Boron-Related Defects in N-Type 4H-SiC Schottky Barrier Diodes.

We report on boron-related defects in the low-doped n-type (nitrogen-doped) 4H-SiC semitransparent Schottky barrier diodes (SBDs) studied by minority carrier transient spectroscopy (MCTS). An unknown concentration of boron was introduced during chemical vapor deposition (CVD) crystal growth. Boron incorporation was found to lead to the appearance of at least two boron-related deep-level defects, namely, shallow (B) and deep boron (D-center), with concentrations as high as 1 × 1015 cm-3. Even though the boron concentration exceeded the nitrogen doping concentration by almost an order of magnitude, the steady-state electrical characteristics of the n-type 4H-SiC SBDs did not deteriorate.

Radiation Response of Large-Area 4H-SiC Schottky Barrier Diodes.

We report on the effects of large-area 4H-SiC Schottky barrier diodes on the radiation response to ionizing particles. Two different diode areas were compared: 1 mm × 1 mm and 5 mm × 5 mm. 6LiF and 10B4C films, which were placed on top of the diodes, were used as thermal neutron converters. We achieved a thermal neutron efficiency of 5.02% with a 6LiF thermal neutron converter, which is one of the highest efficiencies reported to date. In addition, a temperature-dependent radiation response to alpha particles was presented. Neutron irradiations were performed in a JSI TRIGA dry chamber and an Am-241 wide-area alpha source was used for testing the alpha response of the 4H-SiC Schottky barrier diodes.

Preoperative Risk Factors Affecting Outcome in Surgically Treated Pyogenic Spondylodiscitis.

STUDY DESIGN: Retrospective study. OBJECTIVE: The primary aim of this study was to investigate the predictors of severe complications in patients following surgery for pyogenic spondylodiscitis (PS) using a surgeon-maintained database. The secondary aim was to investigate the predictors of early recovery. METHODS: We introduced a surgeon-maintained database of prospectively collected multicenter data that mainly focused on perioperative complications in 2012. Our surgeon-maintained database allows the retrospective collection of detailed data. We analyzed 143 patients who underwent surgery for PS from the 19,056 patients in the prospective surgeon-maintained database at 27 affiliated institutions between 2013 and 2017. Data relating to preoperative patient factors, infection factors, surgical factors, and pre- and postoperative blood tests was retrospectively collected. We performed multivariate regression analysis to evaluate the predictors of postoperative severe complications and early recovery in patients with PS. RESULTS: High updated Charlson comorbidity index (uCCI), chronic pulmonary disease, diabetes, Gram-negative bacteria, pyogenic osteoarthritis, high preoperative white blood cell count, and low preoperative platelet count were significantly associated with severe complications in patients undergoing surgery for PS. A high uCCI was the sole independent negative predictor on early recovery. CONCLUSION: Careful perioperative management is necessary if surgery is performed on patients who are at a high risk of life-threatening events.

Effects of rhBMP-2-loaded hydroxyapatite granules/beta-tricalcium phosphate hydrogel (HA/ß-TCP/hydrogel) composite on a rat model of caudal intervertebral fusion.

The effects and inflammation-related side effects of bone morphogenetic protein (BMP)-2 on posterior lumbar interbody fusion are controversial. One of the potential causes for the inconsistent results is the uncontrolled release of BMP-2 from the collagen carrier. Therefore, BMP delivery systems that support effective bone regeneration while attenuating the side effects are strongly sought for. We developed NOVOSIS putty (NP), a novel composite material of hydroxyapatite (HA), beta-tricalcium phosphate (ß-TCP)/hydrogel, and BMP-2, which can sustainably release BMP-2 over 2 weeks. This study was aimed at comparing the effects and side effects of NP and collagen sponge (CS) containing BMP-2 using a rat caudal intervertebral fusion model. The fusion rates of NP with low and high doses of BMP-2 were significantly higher than those of an iliac bone (IB) graft, but those of CS with low and high doses of BMP-2 were not different from those of the IB graft. Furthermore, the incidences of ectopic bone formation and soft tissue swelling were significantly lower in the NP group than in the CS group. The HA/ß-TCP/hydrogel carrier enabled superior bone induction with low-dose BMP-2 and decreased the incidence of side effects caused by high-dose BMP-2 vis-à-vis the collagen carrier.

