Clinical and Surgical Evaluations of Reoperation After Mechanical Mitral Valve Replacement Due to Different Etiologies

Background:This study aimed to evaluate the clinical and surgical characteristics of patients who required reoperation after mechanical mitral valve replacement (MVR).Methods:We retrospectively identified 204 consecutive patients who underwent reoperation after mechanical MVR between 2009 and 2018. Patients were categorized according the reason for reoperation (perivalvular leakage, thrombus formation, or pannus formation). The patients' medical and surgical records were studied carefully and the rates of in-hospital complications were calculated.Results:The mean age was 51±12 years and 44% of the patients were male. The reasons for reoperation were perivalvular leakage (117 patients), thrombus formation (35 patients), and pannus formation (52 patients). The most common positions for perivalvular leakage were at the 6–10 o'clock positions (proportions of ≥25% for each hour position). Most patients had an interval of >10 years between the original MVR and reoperation. The most common reoperation procedure was re-do MVR (157 patients), and 155 of these patients underwent concomitant cardiac procedures. There were 10 in-hospital deaths and 32 patients experienced complications. The 10-year survival rate was 82.2 ± 3.9% in general, and the group of lowest rate was patients with PVL (77.5 ± 5.2%). The independent risk factors were “male” (4.62, 95% CI 1.57–13.58, P = 0.005) and “Hb <9g/dL before redo MV operation” (3.45, 95% CI 1.13–10.49, P = 0.029).Conclusion:Perivalvular leakage was the most common reason for reoperation after mechanical MVR, with a low survival rate in long term follow-up relatively.

Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

CONTEMPORARY UNDERSTANDING OF THE PATHOGENESIS OF RHEUMATOID ARTHRITIS.

Rheumatoid Arthritis (RA) is one of the most common rheumatologic conditions. Dell et al (2013) denes RA as a systemic autoimmune polyarticular arthritis, which can also have extra-articular manifestations that can lead to various systemic complications,. It is more common in women and can present at any age, however, the peak age of onset is the fth decade. RA mainly involves the synovial membrane leading to synovial inammation, proliferation, pannus formation and destruction of the articular cartilage, peri- articular bone and soft tissues.

Modelling rheumatoid arthritis: A hybrid modelling framework to describe pannus formation in a small joint

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that causes pain, swelling and stiffness in the joints, and negatively impacts the life of affected patients. The disease does not have a cure yet, as there are still many aspects of this complex disorder that are not fully understood. While mathematical models can shed light on some of these aspects, to date there are not many such models that can be used to better understand the disease. As a first step in the mechanistic understanding of RA, in this study we introduce a new hybrid mathematical modelling framework that describes pannus formation in a small proximal interphalangeal (PIP) joint. We perform numerical simulations with this new model, to investigate the impact of different levels of immune cells (macrophages and fibroblasts) on the degradation of bone and cartilage. Since many model parameters are unknown and cannot be estimated due to a lack of experiments, we also perform a sensitivity analysis of model outputs to various model parameters (single parameters or combinations of parameters). Finally, we connect our numerical results with current treatments for RA, by discussing our numerical simulations in the context of various drug therapies using, for example, methotrexate, TNF-inhibitors or tocilizumab, which can impact different model parameters.

SFRP5 Enhances Wnt5a Induced-Inflammation in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

BackgroundTissue derived fibroblast-like synoviocytes (td-FLS) are key actors in pannus formation and contribute to joint destruction and inflammation during rheumatoid arthritis (RA). Several members of the Wnt family, including Wnt5a, may contribute to RA td-FLS activation and can potentially serve as therapeutic targets.ObjectiveThe present work aimed to investigate the expression of Wnt5a signaling elements in RA td-FLS and their potential precursors (fluid derived (fd) FLS and fibrocytes). We also studied the role of Wnt5a in RA td-FLS pro-inflammatory activity and whether the inhibitor SFRP5 could restore Wnt5a-induced synovial dysfunction in vitro.Materials and MethodsThe levels of Wnt5a, SFRP5, Wnt5a receptors/coreceptors and Wnt5a pro-inflammatory targets were determined in cultured RA td-FLS, fd-FLS and fibrocytes using qPCR under basal conditions. The expression of pro-inflammatory molecules was assessed after RA td-FLS stimulation with Wnt5a and SFRP5 at different time points.ResultsOur data showed that td-FLS, fd-FLS and fibrocytes from patients with RA expressed similar levels of Wnt5a and a set of Wnt5a receptors/coreceptors. We also demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1β, IL8 and IL6 in RA td-FLS. Wnt5a-induced inflammation was enhanced in the presence of SFRP5. Furthermore, Wnt5a alone and in conjunction with SFRP5 inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5.ConclusionWnt5a pro-inflammatory effect is not inhibited but enhanced by SFRP5 in RA td-FLS. This research highlights the importance of carefully evaluating changes in Wnt5a response in the presence of SFRP5.

