Anatomic all-epiphyseal ACL reconstruction with "inside-out" femoral tunnel placement in immature patients yields high return to sport rates and functional outcome scores a minimum of 24 months after reconstruction.

PURPOSE: To understand if anatomic physeal-sparing ACL reconstruction in the immature host preserves range of motion, permits a return to sports, and avoids limb length discrepancy and accelerated intra-articular degeneration with a cross-sectional radiographic, physical examination and patient-reported outcomes analysis. METHODS: A cross-sectional recall study included 38 patients aged 7-15 who underwent all-epiphyseal ACL reconstruction with hamstring allograft performed by a single surgeon at a large academic medical center. All-epiphyseal reconstructions were performed using a modified Anderson physeal-sparing technique, with the femoral tunnel placed using an "inside-out" technique. Assessments consisted of a physical exam, long leg cassette radiographs, KT-1000 measurements, subjective patient metrics, and magnetic resonance imaging. RESULTS: Thirty-eight (56.7%) of 66 eligible patients returned for in-person clinical and radiographic exams. Patients were 11.4 ± 1.8 years at the time of surgery. Five patients were females (13.2%). Mean follow-up was 5.5 ± 2.4 years. ACL re-injuries occurred in four patients (10.5%), all of whom underwent revision reconstructions. Thirty-three of the remaining 34 (97.1%) patients returned to sports following their reconstruction, and 24 (70.6%) returned to their baseline level of competition. Mean limb length discrepancy (LLD) was 0.2 ± 1.4 cm. Nine patients had an LLD of > 1 cm (26.5%), which occurred at an equivalent age as those with < 1 cm LLD (10.8 ± 2.0 vs. 11.7 ± 1.7, n.s.). Pre-operative Marx scores (13.1 ± 3.5) were not significantly different from post-operative values (12.3 ± 5.1, n.s.). Patients who required ACL revisions had significantly lower Marx scores than those with intact primary grafts (8.3 ± 7.1 vs. 13.4 ± 4.5, p = 0.047). Cohort mean International Knee Documentation Committee (IKDC) score was 89.7 ± 12.7. CONCLUSION: Anatomic all-epiphyseal anatomic ACL reconstruction appears to be useful in patients with significant projected remaining growth, with good return-to-sport outcomes and minimal risk of clinically significant physeal complications. However, given the limited patient recall possible in the present study, further large sample size, high-quality works are necessary to validate our findings. LEVEL OF EVIDENCE: Level IV.

Lung cells support osteosarcoma cell migration and survival.

BACKGROUND: Osteosarcoma (OS) is the most common primary bone tumor, with a propensity to metastasize to the lungs. Five-year survival for metastatic OS is below 30%, and has not improved for several decades despite the introduction of multi-agent chemotherapy. Understanding OS cell migration to the lungs requires an evaluation of the lung microenvironment. Here we utilized an in vitro lung cell and OS cell co-culture model to explore the interactions between OS and lung cells, hypothesizing that lung cells would promote OS cell migration and survival. The impact of a novel anti-OS chemotherapy on OS migration and survival in the lung microenvironment was also examined. METHODS: Three human OS cell lines (SJSA-1, Saos-2, U-2) and two human lung cell lines (HULEC-5a, MRC-5) were cultured according to American Type Culture Collection recommendations. Human lung cell lines were cultured in growth medium for 72 h to create conditioned media. OS proliferation was evaluated in lung co-culture and conditioned media microenvironment, with a murine fibroblast cell line (NIH-3 T3) in fresh growth medium as controls. Migration and invasion were measured using a real-time cell analysis system. Real-time PCR was utilized to probe for Aldehyde Dehydrogenase (ALDH1) expression. Osteosarcoma cells were also transduced with a lentivirus encoding for GFP to permit morphologic analysis with fluorescence microscopy. The anti-OS efficacy of Disulfiram, an ALDH-inhibitor previously shown to inhibit OS cell proliferation and metastasis in vitro, was evaluated in each microenvironment. RESULTS: Lung-cell conditioned medium promoted osteosarcoma cell migration, with a significantly higher attractive effect on all three osteosarcoma cell lines compared to basic growth medium, 10% serum containing medium, and NIH-3 T3 conditioned medium (p <0.05). Lung cell conditioned medium induced cell morphologic changes, as demonstrated with GFP-labeled cells. OS cells cultured in lung cell conditioned medium had increased alkaline phosphatase staining. CONCLUSIONS: Lung endothelial HULEC-5a cells are attractants for OS cell migration, proliferation, and survival. The SJSA-1 osteosarcoma cell line demonstrated greater metastatic potential than Saos-2 and U-2 cells. ALDH appears to be involved in the interaction between lung and OS cells, and ALP may be a valuable biomarker for monitoring functional OS changes during metastasis.

Comparison of Laser Doppler and Laser-Assisted Indocyanine Green Angiography Prediction of Flap Survival in a Novel Modification of the McFarlane Flap.

