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The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1β (IL-1β). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1β is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1β-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1β-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1β-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1β-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.

Background DHS is characterized by chin-on-chest deformity and devastatingly impedes activities of daily living in affected individuals. There is a paucity of literature about the pathophysiology of DHS including knowledge about spinal sagittal alignment. We conducted this study to clarify the relationship between cervical sagittal alignment and global sagittal balance in DHS. Methods This is a retrospective radiographic study of a case series of DHS. Forty-one patients with diagnosed DHS were enrolled. Measurements were made using lateral standing radiograph. Results C2–C7 sagittal vertical axis (SVA) was estimated as 52.0 ± 2.4 mm. Among sagittal parameters, C7–S1 SVA positively correlated with C2–C7 angle (C2–C7 A) (r = 0.33). For the correlations between C7 and S1 SVA and C2–C7 A, both logistic and linear regression models were used to determine the threshold for C2–C7 A value responsible for global sagittal balance. C2–C7 A of − 15.0 and 6.0 were predicted by logistic and linear regression models and were considered responsible for the occurrence of global positive imbalance. Therefore, we divided into two groups, namely, cervical kyphosis group (C type) and diffuse kyphosis group (D type) by median value of C2–C7 A. Enlarged thoracic kyphosis and global positive imbalance were observed in D type compared to C type. Conclusion C2–C7 A exhibited correlations with cervical balance and also with global balance. There should be various type of thoraco-lumbar alignment in DHS. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

Study design Retrospective study of prospectively collected outcome data. Objective The aim of this study was to investigate reoperation cases and determine whether or not the experience period of a single surgeon was associated with the causes of reoperations following lumbar microendoscopic discectomy for disc herniation (MEDH) and microendoscopic decompression for spinal stenosis (MEDS). Summary of background data There have been few studies that investigated reoperation cases following MEDH and MEDS. Methods Between June 2005 (first experience of MEDH) and September 2013, the same surgeon had been using MEDH and/or MEDS on 441 consecutive patients. The follow-up rate was 89.3%. The causes and rates of reoperations (RORs) were determined at 5 years after the initial operations. We also investigated the experience period of a single surgeon (EPS, interval between June 2005 and initial operation: median, 37 months). Results The 5-year reoperation rate for all patients combined was 12.4% (49/394). The main causes for reoperations were recurrence of disc herniation (ROR, 7.01%) and increase of postoperative spondylolisthesis and/or instability (ROR, 9/394 = 2.28%); two of the nine cases were caused by excessive decompression, and the EPSs were 11 and 16 months. The other causes for reoperations were postoperative epidural hematoma (ROR, 0.76%; median EPS, 20 months), insufficient decompression (ROR, 0.25%; EPS, 17 months), and residual segmental scoliosis (ROR, 7.69%); two segmental scoliosis cases did not provide relief from sciatica, and therefore L4/5 transforaminal interbody fusions were performed. Conclusion Postoperative epidural hematoma and excessive or insufficient decompression were often observed in the initial series of patients as the causes for reoperations. We think that it is important to be aware of and prevent such potential problems in any initial series of patients, as there are limitations to any surgical indications for the use of microendoscopic decompression for degenerative segmental scoliosis because of original traction and/or kinking of nerve roots. Level of evidence 4.

