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OBJECTIVE Teriparatide (TPTD) is a potent promoter of early-stage osteogenesis and may be a useful adjuvant therapy to reduce complications related to bone fragility in spinal surgery patients with osteoporosis. However, effective neoadjuvant TPTD therapy regimens remain poorly understood. This study aimed to examine the effect of preoperative TPTD administration on cancellous bone with bone histomorphometry and to clarify the timing of preoperative TPTD administration for patients with spinal fusion and osteoporosis. METHODS In this longitudinal multicenter study, 57 patients with spinal fusion and osteoporosis, who consented to undergo iliac biopsy, were allocated to the following treatment groups: neoadjuvant TPTD therapy group (n = 42) and no neoadjuvant therapy (NTC) group (n = 15). Patients in the TPTD group were categorized into subgroups on the basis of duration of preoperative TPTD administration, as follows: 1 month (n = 9), 2 months (n = 8), 3 months (n = 9), 4 months (n = 7), and 6 months (n = 9). All patient samples were preoperatively double labeled with tetracycline, and iliac biopsies were performed during spinal fusion surgery. Histomorphometric analyses were performed on nondecalcified, thin-sliced specimens. Specimens were classified on the basis of TPTD administration duration and subsequently compared with those of the NTC group. Postoperative complications and Oswestry Disability Index scores were evaluated at 1 and 2 years after surgery. RESULTS There were no demographic differences between groups. Mineralizing surface/bone surface, a key parameter of dynamic bone formation, started to increase after 1 month of TPTD administration; this increase became significant after 3 months of administration and peaked at 4 months, with a 6-fold increase relative to that of the NTC group. The patients who received preoperative TPTD for 3 months or more had superior clinical results in terms of the osteoporotic complication rate and Oswestry Disability Index scores, except for bisphosphonate-pretreated patients. CONCLUSIONS When considering neoadjuvant TPTD therapy, the authors recommend at least 3 months of preoperative administration to provide a more substantial anabolic effect from the early postoperative stage.

We aimed to investigate the impact of long corrective fusion to the ilium on the physical function in elderly patients with adult spinal deformity and its correlation with spinopelvic parameters and health-related quality of life outcomes.We included 60 female patients who underwent long corrective fusion from T9 or T10 to the pelvis for adult spinal deformities (mean age of 69.8 years, range 55-78 years). The radiographic parameters, health-related quality of life outcomes using the Scoliosis Research Society Outcome Instrument-22 and physical function assessments were reviewed preoperatively and at 1-year postoperatively.All spinopelvic parameters, except for thoracolumbar kyphosis, and all domains of the Scoliosis Research Society Outcome Instrument-22 significantly improved at 1-year postoperatively (p 0.0001). Physical function results, including those for one-leg standing time, timed up-and-go test, and 6-min walk tests, significantly improved at 1-year postoperatively (p 0.005). Based on forward stepwise multivariate logistic regression, the predicted timed up-and-go test and 6-min walk test outcomes at 1-year postoperatively were as follows: timed up-and-go test, 7.8 + 0.47 × preoperative timed up-and-go test - 0.21 × 1-year postoperative grasping power +0.015 × 1-year postoperative C1 sagittal vertical axis (R2 = 0.6209, p 0.0001); 6-min walk test, 309.2-9.1 × body mass index + 11.6 × 1-year postoperative grasping power + 3.3 × 1-year postoperative thoracolumbar kyphosis - 0.59 × 1-year postoperative C1 sagittal vertical axis (R2 = 0.4409, p 0.0001).Corrective long fusion surgery for adult spinal deformity in normalizing sagittal alignment improves trunk balance and gait performance. Postoperative physical function depends on the preoperative physical performance status and skeletal muscle status; thus, preoperative interventions for improved physical function are recommended.

