Chronological comparison of TAVI and SAVR stratified to surgical risk: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been established as a reasonable alternative to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis. However, long-term outcomes including valve durability and the need for reintervention are unanswered, especially in younger patients who tend to be low surgical risk. We performed a meta-analysis comparing clinical outcomes after TAVI and SAVR over 5 years stratified to low, intermediate, and high surgical risks. METHODS: We identified propensity score-matched observational studies and randomised controlled trials comparing TAVI and SAVR. Primary outcomes, including all-cause mortality, moderate or severe aortic regurgitation, moderate or severe paravalvular regurgitation, pacemaker placement, and stroke, were extracted. Meta-analyses of outcomes after TAVI compared to SAVR were conducted for different periods of follow-up. Meta-regression was also performed to analyse the correlation of outcomes over time. RESULTS: A total of 36 studies consisting of 7 RCTs and 29 propensity score-matched studies were selected. TAVI was associated with higher all-cause mortality at 4-5 years in patients with low or intermediate surgical risk. Meta-regression time demonstrated an increasing trend in the risk of all-cause mortality after TAVI compared with SAVR. TAVI was generally associated with a higher risk of moderate or severe aortic regurgitation, moderate or severe paravalvular regurgitation, and pacemaker placement. CONCLUSIONS: TAVI demonstrated an increasing trend of all-cause mortality compared with SAVR when evaluated over a long-term follow-up. More long-term data from recent studies using newer-generation valves and state-of-the-art techniques are needed to accurately assign risks.

Transcatheter aortic valve implantation (TAVI) was associated with increased all-cause mortality at longer periods of follow-up irrespective of surgical risk. Aortic regurgitation, paravalvular regurgitation, major vascular complications, and pacemaker placement favoured surgical aortic valve replacement (SAVR) over TAVI. TAVI remained superior to SAVR in major bleeding and renal failure events. Long-term data on newer generation valves and up-to-date implantation techniques may provide better durability and improved outcomes after TAVI.

Intrapericardial Fibrinolytic Therapy in Purulent Pericarditis: A Review of Two Cases.

Purulent pericarditis is the infection of the pericardial space with pus formation. High mortality and morbidity can be explained by cardiac tamponade and septic shock in the acute phase, while chronically, it can lead to recurrent purulent pericarditis and constrictive pericarditis. We present two cases of purulent pericarditis treated with intrapericardial recombinant tissue plasminogen activator (r-tPA) for three consecutive days in addition to surgical pericardial drainage. In both instances, loculated effusions and re-accumulation of pericardial fluid persisted despite adequate antibiotic coverage and surgical drainage. Intrapericardial fibrinolysis was considered a less invasive alternative to extensive surgery to prevent constrictive pericarditis and improve clinical outcomes. Both patients had complete clinical recovery and there was no evidence of constrictive pericarditis during follow-up. There is scant literature regarding r-tPA therapy for purulent pericarditis, most of which is limited to case reports or case series. The most commonly used regimen is three doses of tPA administered into the pericardial space over three days. It is a safe and potentially effective therapy in preventing constrictive pericarditis and need of pericardiectomy.

Ruptured Sinus of Valsalva Aneurysm: Use of Multimodality Imaging in Delineating Structure and Function.

Sinus of Valsalva aneurysm is a rare defect that can present with fatal complications in case of rupture. Heart failure symptoms are common due to high fraction of the resultant shunt. Multimodality imaging and invasive hemodynamic assessment is essential for comprehensive evaluation of the defect and guiding surgical planning. We describe the case of a 40-year-old woman who presented with heart failure symptoms and was found to have ruptured sinus of Valsalva aneurysm on transthoracic echocardiogram. Cardiac computed tomography angiography further characterized the defect and the associated anomalies. Right heart catheterization assessed the hemodynamic significance of the left to right shunt. Intraoperative findings highlighted the associated congenital anomalies including supracristal ventricular septal defect. The use of intraoperative transesophageal echocardiography proved essential in detecting worsening of the right ventricular outflow track infundibular dynamic obstruction post repair thus delineating the importance of maintaining adequate cardiac preload. This case highlights a stepwise approach in the anatomical characterization of sinus of Valsalva aneurysm using multimodality imaging and the use of hemodynamic assessment and intraoperative imaging to guide surgical planning.

Tocilizumab in the treatment of rheumatoid arthritis and beyond.

Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.

Rheumatologic manifestations of sarcoidosis.

