Our study supports photograph-based goniometry as the new standard goniometric technique, as it has been clinically validated, is performed with greater consistency and better inter-rater reliability when compared with manual goniometry. It also allows for better documentation of measurements and potential incorporation into medical records in direct contrast to visual estimation.
BackgroundOsteosarcoma (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.MethodsThree 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.ResultsLung-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.ConclusionsLung 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.
Given the histologic localization of ICG to only the tumor bed, we envision the clinical use of ICG angiography as an intraoperative margin and tumor detector. Such a tool may be used as an alternative to intraoperative histology to confirm negative primary tumor margins or as a valuable tool for debulking surgeries in vulnerable anatomic locations. Because we have demonstrated the successful preservation of ICG in frozen tumor samples, future work will focus on blinded validation of this modality in observational human trials, comparing the ICG fluorescence of harvested tissue samples with fresh frozen pathology.
IntroductionThe 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.ResultsAll 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.DiscussionDisulfiram 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 MethodsOne-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.
Study design Prospective cohort study.Objectives The objective of this study was to examine intermediate-term progression for a large series of patients with adolescent idiopathic scoliosis (AIS) with curves 40° or greater. Background Curve progression in AIS has been well documented for smaller curves in adolescence up to skeletal maturity; however, the data on curve progression past 40° or into adulthood are limited. With many surgeons recommending surgical correction when patients reach this threshold, it is important to understand the radiographic progression of curves into adulthood. Methods A database of all patients seen by a single surgeon from 1984 through 2018 with AIS curves progressing to at least 40° entered prospectively was utilized for this study. This included a total of 738 patients. Curve progression was analyzed overall and stratified by length of follow-up, curve location, and Risser stage at the time of presentation among other variables. Curve magnitude and Risser stage designations in this study were validated by performing a separate inter-and intrarater agreement study using four independent reviewers reading 50 patients' Cobb angle and Risser stage blinded in triplicate to examine the reliability of the study measurements. Results Annualized curve progression (ACP) averaged 6.3 ± 10.4°. ACP varied with length of follow-up: patients with up to 1 year of follow-up had an average ACP of 11.5 ± 17.0°, while those with 1-2 years had 8.2 ± 8.8°, and 2-5 years had 3.7 ± 4.1°, tapering off further from there. Risser stage 0 or 1 was associated with the highest ACP as compared to Risser stage 2-3 or 4-5. Intraclass correlation (ICC) values for Cobb angle measurement and Risser stage designations from four raters measuring 50 patients' measures, blinded and in triplicate, were all > 0.80, signifying a high degree of reliability within and between readers. Conclusions Annualized curve progression for 40° and greater curves was not linear over time; it was greatest immediately after a curve reaches 40° and tapered off over the next decade. Immature Risser stage at presentation was strongly associated with increasing ACP at all time frames. Level of evidence Prognostic Level I
US of the median nerve cross-sectional area can be efficiently taught and results in measurements consistent with that of an experienced operator.
Introduction: Preoperative axillary nerve palsy is a contraindication to reverse total shoulder arthroplasty (rTSA) due to the theoretical risk of higher dislocation rates and poor functional outcomes. Treatment of fracture-dislocations of the proximal humerus with rTSA is particularly challenging, as these injuries commonly present with concomitant neurologic and soft tissue injury. The aim of the current study was to determine the efficacy of rTSA for this fracture pattern in geriatric patients presenting with occult or profound neurologic injury. Methods: A retrospective case series of all shoulder arthroplasty procedures for proximal humerus fractures from February 2006 to February 2018 was performed. Inclusion criteria were patients aged greater than 65 years at the time of surgery, fracture-dislocations of the proximal humerus, and treatment with rTSA. Patients with preoperative nerve injuries were compared to patients without overt neurologic dysfunction. Forward elevation, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), Visual Analog Scale (VAS), and Subjective Shoulder Value (SSV) were obtained at final follow-up. Results: Forty-six rTSA for acute fracture were performed during the study period, 16 patients met the inclusion criteria and 5 (31%) presented with overt preoperative nerve injuries. At mean 3.1 years follow up, there were no postoperative complications including dislocations and final forward elevation was similar between study groups. Patients with overt nerve palsy had higher QuickDASH and VAS scores with lower SSV and self-rated satisfaction. Discussion: In the majority of patients with or without overt nerve injury, rTSA reliably restored overhead function and led to good or excellent patient-rated treatment outcomes. Overt nerve palsy did not lead to higher complication rates, including dislocation. Despite greater disability and less satisfaction, complete or partial nerve recovery can be expected in the majority of patients. Conclusion: Nerve injury following proximal humeral fracture dislocation may not be an absolute contraindication to rTSA.
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