Impact of the COVID-19 pandemic on the productivity and career prospects of musculoskeletal researchers.

Academic researchers faced a multitude of challenges posed by the COVID-19 pandemic, including widespread shelter-in-place orders, workplace closures, and cessation of in-person meetings and laboratory activities. The extent to which these challenges impacted musculoskeletal researchers, specifically, is unknown. We developed an anonymous web-based survey to determine the pandemic's impact on research productivity and career prospects among musculoskeletal research trainees and faculty. There were 116 musculoskeletal (MSK) researchers with varying demographic backgrounds who completed the survey. Of respondents, 48.3% (n = 56) believed that musculoskeletal funding opportunities decreased because of COVID-19, with faculty members more likely to hold this belief compared to nonfaculty researchers (p = 0.008). Amongst MSK researchers, 88.8% (n = 103) reported research activity was limited by COVID-19, and 92.2% (n = 107) of researchers reported their research was not able to be refocused on COVID-19-related topics, with basic science researchers less likely to be able to refocus their research compared to clinical researchers (p = 0.030). Additionally, 47.4% (n = 55) reported a decrease in manuscript submissions since the onset of the pandemic. Amongst 51 trainee researchers, 62.8% (n = 32) reported a decrease in job satisfaction directly attributable to the COVID-19 pandemic. In summary, study findings indicated that MSK researchers struggled to overcome challenges imposed by the pandemic, reporting declines in funding opportunities, research productivity, and manuscript submission. Trainee researchers experienced significant disruptions to critical research activities and worsening job satisfaction. Our findings motivate future efforts to support trainees in developing their careers and target the recovery of MSK research from the pandemic stall.

Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

Advancing basic and preclinical spine research: Highlights from the ORS PSRS 6th International Spine Research Symposium.

The sixth biennial ORS PSRS International Spine Research Symposium was held from November 6 to 10, 2022, at Skytop Lodge in northeastern Pennsylvania, USA. Organized jointly by the Orthopaedic Research Society and the Philadelphia Spine Research Society, the symposium attracted more than 200 participants from 15 different countries who came together to share the latest advances in basic and preclinical spine research. Following the symposium, selected participants were invited to submit full-length manuscripts to this special issue of JOR Spine.

Socioeconomic status, mental health, and nutrition are the principal traits for low back pain phenotyping: Data from the osteoarthritis initiative.

Background: Low back pain (LBP) is a heterogeneous disease with biological, physical, and psychosocial etiologies. Models for predicting LBP severity and chronicity have not made a clinical impact, perhaps due to difficulty deciphering multidimensional phenotypes. In this study, our objective was to develop a computational framework to comprehensively screen metrics related to LBP severity and chronicity and identify the most influential. Methods: We identified individuals from the observational, longitudinal Osteoarthritis Initiative cohort (N = 4796) who reported LBP at enrollment (N = 215). OAI descriptor variables (N = 1190) were used to cluster individuals via unsupervised learning and uncover latent LBP phenotypes. We also developed a dimensionality reduction algorithm to visualize clusters/phenotypes using Uniform Manifold Approximation and Projection (UMAP). Next, to predict chronicity, we identified those with acute LBP (N = 40) and persistent LBP over 8 years of follow-up (N = 66) and built logistic regression and supervised machine learning models. Results: We identified three LBP phenotypes: a "high socioeconomic status, low pain severity group", a "low socioeconomic status, high pain severity group", and an intermediate group. Mental health and nutrition were also key clustering variables, while traditional biomedical factors (e.g., age, sex, BMI) were not. Those who developed chronic LBP were differentiated by higher pain interference and lower alcohol consumption (a correlate to poor physical fitness and lower soceioeconomic status). All models for predicting chronicity had satisfactory performance (accuracy 76%-78%). Conclusions: We developed a computational pipeline capable of screening hundreds of variables and visualizing LBP cohorts. We found that socioeconomic status, mental health, nutrition, and pain interference were more influential in LBP than traditional biomedical descriptors like age, sex, and BMI.

