ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

Risk Factors Associated with Failure of Cephalomedullary Nail Fixation in the Treatment of Trochanteric Hip Fractures

BACKGROUND: Intramedullary (IM) nailing is widely performed in elderly patients with trochanteric fractures. Thus, it is important to identify causative factors associated with fixation failure. We investigated fixation failures after IM nailing in elderly patients with trochanteric fractures and compared the failure group with nonfailure group to identify risk factors of fixation failure.METHODS: A total of 396 patients aged 65 years or older underwent IM nailing for trochanteric fractures between January 2012 and August 2016 at our institution. Of those, 194 patients who were followed up for more than 12 months were enrolled in this study; 202 patients were excluded due to death during follow-up, bedridden status before injury, and loss to follow-up. All patients underwent plain radiography and preoperative computed tomography (CT).RESULTS: Fixation failure occurred in 11 patients (5.7%). Seven patients had stable fractures (AO/OTA); eight patients had basicervical fractures (confirmed by CT). Five patients had comminution in the greater trochanter (confirmed by CT). Regarding fracture reduction, eight patients showed discontinuity in the anterior cortex. The position of the lag screw on the lateral view was in the center in six patients and in a posterior area in the other five patients. On the basis of comparison with the 183 patients without fixation failure, risk factors of fixation failure were higher body mass index (BMI; p = 0.003), basicervical type of fracture (p = 0.037), posterior placement of the lag screw on the lateral view (p < 0.001), and inaccurate reduction of the anterior cortex (p = 0.011).CONCLUSIONS: Among the risk factors of fixation failure after IM nailing in elderly patients with trochanteric fractures, discontinuity of the anterior cortex and posterior position of the lag screw are modifiable surgeon factors, whereas higher BMI and basicervical type of fracture are nonmodifiable patient factors. Therefore, care should be taken to avoid fixation failure in IM nailing for patients with a basicervical type of fracture or higher BMI or both.

Simulation for Reduction of Transverse Acetabular Fractures in Sawbones Models

PURPOSE: The transversely oriented fracture lines are very difficult to reduce during operations, even after clear exposure of the fracture site, in acetabular fractures. The purpose of this study is to verify the quality of reduction between the different subtypes (transtectal, juxtatectal, and infratectal) of transverse fractures. This study also determined the proper type of clamps to use and the proper zone for achieving accurate reductions in Sawbones models. MATERIALS AND METHODS: Six fractures in 3 different subtypes of transverse fractures were artificially created. Ten different reduction clamps were applied for reduction of the fractures. Twelve holes around the fracture were drilled for the maintenance of the clamps. The fracture displacements were measured at the extra-articular area and the intra-articular joint portion. The pictures of the intra-articular fracture displacements were taken by a camera and these were uploaded and analyzed by the TraumaCad® computer program (Brainlab). RESULTS: The reduction quality was poor in order of transtectal, juxtatectal and infratectal. The intraarticular opening was more prominent in the transtectal subtype. The safe zone, when giving consideration of the neurovascular bundles, was a quadrilateral surface of the ilium. Drill holes are useful for maintenance of the reduction clamps. Reduction clamps with points (Weber clamp) were the best for maintenance and accurate reduction. Regarding the concerns of placement of clamps, the middle to posterior combination was the best. The upper hole among the posterior holes in the ilium was the most likely to well reduce the intra-articular opening. CONCLUSION: Transtectal was the more complicated subtype in the aspect of reduction quality. The Weber type reduction clamp was the best for reduction by centrally located holes in the quadrilateral surface and posteriorly located iliac holes in transverse acetabular fractures. The upper hole, among the posterior holes in the ilium, was the best for reduction of the fracture displacements in the intraarticular portion of acetabulum.