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Study design Cross-sectional cohort analysis of patients with Modic Changes (MC). Objective Our goal was to characterize the molecular and cellular features of MC bone marrow and adjacent discs. We hypothesized that MC associate with biologic cross-talk between discs and bone marrow, the presence of which may have both diagnostic and therapeutic implications. Background Data MC are vertebral bone marrow lesions that can be a diagnostic indicator for discogenic low back pain. Yet, the pathobiology of MC is largely unknown. Methods Patients with Modic type 1 or 2 changes (MC1, MC2) undergoing at least 2-level lumbar interbody fusion with one surgical level having MC and one without MC (control level). Two discs (MC, control) and two bone marrow aspirates (MC, control) were collected per patient. Marrow cellularity was analyzed using flow cytometry. Myelopoietic differentiation potential of bone marrow cells was quantified to gauge marrow function, as was the relative gene expression profiles of the marrow and disc cells. Disc/bone marrow cross-talk was assessed by comparing MC disc/bone marrow features relative to unaffected levels. Results Thirteen MC1 and eleven MC2 patients were included. We observed pro-osteoclastic changes in MC2 discs, an inflammatory dysmyelopoiesis with fibrogenic changes in MC1 and MC2 marrow, and upregulation of neurotrophic receptors in MC1 and MC2 bone marrow and discs. Conclusion Our data reveal a fibrogenic and pro-inflammatory cross-talk between MC bone marrow and adjacent discs. This provides insight into the pain generator at MC levels and informs novel therapeutic targets for treatment of MC-associated LBP.

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Background Total hip arthroplasty (THA) is a beneficial and cost-effective procedure for patients with osteoarthritis. Recent initiatives to improve hospital quality of care include assessing unplanned hospital readmission rates. Patients presenting for THA have different indications and medical comorbidities that may impact rates of readmission. Questions/purposes This study measured (1) the unplanned hospital readmission rate in primary THA, revision THA, and antibiotic-spacer staged revision THA to treat infection. Additionally, we determined (2) the medical and surgical causes of readmission; and (3) the risk factors associated with unplanned readmission. Methods A total of 1415 patients (988 primary THA, 344 revision THA, 82 antibiotic-spacer staged revision THA to treat infection) from a single institution were included. All hospital readmissions within 90 days of discharge were reviewed. Patient demographics and medical comorbidities were included in a Cox proportional hazards model to assess risk of readmission. Results The overall unplanned readmission rate was 4% at 30 days and 7% at 90 days. At 90 days, primary THA (5%) had a lower unplanned readmission rate than revision THA (10%, p \ 0.001) and antibiotic-spacer staged revision THA (18%, p \ 0.001). Medical diagnoses were responsible for almost one-fourth of unplanned readmissions, whereas over half of surgical readmissions were the result of dislocation, surgical site infection, and postoperative hematoma. Type of procedure, hospital stay greater than 5 days, cardiac valvular disease, diabetes with endorgan complications, and substance abuse were each associated with increased risk of unplanned readmission. Conclusions Higher rates of unplanned hospital readmissions in revision THA rather than primary THA suggest that healthcare quality measures that incorporate readmission rates as a proxy for quality of care should distinguish between primary and revision procedures. Failure to do so may negatively impact tertiary referral hospitals that often care for patients requiring complex revision procedures. Level of Evidence Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

There is a growing demand for in vitro assays for toxicity screening in three-dimensional (3D) environments. In this study, 3D cell culture using magnetic levitation was used to create an assay in which cells were patterned into 3D rings that close over time. The rate of closure was determined from time-lapse images taken with a mobile device and related to drug concentration. Rings of human embryonic kidney cells (HEK293) and tracheal smooth muscle cells (SMCs) were tested with ibuprofen and sodium dodecyl sulfate (SDS). Ring closure correlated with the viability and migration of cells in two dimensions (2D). Images taken using a mobile device were similar in analysis to images taken with a microscope. Ring closure may serve as a promising label-free and quantitative assay for high-throughput in vivo toxicity in 3D cultures.

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