Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

Thoracic kyphosis in light of lumbosacral alignment in thoracic adolescent idiopathic scoliosis: recognition of thoracic hypokyphosis and therapeutic implications.

BACKGROUND: The uniqueness of spinal sagittal alignment in thoracic adolescent idiopathic scoliosis (AIS), for example, the drastically smaller thoracic kyphosis seen in some patients, has been recognized but not yet fully understood. The purpose of this study was to clarify the characteristics of sagittal alignment of thoracic AIS and to determine the contributing factors. METHODS: Whole spine radiographs of 83 thoracic AIS patients (73 females) were analyzed. The measured radiographic parameters were the Cobb angle of thoracic scoliosis, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (C7 SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Additionally, max-LL, which was defined as the maximum lordosis angle from the S1 endplate, the inflection point between thoracic kyphosis and lumbar lordosis, and the SVA of the inflection point (IP SVA) were measured. The factors significantly related to a decrease in TK were assessed by stepwise logistic regression analysis. In addition, cluster analysis was performed to classify the global sagittal alignment. RESULTS: The significant factors for a decrease in TK were an increase in SS (p = 0.0003, [OR]: 1.16) and a decrease in max-LL (p = 0.0005, [OR]: 0.89). According to the cluster analysis, the global sagittal alignment was categorized into the following three types: Type 1 (low SS, low max-LL, n = 28); Type 2 (high SS, low max-LL, n = 22); and Type 3 (high SS, high max-LL, n = 33). CONCLUSIONS: In thoracic AIS, a decreased TK corresponded to an increased SS or a decreased max-LL. The sagittal alignment of thoracic AIS patients could be classified into three types based on SS and max-LL. One of these three types includes the unique sagittal profile of very small TK.

Japanese orthopaedic association cervical myelopathy evaluation questionnaire (JOACMEQ): Part 5. Determination of responsiveness.

BACKGROUND: In 1999, the Japanese Orthopaedic Association decided to develop a new Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). The final version of the JOACMEQ, comprising 24 questions and five domains (cervical spine function (CF); upper extremity function (UF); lower extremity function (LF); bladder function (BF); and quality of life (QOL)), was established after three nationwide investigations. The fourth investigation, reported in this paper, was performed to confirm the responsiveness of the questionnaire. METHODS: A total of 137 patients with cervical myelopathy were included in the study. Each patient was interviewed twice using the JOACMEQ before and after treatment. At the second interview, the patients self-rated their condition in five domains for "worse," "somewhat worse," "no change," "somewhat better," or "better," and these scores were defined as the external assessment rating. The difference of the points in five domains between the first and the second interview was calculated against each external assessment. Based on the results, substantial clinical benefit (SCB) thresholds for the JOACMEQ were determined. RESULTS: The statistically significant median values of the acquired points were 17.5 for CF, 16.0 and 21.0 for UF, 27.0 and 20.5 for LF, 13.0 for BF, and 29.0 for QOL. After consideration of the results, the committee decided that an acquired point ≥20 could be interpreted as representing an SCB threshold for the JOACMEQ. CONCLUSION: We have concluded that a treatment can be judged to be effective for a patient if 1) The patient give all answers for the questions necessary to calculate the functional score of a domain and an increase of ≥20 points is obtained for that score, or 2) The functional score after treatment is > 90 points even if the answer for the unanswered questions was supposed to be the worst possible choice.

Osseointegration improves bone-implant interface of pedicle screws in the growing spine: a biomechanical and histological study using an in vivo immature porcine model.

