Guideline contains a list of the recommendations and the rating of strength based on the quality of the supporting evidence. Discussion of how each recommendation was developed and the complete evidence report are contained in the full guideline at www.aaos.org/ guidelines.

Introduction: Endoprosthetic reconstruction presents a significant risk of perioperative blood loss. Tranexamic acid (TXA) is an antifibrinolytic agent used to reduce blood loss in orthopaedic procedures. The safety and efficacy of TXA in arthroplasty are well documented. There is, however, a dearth of literature exploring the safety and efficacy of TXA in musculoskeletal oncology patients. This retrospective, comparative study explores the effects of TXA on perioperative blood loss, blood transfusion rates, venous thromboembolism (VTE) occurrence, and hospital stay in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction. Methods: For the study, charts from a total of 90 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction were reviewed; of these patients, 34 were in the TXA group and 56 in the non-TXA group. Study participants composed of a heterogeneous group of patients with primary bone sarcoma and metastatic osseous disease. Patients in the TXA group received 1 g of topical TXA administered into the wound bed before closure. The Hemoglobin Balance method was used to calculate blood loss. Patients were followed for 6 weeks. Results: Patients undergoing proximal femur replacement and distal femur replacement in the TXA group experienced a 796 and 687 mL reduction in 72-hour mean blood loss, respectively (P = 0.0003 and P = 0.006). Average blood transfusions decreased by 0.45 U of packed red blood cells per patient in the TXA group (P = 0.048) and transfusion incidence decreased by 21.1% compared with the non-TXA group (P = 0.04). Patients undergoing proximal femur replacement in the TXA group left the hospital 2.2 days earlier than those in the non-TXA group (P = 0.0004). No increase in VTE rate was observed with TXA use. Discussion: This study found results similar to total joint arthroplasty with regard to TXA's effect on perioperative blood loss, transfusion rates, hospital stay, and VTE occurrence. It provides initial data to support the efficacy of topical TXA use in this patient cohort. Level of Evidence: Level III, retrospective cohort study

Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and adolescents. OS has a 60% survival rate with current treatments; hence, there is a need to identify novel adjuncts to chemotherapeutic regimens. In this pilot study, we investigated the dose-response to 1a,25-dihdroxyvitamin D 3 (1,a 25(OH) 2 Keywords: osteosarcoma; vitamin D; proliferation; differentiation; apoptosis Osteosarcoma (OS) is a malignant bone tumor predominantly affecting children and adolescents.1 Current chemotherapy regimens and surgical interventions have not led to significant improvement in the present 60-70% survival rate. In addition, therapies in OS have remained relatively unchanged over the past 20 years. 2,3 There is a need to identify novel therapeutic regimens to improve survival rates for individuals over those achieved with the current treatment approaches.The active form of vitamin D, 1a,25-dihdroxyvitamin D 3 (1a,25(OH) 2 D 3 ) is increasingly recognized for its anti-cancer properties. 4,5 The main biologic function of 1a,25(OH) 2 D 3 is to maintain serum calcium levels within normal range by increasing the efficiency of intestinal absorption of dietary calcium 6,7 and mobilizing calcium stores from the bone into circulation.8-10 Extra-skeletal cells and tissues produce 1a,25(OH) 2 D 3 .7 By binding to the nuclear vitamin D receptor (VDR), 1a,25(OH) 2 D 3 regulates expression of genes responsible for cellular proliferation, differentiation, apoptosis, and angiogenesis in local tissues. 11,12Previous studies demonstrate that 1a,25(OH) 2 D 3 inhibits proliferation and enhances differentiation of OS cells. [13][14][15][16] The mechanisms by which 1a, 25(OH) 2 D 3 regulates proliferation and differentiation in OS are not completely understood. Evidence that 1a,25(OH) 2 D 3 induces apoptosis in canine OS cells comes from TUNEL studies detecting DNA fragmentation, a hallmark of apoptotic cells.17 Studies in rodent and human OS cell lines are contradictory. Those studies show that 1a,25(OH) 2 D 3 either inhibits 15,18,19 or has no effect on apoptosis.20 There are significant unknowns and contradictions in the current literature on the effects of 1a,25(OH) 2 D 3 on OS cells. The doseresponse to 1a,25(OH) 2 D 3 by different OS cells is not well-defined or characterized. The mechanisms involving inhibition of proliferation and promotion of differentiation remain unclear.The objectives of this pilot study were to determine the dose-response to 25(OH)D 3 or 1a,25(OH) 2 D 3 by OS cell lines, and thus, to identify the effects of vitamin D (25D or 1a,25(OH) 2 D 3 ) on cellular processes in human OS cell lines: SaOS-2 and 143B. The rationale for choosing the above mentioned cell lines versus other Additional supporting information may be found in the online version of this article.

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Research conducted to date has deepened our understanding of sex and gender differences in the etiology, diagnosis, treatment, and outcomes for many conditions that affect both women and men. The Sex and Gender Women’s Health Collaborative (SGWHC) is supported by the coordinated efforts of our founding partners: the American Medical Women’s Association, the American College of Women’s Health Physicians and Society for Women’s Health Research to address the gaps in medical education with regard to sex and gender competency in the care of women. The SGWHC initiated and continues to build a novel digital resource library of sex and gender specific materials to be adopted and adapted into medical education and clinical practice, residing @ http://www.sgwhc.org. This article presents a case for the inclusion of sex and gender focused content into medical curricula and describes a means for students, faculty, and practitioners to access a centralized, interactive repository for these resources.