Intervertebral disc degeneration (IVDD) is a major cause of global disability that increases with age. IVD age may affect its injury susceptibility, yet few studies examine spine biomechanical changes with age, fewer address multiple injury types, and none investigate the interplay between age and injury. An ex vivo mouse lumbar spine biomechanical study to determine the effects of age, injury, and their interaction. IVDs of 4, 12, and 24 months' mice were subjected to two injury types: Full disc puncture (DP) mimicking advanced IVDD and annulus fibrosus and endplate (AF + EP) injury simulating herniation with endplate junction failure. Spines were tested biomechanically, analyzed radiologically for IVD dimensions, and with FTIR and histology for biochemical content. Both age and injury significantly altered biomechanical properties of IVDs. Injury had a greater effect than age, and DP caused larger changes than AF + EP injury. Injury and age exhibited an interactive effect, resulting in more pronounced biomechanical dysfunction in middle-aged (12 months) and geriatric IVDs (24 months), likely due to age-related loss of proteoglycans and collagen denaturation shown with FTIR and histology. We conclude that both age and injury independently and synergistically affect ex vivo biomechanical properties of mouse lumbar spine. The more severe biomechanical change in middle-aged and geriatric mouse lumbar spines suggests similar injuries may cause greater spinal dysfunction in individuals of comparable ages. These findings provide context for future in vivo studies investigating long-term effects of acute spine injuries.
Traditional assessments of functional recovery after spine surgery rely on patient-reported outcomes, which are prone to bias. Wearables and smartphone activity tracking offer objective monitoring but may be unreliable if devices are not carried continuously. Capacity-oriented measures, such as the 1-min walk test (1MWT) and 6-min walk test (6MWT), may be more reliable. This study evaluated smartphone-derived interval metrics after lumbar spine surgery retrospectively. iPhone Health exports from 41 patients were analyzed. A sliding-window algorithm parsed daily distances to simulate 1MWT and 6MWT. Step counts and active time were extracted. Activity was compared across four intervals: 6-month baseline, final 2 weeks preoperatively, early postoperative (0-2 weeks), and late postoperative (2-6 weeks). Paired t-tests or Wilcoxon signed-rank tests were used, with Simes-Hochberg adjustment for multiple comparisons. Day-to-day stability was summarized by the coefficient of variation (CV). Pearson correlations were calculated. Median 1MWT fell from 98 m at baseline to 82 m in the final two preoperative weeks (p < 0.05) and increased to 105 m by late recovery (p < 0.05 vs. preoperative). Median 6MWT declined from 403 to 345 m preoperatively, with this decline not reaching significance (p = 0.07), and increased to 407 m by late recovery (p < 0.05 vs. preoperative). Steps declined from 5030 to 3825 preoperatively (p < 0.05) and rose to 5538 at 2-6 weeks (p < 0.05 vs. preoperative). The 1MWT and 6MWT were strongly correlated. CV was lower for 1MWT and 6MWT than for steps. Smartphone-derived 1MWT and 6MWT improved significantly from the immediate preoperative period to late postoperative recovery, showed lower day-to-day variability than longitudinal activity metrics, and were strongly correlated with each other. These findings support smartphone-derived interval metrics as a feasible method to monitor recovery following lumbar spine surgery.
The seventh biennial ORS-PSRS International Spine Research Symposium was held from November 10-14, 2024, at Skytop Lodge in Pennsylvania, USA. Jointly organized by the PSRS and ORS, the meeting brought together over 195 participants from 13 countries. Selected contributors were invited to submit full-length manuscripts for this JOR Spine Special Issue.
