Unveiling the mechanisms of Moso bamboo's motor function and internal growth stress.

Bamboo, a renewable resource with rapid growth and an impressive height-to-diameter ratio, faces mechanical instability due to its slender structure. Despite this, bamboo maintains its posture without breaking in its battle against environmental and gravitational forces. But what drives this motor function in bamboo? This study subjected Moso bamboo (Phyllostachys edulis) to gravitational stimulation, compelling it to grow at a 45° angle instead of upright. Remarkably, the artificially inclined bamboo exhibited astonishing shape control and adjustment capabilities. The growth strain was detected at both macroscopic and microscopic levels, providing evidence for the presence of internal stress, namely growth stress. The high longitudinal tensile stress on the upper side, along with a significant asymmetry in stress distribution in tilted bamboo, plays a pivotal role in maintaining its mechanical stability. Drawing upon experimental findings, it can be deduced that the growth stress primarily originates from the broad layers of fiber cells. Bamboo could potentially regulate the magnitude of growth stress by modifying the number of fiber cell layers during its maturation process. Additionally, the microfibril angle and lignin disposition may decisively influence the generation of growth stress.

Fast and Slow-Twitch Actuation via Twisted Liquid Crystal Elastomer Fibers.

The performance of robotic systems can benefit from low-density material actuators that emulate muscle typology (e.g., fast and slow twitch) of natural systems. Recent reports detail the thermomechanical, chemical, electrical, and pneumatic response of twisted and coiled fibers. The geometrical constraints imparted on typically commodity materials realize distinguished stimuli-induced actuation including low density, high force, and moderate stroke. Here, actuators are prepared by twisting fibers composed of liquid crystal elastomers (LCEs). The actuators combine the inherent stimuli-response of LCEs with the geometrical constraints of twisted fiber actuators to dramatically increase the deformation rate, specific work, and achievable force output. In some geometries, the thermomechanical response of the LCE exhibits a pseudo-first-order transition.

The impact of osteoporosis and diabetes on fracture healing under different loading conditions.

BACKGROUND: Osteoporosis and diabetes are two prevalent conditions among the elderly population. Each of these conditions can profoundly influence the fracture healing process by disturbing the associated inflammatory process. However, the combined effects of osteoporosis and diabetes on fracture healing remain unclear. Therefore, the purpose of the present study is to investigate the role of osteoporosis and diabetes in fracture healing and the underlying mechanisms by developing numerical models. METHOD: This study introduces a numerical model that consists of a three-dimensional model of a tibia fracture stabilized by a Locking Compression Plate (LCP), coupled with a two-dimensional axisymmetric model which illustrates the transport and reactions of cells and cytokines throughout the inflammatory phase in early fracture healing. First, the model parameters were calibrated using available experimental data. The model was then implemented to predict the healing outcomes of fractures under five varied conditions, consisting of both osteoporotic and non-osteoporotic bones, each subjected to different physiological loads. RESULTS: The instability of the fracture callus can significantly escalate in osteoporotic fractures (e.g., when a 150 N physiological load is applied, the unstable region of the osteoporotic fracture callus can reach 26 %, in contrast to 12 % in non-osteoporotic fractures). Additionally, the mesenchymal stem cells (MSCs) proliferation and differentiation can be disrupted in osteoporotic fracture compared to non-osteoporotic fractures (e.g., on the 10th day post-fracture, the decrease in the concentration of MSCs, osteoblasts, and chondrocytes in osteoporotic fractures is nearly double that in non-osteoporotic fractures under a 150 N). Finally, the healing process of fractures can suffer significant impairment when osteoporosis coexists with diabetes (e.g., the concentration of MSCs can be drastically reduced by nearly 37 % in osteoporotic fractures under diabetic conditions when subjected to a load of 200 N) CONCLUSIONS: Fracture calluses destabilized by osteoporosis can negatively affect the fracture healing process by disrupting the proliferation and differentiation of mesenchymal stem cells (MSCs). Moreover, when osteoporosis coexists with diabetes, the fracture healing process can severely impair the fracture healing outcomes.

