Sex Diversity in Spine Surgery Fellowship Training: Analysis of Recent Trends and Program Characteristics Associated with Increased Diversity.

BACKGROUND CONTEXT: Sex diversity in the spine surgery workforce remains limited. Accelerated efforts to recruit more female trainees into spine surgery fellowship training may help promote diversity and inclusion in the emerging spine surgery workforce. PURPOSE: This study assessed the representation of female trainees in spine surgery fellowship training and program factors associated with greater sex diversity among fellows. STUDY DESIGN/SETTING: This was a cross-sectional analysis of spine surgery fellows in the United States during the 2016-2017 to 2022-2023 academic years. PATIENT SAMPLE: N/A OUTCOME MEASURES: Representation (%) and participation-to-prevalence ratios (PPRs) defined as the participation of female trainees in spine surgery fellowship training divided by the prevalence of female trainees in previous training cohorts. PPR values <0.8 indicated underrepresentation. METHODS: Sex diversity was assessed among spine surgery faculty, spine surgery fellows, orthopaedic surgery residents, neurosurgery residents, and allopathic medical students. Fellowship program characteristics associated with increased sex diversity were calculated with chi square tests. RESULTS: There were 693 spine surgery fellows and 41 were female (5.9%). Sex diversity in spine surgery fellowship training decreased over the study period (6.4% vs 4.1%, P=0.025). Female trainee representation in spine surgery fellowship training was less than that in orthopaedic surgery residency (14.2%, PPR=0.42), neurosurgery residency (17.1%, PPR=0.35), and allopathic medical school (47.6%, PPR=0.12) training (P<0.001). There were 508 faculty at 78 spine surgery fellowships and 25 were female (4.9%). There were three female fellowship program directors (3.8%). Fellowship program characteristics associated with increased sex diversity included the presence of female faculty (P=0.020). Additional program characteristics including geographic region, accreditation status, number of faculty and fellows were not associated with sex diversity (P>0.05). CONCLUSIONS: Female representation in spine surgery fellowship training decreased over the study period and remains underrepresented relative to earlier stages of medical and surgical training. There was a positive association between female faculty and increased sex diversity among fellows. Greater efforts are needed to create training environments that promote diversity, equity, and inclusion in spine surgery fellowship training.

Diagnosis of spine pseudoarthrosis based on the biomechanical properties of bone.

BACKGROUND CONTEXT: Failure to fuse following anterior cervical discectomy and fusion (ACDF) may result in symptomatic pseudoarthrosis. Traditional diagnosis involves computerized tomography to detect bridging bone and/or flexion-extension radiographs to assess whether segmental motion is above specific thresholds; however, there are currently no well-validated diagnostic tests. We propose a biomechanically rational approach to achieve a reliable diagnostic test for pseudoarthrosis. PURPOSE: Develop and test a biomechanically based approach to the diagnosis of pseudoarthrosis. STUDY DESIGN: Literature review, development of theory, re-analysis of a previously published study with surgical exploration as the gold-standard, and retrospective analysis of pooled studies to understand time to fusion. METHODS: Fully automated methods were used to measure disc space strains (change in disc space height divided by initial height). Measurement error combined with the reported failure strain of trabecular bone led to a proposed strain threshold for diagnosis of pseudoarthrosis following ACDF. We reanalyzed previously reported flexion-extension radiographs for asymptomatic volunteers to assess whether flexion-extension radiographs, in the absence of fusion surgery, can be expected to provide sufficient stress on motion segments to allow for reliable strain-based fusion assessment. The sensitivity and specificity of strain- and rotation-based pseudoarthrosis diagnosis were assessed by reanalysis of previously reported post-ACDF flexion-extension radiographs, where intraoperative fusion assessments were also available. Finally, we assessed changes in strain over time using 9,869 flexion-extension radiographs obtained 6 weeks to 84 months post-ACDF surgery from 1,369 patients. RESULTS: The estimated error in automated measurement of disc space strain from radiographs was approximately 3%, and the reported failure strain of bridging bone was less than 2.5%. On that basis, we propose a 5% strain threshold for pseudoarthrosis diagnosis. Reanalysis of a study in which intraoperative fusion assessments were available revealed 67% sensitivity and 82% specificity for strain-based diagnosis of pseudoarthrosis, which was comparable to rotation-based diagnosis. Analysis of post-ACDF flexion-extension radiographs revealed rapid strain reduction for up to 24 months, followed by a slower decrease for up to 84 months. When rotation is less than 2 degrees, the strain-based diagnosis differed from the rotation-based diagnosis in approximately 14% of the cases. CONCLUSIONS: We propose steps for standardizing diagnosis of pseudoarthrosis based on the failure strain of bone, measurement error, and retrospective data. These steps include obtaining high-quality flexion-extension studies, the application of proposed diagnostic thresholds, and the use of image stabilization for conclusive diagnosis, when motion is near thresholds. The necessity for an accurate diagnosis with minimal radiation exposure underscores the need for further optimization and standardization in diagnosing pseudoarthrosis following ACDF surgery. CLINICAL SIGNIFICANCE: In a symptomatic postspine fusion patient, it is important to diagnose or rule-out pseudoarthrosis. There are currently no well-validated diagnostic tests for this condition. Incorporating strain-based intervertebral motion analysis into the diagnosis could lead to a standardized and validated test for detecting spine pseudoarthrosis.

