Biomechanical Phenotyping of Chronic Low Back Pain: Protocol for BACPAC.

OBJECTIVE: Biomechanics represents the common final output through which all biopsychosocial constructs of back pain must pass, making it a rich target for phenotyping. To exploit this feature, several sites within the NIH Back Pain Consortium (BACPAC) have developed biomechanics measurement and phenotyping tools. The overall aims of this article were to: 1) provide a narrative review of biomechanics as a phenotyping tool; 2) describe the diverse array of tools and outcome measures that exist within BACPAC; and 3) highlight how leveraging these technologies with the other data collected within BACPAC could elucidate the relationship between biomechanics and other metrics used to characterize low back pain (LBP). METHODS: The narrative review highlights how biomechanical outcomes can discriminate between those with and without LBP, as well as among levels of severity of LBP. It also addresses how biomechanical outcomes track with functional improvements in LBP. Additionally, we present the clinical use case for biomechanical outcome measures that can be met via emerging technologies. RESULTS: To answer the need for measuring biomechanical performance, our "Results" section describes the spectrum of technologies that have been developed and are being used within BACPAC. CONCLUSION AND FUTURE DIRECTIONS: The outcome measures collected by these technologies will be an integral part of longitudinal and cross-sectional studies conducted in BACPAC. Linking these measures with other biopsychosocial data collected within BACPAC increases our potential to use biomechanics as a tool for understanding the mechanisms of LBP, phenotyping unique LBP subgroups, and matching these individuals with an appropriate treatment paradigm.

Comparison of paraspinal muscle composition measurements using IDEAL fat-water and T2-weighted MR images.

PURPOSE: The purpose of this study was to evaluate the agreement between paraspinal muscle composition measurements obtained from fat-water images using % fat-signal fraction (%FSF) in comparison to those obtained from T2-weighted magnetic resonance images (MRI) using a thresholding method. METHODS: A sample of 35 subjects (19 females, 16 males; 40.26 ± 11.3 years old) was selected from a cohort of patients with chronic low back pain (LBP). Axial T2-weighted and IDEAL (Lava-Flex, 2 echo sequence) fat and water MR images were obtained using a 3.0 Tesla GE scanner. Multifidus, erector spinae, and psoas major muscle composition measurements were acquired bilaterally at L4-L5 and L5-S1 using both imaging sequences and related measurement methods. All measurements were obtained by the same rater, with a minimum of 7 days between each method. Intra-class correlation coefficients (ICCs) were calculated to assess intra-rater reliability. Pearson Correlation and Bland-Altman 95% limits of agreement were used to assess the agreement between both measurement methods. RESULTS: The intra-rater reliability was excellent for all measurements with ICCs varying between 0.851 and 0.997. Strong positive correlations indicating a strong relationship between composition measurements were obtained from fat-water and T2-weighted images for bilateral multifidus and erector spinae muscles at both spinal levels and the right psoas major muscle at L4-L5, with correlation coefficient r ranging between 0.67 and 0.92. Bland-Altman plots for bilateral multifidus and erector spinae muscles at both levels revealed excellent agreement between the two methods, however, systematic differences between both methods were evident for psoas major fat measurements. CONCLUSION: Our findings suggest that utilizing fat-water and T2-weighted MR images are comparable for quantifying multifidus and erector spinae muscle composition but not of the psoas major. While this suggests that both methods could be used interchangeably for the multifidus and erector spinae, further evaluation is required to expand and confirm our findings to other spinal levels.

Multi-domain biopsychosocial postoperative recovery trajectories associate with patient outcomes following lumbar fusion.