To evaluate the impact of the flexibility of thoracolumbar or lumbar (TL/L) curves on low back pain (LBP) and disc degeneration in adult patients nonoperatively treated for adolescent idiopathic scoliosis (AIS). Forty-seven adult patients (46 women; mean age, 40.5 years) nonoperatively treated for AIS with TL/L curves were included. The patients completed radiological examinations, magnetic resonance imaging, and a questionnaire survey for LBP evaluation. The flexibility of the spinal deformity was evaluated using supine side-bending radiographs. Radiographic measurements were correlated with scores for LBP and disc degeneration. The average magnitude and flexibility of the TL/L curve were 49.0° and 56%, respectively. The magnitudes of the TL/L curve and disc wedging were significantly correlated with LBP (|r|= 0.3–0.4). The flexibility of the TL/L curve and disc wedging, and the lumbar lateral range of motion (ROM) were significantly correlated with LBP and disc degeneration (|r|= 0.3–0.5). After controlling for the magnitudes of the TL/L curve and disc wedging, the flexibility of L4/5 disc wedging and the lumbar lateral ROM remained significantly correlated with the Scoliosis Research Society-22 pain score (partial correlation coefficient [r′] = 0.5 and 0.3), Oswestry Disability Index (− 0.3 and − 0.3), and disc degeneration (− 0.4 and 0.3). In AIS patients with TL/L curves, the flexibility of L4/5 disc wedging and the lumbar lateral ROM were significantly correlated with LBP and disc degeneration, independent of the magnitudes of the coronal deformities. Our findings indicate that maintaining or improving lumbar flexibility may be beneficial for preventing or treating LBP.

Background It is well known that correction surgery for adult spinal deformity (ASD) improves sagittal and coronal spinopelvic alignment, but the surgery effect on lower extremities (LE) is not well clarified. The aim of this study was to test the hypothesis that LE alignment also improves following spinopelvic correction surgery for ASD as a function of compensatory mechanism, and to clarify an effect of the severity of knee osteoarthritis (OA) on the improvement. Methods We retrospectively evaluated spinopelvic alignment, hip knee ankle angle (HKA), knee flexion angle (KF), and severity of the knee OA in thirty-nine patients with ASD before, two weeks and three months after the surgery. The grade of knee OA was evaluated by Kellgren Lawrence grading, and classified grade 0 to 2 into mild, and 3, 4 into severe OA. All the values were compared by paired t test or Wilcoxon signed rank test with significant p value of Results Following the surgery, not only spinopelvic, but also bilateral HKA and KF were significantly improved. HKA in mild OA side was more normalized compared to that in severe side. Although KF of both bilateral mild and bilateral severe OA groups improved, the improvement of mild group was more significant. Conclusion The 3D alignment of LE improved following spinopelvic correction surgery. The improvement was inadequate in cases with severe knee OA.

Background The differences in etiology, clinical manifestation, and whole body standing alignment between single-level LDS (sLDS) and double-level LDS (dLDS) have not been sufficiently clarified. We hypothesized that the etiology and manifestations of dLDS differ from those of sLDS. This study aimed to test this hypothesis. Methods A total of 112 cases with sLDS, 25 cases with dLDS, and 50 healthy volunteers as a normal control were enrolled in the study. Following the data collection on demographic and Health-related quality of life (HRQOL) by ODI and SRS-22, radiologic measurement by EOS system and MRI examination including lumbar spinal stenosis (LSS), facet angle, and segmental instability defined by facet opening were performed. All the parameters were compared among the groups. Correlations among radiologic parameters and HRQOL were analyzed. Risk factors for sLDS and dLDS were investigated respectively using multivariate logistic analysis. Results Age is the most important etiologic factor of sLDS; whereas high PI, age, and sagittally oriented facet joints are the important factors for dLDS. HRQOL significantly correlates with sagittal alignment. HRQOL does not, however, significantly differ between patients with sLDS and dLDS. Although the mean value of %slip was higher in the dLDS group than in the sLDS group, the difference was not statistically significant. %slip positively correlated with the PI. The number of spinal stenoses (LSS) per patient is significantly higher in patients with dLDS than in patients with sLDS. The HRQOL does not, however, correlate with the number of LSS. Conclusions Age is the most important etiologic factor of sLDS; whereas high PI, age, and sagittally oriented facet joints are the important factors for dLDS. HRQOL does not significantly differ between patients with sLDS and dLDS. Number of LSS is significantly higher in dLDS than in sLDS without statistical difference in terms of HRQOL outcome.