Regional structure-function relationships of lumbar cartilage endplates.

Cartilage endplates (CEPs) act as protective mechanical barriers for intervertebral discs (IVDs), yet their heterogeneous structure-function relationships are poorly understood. This study addressed this gap by characterizing and correlating the regional biphasic mechanical properties and biochemical composition of human lumbar CEPs. Samples from central, lateral, anterior, and posterior portions of the disc (n = 8/region) were mechanically tested under confined compression to quantify swelling pressure, equilibrium aggregate modulus, and hydraulic permeability. These properties were correlated with CEP porosity and glycosaminoglycan (s-GAG) content, which were obtained by biochemical assays of the same specimens. Both swelling pressure (142.79 ± 85.89 kPa) and aggregate modulus (1864.10 ± 1240.99 kPa) were found to be regionally dependent (p = 0.0001 and p = 0.0067, respectively) in the CEP and trended lowest in the central location. No significant regional dependence was observed for CEP permeability (1.35 ± 0.97 * 10-16 m4/Ns). Porosity measurements correlated significantly with swelling pressure (r = -0.40, p = 0.0227), aggregate modulus (r = -0.49, p = 0.0046), and permeability (r = 0.36, p = 0.0421), and appeared to be the primary indicator of CEP biphasic mechanical properties. Second harmonic generation microscopy also revealed regional patterns of collagen fiber anchoring, with fibers inserting the CEP perpendicularly in the central region and at off-axial directions in peripheral regions. These results suggest that CEP tissue has regionally dependent mechanical properties which are likely due to the regional variation in porosity and matrix structure. This work advances our understanding of healthy baseline endplate biomechanics and lays a groundwork for further understanding the role of CEPs in IVD degeneration.

Reference Data for Diagnosis of Spondylolisthesis and Disc Space Narrowing Based on NHANES-II X-rays.

Robust reference data, representing a large and diverse population, are needed to objectively classify measurements of spondylolisthesis and disc space narrowing as normal or abnormal. The reference data should be open access to drive standardization across technology developers. The large collection of radiographs from the 2nd National Health and Nutrition Examination Survey was used to establish reference data. A pipeline of neural networks and coded logic was used to place landmarks on the corners of all vertebrae, and these landmarks were used to calculate multiple disc space metrics. Descriptive statistics for nine SPO and disc metrics were tabulated and used to identify normal discs, and data for only the normal discs were used to arrive at reference data. A spondylolisthesis index was developed that accounts for important variables. These reference data facilitate simplified and standardized reporting of multiple intervertebral disc metrics.

Establishing case volume benchmarks for ACGME-accredited orthopedic surgery of the spine fellowship training.