PURPOSE: The purpose of this study is to describe and assess the impact of multi-domain biopsychosocial (BPS) recovery on outcomes following lumbar spine fusion. We hypothesized that discrete patterns of BPS recovery (e.g., clusters) would be identified, and then associated with postoperative outcomes and preoperative patient data. METHODS: Patient-reported outcomes for pain, disability, depression, anxiety, fatigue, and social roles were collected at multiple timepoints for patients undergoing lumbar fusion between baseline and one year. Multivariable latent class mixed models assessed composite recovery as a function of (1) pain, (2) pain and disability, and (3) pain, disability, and additional BPS factors. Patients were assigned to clusters based on their composite recovery trajectories over time. RESULTS: Using all BPS outcomes from 510 patients undergoing lumbar fusion, three multi-domain postoperative recovery clusters were identified: Gradual BPS Responders (11%), Rapid BPS Responders (36%), and Rebound Responders (53%). Modeling recovery from pain alone or pain and disability alone failed to generate meaningful or distinct recovery clusters. BPS recovery clusters were associated with number of levels fused and preoperative opioid use. Postoperative opioid use (p < 0.01) and hospital length of stay (p < 0.01) were associated with BPS recovery clusters even after adjusting for confounding factors. CONCLUSION: This study describes distinct clusters of recovery following lumbar spine fusion derived from multiple BPS factors, which are related to patient-specific preoperative factors and postoperative outcomes. Understanding postoperative recovery trajectories across multiple health domains will advance our understanding of how BPS factors interact with surgical outcomes and could inform personalized care plans.

Ranking essential bacterial processes by speed of mutant death.

Mutant phenotype analysis of bacteria has been revolutionized by genome-scale screening procedures, but essential genes have been left out of such studies because mutants are missing from the libraries analyzed. Since essential genes control the most fundamental processes of bacterial life, this is a glaring deficiency. To address this limitation, we developed a procedure for transposon insertion mutant sequencing that includes essential genes. The method, called transformation transposon insertion mutant sequencing (TFNseq), employs saturation-level libraries of bacterial mutants generated by natural transformation with chromosomal DNA mutagenized heavily by in vitro transposition. The efficient mutagenesis makes it possible to detect large numbers of insertions in essential genes immediately after transformation and to follow their loss during subsequent growth. It was possible to order 45 essential processes based on how rapidly their inactivation inhibited growth. Inactivating ATP production, deoxyribonucleotide synthesis, or ribosome production blocked growth the fastest, whereas inactivating cell division or outer membrane protein synthesis blocked it the slowest. Individual mutants deleted of essential loci formed microcolonies of nongrowing cells whose sizes were generally consistent with the TFNseq ordering. The sensitivity of essential functions to genetic inactivation provides a metric for ranking their relative importance for bacterial replication and growth. Highly sensitive functions could represent attractive antibiotic targets since even partial inhibition should reduce growth.

Paraspinal Muscle in Chronic Low Back Pain: Comparison Between Standard Parameters and Chemical Shift Encoding-Based Water-Fat MRI.

BACKGROUND: Paraspinal musculature (PSM) is increasingly recognized as a contributor to low back pain (LBP), but with conventional MRI sequences, assessment is limited. Chemical shift encoding-based water-fat MRI (CSE-MRI) enables the measurement of PSM fat fraction (FF), which may assist investigations of chronic LBP. PURPOSE: To investigate associations between PSM parameters from conventional MRI and CSE-MRI and between PSM parameters and pain. STUDY TYPE: Prospective, cross-sectional. POPULATION: Eighty-four adults with chronic LBP (44.6 ± 13.4 years; 48 males). FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted fast spin-echo and iterative decomposition of water and fat with echo asymmetry and least squares estimation sequences. ASSESSMENT: T1-weighted images for Goutallier classification (GC), muscle volume, lumbar indentation value, and muscle-fat index, CSE-MRI for FF extraction (L1/2-L5/S1). Pain was self-reported using a visual analogue scale (VAS). Intra- and/or interreader agreement was assessed for MRI-derived parameters. STATISTICAL TESTS: Mixed-effects and linear regression models to 1) assess relationships between PSM parameters (entire cohort and subgroup with GC grades 0 and 1; statistical significance α = 0.0025) and 2) evaluate associations of PSM parameters with pain (α = 0.05). Intraclass correlation coefficients (ICCs) for intra- and/or interreader agreement. RESULTS: The FF showed excellent intra- and interreader agreement (ICC range: 0.97-0.99) and was significantly associated with GC at all spinal levels. Subgroup analysis suggested that early/subtle changes in PSM are detectable with FF but not with GC, given the absence of significant associations between FF and GC (P-value range: 0.036 at L5/S1 to 0.784 at L2/L3). Averaged over all spinal levels, FF and GC were significantly associated with VAS scores. DATA CONCLUSION: In the absence of FF, GC may be the best surrogate for PSM quality. Given the ability of CSE-MRI to detect muscle alterations at early stages of PSM degeneration, this technique may have potential for further investigations of the role of PSM in chronic LBP. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Spatial distribution of fat infiltration within the paraspinal muscles: implications for chronic low back pain.