A retrospective long-term follow-up study.To investigate the health-related quality of life (HRQOL) status in middle-aged patients with adolescent idiopathic scoliosis (AIS) treated non-surgically.The HRQOL status using various established questionnaires for non-operated AIS patients has not been fully investigated in long-term follow-up surveys.Inclusion criteria were non-surgical treatment for AIS, more than or equl to 30° major scoliosis at skeletal maturity (Risser grade ≥4), and age more than or equl to 30 years at the time of the survey. A total of 107 AIS patients were included and divided into three groups (single main thoracic [MT] curve group; n = 50, single thoracolumbar/lumbar [TL/L] curve group; n = 19, and double-major [DM] curve group; n = 38) based on curve location at skeletal maturity. Age- and sex-matched volunteers were selected as the control group.There were no significant differences in age at survey, body mass index, bone mineral density of the femoral neck, and skeletal muscle mass index among the groups. In all groups, major scoliosis progressed by approximately 0.5°/yr from the time of skeletal maturity to the survey. The thoracolumbar (TL/L) and double-major (DM) groups showed significantly worse visual analog scale scores for low back pain compared with the main thoracice (MT) group (P 0.05). The all-scoliosis groups showed significantly worse scores for self-image domain of the Scoliosis Research Society Outcome Instrument-22 (SRS-22) than the control group (P 0.0001). The TL/L group showed significantly worse scores for walking ability and social function domains of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) (P 0.05). There were no significant differences in Oswestory Disability Index and Short-Form-12 among the four groups.AIS patients with single MT curve maintain equal HRQOL status compared with healthy controls. Patients with structural TL/L curves are likely to experience greater annual TL/L curve progression and have substantial low back pain or worse low back pain-specific HRQOL status during middle age.4.

Study design Retrospective case series. Purpose To investigate the oncological outcomes, including distant relapse, after en bloc spondylectomy (EBS) for spinal metastases in patients with a minimum of 2-year follow-up. Overview of literature Although EBS has been reported to be locally curative and extend survival in select patients with spinal metastases, detailed reports regarding the control of distant relapse after EBS are lacking. Methods We conducted a retrospective review of 18 consecutive patients (median age at EBS, 62 years; range, 40-77 years) who underwent EBS for spinal metastases between 1991 and 2015. The primary cancer sites included the kidney (n=7), thyroid (n=4), liver (n=3), and other locations (n=4). Survival rates were estimated using the Kaplan-Meier method, and groups were compared using the log-rank method. Results The median operative time and intraoperative blood loss were 767.5 minutes and 2,375 g, respectively. Twelve patients (66.7%) experienced perioperative complications. Five patients (27.8%) experienced local recurrence of the tumor at a median of 12.5 months after EBS, four of which had a positive resection margin status. Thirteen patients (72.2%) experienced distant relapse at a median of 21 months after EBS. The estimated median survival period after distant relapse was 20 months (95% confidence interval, 0.71-39.29 months). No association was found between resection margin status and distant relapse. Overall, the 2-year, 5-year, and 10-year survival rates after EBS were 72.2%, 48.8%, and 27.1%, respectively. Importantly, the era in which EBS was performed did not impact the oncological outcomes. Conclusions Our results suggest that EBS by itself, even if margin-free, cannot prevent further dissemination, which occurred in >70% of patients at a median of 21 months after EBS. These results should be considered and conveyed to patients for clinical decision-making.

Tubules interact with glomeruli, which are composed of podocytes, parietal epithelial cells, mesangial cells, and glomerular endothelial cells. Glomerular-tubular balance and tubuloglomerular feedback are the two components of the tubular-glomerular interplay, which has been demonstrated to play roles in physiological renal function and in diabetic kidney disease (DKD), in which proteins leaking from glomeruli arrive at tubular regions, leading to further tubular injury caused by the accumulation of proteinuria-inducing reactive oxygens species and various cytokines. In the current review, we present our recent work identifying a novel tubular-glomerular interplay in DKD mediated by sirtuin 1 and nicotinamide mononucleotide.