BACKGROUND CONTEXT: There has been increasing scrutiny on the standardization of surgical training in the US. PURPOSE: This study provides case volume benchmarks for Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopedic spine surgery fellowship training. STUDY DESIGN/SETTING: This was a retrospective cross-sectional study of fellows at ACGME-accredited orthopedic spine surgery fellowships (2017-2022). PATIENT SAMPLE: N/A. OUTCOME MEASURES: Reported case volume during fellowship training. METHODS: Case volume percentiles were calculated across ACGME-defined case categories and temporal changes assessed via linear regression. Variability between the highest and lowest deciles by case volume was calculated as fold-differences (90th percentile/10th percentile). Sensitivity analyses were performed to identify potential targets for case minimum requirements. RESULTS: A total of 163 spine surgery fellows were included in this study. Total mean reported spine surgery case volume increased from 313.2±122 in 2017 to 382.0±164 in 2022 (p=.19). Most cases were classified as adult (range, 97.2%-98.0%) over pediatric cases (range, 2.0%-2.8%). An average of 322.0 cases were reported and most were classified as laminectomy (32%), posterior arthrodesis (29%), and anterior arthrodesis (20%). Overall variability in total case volume was 2.4 and the greatest variability existed for posterior instrumentation (38.1), application of cage (34.6), anterior instrumentation (20.8), and fractures and dislocations (17.3). If case minimum requirements for total reported cases was assumed at 200 cases, then all spine fellows included in this study would achieve this requirement. However, if case minimum requirements were assumed at 250 total cases, then approximately thirty percent of fellows (n=49) would not achieve this requirement for graduation. CONCLUSIONS: Increasingly, national societies and accrediting bodies for surgical education recognize the need for standardized training. This study provides benchmarks to inform potential case minimum requirements and help reduce variability during spine fellowship training. Future studies are needed to establish case minimum requirements for spine surgery fellowship training across comprehensive and granular case categories that cover the full gamut of orthopedic spine surgery.

Applications of SPECT/CT in the Evaluation of Spinal Pathology: A Review.

BACKGROUND: Accurate identification of pain generators in the context of low back and spine-related pain is crucial for effective treatment. This review aims to evaluate the potential usefulness of single photon emission computed tomography with computed tomography (SPECT/CT) as an imaging modality in guiding clinical decision-making. METHODS: A broad scoping literature review was conducted to identify relevant studies evaluating the use of SPECT/CT in patients with spine-related pain. Studies were reviewed for their methodology and results. RESULTS: SPECT/CT appears to have advantages over traditional modalities, such as magnetic resonance imaging and CT, in certain clinical scenarios. It may offer additional information to clinicians and improve the specificity of diagnosis. However, further studies are needed to fully assess its diagnostic accuracy and clinical utility. CONCLUSIONS: SPECT/CT is a promising imaging modality in the evaluation of low back pain, particularly in cases where magnetic resonance imaging and CT are inconclusive or equivocal. However, the current level of evidence is limited, and additional research is needed to determine its overall clinical relevance. CLINICAL RELEVANCE: SPECT/CT may have a significant impact on clinical decision-making, particularly in cases in which traditional imaging modalities fail to provide a clear diagnosis. Its ability to improve specificity could lead to more targeted and effective treatment for patients with spinal pathology.

ACR Appropriateness Criteria® Management of Vertebral Compression Fractures: 2022 Update.

Vertebral compression fractures (VCFs) can have a variety of etiologies, including trauma, osteoporosis, or neoplastic infiltration. Osteoporosis related fractures are the most common cause of VCFs and have a high prevalence among all postmenopausal women with increasing incidence in similarly aged men. Trauma is the most common etiology in those >50 years of age. However, many cancers, such as breast, prostate, thyroid, and lung, have a propensity to metastasize to bone, which can lead to malignant VCFs. Indeed, the spine is third most common site of metastases after lung and liver. In addition, primary tumors of bone and lymphoproliferative diseases such as lymphoma and multiple myeloma can be the cause of malignant VCFs. Although patient clinical history could help raising suspicion for a particular disorder, the characterization of VCFs is usually referred to diagnostic imaging. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Diffusivity of Human Cartilage Endplates in Healthy and Degenerated Intervertebral Disks.