Development of an Amorphous Solid Dispersion Formulation for Mitigating Mechanical Instability of Crystalline Form and Improving Bioavailability for Early Phase Clinical Studies.

In this work, an amorphous solid dispersion (ASD) formulation was systematically developed to simultaneously enhance bioavailability and mitigate the mechanical instability risk of the selected crystalline form of a development drug candidate, GDC-0334. The amorphous solubility advantage calculation was applied to understand the solubility enhancement potential by an amorphous formulation for GDC-0334, which showed 2.7 times theoretical amorphous solubility advantage. This agreed reasonably well with the experimental solubility ratio between amorphous GDC-0334 and its crystalline counterpart (∼2 times) in buffers of a wide pH range. Guided by the amorphous solubility advantage, ASD screening was then carried out, focusing on supersaturation maintenance and dissolution performance. It was found that although the type of polymer carrier did not impact ASD performance, the addition of 5% (w/w) sodium dodecyl sulfate (SDS) significantly improved the GDC-0334 ASD dissolution rate. After ASD composition screening, stability studies were conducted on selected ASD powders and their hypothetical tablet formulations. Excellent stability of the selected ASD prototypes with or without tablet excipients was observed. Subsequently, ASD tablets were prepared, followed by in vitro and in vivo evaluations. Similar to the effect of facilitating the dissolution of ASD powders, the added SDS improved the disintegration and dissolution of ASD tablets. Finally, a dog pharmacokinetic study confirmed 1.8 to 2.5-fold enhancement of exposure by the developed ASD tablet over the GDC-0334 crystalline form, consistent with the amorphous solubility advantage of GDC-0334. A workflow of developing an ASD formulation for actual pharmaceutical application was proposed according to the practice of this work, which could provide potential guidance for ASD formulation development in general for other new chemical entities.

The effects of mechanical instability on PDGF mediated inflammatory response at early stage of fracture healing under diabetic condition.

BACKGROUND AND OBJECTIVE: Mechanical stability plays an important role in fracture healing process. Excessive interfragmentary movement will continuously damage the tissue and newly formed capillaries at the fracture site, which leads to overproduction of platelet-derived growth factor (PDGF) that attracts more macrophages into fracture callus, ultimately persistent and enhanced inflammatory response happens. For diabetic condition, the impact of mechanical instability of fracture site on inflammatory response could be further compliciated and the relevant research in this field is relatively limited. METHODS: Building on previous experimental studies, this study presents a numerical model consisting of a system of reactive-transport equations representing the transport as well as interactions of different cells and cytokines within the fracture callus. The model is initially validated by available experimental data, and then implemented to investigate the role of mechanical stability of fracture site in inflammatory response during early stage of healing. It is assumed that there is an increased release of PDGF due to the rupture of blood vessels resulting from mechanical instability, which leads to increased production of inflammatory cytokines (i.e., TNF-α). The bone healing process under three different conditions were investigated, i.e., mechanically stable condition with normal inflammatory response (Control, Case 1), mechanically unstable condition with normal inflammatory response (Case 2) and mechanically unstable condition with diabetes (Case 3). RESULTS: Mechanical instability can promote the macrophage infiltration and thus induce an enhanced and prolonged inflammatory response, which could impede the MSCs proliferation during the early fracture healing stage (e.g., compared with the control condition, the MSCs concentration in unstable fracture with normal inflammatory response can be reduced by 3.2% and 5.2% on day 2 and day 10 post-fracture, respectively). Under diabetic condition, the mechanical instability of fracture site could lead to a significant increase of TNF-α concentration in fracture callus (Case 3) in comparison to control (Case 1) (e.g., three-fold increase in TNF-α concentration compared to control). In addition, the results show that the mechanical instability affects the cell differentiation and proliferation in fracture callus in a spatially dependent manner, e.g., for diabetic fracture patients, the mechanical instability could potentially decrease the concentration of MSCs, osteoblasts and chondrocytes by around 39%, 30% and 29% in cortical callus, respectively, in comparison to control. CONCLUSION: The mechanical instability together with diabetic condition can significantly affect the natural resolution of inflammation during early stage of healing by turning acute inflammation into chronic inflammation which is characterized by a continuously upregulated TNF-α pathway.