Study design A retrospective, long-term follow-up study. Objective We investigated the natural course of compensatory lumbar curves in patients with primary thoracic adolescent idiopathic scoliosis (AIS). Summary of background data The natural course of compensatory lumbar curves in primary thoracic AIS remains unknown. Methods Inclusion criteria were right-sided primary thoracic AIS ≥30° with a Lenke lumbar modifier of A or B at skeletal maturity and ≥30 years of age at the time of the survey. Fifty-one patients (mean age, 40.2 yr) returned for a follow-up evaluation (follow-up rate, 34.2%). Patients were classified into three groups based on the lumbar modifier (A or B) and direction of L4 tilt [right (R) or left (L)] (AR, n.11; AL, n.18; and B, n.22). At the time of the survey, 42 patients underwent radiological examinations and 37 underwent lumbar magnetic resonance imaging. Quality of life questionnaires were completed in all patients and in a 1:1 matched control group (no history of scoliosis). Results The thoracic curves had significantly progressed in all patient groups, while the compensatory lumbar curve progressed only in the B group. The C7 translation and L4 tilt shifted to the right in the AR and AL groups, but did not change in the B group. As a result, the L4 tilt (median, 11°) and C7 translation (18.6 mm) tended to be the greatest in the AR group. The incidences of Modic changes at L4/5 discs and ≥3 cm on the visual analogue scale for low back pain were significantly higher in the AR group (77.8% and 54.5%, respectively) compared with that in the other groups. Conclusion The natural course of compensatory lumbar curves is dependent on the lumbar modifier and direction of L4 tilt. Adolescent patients with right-sided primary thoracic AIS (≥30°) with L4 tilted to the right should be considered for periodic follow-ups into adulthood. Level of evidence 4.

Phospholipase A2 receptor (PLA2R) is the most common primary target antigen of idiopathic membranous nephropathy (MN) although PLA2R antibodies are also reported to be present in malignancy-associated MN. However, a case of PLA2R-positive MN secondary to PLA2R-positive carcinoma has not been reported. A 26-year-old Japanese woman presented with general fatigue, fever, and nonproductive cough. Computed tomography demonstrated a left kidney mass with pathologic diagnosis of Xp11.2 translocation renal cell carcinoma (RCC). After the second time of administration with Sunitinib, the patients exhibited significant proteinuria and hypoalbuminemia. Renal biopsy revealed a diagnosis of diffuse MN secondary to RCC. Immunofluorescence staining showed granular patterns positive for immunoglobulin (Ig) G, IgA, and C3c. PLA2R and IgG1-3 were positive, while IgG4 was negative. For the treatment of severe nephrotic syndrome, we attempted steroid therapy without any clinical improvement. Open nephrectomy was performed and surprisingly, RCC was stained for PLA2R with polarity for the basal side. At outpatient follow-up, 4 months after the operation, urinary protein had still persisted, although serum albumin was slightly increased. We report a case of PLA2R-positive MN secondary to PLA2R-positive RCC.