Postoperative improvement in leg length discrepancy in adolescent idiopathic scoliosis differs between right and left legs.

Background: In adolescent idiopathic scoliosis (AIS) patients, leg length discrepancies (LLDs) often occur to compensate for scoliosis. However, there have been no reports on the LLD changes after corrective surgery for AIS. This study aimed to clarify the difference of LLD changes after corrective surgery for AIS by classifying LLD based on the shortened side. Methods: We analyzed preoperative and postoperative radiographs of 94 consecutive AIS patients who underwent posterior corrective surgery between 2012 and 2018. The patients enrolled were divided into three groups according to the presence of preoperative LLD of more than 5 mm and the LLD side: the left leg shortened group (L group), the non-LLD group (N group), and the right leg shortened group (R group). The three groups were compared with regard to age, sex, Lenke classification, Risser grade, fused levels, and radiographic parameters before surgery and at 6-month follow-up (thoracic Cobb angle, lumbar Cobb angle, L4 tilt, coronal balance, T1 tilt, and LLD). Results: The L, N, and R groups included 23 (24%), 60 (64%), and 11 patients (12%), respectively. The demographics and radiographic parameters were not significantly different among the groups except for preoperative L4 tilt. In the L group only, the LLD decreased from 7.9 ± 2.2 mm to 5.7 ± 3.7 mm (p = 0.002) after surgery. In contrast, the LLD in the N and R groups did not change significantly. Conclusions: The postoperative improvement of LLD in AIS patients differed between the left and right sides. Different pathologies may contribute to the LLD on the left and right sides.

Prostaglandin EP4 Selective Agonist AKDS001 Enhances New Bone Formation by Minimodeling in a Rat Heterotopic Xenograft Model of Human Bone.

To enhance bone regeneration, the use of bone morphogenetic protein (BMP)-2 is an attractive option. Unfortunately, the dose-dependent side effects prevent its widespread use. Therefore, a novel osteogenic agent using a different mechanism of action than BMP-2 is highly desirable. Previous reports demonstrated that prostaglandin E2 receptor 4 (EP4) agonists have potent osteogenic effects on non-human cells and are one of the potential alternatives for BMP-2. Here, we investigated the effects of an EP4 agonist (AKDS001) on human cells with a rat heterotopic xenograft model of human bone. Bone formation in the xenograft model was significantly enhanced by AKDS001 treatment. Histomorphometric analysis showed that the mode of bone formation by AKDS001 was minimodeling rather than remodeling. In cultured human mesenchymal stem cells, AKDS001 enhanced osteogenic differentiation and mineralization via the cAMP/PKA pathway. In cultured human preosteoclasts, AKDS001 suppressed bone resorption by inhibiting differentiation into mature osteoclasts. Thus, we conclude that AKDS001 can enhance bone formation in grafted autogenous bone by minimodeling while maintaining the volume of grafted bone. The combined use of an EP4 agonist and autogenous bone grafting may be a novel treatment option to enhance bone regeneration. However, we should be careful in interpreting the results because male xenografts were implanted in male rats in the present study. It remains to be seen whether females can benefit from the positive effects of AKDS001 MS by using female xenografts implanted in female rats in clinically relevant animal models.

Comparison of Short-Term Radiographical and Clinical Outcomes After Posterior Lumbar Interbody Fusion With a 3D Porous Titanium Alloy Cage and a Titanium-Coated PEEK Cage.