PURPOSE: Implant failure is a frequent complication in corrective surgery for early onset scoliosis, since considerable forces are acting on small and fragile vertebrae. Osseointegration showing biomechanical and histological improvement in bone-implant interface (BII) after dental implant placement has been well investigated. However, there are no studies regarding osseointegration in immature vertebral bone. The purpose was to evaluate the timecourse of biomechanical and histological changes at BII after pedicle screw placement using in vivo immature porcine model. METHODS: Ten immature porcine were instrumented with titanium pedicle screws in the thoracic spine. After a 0-, 2-, 4-, and 6-month survival periods, the spines were harvested at the age of 12 months. Histological evaluation of BII was conducted by bone volume/tissue volume (BV/TV) and bone surface/implant surface (BS/IS) measurements. Bone mineral density (BMD) measurement and biomechanical testing of BII were done. RESULTS: Contact surface and bone volume around the screw threads were significantly increased over the time. BV/TV and BS/IS were improved with statistically significant differences between 0- and ≥4-month (p ≤ 0.001) periods. BMD in all subjects was determined to be the same (p ≥ 0.350). Pullout strength was also increased over time with significant differences between 0- and ≥2-month (p ≤ 0.011) periods. CONCLUSION: Improved stability at BII caused by osseointegration was confirmed by in vivo immature porcine model. A two-stage operation is proposed based on the osseointegration theory, in which an implant is installed in advance in the vertebrae at the first stage and deformity correction surgery is performed after sufficient stability is obtained by osseointegration at a later stage.

Multiple concave rib head resection improved correction rate of posterior spine fusion in treatment of adolescent idiopathic scoliosis.

BACKGROUND: Hybrid constructs have been widely used to surgically correct thoracic adolescent idiopathic scoliosis (AIS). To enhance the correction obtained with hybrid constructs, we perform concave rib head resection and convex costovertebral release as posterior release procedures. The objective of the study was to evaluate coronal and sagittal curve correction in patients with adolescent idiopathic scoliosis (AIS) treated with hybrid constructs combined with concave rib head resection and convex transverse process resection as posterior release procedures. METHODS: The records of 24 patients with Lenke type 1 or 2 AIS treated with hybrid constructs combined with posterior release procedures were retrospectively reviewed. The mean age at surgery was 14.3 years. The mean follow-up period was 33.0 months (range, 24-60 months). Radiographs were evaluated before surgery, immediately postoperatively, and at latest follow-up. RESULTS: The average preoperative Cobb angle of the main thoracic (MT) curve was 58.1 ± 12.6° (range, 45-88°). The MT curve was corrected to 12.8 ± 9.0° (range, 0-38°) immediately after surgery. At the latest follow-up, the average Cobb angle was 13.6 ± 9.9° (range, 0-44°; correction, 77.5 ± 14.0%). The average loss of coronal correction was 0.8°. The average preoperative flexibility of the MT curve was 54.6 ± 17.4%. The average Cincinnati correction index was 1.53 ± 0.48 at the latest follow-up. The average preoperative thoracic kyphosis (TK) was 13.7 ± 12.0° (range, -12-34°). Immediately after surgery, TK was corrected to 18.6 ± 5.9° (range, 10-29°). At the latest follow-up, TK measured 18.1 ± 6.5° (range, 6-32°). CONCLUSIONS: Hybrid instrumentation combined with concave rib head resection and convex transverse process resection as posterior release procedures achieved satisfactory coronal and sagittal curve correction with little loss of correction at 2-year follow-up.

Verification of the sensitivity of functional scores for treatment results - Substantial clinical benefit thresholds for the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ).