Aims The aim of this study is to test the hypothesis that three grades of sagittal compensation for standing posture (normal, compensated, and decompensated) correlate with health-related quality of life measurements (HRQOL). Methods A total of 50 healthy volunteers (normal), 100 patients with single-level lumbar degenerative spondylolisthesis (LDS), and 70 patients with adult to elderly spinal deformity (deformity) were enrolled. Following collection of demographic data and HRQOL measured by the Scoliosis Research Society-22r (SRS-22r), radiological measurement by the biplanar slot-scanning full body stereoradiography (EOS) system was performed simultaneously with force-plate measurements to obtain whole body sagittal alignment parameters. These parameters included the offset between the centre of the acoustic meatus and the gravity line (CAM-GL), saggital vertical axis (SVA), T1 pelvic angle (TPA), McGregor slope, C2-7 lordosis, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), PI-LL, sacral slope (SS), pelvic tilt (PT), and knee flexion. Whole spine MRI examination was also performed. Cluster analysis of the SRS-22r scores in the pooled data was performed to classify the subjects into three groups according to the HRQOL, and alignment parameters were then compared among the three cluster groups. Results On the basis of cluster analysis of the SRS-22r subscores, the pooled subjects were divided into three HRQOL groups as follows: almost normal (mean 4.24 (SD 0.32)), mildly disabled (mean 3.32 (SD 0.24)), and severely disabled (mean 2.31 (SD 0.35)). Except for CAM-GL, all the alignment parameters differed significantly among the cluster groups. The threshold values of key alignment parameters for severe disability were TPA > 30°, C2-7 lordosis > 13°, PI-LL > 30°, PT > 28°, and knee flexion > 8°. Lumbar spinal stenosis was found to be associated with the symptom severity. Conclusion This study provides evidence that the three grades of sagittal compensation in whole body alignment correlate with HRQOL scores. The compensation grades depend on the clinical diagnosis, whole body sagittal alignment, and lumbar spinal stenosis. The threshold values of key alignment parameters may be an indication for treatment. Cite this article: Bone Joint J 2020;102-B(10):1359–1367.

The frequency of intraoperative periprosthetic occult fracture of the acetabulum (IPOA) in primary total hip arthroplasty (THA) is relatively high. However, the effect of this fracture on clinical outcome and survival of primary THA remains unknown. This study aimed to determine the impact of IPOA on the outcomes of primary THA during a minimum follow-up of 5 years. This retrospective case–control study compared the outcomes of primary THA with or without IPOA during a minimum 5-year follow-up. Thirty-eight patients who underwent primary THA with IPOA (O group) were matched to 76 patients without IPOA (C group) between 2004 and 2013 based on age, sex, body mass index, primary diseases, cup diameter, cup design, and additional dome screw. Both groups underwent the same rehabilitation programs after surgery. We evaluated the Japanese Orthopaedic Association clinical outcomes score; postoperative complications, such as nerve injury, dislocation, heterotopic ossification, iliopsoas impingement, or infection; and radiographic outcomes. Additionally, we performed Kaplan–Meier survival analysis with cup aseptic loosening, cup failure revision, and all-cause revision as the endpoints. There were no significant differences in the pre- and postoperative clinical scores, postoperative complication rates, and cup sagittal rotation between the two groups. Radiographic evaluations showed no aggravation of cases to overt fractures. Bone ingrowth was observed in all cases, and none of the acetabular cups had a progressive radiolucent line ≥ 2 mm in all the 3 acetabular zones. Ten-year survival rates for cup aseptic loosening and cup failure revision were 100% in both groups; those for all-cause revision were 97.4% (92.0–100%) and 100% in the O and C groups, respectively (p = 0.157). Primary THA with IPOA provides favorable mid- to long-term outcomes. On IPOA diagnosis, although radiographic follow-up is necessary, additional treatments or rehabilitation programs are not required. Furthermore, postoperative computed tomography images for the detection of IPOA may be unnecessary.

Background The activation of NAD+-dependent deacetylase, Sirt1, by the administration of nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases. Methods Diabetic db/db mice were treated with NMN transiently for 2 weeks and observed for effects on diabetic nephropathy (DN). Results At 14 weeks after the treatment period, NMN attenuated the increases in urinary albumin excretion in db/db mice without ameliorating hemoglobin A1c levels. Short-term NMN treatment mitigated mesangium expansion and foot process effacement, while ameliorating decreased Sirt1 expression and increased claudin-1 expression in the kidneys of db/db mice. This treatment also improved the decrease in the expression of H3K9me2 and DNMT1. Short-term NMN treatment also increased kidney concentrations of NAD+ and the expression of Sirt1 and nicotinamide phosphoribosyltransferase (Nampt), and it maintained nicotinamide mononucleotide adenyltransferase1 (Nmnat1) expression in the kidneys. In addition, survival rates improved after NMN treatment. Conclusions Short-term NMN treatment in early-stage DN has remote renal protective effects through the upregulation of Sirt1 and activation of the NAD+ salvage pathway, both of which indicate NMN legacy effects on DN.