Spinal implant development demands integration of biomechanical rigor with regulatory compliance. For surgeons, researchers, and biomedical engineers engaged in translational research, understanding the regulatory pathway, from the Design History File (DHF) through post-market surveillance, is essential to smoothly transform an innovative idea into a safe and effective clinical product. This paper reviews the major regulatory frameworks governing spinal implants, including the United States Food and Drug Administration (FDA) pathways such as Premarket Notification [510(k)] and Premarket Approval (PMA), as well as the European Union Medical Device Regulation (EU MDR) leading to Conformité Européenne (CE) marking. International standards such as ISO 13485 for quality systems, ISO 14971 for risk management, ISO 10993 for biocompatibility, and ASTM mechanical testing standards are discussed. Particular attention is given to how biomechanics, including Finite Element Analysis (FEA), bench testing, and fatigue studies, are integrated into the pre-market submission dossier. Key elements of the regulatory process include design controls and documentation (DHF/technical file), Chemistry, Manufacturing, and Controls (CMC), preclinical validation through simulation, bench, cadaver, and animal testing, regulatory submissions across FDA and EU systems, and post-market surveillance and lifecycle management. Common pitfalls involve overreliance on simulations without validation, inadequate risk management, and insufficient traceability. Emerging trends such as in silico trials, digital twins, and smart implants show promise, while global differences in classification, clinical requirements, and post-market expectations highlight the ongoing challenge of regulatory divergence. Understanding the biomechanical foundations of the development process is crucial for the safe and successful translation of spine implants into clinical use. Surgeons and implant designers should engage early, understand the critical steps, and advocate for rigorous validation aligned with regulatory expectations to deliver safer and more effective implants to clinical practice.
This study investigated the effect of bone metastasis on the biomechanical environment of human vertebrae in patients with metastatic spine disease through the metric of load-to-strength ratio (LSR). Specifically, we compared the patients' LSRs to age and sex-similar noncancer controls from the Framingham Heart Study. Derived from clinical CT data of 135 metastatic spine disease patients planned for radiotherapy and 246 normative controls from the Framingham Heart Study, individualized spinal musculoskeletal models and vertebral strength estimates were used to compute level-specific LSR under natural standing and three weight-holding conditions (standing + weight, flexion + weight, and lateral bending + weight). Adjusted for age, BMI, and spinal region, osteosclerotic and mixed lesion vertebrae had higher strength than osteolytic and control vertebrae. The musculoskeletal models suggested breast, prostate, and male lung cancer patients had higher compressive vertebral loading, and female lung cancer patients had lower compressive vertebral loading than controls. Male patients had higher standardized LSRs in natural standing, while female patients had lower LSRs for all activities than controls. Independent of sex, vertebrae with osteosclerotic and mixed bone metastasis had lower LSRs than controls, while, for osteolytic bone lesions, males had higher and females lower LSRs than controls. Vertebrae with no observed lesion on CT had higher LSRs than controls in males and lower LSRs in females. Our findings highlighted that primary cancer and lesion type differentially affected task-specific vertebral loading and strength, thus modifying the vertebral LSRs. Sex-mediated differences in LSRs between FHS controls and vertebrae with no observed metastatic lesions suggest that considering the latter as "normal" should be taken with care. Our initial assessment supports further examination of whether vertebral LSR measurements are associated with vertebral risk and, if so, what threshold values indicate risk. 3.