BACKGROUND: Validity and reliability of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) had already been verified as the patients' self-rating assessment of low back pain and lumbar spinal disease and, the present study demonstrated the responsiveness of this measure. METHODS: 192 subjects who were determined by medical instructors of the Japanese Society for Spine Surgery and Related Research were analyzed. They had completed a series of treatment and both surveys before and after the treatment. Authors investigated rates of concordance between assessment by physicians and subjective assessment by patients. The mean, standard deviation, minimum, 25th percentile, median, 75th percentile and maximum values for pre-treatment, post-treatment, and acquired points were calculated, and then, we also investigated the trend between subjective assessment by patients and mean acquired points for each JOABPEQ domain and substantial clinical benefit thresholds for the JOABPEQ. RESULTS: Symptom changes as assessed by physicians did not coincide with those by patients, and acquired points in each JOABPEQ domain were significantly increased with improved self-rating by patients. In addition, patients who rated symptom changes as "slightly improved" showed a mean acquired points of ≥20, and those reporting "improved" showed a 25th percentile points of the acquired points of ≥20 approximately. CONCLUSION: A significant correlation was noted between the self-rating of patients and acquired points JOABPEQ, suggesting that ≥20 acquired points can be interpreted as substantial clinical benefit thresholds for the JOABPEQ.

Dynamic global sagittal alignment evaluated by three-dimensional gait analysis in patients with degenerative lumbar kyphoscoliosis.

PURPOSE: Sagittal vertical axis (SVA) is the most commonly used parameter for evaluating global sagittal alignment (GSA) in a static condition. However, its dynamic statuses remain unclear. The aim of this study was to evaluate dynamic GSA of degenerative lumbar kyphoscoliosis (DLKS) using three-dimensional motion analysis system (3D-MAS). METHODS: Twenty-six patients with DLKS underwent gait analysis using 3D-MAS. Static (S-) and dynamic (D-) trunk angle (TA) (the angle between the vertical axis and the line connecting C7 and S1 spinous processes) and S-sagittal trunk shift (STS) and D-STS (the distance between the two vertical lines running through C7 and S1 spinous process) were recorded during treadmill walking. Pelvic angle (PA) (the angle between the horizontal axis and the line connecting the posterior and anterior superior iliac spine) were also recorded. S-PA and D-PA represent retroversion or anteversion of the pelvis, which can be substituted for pelvic tilt. As to dynamic parameters, those at the initial five steps (Di) and the final five steps (Df) of treadmill walking were also recorded. RESULTS: The median S-TA, S-STS, and S-PA were 16.0°, 11.9 cm, and -5.5° (retroversion). The median D parameters were Di-TA/Df-TA 21.8°/26.9°; Di-STS/Df-STS 14.1/21.1 cm; and Di-PA/Df-PA 15.7°/22.8° (anteversion). All D parameters were significantly greater than S parameters (P < 0.01) and all Df parameters were also significantly worse than Di parameters (P < 0.001). Thus, compensated GSA by pelvic retroversion in static condition was lost due to anteversion change of the pelvis immediately after start of walking and worsened over time. CONCLUSION: Dynamic GSA assessment using 3D-MAS can avoid underestimation of GSA loss that is detected by static standing full-length radiography.

Optimum pelvic incidence minus lumbar lordosis value can be determined by individual pelvic incidence.

PURPOSE: Adult spinal deformity (ASD) classification showing that ideal pelvic incidence minus lumbar lordosis (PI-LL) value is within 10° has been received widely. But no study has focused on the optimum level of PI-LL value that reflects wide variety in PI among patients. This study was conducted to determine the optimum PI-LL value specific to an individual's PI in postoperative ASD patients. METHODS: 48 postoperative ASD patients were recruited. Spino-pelvic parameters and Oswestry Disability Index (ODI) were measured at the final follow-up. Factors associated with good clinical results were determined by stepwise multiple regression model using the ODI. The patients with ODI under the 75th percentile cutoff were designated into the "good" health related quality of life (HRQOL) group. In this group, the relationship between the PI-LL and PI was assessed by regression analysis. RESULTS: Multiple regression analysis revealed PI-LL as significant parameters associated with ODI. Thirty-six patients with an ODI <22 points (75th percentile cutoff) were categorized into a good HRQOL group, and linear regression models demonstrated the following equation: PI-LL = 0.41PI-11.12 (r = 0.45, P = 0.0059). CONCLUSIONS: On the basis of this equation, in the patients with a PI = 50°, the PI-LL is 9°. Whereas in those with a PI = 30°, the optimum PI-LL is calculated to be as low as 1°. In those with a PI = 80°, PI-LL is estimated at 22°. Consequently, an optimum PI-LL is inconsistent in that it depends on the individual PI.

