Orthopaedic surgery is one of the most competitive but least diverse surgical specialties, with ever-increasing academic achievements (such as test scores) shown by applicants. Prior research shows ...that white applicants had higher United States Medical Licensing Exam (USMLE) Step 1 and Step 2 Clinical Knowledge scores as well as higher odds of Alpha Omega Alpha status compared with Black, Hispanic, and other applicant groups. Yet, it still remains unknown whether differences in application metrics by race/ethnicity sufficiently explain the underrepresentation of certain racial or ethnic minority groups in orthopaedic residency programs.
In this study, we sought to determine (1) the relative weight of academic variables for admission into orthopaedic residency, and (2) whether race and gender are independently associated with admission into an orthopedic residency.
The Electronic Residency Application System (ERAS) data from the Association of American Medical Colleges (AAMC) and the National Board of Medical Examiners (NBME) of first-time MD applicants (n = 8966) for orthopaedic surgery residency positions in the United States and of admitted orthopaedic residents (n = 6218) from 2005 to 2014 were reviewed. This dataset is the first and most comprehensive of its kind to date in orthopaedic surgery. Academic metrics, such as USMLE Step 1 and Step 2 Clinical Knowledge scores, number of publications, Alpha Omega Alpha status, volunteer experiences, work experience, as well as race and gender, were analyzed using hierarchical logistic regression models. The first model analyzed the association of academic metrics with admission into orthopaedic residency. In the second model, we added race and gender and controlled for metrics of academic performance. To determine how well the models simulated the actual admissions data, we computed the receiver operating characteristics (ROC) including the area under curve (AUC), which measures the model's ability to simulate which applicants were admitted or not admitted, with an AUC = 1.0 representing a perfect simulation. The odds ratio and confidence interval of each variable were computed.
When only academic variables were analyzed in the first model, Alpha Omega Alpha status (odds ratio 2.12 95% CI 1.80 to 2.50; p < 0.001), the USMLE Step 1 score (OR 1.04 95% CI 1.03 to 1.04; p < 0.001), the USMLE Step 2 Clinical Knowledge score (OR 1.01 95% CI 1.01 to 1.02; p < 0.001), publication count (OR 1.04 95% CI 1.03 to 1.05; p < 0.001), and volunteer experience (OR 1.03 95% CI 1.01 to 1.04; p < 0.001) were associated with admissions into orthopaedics while work and research experience were not. This model yielded a good prediction of the results with an AUC of 0.755. The second model, in which the variables of race and gender were added to the academic variables, also had a good prediction of the results with an AUC of 0.759. This model indicates that applicant race, but not gender, is associated with admissions into orthopaedic residency. Applicants from Asian (OR 0.78 95% CI 0.67 to 0.92), Black (OR 0.63 95% CI 0.51 to 0.77, Hispanic (OR 0.48 95% CI 0.36 to 0.65), or other race groups (OR 0.65 95% CI 0.55 to 0.77) had lower odds of admission into residency compared with white applicants.
Minority applicants, but not women, have lower odds of admission into orthopaedic surgery residency, even when accounting for academic performance metrics. Changes in the residency selection processes are needed to eliminate the lower admission probability of qualified minority applicants in orthopaedic residency and to improve the diversity and inclusion of orthopaedic surgery. Changes including increasing the diversity of the selection committee, bias training, blinding applications before review, removal of metrics with history of racial disparities from an interviewer's candidate profile before an interview, and use of holistic application review (where an applicants' experiences, attributes, and academic metrics are all considered) can improve the diversity landscape in training. In addition, cultivating an environment of inclusion will be necessary to address these long-standing trends in orthopaedic surgery.
Race, but not gender, is associated with the odds of acceptance into orthopaedic surgery residency despite equivalent academic metrics. Changes in residency selection processes are suggested to eliminate the lower admission probability of qualified minority applicants into orthopaedic residency and to improve the diversity and inclusion of orthopaedic surgery.
