Andriy Noshchenko

Predictors of spine deformity progression in adolescent idiopathic scoliosis: A systematic review with meta-analysis

AIM To evaluate published data on the predictors of progressive adolescent idiopathic scoliosis (AIS) in order to evaluate their efficacy and level of evidence. METHODS SELECTION CRITERIA (1) study design: randomized controlled clinical trials, prospective cohort studies and case series, retrospective comparative and none comparative studies; (2) participants: adolescents with AIS aged from 10 to 20 years; and (3) treatment: observation, bracing, and other. SEARCH METHOD Ovid MEDLINE, Embase, the Cochrane Library, PubMed and patent data bases. All years through August 2014 were included. Data were collected that showed an association between the studied characteristics and the progression of AIS or the severity of the spine deformity. Odds ratio (OR), sensitivity, specificity, positive and negative predictive values were also collected. A meta-analysis was performed to evaluate the pooled OR and predictive values, if more than 1 study presented a result. The GRADE approach was applied to evaluate the level of evidence. RESULTS The review included 25 studies. All studies showed statistically significant or borderline association between severity or progression of AIS with the following characteristics: (1) An increase of the Cobb angle or axial rotation during brace treatment; (2) decrease of the rib-vertebral angle at the apical level of the convex side during brace treatment; (3) initial Cobb angle severity (> 25(o)); (4) osteopenia; (5) patient age < 13 years at diagnosis; (6) premenarche status; (7) skeletal immaturity; (8) thoracic deformity; (9) brain stem vestibular dysfunction; and (10) multiple indices combining radiographic, demographic, and physiologic characteristics. Single nucleotide polymorphisms of the following genes: (1) calmodulin 1; (2) estrogen receptor 1; (3) tryptophan hydroxylase 1; (3) insulin-like growth factor 1; (5) neurotrophin 3; (6) interleukin-17 receptor C; (7) melatonin receptor 1B, and (8) ScoliScore test. Other predictors included: (1) impairment of melatonin signaling in osteoblasts and peripheral blood mononuclear cells (PBMC); (2) G-protein signaling dysfunction in PBMC; and (3) the level of platelet calmodulin. However, predictive values of all these findings were limited, and the levels of evidence were low. The pooled result of brace treatment outcomes demonstrated that around 27% of patents with AIS experienced exacerbation of the spine deformity during or after brace treatment, and 15% required surgical correction. However, the level of evidence is also low due to the limitations of the included studies. CONCLUSION This review did not reveal any methods for the prediction of progression in AIS that could be recommended for clinical use as diagnostic criteria.

Perioperative and long-term clinical outcomes for bone morphogenetic protein versus iliac crest bone graft for lumbar fusion in degenerative disk disease: systematic review with meta-analysis.

Study Design: Systematic review with meta-analysis. Objectives: To compare the perioperative and long-term postoperative effectiveness of bone morphogenetic protein (BMP) for lumbar arthrodesis in skeletally mature adults with degenerative disk disease (DDD) to that of the current golden standard treatment, iliac crest autologous bone graft (ICBG). Summary of Background Data: The treatment efficacy of lumbar arthrodesis in DDD is a complex clinical and economic issue for patients and health care providers. Methods: Comprehensive electronic literature search was performed using following databases: Ovid MEDLINE; Embase; Cochrane Library; Central Register of Controlled Trials (CENTRAL); Database of Abstracts of Reviews of Effects; Methodology Register; Technology Assessment Database; and Economic Evaluation Database. The full year ranges of each database until May of 2012 were included. Results: Eight randomized controlled clinical trials of 383 citations were selected. The included studies involved 1138 participants. The pooled 2-year postoperative clinical outcomes were equivalent in BMP and ICBG groups, and exceeded minimum clinically important differences for Oswestry Disability Index, SF-36 (physical scale), and numeric rating scale (back pain). ICBG was associated with increased pain and complications at the donor site (P<0.01). The pooled average operative time was 21 minutes less in BMP versus ICBG (P<0.001). The pooled rate of additional surgical treatment was 2 times less in the BMP than in the ICBG groups (P=0.006). The pooled risk of nonunion at 24-month follow-up was 2 times less in the BMP than in the ICBG groups (P=0.037), however, this effect was likely biased. Conclusions: BMP, in particular rhBMP-2, is a good alternative to autogenous bone graft, especially in cases when harvesting of autologous bone is contraindicated or undesirable, operation time is limited, and there are no contraindications for BMP use. However, the current study did not reveal evidence robust enough to develop strong medical recommendations concerning BMP use for lumbar arthrodesis in degenerative disk disease.