The progression of chronic kidney disease (CKD) cannot be completely inhibited. We first explored factors contributing to CKD progression in patients with CKD in a prospective observational study. In the next phase, we focused on the effects of aldosterone, conducting a single-blinded placebo-controlled study using the selective mineralocorticoid receptor antagonist (MRA), eplerenone (25 mg/day). We recruited patients with CKD stage 2 and 3 whose plasma aldosterone concentration was above 15 ng/dL based on the prior data of a prospective observational study. In the CKD cohort study (n = 141), baseline plasma aldosterone concentration was identified as an independent contributory factor for the future rate of change in estimated glomerular filtration rate (eGFR). When the cut-off value for aldosterone was set at 14.5 ng/dL, the decline rate was significantly higher in patients with higher plasma aldosterone concentration (− 1.22 ± 0.39 ml/min/1.73 m2/year vs. 0.39 ± 0.40 ml/min/1.73 m2/year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone.

Background Although pelvic incidence (PI) is a key morphologic parameter in assessing spinopelvic sagittal alignment, accurate measurements of PI become difficult in patients with severe hip dislocation or femoral head deformities. This study aimed to investigate the reliability of our novel morphologic parameters and the correlations with established sagittal spinopelvic parameters. Methods One hundred healthy volunteers (25 male and 75 female), with an average age of 38.9 years, were analysed. Whole-body alignment in the standing position was measured using a slot-scanning X-ray imager. We measured the established spinopelvic sagittal parameters and a novel parameter: the sacral incidence to pubis (SIP). The correlation coefficient of each parameter, regression equation of PI using SIP, and regression equation of lumbar lordosis (LL) using PI or SIP were obtained. The intraclass correlation coefficient (ICC) was calculated as an evaluation of the measurement reliability. Results Reliability analysis showed high intra- and inter-rater agreements in all the spinopelvic parameters, with ICCs > 0.9. The SIP and pelvic inclination angle (PIA) demonstrated strong correlation with PI (R = 0.96) and pelvic tilt (PT) (R = 0.92). PI could be predicted according to the regression equation: PI = − 9.92 + 0.905 * SIP (R = 0.9596, p R = 0.6033, p R = 0.6177, p Conclusions Both SIP and PIA were reliable parameters for determining the morphology and orientation of the pelvis, respectively. Ideal LL was accurately predicted using the SIP with equal accuracy as the PI. Our findings will assist clinicians in the assessment of spinopelvic sagittal alignment. Trial registration This study was retrospectively registered with the UMIN Clinical Trials Registry (UMIN000042979; January 13, 2021).

To clarify the relationship between whole body sagittal radiographic parameters and health related quality of life (HRQOL) in patients with spinal disease, and further analyse such relationship based on the pelvic incidence (PI) value.100 patients (mean age: 64.4 years, M/F=50/50) with lumbar degenerative disease or spinal deformity were prospectively investigated. Following oswestry disability index (ODI) and scoliosis research society score 22 (SRS-22) questionnaire, whole body sagittal x-ray parameters were measured using a slot-scanning 3D x-ray imager (EOS). Correlations between such radiographic parameters and ODI/SRS-22 scores were analysed. Then, patients were divided into three groups based on the PI value (PI≤45°, 45PI≤60°, and 60PI), and correlations between the significantly correlated parameters and ODI/SRS-22 scores were analysed for each PI group.C2-7 lordosis, pelvic tilt (PT), pelvic incidence (PI), PI minus lumbar lordosis (PI-LL), sagittal vertical axis (SVA), full balance integrated index (FBI), and knee flexion angle (KneeFlex) had a significant correlation with ODI or SRS-22 scores. Among those parameters, PI and FBI showed a significant correlation with both ODI and SRS-22 scores. High PI (60°) group showed a strong correlation (R0.4) with both ODI and SRS-22 scores for PI-LL parameter.PI and FBI showed a significant correlation with both ODI and SRS-22 scores. PI-LL mismatch was strongly correlated with disability in high PI patients. Our study results may indicate that it is important to pay attention to the PI value in addition to the spinopelvic relationship.II, prospective study.