Achieving rapid bone fusion is critical for preventing complications in Extreme Lateral Interbody Fusion (XLIF), yet harvesting sufficient autologous bone presents surgical limitations. Platelet-rich fibrin (PRF), an autologous biomaterial rich in osteogenic growth factors, offers potential as a bone graft enhancer. This study evaluated the efficacy of PRF combined with allogeneic bone in promoting interbody fusion using an XLIF-simulated rabbit model. In vitro, bone marrow mesenchymal stem cells were cultured with PRF, allogeneic bone, or PRF/allogeneic bone composites. Assessments included biocompatibility (CCK-8, Calcein-AM/PI), cell adhesion (phalloidin/DAPI), and osteogenic differentiation (alkaline phosphatase activity/staining, Alizarin Red S). PRF, allogeneic bone, and their composite (PRF/allogeneic bone) were evaluated in a rabbit XLIF model. Autologous iliac crest bone served as a positive control, while empty cages provided negative controls. Endpoints included radiographic (micro-CT), mechanical (biomechanical testing), histological (H&E, methylene blue-acid fuchsin, TRAP), and biochemical (ELISA) evaluation at postoperative 2, 4, 8, and 12 weeks. In vitro experiments demonstrated that PRF/allogeneic bone composites exhibited noncytotoxic properties and osteogenic-promoting effects when combined with titanium alloy cages. In vivo, fusion progressed temporally across all groups, with the PRF/allogeneic bone composite yielding 12-week fusion rates by manual palpation and micro-CT equivalent to autograft. Biomechanical strength and bone mineral density of PRF/allogeneic bone matched autograft, exceeding allogeneic bone. Histology demonstrated accelerated fusion kinetics: early angiogenesis (2 weeks), fibrocartilage formation (4 weeks), and complete trabecular bridging by 12 weeks. ELISA confirmed earlier BMP-2/VEGF peaks (2-4 weeks) versus allogeneic bone. These results indicated that the combination of PRF and allogeneic bone successfully induced intervertebral bone formation in the rabbit XLIF model. PRF can serve as a physiological natural fusion material, inducing osteogenesis and achieving spinal fusion. Its osteopromotive effects, cost-effectiveness, and autologous origin support its potential as a superior graft alternative for XLIF procedures.
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To evaluate the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) in infectious diseases of the spine (IDS). Systematic literature on the application of mNGS in the diagnosis of IDS was retrieved by two independent researchers from databases including Pubmed, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP from the inception to 30 November 2024. Meta-analysis was conducted using Meta-Disc 1.4 and Stata 18.0 software. The initial search identified 314 articles. After applying predefined inclusion and exclusion criteria, 15 studies were included, encompassing 1236 patients, of which 835 had confirmed IDS. Meta-analysis revealed that the pooled sensitivity and specificity of mNGS for IDS diagnosis were 0.95 (95% CI: 0.88-0.98) and 0.60 (95% CI: 0.48-0.71), respectively. The positive likelihood ratio was 2.3 (95% CI: 1.7-3.2), and the negative likelihood ratio was 0.09 (95% CI: 0.04-0.22). The pooled diagnostic odds ratio was 26 (95% CI: 9-75), with an area under the summary receiver operating characteristic curve of 0.85 (95% CI: 0.82-0.88). The primary diagnostic value of mNGS lies in its ability to serve as a rapid screening tool for disease exclusion. However, for diagnosing IDS, it is essential to integrate other clinical indicators for a comprehensive assessment to confirm the diagnosis.
Pedicle screw fixation in osteoporotic spines remains challenging. Bazedoxifene (BZA) and denosumab (Dmab) are widely used agents for osteoporosis, but their comparative effects on spinal instrumentation are not well understood. This study aimed to evaluate the effects of BZA and Dmab on biomechanical parameters of spinal instrumentation using finite element analysis (FEA). In this prospective, open-label study, postmenopausal women with primary osteoporosis were assigned to receive either BZA (daily oral, 20 mg) or Dmab (subcutaneous, 60 mg every 6 months) for 12 months. FEA models of the L4 vertebra were generated from CT scans using a calibration phantom (Mindways, Austin, TX, USA). Vertebral compression force was evaluated to represent overall vertebral strength. Pedicle screw fixation strength was assessed under axial (pullout strength) and non-axial directional forces (cranial, caudal, lateral, medial). Inverse probability of treatment weighting (IPTW) and multivariable regression were used to balance baseline differences and compare biomechanical outcomes between groups. Thirty patients were enrolled (15 per group); the final analysis included 12 in the BZA group and 13 in the Dmab group. Compared to BZA, Dmab significantly improved compression strength (adjusted mean difference: 8.1% [95% CI, 0.9-15.3], p = 0.030) and pullout strength (15.8% [95% CI, 6.2-25.4], p = 0.003). Directional FEA revealed greater resistance to cranial (17.4% [95% CI, 4.9-30.0], p = 0.009) and lateral (10.8% [95% CI, 0.9-20.8], p = 0.035) loading with Dmab, while no significant difference was observed in caudal- and medial-directed force. Finite element modeling suggested that Dmab enhanced pedicle screw fixation more effectively than BZA, particularly against axial and cranial/lateral-directed forces. These biomechanical differences underscore the potential advantage of Dmab in preoperative osteoporosis management to improve pedicle screw stability.
Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity characterized by three-dimensional curvature of the spine with an unknown etiology. Previous genome-wide association studies have identified a single-nucleotide polymorphism (rs6137473) located downstream of PAX1, which is significantly associated with female AIS risk. To investigate the role of this region in spinal development and AIS pathogenesis, we generated a mouse model with deletion of a nearby conserved sex-associated region (Pax1-SARΔ). Spines were examined by both micro-CT and histology. Gene expression analysis (by RNA-sequencing and quantitative PCR) was carried out on E12.5 and E18.5 developing spines. Glycosaminoglycan (GAG) content was also measured by high-performance liquid chromatography. Micro-CT analysis revealed increased vertebral rotation at T4 in female Pax1-SARΔ mice at 4 months and at T9 in male Pax1-SARΔ mice at 6 months, along with kyphotic and lordotic sagittal curvatures. Histological examination revealed significant intervertebral disc degeneration, with the most severe changes observed in the female Pax1-SARΔ mice. GAG analysis found decreased chondroitin sulfate and dermatan sulfate content in male and female Pax1-SARΔ mice. Gene expression analysis at E12.5 showed upregulation of Pax1, Stat3, Ar, Foxa2, and Nkx2.2, while RNA-sequencing at E18.5 revealed sex-dependent changes in gene expression related to extracellular matrix components, immune and inflammatory responses, and scoliosis. These findings highlight the pivotal role of the Pax1 sex-associated genomic region in the development and maintenance of functional cartilage, extracellular matrix integrity, and intervertebral disc health, offering insights into the mechanisms underlying spinal degeneration and instability in AIS.
Adolescent idiopathic scoliosis (AIS) describes an asymmetrical formation of the spine that develops rapidly during adolescence. It is well known that the forces applied to bones, such as from paraspinal muscles, are substantial moderators of growth and adaptation. Despite the intimate relationship between the paraspinal muscles and the spine, very little is known about these muscles, particularly during adolescence when there is the greatest risk of the development and progression of AIS. Here, we aimed to quantify paraspinal muscle volume, intramuscular fat, and fat-free muscle asymmetry in female adolescents with AIS and a healthy adolescent control cohort. Twenty-nine female adolescents with primary-right-thoracic scoliosis (range: Cobb angle mean [SD]: 39 [15]°; age mean [SD]: 13.8 [1.5] years) and 19 age-matched female control participants without scoliosis (age mean [SD]: 13.1 [1.8] years). Participants underwent T1-weighted and coronal mDixon magnetic resonance image scans. An Asymmetry index of muscle volume, intramuscular-fat, and fat-free muscle were determined for five paraspinal muscles across 11 vertebral levels (T4-L4/5) (Asymmetry index  = Ln [right-side/left-side]). AIS participants have greater asymmetry in paraspinal muscle volume, intramuscular fat, and fat-free muscle compared to controls (p < 0.05, linear mixed effects analysis). Across numerous vertebral levels adjacent to the primary thoracic curve apex in AIS, multifidus volume and multifidus, longissimus, and spinalis intramuscular fat asymmetries were greater in AIS (13%-57% larger on the left side) than in the control group (1%-20%), p < 0.05. In the lumbar spine, multifidus volume and multifidus, longissimus, and psoas intramuscular fat were greater on the right side of the lumbar curve in AIS (18%-54%) than in controls (1%-14%), p < 0.05. Scoliosis curve severity was moderately correlated with asymmetries in muscle volume, intramuscular fat, and fat-free muscle (range: R = 0.40-0.64, p < 0.05). These findings provide evidence that asymmetries in paraspinal muscle size and composition exist along the length of the scoliotic spine. The asymmetries are associated with curve severity; therefore, supporting the need to further consider muscle in the pathogenesis of AIS.