The cartilage endplates (CEPs) on the superior and inferior surfaces of the intervertebral disk (IVD), are the primary nutrient transport pathways between the disk and the vertebral body. Passive diffusion is responsible for transporting small nutrient and metabolite molecules through the avascular CEPs. The baseline solute diffusivities in healthy CEPs have been previously studied, however alterations in CEP diffusion associated with IVD degeneration remain unclear. This study aimed to quantitatively compare the solute diffusion in healthy and degenerated human CEPs using a fluorescence recovery after photobleaching (FRAP) approach. Seven healthy CEPs and 22 degenerated CEPs were collected from five fresh-frozen human cadaveric spines and 17 patients undergoing spine fusion surgery, respectively. The sodium fluorescein diffusivities in CEP radial and vertical directions were measured using the FRAP method. The CEP calcification level was evaluated by measuring the average X-ray attenuation. No difference was found in solute diffusivities between radial and axial directions in healthy and degenerated CEPs. Compared to healthy CEPs, the average solute diffusivity was 44% lower in degenerated CEPs (Healthy: 29.07 µm2/s (CI: 23.96-33.62 µm2/s); degenerated: 16.32 µm2/s (CI: 13.84-18.84 µm2/s), p < 0.001). The average solute diffusivity had an inverse relationship with the degree of CEP calcification as determined by the normalized X-ray attenuation values (ß = -22.19, R2 = 0.633; p < 0.001). This study suggests that solute diffusion through the disk and vertebral body interface is significantly hindered by CEP calcification, providing clues to help further understand the mechanism of IVD degeneration.

DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence.

Bone marrow skeletal stem cells (SSCs) secrete many cytokines including stromal derived factor-1 or CXCL12, which influences cell proliferation, migration, and differentiation. All CXCL12 splice variants are rapidly truncated on their N-terminus by dipeptidyl peptidase 4 (DPP4). This includes the common variant CXCL12 alpha (1-68) releasing a much less studied metabolite CXCL12(3-68). Here, we found that CXCL12(3-68) significantly inhibited SSC osteogenic differentiation and RAW-264.7 cell osteoclastogenic differentiation and induced a senescent phenotype in SSCs. Importantly, pre-incubation of SSCs with CXCL12(3-68) significantly diminished their ability to migrate toward CXCL12(1-68) in transwell migration assays. Using a high-throughput G-protein-coupled receptor (GPCR) screen (GPCRome) and bioluminescent resonance energy transfer molecular interaction assays, we revealed that CXCL12(3-68) acts via the atypical cytokine receptor 3-mediated ß-arrestin recruitment and as a competitive antagonist to CXCR4-mediated signaling. Finally, a reverse phase protein array assay revealed that DPP4-cleaved CXCL12 possesses a different downstream signaling profile from that of intact CXCL12 or controls. The data presented herein provides insights into regulation of CXCL12 signaling. Importantly, it demonstrates that DPP4 proteolysis of CXCL12 generates a metabolite with significantly different and previously overlooked bioactivity that helps explain discrepancies in the literature. This also contributes to an understanding of the molecular mechanisms of osteoporosis and bone fracture repair and could potentially significantly affect the interpretation of experimental outcomes with clinical consequences in other fields where CXCL12 is vital, including cancer biology, immunology, cardiovascular biology, neurobiology, and associated pathologies.

Opioid Use Patterns in a Statewide Adult Medicaid Population Undergoing Elective Lumbar Spine Surgery.

