Background/Objectives: The recommendations for antithrombotic therapy after transcatheter edge-to-edge mitral valve repair (TEER) are empirical, and the benefit of antiplatelet (APT) or anticoagulation therapy (ACT) remains undetermined. The study sought to investigate the degree and the timing of coagulation and platelet marker activation after TEER. Methods: This was a prospective study including 46 patients undergoing TEER. The markers of coagulation activation, namely prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III (TAT), and the markers of platelet activation, namely soluble P-Selectin and soluble CD-40 ligand (sCD40L), were measured at baseline, 24 h, 1 month, and 1 year after TEER. Results: At discharge, 20 (43%) patients received APT (single: 16, dual: 4), 24 (52%) received ACT, and 2 (4%) had both single APT and ACT. Levels of F1 + 2 and TAT significantly increased at 24 h post TEER (both p < 0.001), rapidly returning to baseline levels at 1 month. However, levels of F1 + 2 and TAT remained higher at 1 month in patients without ACT compared to patients with ACT (respectively, 303.1 vs. 148.1 pmol/L; p < 0.001 and 4.6 vs. 3.0 µg/L; p = 0.020), with a similar trend at 1 year. Levels of soluble P-selectin and sCD40L remained stable at all times after TEER (respectively, p = 0.071 and p = 0.056), regardless of the APT. Conclusions: TEER is associated with an acute activation of the coagulation system, with no increase in platelet activation markers. Hence, the use of dual APT is questionable in this population. Our results raise the hypothesis that the optimal antithrombotic therapy after TEER could be short-term ACT over APT. Further larger studies are warranted.

Background:Residual mitral regurgitation (MR) is associated with worse outcomes after transcatheter edge-to-edge mitral valve repair (TEER). Shear stress induced by MR leads to altered von Willebrand factor activity (vWF:Act) and increased closure time with adenosine diphosphate (CT-ADP). Objectives:The purpose of this study was to investigate the use of CT-ADP to monitor MR during TEER and the association between the vWF, residual MR, and clinical events post-TEER. Methods:Sixty-five patients undergoing TEER were enrolled. CT-ADP was measured at baseline, after each clip deployment, 1 hour and 24 hours post-TEER. CT-ADP values were related to vWF:Act/vWF antigen (vWF:Ag) ratio at the same time points, and MR severity was assessed by echocardiography at 1 month. Combined events of all-cause mortality and heart failure hospitalizations were evaluated at 1 year. Results:At 1 month, 32 (49%) patients had residual MR > mild (of those, 14% had MR > moderate). There was no significant change in CT-ADP values during the procedure. However, CT-ADP significantly decreased 1-hour post-TEER (P < 0.001). Patients with corrected MR demonstrated an increase in vWF:Act/vWF:Ag ratio 1-hour post-TEER. Elevated baseline vWF:Act/vWF:Ag ratio and the periprocedural percentage changes of the vWF:Act/vWF:Ag ratio (1 hour post-TEER - baseline values) were associated with the combined clinical outcome. Conclusions:CT-ADP evolution in time was not quick enough to provide real-time monitoring of MR severity during TEER. However, vWF:Act/vWF:Ag ratio at baseline and its variations following the procedure were associated with clinical outcomes. Those findings will need external validation.

In the last two decades, human immunodeficiency virus (HIV), the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), is one of the leading causes of morbidity and mortality, worldwide. Providing the optimum management of HIV/AIDS is a major challenge in the 21st century. Since, HIV-infected persons have an extended lifespan due to the development of effective antiretroviral therapies, malnutrition is becoming central factors of long-term survivors. The nutrition status of AIDS patients has a significant influence on the maintenance and optimal effectiveness of the immune system. Micronutrient therapy in combination with allopathic treatments can extend and improve the quality and quantity of life in individuals infected with HIV/AIDS. HIV infection is thought to lead to augmented oxidative stress which may in turn lead to faster development of HIV disease. Hence, antioxidants might have a significant role in the treatment of HIV/AIDS. An additional approach to treating HIV infection is fortifying the immune response of infected people. Immune modulators help to activate and boost the normal immune function. The present review first describes the boon of antioxidants (especially Vitamin A) and immune modulators (cytolin, resveratrol, murabutide, setarud, tucaresol, AVR118, Immunitin (HE2000), reticulose, and interleukin-7) in the treatment of HIV/AIDS. Then, providing a comparatively succinct outline on updated patents study on antioxidants and immune modulators to treat HIV/AIDS will be discussed.

Un homme de 59 ans est venu consulter au service des urgences pour de la fièvre et des frissons persistant depuis 6 semaines, soit depuis qu’on lui avait diagnostiqué une thrombose veineuse profonde (TVP) symptomatique dans la veine tibiale postérieure droite. Au cours de cette nouvelle

A 59-year-old man presented to the emergency department with fever and chills that began 6 weeks earlier, when a symptomatic deep vein thrombosis (DVT) of the right posterior tibial vein had been diagnosed. The patient had also noticed word-finding difficulties and mild headache for the week before

About one-half of transcatheter aortic valve replacement (TAVR) candidates have coronary artery disease (CAD), and controversial results have been reported regarding the effect of the presence and severity of CAD on clinical outcomes post-TAVR. In addition to coronary angiography, promising data has been recently reported on both the use of computed tomography angiography and the functional invasive assessment of coronary lesions in the work-up pre-TAVR. While waiting for the results of ongoing randomized trials, percutaneous revascularization of significant coronary lesions has been the routine strategy in TAVR candidates with CAD. Also, scarce data exists on the incidence, characteristics, and management of coronary events post-TAVR, and increasing interest exist on potential coronary access challenges in patients requiring coronary angiography/intervention post-TAVR. This review provides an updated overview of the current landscape of CAD in TAVR recipients, focusing on its prevalence, clinical impact, pre- and post-procedural evaluation and management, unresolved issues and future perspectives.