Tumor necrosis is an underappreciated histopathologic factor in the grading of chondrosarcoma.

BACKGROUND: Cartilaginous neoplasms can be challenging to grade; there is a need to create an evidence-based rubric for grading. The goal of this study was to identify histopathologic features of chondrosarcoma that were associated with 5-year survival and to compare these to traditional patient, tumor and treatment variables. METHODS: This was a retrospective review of all patients undergoing surgical resection of a primary chondrosarcoma with at least 2 years of follow up. All specimens were independently reviewed by two pathologists and histopathologic features scored. Univariate and multivariate analyses were performed utilizing Kaplan Meier and proportional hazards methods to identify variables associated with 5-year disease specific survival (DSS) and disease free survival (DFS). RESULTS: We identified 51 patients with an average follow up of 49 months eligible for inclusion. 30% of tumors were low grade, 45% were intermediate grade, and 25% were high grade. In a univariate analysis considering histopathologic factors, higher tumor mitotic rate (HR 8.9, p < 0.001), tumor dedifferentiation (HR 7.3, p < 0.001), increased tumor cellularity (HR 5.8, p = 0.001), increased tumor atypia (HR 5.8, p = 0.001), LVI (HR 4.7, p = 0.04) and higher tumor necrosis (HR 3.7, p = 0.02) were all associated with worse 5-year DSS. In a multivariate analysis controlling for potentially confounding variables, higher tumor necrosis was significantly associated with disease specific survival survival (HR 3.58, p = 0.035); none of the factors were associated with DFS. CONCLUSIONS: This study provides an evidence-based means for considering histopathologic markers and their association with prognosis in chondrosarcoma. Our findings suggest that necrosis and LVI warrant further study.

Bullying, harassment, and discrimination of musculoskeletal researchers and the impact of the COVID-19 pandemic: an international study.

PURPOSE: Bullying, harassment, and discrimination (BHD) are prevalent in academic, scientific, and clinical departments, particularly orthopedic surgery, and can have lasting effects on victims. As it is unclear how BHD affects musculoskeletal (MSK) researchers, the following study assessed BHD in the MSK research community and whether the COVID-19 pandemic, which caused hardships in other industries, had an impact. METHODS: A web-based anonymous survey was developed in English by ORS Spine Section members to assess the impact of COVID-19 on MSK researchers in North America, Europe, and Asia, which included questions to evaluate the personal experience of researchers regarding BHD. RESULTS: 116 MSK researchers completed the survey. Of respondents, 34.5% (n = 40) focused on spine, 30.2% (n = 35) had multiple areas of interest, and 35.3% (n = 41) represented other areas of MSK research. BHD was observed by 26.7% (n = 31) of respondents and personally experienced by 11.2% (n = 13), with mid-career faculty both observing and experiencing the most BHD. Most who experienced BHD (53.8%, n = 7) experienced multiple forms. 32.8% (n = 38) of respondents were not able to speak out about BHD without fear of repercussions, with 13.8% (n = 16) being unsure about this. Of those who observed BHD, 54.8% (n = 17) noted that the COVID-19 pandemic had no impact on their observations. CONCLUSIONS: To our knowledge, this is the first study to address the prevalence and determinants of BHD among MSK researchers. MSK researchers experienced and observed BHD, while many were not comfortable reporting and discussing violations to their institution. The COVID-19 pandemic had mixed-effects on BHD. Awareness and proactive policy changes may be warranted to reduce/eliminate the occurrence of BHD in this community.

Self-paced acceptance and commitment training reduces burden transfer, stress, and burnout in veterinary healthcare teams.