Sagittal spinal alignment has mainly analyzed in the standing position. According to previous studies, there are significant differences in lumbopelvic alignment between the standing and sitting positions and cervical alignment is affected by lumbopelvic alignment. In this study, therefore, we hypothesized that cervical sagittal alignments are different between the standing and sitting positions.A total of 108 patients with spinal degenerative diseases underwent whole spine radiography. Cervical lordosis (CL), C2-7 SVA, T1S, C7-S1 SVA, TK, LL, SS, PT, and PI were measured in the standing and sitting positions. Patients were classified into 3 groups according to the changes in CL (ΔCL, CL in the sitting position - CL in the standing position); ΔCL -3° (Decreased group: DG; 28.7%), -3° ≤ ΔCL ≤ 3° (Unchanged group: UG; 41.7%), and ΔCL 3° (Increased group: IG; 29.6%).The parameters of the UG in the standing position were closer to the ideal alignment (SRS-Schwab classification). In the DG, CL, T1S, and C7-S1 SVA in the standing position were significantly higher than in the UG. In the IG, PI-LL in the standing position was significantly higher than in the UG. In the sitting position, pelvis was rotated posteriorly (decrease in SS and increase in PT) and lumbar lordosis was flattened (decrease in LL) in all groups, and C2-7 SVA was significantly higher in the DG than in the UG.CL was different between the standing and sitting positions in 58.3% of individuals. However, patients with good spinal sagittal alignment appeared to not undergo any changes in cervical alignment. Our results suggest the possibility that patients who had a positive imbalance and large PI-LL mismatch in the standing position had decreased CL and increased CL, respectively, when in the sitting position.

Characteristic features of osteoarthritis (OA) are joint pain and cartilage degeneration. The degeneration is caused by excess induction of matrix metalloproteinases (MMPs) and the pain is caused by nerve growth factor (NGF)-dependent nerve invasion into synovial tissue in addition to nociceptive pain by prostaglandin (PG)E

Purpose: Dropped head syndrome (DHS) is characterized by the passively correctable chin-on-chest deformity. The characteristic feature is emphasized in the cervical flexion position. The purpose of this study was to analyze the influence of cervical flexion on sagittal spinal alignment in patients with DHS. Methods: The study included 15 DHS subjects and 55 cervical spondylosis (CS) subjects as the control group. The following parameters were analyzed: cervical sagittal vertical axis (C-SVA), occipitoaxial angle (O–C2A), C2 slope (C2S), C2–C7 angle (C2–C7A), T1 slope (T1S), sagittal vertical axis, T1–T4 angle (T1–T4A), T5–T8 angle (T5–T8A), T9–T12 angle, lumbar lordosis, sacral slope, and pelvic tilt, in cervical flexion and neutral positions. Results: The values of C-SVA, O–C2A, C2S, and T1S were significantly different between CS and DHS at cervical neutral and flexion positions. C2–C7A showed significant difference in cervical neutral position, but the difference disappeared in flexion position. T1–T4A did not present a significant difference, but T5–T8A showed a difference in neutral and flexion positions. Conclusions: Malalignment of DHS extended not only to cervical spine but also to cranio-cervical junction and thoracic spine, except T1–T4. It is known that global sagittal spinal alignment is correlated with adjacent parameters, although in DHS the reciprocal change was lost from cranio-cervical junction to the middle part of thoracic spine at cervical flexion.

Background Although intravesical bacille Calmette-Guérin (BCG) therapy is accepted as an effective treatment for bladder cancer, serious complications may occur in rare cases. To date, only 4 cases have been reported in which the patient developed a combination of mycotic aortic aneurysm and BCG spondylitis. Accurate diagnosis of BCG spondylitis is important because it is an iatrogenic disease, and its treatment is different from usual tuberculous spondylitis. However, distinguishing BCG spondylitis from usual tuberculous spondylitis is very difficult and takes a long time. In this study, we were able to suspect BCG spondylitis at an early stage from the result of the interferon-gamma release assay (IGRA). Case presentation We encountered a case of BCG spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy in a 76-year-old man. We performed a 2-stage operation to obtain spine stabilization and replace the aneurysm with a synthetic graft. We started multidrug therapy with antituberculosis medication, excluding pyrazinamide, because the patient’s history of BCG therapy, negative IGRA, and positive of tuberculosis-polymerase chain reaction (Tb-PCR) suggested that the pathogenic bacteria of the spondylitis was BCG. Eventually the bacterial strain was identified as BCG by PCR-based genomic deletion analysis. Conclusions BCG infection should be considered in patients who have been treated with BCG therapy, even if the treatment was performed several months to several years previously. In the case of a patient with a history of BCG therapy, a positive Tb-PCR result and negative IGRA result probably suggest BCG infections, if the possibility of false-negative IGRA result can be excluded.