PURPOSE: Fat infiltration (FI) of the paraspinal muscles (PSMs) measured using MRI is an aspect of muscle quality and is considered to be worse in chronic low back pain (cLBP) patients. However, there is not a clear association between paraspinal muscle FI and cLBP, leaving the clinical importance of paraspinal muscle composition unestablished. The spatial distribution of FI in the PSMs may inform mechanistic understanding of non-specific cLBP as it relates to degenerative intervertebral disc (IVD) pathology. We hypothesized that paraspinal muscle fat-mapping would reveal distinct FI distribution patterns in relation to cLBP symptoms and proximity to symptomatic IVD degeneration. METHODS: From advanced-sequence water-fat MRI of 40 axial cLBP patients and 21 controls, we examined the spatial distribution of paraspinal muscle FI in relation to the center of rotation at the L4L5 disc. Using statistical parametric mapping, we compared FI patterns for multifidus (MF), erector spinae (ES), and psoas between patients and controls, and to the presence and severity of adjacent degenerative IVD pathology. RESULTS: The spatial distribution of PSMs FI differs between PSMs and according to symptoms and the adjacent degenerative IVD pathology. Furthermore, the region of MF closest to the disc center of rotation appears most susceptible to FI in the presence of symptomatic IVD degeneration. CONCLUSION: Our study identified spatial distribution patterns of FI in the PSMs as a potential diagnostic biomarker that may also provide granular mechanistic insights into spine biomechanics related to cLBP, as well as advancing the use of prior summary measures limited to overall muscle FI.

Compensatory biomechanics and spinal loading during dynamic maneuvers in patients with chronic low back pain.

PURPOSE: This study explores the biomechanics underlying the sit-to-stand (STS) functional maneuver in chronic LBP patients to understand how different spinal disorders and levels of pain severity relate to unique compensatory biomechanical behaviors. This work stands to further our understanding of the relationship between spinal loading and symptoms in LBP patients. METHODS: We collected in-clinic motion data from 44 non-specific LBP (NS-LBP) and 42 spinal deformity LBP (SD-LBP) patients during routine clinical visits. An RGB-depth camera tracked 3D joint positions from the frontal view during unassisted, repeated STS maneuvers. Patient-reported outcomes (PROs) for back pain (VAS) and low back disability (ODI) were collected during the same clinical visit. RESULTS: Between patient groups, SD-LBP patients had 14.3% greater dynamic sagittal vertical alignment (dSVA) and 10.1% greater peak spine torque compared to NS-LBP patients (p < 0.001). SD-LBP patients also had 11.8% greater hip torque (p < 0.001) and 86.7% greater knee torque (p = 0.04) compared to NS-LBP patients. There were no significant differences between patient groups in regard to anterior or vertical torso velocities, but anterior and vertical torso velocities correlated with both VAS (r = - 0.38, p < 0.001) and ODI (r = - 0.29, p = 0.01). PROs did not correlate with other variables. CONCLUSION: Patients with LBP differ in movement biomechanics during an STS transfer as severity of symptoms may relate to different compensatory strategies that affect spinal loading. Further research aims to establish relationships between movement and PROs and to inform targeted rehabilitation approaches.

Using hierarchical unsupervised learning to integrate and reduce multi-level and multi-paraspinal muscle MRI data in relation to low back pain.

PURPOSE: The paraspinal muscles (PSM) are a key feature potentially related to low back pain (LBP), and their structure and composition can be quantified using MRI. Most commonly, quantifying PSM measures across individual muscles and individual spinal levels renders numerous separate metrics that are analyzed in isolation. However, comprehensive multivariate approaches would be more appropriate for analyzing the PSM within an individual. To establish and test these methods, we hypothesized that multivariate summaries of PSM MRI measures would associate with the presence of LBP symptoms (i.e., pain intensity). METHODS: We applied hierarchical multiple factor analysis (hMFA), an unsupervised integrative method, to clinical PSM MRI data from unique cohort datasets including a longitudinal cohort of astronauts with pre- and post-spaceflight data and a cohort of chronic LBP subjects and asymptomatic controls. Three specific use cases were investigated: (1) predicting longitudinal changes in pain using combinations of baseline PSM measures; (2) integrating baseline and post-spaceflight MRI to assess longitudinal change in PSM and how it relates to pain; and (3) integrating PSM quality and adjacent spinal pathology between LBP patients and controls. RESULTS: Overall, we found distinct complex relationships with pain intensity between particular muscles and spinal levels. Subjects with high asymmetry between left and right lean muscle composition and differences between spinal segments PSM quality and structure are more likely to increase in pain reported outcome after prolonged time in microgravity. Moreover, changes in PSM quality and structure between pre and post-spaceflight relate to increase in pain after prolonged microgravity. Finally, we show how unsupervised hMFA recapitulates previous research on the association of CEP damage and LBP diagnostic. CONCLUSION: Our analysis considers the spine as a multi-segmental unit as opposed to a series of discrete and isolated spine segments. Integrative and multivariate approaches can be used to distill large and complex imaging datasets thereby improving the clinical utility of MRI-based biomarkers, and providing metrics for further analytical goals, including phenotyping.

