Varus displacement of intertrochanteric femur fractures on injury radiographs is associated with screw cutout.

INTRODUCTION: The purpose of this study was to determine if varus displacement of intertrochanteric femur fractures on injury radiographs is associated with screw cutout after fixation. METHODS: A retrospective review performed at two urban level 1 trauma centers identified 334 patients with intertrochanteric femur fractures treated with either a cephalomedullary nail (CMN) or a sliding hip screw (SHS). Median patient age was 75 years, 69% were female and 46% had unstable fractures. Varus fracture displacement on injury radiographs, defined as the most proximal aspect of the femoral head being at or below the most proximal aspect of the greater trochanter, was present in 38% of patients. Screw cutout was recorded. RESULTS: Varus displacement was associated with unstable fracture patterns (62% vs. 37%, difference (D) 25%, 95% confidence interval (CI) 15-35%), female gender (77% vs. 64%, D 13%, CI 3-22%) and poor/adequate reductions (54% vs. 41%, D 13%, CI 2-23%). Cutout occurred in 9 (3%) patients, 8 of which had varus displacement. There was no detectable difference, with wide confidence intervals, between patients that did and did not experience cutout in terms of age, gender, unstable fractures, implants, tip-apex distance (TAD) or poor/adequate reductions. On univariate and multivariate analysis, varus displacement was the only variable associated with cutout. Patients with and without varus displacement had a cutout incidence of 6 and 0.5% (Odds ratio 13, CI 1.6-108). CONCLUSION: Intertrochanteric fractures presenting with varus displacement were more likely to experience cutout. This potential risk factor for cutout warrants further study. LEVEL OF EVIDENCE: Level 3, retrospective cohort.

Variables Associated With Lag Screw Sliding After Single-Screw Cephalomedullary Nail Fixation of Intertrochanteric Fractures.

OBJECTIVES: To evaluate variables associated with lag screw sliding after single-screw cephalomedullary nail (CMN) fixation of intertrochanteric femur fractures. DESIGN: Retrospective cohort study. SETTING: Level-one trauma center. PATIENTS/PARTICIPANTS: One hundred fifty-eight intertrochanteric fractures in patients older than 65 years with an average follow-up of 22 months. INTERVENTION: Single-screw CMN fixation. MAIN OUTCOME MEASUREMENTS: Lag screw sliding and revision surgeries. RESULTS: The average amount of lag screw sliding was 5 ± 5 mm (range, 0-21 mm). Lag screw sliding was greater with unstable fracture patterns (mean difference 2 mm, 95% confidence interval 0.4-3.5 mm, P = 0.01) and calcar gapping >4 mm (mean difference 3.7 mm, 95% confidence interval 2-5 mm, P < 0.01). No association was found between lag screw sliding and age, female gender, implants, long versus short nails, distal interlock screw use, postoperative neck-shaft angle, or tip-apex distance (P > 0.05). Revision surgeries were performed in 6 (4%) patients. Indications included symptomatic lag screw removal (n = 2), avascular necrosis (n = 1), cutout (n = 1), loss of reduction (n = 1), and perimplant fracture (n = 1). CONCLUSIONS: Unstable fracture patterns are unavoidable; however, careful attention to calcar reduction and selection of dual-screw CMN implants may minimize lag screw sliding and its detrimental effects on outcomes. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Enzymatic cleavage of uracil-containing single-stranded DNA linkers for the efficient release of affinity-selected circulating tumor cells.

We report a novel strategy to enzymatically release affinity-selected cells, such as circulating tumor cells (CTCs), from surfaces with high efficiency (∼90%) while maintaining cell viability (>85%). The strategy utilizes single-stranded DNAs that link a capture antibody to the surfaces of a CTC selection device. The DNA linkers contain a uracil residue that can be cleaved.

PTEN deficiency mediates a reciprocal response to IGFI and mTOR inhibition.

UNLABELLED: Recent evidence implicates the insulin-like growth factor (IGF) pathway in development of Ewing sarcoma, a highly malignant bone and soft-tissue tumor that primarily affects children and young adults. Despite promising results from preclinical studies of therapies that target this pathway, early-phase clinical trials have shown that a significant fraction of patients do not benefit, suggesting that cellular factors determine tumor sensitivity. Using FAIRE-seq, a chromosomal deletion of the PTEN locus in a Ewing sarcoma cell line was identified. In primary tumors, PTEN deficiency was observed in a large subset of cases, although not mediated by large chromosomal deletions. PTEN loss resulted in hyperactivation of the AKT signaling pathway. PTEN rescue led to decreased proliferation, inhibition of colony formation, and increased apoptosis. Strikingly, PTEN loss decreased sensitivity to IGF1R inhibitors but increased responsiveness to temsirolimus, a potent mTOR inhibitor, as marked by induction of autophagy. These results suggest that PTEN is lost in a significant fraction of primary tumors, and this deficiency may have therapeutic consequences by concurrently attenuating responsiveness to IGF1R inhibition while increasing activity of mTOR inhibitors. The identification of PTEN status in the tumors of patients with recurrent disease could help guide the selection of therapies. IMPLICATIONS: PTEN status in Ewing sarcoma affects cellular responses to IGFI and mTOR-directed therapy, thus justifying its consideration as a biomarker in future clinical trials.