Effective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species to induce ferroptosis. Interestingly, we find that drug sensitivity is highest in tumor cells with a mesenchymal phenotype. Furthermore, these compounds showed enhanced toxicity towards mesenchymal breast cancer populations with cancer stem cell properties in vitro . In summary, we have identified a new class of small molecule ferroptotic agents that warrant further investigation.

In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner. Results of the preliminary studies are consistent with the recently described cell death mechanism ferroptosis. Studies are in progress to confirm ferroptosis as the cell death mechanism and to identify the specific molecular targets of these small molecule anticancer agents.

BACKGROUND-Donor to recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC)ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC-ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT).

Purpose The purpose of this study was to identify risk factors for developing a subsequent contralateral slipped capital femoral epiphysis (SCFE) and provide a prediction score to quantify risk of subsequent slip at the time of initial presentation. Methods This retrospective study included patients that presented with a unilateral SCFE between 2006 and 2017. Chart and radiographic review were performed to collect demographic, clinical and radiographic risk factors. Descriptive statistics, univariate analyses and multivariate regression analysis were used to compare risk factors between patients that did or did not develop a subsequent contralateral SCFE. Results This study included 183 patients and 33 patients (18%) developed a subsequent contralateral SCFE. Younger age at time of initial presentation, lower modified Oxford Score and smaller difference in epiphyseal-diaphyseal angle between both sides during index presentation were significant predictors of subsequent contralateral SCFE. Specifically, age ≤ 11 years, modified Oxford Score ≤ 20 and difference in epiphyseal-diaphyseal angle of ≤ 21° between both hips were predictive of a contralateral slip (Area Under the Curve = 0.78; p < 0.05). The presence of each risk factor increased the risk of subsequent contralateral SCFE and having all three risk factors increased the risk to 73%. Conclusion There is a significant risk of subsequent contralateral SCFE in patients with unilateral SCFE, and predictive risk factors include younger age, lower modified Oxford Score and smaller difference in epiphyseal-diaphyseal angle between the affected and unaffected hips. Level of Evidence Level III

Key Points

An 81-year-old woman presented with progressive groin pain after metal-on-polyethylene total hip arthroplasty with a modular neck stem and was found to have adverse local tissue reaction. As we report for the first time with this implant, we observed titanium neck-titanium stem taper corrosion intraoperatively. We also found head-neck taper corrosion. The patient underwent revision surgery to a modular fluted tapered stem with ceramic head and was asymptomatic at 3-year follow-up visit. In conclusion, consideration should be given to avoiding the routine use of this modular neck stem in total hip arthroplasty. Patients with this prosthesis should be closely monitored for adverse local tissue reaction.

AIMTo analyze the literature on efficacy of dynamamization vs exchange nailing in treatment of delayed and non-union femur fractures.METHODSUltimately, 31 peer-reviewed articles with 644 exchanged nailing patients and 131 dynamization patients were identified and analyzed. The following key words were inputted in different combinations in order to search the field of publications in its entirety: “non-union”, “delayed union”, “ununited”, “femur fracture”, “femoral fracture”, “exchange nailing”, “dynaiz(s)ation”, “secondary nailing”, “dynamic”, “static”, and “nail revision”. The initial search yielded over 150 results, and was refined based on the inclusion criteria: Only studies reporting on humans, non-unions and delayed unions, and the usage of exchange nailing and/or dynamization as a secondary treatment after failed IM nailing. The resulting 66 articles were obtained through online journal access. The results were filtered further based on the exclusion criteria: No articles that failed to report overall union rates, differentiate between success rates of their reported techniques, or articles that analyzed less than 5 patients.RESULTSExchange nailing lead to fracture union in 84.785% of patients compared to the 66.412% of dynamization with statistically comparable durations until union (5.193 ± 2.310 mo and 4.769 ± 1.986 mo respectively). Dynamically locking exchange nails resulted in an average union time of 5.208 ± 2.475 mo compared to 5.149 ± 2.366 mo (P = 0.8682) in statically locked exchange nails. The overall union rate of the two procedures, statically and dynamically locked exchange nailing yielded union rates of 84.259% and 82.381% respectively. Therefore, there was no significant difference between the different locking methods of exchange nailing for union rate or time to union at a significance value of P < 0.05. The analysis showed exchange nailing to be the more successful choice in the treatment of femoral non-unions in respect to its higher success rate (491/567 EN, 24/57 dynam, P < 0.0001). However, there was no significant difference between the success rates of the two procedures for delayed union fractures (25/27 EN, 45/55 dynam, P = 0.3299). Nevertheless, dynamization was more efficient in the treatment of delayed unions (at rates comparable to exchange nailing) than in the treatment of non-unions.CONCLUSIONIn conclusion, after examination of factors, dynamization is recommended treatment of delayed femur fractures, while exchange nailing is the treatment of choice for non-unions.

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