Essential gene deletions producing gigantic bacteria.

To characterize the consequences of eliminating essential functions needed for peptidoglycan synthesis, we generated deletion mutations of Acinetobacter baylyi by natural transformation and visualized the resulting microcolonies of dead cells. We found that loss of genes required for peptidoglycan precursor synthesis or polymerization led to the formation of polymorphic giant cells with diameters that could exceed ten times normal. Treatment with antibiotics targeting early or late steps of peptidoglycan synthesis also produced giant cells. The giant cells eventually lysed, although they were partially stabilized by osmotic protection. Genome-scale transposon mutant screening (Tn-seq) identified mutations that blocked or accelerated giant cell formation. Among the mutations that blocked the process were those inactivating a function predicted to cleave murein glycan chains (the MltD murein lytic transglycosylase), suggesting that giant cell formation requires MltD hydrolysis of existing peptidoglycan. Among the mutations that accelerated giant cell formation after ß-lactam treatment were those inactivating an enzyme that produces unusual 3->3 peptide cross-links in peptidoglycan (the LdtG L,D-transpeptidase). The mutations may weaken the sacculus and make it more vulnerable to further disruption. Although the study focused on A. baylyi, we found that a pathogenic relative (A. baumannii) also produced giant cells with genetic dependencies overlapping those of A. baylyi. Overall, the analysis defines a genetic pathway for giant cell formation conserved in Acinetobacter species in which independent initiating branches converge to create the unusual cells.

Clinical outcomes one year after a digital musculoskeletal (MSK) program: an observational, longitudinal study with nonparticipant comparison group.

BACKGROUND: The evidence base for the impact of digital health on musculoskeletal (MSK) outcomes is growing, but it is unclear how much digital MSK programs address pain and function in the intermediate and long term. METHODS: This observational study of digital MSK program participants versus nonparticipants (n = 2570) examined pain, function, depression, and anxiety at 3, 6, and 12 months, and health care use at 12 months. The intervention group engaged in a digital MSK program that included exercise, education, and coaching for at least 3 months. The nonparticipant group registered, but never started the program. We collected data in app or by emailed survey at 3, 6, and 12 months after registering for the program. We conducted descriptive analyses and unadjusted and adjusted regression modeling. RESULTS: The odds ratio of achieving a minimally clinically important difference (MCID) in pain improvement for the intervention versus the nonparticipant group was 1.97 (95% CI: 1.28, 3.02; p = .002) at 3 months, 1.44 (95% CI: 0.91, 2.25; p = .11) at 6 months, and 2.06 (95% CI: 1.38, 3.08; p = .004) at 12 months in adjusted models. The odds ratio of achieving a MCID in functional improvement for the intervention versus the nonparticipant group was 1.56 (95% CI: 1.03, 2.38; p = .01) at 3 months, 1.55 (95% CI: 1.02, 2.37; p = .04) at 6 months, and 1.35 (95% CI: 0.89, 2.06, p = 0.16) at 12 months in adjusted models. For those with moderate to severe depression or anxiety at baseline, we observed statistically significant lower odds of moderate to severe depression or anxiety at 3 months, 6 months, and 12 months for the intervention versus the nonparticipant group in adjusted models (p < .05). At 12 months, the percentage with invasive, imaging, and conservative services was higher for the nonparticipant versus intervention group by 5.7, 8.1, and 16.7 percentage points, respectively (p < 0.05). CONCLUSIONS: A digital MSK program may offer participants sustained improvement in pain, depression, and anxiety with concomitant decreases in health care use.