Spine slenderness is not an early sign of progression in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine. Spine slenderness, which represents its potential instability to buckling under compressive loads, was shown to be higher in AIS patients than non-scoliotic subjects, but it is not clear at what stage of the progression this difference appeared, nor if slenderness could be used as an early sign of progression. In this study, we hypothesized that slenderness could be an early sign of progression. One-hundred thirty-eight patients and 93 non-scoliotic subjects were included. They underwent standing biplanar radiography and 3D reconstruction of the spine, which allowed computing vertebra and disc slenderness ratio. Then, patients were followed until progression of the deformity or skeletal maturity (stable patients). Vertebral slenderness ratio in AIS patients varied between 2.9 [2.7; 3.0] (T9) and 3.4 [3.2; 3.6] (T1), while disc slenderness ranged from 0.6 [0.6; 0.7] at T6-T7 to 1.2 [1.1; 1.3] at L4-L5. Slenderness ratio increased with age, while disc slenderness tended to decrease with age and Cobb angle. Slenderness was similar between progressive and stable patients, and also between patients and non-scoliotic subjects. In conclusion, spinal slenderness does not appear to be an early sign of progression. Further studies should analyse the development of slenderness during growth, and how it could be affected by non-operative treatment.

Smooth or with a Snap! Biomechanics of Trap Reopening in the Venus Flytrap (Dionaea muscipula).

Fast snapping in the carnivorous Venus flytrap (Dionaea muscipula) involves trap lobe bending and abrupt curvature inversion (snap-buckling), but how do these traps reopen? Here, the trap reopening mechanics in two different D. muscipula clones, producing normal-sized (N traps, max. ≈3 cm in length) and large traps (L traps, max. ≈4.5 cm in length) are investigated. Time-lapse experiments reveal that both N and L traps can reopen by smooth and continuous outward lobe bending, but only L traps can undergo smooth bending followed by a much faster snap-through of the lobes. Additionally, L traps can reopen asynchronously, with one of the lobes moving before the other. This study challenges the current consensus on trap reopening, which describes it as a slow, smooth process driven by hydraulics and cell growth and/or expansion. Based on the results gained via three-dimensional digital image correlation (3D-DIC), morphological and mechanical investigations, the differences in trap reopening are proposed to stem from a combination of size and slenderness of individual traps. This study elucidates trap reopening processes in the (in)famous Dionaea snap traps - unique shape-shifting structures of great interest for plant biomechanics, functional morphology, and applications in biomimetics, i.e., soft robotics.

Metamorphism-facilitated faulting in deforming orthopyroxene: Implications for global intermediate-depth seismicity.

SignificanceThe exothermic metamorphic reaction in orthopyroxene (Opx), a major component of oceanic lithospheric mantle, is shown to trigger brittle failure in laboratory deformation experiments under conditions where garnet exsolution takes place. The reaction product is an extremely fine-grained material, forming narrow reaction zones that are mechanically weak, thereby facilitating macroscopic faulting. Oceanic subduction zones are characterized by two separate bands of seismicity, known as the double seismic zone. The upper band of seismicity, located in the oceanic crust, is well explained by dehydration-induced mechanical instability. Our newly discovered metamorphism-induced mechanical instability provides an alternative physical mechanism for earthquakes in the lower band of seismicity (located in the oceanic lithospheric mantle), with no requirement of hydration/dehydration processes.

circPhc3 sponging microRNA­93­3p is involved in the regulation of chondrocyte function by mechanical instability in osteoarthritis.

