The Role of Leukocyte-Associated Ig-like Receptor-1 in Suppressing Collagen-Induced Arthritis.

Several observations implicate a critical role for T cell dysregulation as a central problem in rheumatoid arthritis. We investigated a mechanism for suppressing T cell activation by stimulating a natural inhibitory receptor called leukocyte-associated Ig-like receptor-1 (LAIR-1). The collagen-induced arthritis (CIA) model and DR-1 transgenic mice were used to study the importance of LAIR-1 in autoimmune arthritis. Splenocytes from wild-type or LAIR-1-/- mice were stimulated with soluble anti-CD3 Ab in the presence or absence of α1(II) and supernatants were collected for cytokine analysis. B6.DR1 mice were immunized with type II collagen/CFA to induce arthritis and were treated with either the stimulatory mAb to LAIR-1 or a hamster IgG control. Finally, B6.DR1/LAIR-1-/- and B6.DR1/LAIR-1+/+ mice were challenged for CIA and mean severity scores were recorded thrice weekly. Using splenocytes or purified CD4+ cells that were sufficient in LAIR-1, CD3-induced cytokine secretion was significantly suppressed in the presence of collagen, whereas LAIR-1-deficient splenocytes had no attenuation. Treatment with a stimulatory mAb to LAIR-1 also significantly attenuated CIA in the LAIR+/+ mice. When B6.DR1/LAIR-1-/- mice were immunized with type II collagen they developed more severe arthritis and had a greater percentage of affected limbs than the wild-type mice. These data demonstrate that collagen can suppress the T cell cytokine response through the action of LAIR-1. Treatment with stimulating LAIR-1 Abs suppresses CIA whereas B6.DR1/LAIR-1-/- mice develop more severe arthritis than wild-type controls. These data suggest that LAIR-1 may be a potential therapeutic target for suppressing rheumatoid arthritis.

Clinical Experience With Sternotomy Versus Subcostal Approach for Exchange of HeartMate II Left Ventricular Assist Device.

BACKGROUND: The safety and efficacy of exchanging the HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) through a less invasive subcostal approach remains unclear. METHODS: We reviewed the records of 17 patients who underwent exchange of their HeartMate II device at our institution since 2007. We divided the cohort into devices exchanged through a subcostal (SC) approach versus a median sternotomy (MS) approach and obtained data pertaining to the short- and long-term outcomes. RESULTS: Nine patients had pump exchange through an MS approach versus 8 patients who underwent an SC approach. The mean duration of support with the first pump was 540 ± 450 days. The reason for exchange was electromechanical failure (7 patients), thrombosis (8 patients), and infection (2 patients). There were no 30-day perioperative deaths with either approach. Compared with sternotomy, patients who underwent an SC approach had significantly shorter operative times (131 vs 222 minutes; p = 0.001) and lower reoperation rates for bleeding (0 vs 44.4%; P = 0.05) and required fewer transfused blood products (packed red cells, 3.5 units vs 7.1 units; p < 0.05; cryoprecipitate, 50.7 mL vs 209.3 mL; p = 0.01; and platelets, 292 mL versus 762 mL; p < 0.05). Additionally, patients who underwent an SC approach had shorter postoperative stays in the intensive care unit (ICU) (5 days vs 13.8 days; p < 0.05) and shorter total hospital stays (16.4 days vs 27.2 days; p < 0.05). Long-term survival after mean follow-up of 260 days for the SC group and 232 days for the sternotomy group was 75% and 33%, respectively. CONCLUSIONS: Exchange of the HeartMate II pump can be accomplished with low morbidity and mortality and good long-term outcomes through a less invasive SC approach.