Paraspinal muscle imaging measurements for common spinal disorders: review and consensus-based recommendations from the ISSLS degenerative spinal phenotypes group.

PURPOSE: Paraspinal muscle imaging is of growing interest related to improved phenotyping, prognosis, and treatment of common spinal disorders. We reviewed issues related to paraspinal muscle imaging measurement that contribute to inconsistent findings between studies and impede understanding. METHODS: Three key contributors to inconsistencies among studies of paraspinal muscle imaging measurements were reviewed: failure to consider possible mechanisms underlying changes in paraspinal muscles, lack of control of confounding factors, and variations in spinal muscle imaging modalities and measurement protocols. Recommendations are provided to address these issues to improve the quality and coherence of future research. RESULTS: Possible pathophysiological responses of paraspinal muscle to various common spinal disorders in acute or chronic phases are often overlooked, yet have important implications for the timing, distribution, and nature of changes in paraspinal muscle. These considerations, as well as adjustment for possible confounding factors, such as sex, age, and physical activity must be considered when planning and interpreting paraspinal muscle measurements in studies of spinal conditions. Adoption of standardised imaging measurement protocols for paraspinal muscle morphology and composition, considering the strengths and limitations of various imaging modalities, is critically important to interpretation and synthesis of research. CONCLUSION: Study designs that consider physiological and pathophysiological responses of muscle, adjust for possible confounding factors, and use common, standardised measures are needed to advance knowledge of the determinants of variations or changes in paraspinal muscle and their influence on spinal health.

Measurement of vertebral endplate bone marrow lesion (Modic change) composition with water-fat MRI and relationship to patient-reported outcome measures.

PURPOSE: Vertebral endplate bone marrow lesions ("Modic changes", MC) are associated with chronic low back pain (CLBP). Bone marrow composition in MC is poorly understood. The goals of this study were to: (1) measure bone marrow fat fraction (BMF) in CLBP patients with MC using water-fat MRI and (2) assess the relationship between BMF measurements and patient-reported clinical characteristics. METHODS: In this cross-sectional study, 42 CLBP patients (men, n = 21; age, 48 ± 12.4 years) and 18 asymptomatic controls (men, n = 10; 42.7 ± 12.8 years) underwent 3 T MRI between January 2016 and July 2018. Imaging consisted of T1- and T2-weighted sequences to evaluate MC and spoiled gradient-recalled echo sequence with asymmetric echoes and least-squares fitting to measure BMF. BMF was compared between vertebrae with and without MC using mixed effects models. The relationship between the BMF measurements and patient-reported disability scores was examined using regression. RESULTS: Twenty-seven subjects (26 CLBP, 1 control) had MC, and MC presence coincided with significantly altered BMF. In MC 1, BMF was lower than endplates without MC (absolute difference -22.3%; p < 0.001); in MC 2, BMF was higher (absolute difference 21.0%; p < 0.001). Absolute BMF differences between affected and unaffected marrow were larger in patients with greater disability (p = 0.029-0.032) and were not associated with pain (p = 0.49-0.83). CONCLUSION: BMF is significantly altered in MC. Water-fat MRI enables BMF measurements that may eventually form the basis for quantitative assessments of MC severity and progression.

Digital Care for Chronic Musculoskeletal Pain: 10,000 Participant Longitudinal Cohort Study.