Cartilage extracellular matrix (ECM) metabolism disorder caused by mechanical instability is a leading cause of osteoarthritis (OA), but the exact mechanisms have not been fully elucidated. Recent studies have suggested an important role of circular RNAs (circRNAs/circs) in OA. The present study aimed to investigate whether circRNAs might have a role in mechanical instability­regulated chondrocyte matrix metabolism in OA. The expression levels of circPhc3 in human and mouse OA cartilage samples were measured using reverse transcription­quantitative PCR and fluorescence in situ hybridization. The effects of circPhc3 on chondrocyte ECM metabolism were further investigated by overexpressing and knocking down circPhc3 in OA chondrocytes. The downstream target of circPhc3 was examined by performing a luciferase reporter assay. The results showed that the expression of circPhc3 was reduced in human and mouse OA cartilage. Moreover, circPhc3 was involved in mechanical loading­regulated production of ECM and cartilage­degrading enzymes. Further studies showed that circPhc3 regulated chondrocyte matrix metabolism primarily by binding to microRNA (miR)­93­3p, and mechanistic studies found that miR­93­3p targeting of FoxO1 was involved in chondrocyte matrix metabolism. Taken together, these results indicated that circPhc3 may serve an important role in the progression of OA and may be a good target for the treatment of OA.

Remodeling of Architected Mesenchymal Microtissues Generated on Mechanical Metamaterials.

Mechanical metamaterials constitute a nascent category of architected structures comprising arranged periodic components with tailored geometrical features. These materials are now being employed as advanced medical implants due to their extraordinary mechanical properties over traditional devices. Nevertheless, to achieve desired tissue integration and regeneration, it is critical to study how the microarchitecture affects interactions between metamaterial scaffolds and living biological tissues. Based on human induced pluripotent stem cell technology and multiphoton lithography, we report the establishment of an in vitro microtissue model to study the integration and remodeling of human mesenchymal tissues on metamaterial scaffolds with different unit geometries. Microtissues showed distinct tissue morphologies and cellular behaviors between architected octet-truss and bowtie structures. Under the active force generated from mesenchymal tissues, the octet-truss and bowtie metamaterial scaffolds demonstrated unique instability phenomena, significantly different from uniform loading using conventional mechanical testing.

Complex pathways and memory in compressed corrugated sheets.

The nonlinear response of driven complex materials-disordered magnets, amorphous media, and crumpled sheets-features intricate transition pathways where the system repeatedly hops between metastable states. Such pathways encode memory effects and may allow information processing, yet tools are lacking to experimentally observe and control these pathways, and their full breadth has not been explored. Here we introduce compression of corrugated elastic sheets to precisely observe and manipulate their full, multistep pathways, which are reproducible, robust, and controlled by geometry. We show how manipulation of the boundaries allows us to elicit multiple targeted pathways from a single sample. In all cases, each state in the pathway can be encoded by the binary state of material bits called hysterons, and the strength of their interactions plays a crucial role. In particular, as function of increasing interaction strength, we observe Preisach pathways, expected in systems of independently switching hysterons; scrambled pathways that evidence hitherto unexplored interactions between these material bits; and accumulator pathways which leverage these interactions to perform an elementary computation. Our work opens a route to probe, manipulate, and understand complex pathways, impacting future applications in soft robotics and information processing in materials.

Buckling of Arteries With Noncircular Cross Sections: Theory and Finite Element Simulations.