OBJECTIVE: An acceptance and commitment training (ACT) educational program targeting reaction to difficult client interactions recently demonstrated efficacy in reducing burden transfer, stress, and burnout in veterinary healthcare teams. The current noninferiority trial compared effectiveness of the original program with a self-paced version. SAMPLE: Employees of 2 corporate veterinary groups were randomized to live (n = 128) or self-paced (124) conditions. The workshop and assessments were completed by 137 (55 live and 82 self-paced). PROCEDURES: Asynchronous modules containing the same content as the original program were placed on in-house veterinary clinic learning systems. Participants of this parallel arms trial completed pretest measures of burden transfer, stress, and burnout. Following assessment, the 3-week ACT program was delivered via videoconferencing (live) or asynchronous modules (self-paced). At post-test and 1-month follow-up, measures were repeated, with added assessment of knowledge, helpfulness ratings, and usage of techniques. A subset (n = 33) of participants repeated measures 9 to 12 months as an extended follow-up. RESULTS: Program helpfulness was rated more highly by live versus self-paced participants. Self-paced showed better program retention. No differences in knowledge or use of program techniques (> 5 times daily) emerged. Relative to pretest, both conditions showed reduced burden transfer, stress, and burnout at post-test and follow-up; no differences by condition emerged. Participants completing extended follow-up maintained improvement from baseline. CLINICAL RELEVANCE: Findings suggest a learning system-based version of this program can improve occupational distress in veterinary healthcare teams, with gains maintained over time. The flexibility of this format promotes program completion and allows broader dissemination.

Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

Validation of the Burden Transfer Inventory-abbreviated and examination across veterinary medicine positions and settings in the United States.

Background: Burden transfer, when veterinary client caregiver burden underlies stressful encounters with providers, elevates risk for occupational distress in veterinary medicine. To date, burden transfer has been primarily examined in veterinarians working in general practice, using methods that are time consuming. The current work validates an abbreviated Burden Transfer Inventory (BTI-A) and explores burden transfer across positions of employment and veterinary settings. Methods: Participants completed online measures of burden transfer, stress and burnout. A BTI-A with items representing each BTI domain was created with an initial validation sample (n = 1151 veterinarians). Confirmatory psychometric analyses were conducted in a cross-validation sample (n = 440 veterinarians and support staff), followed by exploration of the BTI and BTI-A across veterinary settings and position of employment. Results: The BTI-A correlated with the full-length BTI (r = 0.89-0.96) shows good internal consistency (α = 0.72-0.88) and 1-month test-retest reliability (r = 0.69-0.74). The BTI-A correlated significantly (p < 0.001) with stress and burnout. Exploratory comparisons suggested group differences including greater reactivity in general compared to specialty referral/emergency practice (p = 0.02). Conclusion: The BTI-A can be used in place of the original measure when brevity is important. Use of the BTI-A may help guide allied mental health professionals in providing support for wellbeing in veterinary healthcare team members.

An acceptance and commitment training program reduces burden transfer, stress, and burnout among veterinary healthcare teams.

OBJECTIVE: To determine whether an acceptance and commitment training (ACT) program targeting reactions to difficult client interactions would reduce burden transfer, stress, and burnout among veterinary healthcare teams. SAMPLE: Small animal veterinary hospital employees randomly assigned to participate in an ACT program (intervention group; n = 72) or to not undergo the training program (control group; 71). PROCEDURES: The study was designed as a randomized, controlled, parallel-arms trial. All participants completed prestudy assessments of burden transfer, stress, and burnout. The ACT program consisted of 3 small-group-format educational sessions tailored to reducing reactivity to difficult veterinary client interactions; sessions were delivered via video teleconference. At the end of the educational sessions (posttest) and 1 month later (1-month follow-up), assessments of burden transfer, stress, and burnout were repeated, and participants in the intervention group provided ratings of program helpfulness and frequency of use for techniques taught in the program. RESULTS: Participants receiving the program rated it as helpful and reported frequent use of program techniques. Relative to the control group, the intervention group showed significantly reduced burden transfer, stress, work-related burnout, and client-related burnout after completing the educational sessions. These improvements were maintained at the 1-month follow-up. CLINICAL RELEVANCE: Findings support the usefulness of this program in reducing occupational distress in veterinary medicine. Future work is needed to examine whether it is similarly effective in formats that could be more broadly disseminated (eg, asynchronous, self-paced, independent learning).

