TNX-1500, a crystallizable fragment-modified anti-CD154 antibody, prolongs nonhuman primate renal allograft survival.

The blockade of the CD154-CD40 pathway with anti-CD154 monoclonal antibody has been a promising immunomodulatory approach to prevent allograft rejection. However, clinical trials of immunoglobulin G1 antibodies targeting this pathway revealed thrombogenic properties, which were subsequently shown to be mediated by crystallizable fragment (Fc)-gamma receptor IIa-dependent platelet activation. To prevent thromboembolic complications, an immunoglobulin G4 anti-CD154 monoclonal antibody, TNX-1500, which retains the fragment antigen binding region of ruplizumab (humanized 5c8, BG9588), was modified by protein engineering to decrease Fc binding to Fc-gamma receptor IIa while retaining certain other effector functions and pharmacokinetics comparable with natural antibodies. Here, we report that TNX-1500 treatment is not associated with platelet activation in vitro and consistently inhibits kidney allograft rejection in vivo without clinical or histologic evidence of prothrombotic phenomena. We conclude that TNX-1500 retains efficacy similar to that of 5c8 to prevent kidney allograft rejection while avoiding previously identified pathway-associated thromboembolic complications.

Outcomes of Medial Collateral Ligament Injuries during Total Knee Arthroplasty.

Intraoperative medial collateral ligament (MCL) disruption during total knee arthroplasty (TKA) is often managed with either primary repair or use of a constrained implant. A total of 23 patients with an MCL injury during TKA between 2003 and 2009 were compared with 92 matched controls. Of the 23 patients, 10 were treated with an unconstrained implant and primary MCL repair, 8 with constrained implants, 3 with constrained implants and MCL repair, and 2 with unconstrained implants and no MCL repair. After an average 5-year follow-up, patients had lower Knee Society Scores (KSS), 79 versus 87 (p = 0.03), but similar Knee Function Scores (KFS), 68 versus 72 (p = 0.35). The improvement between preoperative and postoperative KSS and KFS did not vary among the two groups (p = 0.88 and p = 0.77, respectively). Postoperative scores did not vary significantly among the four treatment modalities. Conservative treatment can provide satisfactory outcomes and avoid potential complications of increased constraint.

Novel angle measurements for assessment of shoulder location using the scapular y radiograph.

Shoulder dislocation is an injury with potential long-term consequences that requires prompt diagnosis and treatment. Patient positioning and imperfect radiographic views may result in discomfort, added examination time, and problematic diagnosis. The scapular Y radiograph has been shown to be useful in diagnosing shoulder dislocation but is not considered sufficient in isolation. Using a synthetic bone shoulder model, we propose a novel technique wherein osseous landmarks are used to form angles that significantly improved diagnostic accuracy for shoulder dislocation, even in significantly rotated and otherwise indeterminate scapular Y radiographs.