Characteristic features of osteoarthritis (OA) are joint pain and cartilage degeneration. The degeneration is caused by excess induction of matrix metalloproteinases (MMPs) and the pain is caused by nerve growth factor (NGF)-dependent nerve invasion into synovial tissue in addition to nociceptive pain by prostaglandin (PG)E2. The objective of this study was to clarify the suppressive mechanism of PGE2 on the regulation of MMPs and NGF by focusing on mitogen-activated protein kinases (MAPKs) and their endogenous phosphatase, dual-specificity phosphatase (DUSP)-1 in human synovial fibroblasts. PGE2 strongly increased DUSP-1 and suppressed IL-1β-induced MAPKs phosphorylation. Inhibition of MAPKs by selective inhibitors differentially regulated the IL-1β-induced expression of MMPs and NGF expression. IL-1β-induced MAPKs phosphorylation was prolonged and enhanced in DUSP-1 knockdown cells and the expression of MMPs and NGF was also increased. This study revealed that PGE2 has novel biological activity that suppresses NGF and MMPs expression by inducing DUSP-1 expression.

Study Design Retrospective study of prospectively collected outcome data. Background No studies have evaluated the long-term outcomes following microendoscopic diskectomy for lumbar disk herniation (MEDH) and microendoscopic decompression for lumbar spinal stenosis (MEDS) using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). Objective To assess the minimum 10-year outcomes following MEDH and MEDS. Patients and Methods Seventy-six patients were classified into three groups: disk herniation (DH) group (33 patients underwent MEDH); spinal stenosis (SS) group (23 patients underwent MEDS); and degenerative spondylolisthesis (DS) group (20 DS patients underwent MEDS). The follow-up rate was 50.3% (76/151). The results were statistically compared using Scheffé's F test for differences among the DH, SS, and DS groups. The paired t test was used to compare the preoperative and postoperative visual analog scale (VAS) scores. The degrees of improvement (DOIs) on JOABPEQ and the intensities of improvement (IOIs) on VAS at the first follow-up evaluation (FFE) (mean: 12 months after the operation) and at the most recent follow-up evaluation (MRFE) (mean: 126 months) of the DH group were statistically compared by the paired t test. DOIs and IOIs at MRFE of the SS group (mean: 126 months) and DS group (mean: 125 months) were statistically compared by the unpaired t test. A p value Results Statistical comparisons of the DOIs in all five functional scores and IOIs in low back pain (LBP), leg pain, and leg numbness showed no significant differences among the DH, SS, and DS groups. The effectiveness rates of pain-related disorders, gait disturbance, and social life disturbance in JOABPEQ were almost equally high in all three groups. Significant decreases in LBP, leg pain, and numbness, as measured with VAS, were noted at MRFE in all three groups. No significant differences were observed between FFE and MRFE concerning the DOIs and IOIs of the DH group, and between the SS and DS groups concerning the DOIs and IOIs at MRFE. Conclusion Clinical 1-year outcomes of MEDH were thought to be maintained for > 10 years, and MEDS leads to the same clinical long-term outcomes with DS as without DS. Moreover, MEDH and MEDS were almost equally effective for > 10 years not only in improving LBP, leg pain, and numbness but also especially in improving pain-related disorders, gait disturbance, and social life disturbance by detailed quality-of-life assessment using JOABPEQ.