An innovative low-dose X-ray biplanar imager (EOS®) allows measurement of the whole-body in standing-position which is necessary for the evaluation of spinal deformities. A total of 60 asymptomatic subjects (ages 20–81 years) were evaluated using the 3D workflow called postural assessment and 2D measures. Subjects were measured twice each by two new observers following training, including: lordosis/kyphosis, pelvic parameters, sagittal-vertical axis, and spinal-sacral angle. Intra- and inter-observer reproducibility and similarity were compared between 2D and 3D measures. The intraclass correlation coefficient (ICC) was very high for the 3D measures (>0.9) and excellent for the 2D measures (>0.75). In all cases, the overall mean absolute difference between repeated 3D measures was less than 2°, or 2 mm. For all parameters, the inter- and intra-observer reproducibility in 3D measures were significantly superior to 2D measures (p < 0.03). This study demonstrated that 3D measures have better reproducibility than 2D for sagittal balance. • Reproducibility of sagittal balance 2D/3D measurements was evaluated using EOS® full-body radiographs. • Inter- and intra-observer reproducibility were significantly superior for 3D measures vs. 2D. • 3D measures have better reproducibility than 2D for sagittal balance.

Background Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment. Method Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact. Results The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects. Conclusion AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.

Tumor growth is closely related to the development of an intrinsic vascular network. However, microvascular appearance was not regarding highly to pathological diagnosis, though clinical applicability of endoscopic narrow-bad imaging (NBI) is developed in the oral cavity. To analyze changes of intraepithelial papillary capillary loop (IPCLs) patterns as the utility for pathological diagnosis, comparative histomorphometric analysis of IPCLs among squamous cell hyperplasia, leukoplakia with low- or high-grade dysplasia, and oral squamous cell carcinoma (OSCC) had performed. Subjects were 40 clinically hyperkeratosis, histologically consisted 5 groups; each 10 of squamous cell hyperplasia, low- or high-grade dysplasia, OSCC and normal mucosae. Sections with smooth muscle actin and CD34 immunoreactivities were used to examine comparative histomorphometric analysis on the basis of IPCL irregularities. The area, shortest diameter, proximity to the basement membrane and circularity were measured using Win Roof image analysis software. Statistical analyses were done by Kruskal–Wallis and Steel–Dwass tests. Values of p

European Journal of Orthopaedic Surgery and Traumatology (EJOST) was founded in 1991. It was initially named as Orthopédie-Traumatologie, and since then it is dedicated in sharing knowledge and new evidence in the field of orthopaedics. Within 28 volumes and 157 issues, it has published 3218 scientific articles. In the early years of its distribution, published articles were in French, while the last two decades EJOST only hosts English articles between its pages. By the very beginning of its launch, it has been publishing high-quality research articles in all orthopaedic subspecialties and has gradually become one of the leading journals in its specific subject area. The aim of this study was to identify, analyse and categorize the most frequently cited articles, published by EJOST since its launch.

STUDY DESIGN Retrospective case series. OBJECTIVE The aim of this study was to investigate clinical outcomes after posterior spinal fusion (PSF) using cervical pedicle screw (CPS) constructs for cervical disorders associated with athetoid cerebral palsy (CP). SUMMARY OF BACKGROUND DATA Traditionally, most patients with cervical myelopathy associated with CP have required combined anterior and posterior fusion to achieve solid stability against severe involuntary movement. METHODS Thirty-one CP patients with cervical disorders who underwent PSF alone with a minimum 2-year follow-up (mean 58 months) were analyzed. All patients were treated with PSF using CPS constructs with or without decompression procedures. The average number of fused segments was 5.1 (range, 1-10 segments), and a halo jacket was applied in 16 patients for at least 2 months after surgery. Clinical outcomes using the Japanese Orthoedic Association scoring system (JOA score) and walking ability, radiographic sagittal alignment, fusion status, and surgery-related complications were evaluated. RESULTS The JOA score improved from 8.3 points preoperatively to 10.9 points at the final follow-up (P