Evaluation of spinal instrumentation rod bending characteristics for In-Situ contouring

Bending characteristics were studied in rods used for spinal instrumentation at in-situ contouring conditions. Five groups of five 6 mm diameter rods made from: cobalt alloy (VITALLIUM), titanium-aluminum-vanadium alloy (SDI™), β-titanium alloy (TNTZ), cold worked stainless steel (STIFF), and annealed stainless steel (MALLEABLE) were studied. The bending procedure was similar to that typically applied for in-situ contouring in the operating room and included two bending cycles: first--bending to 21-24° under load with further release of loading for 10 min, and second--bending to 34-37° at the previously bent site and release of load for 10 min. Applied load, bending stiffness, and springback effect were studied. Statistical evaluation included ANOVA, correlation and regression analysis. TNTZ and SDI™ rods showed the highest (p < 0.05) springback at both bending cycles. VITALLIUM and STIFF rods showed mild springback (p < 0.05). The least (p < 0.05) springback was observed in the MALLEABLE rods. Springback significantly correlated with the bend angle under load (p < 0.001). To reach the necessary bend angle after unloading, over bending should be 37-40% of the required angle in TNTZ and SDI™ rods, 27-30% in VITALLIUM and STIFF rods, and around 20% in MALLEABLE rods.

Long-term Treatment Effects of Lumbar Arthrodeses in Degenerative Disk Disease: A Systematic Review With Meta-Analysis.

Study Design: Systematic review with meta-analysis. Objective: To (1) evaluate long-term patient-centered clinical outcomes after lumbar arthrodesis with or without decompression for lumbar spondylosis (LS); and (2) compare these outcomes with those of alternative treatments, including nonsurgical and surgical which maintain mobility of the lumbar spine. Summary of Background Data: The effective treatment of LS is a complex clinical and economic concern for patients and health care providers. Methods: Selection criteria: (1) randomized controlled clinical trials (RCTs) comparing treatment effects of lumbar arthrodesis with other interventions; (2) participants: skeletally mature adults with lumbar degenerative disk disease. Search methods: Ovid MEDLINE, Embase, the Cochrane Library, and others. All years through February of 2013 were included. Patient-centered clinical outcomes before treatment, at 12, 24, or >24 months of follow-up, and rate of complications and additional surgical treatment were collected. A meta-analysis was performed to evaluate pooled treatment effects. The GRADE approach was applied to evaluate the level of evidence. Results: The review included 38 studies of 5738 participants. All studies showed strong or at least moderate treatment effects of lumbar arthrodesis at 12, 24, and 48–72 months of follow-up. The level of evidence was moderate at 12 and 24 months, and low at 48–72 months. The pooled long-term treatment effect of lumbar arthrodesis exceeded those of: nonsurgical treatment (P<0.0001) with a moderate level of evidence, and decompression without fusion (P=0.005) with a low level of evidence. The treatment effect of lumbar arthrodesis showed a small inferiority versus arthroplasty at 12 and 24 months of follow-up (P<0.001), but not after 24 months postoperative. Conclusions: This review indicates that surgical stabilization of the lumbar spine is an effective treatment for LS; in particular, for patients with severe chronic low back pain that has been resistant to ≥3 months of conservative therapy.

Nucleus replacement device failure: a case report and biomechanical study.