Preoperative factors affecting the two-year postoperative patient-reported outcome in single-level lumbar grade I degenerative spondylolisthesis.

Background: The choice of operative method for lumbar spinal stenosis with Meyerding grade I degenerative spondylolisthesis remains controversial. The purpose of this study was to identify the preoperative factors affecting the 2-year postoperative patient-reported outcome in Meyerding grade I degenerative spondylolisthesis. Methods: Seventy-two consecutive patients who had minimally invasive decompression alone (D group; 28) or with fusion (DF group; 44) were enrolled. The parameters investigated were the Japanese Orthopaedic Association back pain evaluation questionnaire as patient-reported assessment, and L4 slippage (L4S), lumbar lordosis (LL), and lumbar axis sacral distance (LASD) as an index of sagittal alignment for radiological evaluation. Data collected prospectively at 2 years postoperatively were examined by statistical analysis. Results: Sixty-two cases (D group; 25, DF group; 37) were finally evaluated. In multiple logistic regression analysis, preoperative L4S and LASD were extracted as significant preoperative factors affecting the 2-year postoperative outcome. Patients with preoperative L4S of 6 mm or more have a lower rate of improvement in lumbar spine dysfunction due to low back pain (risk ratio=0.188, p=.043). Patients with a preoperative LASD of 30 mm or more have a higher rate of improvement in lumbar dysfunction due to low back pain (risk ratio=11.48, p=.021). The results of multiple logistic analysis by operative method showed that there was a higher rate of improvement in lumbar spine dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more in DF group (risk ratio=172.028, p=.01). Conclusions: Preoperative L4S and LASD were extracted as significant preoperative factors affecting patient-reported outcomes at 2 years postoperatively. Multiple logistic analyses by the operative method suggested that DF may be advantageous in improving lumbar dysfunction due to low back pain in patients with preoperative LASD of 30 mm or more.

Anterior instrumentation surgery for the treatment of Lenke type 1AR curve patterns.

OBJECTIVE: Previous studies have demonstrated that Lenke lumbar modifier A contains 2 distinct types (AR and AL), and the AR curve pattern is likely to develop adding-on (i.e., a progressive increase in the number of vertebrae included within the primary curve distally after posterior surgery). However, the results of anterior surgery are unknown. The purpose of this study was to present the surgical results in a cohort of patients undergoing scoliosis treatment for type 1AR curves and to compare anterior and posterior surgeries to consider the ideal indications and advantages of anterior surgery for type 1AR curves. METHODS: Patients with a Lenke type 1 or 2 and lumbar modifier AR (L4 vertebral tilt to the right) and a minimum 2-year postoperative follow-up were included. The incidence of adding-on and radiographic data were compared between the anterior and posterior surgery groups. The numbers of levels between the end, stable, neutral, and last touching vertebra to the lower instrumented vertebra (LIV) were also evaluated. RESULTS: Forty-four patients with a mean follow-up of 57 months were included. There were 14 patients in the anterior group and 30 patients in the posterior group. The main thoracic Cobb angle was not significantly different between the groups preoperatively and at final follow-up. At final follow-up, the anterior group had significantly less tilting of the LIV than the posterior group (-0.8° ± 4.5° vs 3° ± 4°). Distal adding-on was observed in no patient in the anterior group and in 6 patients in the posterior group at final follow-up (p = 0.025). In the anterior group, no LIV was set below the end vertebra, and all LIVs were set above last touching vertebra. The LIV was significantly more proximal in the anterior group than in the posterior surgery patients without adding-on for all reference vertebrae (p < 0.001). CONCLUSIONS: This is the first study to investigate the surgical results of anterior surgery for Lenke type 1AR curve patterns, and it showed that anterior surgery for the curves could minimize the distal extent of the instrumented fusion without adding-on. This would leave more mobile disc space below the fusion.