The stability of blood vessels is essential for maintaining the normal arterial function, and loss of stability may result in blood vessel tortuosity. The previous theoretical models of artery buckling were developed for circular vessel models, but arteries often demonstrate geometric variations such as elliptic and eccentric cross-sections. The objective of this study was to establish the theoretical foundation for noncircular blood vessel bent (i.e., lateral) buckling and simulate the buckling behavior of arteries with elliptic and eccentric cross-sections using finite element analysis. A generalized buckling equation for noncircular vessels was derived and finite element analysis was conducted to simulate the artery buckling behavior under lumen pressure and axial tension. The arterial wall was modeled as a thick-walled cylinder with hyper-elastic anisotropic and homogeneous material. The results demonstrated that oval or eccentric cross-section increases the critical buckling pressure of arteries and having both ovalness and eccentricity would further enhance the effect. We conclude that variations of the cross-sectional shape affect the critical pressure of arteries. These results improve the understanding of the mechanical stability of arteries.

Lack of Definition of Chronic Ankle Instability With Arthrometer-Assisted Ankle Joint Stress Testing: A Systematic Review of In Vivo Studies.

Despite extensive research on ankle instability a consensual and clear objective definition for pathological mechanical lateral ankle instability is yet to be determined. This systematic review aimed to summarize current available arthrometric devices, measuring methods and lateral ankle laxity outcomes in patients with chronic ankle instability that underwent objective arthrometric stress measurement. Sixty-eight studies comprising a total of 3,235 ankles with chronic ankle instability were included. Studies reported a wide range of arthrometric devices, testing position and procedures, and measuring methods. For the anterior drawer test, the average mean differences between injured and uninjured ankles ranged from -0.9 to 4.1 mm, and total translation in the injured ankle from 3.2 to 21.0 mm. Most common pathological threshold was ≥4 mm or ≥10 mm unilaterally and ≥3 mm bilaterally. For the talar tilt test, the average mean differences between injured and uninjured ankles ranged from 0.0° to 8.0°, and total tilt from injured ankle from 3.3 to 60.2°. Most common pathological threshold was ≥ 10° unilaterally and ≥ 6° mm bilaterally. It was found high heterogeneity in the scientific literature regarding the arthrometric devices, use of concomitant imaging and measuring methods of arthrometer-assisted anterior drawer and talar tilt tests which led to variable laxity outcomes in individuals with chronic ankle instability. Future studies should focus on standardizing the testing and measuring methods for an objective definition of mechanical ankle instability.

The anterior talofibular ligament-posterior talofibular ligament angle decreased after ankle lateral stabilization surgery.

PURPOSE: The angle between the anterior talofibular ligament (ATFL) and the posterior talofibular ligament (PTFL) is increased in patients with chronic ATFL injury. This study aimed to compare the AFTL-PTFL angle before versus after ankle lateral stabilization surgery, and to evaluate whether the ATFL-PTFL angle correlates with the ligament injury severity. METHODS: This retrospective study included 48 patients with mechanical ankle instability treated between 2016 and 2018. After arthroscopic evaluation, all patients underwent ankle lateral stabilization surgery comprising ligament repair (n = 28) or reconstruction (n = 20). The ATFL-PTFL angle was measured in the axial plane on pre- and postoperative MRI. Comparisons were made of the pre- versus postoperative ATFL-PTFL angles, and the ATFL-PTFL angle of the repair versus reconstruction groups. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the ATFL-PTFL angle in selecting the surgical technique. RESULTS: The postoperative ATFL-PTFL angle was significantly decreased compared with preoperatively. The ATFL-PTFL angle was significantly smaller in the repair group than the reconstruction group preoperatively and postoperatively. The area under the ROC curve was 0.741 (P < 0.01). The optimal cutoff point for the selection of ligament reconstruction was an ATFL-PTFL angle of 89.4° (sensitivity 0.85, specificity 0.61). CONCLUSION: The ATFL-PTFL angle decreases after ankle lateral stabilization surgery. The ATFL-PTFL angle is related to the severity of the ATFL injury. Ankle lateral ligament reconstruction should be considered when the ATFL-PTFL angle is > 89.4°. LEVEL OF EVIDENCE: Level III.