STUDY DESIGN: Retrospective administrative database review. OBJECTIVE: Analyze patterns of opioid use in patients undergoing lumbar surgery and determine associated risk factors in a Medicaid population. SUMMARY OF BACKGROUND DATA: Opioid use in patients undergoing surgery for degenerative lumbar spine conditions is prevalent and impacts outcomes. There is limited information defining the scope of this problem in Medicaid patients. MATERIALS AND METHODS: Longitudinal cohort study of adult South Carolina (SC) Medicaid patients undergoing lumbar surgery from 2014 to 2017. All patients had continuous SC Medicaid coverage for 15 consecutive months, including six months before and nine months following surgery. The primary outcome was a longitudinal assessment of postoperative opioid use to determine trajectories and group-based membership using latent modeling. Univariate and multivariable modeling was conducted to assess risk factors for group-based trajectory modeling and chronic opioid use (COU). RESULTS: A total of 1455 surgeries met inclusion criteria. Group-based trajectory model demonstrated patients fit into five groups; very low use (23.4%), rapid wean following surgery (18.8%), increasing use following surgery (12.9%), slow wean following surgery (12.6%) and sustained high use (32.2%). Variables predicting membership in high opioid use included preoperative opioid use, younger age, longer length of stay, concomitant medications, and readmissions. More than three quarter of patients were deemed COUs (76.4%). On bivariate analysis, patients with degenerative disk disease were more likely to be COUs (24.8% vs. 18.6%; P =0.0168), more likely to take opioids before surgery (88.5% vs. 61.9%; P <0.001) and received higher amounts of opioids during the 30 days following surgery (mean morphine milligram equivalents 59.6 vs. 25.1; P <0.001). CONCLUSIONS: Most SC Medicaid patients undergoing lumbar elective lumbar spine surgery were using opioids preoperatively and continued long-term use postoperatively at a higher rate than previously reported databases. Preoperative and perioperative intake, degenerative disk disease, multiple prescribers, depression, and concomitant medications were significant risk factors.

Surgical prescription opioid trajectories among state Medicaid enrollees.

OBJECTIVE: The objective of this study was to evaluate opioid use trajectories among a sample of 10,138 Medicaid patients receiving one of six index surgeries: lumbar spine, total knee arthroplasty, cholecystectomy, appendectomy, colon resection, and tonsillectomy. DESIGN: Retrospective cohort. SETTING: Administrative claims data. PATIENTS AND PARTICIPANTS: Patients, aged 13 years and older, with 15-month continuous Medicaid eligibility surrounding index surgery, were selected from single-state Medicaid medical and pharmacy claims data for surgeries performed between 2014 and 2017. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Baseline comorbidities and presurgery opioid use were assessed in the 6 months prior to admission, and patients' opioid use was followed for 9 months post-discharge. Generalized linear model with log link and Poisson distribution was used to determine risk of chronic opioid use for all risk factors. Group-based trajectory models identified groups of patients with similar opioid use trajectories over the 15-month study period. RESULTS: More than one in three (37.7 percent) patients were post-surgery chronic opioid users, defined as the dichotomous outcome of filling an opioid prescription 90 or more days after surgery. Key variables associated with chronic post-surgery opioid use include presurgery opioid use, 30-day post-surgery opioid use, and comorbidities. Latent trajectory modeling grouped patients into six distinct opioid use trajectories. Associates of trajectory group membership are reported. CONCLUSIONS: Findings support the importance of surgeons setting realistic patient expectations for post-surgical opioid use, as well as the importance of coordination of post-surgical care among patients failing to fully taper off opioids within 1-3 months of surgery.

ACR Appropriateness Criteria® Osteoporosis and Bone Mineral Density: 2022 Update.

Osteoporosis constitutes a significant public health risk. An estimated 10.2 million adults in the United States >50 years of age have osteoporosis, a systemic condition that weakens the bones increasing the susceptibility for fractures. Approximately one-half of women and nearly one-third of men >50 years of age will sustain an osteoporotic fracture. These fractures are associated with a decrease in quality of life, diminished physical function, and reduced independence. Dual-energy X-ray absorptiometry (DXA) is the primary imaging modality used to screen for osteoporosis in women >65 years of age and men >70 years of age. DXA may be used in patients <65 years of age to evaluate bone mass density if there are additional risk factors. In certain situations, vertebral fracture assessment and trabecular bone score may further predict fracture risk, particularly in patients who are not yet osteoporotic but are in the range of osteopenia. Quantitative CT is useful in patients with advanced degenerative changes in the spine. Given the proven efficacy of pharmacologic therapy, the role of imaging to appropriately identify and monitor high-risk individuals is critical in substantially reducing osteoporosis-associated morbidity and mortality, and reducing the considerable cost to the health care system. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Definition of Normal Vertebral Morphometry Using NHANES-II Radiographs.