Specific agitation behaviours in dementia differentially contribute to aspects of caregiver burden.

BACKGROUND: Agitation is a common symptom in dementia and linked to caregiver burden, but both agitation and burden are multidimensional constructs. The current study sought to determine whether specific presentations of agitation differentially relate to aspects of caregiver burden. METHODS: Medical record data from an outpatient memory clinic were extracted for 609 persons with dementia, including caregiver-reported burden and care recipient agitation. RESULTS: Exploratory factor analysis yielded three domains of agitation on the Cohen Mansfield Agitation Inventory ('Physically Aggressive', 'Physically Non-Aggressive', 'Verbally Agitated') and four domains of burden on the Zarit Burden Interview ('Impact on Life', 'Guilt/Uncertainty', 'Embarrassment/Frustration', 'Overwhelm'). Regression analyses demonstrated all domains of agitation positively predicted overall burden. Regarding specific aspects of burden, Physically Aggressive behaviours predicted Embarrassment/Frustration. Physically Non-Aggressive behaviours predicted Impact on Life and Guilt/Uncertainty. Verbally Agitated behaviours predicted all burden dimensions. CONCLUSIONS: Results suggest specific aspects of agitation may differentially contribute to facets of caregiver burden.

In vivo fluid transport in human intervertebral discs varies by spinal level and disc region.

Background: The lumbar discs are large, dense tissues that are primarily avascular, and cells residing in the central region of the disc are up to 6-8 mm from the nearest blood vessel in adults. To maintain homeostasis, disc cells rely on nutrient transport between the discs and adjacent vertebrae. Thus, diminished transport has been proposed as a factor in age-related disc degeneration. Methods: In this study, we used magnetic resonance imaging (MRI) to quantify diurnal changes in T2 relaxation time, an MRI biomarker related to disc hydration, to generate 3D models of disc fluid distribution and determine how diurnal changes in fluid varied by spinal level. We recruited 10 participants (five males/five females; age: 21-30 years; BMI: 19.1-29.0 kg/m2) and evaluated the T2 relaxation time of each disc at 8:00 AM and 7:00 PM, as well as degeneration grade (Pfirrmann). We also measured disc height, volume, and perimeter in a subset of individuals as a preliminary comparison of geometry and transport properties. Results: We found that the baseline (AM) T2 relaxation time and the diurnal change in T2 relaxation time were greatest in the cranial lumbar discs, decreasing along the lumbar spine from cranial to caudal. In cranial discs, T2 relaxation times decreased in each disc region (nucleus pulposus [NP], inner annulus fibrosus [IAF], and outer annulus fibrosus [OAF]), whereas in caudal discs, T2 relaxation times decreased in the NP but increased in the AF. Conclusions: Fluid transport varied by spinal level, where transport was greatest in the most cranial lumbar discs and decreased from cranial to caudal along the lumbar spine. Future work should evaluate what level-dependent factors affect transport.

Lumbar intervertebral disc diurnal deformations and T2 and T1rho relaxation times vary by spinal level and disc region.