STUDY DESIGN: Clinical case series. OBJECTIVES: To compare the short-term (≤1 year) radiographical and clinical outcomes between posterior lumbar interbody fusion (PLIF) with a titanium-coated poly-ether-ether-ketone (TCP) cage and PLIF with a three-dimensional porous titanium alloy (PTA) cage. METHODS: Overall, 63 patients who had undergone 1- or 2-level PLIF since March 2015 were enrolled (median age, 71 years). The first 34 patients underwent PLIF with TCP cages (until June 2017) and the next 29 patients with PTA cages. Fusion status, vertebral endplate cyst formation (cyst sign: grade 0, none; grade 1, focal; and grade 2, diffuse), cage subsidence (grade 0, <1 mm; grade 1, 1-3 mm; and grade 2, >3 mm), and patient-reported quality of life (QOL) outcomes based on the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) were compared at 6 months and 1 year postoperatively between the 2 cage groups. RESULTS: Cyst sign and cage subsidence grades were significantly lower in the PTA cage group than in the TCP cage group at 6 months postoperatively (cyst sign, p = 0.044; cage subsidence, p = 0.043). In contrast, the fusion rate and surgery effectiveness based on JOABPEQ at both 6 months and 1 year postoperatively were not different between the 2 groups. CONCLUSIONS: Patient-reported QOL outcomes were similar between the TCP and PTA cage groups until 1 year postoperatively. However, a higher incidence and severity of postoperative vertebral endplate cyst formation in patients with the TCP cage was a noteworthy radiographical finding.

Effect of Early vs Delayed Surgical Treatment on Motor Recovery in Incomplete Cervical Spinal Cord Injury With Preexisting Cervical Stenosis: A Randomized Clinical Trial.

Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown. Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020. Interventions: Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment. Main Outcomes and Measures: The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury. Results: Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment). Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, -4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients). Conclusions and Relevance: These findings suggest that among patients with cervical SCI, early surgical treatment produced similar motor regain at 1 year after injury as delayed surgical treatment but showed accelerated recovery within the first 6 months. These exploratory results suggest that early surgical treatment leads to faster neurological recovery, which requires further validation. Trial Registration: ClinicalTrials.gov Identifier: NCT01485458; umin.ac.jp/ctr Identifier: UMIN000006780.

Amine modification of calcium phosphate by low-pressure plasma for bone regeneration.

Regeneration of large bone defects caused by trauma or tumor resection remains one of the biggest challenges in orthopedic surgery. Because of the limited availability of autograft material, the use of artificial bone is prevalent; however, the primary role of currently available artificial bone is restricted to acting as a bone graft extender owing to the lack of osteogenic ability. To explore whether surface modification might enhance artificial bone functionality, in this study we applied low-pressure plasma technology as next-generation surface treatment and processing strategy to chemically (amine) modify the surface of beta-tricalcium phosphate (ß-TCP) artificial bone using a CH4/N2/He gas mixture. Plasma-treated ß-TCP exhibited significantly enhanced hydrophilicity, facilitating the deep infiltration of cells into interconnected porous ß-TCP. Additionally, cell adhesion and osteogenic differentiation on the plasma-treated artificial bone surfaces were also enhanced. Furthermore, in a rat calvarial defect model, the plasma treatment afforded high bone regeneration capacity. Together, these results suggest that amine modification of artificial bone by plasma technology can provide a high osteogenic ability and represents a promising strategy for resolving current clinical limitations regarding the use of artificial bone.

4H-SiC Schottky Barrier Diodes for Efficient Thermal Neutron Detection.

In this work, we present the improved efficiency of 4H-SiC Schottky barrier diodes-based detectors equipped with the thermal neutron converters. This is achieved by optimizing the thermal neutron converter thicknesses. Simulations of the optimal thickness of thermal neutron converters have been performed using two Monte Carlo codes (Monte Carlo N-Particle Transport Code and Stopping and Range of Ions in Matter). We have used 6LiF and 10B4C for the thermal neutron converter material. We have achieved the thermal neutron efficiency of 4.67% and 2.24% with 6LiF and 10B4C thermal neutron converters, respectively.

Severe orthostatic hypotension associated with lesions of the area postraema in neuromyelitis optica spectrum disorder.

Hiccups, nausea and vomiting are known as the clinical manifestations of neuromyelitis optica spectrum disorder (NMOSD) linked to lesions of the area postraema in the medullary tegmentum. Here, we describe a 74-year-old male patient with NMOSD who presented with recurrent syncope due to severe orthostatic hypotension (OH) following symptoms of hiccups, nausea and vomiting. Brain magnetic resonance imaging revealed the lesion of the area postraema and it could be responsible for the symptom of OH. Considering the numerous related reports, we suspect that the prevalence of OH is underreported in the patients with NMOSD. OH may transition into more serious conditions, so it should be evaluated carefully in all patients with NMOSD, particularly when there is a lesion of the area postraema.