BACKGROUND: Chronic musculoskeletal pain has a vast global prevalence and economic burden. Conservative therapies are universally recommended but require patient engagement and self-management to be effective. OBJECTIVE: This study aimed to evaluate the efficacy of a 12-week digital care program (DCP) in a large population of patients with chronic knee and back pain. METHODS: A longitudinal observational study was conducted using a remote DCP available through a mobile app. Subjects participated in a 12-week multimodal DCP incorporating education, sensor-guided exercise therapy (ET), and behavioral health support with 1-on-1 remote health coaching. The primary outcome was pain measured by the visual analog scale (VAS). Secondary measures included engagement levels, program completion, program satisfaction, condition-specific pain measures, depression, anxiety, and work productivity. RESULTS: A total of 10,264 adults with either knee (n=3796) or low back (n=6468) pain for at least three months were included in the study. Participants experienced a 68.45% average improvement in VAS pain between baseline intake and 12 weeks. In all, 73.04% (7497/10,264) participants completed the DCP into the final month. In total, 78.60% (5893/7497) of program completers (7144/10,264, 69.60% of all participants) achieved minimally important change in pain. Furthermore, the number of ET sessions and coaching interactions were both positively associated with improvement in pain, suggesting that the amount of engagement influenced outcomes. Secondary outcomes included a 57.9% and 58.3% decrease in depression and anxiety scores, respectively, and 61.5% improvement in work productivity. Finally, 3 distinct clusters of pain response trajectories were identified, which could be predicted with a mean 76% accuracy using baseline measures. CONCLUSIONS: These results support the efficacy and scalability of a DCP for chronic low back and knee pain in a large, diverse, real-world population. Participants demonstrated high completion and engagement rates and a significant positive relationship between engagement and pain reduction was identified, a finding that has not been previously demonstrated in a DCP. Furthermore, the large sample size allowed for the identification of distinct pain response subgroups, which may prove beneficial in predicting recovery and tailoring future interventions. This is the first longitudinal digital health study to analyze pain outcomes in a sample of this magnitude, and it supports the prospect for DCPs to serve the overwhelming number of musculoskeletal pain sufferers worldwide.

Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI.

BACKGROUND: There is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP). PURPOSE: To apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD. STUDY TYPE: Prospective. SUBJECTS: Forty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years. FIELD STRENGTH/SEQUENCE: 3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm. ASSESSMENT: Using quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed. STATISTICAL TESTS: Mixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF. RESULTS: The relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ /T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13). DATA CONCLUSION: Our study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:1219-1226.

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2019: biomechanical changes in dynamic sagittal balance and lower limb compensatory strategies following realignment surgery in adult spinal deformity patients.

STUDY DESIGN: A longitudinal cohort study. OBJECTIVE: To define a set of objective biomechanical metrics that are representative of adult spinal deformity (ASD) post-surgical outcomes and that may forecast post-surgical mechanical complications. Current outcomes for ASD surgical planning and post-surgical assessment are limited to static radiographic alignment and patient-reported questionnaires. Little is known about the compensatory biomechanical strategies for stabilizing sagittal balance during functional movements in ASD patients. METHODS: We collected in-clinic motion data from 15 ASD patients and 10 controls during an unassisted sit-to-stand (STS) functional maneuver. Joint motions were measured using noninvasive 3D depth mapping sensor technology. Mathematical methods were used to attain high-fidelity joint-position tracking for biomechanical modeling. This approach provided reliable measurements for biomechanical behaviors at the spine, hip, and knee. These included peak sagittal vertical axis (SVA) over the course of the STS, as well as forces and muscular moments at various joints. We compared changes in dynamic sagittal balance (DSB) metrics between pre- and post-surgery and then separately compared pre- and post-surgical data to controls. RESULTS: Standard radiographic and patient-reported outcomes significantly improved following realignment surgery. From the DSB biomechanical metrics, peak SVA and biomechanical loads and muscular forces on the lower lumbar spine significantly reduced following surgery (- 19 to - 30%, all p < 0.05). In addition, as SVA improved, hip moments decreased (- 28 to - 65%, all p < 0.05) and knee moments increased (+ 7 to + 28%, p < 0.05), indicating changes in lower limb compensatory strategies. After surgery, DSB data approached values from the controls, with some post-surgical metrics becoming statistically equivalent to controls. CONCLUSIONS: Longitudinal changes in DSB following successful multi-level spinal realignment indicate reduced forces on the lower lumbar spine along with altered lower limb dynamics matching that of controls. Inadequate improvement in DSB may indicate increased risk of post-surgical mechanical failure. These slides can be retrieved under Electronic Supplementary Material.

Cross-sectional area of lumbar spinal muscles and vertebral endplates: a secondary analysis of 91 computed tomography images of children aged 2-20.