Can we use shorter constructs while maintaining satisfactory sagittal plane alignment for adult spinal deformity?

OBJECTIVE: Issues with spinopelvic fixation for adult spinal deformity (ASD) include loss of the physiological mobility of the entire lumbar spine, perioperative complications, and medical costs. Little is known about the factors associated with successful short fusion for ASD. The authors evaluated radiographic and clinical outcomes after shorter fusion for different subtypes of ASD at 2 years postoperatively and examined factors associated with successful short fusion. METHODS: This was a single-center study of 37 patients who underwent short fusion and a minimum 2 years of follow-up for ASD in which lumbar kyphosis was the main deformity. The exclusion criteria were 1) age < 40 years, 2) previous lumbar vertebral fracture, 3) severe osteoporosis, 4) T10-L2 kyphosis > 20°, 5) scoliotic deformity with an upper end vertebra (UEV) above T12, and 6) concomitant Parkinson's disease or neurological disease. The surgical procedures, radiographic course, and Oswestry Disability Index (ODI) were assessed, and correlations between radiographic parameters and postoperative ODI at 2 years were analyzed. RESULTS: A mean of 3.5 levels were fused. The mean radiographic parameters preoperatively, at 2 weeks, and at 2 years, respectively, were as follows: coronal Cobb angle: 22.9°, 11.5°, and 12.6°; lumbar lordosis (LL): 12.9°, 35.8°, and 32.2°; pelvic incidence (PI) minus LL: 35.5°, 14.7°, and 19.2°; pelvic tilt: 29.4°, 23.1°, and 25.0°; and sagittal vertical axis 85.3, 36.7, and 59.2 mm. Abnormal proximal junctional kyphosis occurred in 8 cases. Revision surgery was performed to extend the length of fusion from a lower thoracic vertebra to the pelvis in 2 cases. The mean ODI scores preoperatively and at 2 years were 50.7% and 24.1%, respectively. Patient age, number of fused intervertebral segments, and radiographic parameters were analyzed by the stepwise method to identify factors contributing to the ODI score at 2 years, preoperative PI, and sagittal vertical axis at 2 years. On receiver operating characteristic curve analysis of the minimal clinically important difference of ODI (15%) and preoperative PI, the cutoff value of the preoperative PI was 47° (area under the curve 0.75). CONCLUSIONS: In terms of subtypes of ASD in which lumbar kyphosis is the main deformity, if the PI is < 47°, then the use of short fusion preserving mobile intervertebral segments can produce adequate LL for the PI, improving both postoperative global spinal alignment and quality of life.

Can we stop the long fusion at L5 for selected adult spinal deformity patients with less severe disability and less complex deformity?

OBJECTIVES: It is controversial whether to stop the fusion at L5 or S1 in adult spinal deformity (ASD) surgery. Our hypothesis is that we can stop long fusion at L5 for selected patients with less severe disability and less complex deformity. Aim was to compare minimum 5-year outcomes between ASD patients with fusion to L5 versus S1. PATIENTS AND METHODS: Consecutive 40 patients (≥50 years of age) with ASD underwent spinal fusion from lower thoracic spine to L5 or S1 between 2008 and 2011. 33 patients (82.5 %) had a minimum 5-year follow-up. Lower instrumented vertebra (LIV) was L5 in 12 patients (L5 group) and S1 in 21 (S1 group). Clinical and radiographical parameters were compared between L5 and S1 group. RESULTS: There were statistically significant differences between two groups (L5 vs S1) in %male (50 % vs 14 %), %type-N of SRS-Schwab classification (83 % vs 38 %), preop ODI (40.5 vs 56), correction loss of LL (11˚ vs 3˚), final TK (32˚ vs 50˚), correction loss of TK (-1˚ vs 17˚), final improvement of PT (3˚ vs 10˚), final improvement of PI-LL (26˚ vs 39˚), PJK (8% vs 48 %), and revision surgery rate (50 % vs 14 %). Causes of revision surgery in L5 group were distal junctional failure in 5 patients and foraminal stenosis at L5-S1 in 1. All of them underwent additional spinal fusion to the sacrum. Whereas, causes of revision surgery in S1 group were rod fracture in 2 patients and proximal junctional failure in 1. CONCLUSION: Although fusion to L5 was conducted for selected ASD patients with less severe disability (better ODI) and less complex deformity (type N), 50 % of the patients required additional fusion to the pelvis. Decision making to stop the long fusion at L5 for ASD patients ≥50 years of age should be made with careful considerations.