Buckling and Torsional Instabilities of a Nanoscale Biological Rope Bound to an Elastic Substrate.

Rope-like structures are ubiquitous in Nature. They are supermolecular assemblies of macromolecules responsible for the structural and mechanical integrity of plant and animal tissues. Collagen fibrils with diameters between 50 and 500 nm and their helical supermolecular structure are good examples of such nanoscale biological ropes. Like man-made laid ropes, fibrils are typically loaded in tension, and due to their large aspect ratio, they are, in principle, prone to buckling and torsional instabilities. One way to study buckling of a rigid rod is to attach it to a stretched elastic substrate that is then returned to its original length. In the case of single collagen fibrils, the observed behavior depends on the degree of hydration. By going from buckling in ambient conditions to immersed in a buffer, fibrils go from the well-known sine wave response to a localized behavior reminiscent of the bird-caging of laid ropes. In addition, in ambient conditions, the sine wave response coexists with the formation of loops along the length of the fibrils, as observed for the torsional instability of a twisted filament when tension is decreased. This work provides direct evidence that single collagen fibrils are highly susceptible to axial compression because of their helical supermolecular structure. As a result, mammals that use collagen fibrils as their main load-bearing element in many tissues have evolved mitigating strategies that protect single fibrils from axial compression damage.

Skipping Pedicle Screw Insertion Into Infected Vertebra is a Risk Factor for Revision Surgery for Pyogenic Spondylitis in the Lower Thoracic and Lumbar Spine.

BACKGROUND: Surgical intervention for pyogenic spondylitis is indicated when conservative treatment fails and biomechanical instability persists. Whether to insert pedicle screws into all vertebrae, including the most erosive vertebrae, or whether to skip 1 vertebra in pedicle screw insertion remains controversial. METHODS: A single-institution retrospective cohort study was conducted in consecutive patients with pyogenic spondylitis in the lower thoracic and lumbar spine (T9-S1) between January 2008 and December 2016. The patients were treated with interbody fusion plus posterior stabilization using pedicle screws and were divided into 2 groups as follows: (1) patients in whom 1 vertebra, usually the most erosive, was skipped in pedicle screw insertion (Group Skipping) and (2) pedicle screw insertion into all vertebrae (Group All). Patients' operation data were evaluated, and clinical outcomes were compared between the 2 groups. There were no significant differences between the 2 groups in terms of age, sex, past histories, blood loss, operation time, the presence of abscesses, or operative approach. RESULTS: The length of fixation was greater by 1 vertebral level in the Group Skipping than in the Group All, and the rate of revision surgery for pseudarthrosis was higher in the Group Skipping than in the Group All (P = .02). There was no statistically significant difference between the 2 groups in terms of the mean segmental lordotic angle or Barthel Index. CONCLUSIONS: Skipping pedicle screw insertion for pyogenic spondylitis in posterior fixation led to an increased number of fixed vertebrae and may be a risk factor for revision surgery for pseudarthrosis. LEVEL OF EVIDENCE: 4. CLINICAL RELEVANCE: The insertion of short pedicle screws at the infected vertebra can prevent early treatment failure and increase the biomechanical stability of construct.

Increased ATFL-PTFL angle could be an indirect MRI sign in diagnosis of chronic ATFL injury.