Impact of mechanical stability on the progress of bone ongrowth on the frame surfaces of a titanium-coated PEEK cage and a 3D porous titanium alloy cage: in vivo analysis using CT color mapping.

PURPOSE: To determine the impact of mechanical stability on the progress of bone ongrowth on the frame surfaces of a titanium-coated polyether ether ketone (TCP) cage and a three-dimensional porous titanium alloy (PTA) cage following posterior lumbar interbody fusion (PLIF) until 1 year postoperatively. METHODS: A total of 59 patients who underwent one- or two-level PLIF for degenerative lumbar disorders since March 2015 were enrolled. Bone ongrowth of all cage frame surfaces (four surfaces per cage: TCP, 288 surfaces and PTA, 284 surfaces) was graded by 6-month and 1-year postoperative computed tomography color mapping (grade 0, 0‒25% of bone ongrowth; grade 1, 26‒50%; grade 2, 51‒75%; and grade 3, 76‒100%). RESULTS: Bone ongrowth (≥ grade 1) was observed on 58.0% and 69.0% of the surfaces of TCP and PTA cages 6 months postoperatively and on 63.5% and 75.0% of those 1 year postoperatively, respectively. In the TCP cages, bone ongrowth grade increased from 6 months to 1 year postoperatively only in the union segments (median, 1 [interquartile range, IQR, 0-2] to 1 [IQR, 0-3], p = 0.006). By contrast, in the PTA cages, it increased at 6 months postoperatively in the union (1 [IQR, 1-2] to 2 [IQR, 1-3], p = 0.003) and non-union (0.5 [IQR, 0-2] to 1 [IQR, 0-2.75], p = 0.002) segments. CONCLUSION: Early postoperative mechanical stability has a positive impact on the progress of bone ongrowth on both the TCP and PTA cage frame surfaces after PLIF.

Factors related to length of hospital stay after two-stage corrective surgery for adult spinal deformity in elderly Japanese.

BACKGROUND: Postoperative recovery of activities of daily living after surgery in elderly patients often takes a longer time because of their frailty. However, it is unclear how long it takes for patients with adult spinal deformity (ASD) to recover their abilities to live their daily lives in their home after corrective fusion surgery. This study aimed to investigate the length of hospital stay required to perform activities of daily living (ADL) in patients undergoing two-stage corrective fusion surgery for ASD in our institution and to detect factors associated with the length of hospital stay. METHODS: Thirty-four consecutive female ASD patients (median age, 70 years) who underwent two-stage corrective fusion surgery (lateral lumbar interbody fusion at the first stage and posterior corrective fusion at the second stage) from T9 or T10 to the pelvis were included. The length of hospital stay from admission to return home was determined, and correlations between length of hospital stay and demographics, skeletal muscle mass, operative invasion and perioperative complications, and spino-pelvic alignment were investigated. RESULTS: The median length of hospital stay was 51 days, exceeding 100 days in 25% of cases. Age at surgery (ρ = 0.545, p = 0.001), estimated glomerular filtration rate (ρ = -0.603, p < 0.001), age-adjusted Charlson comorbidity index (ρ = 0.437, p = 0.01), and preoperative pelvic incidence (ρ = 0.356, p = 0.04) were correlated with length of hospital stay. Preoperative skeletal muscle mass, preoperative spinal imbalance, perioperative changes in spino-pelvic alignment, operative invasion, and perioperative complications were not correlated with length of hospital stay. CONCLUSIONS: After >50 days, ADL performance of each patient reached the extent required for daily living to return home after two-stage corrective fusion surgery for ASD. Factors related to length of hospital stay were age and indices related to frailty.

Risk factor analysis of surgery-related complications in primary cervical spine surgery for degenerative diseases using a surgeon-maintained database.