BACKGROUND: The McFarlane rat ischemic dorsal skin flap model has been commonly used for clinical vector studies, as well as the testing of noninvasive diagnostics. However, variability of this model secondary to flap contact with the wound bed has led many to question its validity. Here we present a novel modification to the McFarlane skin flap using sterile silicone. We also use this model to test the prognostic efficacy of laser-assisted indocyanine green (ICG) angiography and laser Doppler imaging (LDI). METHODOLOGY: A 3 × 9-cm dorsal skin flap with a cranially based pedicle was created, centered 1 cm distal to the scapulae. The flap was undermined, and in one of the 2 groups, a sterile silicone sheet was placed onto the wound bed. All flaps were then reapproximated with sutures 1-cm intervals. Clinical assessment and perfusion imaging was performed immediately postoperative, and at 24, 48, and 72 hours postsurgery. Postoperative day 7 clinical assessment was obtained before euthanasia. RESULTS: A comparative study using silicone blocked versus unblocked models (n = 6 per group) showed that, clinically, both models had equivalent flap survival [8.5 (0.913) vs 9.5 (1.01) cm]. However, a statistically significant increase in perfusion in the mid-third of unblocked models was observed on POD3 [20.28% (2.7%) vs blocked 13.45% (2.5%), P < 0.05], with a similar increase in the distal third on POD7 [18.73% (2.064%) vs 10.91% (4.19%), P < 0.05]. A prognostic study comparing LDI and ICG angiography prediction of POD7 survival at early time points (n = 10) found that LDI underpredicted flap survival at early time points [84.2% (12.03%) on POD0, 87.35% (16.11%) on POD1]. In contrast, ICG was more proficient [100.1% (10.1%) on POD0]. CONCLUSIONS: We present a modification of the McFarlane skin flap model that results in similar clinical results, but with a noted reduction in perfusion inconsistencies noted in unblocked models. The ICG angiography is superior to LDI in predicting POD7 flap necrosis within the first 48 hours postinjury. Future work will focus on histologic validation of our model, and vector efficacy testing.

Total Hip Replacement Interrupted by Intraoperative Arrest with a Final Component in Place: A Case Report.

No consensus recommendations exist as to the management of implants exposed during an interrupted total hip arthroplasty (THA). Given the infrequency of such events, documentation of successful outcomes in single case reports aids in decision-making. A 71-year-old male with a history of coronary artery disease and a BMI of 39.5 went into ventricular fibrillation half-way through a THA, after placement of a cementless acetabular component but before femoral preparation could begin. Continuation of the planned arthroplasty was aborted, the patient's wound was packed with sterile sponges and covered with an iodoform dressing, and he was flipped supine for CPR. He returned to the OR 6-hours following his arrest and his arthroplasty was completed with the original acetabular implant left in place. The patient was placed empirically on 2 weeks of IV vancomycin and 3 months of oral doxycycline based on infectious disease recommendations, and healed uneventfully. While validation of our strategy is challenging due to the infrequent nature of this event, it is hoped that this description and discussion may provide a template to those who encounter a similar challenging situation.

Disulfiram reduces metastatic osteosarcoma tumor burden in an immunocompetent Balb/c or-thotopic mouse model.

INTRODUCTION: The overall survival rate of patients with osteosarcoma (OS) and pulmonary metastases has remained stagnant at 15-30% for several decades. Disulfiram (DSF) is an FDA-approved aldehyde dehydrogenase inhibitor that reduces the metastatic phenotype of OS cells in vitro. Here we evaluate its in vivo efficacy, as compared to doxorubicin chemotherapy, in a previously-validated orthotopic model of metastatic OS. RESULTS: All treatment groups displayed a significantly reduced quantitative OS metastatic burden compared with controls. The metastatic burden of Lo DSF-treated animals was equivalent to the DXR group. Ninety-five percent of control animals displayed evidence of metastatic disease, which was significantly greater than all treatment groups. DISCUSSION: Disulfiram treatment resulted in a reduced burden of OS metastatic disease compared with controls. This was statistically-equivalent to doxorubicin. No additive effect was observed between these two therapies. MATERIALS AND METHODS: One-hundred twenty immunocompetent Balb/c mice received proximal tibia paraphyseal injections of 5 × 105 K7M2 murine OS cells. Therapy began three weeks after injection: saline (control), low-dose disulfiram (Lo DSF), high-dose disulfiram (Hi DSF), doxorubicin (DXR), Lo DSF + DXR, and Hi DSF + DXR. Transfemoral amputations were performed at 4 weeks. Quantitative metastatic tumor burden was measured using near-infrared indocyanine green (ICG) angiography.

Risk Factors for Failure of Nonoperative Treatment for Unilateral Cervical Facet Fractures.

STUDY DESIGN: Retrospective clinical study. PURPOSE: The purpose of this study was to determine what percentage of patients who underwent nonoperative management of unilateral non-displaced or minimally displaced facet fractures progressed radiographically and to determine what percentage of patients required surgical intervention and to identify risk factors for failure of conservative management. OVERVIEW OF LITERATURE: According to most commonly used classification systems, unilateral, non-and minimally displaced facet fractures are be amendable to nonoperative management. METHODS: A retrospective review of the Trauma Registry of a Level I trauma center was performed to identify all patients diagnosed with a non- or minimally displaced unilateral facet fracture which was managed nonoperatively. Several demographic variables and clinical outcomes were recorded. Using computed tomography scanning and plain radiographs, fracture pattern, listhesis, displacement, angle and percentage of the facet that included the fracture were determined. Radiographic progression was defined as the occurrence of listhesis of more than 10% of the anterior-posterior dimensions of the inferior vertebral body during radiographic follow-up. Failure of conservative management was defined as a patient requiring surgical intervention after initially being managed nonoperatively. RESULTS: Seventy-four patients were included. Fifteen patients (20%) progressed radiographically. However, only 2 developed radicular symptoms and none developed myelopathy or other catastrophic cord related symptoms. Seven patients (9%) underwent surgery. Indications for surgery included significant radiographic progression and/or radicular symptoms. Risk factors for failure of conservative management included presence of radiculopathy at the time of presentation, a higher body mass index, increased Injury Severity Score, greater initial fracture displacement and more than 2 mm of listhesis. CONCLUSIONS: Patients with non-displaced or minimally displaced facet fractures who do not have neurological symptoms at the time of presentation can safely be managed conservatively with careful observation and follow-up.