The chemokine, stromal-derived factor-1/CXCL12, is expressed by normal and neoplastic tissues and is involved in tumor growth, metastasis, and modulation of tumor immunity. T cell-mediated tumor immunity depends on the migration and colocalization of CTL with tumor cells, a process regulated by chemokines and adhesion molecules. It has been demonstrated that T cells are repelled by high concentrations of the chemokine CXCL12 via a concentration-dependent and CXCR4 receptor-mediated mechanism, termed chemorepulsion or fugetaxis. We proposed that repulsion of tumor Ag-specific T cells from a tumor expressing high levels of CXCL12 allows the tumor to evade immune control. Murine B16/OVA melanoma cells (H2b) were engineered to constitutively express CXCL12. Immunization of C57BL/6 mice with B16/OVA cells lead to destruction of B16/OVA tumors expressing no or low levels of CXCL12 but not tumors expressing high levels of the chemokine. Early recruitment of adoptively transferred OVA-specific CTL into B16/OVA tumors expressing high levels of CXCL12 was significantly reduced in comparison to B16/OVA tumors, and this reduction was reversed when tumor-specific CTLs were pretreated with the specific CXCR4 antagonist, AMD3100. Memory OVA-specific CD8+ T cells demonstrated antitumor activity against B16/OVA tumors but not B16/OVA.CXCL12-high tumors. Expression of high levels of CXCL12 by B16/OVA cells significantly reduced CTL colocalization with and killing of target cells in vitro in a CXCR4-dependent manner. The repulsion of tumor Ag-specific T cells away from melanomas expressing CXCL12 confirms the chemorepellent activity of high concentrations of CXCL12 and may represent a novel mechanism by which certain tumors evade the immune system.

Background: The representation of women in orthopaedics in the United States remains among the lowest in all fields of medicine, and prior research has suggested that this underrepresentation may stem from lower levels of interest among female medical students. Of the many proposed reasons for this lack of interest, the male-dominated nature of the field is one of the most commonly cited. The purpose of this study was to determine the degree to which the representation of women among orthopaedic faculty and residents influences female medical students at that institution to apply for a residency in orthopaedics. Methods: Using data provided by the Association of American Medical Colleges, we identified all U.S. medical schools that were affiliated with an orthopaedic surgery department and an orthopaedic surgery residency program (n = 107). For each institution, data on the representation of women among the orthopaedic faculty and residents from 2014 through 2016 were collected, as well as data on the proportion of female medical school graduates who applied to an orthopaedic residency program from 2015 through 2017. The association between institutional factors and the female medical student orthopaedic application rate was assessed. Results: Of 22,707 women who graduated from medical school during the 3-year study period, 449 (1.98%) applied to an orthopaedic surgery residency program. Women who attended medical school at institutions with high orthopaedic faculty sex diversity were more likely to apply for a residency in orthopaedics (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.04 to 1.64; p = 0.023), as were women who attended medical school at institutions with high orthopaedic resident sex diversity (OR, 1.30; 95% CI, 1.05 to 1.61; p = 0.019). Conclusions: In this study, we found that increased sex diversity among orthopaedic faculty and residents was associated with a greater likelihood that female medical students at that institution would apply for an orthopaedic residency. These results suggest that at least some of the factors currently impeding female medical student interest in orthopaedics may be modifiable. These findings may have important implications for efforts to improve the sex diversity of the field of orthopaedics going forward.

Background: With the worsening of the opioid epidemic, there has been an increasing number of cases in which patients are “found down” following a drug overdose and develop a crush injury resulting in muscle necrosis, rhabdomyolysis, and elevated compartment pressures in a unique presentation of compartment syndrome. The purpose of the present study is to summarize our experience at a trauma center in a region with a high endemic rate of opiate abuse to provide guidance for the management of patients with “found down” compartment syndrome. Methods: We performed a retrospective review of the records of patients who had been found unconscious as the result of overdose, with findings that were concerning for compartment syndrome, and had been managed with fasciotomy or observation at the discretion of the surgeon. The patients were divided into 3 groups based on presentation (partial deficits, complete deficits, or unexaminable), and the operative findings, hospital course, laboratory values, and functional status were compared between the groups. Results: Over 12 years, we identified 30 “found down” patients who had an examination that was concerning for compartment syndrome. Twenty-five patients were managed with fasciotomy; this group required an average of 4.2 operations and had a 20% infection rate and a 12% amputation rate. Lactate, creatine phosphokinase, and creatinine levels typically were elevated but did not correspond with muscle viability or return of function. At the time of initial debridement, 56% of patients had muscle that appeared nonviable, although muscle function returned in 28% of the patients who had questionable viability. Four patients had no motor or neurological function on initial examination, and none had meaningful return of function at the time of the latest follow-up. Of the 10 patients who had partial neurological deficits at the time of presentation and underwent fasciotomy, over half (70%) had some improvement in ultimate function. Conclusions: Patients who are “found down” following an opiate overdose with crush injuries resulting in compartment syndrome have a high surgical complication rate and poor recovery of function. The limited data from the present study suggest that those with absent function at the time of presentation are unlikely to gain function after fasciotomy, and the risk-benefit ratio of fasciotomy in this patient population may be different from that for patients with traumatic compartment syndrome. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Supracondylar humerus fractures are common pediatric injuries encountered by orthopedic surgeons. Displaced fractures are treated operatively with closed reduction and percutaneous pinning or open reduction of injuries that cannot be adequately closed reduced. The purpose of this study is to identify preoperative injury characteristics associated with open reduction. Retrospective chart review was performed on all AO type 13A (Gartland type) supracondylar humerus fractures in patients 2–13 years old treated surgically at a single level 1 trauma center over 6 years. Preoperative demographics and radiographic parameters were obtained for all patients. Primary outcomes were closed reduction or conversion to open reduction of fractures prior to k-wire fixation. Initial bivariate analysis was done using Chi-square tests. Final multivariate analysis with Bonferonni correction was performed using a backward, stepwise regression model including potential predictor variables identified in the bivariate analysis. A total of 211 patients received surgical treatment and 18 of those patients (8.5%) failed closed reduction and underwent open reduction. Final multivariate analysis demonstrated that only flexion type [relative risk (RR), 10.2] and coronal displacement more than 7 mm (RR, 4.49) were significant preoperative factors for conversion to open reduction. Patients with significant coronal displacement and flexion-type injuries are markers of challenging reduction and are at high risk for conversion to open reduction.