The purpose of this study is to learn about the experience of women with vasculitis who become pregnant. In particular, the study will consist of several online surveys to assess 1. each woman's vasculitis severity and pregnancy-related experiences, and 2. pregnancy outcomes.

Generative AI (GenAI) based on large language models (LLMs) is expected to improve the diagnosis and treatment of autoimmune diseases. We are studying how GenAI may affect the diagnosis of various complications of rheumatoid arthritis (RA). In a retrospective study using RA patients' EHR records, we will quantify physician adoption of GenAI predictions for RA complications and co-existing diseases. In a prospective observational study, we will assess the feasibility of using GenAI predictions as additional clinical information to help physicians make more complete diagnoses of RA complications and co-existing diseases, including complex, uncommon, or rare conditions.

This is a study of biomarkers obtained from prospectively collected subject samples and their correlation with cardiovascular and metabolic diseases. The purpose of this initiative is to develop an enduring tool to allow for collaborative research between clinicians at Cleveland Clinic Main Campus and basic scientists at the Lerner Research Institute. This collaboration will allow resources to be available to clinical and basic researchers alike. This tool will enable research of vascular disease in the Vascular Lab and will leverage this valuable asset to the fullest extent to allow for interdepartmental collaboration.

Acute kidney injury (AKI) is common and costly.1 Although patients who suffer an episode of AKI may recover, many will go on to develop cardiovascular disease and chronic kidney disease (CKD). Cardiovascular disease is an important complication of AKI.2 Similar to AKI, CKD and kidney transplantation and kidney donation associations with cardiovascular disease.1 The risk of cardiovascular disease complications is also increased in patients with inflammatory diseases that affect the kidneys, such as vasculitis. Currently, there are no reliable biomarkers that will identify those patients with kidney disease that will go on to develop cardiovascular disease. This study will explore the potential of manganese-enhanced magnetic resonance imaging (MEMRI) to act as a biomarker of AKI and its cardiovascular and renal complications. An analogue of calcium, manganese is readily taken-up into viable cells where it increases T1 relaxivity. Preliminary data show rapid manganese uptake in the heart and kidneys of healthy subjects. The investigators propose to use MEMRI to demonstrate differences in renal and myocardial calcium handling in patients with acute insults (such as AKI, transplant rejection, donation or episodes of rejection or new vasculitis presentations) or improvements (such as transplantation). The investigators will also investigate whether these abnormalities reverse in those whose injury resolves or persist in those who clearly develop CKD, or who are at risk of future cardiovascular disease and CKD.

Based on mass spectrometry flow method, this study analyzed the typing of new T, B, NK and DC cell subsets in peripheral blood of common autoimmune diseases and their correlation with disease activity, aiming at establishing an early screening and diagnosis model of autoimmune diseases.

VASCO is a prospective observational cohort study which aim to describe the presentation, comorbidities, management, outcomes and damage of vasculitis patients, from the analysis of the clinical, biological and immunological data.

WOUNDJOURNEY is a longitudinal, real-world, observational registry designed to capture the full clinical course and patient journey associated with chronic wounds and ulcers. Data are collected during routine care from over 1,400 clinicians across the USA and Puerto Rico using a highly structured certified electronic health record (EHR) or electronic data capture (EDC) system. Data are transmitted daily to the U.S. Wound Registry (USWR), a CMS-recognized Qualified Clinical Data Registry (QCDR). The registry captures real-time, research-ready data on patient demographics, comorbidities, wound characteristics, standard-of-care treatments, complications, and advanced therapeutics. It supports robust, fit-for-purpose real-world evidence generation by enabling risk-adjusted outcome analysis, comparative effectiveness research, and quality improvement across diverse sites of care.

The objective of this work is to identify, in patients with autoimmune diseases, systemic vasculitis and autoinflammatory disease, cytokine and lymphocyte biomarkers of activity of these diseases to identify follow-up biomarkers, in order to personalize the follow-up and the treatments for each patient. Immunological data will be obtained from biological samples collected as part of the usual patient care pathway (Blood and tissues sampling) The study will take place in the Department of Internal Medicine and Clinical Immunology (DMIIC), that is certified as the National Reference Centre for Rare Systemic Autoimmune Diseases and the National Reference Centre for Inflammatory Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA). Its objective is to contribute to the advancement of fundamental knowledge in immunology, in particular to develop prognostic biomarkers of the activity of autoimmune diseases, systemic vasculitis and autoinflammatory diseases by using blood tests.

To date, there are no reliable diagnostic blood markers of adult vasculitis. To date, the diagnosis of vasculitis is based on invasive procedure, biopsy of affected tissues potentially at risk of complication . In addition, there are no reliable biomarkers to predict the evolution of vasculitis (relapse, refractory form ...) necessary for the management of patients (type of treatment, duration ..) Prospective study, monocentric (CHU de Tours), non-interventional, aimed at finding diagnostic and prognostic biomarkers (both metabolomic and immunologic) in adult vasculitis patients.

The goal of this multicenter retrospective observational study is to provide an inventory of the specific and non specific cord vocal lesions that can cause dysphonia in patients with systemic autoimmune diseases. The main question it aims to answer is: * What are the main cord vocal lesions responsible for dysphonia in patients with a systemic autoimmune disease? * Is there a diagnosis delay regarding those lesions? * How are those lesions managed? Participants suffering from dysphonia in a context of a systemic autoimmune disease will be identified, with a review of their medical record.

Cryoglobulinemia vasculitis (CV) is a systemic immune-mediated small vessel vasculitis. Rituximab proved effective on main vasculitis signs, with a complete clinical response of 65%. However, CV relapse is noted in up to 40% of patients. Following rituximab, serum Blys concentration significantly increased and may favor relapses. Tribeca is a multicentre randomized controled study comparing safety and efficacy of belimumab to placebo in non infectious cryoglobulinemia vasculitis.

The goal of this National Registry is to is to collect information from patients with rare kidney diseases, so that it that can be used for research. The purpose of this research is to: * Develop Clinical Guidelines for specific rare kidney diseases. These are written recommendations on how to diagnose and treat a medical condition. * Audit treatments and outcomes. An audit makes checks to see if what should be done is being done and asks if it could be done better. * Further the development of future treatments. Participants will be invited to participate on clinical trials and other studies. The registry has the capacity to feedback relevant information to patients and in conjunction with Patient Knows Best (Home - Patients Know Best), allows patients to provide information themselves, including their own reported quality of life and outcome measures.

The FAMILYVASC study is a prospective observational study which will aim to identify susceptibility loci and genes for systemic vasculitis risk in patients with familial or pediatric forms of vasculitis. Genetic analysis based on whole exome sequencing will be carried out through salivary DNA.