Growing rod technique with prior foundation surgery and sublaminar taping for early-onset scoliosis.

OBJECTIVE: The aim of this study was to show the surgical results of growing rod (GR) surgery with prior foundation surgery (PFS) and sublaminar taping at an apex vertebra. METHODS: Twenty-two early-onset scoliosis (EOS) patients underwent dual GR surgery with PFS and sublaminar taping. PFS was performed prior to rod placement, including exposure of distal and proximal anchor areas and anchor instrumentation filled with a local bone graft. After a period of 3-5 months for the anchors to become solid, dual rods were placed for distraction. The apex vertebra was exposed and fastened to the concave side of the rods using sublaminar tape. Preoperative, post-GR placement, and final follow-up radiographic parameters were measured. Complications during the treatment period were evaluated using the patients' clinical records. RESULTS: The median age at the initial surgery was 55.5 months (range 28-99 months), and the median follow-up duration was 69.5 months (range 25-98 months). The median scoliotic curves were 81.5° (range 39°-126°) preoperatively, 30.5° (range 11°-71°) after GR placement, and 33.5° (range 12°-87°) at the final follow-up. The median thoracic kyphotic curves were 45.5° (range 7°-136°) preoperatively, 32.5° (range 15°-99°) after GR placement, and 42° (range 11°-93°) at the final follow-up. The median T1-S1 lengths were 240.5 mm (range 188-305 mm) preoperatively, 286.5 mm (range 232-340 mm) after GR placement, and 337.5 mm (range 206-423 mm) at the final follow-up. Complications occurred in 6 patients (27%). Three patients had implant-related complications, 2 patients had alignment-related complications, and 1 patient had a wound-related complication. CONCLUSIONS: A dual GR technique with PFS and sublaminar taping showed effective correction of scoliotic curves and a lower complication rate than previous reports when a conventional dual GR technique was used.

Pedicle screws with a thin hydroxyapatite coating for improving fixation at the bone-implant interface in the osteoporotic spine: experimental study in a porcine model.