Study Design. Case report and biomechanical study. Objective. The objectives of this study were to report on a single case of a failed nucleus replacement device and to test the biomechanical properties of the failed device. Summary of Background Data. The use of spine arthroplasty techniques in the treatment of degenerative disc disease is becoming a popular alternative to spinal fusion and discectomy. Nucleus replacement is an emerging surgical treatment that is in the early stages of development. Methods. A 36-year-old woman presented to our institution with excruciating low back pain 15 months after receiving a prosthetic disc nucleus (PDN; Raymedica, Inc.) at L5–S1 as part of an IDE clinical trial. A computed tomography scan showed subsidence of the PDN into the endplates and asymmetric collapse of the L5–S1 disc space. The patient underwent surgery for removal of the device and fusion of L5–S1. After removal, the nucleus replacement device underwent micro-computed tomography imaging and was tested in unconfined and confined compression. Results. The density of the inner core of the PDN was estimated to be 105 g/cm3. Compression testing revealed that the stiffness of the PDN was grossly elevated in comparison to previously published values for human lumbar nuclei and other candidate nucleus replacement hydrogels. The linear-region modulus values were 0.94 MPa for unconfined compression and 32.4 MPa for confined compression. Conclusion. The PDN device excised from this patient failed to reproduce the function of a healthy nucleus. Because preoperative mechanical values were not available for this device, it is difficult to know if the PDN was abnormally stiff at implantation or if it became increasingly stiff after implantation. Whether this was a result of manufacturing, the patients biologic response to the PDN, or some yet unknown contraindication to PDN placement in this specific patient is unclear.

Correlation of Vertebral Strength Topography With 3-Dimensional Computed Tomographic Structure

Study Design. Biomechanical and radiographical study. Objective. To test the hypothesis that stiffness and strength at discrete sites of human lumbar vertebrae depend on the 3-dimentional structure and density of the vertebral-body bone elements, and can be evaluated using models based on vertebral bone characteristics obtained from quantitative computed tomogrphy. Summary of Background Data. We have not found published methods that allow in vivo evaluation of bone mechanical properties at discrete sites of vertebral body applicable for clinical use. We hypothesize that human lumbar vertebral strength topography depends on the local 3-dimensional structural features of the bone structure, and that the stiffness and strength can be evaluated at discrete sites using models based on data obtained from quantitative computed tomographic (CT) images. Methods. Forty-eight vertebrae (8 L1, 8 L2, 8 L3, 10 L4, and 14 L5) from 14 cadaveric subjects (9 men and 5 women; age, 43–99 yr) were studied. Stiffness (modulus of elasticity) and strength (maximum load and maximum tolerable pressure) were defined by an indentation test at 11 discrete sites on the cranial and caudal surfaces of each vertebral endplate. Before the indentation test radiography, dual-energy x-ray absorptiometry, micro-CT, and conventional-CT (con-CT) of the vertebrae were performed. Micro-CT characteristics of cortical and cancellous bones of 18 vertebrae were measured at each region of interest defined by a 3-dimensional coordinate system. The most informative indices regarding endplate strength were selected by correlation analysis. Predictive models of local stiffness and strength were created using selected indices obtained by micro-CT and con-CT (40 vertebrae) images. Results. Local stiffness and strength of the tested specimens were highly variable. Endplate thickness and density in combination with adjacent trabecular bone density, existence of endplate defects, and subjects age were good predictors of local stiffness and strength, applicable for con-CT. Polynomial multiple regression of these characteristics provides the best correlation with stiffness (r2 = 0.82; P < 0.001) and strength (r2 = 0.74). Conclusion. Stiffness and strength at discrete sites of human lumbar vertebrae depend on the superficial vertebral bone structure and density and can be evaluated using models based on quantitative analysis of micro-CT and con-CT images.

