Citations

ABSTRACTThe mechanism underlying non‐contact anterior cruciate ligament (ACL) injury is multi‐factorial and still an object of debate. Computational models, in combination with in vivo and cadaveric studies, can provide valuable insight into the contribution of the different factors involved. The goal of this study was to validate four knee finite element models (two males and two females) to kinematic and strain data collected in vitro with an impact‐driven simulator and use them to assess how secondary external knee loads (knee abduction moment [KAM], anterior shear force, and internal rotation torque [ITR]) affect tibiofemoral contact forces and ACL force during impact. Four subject‐specific knee models were developed from specimen computed tomography and magnetic resonance imaging. Patellofemoral and tibiofemoral ligament properties were calibrated to match experimentally measured kinematics and ligament strain. Average root mean square errors and correlations between experimental and model‐predicted knee kinematics were below 1.5 mm and 2°, and above 0.75, respectively. Similar errors and correlations were obtained for ACL strain (< 2% and > 0.9). Model‐predicted ACL forces were highly correlated with the anterior component of the tibiofemoral contact force on the lateral plateau occurring during impact (r = 0.99), which was increased by larger KAM and ITR through the posterior tibial slope and a larger contact force on the lateral side. This study provides a better understanding of the mechanism through which secondary external knee loads increase ACL injury risk during landing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1730–1742, 2019

Abstract Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16 Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra‐abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity‐related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity‐related metabolic dysfunction and its complications.

PURPOSEPatients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab.METHODSA phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review.RESULTSA total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively.CONCLUSIONLenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.

ABSTRACTIntroductionNeuropathy after total knee arthroplasty (TKA) can cause significant morbidity but is inconsistently reported.MethodsWe reviewed the clinical, electrodiagnostic and perioperative features of all patients who underwent primary TKA at our institution and developed a new neuropathy within 8 weeks postoperatively.ResultsFifty‐four cases were identified (incidence 0.37% [95% confidence interval, 0.28–0.49]) affecting the following nerve(s): peroneal (37), sciatic (11), ulnar (2), tibial (2), sural (1), and lumbosacral plexus (1). In all cases with follow‐up data, motor recovery typically occurred within 1 year and was complete or near‐complete.ConclusionsPost‐TKA neuropathy is uncommon, typically does not require intervention and usually resolves within 1 year. Post‐TKA neuropathy most often affects the nerves surgically at risk. Anesthesia type does not correlate with post‐TKA neuropathy. An inflammatory etiology for post‐TKA neuropathy is rare but should be considered in specific cases. Muscle Nerve 59:679–682, 2019

Introduction: Frailty and decreased physical performance are associated with poor outcomes after kidney transplant. Less is known about their relationship with pretransplant outcomes. The aim of this study was to characterize associations between frailty and physical performance with death on the kidney transplant waiting list. Design: Since December 2014, high-risk kidney transplant candidates at our center (age > 59, diabetic and/or history of >3 years dialysis) have undergone frailty and physical performance testing using Fried Criteria and the Short Physical Performance Battery. Results: Between December 2014 and November 2016, 272 high-risk candidates underwent testing and were approved for transplant. Both frailty and physical performance score were significantly associated with death on the waiting list (hazard ratio [HR]: 6.7, confidence interval [CI]: 1.5-30.1; P = .01; HR: 0.8 per 1-point increase, CI: 0.7-1.0; P = .02, respectively). The relationship between frailty, physical performance score, and death on the waiting list appeared to be independent of age, diabetes, or duration of dialysis. Discussion: Frailty and decreased physical performance appear to be independently associated with increased mortality on the kidney transplant waiting list. Further studies are needed to determine whether improving frailty and physical performance prior to transplant can decrease waiting list mortality.