PURPOSE: Magnetic resonance imaging (MRI) is routinely used to evaluate spine pathology; however, standard imaging findings weakly correlate to low back pain. Abnormal disc mechanical function is implicated as a cause of back pain but is not assessed using standard clinical MRI. Our objective was to utilize our established MRI protocol for measuring disc function to quantify disc mechanical function in a healthy cohort. METHODS: We recruited young, asymptomatic volunteers (6 male/6 female; age 18-30 years; BMI < 30) and used MRI to determine how diurnal deformations in disc height, volume, and perimeter were affected by spinal level, disc region, MRI biomarkers of disc health (T2, T1rho), and Pfirrmann grade. RESULTS: Lumbar discs deformed by a mean of -6.1% (95% CI: -7.6%, -4.7%) to -8.0% (CI: -10.6%, -5.4%) in height and -5.4% (CI: -7.6%, -3.3%) to -8.5% (CI: -11.0%, -6.0%) in volume from AM to PM across spinal levels. Regional deformations were more uniform in cranial lumbar levels and concentrated posteriorly in the caudal levels, reaching a maximum of 13.1% at L5-S1 (CI:-16.1%, -10.2%). T2 and T1rho relaxation times were greatest in the nucleus and varied circumferentially within the annulus. T2 relaxation times were greatest at the most cranial spinal levels and decreased caudally. In this young healthy cohort, we identified a weak association between nucleus T2 and the diurnal change in the perimeter. CONCLUSIONS: Spinal level is a key factor in determining regional disc deformations. Interestingly, deformations were concentrated in the posterior regions of caudal discs where disc herniation is most prevalent.

Factors of Dementia Caregiver Burden Differentially Contribute to Desire to Institutionalize.

The experience of dementia caregiver burden is multidimensional. Little is known about how different aspects of burden contribute to the consideration of moving a loved one to a structured living facility. In the present study, caregiver burden (Zarit Burden Interview; ZBI) and consideration of structured living arrangements (Desire to Institutionalize Scale; DIS) were self-reported by 339 caregivers. Exploratory factor analysis was used to determine the ZBI factor structure; these factors were then examined via hierarchical linear regression for prediction of DIS. Factor analysis indicated a 4-factor ZBI solution: Impact on Life, Guilt, Embarrassment/Frustration, and Escape/Uncertainty. Regression analyses indicated that only Escape/Uncertainty (p < .001) was associated with DIS. Of the 4 identified factors of caregiver burden, desire to escape the caregiving role was most related to consideration of structured living arrangements. Future work should explore longitudinal contribution of this factor to determine its role in actual changes made in living arrangements.

The Moderating Role of Pain Self-efficacy in the Relationships Among Caregiver Burden and Care Recipient Pain and Neuropsychiatric Symptoms in a Sample of Persons With Dementia.

Past research suggests relationships among dementia caregiver burden and care recipient pain and neuropsychiatric symptoms, but no prior work has examined the influence of pain self-efficacy on these associations. A sample of 502 dementia caregivers completed an online protocol assessing caregiver burden and care recipient neuropsychiatric symptoms, presence of pain, and pain self-efficacy in this cross-sectional, observational study. The indirect effect of neuropsychiatric symptoms on the relationship between pain and caregiver burden was significant. Pain self-efficacy significantly moderated the effect of pain on neuropsychiatric symptoms (P=0.04) and the direct association between pain and caregiver burden (P=0.004), but did not moderate the indirect effect. Future research should explore how pain influences neuropsychiatric symptoms, and whether improvement in pain self-efficacy in dementia care recipients attenuates the influence of pain on neuropsychiatric symptoms and caregiver burden in other samples.

In vivo relationships between lumbar facet joint and intervertebral disc composition and diurnal deformation.