Background The influence of coronary artery disease (CAD) on clinical and echocardiographic outcomes after transcatheter aortic valve replacement (TAVR) is still controversial. We sought to evaluate the impact of CAD severity as measured by the SYNTAX score (SS) on patients undergoing TAVR. Methods and Results A total of 377 patients who underwent TAVR in 2 high‐volume centers in North America were included in our retrospective analysis. A blinded angiographic core laboratory calculated the SS on all available coronary angiograms with the use of quantitative coronary analysis. Patients were stratified into 4 groups: (1) no CAD (SS=0); (2) low SS (SS between 1 and 22); (3) intermediate SS (SS between 23 and 32); and (4) high SS (SS ≥33). Patients who had undergone percutaneous coronary intervention within 6 months prior to TAVR were separated into 2 categories based on their residual SS (<8 and ≥8). Patients with previous coronary artery bypass grafting (CABG) were divided into 2 groups: (1) low CABG SS and (2) high CABG SS. The primary end point was a composite of all‐cause mortality, myocardial infarction, and stroke. At 30 days and 1 year, both the presence and the severity of CAD had no impact on the rate of the combined primary end point and on all‐cause mortality, cardiovascular mortality, and myocardial infarction. Patients with less complete revascularization (residual SS ≥8 versus residual SS <8 and low CABG SS versus high CABG SS, had similar rates of the combined primary end point, all‐cause mortality, cardiovascular mortality, MI, and stroke, at both 30 days and 1 year. Conclusions In our core laboratory–validated study, neither the severity of CAD nor completeness of revascularization after percutaneous coronary intervention or CABG were associated with clinical outcomes after TAVR, at both 30 days and 1 year.

Concomitant coronary artery disease (CAD) is highly prevalent among patients with severe aortic stenosis (AS). Historically, surgical aortic valve replacement with coronary artery bypass grafting was the only treatment option for patients with severe AS and significant CAD. The rapid expansion of transcatheter aortic valve replacement has led to significant paradigm shifts in the treatment of severe AS and has raised new questions regarding the optimal management of CAD in these patients. We review the evidence regarding management of concomitant CAD in severe AS patients, specifically focusing on issues surrounding transcatheter aortic valve replacement. In the absence of robust evidence supporting specific treatment strategies, decisions regarding coronary revascularization in severe AS should be individualized and made within the context of a multidisciplinary heart team.

A 85-year-old man was admitted due to severe symptomatic aortic stenosis. Echocardiogram demonstrated a normal left ventricular ejection fraction, an aortic valve area of 0.5 cm2, and a left ventricular outflow tract of 19 mm. Computed tomography scan showed a porcelain aorta with an aortic annulus

Achieving optimal bone defect repair is a clinical challenge driving intensive research in the field of bone tissue engineering. Many strategies focus on seeding graft materials with progenitor cells prior to in vivo implantation. Given the benefits of closely mimicking tissue structure and function with natural materials, the authors hypothesize that under specific culture conditions, human adipose-derived stem/stromal cells (hASCs) can solely be used to engineer human reconstructed osseous tissues (hROTs) by undergoing osteoblastic differentiation with concomitant extracellular matrix production and mineralization. Therefore, the authors are developing a self-assembly methodology allowing the production of such osseous tissues. Three-dimensional (3D) tissues reconstructed from osteogenically-induced cell sheets contain abundant collagen type I and are 2.7-fold less contractile compared to non-osteogenically induced tissues. In particular, hROT differentiation and mineralization is reflected by a greater amount of homogenously distributed alkaline phosphatase, as well as higher calcium-containing hydroxyapatite (P < 0.0001) and osteocalcin (P < 0.0001) levels compared to non-induced tissues. Taken together, these findings show that hASC-driven tissue engineering leads to hROTs that demonstrate structural and functional characteristics similar to native osseous tissue. These highly biomimetic human osseous tissues will advantageously serve as a platform for molecular studies as well as for future therapeutic in vivo translation.

In the past years, adipose tissue has spurred a wide interest, not only as a source of adult multipotent stem cells but also as a highly eligible tissue for reconstructive surgery procedures. Tissue engineering is one field of regenerative medicine progressing at great strides in part due to its important use of adipose-derived stem/stromal cells (ASCs). The development of diversified technologies combining ASCs with various biomaterials has lead to the reconstruction of numerous types of tissue-engineered substitutes such as bone, cartilage, and adipose tissues from rodent, porcine, or human ASCs. We have recently achieved the reconstruction of connective and adipose tissues composed entirely of cultured human ASCs and their secreted endogenous extracellular matrix components by a methodology known as the self-assembly approach of tissue engineering. The latter is based on the stimulation of ASCs to secrete and assemble matrix components in culture, leading to the production of cell sheets that can be manipulated and further assembled into thicker multilayer tissues. In this chapter, protocols to generate both reconstructed connective and adipocyte-containing tissues using the self-assembly approach are described in detail. The methods include amplification and cell banking of human ASCs, as well as culture protocols for the production of individual stromal and adipose sheets, which are the building blocks for the reconstruction of multilayered human connective and adipose tissues, respectively.