Percutaneous Interventions for Secondary Mitral Regurgitation.

Mitral regurgitation is frequently associated with ventricular dysfunction and carries a high mortality. Guideline-directed medical therapy, surgical mitral valve repair or replacement, and, in the setting of advanced heart failure, heart transplant and left ventricular assist devices have been the mainstay of treatment. However, rapid advancement in the field has resulted in approval of edge-to-edge mitral valve repair with the MitraClip, and there are several novel catheter-based percutaneous options in clinical trials. Percutaneous options, while promising, must be deployed in patients who are most likely to benefit, and thus, understanding the pathophysiology of specific subgroups of patients with functional mitral regurgitation (eg, disproportionate versus proportionate mitral regurgitation) is key to the success of new devices. We review the pathophysiology, percutaneous therapeutic treatment options, and ongoing clinical trials for functional mitral regurgitation.

Venous thrombosis after nitrous oxide abuse, a case report.

Nitrous oxide is a commonly abused inhalant by adolescents and young adults. There is limited data describing the adverse effects of nitrous oxide abuse, known colloquially as "whippets". We present a 21-year-old female with no medical history who presented to the emergency department for confusion, hallucinations, weakness, and falls. She was accompanied by her roommates, who endorsed significant nitrous oxide abuse. Imaging revealed a large cerebral sinus venous thrombus with extension into the transverse sinus, sigmoid sinus and internal jugular vein. She had no prior history of venous or arterial thrombosis. Hypercoagulability workup demonstrated an elevated homocysteine level, elevated methylmalonic acid level, and normal cobalamin and folate levels. Additionally, she was found to be 11 weeks pregnant, with no prior spontaneous abortions. Genetic testing was significant for methylenetetrahydrofolate reductase polymorphisms. She was managed with enoxaparin, cobalamin and folate supplementation. Homocysteine and methylmalonic acid levels normalized after cessation of nitrous oxide use, with no recurrence of venous thrombosis. This case represents the first reported patient with a venous thrombus associated with nitrous oxide abuse.

An evolutionarily conserved program of B-cell development and activation in zebrafish.

Teleost fish are among the most ancient vertebrates possessing an adaptive immune system with B and T lymphocytes that produce memory responses to pathogens. Most bony fish, however, have only 2 types of B lymphocytes, in contrast to the 4 types available to mammals. To better understand the evolution of adaptive immunity, we generated transgenic zebrafish in which the major immunoglobulin M (IgM(+)) B-cell subset expresses green fluorescence protein (GFP) (IgM1:eGFP). We discovered that the earliest IgM(+) B cells appear between the dorsal aorta and posterior cardinal vein and also in the kidney around 20 days postfertilization. We also examined B-cell ontogeny in adult IgM1:eGFP;rag2:DsRed animals, where we defined pro-B, pre-B, and immature/mature B cells in the adult kidney. Sites of B-cell development that shift between the embryo and adult have previously been described in birds and mammals. Our results suggest that this developmental shift occurs in all jawed vertebrates. Finally, we used IgM1:eGFP and cd45DsRed;blimp1:eGFP zebrafish to characterize plasma B cells and investigate B-cell function. The IgM1:eGFP reporter fish are the first nonmammalian B-cell reporter animals to be described. They will be important for further investigation of immune cell evolution and development and host-pathogen interactions in zebrafish.