OBJECTIVE Instrumentation failure caused by the loosening of pedicle screws (PSs) in patients with osteoporosis is a serious problem after spinal surgery. The addition of a thin hydroxyapatite (HA) surface coating applied by using a sputtering process was reported recently to be a promising method for providing bone conduction around an implant without a significant risk of coating-layer breakage. In this study, the authors evaluated the biomechanical and histological features of the bone-implant interface (BII) of PSs with a thin HA coating in an in vivo porcine osteoporotic spine model. METHODS Three types of PSs (untreated/standard [STPS], sandblasted [BLPS], and HA-coated [HAPS] PSs) were implanted into the thoracic and lumbar spine (T9-L6) of 8 mature Clawn miniature pigs (6 ovariectomized [osteoporosis group] and 2 sham-operated [control group] pigs). The spines were harvested from the osteoporosis group at 0, 2, 4, 8, 12, or 24 weeks after PS placement and from the control group at 0 or 24 weeks. Their bone mineral density (BMD) was measured by peripheral quantitative CT. Histological evaluation of the BIIs was conducted by performing bone volume/tissue volume and bone surface/implant surface measurements. The strength of the BII was evaluated with extraction torque testing. RESULTS The BMD decreased significantly in the osteoporosis group (p < 0.01). HAPSs exhibited the greatest mean extraction peak torque at 8 weeks, and HAPSs and BLPSs exhibited significantly greater mean torque than the STPSs at 12 weeks (p < 0.05). The bone surface/implant surface ratio was significantly higher for HAPSs than for STPSs after 2 weeks (p < 0.05), and bonding between bone and the implant surface was maintained until 24 weeks with no detachment of the coating layer. In contrast, the bone volume/tissue volume ratio was significantly higher for HAPSs than for BLPSs or STPSs only at 4 weeks. CONCLUSIONS Using PSs with a thin HA coating applied using a sputtering process strengthens bonding at the BII, which might improve early implant fixation after spinal surgery for osteoporosis. However, the absence of increased bone mass around the screw remains a concern; prescribing osteoporosis treatment to improve bone quality might be necessary to prevent fractures around the screws.

Postoperative Status of Global Sagittal Alignment With Compensation in Adult Spinal Deformity.

STUDY DESIGN: A retrospective study of consecutive patients undergoing surgery for adult spinal deformity (ASD). OBJECTIVE: The aim of this study was to classify postoperative ASD patients by sagittal compensation and characterize the features of each group. SUMMARY OF BACKGROUND DATA: Sagittal compensatory mechanisms to keep the erect position would function in not only nonoperative ASD patients but also in postoperative patients. However, details of sagittal compensatory mechanisms after surgery have been unclear, because the majority of previous studies examined the compensatory mechanisms in nonoperative patients. METHODS: A total of 73 postoperative ASD patients were recruited. Spinopelvic parameters and Oswestry Disability Index (ODI) were measured before surgery, at 1-month and 2-year follow-up. The changes in parameters (Δ) between postoperative 1-month and 2-year were also evaluated. Cluster analysis based on pelvic tilt (PT) and sagittal vertical axis (SVA) at 2-year follow-up was performed, and then the parameters were compared among clusters. RESULTS: Cluster analysis identified three clusters: the physiological group (n = 38, PT = 19.6°, SVA = 17.2 mm), the compensated group (n = 23, PT = 34.3°, SVA = 45.6 mm), and the decompensated group (n = 12, PT = 36.6°, SVA = 118.8 mm). Comparisons of the parameters among the groups showed that the physiological group had smaller pelvic incidence minus lumbar lordosis (PI-LL) and better ODI. The compensated group had significantly larger Δ thoracic kyphosis (TK), Δ proximal junctional angle (PJA), and ΔPT than the physiological group. The decompensated group had significantly higher PI and higher age. CONCLUSION: Three groups were defined in terms of postoperative compensatory mechanisms. Patients in the physiological group had little postoperative alignment change and good ODI value. The compensated group had pelvic retroversion to keep SVA in the physiological range, but the compensation in the thoracic spine was unlikely to work. High PI and advanced age were characteristics of the decompensated group. LEVEL OF EVIDENCE: 4.

Ethnic Variations in Radiographic Parameters and SRS-22 Scores in Adult Spinal Deformity: A Comparison Between North American and Japanese Patients Above 50 Years of Age With Minimum 2-Year Follow-up.