Strain in Posterior Instrumentation Resulted by Different Combinations of Posterior and Anterior Devices for Long Spine Fusion Constructs

STUDY DESIGN Clinically related experimental study. OBJECTIVE Evaluation of strain in posterior low lumbar and spinopelvic instrumentation for multilevel fusion resulting from the impact of such mechanical factors as physiologic motion, different combinations of posterior and anterior instrumentation, and different techniques of interbody device implantation. Currently different combinations of posterior and anterior instrumentation as well as surgical techniques are used for multilevel lumbar fusion. Their impact on risk of device failure has not been well studied. Strain is a well-known predictor of metal fatigue and breakage measurable in experimental conditions. METHODS Twelve human lumbar spine cadaveric specimens were tested. Following surgical methods of lumbar pedicle screw fixation (L2-S1) with and without spinopelvic fixation by iliac bolt (SFIB) were experimentally modeled: posterior (PLF); transforaminal (TLIF); and a combination of posterior and anterior interbody instrumentation (ALIF+PLF) with and without anterior supplemental fixation by anterior plate or diverging screws through an integrated plate. Strain was defined at the S1 screws, L5-S1 segment of posterior rods, and iliac bolt connectors; measurement was performed during flexion, extension, and axial rotation in physiological range of motion and applied force. RESULTS The highest strain was observed in the S1 screws and iliac bolt connectors specifically during rotation. The S1 screw strain was lower in ALIF+PLF during sagittal motion but not rotation. Supplemental anterior fixation in ALIF+PLF diminished the S1 strain during extension. Strain in the posterior rods was higher after TLIF and PLF and was increased by SFIB; this strain was lowest after ALIF+PLF, as supplemental anterior fixation diminished the strain during extension, in particular, cages with anterior screws more than anterior plate. Strain in the iliac bolt connectors was mainly determined by direction of motion. CONCLUSIONS Different devices modify strain in low posterior instrumentation, which is higher after transforaminal and posterior techniques, specifically with spinopelvic fixation. LEVEL OF EVIDENCE N/A.STUDY DESIGN Clinically related experimental study. OBJECTIVE Evaluation of strain in posterior low lumbar and spinopelvic instrumentation for multilevel fusion resulting from the impact of such mechanical factors as physiologic motion, different combinations of posterior and anterior instrumentation, and different techniques of interbody device implantation. SUMMARY OF BACKGROUND DATA Currently different combinations of posterior and anterior instrumentation as well as surgical techniques are used for multilevel lumbar fusion. Their impact on risk of device failure has not been well studied. Strain is a well-known predictor of metal fatigue and breakage measurable in experimental conditions. METHODS Twelve human lumbar spine cadaveric specimens were tested. Following surgical methods of lumbar pedicle screw fixation (L2-S1) with and without spinopelvic fixation by iliac bolt (SFIB) were experimentally modeled: posterior (PLF); transforaminal (TLIF); and a combination of posterior and anterior interbody instrumentation (ALIF+PLF) with and without anterior supplemental fixation by anterior plate or diverging screws through an integrated plate. Strain was defined at the S1 screws, L5-S1 segment of posterior rods, and iliac bolt connectors; measurement was performed during flexion, extension, and axial rotation in physiological range of motion and applied force. RESULTS The highest strain was observed in the S1 screws and iliac bolt connectors specifically during rotation. The S1 screw strain was lower in ALIF+PLF during sagittal motion but not rotation. Supplemental anterior fixation in ALIF+PLF diminished the S1 strain during extension. Strain in the posterior rods was higher after TLIF and PLF and was increased by SFIB; this strain was lowest after ALIF+PLF, as supplemental anterior fixation diminished the strain during extension, in particular, cages with anterior screws more than anterior plate. Strain in the iliac bolt connectors was mainly determined by direction of motion. CONCLUSIONS Different devices modify strain in low posterior instrumentation, which is higher after transforaminal and posterior techniques, specifically with spinopelvic fixation. LEVEL OF EVIDENCE N/A.

What Is the Clinical Relevance of Radiographic Nonunion After Single-Level Lumbar Interbody Arthrodesis in Degenerative Disc Disease?: A Meta-Analysis of the YODA Project Database.