AIMS: This study, using a surgeon-maintained database, aimed to explore the risk factors for surgery-related complications in patients undergoing primary cervical spine surgery for degenerative diseases. METHODS: We studied 5,015 patients with degenerative cervical diseases who underwent primary cervical spine surgery from 2012 to 2018. We investigated the effects of diseases, surgical procedures, and patient demographics on surgery-related complications. As subcategories, the presence of cervical kyphosis ≥ 10°, the presence of ossification of the posterior longitudinal ligament (OPLL) with a canal-occupying ratio ≥ 50%, and foraminotomy were selected. The surgery-related complications examined were postoperative upper limb palsy (ULP) with a manual muscle test (MMT) grade of 0 to 2 or a reduction of two grade or more in the MMT, neurological deficit except ULP, dural tear, dural leakage, surgical-site infection (SSI), and postoperative haematoma. Multivariate logistic regression analysis was performed. RESULTS: The significant risk factors (p < 0.050) for ULP were OPLL (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.29 to 2.75), foraminotomy (OR 5.38, 95% CI 3.28 to 8.82), old age (per ten years, OR 1.18, 95% CI 1.03 to 1.36), anterior spinal fusion (OR 2.85, 95% CI 1.53 to 5.34), and the number of operated levels (OR 1.25, 95% CI 1.11 to 1.40). OPLL was also a risk factor for neurological deficit except ULP (OR 5.84, 95% CI 2.80 to 12.8), dural tear (OR 1.94, 95% CI 1.11 to 3.39), and dural leakage (OR 3.15, 95% CI 1.48 to 6.68). Among OPLL patients, dural tear and dural leakage were frequently observed in those with a canal-occupying ratio ≥ 50%. Cervical rheumatoid arthritis (RA) was a risk factor for SSI (OR 10.1, 95% CI 2.66 to 38.4). CONCLUSION: The high risk of ULP, neurological deficit except ULP, dural tear, and dural leak should be acknowledged by clinicians and OPLL patients, especially in those patients with a canal-occupying ratio ≥ 50%. Foraminotomy and RA were dominant risk factors for ULP and SSI, respectively. An awareness of these risks may help surgeons to avoid surgery-related complications in these conditions. Cite this article: Bone Joint J 2021;103-B(1):157-163.

Direct Involvement of Concomitant Foraminotomy for Radiculomyelopathy in Postoperative Upper Limb Palsy in Cervical Laminoplasty.

OBJECTIVE: Although concomitant foraminotomy has been reported to increase the risk of postoperative upper limb palsy (ULP) in cervical laminoplasty, the specific effects of concomitant foraminotomy on ULP remain uncertain. This study aimed to clarify the effect of concomitant foraminotomy on ULP in cervical laminoplasty. METHODS: We identified 19 patients who developed ULP after laminoplasty with concomitant foraminotomy for radiculomyelopathy with nerve root impingement (laminoplasty with concomitant foraminotomy group [F-group]) from 4080 patients who underwent primary cervical laminoplasty at 27 affiliated institutions between 2012 and 2018. An age- and sex-matched control group comprised patients who developed ULP after laminoplasty without concomitant foraminotomy (n = 76, 4:1 ratio with F-group). Collected data included the time of onset and distribution of ULP (side and level). The site of foraminotomy was recorded in the F-group. RESULTS: The F-group showed a significantly higher incidence of ULP than the candidates for the control group (15.1% vs. 3.1%, P < 0.001). The site of foraminotomy was consistent with the distribution of ULP in 79% (15 of 19 patients) of the F-group. The F-group showed a significantly higher proportion of preoperative upper-limb muscle weakness (74% vs. 37%, P = 0.005) and early-onset ULP occurring by postoperative day 1 (63% vs. 33%, P = 0.02) compared with the control group. CONCLUSIONS: Our results indicate that the foraminotomy procedure in the stenotic foramen is directly involved in ULP. Combined with a previous report suggesting that early-onset ULP is associated with thermal nerve damage, our results indicate that thermal nerve damage partly explains the increased incidence of ULP in the F-group.

Utility of duct-washing cytology for detection of early breast cancer in patients with pathological nipple discharge: A comparative study with fine-needle aspiration cytology.