Chronic low back pain (cLBP) is often accompanied by changes in lumbar spine bony morphology, including osteophyte growth. Knowledge of the volume and location of osteophytes could provide insight into habitual loading that may induce symptomatic disc degeneration and serve to guide treatment. The aim of this study was to develop an automated method to calculate osteophyte volume in lumbar vertebral bodies and to evaluate the relationships between osteophyte volume and vertebral level, age, and sex. Patients with cLBP received computed tomography (CT) scans of their entire lumbar spine. Lumbar bone models were created from the segmented CT scans. A Procrustes-based registration algorithm transformed vertebral bodies from a reference library of bones with no osteophytes to match the patient's vertebral bodies. The best-matched reference bone was then subtracted from the original bone to create a model of the osteophytes. Osteophyte volume and location were calculated from the model, and associations were explored between osteophyte volume, vertebral level, sex, and age. Regional differences in osteophyte volume were also evaluated. The osteophyte identification algorithm was validated to have a bias of -4.7 mm3 and accuracy of 109.7 mm3. Osteophyte volume increased an average of 147.8 mm3 with each caudal vertebral level. Osteophyte volume was greater in men than in women and increased between 34.3 and 47.7 mm3 with each year of age. The superior half of L1 and L2 had 20%-35% greater osteophyte volume than the inferior half. Osteophyte volume increased with more caudal vertebrae, was greater in men than in women, and increased by approximately 40 mm3 with each year of age in 264 individuals with cLBP.
Intervertebral disc (IVD) degeneration contributes significantly to chronic low back pain and represents a major clinical challenge. Quantitative MRI (qMRI) techniques offer the potential to assess biochemical and structural disc changes noninvasively, but its use has been slow to be incorporated into studies utilizing spontaneous large animal models. This study characterizes qMRI-derived biomarkers of IVD degeneration across the lifespan in a clinically relevant ovine model. Ex vivo thoracolumbar spine segments from 10 sheep (13-130 months old) were assessed using 3T MRI, including T2, T2*, T1ρ, adiabatic T1ρ, adiabatic T2ρ, and ADC mapping. Relaxation times were compared with Pfirrmann grade, disc height index, biomechanical testing, GAG/water content, and histological scores. T2 and T2* values in the nucleus pulposus (NP) were negatively correlated with age, Pfirrmann grade, and histological degeneration, and positively correlated with GAG and water content. T2 relaxation times in the annulus fibrosus (AF) were inversely related to biomechanical stiffness, whereas T2* relaxation times in the NP were positively associated. Strong inter-metric correlations were observed between most qMRI measures, but aT1ρ and ADC showed more distinct profiles. These findings support the sensitivity of qMRI in detecting regional and age-related IVD changes and reinforce its utility for noninvasive disc assessment in translational models of degeneration.
Major cause of low-back pain is intervertebral disc degeneration (IVDD), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1, is involved in various musculoskeletal tissues, but its role in the annulus fibrosus (AF) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation. Primary rat AF cells were subjected to cyclic tensile strain (CTS) at low (2%) and high (12%) strain levels to investigate strain-dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1, Piezo2, and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA-sequencing analysis and evaluation of its effects on BMP2-induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells. Low-strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti-osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2-induced osteogenesis and nuclear translocation of p-Smad1/5/9. Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin-mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD.