Study Design. Meta-analysis of 4 randomized controlled clinical trials (RCTs). Objective. The aim of the study was to determine if patients with degenerative disc disease who achieve radiographic fusion after single-level lumbar interbody arthrodesis have better clinical outcomes than patients with radiographic pseudarthrosis at 12 and 24 months postoperative. Summary of Background Data. The clinical relevance of successful fusion after lumbar arthrodesis with recombinant human bone morphogenetic protein-2 or iliac crest bone autograft has recently been questioned in the literature. Methods. Individual patient-level data of 4 RCTs were obtained from the Yale University Open Data Access Project project and analyzed. Clinical outcomes (Oswestry Disability Index [ODI]; Numeric Rating Scales [NRSs] for back and leg pain) were compared between patients with radiographically confirmed fusion and those with radiographic nonunion 1 and 2 years postoperative. The results of each study were first analyzed separately, and then were pooled by meta-analysis. The GRADE approach was applied to evaluate the level of evidence. Results. A total of 496 patients with clinical and radiographic data at 1- and 2-year follow-ups were identified. Of these, 5.5% (95% confidence interval: 3.7; 8.3) had radiographic nonunion which did not require reoperation. Patients with fusion had better improvements in ODI (P < 0.001) and NRS back pain scores (P < 0.001). The overall percentage of fused patients with ODI and NRS back pain scores that exceeded the criteria for minimal clinically important differences was also significantly higher than that of patients with nonunion (ODI, odds ratio [OR] = 2.7, P = 0.019; NRS back pain, OR = 3.5, P = 0.033). The predictive values of fusion for clinical outcomes, however, were poor, with low specificity and low negative predictive values. Conclusion. The presence of radiographic fusion is clinically significant, as patients with fusion had better clinical outcomes at 1 and 2 years postoperative than those with nonunion; however, patient-centered clinical outcomes should also be taken into consideration as independent, complimentary variables when assessing treatment success. Level of Evidence: 1

Early Experience and Initial Outcomes With Patient-Specific Spine Rods for Adult Spinal Deformity

The objectives of this study were to describe the process of preoperative planning and using patient-specific rods. This retrospective case series involved 18 patients with adult spinal deformity who were treated with posterior instrumentation and spine fusion, with lumbar or thoracic osteotomies, using patient-specific rods. Data extracted included demographic/surgical variables and preoperative, predicted (surgical plan), and postoperative spinopelvic parameters. The outcome analysis involved assessment of preoperative, planned, and postoperative variables. Treatment effect evaluation involved assessing differences between preoperative and postoperative values and correspondence between planned and achieved results. Surgery using preoperative planned patient-specific rods led to excellent adult spinal deformity correction and spinopelvic alignment.

Ultrastructure of Intervertebral Disc and Vertebra-Disc Junctions Zones as a Link in Etiopathogenesis of Idiopathic Scoliosis

Background Context. There is no general accepted theory on the etiology of idiopathic scoliosis (IS). An important role of the vertebrae endplate physes (VEPh) and intervertebral discs (IVD) in spinal curve progression is acknowledged, but ultrastructural mechanisms are not well understood. Purpose. To analyze the current literature on ultrastructural characteristics of VEPh and IVD in the context of IS etiology. Study Design/Setting. A literature review. Results. There is strong evidence for multifactorial etiology of IS. Early wedging of vertebra bodies is likely due to laterally directed appositional bone growth at the concave side, caused by a combination of increased cell proliferation at the vertebrae endplate and altered mechanical properties of the outer annulus fibrosus of the adjacent IVD. Genetic defects in bending proteins necessary for IVD lamellar organization underlie altered mechanical properties. Asymmetrical ligaments, muscular stretch, and spine instability may also play roles in curve formation. Conclusions. Development of a reliable, cost effective method for identifying patients at high risk for curve progression is needed and could lead to a paradigm shift in treatment options. Unnecessary anxiety, bracing, and radiation could potentially be minimized and high risk patient could receive surgery earlier, rendering better outcomes with fewer fused segments needed to mitigate curve progression.