Osteoporotic vertebral fracture (OVF) with nonunion or neurological deficit may be a candidate for surgical treatment. However, some patients do not show improvement as expected. Therefore, we conducted a nationwide multicenter study to determine the predictors for postoperative poor activity of daily living (ADL) in patients with OVF. We retrospectively reviewed the case histories of 309 patients with OVF who underwent surgery. To determine the factors predicting postoperative poor ADL, uni- and multivariate statistical analyses were performed. The frequency of poor ADL at final follow-up period was 9.1%. In univariate analysis, preoperative neurological deficit (OR, 4.1; 95% CI, 1.8–10.3; P

Purpose: The initial treatment of dropped head syndrome (DHS) is basically nonsurgical, but the mode of onset of DHS and efficacy of conservative treatment have not been fully clarified. Methods: The subjects were 38 DHS patients without neuromuscular disease (11 men and 27 women, average age 74.5 years). Cervical collar, physical therapy, and temporary medication for cervical pain were provided for all DHS patients. The following parameters were measured on lateral global spine standing radiographs: sagittal vertical axis (SVA), cervical sagittal vertical axis, C2–C7 angle, first thoracic slope, thoracic kyphosis, lumbar lordosis, sacral slope, pelvic tilt, and pelvic incidence. According to the mode of onset of DHS, the subjects were classified into acute-onset group (Results: Acute- and chronic-onset DHS were observed in 20 and 18 patients, respectively. A history of cervical trauma was involved in nine and two cases of acute- and chronic-onset DHS, respectively. Acute-onset DHS included more balanced-SVA (B-SVA: −30 mm Conclusions: Acute-onset DHS includes more balanced SVA and a history of cervical trauma, while acute-onset DHS without a history of cervical trauma has better prognosis by conservative treatment. Surgical indications for DHS should be carefully determined, and sufficient conservative treatment is essential.

Background: A three-dimensional (3D) digital pre-operative planning system for the osteosynthesis of distal radius fracture was developed. The objective of this study was to evaluate screw choices for three-dimensional (3D) digital pre-operative planning of osteosynthesis of distal radius fractures and to compare with the screw choices for the conventional method.Methods: Distal radius fracture patients who underwent osteosynthesis using volar locking plates were evaluated. Thirty wrists in the plan group utilized 3D preoperative planning, and nineteen wrists in the control group utilized conventional preoperative assessment. In the plan group, the 3D preoperative planning was performed prior to surgery. The reduction was simulated with 3D image, and the implant choice/placement also simulated on the 3D image. In the control group, standard preoperative planning was performed using posterior-anterior and lateral view radiographs, and CT scan. After the planning, osteosynthesis was performed. During the surgery, the operator performed the reduction and the placement of the plate while comparing images between the pre-operative plan and fluoroscopy. The distal screw lengths and the anteroposterior diameter of the radius along the axis of the distal screws were measured. The ratios of the screw length and radius diameter were evaluated. The screw/radius ratios within the range of 0.75–1.00 were considered appropriate. The screw choices less than 0.75, or greater than 1.00 were considered inappropriate. The rate of appropriate screw choices were compared between plan and control groups.Results: The results of appropriate screw choices were 86.1% and 74.8% in the plan group and the control group, respectively. The inappropriate screw choices were 14.0% and 25.2% in the plan group and the control group, respectively. The three-dimensional planning significantly increased appropriate screw choices compared to the conventional planning (p < 0.05).Conclusions: Three-dimensional digital preoperative planning is useful for the optimization of screw lengths in osteosynthesis of distal radius fractures.

Lumbo-pelvic sagittal alignment is affected by pelvic incidence (PI), and the PI represents the compensatory capacity of lumbo-pelvic sagittal alignment. The purpose of this study was to analyze changes in lumbo-pelvic sagittal alignment between the standing and sitting positions and to analyze its association with PI. This study included 253 subjects (160 men and 93 women; age 53.6 ± 7.4 years). The subjects were divided into three groups (younger age group (YG), from 20 to 49 years; middle age group, from 50 to 69 years, and older age group (OG), of 70 years and above). Lumbar lordotic angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and the associations between the changes in LL (∆LL), SS (∆SS), PT (∆PT), and PI were analyzed. In the YG, the amount of change in LL, SS, and PT was larger than in the OG. These parameters correlated with age in the standing position but not in the sitting position. On the other hand, in all groups, there were positive correlations between PI and changes between the standing and sitting positions. Multiple logistic regression analysis demonstrated that ∆LL = 3.81 − 0.72 × PT + 0.52 × PI, ∆SS = − 4.50 − 5.3 × PT + 0.34 × PI, and ∆PT = − 9.1 + 3.5 × PT − 0.21 × PI. Change in lumbo-pelvic parameters between the sitting and standing positions correlated with PI. These slides can be retrieved under Electronic Supplementary Material.