Intervertebral disc (IVD) degeneration is a major contributor to low back pain, yet its initiating factors remain unclear. While the individual effects of pro-inflammatory cytokines and mechanical loading on IVDs have been studied, their combined impact is poorly understood. This study investigated how dynamic compression and torsion interact with interleukin-1 beta (IL-1β) and its inhibitor, interleukin-1 receptor antagonist (IL-1Ra), using bovine IVDs in an ex vivo organ culture system. Whole bovine caudal IVDs were cultured for one week in a custom bioreactor applying diurnal dynamic compression (0.1-0.5 MPa) and torsion (±6°) under three media conditions: physiological, catabolic (10 ng/mL IL-1β), and inhibitory (10 ng/mL IL-1Ra). Static compression (0.1 MPa) served as control. 3 T magnetic resonance imaging (MRI) was used pre- and post-culture for imaging and segmentation using 3DSlicer. Subject-personalized finite element (FE) models were generated via morphing algorithms and coupled with a parallel network (PN) model to analyze metabolite transport and its impact on gene expression. Outcomes included disc height, glycosaminoglycan (GAG) content, qPCR, and cell metabolic activity. Degenerative changes were detected in all treatment groups. Results of decreased disc height, hydration, and ACAN expression, alongside increased MMP-13, indicated that the applied loading was supraphysiological and induced catabolic responses. IL-1Ra, at the given dose, did not counteract degeneration. MRI-based FE modeling effectively captured patterns of tissue consolidation and degeneration, providing valuable insights into IVD responses under combined mechanical and inflammatory stress. This integrative platform highlights the importance of modeling complex IVD environments and may inform the design of improved anti-catabolic therapies.
Aging is a major risk factor for IVD degeneration and chronic lower back pain. Comparing degenerative patterns in human and mice, a commonly used pre-clinical model, is crucial for validating it in preclinical mechanistic research. The goal of the study was to compare the effect of age and spine level on degeneration in human and mouse lumbar IVDs. T2-weighted MRI images of human lumbar spine were graded using the Pfirrmann system. H&E-stained mid-coronal sections of mouse lumbar IVDs were scored using the Melgoza and Chenna system. Age, gender, IVD level, and lumbar IVD degeneration scores, respectively, were used for statistical analysis in each species. Linear regression and one-way ANOVA with post hoc Tukey analysis were used to compare regression slopes and intercepts. Age conversion from mouse to human was performed according to the Jackson Laboratory's outline of mouse age and its human equivalents. Generalized estimating equations (GEE) were used to model continuous degeneration scores, accounting for intra-subject correlation due to multiple IVD levels per subject. Main effects included sex, IVD level (L1-S1), and age, with an interaction term assessing the impact of age across levels. An autoregressive correlation structure was specified. Age significantly correlated with IVD degeneration in humans (p < 0.0001) and mice (p < 0.0002). And the IVD level predicted degeneration in both species (L5-S1 in human, and L6-S1 in mice). Normalizing age and pathology revealed an earlier onset of degeneration in humans than in mice. Age and spinal IVD level influence lumbar IVD degeneration in both human and mice with a higher rate of degeneration at the lumbosacral junction in both species. These findings suggest that mice are a suitable model for studying the cellular and molecular basis of IVD degeneration and associated neurological symptoms, with the L6-S1 level being the most relevant.
Back pain and spinal injury are leading contributors to premature retirement, particularly in physically demanding occupations. Direct and practical methods of spinal assessment are needed to evaluate interventions aimed at reducing spinal loading and injury risk. Ultrasonography has been reliably used to estimate spinal compression via intervertebral disc height, but its reliability for measuring inter-transverse process distances under load has not been established. Eleven healthy adults underwent ultrasonographic measurement of inter-transverse process distances at each lumbar level (L1-L5), and the total lumbar distance under four loading conditions: (1) immediately on standing while unloaded, (2) after 15 min of unloaded standing, (3) after 15 min of standing loaded with a 25 kg weighted vest, and (4) after 30 min of loaded standing. These procedures were repeated after 1-7 days. Inter-rater, within-visit, and between-visit reliability were assessed using intraclass correlation coefficients (ICCs) and coefficients of variation (CV). Bland-Altman plots were used to assess agreement. A one-way analysis of variance was used to determine the effects of each loading condition on inter-transverse process distances. Inter-rater, within-visit, and between-visit reliability was good to excellent with ICCs between 0.81 and 0.99 and CVs between 5.24% and 13.0% for all measurements. Inter-transverse process distances were reduced at L2/3 (p = 0.007), L3/4 (p = 0.006), and across the total lumbar distance (p = 0.02) following 15 and 30 min of loaded standing. Ultrasonography is a reliable, low-cost method for quantifying changes in lumbar spine geometry during loaded standing. This technique may have value in occupational and clinical settings for assessing spinal compression in response to mechanical load.