Intervertebral disc degeneration is accompanied by elevated levels of inflammatory cytokines that have been implicated in disease etiology and matrix degradation. While the effects of inflammatory ...stimulation on disc cell metabolism have been well-studied, their effects on cell biophysical properties have not been investigated. The hypothesis of this study is that inflammatory stimulation alters the biomechanical properties of isolated disc cells and volume responses to step osmotic loading. Cells from the nucleus pulposus (NP) of bovine discs were isolated and treated with either lipopolysaccharide (LPS), an inflammatory ligand, or with the recombinant cytokine TNF-α for 24 hours. We measured cellular volume regulation responses to osmotic loading either immediately after stimulation or after a 1 week recovery period from the inflammatory stimuli. Cells from each group were tested under step osmotic loading and the transient volume-response was captured via time-lapse microscopy. Volume-responses were analyzed using mixture theory framework to investigate two biomechanical properties of the cell, the intracellular water content and the hydraulic permeability. Intracellular water content did not vary between treatment groups, but hydraulic permeability increased significantly with inflammatory treatment. In the 1 week recovery group, hydraulic permeability remained elevated relative to the untreated recovery control. Cell radius was also significantly increased both after 24 hours of treatment and after 1 week recovery. A significant linear correlation was observed between hydraulic permeability and cell radius in untreated cells at 24 hours and at 1-week recovery, though not in the inflammatory stimulated groups at either time point. This loss of correlation between cell size and hydraulic permeability suggests that regulation of volume change is disrupted irreversibly due to inflammatory stimulation. Inflammatory treated cells exhibited altered F-actin cytoskeleton expression relative to untreated cells. We also found a significant decrease in the expression of aquaporin-1, the predominant water channel in disc NP cells, with inflammatory stimulation. To our knowledge, this is the first study providing evidence that inflammatory stimulation directly alters the mechanobiology of NP cells. The cellular biophysical changes observed in this study are coincident with documented changes in the extracellular matrix induced by inflammation, and may be important in disease etiology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Biomarkers are biological characteristics that can be used to indicate health or disease. This paper reviews studies on biomarkers of low back pain (LBP) in human subjects. LBP is the leading cause ...of disability, caused by various spine‐related disorders, including intervertebral disc degeneration, disc herniation, spinal stenosis, and facet arthritis. The focus of these studies is inflammatory mediators, because inflammation contributes to the pathogenesis of disc degeneration and associated pain mechanisms. Increasingly, studies suggest that the presence of inflammatory mediators can be measured systemically in the blood. These biomarkers may serve as novel tools for directing patient care. Currently, patient response to treatment is unpredictable with a significant rate of recurrence, and, while surgical treatments may provide anatomical correction and pain relief, they are invasive and costly. The review covers studies performed on populations with specific diagnoses and undefined origins of LBP. Since the natural history of LBP is progressive, the temporal nature of studies is categorized by duration of symptomology/disease. Related studies on changes in biomarkers with treatment are also reviewed. Ultimately, diagnostic biomarkers of LBP and spinal degeneration have the potential to shepherd an era of individualized spine medicine for personalized therapeutics in the treatment of LBP.
INTRODUCTION:Orthopaedic surgery residency programs have the lowest representation of ethnic/racial minorities compared with other specialties. This study compared orthopaedic residency enrollment ...rates and academic metrics of applicants and matriculated residents by race/ethnicity.
METHODS:Data on applicants from US medical schools for orthopaedic residency and residents were analyzed from 2005 to 2014 and compared between race/ethnic groups (White, Asian, Black, Hispanic, and Other).
RESULTS:Minority applicants comprised 29% of applicants and 25% of enrolled candidates. Sixty-one percent of minority applicants were accepted into an orthopaedic residency versus 73% of White applicants (P < 0.0001). White and Asian applicants and residents had higher USMLE Step 1. White applicants and matriculated candidates had higher Step 2 Clinical Knowledge scores and higher odds of Alpha Omega Alpha membership compared with Black, Hispanic, and Other groups. Publication counts were similar in all applicant groups, although Hispanic residents had significantly more publications. Black applicants had more volunteer experiences.
CONCLUSIONS:In orthopaedic surgery residency, minority applicants enrolled at a lower rate than White and Asian applicants. The emphasis on USMLE test scores and Alpha Omega Alpha membership may contribute to the lower enrollment rate of minority applicants. Other factors such as conscious or unconscious bias, which may contribute, were not evaluated in this study.
Cartilage is a hydrated soft tissue whose solid matrix consists of negatively charged proteoglycans enmeshed within a fibrillar collagen network. Though many aspects of cartilage mechanics are well ...understood today, most notably in the context of porous media mechanics, there remain a number of responses observed experimentally whose prediction from theory has been challenging. In this study the solid matrix of cartilage is modeled with a continuous fiber angular distribution, where fibers can only sustain tension, swelled by the osmotic pressure of a proteoglycan ground matrix. It is shown that this representation of cartilage can predict a number of observed phenomena in relation to the tissue's equilibrium response to mechanical and osmotic loading, when flow-dependent and flow-independent viscoelastic effects have subsided. In particular, this model can predict the transition of Poisson's ratio from very low values in compression (approximately 0.02) to very high values in tension (approximately 2.0). Most of these phenomena cannot be explained when using only three orthogonal fiber bundles to describe the tissue matrix, a common modeling assumption used to date. The main picture emerging from this analysis is that the anisotropy of the fibrillar matrix of articular cartilage is intimately dependent on the mechanism of tensed fiber recruitment, in the manner suggested by our recent theoretical study (Ateshian, 2007, ASME J. Biomech. Eng., 129(2), pp. 240-249).
Many intervertebral disc diseases cause low back pain (LBP). Proinflammatory cytokines and matrix metalloproteinases (MMPs) participate in disc pathology. In this study, we examined levels of serum ...cytokines and MMPs in human subjects with diagnoses of disc herniation (DH), spinal stenosis (SS), or degenerative disc disease (DDD) relative to levels in control subjects. Comparison between subjects with DH and those with other diagnoses (Other Dx, grouped from SS and DDD) was performed to elaborate a pathological mechanism based on circulating cytokine levels.