A three-dimensional (3D) digital preoperative planning system for the osteosynthesis of distal radius fractures was developed for clinical practice. To assess the usefulness of the 3D planning for osteosynthesis, we evaluated the reproducibility of the reduction shapes and selected implants in the patients with distal radius fractures. Twenty wrists of 20 distal radius fracture patients who underwent osteosynthesis using volar locking plates were evaluated. The 3D preoperative planning was performed prior to each surgery. Four surgeons conducted the surgeries. The surgeons performed the reduction and the placement of the plate while comparing images between the preoperative plan and fluoroscopy. Preoperative planning and postoperative reductions were compared by measuring volar tilt and radial inclination of the 3D images. Intra-class correlation coefficients (ICCs) of the volar tilt and radial inclination were evaluated. For the implant choices, the ICCs for the screw lengths between the preoperative plan and the actual choices were evaluated. The ICCs were 0.644 (p 0.01) and 0.625 (p 0.01) for the volar tilt and radial inclination in the 3D measurements, respectively. The planned size of plate was used in all of the patients. The ICC for the screw length between preoperative planning and actual choice was 0.860 (p 0.01). Good reproducibility for the reduction shape and excellent reproducibility for the implant choices were achieved using 3D preoperative planning for distal radius fracture. Three-dimensional digital planning was useful to visualize the reduction process and choose a proper implant for distal radius fractures. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2646-2651, 2017.

Vor allem die steigende Komplexitaet der allradgetriebenen Fahrzeuge (Visco-Kupplung, Drehmomentsensor, aktive Drehmomentverteilung, hybrid-elektrischer Allradantrieb etc.) erschwert es zunehmend, sie fuer Kraftstoffverbrauchspruefungen auf Rollenpruefstaenden auf Einachsantrieb (2WD) umzuruesten, wie es in der Praxis bisher immer erforderlich war. Deshalb haben Allrad(4WD)-Rollenpruefstaende in die Verbrauchs- und Emissionsmessung Einzug gehalten. Auf Allradpruefstaenden durchgefuehrte Kraftstoffverbrauchspruefungen zeigten, dass ein Grossteil der aufgetretenen mechanischen Verluste auf den Reifenschlupf zurueckzufuehren ist. Fuer die Reproduzierbarkeit der Pruefungen ist dessen Stabilisierung daher entscheidend. Vor diesem Hintergrund wurden Fahr- und Auslaufpruefungen von Toyota Motor Corporation und Horiba, Ltd. nach dem japanischen Modus 10-15 parallel auf einem Allrad-Rollenpruefstand und auf der Strasse durchgefuehrt. Die Untersuchungen zeigen, dass sich die Belastungen in einem Allrad-Rollenpruefstand stabil regeln lassen. Bei der Pruefung traegt vor allem der Reifenschlupf zum Fahrwiderstand bei. Veraenderungen des Reifenschlupfs korrelieren mit den Schwankungen der Reifentemperatur; dabei zeigen sich innerhalb kurzer Zeitraeume erhebliche Veraenderungen. Wird der Fahrwiderstand auf einem Rollenpruefstand mit einem abweichenden Reifenschlupf eingestellt, hat dies betraechtliche Auswirkungen auf die Reproduzierbarkeit der Kraftstoffverbrauchsmessung. Fuer stabile und genaue Verbrauchsmessungen zeigte sich, dass fuer das Erwaermen von Pruefstand und Fahrzeug ein bestimmtes Verfahren angemessen ist.