Chronic low back pain (cLBP) is a prevalent and debilitating condition. Gaining insight into the daily experiences of those with cLBP is crucial for developing effective management. Pain and activity are typically assessed at a single time point and often rely on retrospective self-reports, which can be prone to recall bias and may not reflect the day-to-day variability of these experiences. As a part of the University of Pittsburgh LB3P Mechanistic Research Center, this study used ecological momentary assessment (EMA) and wearable devices to collect real-time data in a large cohort of adults with cLBP. The primary aims were to collect and characterize pain and activity profiles of individuals with cLBP. This study enrolled 1007 adults with cLBP who met the National Institutes of Health defined criteria. Over 7 days, participants were assessed in their own environment. EMA was gathered in real-time via a custom mobile app, prompting participants three times daily to provide their perceptions of current pain intensity (0-10), pain interference (0-10), and activity level (very light to vigorous). Time of falling asleep and waking was also reported. Participants wore ActiGraph GT9X devices on their wrist and waist. A custom back sensor was also adhered to the skin over the lumbar (L5) segment. Activity counts, wear time, and step counts were calculated, utilizing algorithms provided by ActiGraph. Sensor data were filtered to include at least 4 days of 10 or more hours each. Activity counts were categorized into sedentary, light, and moderate-to-very-vigorous based on Freedson Adult cutpoints. Out of 1007 participants, 989 submitted EMA data (58.8 ± 16.5 years old; 40% male and 60% female; mean pain intensity at enrollment of 5.4 (SD 2.1) and a median of 5 (interquartile range [IQR] 3) on a 0-10 scale; mean PROMIS Pain Interference T-score at enrollment of 60.5 (SD 7.5) and a median of 61.2 (IQR 9.6)). The median reported pain intensity level from the EMA was 1 (IQR = 3), while pain interference was 3 (IQR = 3). More than half of the participants reported a median pain intensity of either 0 or 1 (54.0%) and a median pain interference between 0 and 3 (57.4%). Most participants self-reported their activity levels as moderate (36%) or light (33%). Based on pain ratings during each day, most participants had their pain intensity (30%) and pain interference (40%) peaking in the evening. ActiGraph data from 884 wrist-worn and 785 waist-worn devices were analyzed. Wrist data showed a median of 1 765 325 (IQR 796 995) activity counts/day and 9575 (IQR 4228) steps/day. Waist data showed 358 390 (IQR 223 758) activity counts/day and 4114 (IQR 3146) steps/day. The percentage of daily sedentary activity was 47.3% for wrist and 72.8% for waist. The back sensor data from 586 participants showed a median of 340 345 (IQR = 223 399) activity counts/day and a median of 3695 (IQR = 2743) steps/day. The percentage of time spent in daily sedentary activity was 82.6%. Both ActiGraph devices and the back sensor indicated that the majority of the time was spent in sedentary activity level, which is lower than the activity level reported in the EMA. Despite having cLBP with self-reported moderate pain levels, participants generally reported periods of relatively low levels of pain intensity and interference in their EMA. In addition, their EMA-reported activity levels differed from the sensor data. Participants self-reported higher levels of activity compared to the activity levels calculated by the wearable sensors. This suggests that participants overestimated their activity levels on EMA, or that the activity level cut-points may need to be re-evaluated for the cLBP population. Additionally, sensors placed on different body locations showed varying activity and step counts. The activity counts calculated from the waist ActiGraph and the back sensor from this cohort were lower than the average activity counts in the US adult population. Further research is needed to better quantify these differences for people with cLBP to develop a more comprehensive understanding of the pain experience.