Synovial Fibrosis Involvement in Osteoarthritis

Bone changes have always been the focus of research on osteoarthritis, but the number of studies on synovitis has increased only over the last 10 years. Our current understanding is that the mechanism of osteoarthritis involves all the tissues that make up the joints, including nerve sprouting, pannus formation, and extracellular matrix environmental changes in the synovium. These factors together determine synovial fibrosis and may be closely associated with the clinical symptoms of pain, hyperalgesia, and stiffness in osteoarthritis. In this review, we summarize the consensus of clinical work, the potential pathological mechanisms, the possible therapeutic targets, and the available therapeutic strategies for synovial fibrosis in osteoarthritis to gain insight and provide a foundation for further study.

Interleukin 6 in Patients with Rheumatoid Arthritis

Rheumatoid Arthritis is a widespread disease causing varying degrees of disability. It is characterised by flares and remissions and since ancient times, every culture has tried to get the better of it. Even now, research is aimed at finding novel serum biomarkers as surrogates for disease activity and newer targets to sharpen therapy. One such target is IL-6.It mediates neutrophil migration, osteoclast maturation and pannus formation through vascular endothelial growth factor (VEGF) stimulation causing synovitis and joint destruction.IL-6 leads to various systemic manifestations like hepcidin production causing anemia hypothalamo-pituitary–adrenal (HPA) axis activation causing fatigue and mood changes and osteoclast activation causes osteoporosis while increase in acute phase reactants (ESR and CRP). The literature we reviewed and our research, enrolling 40 patients of RA as well describes the role of IL-6 in pathogenesis and various manifestations of RA including articular, extra-articular and other comorbid states. It supports that Serum IL-6 levels correlate with disease activity (DAS-28ESR and BRAF-MDQ) and that IL-6 remains a viable target for drug therapy.

An Unusual Case of Pannus Formation - A Late Postoperative Complication of a Prosthetic Valve Replacement Causing Severe Cardiomyopathy

There are several well-known long-term complications following prosthetic valve replacement. Pannus formation is one of the rare complications whose estimated incidence varies between 0.3% and 1.3% per patient-year [1]. The exact etiology of pannus formation is unknown but histopathologically, pannus formation is due to fibroelastic hyperplasia that variably occurs after valve implantation [2]. The rarity and acute coronary syndrome like clinical presentation makes pannus formation a clinically important diagnosis during initial presentation. Workup preferably includes Transthoracic Echocardiography (TEE) with or without CT angiography. Management includes urgent or emergent surgical excision of the pannus with or without re-replacement of the aortic valve [1]. We present a 66-year-old female who presented with typical angina symptoms along with diffuse ischemic EKG changes five years after aortic valve replacement surgery with Trifecta Bioprosthesis due to severe aortic stenosis with Non-ST Elevation Myocardial Infarction (NSTEMI). Coronary angiography done on admission showed left main ostial stenosis of 90-95 % in proximity to the aortic valve prosthesis. A Transthoracic Echocardiogram (TTE) revealed an ejection fraction of 30-35 % with global hypokinesia but did not suggest any valve dysfunction. CT angiogram was done the next day which revealed a noncalcified plaque (pannus) greater than 75% occlusion in the left main in proximity of the aortic valve. Despite expedited care and surgical evaluation, unfortunately the patient decompensated in the surgical operating room and did not survive.