A robust definition of normal vertebral morphometry is required to confidently identify abnormalities such as fractures. The Second National Health and Nutrition Examination Survey (NHANES-II) collected a nationwide probability sample to document the health status of the United States. Over 10,000 lateral cervical spine and 7,000 lateral lumbar spine X-rays were collected. Demographic, anthropometric, health, and medical history data were also collected. The coordinates of the vertebral body corners were obtained for each lumbar and cervical vertebra using previously validated, automated technology consisting of a pipeline of neural networks and coded logic. These landmarks were used to calculate six vertebral body morphometry metrics. Descriptive statistics were generated and used to identify and trim outliers from the data. Descriptive statistics were tabulated using the trimmed data for use in quantifying deviation from average for each metric. The dependency of these metrics on sex, age, race, nation of origin, height, weight, and body mass index (BMI) was also assessed. There was low variation in vertebral morphometry after accounting for vertebrae (eg, L1, L2), and the R 2 was high for ANOVAs. Excluding outliers, age, sex, race, nation of origin, height, weight, and BMI were statistically significant for most of the variables, though the F-statistic was very small compared to that for vertebral level. Excluding all variables except vertebra changed the ANOVA R 2 very little. Reference data were generated that could be used to produce standardized metrics in units of SD from mean. This allows for easy identification of abnormalities resulting from vertebral fractures, atypical vertebral body morphometries, and other congenital or degenerative conditions. Standardized metrics also remove the effect of vertebral level, facilitating easy interpretation and enabling data for all vertebrae to be pooled in research studies. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

ACR Appropriateness Criteria® Inflammatory Back Pain: Known or Suspected Axial Spondyloarthritis: 2021 Update.

Inflammatory back pain is a hallmark feature of axial spondyloarthritis, a heterogeneous group of inflammatory disorders which affects the sacroiliac joints and spine. Imaging plays a key role in diagnosis of this disease and in facilitating appropriate treatment. This document provides evidence-based recommendations on the appropriate use of imaging studies during multiple stages of the clinical evaluation of patients with suspected or known axial spondyloarthritis. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Low Back Pain: 2021 Update.

In the United States, acute low back pain, with or without radiculopathy, is the leading cause of years lived with disability and the third ranking cause of disability-adjusted life-years. Uncomplicated acute low back pain and/or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags, raising suspicion for a serious underlying condition, such as cauda equina syndrome, malignancy, fracture, or infection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Suspected Spine Infection.

Spine infection is both a clinical and diagnostic imaging challenge due to its relatively indolent and nonspecific clinical presentation. The diagnosis of spine infection is based upon a combination of clinical suspicion, imaging evaluation and, when possible, microbiologic confirmation performed from blood cultures or image-guided percutaneous or open spine biopsy. With respect to the imaging evaluation of suspected spine infection, MRI without and with contrast of the affected spine segment is the initial diagnostic test of choice. As noncontrast MRI of the spine is often used in the evaluation of back or neck pain not responding to conservative medical management, it may show findings that are suggestive of infection, hence this procedure may also be considered in the evaluation of suspected spine infection. Nuclear medicine studies, including skeletal scintigraphy, gallium scan, and FDG-PET/CT, may be helpful in equivocal or select cases. Similarly, radiography and CT may be appropriate for assessing overall spinal stability, spine alignment, osseous integrity and, when present, the status of spine instrumentation or spine implants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Age-associated changes in microRNAs affect the differentiation potential of human mesenchymal stem cells: Novel role of miR-29b-1-5p expression.