Traumatic cervical spinal cord injury (TCSCI) often leads to significant patient paralysis. Current clinical diagnosis relies heavily on empirical interpretation of magnetic resonance imaging (MRI) and the American Spinal Injury Association Impairment Scale (AIS) grade, lacking robust quantitative markers to precisely reflect injury severity. This study aimed to build an artificial intelligence (AI) pipeline for AIS grade prediction based on radiomic features extracted from manually defined regions. We included 189 patients with TCSCI who underwent MRI within 48 h post-injury. MRI images from 130 patients were used for developing an AI model encompassing image segmentation. Radiomic features were extracted from manually delineated volumes of interest (VOIs). T2-weighted imaging (T2WI) sagittal images were randomly divided into training (n = 104), validation (n = 13), and test (n = 13) sets for segmentation. A total of 183 patients (excluding AIS E) were included in the AIS grade prediction task. Model performance was evaluated using mean dice similarity coefficient (mDICE), mean intersection over union (mIOU), mean specificity, and mean sensitivity. An optimized UCTransnet network, leveraging a Transformer architecture for formal training, combined with a U-Net++ network for pretraining, achieved promising results in segmenting the spinal cord injury site on T2WI sagittal images (mDICE: 0.777 ± 0.021, mIOU: 0.646 ± 0.025, mean specificity: 0.998 ± 0.001, mean sensitivity: 0.895 ± 0.015). Subsequently, an ensemble model (we named Em-En) constructed using selected radiomic features from the manual VOIs demonstrated superior performance for predicting AIS grades in terms of sensitivity, specificity, accuracy, and clinical decision-making benefit compared to other tested models. This study presents an AI-assisted pipeline for predicting the severity of TCSCI. The developed resources provide a theoretical foundation for the clinical application of AI-assisted diagnostic methods, potentially lowering the interpretation barrier for MRI and offering clinicians preliminary quantitative indicators of injury severity. The source code is publicly available.
The intervertebral disc (IVD) microenvironment plays a crucial role in cellular function and viability. Although the precise cause of IVD degeneration remains unclear, it is associated with progressive disruption of nutrient, metabolite, and pH homeostasis. Despite growing interest in regenerative therapies, the complex IVD microenvironment is often overlooked in preclinical development. This study investigates the effects of clinically relevant combinations of oxygen, glucose, pH, and osmolarity on the metabolic activity and matrix synthesis of goat nucleus pulposus (NP) cells. Goat NP cells were embedded in 3D alginate beads and exposed to 24 distinct microenvironments across four factors in combination: oxygen (2% and 5%), glucose (0.5 and 1.0 mM), pH (6.5, 6.8, and 7.1), and osmolarity (350 and 500 mOsm). Alginate beads were primed for 10 days before subjection to altered microenvironmental conditions for a further 14 days. Cell viability, DNA content, glycosaminoglycan (GAG), and collagen synthesis, as well as oxygen consumption and lactate production rates, were quantified. Experimental data informed in silico modeling of a goat IVD, profiling nutrient and metabolite gradients and GAG accumulation to determine the effects of microenvironmental changes at the whole-organ level. pH was the most influential factor, significantly reducing cell viability, DNA content, and GAG production under degenerated conditions at pH 6.5. Collagen production remained unchanged. Oxygen and glucose significantly affected metabolic rates. Combined analysis revealed the interdependent nature of these factors, better reflecting in vivo interactions. In silico modeling demonstrated that microenvironment-driven changes directly altered disc-wide nutrient profiles and long-term GAG accumulation. These findings highlight the critical role of pH in regulating NP cell function and show that interactions between microenvironmental factors impact cell behavior more than isolated effects. Incorporating physiologically relevant microenvironments may improve regenerative therapy development and enhance translation from preclinical models to clinical application.