Spinal muscle cross-sectional area has been highly associated with spinal pathology. Despite the medium-high prevalence of spinal pathology in children, there is very limited knowledge regarding muscle size and growth pattern in individuals younger than 20 years of age. The aim of this study is to analyze the change in size and symmetry of spinal muscles (erector spinae, multifidus, psoas and quadratus lumborum) in children 2-20 years of age. We studied reformatted images from 91 abdominal computed tomographic scans of children aged 2-20 years, from an existing imaging dataset. The cross-sectional area of the muscles was bilaterally measured parallel to the upper endplate of the lumbar vertebrae L3-L5 and at true horizontal for S1. The cross-sectional area of the upper vertebral endplate was measured at spinal levels L3-L5. Results were analyzed according to six groups based on children's age: 2-4 years (group 1), 5-7 years (group 2), 8-10 years (group 3), 11-13 years (group 4), 14-16 years (group 5) and 17-20 years (group 6). Vertebral endplate and spinal muscles cross-sectional area increased with age. Two patterns were observed: Endplate, psoas and quadratus lumborum increased up to our 6th oldest age group (17-20), and multifidus and erector spinae reached their largest size in the 5th age group (14-16). The epaxial muscles (erector spinae and multifidus) reached their maximal cross-sectional area before skeletal maturity (18-21 years of age). The hypaxial muscles (psoas and quadratus lumborum) continued to increase in size at least until spinal maturity. Contributing factors for the differences in developmental pattern between the epaxial and hypaxial muscles might include functional, embryological and innervation factors. In conclusion, this research is the first to describe the cross-sectional area of spinal muscles in children. Future longitudinal studies are needed for further understanding of muscle development during childhood and adolescence. LEVEL OF EVIDENCE: level 2b, Retrospective cohort study.

Morphological and postural sexual dimorphism of the lumbar spine facilitates greater lordosis in females.

Previous work suggests females are evolutionarily adapted to have greater lumbar lordosis than males to aid in pregnancy load-bearing, but no consensus exists. To explore further sex-differences in the lumbar spine, and to understand contradictions in the literature, we conducted a cross-sectional retrospective study of sex-differences in lumbar spine morphology and sacral orientation. In addition, our sample includes data for separate standing and supine samples of males and females to examine potential sex-differences in postural loading on lumbosacral morphology. We measured sagittal lumbosacral morphology on 200 radiographs. Measurements include: lumbar angle (L1-S1), lumbar vertebral body and disc wedging angles, sacral slope and pelvic incidence. Lumbar angle, representative of lordotic curvature between L1 and S1, was 7.3° greater in females than males, when standing. There were no significant sex-differences in lumbar angle when supine. This difference in standing lumbar angle can be explained by greater lordotic wedging of the lumbar vertebrae (L1-L5) in females. Additionally, sacral slope was greater in females than males, when standing. There were no significant sex-differences in pelvic incidence. Our results support that females have greater lumbar lordosis than males when standing, but not when supine - suggesting a potentially greater range of motion in the female spine. Furthermore, sex-differences in the lumbar spine appear to be supported by postural differences in sacral-orientation and morphological differences in the vertebral body wedging. A better understanding of sex-differences in lumbosacral morphology may explain sex-differences in spinal conditions, as well as promote necessary sex-specific treatments.

Neural innervation patterns in the sacral vertebral body.

PURPOSE: To characterize the distribution of nerves within a single S1 vertebral body, with particular emphasis on the superior endplate that interfaces with the L5/S1 disc. METHODS: Musculature and connective tissue surrounding the sacrum was carefully dissected away for close visual inspection of penetrating nerve fibers. The S1 vertebral body was then isolated for histology and serial coronal sections were cut and stained with a ubiquitous neural antibody marker (PGP 9.5). Slides were analyzed and nerves were manually marked on high resolution, composite captured images, rendering 3D depictions of internal nerve distribution. RESULTS: The vast majority of nerves were closely associated with blood vessels within the marrow space with a uniform distribution in both the superior and inferior endplates of the S1 vertebral body. The highest nerve density was seen at the centrum (anatomic center) of the S1 vertebral body with smaller peaks seen at the lateral borders. Nerve fibers were observed branching from anterior sacral nerves and penetrating the lateral border of the S1 (during dissection), corresponding with peaks on nerve density maps. CONCLUSIONS: Our results demonstrate that the S1 body and endplate are densely innervated and the peak in nerve density at the vertebral center coincides with vasculature patterns previously described in lumbar vertebral bodies. In the sacrum, however, there is no posterior nutrient foramen that facilitates nerve penetration through the vertebral cortex. Rather, our data indicate that nerves penetrate the S1 via the lateral aspects, consistent with being branches of the anterior sacral nerve. Since PGP 9.5 is a ubiquitous neural marker these identified nerves are likely composed of a mixed population of nociceptive and autonomic fibers.