BACKGROUND: Spinal motion is facilitated by a "three joint complex", two facet joints and one intervertebral disc at each spinal level. Both the intervertebral discs and facet joints are subject to natural age-related degeneration, and while these processes may be linked it is not clear how. As instability in the disc could underlie facet arthritis, we evaluated the hypothesis that the discs and facet joints are mechanically coupled. METHODS: We recruited young, asymptomatic volunteers (n = 10; age: mean 25, range 21-30 years; BMI: mean 23.1, range 19.1-29.0 kg/m2) and applied magnetic resonance imaging (MRI) and three-dimensional (3D) modeling to measure facet and disc composition (MRI T1rho relaxation time) and facet and disc function (diurnal changes in facet space width, disc height) in the lumbar spine. FINDINGS: We found that facet space width was positively associated with facet T1rho relaxation time (fluid content) and negatively associated with disc T1rho, and that facets adjacent to degenerated discs were significantly thicker and had significantly higher T1rho. Furthermore, the diurnal change in wedge angle was positively associated the diurnal change in facet space width, while disc degeneration, the diurnal change in disc height, and facet T1rho were not. INTERPRETATION: These data demonstrate an interdependence between disc and facet health, but not between disc and facet mechanical function. Furthermore, the weak relationship between facet cartilage composition and in vivo function suggests that other factors, like spinal curvature, determine in vivo spine mechanics. Future work in symptomatic or aged populations are warranted to confirm these findings.

Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes.

BACKGROUND: Majority of chondrosarcomas are associated with a number of genetic alterations, including somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, but the downstream effects of these mutated enzymes on cellular metabolism and tumor energetics are unknown. As IDH mutations are likely to be involved in malignant transformation of chondrosarcomas, we aimed to exploit metabolomic changes in IDH mutant and non-mutant chondrosarcomas. METHODS: Here, we profiled over 69 metabolites in 17 patient-derived xenografts by targeted mass spectrometry to determine if metabolomic differences exist in mutant IDH1, mutant IDH2, and non-mutant chondrosarcomas. UMAP (Uniform Manifold Approximation and Projection) analysis was performed on our dataset to examine potential similarities that may exist between each chondrosarcoma based on genotype. RESULTS: UMAP revealed that mutant IDH chondrosarcomas possess a distinct metabolic profile compared with non-mutant chondrosarcomas. More specifically, our targeted metabolomics study revealed large-scale differences in organic acid intermediates of the tricarboxylic acid (TCA) cycle, amino acids, and specific acylcarnitines in chondrosarcomas. Lactate and late TCA cycle intermediates were elevated in mutant IDH chondrosarcomas, suggestive of increased glycolytic metabolism and possible anaplerotic influx to the TCA cycle. A broad elevation of amino acids was found in mutant IDH chondrosarcomas. A few acylcarnitines of varying carbon chain lengths were also elevated in mutant IDH chondrosarcomas, but with minimal clustering in accordance with tumor genotype. Analysis of previously published gene expression profiling revealed increased expression of several metabolism genes in mutant IDH chondrosarcomas, which also correlated to patient survival. CONCLUSIONS: Overall, our findings suggest that IDH mutations induce global metabolic changes in chondrosarcomas and shed light on deranged metabolic pathways.

In Vivo Mechanical Function of the Distal Radial Ulnar Ligaments During Rotation of the Wrist.

PURPOSE: The purpose of this study was to investigate changes in length of the volar and dorsal radioulnar ligaments (VRULs and DRULs), and the distal radioulnar joint (DRUJ) space during unweighted and weighted rotation of the wrist using magnetic resonance imaging and biplanar fluoroscopy. METHODS: Fourteen wrists in 7 normal adult volunteers were imaged to define the 3-dimensional geometry of the DRUJ and the insertion sites of the superficial and deep bundles of the VRULs and DRULs. Subjects were imaged at 10 positions of forearm rotation ranging from full pronation to full supination, with or without a 5-pound weight. Lengths of the superficial and deep VRUL and DRUL bundles and DRUJ space were measured (in millimeters) at each position to evaluate ligament function and DRUJ stability. RESULTS: In the unweighted and weighted trials, maximal elongation of both deep and superficial VRUL bundles occurred in supination and maximal lengths of the deep and superficial DRUL bundles occurred in pronation. Maximum DRUJ space occurred during pronation and a minimum occurred in 30° of supination. In weighted trials, there was a significant increase in deep and superficial VRUL bundle length at positions between 30° of pronation and 30° of supination; however, there was no effect of weight on DRULs length. In weighted trials, there was a significant increase in DRUJ space at positions between full pronation and 15° of supination. CONCLUSIONS: This study demonstrates elongation of the VRULs in supination and the DRULs in pronation. There was no evidence of reciprocal loading of superficial/deep ligament bundles on either the dorsal or the volar aspects of the DRUJ. The effect of loading the wrist during rotation was apparent primarily in the VRULs, but not the DRULs. The DRUJ space was lowest at approximately 30° of supination. CLINICAL RELEVANCE: These results add information to the literature regarding the complicated biomechanics of the triangular fibrocartilage complex and DRUJ. Future work should evaluate changes in biomechanics caused by triangular fibrocartilage complex tears to determine how tear severity and location relate to clinical symptoms.