Age-associated osteoporosis is widely accepted as involving the disruption of osteogenic stem cell populations and their functioning. Maintenance of the local bone marrow (BM) microenvironment is critical for regulating proliferation and differentiation of the multipotent BM mesenchymal stromal/stem cell (BMSC) population with age. The potential role of microRNAs (miRNAs) in modulating BMSCs and the BM microenvironment has recently gained attention. However, miRNAs expressed in rapidly isolated BMSCs that are naïve to the non-physiologic standard tissue culture conditions and reflect a more accurate in vivo profile have not yet been reported. Here we directly isolated CD271 positive (+) BMSCs within hours from human surgical BM aspirates without culturing and performed microarray analysis to identify the age-associated changes in BMSC miRNA expression. One hundred and two miRNAs showed differential expression with aging. Target prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the up-regulated miRNAs targeting genes in bone development pathways were considerably enriched. Among the differentially up-regulated miRNAs the novel passenger strand miR-29b-1-5p was abundantly expressed as a mature functional miRNA with aging. This suggests a critical arm-switching mechanism regulates the expression of the miR-29b-1-5p/3p pair shifting the normally degraded arm, miR-29b-1-5p, to be the dominantly expressed miRNA of the pair in aging. The normal guide strand miR-29b-1-3p is known to act as a pro-osteogenic miRNA. On the other hand, overexpression of the passenger strand miR-29b-1-5p in culture-expanded CD271+ BMSCs significantly down-regulated the expression of stromal cell-derived factor 1 (CXCL12)/ C-X-C chemokine receptor type 4 (SDF-1(CXCL12)/CXCR4) axis and other osteogenic genes including bone morphogenetic protein-2 (BMP-2) and runt-related transcription factor 2 (RUNX2). In contrast, blocking of miR-29b-1-5p function using an antagomir inhibitor up-regulated expression of BMP-2 and RUNX2 genes. Functional assays confirmed that miR-29b-1-5p negatively regulates BMSC osteogenesis in vitro. These novel findings provide evidence of a pathogenic anti-osteogenic role for miR-29b-1-5p and other miRNAs in age-related defects in osteogenesis and bone regeneration.

Cervical fusion for treatment of degenerative conditions: development of appropriate use criteria.

BACKGROUND CONTEXT: High quality evidence is difficult to generate, leaving substantial knowledge gaps in the treatment of spinal conditions. Appropriate use criteria (AUC) are a means of determining appropriate recommendations when high quality evidence is lacking. PURPOSE: Define appropriate use criteria (AUC) of cervical fusion for treatment of degenerative conditions of the cervical spine. STUDY DESIGN/SETTING: Appropriate use criteria for cervical fusion were developed using the RAND/UCLA appropriateness methodology. Following development of clinical guidelines and scenario writing, a one-day workshop was held with a multidisciplinary group of 14 raters, all considered thought leaders in their respective fields, to determine final ratings for cervical fusion appropriateness for various clinical situations. OUTCOME MEASURES: Final rating for cervical fusion recommendation as either "Appropriate," "Uncertain" or "Rarely Appropriate" based on the median final rating among the raters. METHODS: Inclusion criteria for scenarios included patients aged 18 to 80 with degenerative conditions of the cervical spine. Key modifiers were defined and combined to develop a matrix of clinical scenarios. The median score among the raters was used to determine the final rating for each scenario. The final rating was compared between modifier levels. Spearman's rank correlation between each modifier and the final rating was determined. A multivariable ordinal regression model was fit to determine the adjusted odds of an "Appropriate" final rating while adjusting for radiographic diagnosis, number of levels and symptom type. Three decision trees were developed using decision tree classification models and variable importance for each tree was computed. RESULTS: Of the 263 scenarios, 47 (17.9 %) were rated as rarely appropriate, 66 (25%) as uncertain and 150 (57%) were rated as appropriate. Symptom type was the modifier most strongly correlated with the final rating (adjusted ρ2 = 0.58, p<.01). A multivariable ordinal regression adjusting for symptom type, diagnosis, and number of levels and showed high discriminative ability (C statistic = 0.90) and the adjusted odds ratio (aOR) of receiving a final rating of "Appropriate" was highest for myelopathy (aOR, 7.1) and radiculopathy (aOR, 4.8). Three decision tree models showed that symptom type and radiographic diagnosis had the highest variable importance. CONCLUSIONS: Appropriate use criteria for cervical fusion in the setting of cervical degenerative disorders were developed. Symptom type was most strongly correlated with final rating. Myelopathy or radiculopathy were most strongly associated with an "Appropriate" rating, while axial pain without stenosis was most associated with "Rarely Appropriate."