Etiology of lumbar lordosis and its pathophysiology: a review of the evolution of lumbar lordosis, and the mechanics and biology of lumbar degeneration.

The goal of this review is to discuss the mechanisms of postural degeneration, particularly the loss of lumbar lordosis commonly observed in the elderly in the context of evolution, mechanical, and biological studies of the human spine and to synthesize recent research findings to clinical management of postural malalignment. Lumbar lordosis is unique to the human spine and is necessary to facilitate our upright posture. However, decreased lumbar lordosis and increased thoracic kyphosis are hallmarks of an aging human spinal column. The unique upright posture and lordotic lumbar curvature of the human spine suggest that an understanding of the evolution of the human spinal column, and the unique anatomical features that support lumbar lordosis may provide insight into spine health and degeneration. Considering evolution of the skeleton in isolation from other scientific studies provides a limited picture for clinicians. The evolution and development of human lumbar lordosis highlight the interdependence of pelvic structure and lumbar lordosis. Studies of fossils of human lineage demonstrate a convergence on the degree of lumbar lordosis and the number of lumbar vertebrae in modern Homo sapiens. Evolution and spine mechanics research show that lumbar lordosis is dictated by pelvic incidence, spinal musculature, vertebral wedging, and disc health. The evolution, mechanics, and biology research all point to the importance of spinal posture and flexibility in supporting optimal health. However, surgical management of postural deformity has focused on restoring posture at the expense of flexibility. It is possible that the need for complex and costly spinal fixation can be eliminated by developing tools for early identification of patients at risk for postural deformities through patient history (genetics, mechanics, and environmental exposure) and tracking postural changes over time.

Predicting Recovery Following Total Hip and Knee Arthroplasty Using a Clustering Algorithm.

Background: Recovery following total joint arthroplasty is patient-specific, yet groups of patients tend to fall into certain similar patterns of recovery. The purpose of this study was to identify and characterize recovery patterns following total hip arthroplasty (THA) and total knee arthroplasty (TKA) using patient-reported outcomes that represent distinct health domains. We hypothesized that recovery patterns could be defined and predicted using preoperative data. Methods: Adult patients were recruited from a large, urban academic center. To model postoperative responses to THA and TKA across domains such as physical health, mental health, and joint-specific measures, we employed a longitudinal clustering algorithm that incorporates each of these health domains. The clustering algorithm from multiple health domains allows the ability to define distinct recovery trajectories, which could then be predicted from preoperative and perioperative factors using a multinomial regression. Results: Four hundred forty-one of 1134 patients undergoing THA and 346 of 921 undergoing TKA met eligibility criteria and were used to define distinct patterns of recovery. The clustering algorithm was optimized for 3 distinct patterns of recovery that were observed in THA and TKA patients. Patients recovering from THA were divided into 3 groups: standard responders (50.8%), late mental responders (13.2%), and substandard responders (36.1%). Multivariable, multinomial regression suggested that these 3 groups had defined characteristics. Late mental responders tended to be obese (P = .05) and use more opioids (P = .01). Substandard responders had a larger number of comorbidities (P = .02) and used more opioids (P = .001). Patients recovering from TKA were divided among standard responders (55.8%), poor mental responders (24%), and poor physical responders (20.2%). Poor mental responders were more likely to be female (P = .04) and American Society of Anesthesiologists class III/IV (P = .004). Poor physical responders were more likely to be female (P = .03), younger (P = .04), American Society of Anesthesiologists III/IV (P = .04), use more opioids (P = .02), and be discharged to a nursing facility (P = .001). The THA and TKA models demonstrated areas under the curve of 0.67 and 0.72. Conclusions: This multidomain, longitudinal clustering analysis defines 3 distinct patterns in the recovery of THA and TKA patients, with most patients in both cohorts experiencing robust improvement, while others had equally well defined yet less optimal recovery trajectories that were either delayed in recovery or failed to achieve a desired outcome. Patients in the delayed recovery and poor outcome groups were slightly different between THA and TKA. These groups of patients with similar recovery patterns were defined by patient characteristics that include potentially modifiable comorbid factors. This research suggests that there are multiple defined recovery trajectories after THA and TKA, which provides a new perspective on THA and TKA recovery. Level of Evidence: III.