Fabrication, maturation, and implantation of composite tissue-engineered total discs formed from native and mesenchymal stem cell combinations.

Low back pain arising from disc degeneration is one of the most common causes of limited function in adults. A number of tissue engineering strategies have been used to develop composite tissue engineered total disc replacements to restore native tissue structure and function. In this study we fabricated a composite engineered disc based on the combination of a porous polycaprolactone (PCL) foam annulus fibrosus (AF) and a hyaluronic acid (HA) hydrogel nucleus pulposus (NP). To evaluate whether native tissue cells or mesenchymal stem cells (MSCs) would perform better, constructs were seeded with native AF/NP cells or with MSCs in the foam and/or gel region. Maturation of these composite engineered discs was evaluated for 9 weeks in vitro culture by biochemical content, histological analysis and mechanical properties. To evaluate the performance of these constructs in the in vivo space, engineered discs were implanted into the caudal spines of athymic rats for 5 weeks. Our findings show that engineered discs comprised of AF/NP cells and MSCs performed similarly and maintained their structure after 5 weeks in vivo. However, for both cell types, loss of proteoglycan was evident in the NP region. These data support the continued development of the more clinically relevant MSCs population for disc replacement applications. STATEMENT OF SIGNIFICANCE: A number of tissue engineering strategies have emerged that are focused on the creation of a composite disc replacement. We fabricated a composite engineered disc based on the combination of a porous foam AF and a HA gel NP. We used these constructs to determine whether the combination of AF/NP cells or MSCs would mature to a greater extent in vitro and which cell type would best retain their phenotype after implantation. Engineered discs comprised of AF/NP cells and MSCs performed similarly, maintaining their structure after 5 weeks in vivo. These data support the successful fabrication and in vivo function of an engineered disc composed of a PCL foam AF and a hydrogel NP using either disc cells or MSCs.

Influence of Genetic Background and Sex on Gene Expression in the Mouse (Mus musculus) Tail in a Model of Intervertebral Disc Injury.

To facilitate rational experimental design and fulfill the NIH requirement of including sex as a biologic variable, we examined the influences of genetic background and sex on responses to intervertebral disc (IVD) injury in the mouse tail. The goal of this study was to compare gene expression and histologic changes in response to a tail IVD injury (needle puncture) in male and female mice on the DBA and C57BL/6 (B6) backgrounds. We hypothesized that extracellular matrix gene expression in response to IVD injury differs between mice of different genetic backgrounds and sex. Consistent changes were detected in gene expression and histologic features after IVD injury in mice on both genetic backgrounds and sexes. In particular, expression of col1a1 and adam8 was higher in the injured IVD of DBA mice than B6 mice. Conversely, col2a1 expression was higher in B6 mice than DBA mice. Sex-associated differences were significant only in B6 mice, in which col2a1 expression was greater in male mice than in female. Histologic differences in response to injury were not apparent between DBA and B6 mice or between males and females. In conclusion, mouse tail IVD showed sex- and strain-related changes in gene expression and histology after needle puncture. The magnitude of change in gene expression differed with regard to genetic background and, to a lesser degree, sex.