BACKGROUND: Pathological nipple discharge (PND) is a relatively common symptom of breast cancer affecting the nipple. Mammary ductscopy (MD) allows direct visualization of the ductal lumen and collection of a cytological specimen using duct-washing cytology (DWC). Herein, we clarified the diagnostic efficacy of DWC for the detection of breast cancers with PND, compared with fine-needle aspiration cytology (FNAC). METHODS: We retrospectively examined 48 patients with PND who underwent DWC by MD (ductosccopy group; histologically determined by intraductal biopsy [IDB] or surgical specimen). The results of sensitivity and specificity of DWC were compared with that of FNAC (conventional group; histologically determined by core needle biopsy). Clinicopathological factors were compared between the ductoscopy and the conventional groups. RESULTS: Of eight histologically malignant cases in the ductoscopy group, one case was cytologically judged as malignant and three as indeterminate. Sensitivity and specificity of DWC were 50.0% and 82.5%, respectively. Malignant cases were mostly solid papillary carcinomas (SPCs), and benign cases were intraductal papillomas (IDPs). In the conventional group, sensitivity and specificity of FNAC were 88.0% and 38.2%, respectively, and malignant cases were mainly invasive carcinomas of no special type. Tumors in the ductocsopy group had more favorable prognostic features than those in the conventional group. CONCLUSION: DWC has limited diagnostic value due to the high incidence of SPC, whose cytological features are indistinguishable from IDP. As DWC alone may be unreliable, comprehensive examination with IDB and MD findings is recommended.

Postoperative T1 tilt is a risk factor for postoperative distal adding-on in Lenke type 1 adolescent idiopathic scoliosis: A preliminary report.

Retrospective comparable study.Postoperative loss of correction, which is referred to as the distal adding-on phenomenon, sometimes occurs during the postoperative course in Lenke type 1 adolescent idiopathic scoliosis (AIS). Selection of the lowest instrumented vertebra (LIV) has been reported to be one of the significant factors for preventing distal adding-on. However, proximal parameters, such as the Cobb angle of the proximal thoracic (PT) curve, radiographic shoulder height, and T1 tilt, were rarely described in previous reports. This study aimed to identify the risk factors for postoperative distal adding-on, including proximal radiographic parameters, in Lenke type 1 AIS.Preoperative and postoperative radiographs of 34 consecutive patients with Lenke type 1 curve who underwent selective thoracic fusion were analyzed. The patients were divided into an adding-on group and a no-adding-on group according to the presence of adding-on at a 2-year follow-up. The 2 groups were compared with regard to age at surgery, Lenke lumbar modifier, Risser grade, instrumentation type, and radiographic parameters.Distal adding-on was noted in 10 patients (29%). The adding-on group had significant variables including preoperative larger PT Cobb angle (P = .002), larger main thoracic (MT) flexibility (P = .006), smaller thoracolumbar (TL) Cobb angle (P = .012), larger LIV shift (P < .001), larger T1 tilt (P = .001), postoperative larger PT Cobb angle (P = .012), smaller MT Cobb angle (P = .016), smaller TL Cobb angle (P < .001), larger PT-MT mismatch (P < .001), larger LIV shift (P = .026), and larger T1 tilt (P = .006) when compared with the findings in the no-adding-on group. Postoperative T1 tilt was significantly correlated with PT-MT mismatch.Our findings suggest that not only the LIV but also proximal parameters, including T1 tilt and PT-MT mismatch, are associated with postoperative distal adding-on in Lenke type 1 AIS. Strategies to reduce postoperative T1 tilt and PT-MT mismatch are required to prevent distal adding-on.

Resting-state Amplitude of Low-frequency Fluctuation is a Potentially Useful Prognostic Functional Biomarker in Cervical Myelopathy.