Study participants were recruited from a spine neurosurgery practice (n = 80), a back pain management practice (n = 27), or a control cohort (n = 26). Serum samples were collected before treatment and were assayed by multiplex assays for levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, tumor necrosis factor-α, MMP-1, MMP-3, and MMP-9. Inflammatory and degradative mediator levels were compared for subjects with LBP and control subjects, by diagnosis and by treatment groups, controlling for effects of sex, age, and reported history of osteoarthritis. Spearman's correlation coefficient was used to examine relationships with age, body mass index (BMI), symptom duration, and smoking history.
Serum levels of IL-6 were significantly higher in subjects with LBP compared with control subjects. Participants with LBP due to Other Dx had significantly higher levels of IL-6 than DH and controls. Serum levels of MMP-1 were significantly lower in LBP subjects, specifically those with DH, than in control subjects. Positive correlations were found between IL-6 levels and BMI, symptom duration, and age. MMP-1 levels were positively correlated with age.
The findings of the present clinical study are the results of the first examination of circulating cytokine levels in DDD and SS and provide evidence for a more extensive role of IL-6 in disc diseases, where patients with DDD or SS have higher serum cytokine levels than those with DH or control subjects. These findings suggest that LBP subjects have low-grade systemic inflammation, and biochemical profiling of circulating cytokines may assist in refining personalized diagnoses of disc diseases.
Degeneration of the intervertebral disc (IVD) results in a range of symptomatic (i.e., painful) and asymptomatic experiences. Components of the degenerative environment, including structural ...disruption and inflammatory cytokine production, often correlate with pain severity. However, the role of inflammation in the activation of pain and degenerative changes has been complex to delineate. The most common IVD injury model is puncture; however, it initiates structural damage that is not representative of the natural degenerative cascade. In this study, we utilized in vivo injection of lipopolysaccharide (LPS), a pro‐inflammatory stimulus, into rat caudal IVDs using 33G needles to induce inflammatory activation without the physical tissue disruption caused by puncture using larger needles. LPS injection increased gene expression of pro‐inflammatory cytokines (Tnfa, Il1b) and macrophage markers (Inos, Arg1), supported by immunostaining of macrophages (CD68, CCR7, Arg1) and systemic changes in blood cytokine and chemokine levels. Disruption of the IVD structural integrity after LPS injection was also evident through changes in histological grading, disc height, and ECM biochemistry. Ultimately, intradiscal inflammatory stimulation led to local mechanical hyperalgesia, demonstrating that pain can be initiated by inflammatory stimulation of the IVD. Gene expression of nociceptive markers (Ngf, Bdnf, Cgrp) and immunostaining for neuron ingrowth (PGP9.5) and sensitization (CGRP) in the IVD were also shown, suggesting a mechanism for the pain exhibited. To our knowledge, this rat IVD injury model is the first to demonstrate local pain behavior resulting from inflammatory stimulation of caudal IVDs. Future studies will examine the mechanistic contributions of inflammation in mediating pain.
A new rat model of intervertebral disc (IVD) degeneration initiated by inflammatory stimulation using intradiscal injection of lipopolysaccharide (LPS) was developed. It decreased structural integrity of the IVD, increased local and systemic inflammatory cytokines, and increased macrophage presence in the disc. In vivo intradiscal inflammatory stimulation also increased expression of neurons, nociceptive markers, and localized spinal pain behavior.
Mechanical loading of the intervertebral disc (IVD) initiates cell‐mediated remodeling events that contribute to disc degeneration. Cells of the IVD, nucleus pulposus (NP) and anulus fibrosus (AF), ...will exhibit various responses to different mechanical stimuli which appear to be highly dependent on loading type, magnitude, duration, and anatomic zone of cell origin. Cells of the NP, the innermost region of the disc, exhibit an anabolic response to low‐moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure, while higher magnitudes promote a catabolic response marked by increased protease expression and activity. Cells of the outer AF are responsive to physical forces in a manner that depends on frequency and magnitude, as are cells of the NP, though they experience different forces, deformations, pressure, and osmotic pressure in vivo. Much remains to be understood of the mechanotransduction pathways that regulate IVD cell responses to loading, including responses to specific stimuli and also differences among cell types. There is evidence that cytoskeletal remodeling and receptor‐mediated signaling are important mechanotransduction events that can regulate downstream effects like gene expression and posttranslational biosynthesis, all of which may influence phenotype and bioactivity. These and other mechanotransduction events will be regulated by known and to‐be‐discovered cell‐matrix and cell‐cell interactions, and depend on composition of extracellular matrix ligands for cell interaction, matrix stiffness, and the phenotype of the cells themselves. Here, we present a review of the current knowledge of the role of mechanical stimuli and the impact upon the cellular response to loading and changes that occur with aging and degeneration of the IVD.
Substructures of the intervertebral disc (IVD) include the anulus fibrosus (AF), cartilage endplate (CEP) and nucleus pulposus (NP) drawn as shown. These structures experience a wide range of physical stimuli that generate cellular responses through cytoskeletal remodeling, and cell‐matrix and cell‐cell interactions, that can drive changes to extracellular matrix (ECM). Altered magnitudes of physical stimuli with disc degeneration can drive degenerative changes.
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