Sarcoidosis is a systemic, clinically heterogeneous disease characterized by the development of granulomas. Any organ system can be involved, and patients may present with any number of rheumatologic symptoms. There are no U.S. Food and Drug Administration-approved therapies for the treatment of sarcoidosis. Diagnosing sarcoidosis becomes challenging, particularly when its complications cause patients' symptoms to mimic other conditions, including polymyositis, Sjögren syndrome, or vasculitis. This review presents an overview of the etiology of and biomarkers associated with sarcoidosis. We then provide a detailed description of the rheumatologic manifestations of sarcoidosis and present a treatment algorithm based on current clinical evidence for patients with sarcoid arthritis. The discussion will focus on characteristic findings in patients with sarcoid arthritis, osseous involvement in sarcoidosis, and sarcoid myopathy. Arthritic conditions that sometimes coexist with sarcoidosis are described as well. We present two cases of sarcoidosis with rheumatologic manifestations. Our intent is to encourage a multidisciplinary, translational approach to meet the challenges and difficulties in understanding and treating sarcoidosis.

Diagnosis and management of pulmonary hypertension in systemic sclerosis.

Patients with systemic sclerosis (SSc) can develop pulmonary hypertension (PH; mean pulmonary artery pressure >/= 25 mm Hg) caused by pulmonary arterial hypertension (PAH), left ventricular disease, or pulmonary fibrosis. PAH is a pulmonary vascular disease, the diagnosis of which requires pulmonary capillary wedge pressure less than 15 mm Hg, pulmonary vascular resistance greater than 3 Wood Units, and exclusion of thromboembolism and parenchymal lung disease. Molecular mechanisms underlying PAH-SSc include activation of inflammatory and fibrogenic pathways in the vasculature and right ventricle. Circulating autoantibodies trigger endothelial damage and fibroblast activation. PAH most commonly occurs as a late complication in patients with limited cutaneous disease and anticentromere antibodies. Although echocardiography is a useful screening tool, heart catheterization is required to diagnose PAH before initiating therapy. Prognosis and therapeutic response are worse in PAH-SSc than in other PAH categories (median survival, 1-3 y). Approved therapies include prostacyclins, endothelin antagonists, and phosphodiesterase type 5 inhibitors. Research is needed to define disease mechanisms and develop effective therapies.

Critical appraisal of tocilizumab in the treatment of moderate to severe rheumatoid arthritis.

Recent advances in our understanding of the role of interleukin (IL)-6 in autoimmunity and in particular rheumatoid arthritis (RA) have brought about important changes in the way we think about autoimmune diseases. Encouraging data from several phase III clinical trials of tocilizumab, a humanized monoclonal antibody against IL-6R, have led to its approval in Europe for the treatment of moderate to severe RA. Data on clinical efficacy, patient-reported outcomes, safety, and cost-effectiveness with the use of tocilizumab in patients with RA will be summarized in this review, with particular emphasis on phase III clinical trials. Furthermore, adverse events associated with the use of tocilizumab will be reviewed. Future clinical trials will evaluate the role of tocilizumab in other autoimmune diseases. The goal of this review is to describe the current understanding of the role of IL-6 in mediating the inflammatory response in RA, as well as the role of tocilizumab in the treatment of RA and the evolving role of this agent in other autoimmune diseases.

Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations.

BACKGROUND: Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. METHODOLOGY/PRINCIPAL FINDINGS: Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. CONCLUSIONS/SIGNIFICANCE: Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment.

Ocrelizumab: a step forward in the evolution of B-cell therapy.

Recent advances in our understanding of B-cell dysregulation and its important link to autoimmunity have brought about a radical change in the management of autoimmune diseases. Over the past few years, encouraging data from several clinical trials of rituximab, a chimeric anti-CD20 antibody, have led to its approval for use in rheumatoid arthritis (RA). These data, regarding clinical efficacy, safety, improved patient-reported outcomes and cost-effectiveness with the use of rituximab in patients with RA, have led to the exploration of other agents targeting B-cell functions. Ocrelizumab, a novel humanized anti-CD20 antibody, has shown clinical efficacy and safety in a recently reported trial in patients with RA. Future clinical trials will help evaluate further the role of ocrelizumab in RA and its potential use in other autoimmune diseases. This review describes current understanding of B-cell therapy, the role of rituximab in the treatment of RA and the evolving role of ocrelizumab as a B-cell-targeted therapy.

Use of the aberrant right subclavian artery in complex aortic arch reconstruction.

An aberrant right subclavian artery can be used in a variety of ways in complex aortic arch reconstructions. Four patients (3 with interrupted aortic arch and 1 with coarctation) in whom this technique was used are presented.