PURPOSE: Magnetic resonance imaging (MRI) has relatively low accuracy in diagnosing chronic anterior talofibular ligament (ATFL) injury. This study's purpose was to evaluate the angle between the ATFL and posterior talofibular ligament (PTFL) as a new indirect MRI sign of chronic ATFL injury in patients with mechanical ankle instability (MAI). METHODS: This study included 200 participants: 105 patients with MAI and 95 patients seen at our institution for reasons unrelated to ankle instability. MR images of all 200 participants were reviewed. The ATFL-PTFL angle in the axial plane was measured and compared between groups. Receiver operating characteristic curves (ROC) were used to analyze ATFL-PTFL angles in participants with and without ATFL injury. The sensitivity and specificity of this method for diagnosing ATFL injury were calculated. RESULTS: The mean ATFL-PTFL angle was significantly larger among MAI patients than among control patients (81.5° ± 9.8° vs 75.2° ± 8.9°, respectively; P < 0.01). The area under the ROC was 0.789 (P < 0.01). The optimal cut-off point for diagnosing ATFL injury on the basis of the ATFL-PTFL angle was 79.0° (sensitivity 0.89, specificity 0.67). CONCLUSION: The ATFL-PTFL angle was significantly larger among MAI patients than among those without MAI. Increased ATFL-PTFL angle offers a new indirect MRI sign for diagnosing chronic ATFL injury. The ATFL-PTFL angle can be used not only to improve the accuracy of diagnosis of chronic ATFL injury, but also to evaluate the restoration of normal ankle joint geometry after lateral ligament reconstruction. LEVEL OF EVIDENCE: III.

Computational simulations of the helical buckling behavior of blood vessels.

Tortuous vessels are often observed in vivo and could hinder or even disrupt blood flow to distal organs. Besides genetic and biological factors, the in vivo mechanical loading seems to play a role in the formation of tortuous vessels, but the mechanism for formation of helical vessel shape remains unclear. Accordingly, the aim of this study was to investigate the biomechanical loads that trigger the occurrence of helical buckling in blood vessels using finite element analysis. Porcine carotid arteries were modeled as thick-walled cylindrical tubes using generalized Fung and Holzapfel-Gasser-Ogden constitutive models. Physiological loadings, including axial tension, lumen pressure, and axial torque, were applied. Simulations of various geometric dimensions, different constitutive models and at various levels of axial stretch ratios, lumen pressures, and twist angles were performed to identify the mechanical factors that determine the helical stability. Our results demonstrated that axial torsion can cause wringing (twist buckling) that leads to kinking or helical coiling and even looping and winding. The specific buckling patterns depend on the combination of lumen pressure, axial torque, axial tension, and the dimensions of the vessels. This study elucidates the mechanism of how blood vessels buckle under various mechanical loads and how complex mechanical loads yield helical buckling.

Intra- and interobserver reliability of the Spinal Instability Neoplastic Score system for instability in spine metastases: a systematic review and meta-analysis.

Mechanical instability is one of the two main indications for surgical intervention in patients with metastatic spine disease. Since its publication in 2010, the Spinal Instability Neoplastic Score (SINS) has been the most commonly used means of assessing mechanical instability. To prove clinically valuable though, diagnostic tests must demonstrate consistency across measures and across observers. Here we report a systematic review and meta-analysis of all prior reports of intraobserver and interobserver reliability of the SINS score. To identify articles, we queried the PubMed, CINAHL, EMBASE, Cochrane, and Web of Science databases for all full-text English articles reporting interobserver or intraobserver reliability for the SINS score, category, or a domain of the SINS score. Articles reporting confidence intervals for these metrics were then subjected to meta-analysis to identify pooled estimates of reliability. Of 167 unique studies identified, seven met inclusion criteria and were subjected to qualitative review and meta-analysis. Intraobserver reliability for SINS score was found to be near perfect [estimate =0.815; 90% CI (0.661-0.969)] and interobserver reliability was substantial [0.673; (0.227-1.12)]. Intraobserver and interobserver reliability among spine surgeons was significantly better than reliability across all observers (both P<0.0001). Qualitative analysis suggested that increased surgeon experience may be associated with greater intraobserver and interobserver reliability among spine surgeons. On the whole, meta-analysis of the available literature suggests SINS to have good intraobserver and interobserver reliability, giving it the potential to be a valuable guide to the management of patients with spinal metastases. Further research is required to demonstrate that SINS score correlates with the clinical decision to stabilize.