BACKGROUND: Cervical MRI is the standard diagnostic imaging technique for patients with cervical myelopathy. However, the utility of conventional cervical MRI as a predictive biomarker for surgical recovery remains unclear, partly because of the limited information obtained from this anatomically small area. Brain resting-state functional MRI (rs-fMRI) may help identify candidate predictive biomarkers. Two analytical methods that assess local spontaneous brain activity are widely used for rs-fMRI: functional connectivity between two brain regions and amplitude of low-frequency fluctuation (ALFF). In our previous analysis of functional connectivity, we discovered that brain functional connectivity may be a predictive biomarker for neurologic recovery in patients with cervical myelopathy; however, the functional connectivity analysis identified a correlation with only one clinical outcome (the 10-second test). To establish a comprehensive prediction measure, we need to explore other brain biomarkers that can predict recovery of other clinical outcomes in patients with cervical myelopathy. QUESTIONS/PURPOSES: We aimed to (1) elucidate preoperative ALFF alterations in patients with cervical myelopathy and how ALFF changes after surgery, with a focus on postoperative normalization and (2) establish a predictive model using preoperative ALFF by investigating the correlation between preoperative ALFF and postoperative clinical recovery in patients with cervical myelopathy. METHODS: Between August 2015 and June 2017, we treated 40 patients with cervical myelopathy. Thirty patients met our prespecified inclusion criteria, all were invited to participate, and 28 patients opted to do so (93%; 14 men and 14 women; mean age: 67 years). The 28 patients and 28 age- and sex-matched controls underwent rs-fMRI (twice for patients with cervical myelopathy: before and 6 months after cervical decompression surgery). We analyzed the same study population that was used in our earlier study investigating functional connectivity. Controls had none of the following abnormalities: neck or arm pain, visual or auditory disorders, cognitive disorder, structural brain disorder, a history of brain surgery, mental and neurologic disorders, and medications for the central nervous system. We performed ALFF comparisons between preoperative patients with cervical myelopathy and controls, analyzed postoperative ALFF changes in patients with cervical myelopathy, and performed a correlation analysis between preoperative ALFF and clinical recovery in these patients. Clinical outcomes in the cervical myelopathy group were assessed using the 10-second test, the Japanese Orthopaedic Association upper-extremity motor (JOA-UEM) score, JOA upper-extremity sensory score (JOA-UES), and Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire for upper-extremity function (JOACMEQ-UEF) score before and 6 months after surgery, which is when we believe these scores generally reach a plateau. A total of 93% of those enrolled (26 of 28 patients) were analyzed both preoperatively and postoperatively; the other two were lost to follow-up. RESULTS: The cervical myelopathy group had an increase in ALFF in the bilateral primary sensorimotor cortices (right, cluster size = 850 voxels, t-value = 6.10; left, cluster size = 370 voxels, t-value = 4.84) and left visual cortex (cluster size = 556 voxels, t-value = 4.21) compared with the control group. The cervical myelopathy group had a decrease in ALFF in the bilateral posterior supramarginal gyrus (right, cluster size = 222 voxels, t-value = 5.09; left, cluster size = 436 voxels, t-value = 5.28). After surgery, the bilateral sensorimotor cortices (right, cluster size = 468 voxels, t-value = 6.74; left, cluster size = 167 voxels, t-value = 5.40) and left visual cortex (cluster size = 3748 voxels, t-value = 6.66) showed decreased ALFF compared with preoperative ALFF, indicating postoperative normalization of spontaneous brain activities in these regions. However, the bilateral posterior supramarginal gyrus did not show an increase in ALFF postoperatively, although ALFF in this region decreased preoperatively. Greater levels of ALFF at the left and right frontal pole and left pars opercularis of the inferior frontal gyrus before surgery in the cervical myelopathy group were correlated with larger improvements in the JOACMEQ-UEF score 6 months after surgery (r = 0.784; p < 0.001, r = 0.734; p < 0.001 and r = 0.770, respectively; p < 0.001). The prediction formula, based on preoperative ALFF values in the left frontal pole, was as follows: the predicted postoperative improvement in the JOACMEQ-UEF score = 34.6 × preoperative ALFF value - 7.0 (r = 0.614; p < 0.001). CONCLUSIONS: Our findings suggest that preoperative ALFF may be a biomarker for postoperative recovery in that it predicted postoperative JOACMEQ-UEF scores. To establish a comprehensive prediction measure for neurologic recovery in patients with cervical myelopathy, a multicenter study is underway. LEVEL OF EVIDENCE: Level II, diagnostic study.

Assessment of effects of rhBMP-2 on interbody fusion with a novel rat model.