STUDY DESIGN: Retrospective review of North American and Japanese adult spinal deformity (ASD) database. OBJECTIVE: To investigate the ethnical differences in radiographic parameters and Scoliosis Research Society (SRS)-22 between North American and Japanese ASD. SUMMARY OF BACKGROUND DATA: Previous comparison study between North American and Japanese ASD patients has revealed Japanese patients had marked pelvic tilt deformity and had lower Oswestry Disability Index scores corresponding to established thresholds of radiographic deformity. However, the subjects of the previous study included relatively younger ASD patients (above 18 y) of idiopathic origin. MATERIALS AND METHODS: Total 282 ASD patients older than 50 years, 211 patients from North America (United States) and 71 patients from Japan (JP), with minimum 2-year follow-up postoperatively were included in the study. Radiologic parameters were compared at the baseline and at 2-year follow-up. SRS-22 score was used for the comparison of clinical outcome. RESULTS: At baseline, Japan showed significantly worse sagittal alignment such as smaller lumbar lordosis (LL), larger pelvic incidence (PI), and larger sagittal vertical axis than United States. However, Japan had significantly fewer levels fused than United States (US, 12.66±4.6; JP, 8.49±2.7). At 2 years after the surgery, Japan still had significantly worse residual sagittal deformity. Comparison of SRS-22 scores revealed Japan had better pain but worse functional domain scores at baseline which improved to comparable levels to the United States at 2 years. Self-image and mental health scores in Japan were significantly worse both at baseline and at 2 years. Analysis of factors affecting SRS-22 satisfaction score at 2 years revealed that previous spinal fusion surgery in the United States and LL, PI-LL, and sagittal vertical axis at 2 years in Japan had significant correlation. CONCLUSIONS: These similarities and discrepancies may be influenced by the cultural or lifestyle differences between both nations and should be considered when interpreting the results of ASD studies among different ethnicities.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury.

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. METHODS AND ANALYSIS: The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). ETHICS AND DISSEMINATION: The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. TRIAL REGISTRATION NUMBER: UMIN000018752.

Role of Ethnicity in Alignment Compensation: Propensity Matched Analysis of Differential Compensatory Mechanism Recruitment Patterns for Sagittal Malalignment in 288 ASD Patients From Japan, Korea, and United States.

STUDY DESIGN: Retrospective review of adult spinal deformity patients in a multiethnic database. OBJECTIVE: To investigate the role of ethnicity on recruitment of compensatory mechanisms for sagittal spinal deformity. SUMMARY OF BACKGROUND DATA: While the impacts of age, sex, and pelvic morphology on the ability to compensate for sagittal malalignment have been investigated, the role of ethnicity in compensatory mechanism recruitment is poorly understood. METHODS: Patients from USA (85% Caucasian) >25 y/o were propensity matched by age, sex, and pelvic incidence with patients from Korea and Japan. Only primary patients or those with existing fusion below T12 were retained for analysis. Groups were subclassified by deformity severity (aligned: sagittal vertical axis (SVA) <50 mm; moderate malalignment: SVA 50-100 mm; severe malalignment: SVA >100 mm). Radiographic measurements including pelvic retroversion, thoracic kyphosis, loss of lumbar lordosis (PI minus LL), cervical lordosis, and cervical SVA were compared between the groups. RESULTS: There were 288 patients (96 each in USA, KOR, JPN), with similar age (64-67 yr) and PI (49-53°). USA had smaller pelvic incidence minus lumbar lordosis in every alignment group (P <0.05). In moderate malalignment, JPN had more pelvic retroversion than USA (30° vs. 20°), and KOR had more thoracic hypokyphosis than USA (15 vs. 31°). In severe malalignment, JPN had more pelvic retroversion than USA (39° vs. 27°), and KOR had more thoracic hypokyphosis than USA (15° vs. 31°). KOR had smaller cSVA than USA in both aligned (11 vs. 27 mm) and moderate (19 vs. 31 mm) malalignment. In severe malalignment, KOR had less cervical lordosis (13° KOR vs. 15° USA vs. 27° JPN). All differences with P <0.05. CONCLUSION: Compensation for sagittal is ethnicity dependent. Korean patients favor thoracic compensation via hypokyphosis, and Japanese patients favor pelvic compensation via retroversion. Patient ethnicity should be considered when evaluating the sagittal plane and surgical correction strategies. LEVEL OF EVIDENCE: 3.