BACKGROUND CONTEXT: The effects of using off-label recombinant human bone morphogenetic protein (rhBMP)-2 for interbody fusion are controversial. Although animal models of posterolateral fusion are well-established, establishing animal models to validate the safety and efficacy of interbody fusion is difficult, which may contribute to the inconsistent clinical results. PURPOSE: To develop a novel animal model of interbody fusion in rat coccygeal vertebrae without destroying bony endplates. STUDY DESIGN: An experimental animal study. METHODS: Forty-five male Sprague-Dawley rats underwent coccygeal interbody fusion without violating vertebral endplates. The animals were divided into three different groups based on the materials that were implanted into the interbody space (1) allogeneic iliac bone (IB) alone (IB group), (2) IB and 3 µg of rhBMP-2 (BMP low-dose group), or (3) IB and 10 µg of rhBMP-2 (BMP high-dose group). Fusion rates were investigated using microcomputed tomography 6 weeks after the operation. The incidence of adverse events, including soft-tissue swelling, delayed wound healing, osteolysis, and ectopic bone formation were evaluated. The total number of adverse events (using the adverse event score) in each group and the swelling ratio (calculated using the surgical site tissue volume [TV; TV on postoperative day 1/preoperative TV]) were also evaluated. RESULTS: The fusion rates in the BMP low- and high-dose groups (33.3% and 46.7%) were not significantly different, but both were significantly higher than that in the IB group (0%) (p=.042 and .006, respectively). Significant differences in the incidence of osteolysis, adverse event scores, and swelling ratios were observed only between the BMP high-dose and IB groups (p=.043, .006 and .014, respectively). CONCLUSIONS: We developed a novel rat model of interbody fusion in which the vertebral endplates were not violated, reflecting the normal clinical setting. rhBMP-2 use increased the fusion rate, but a higher dose of rhBMP-2 did not lead to a higher fusion rate than that for low-dose rhBMP-2; conversely, it led to an increase in the occurrence of adverse events. CLINICAL SIGNIFICANCE: This novel rat model of coccygeal interbody fusion that preserved bony endplates has clinical significance for validating the effectiveness of biologics or bone graft substitutes before clinical trial.

The combined effects of teriparatide and anti-RANKL monoclonal antibody on bone defect regeneration in ovariectomized mice.

OBJECTIVE: The purpose of this study was to investigate the combined effects of teriparatide (TPTD) and anti-murine receptor activator of nuclear factor-κB ligand monoclonal antibody (anti-RANKL Ab) on both cancellous and cortical bone healing in ovariectomized mice. METHODS: Thirteen-week-old mice were divided into the sham-operated group (n=11) or the ovariectomized group (n=44). At 1 month post-operation, all mice underwent bone defect surgery on the left femoral metaphysis (cancellous bone healing model) and right femoral mid-diaphysis (cortical bone healing model). After creating the bone defects, all ovariectomized mice were assigned to one of four groups to receive 1) saline (5 times a week; CNT group), 2) TPTD (40µg/kg 5 times a week; TPTD group), 3) anti-RANKL Ab (5mg/kg once; Ab group), or 4) a combination of TPTD and anti-RANKL Ab (COMB group). The following analyses were performed: Time-course microstructural analysis of healing in both cancellous and cortical bone in the bone defect, measuring the volumetric bone mineral density and the cortical bone thickness of the tibia as a representative of whole body bone with the use of micro-computed tomography, and histological analysis. RESULTS: Regeneration of cancellous bone volume in the COMB group was the highest among the four groups, and combined treatment accelerated the formation of medullary callus during the early phase of bone regeneration. On the other hand, there were no significant differences in the regeneration of cortical bone volume during the early phase of bone regeneration among the four groups. Furthermore, lamellar bone was not well identified in the all four groups. Volumetric bone mineral density in the tibia in the COMB group was significantly higher compared with that in the CNT and TPTD groups and tended to be higher compared with that in the Ab group. The mean values of cortical bone thickness in the TPTD and COMB groups were significantly higher than that in the CNT group. CONCLUSION: In a mouse model of postmenopausal osteoporosis, combination therapy of TPTD and anti-RANKL Ab accelerates regeneration of cancellous bone more effectively than either agent alone during the early phase of bone regeneration.