STUDY DESIGN A retrospective analysis of population-based national hospital discharge data collected for the Nationwide Inpatient Sample. OBJECTIVE To examine the demographics and in-hospital outcomes of patients with solid organ transplant (SOT) undergoing spinal fusion on a national level. SUMMARY OF BACKGROUND DATA Solid organ transplantation has become more common in recent years and some of these patients undergo spinal fusion surgery. There is, however, little information regarding the trends and outcomes in such patients. METHODS Clinical data were derived from the US Nationwide Inpatient Sample between 2000 and 2009. Patients with or without SOT who underwent spinal fusion were identified. Data regarding, patient- and healthcare system-related characteristics, comorbidities, in-hospital complications, and mortality were retrieved and analyzed. In-hospital outcomes were compared between patients with or without SOT and analyzed with the use of multivariate logistic regression. RESULTS A total of 5984 patients with SOT underwent spinal fusion in the United States during the last decade. From 2000 to 2009, population growth-adjusted incidence of patients with SOT who underwent spinal fusion has increased more than two fold (0.102 in 2000 to 0.236 in 2009, per 100,000, P

Past reports have shown the tendency of posterior pelvic tilt to increase over time after total hip arthroplasty (THA). We have hypothesized that the volume and extent of released joint capsule may influence the change in postoperative pelvic tilt. This study was conducted to ascertain whether surgical approach during THA (posterior or anterior) has an effect on postoperative changes in pelvic tilt. We conducted a retrospective review of 81 hips in 60 patients. Patients classified as Crowe group 2, 3, and 4, those who had multiple previous compression fractures, and those with spinal fusion due to spinal arthrosis were excluded. Also, those who had previously undergone THA or total hip resurfacing also were excluded. Patients were divided into two groups, those with preoperative anterior pelvic tilt and those with posterior tilt. Preoperative and postoperative X-rays and CT scans for each group were assessed to determine the chronological change in pelvic tilt, and the data were statistically analyzed for patients who had experienced both the posterior and anterior approaches. Regardless of surgical approach, there was no significant difference in the mean change in postoperative APP angle over time in either the bilateral or unilateral cases or in the groups of preoperative anterior or posterior pelvic tilt. Our results showed that surgical approach does not influence postoperative pelvic tilt after THA. In preoperative planning for THA, therefore, surgeons may need not to consider the difference of surgical approach with regard to postoperative changes in pelvic tilt.

Periprosthetic fractures of the acetabulum occurring during primary THA are rare. Periprosthetic occult fractures are defined as those not identified by the surgeon during the procedure which might be missed on a routine postoperative radiograph. However, it is unclear how frequently these fractures occur and whether their presence affects functional recovery. In this study, using routine CT scans that were obtained as part of another primary hip arthroplasty study protocol, we retrospectively assessed (1) the prevalence of occult fractures of the acetabulum occurring during primary THA, (2) the location of occult fractures of the acetabulum during THA, and (3) risk factors contributing to such occult fractures. Between 2004 and 2013, our institute performed 585 primary THAs (cementless or hybrid) in 494 patients with DICOM pre- and postoperative CT; during the period in question, all patients undergoing THA underwent CT before and after surgery. Preoperative CT images were taken as part of a CT-based three-dimensional templating software and navigation system. Postoperative CT images were taken an average of 1 week after surgery as part of a different protocol to evaluate cup position, restoration of leg length and offset, volume of postoperative hematoma to assess anticoagulation effects after THA, and fractures that were not found on routine postoperative radiographs (which we defined as occult fractures). Patients with a history of prior pelvic osteotomy, trauma, and infection were excluded (88 patients/99 hips); 406 patients (102 males and 304 females; 486 hips) form the basis of this report. The mean age of the patients was 60 ± 11 years, with a mean BMI of 23 ± 4 kg/m2. The mean followup of the patients with periprosthetic fracture of the acetabulum was 58 ± 28 months (range, 12–131 months). Potential risk factors for occult acetabular fracture including age, sex, BMI, preoperative diagnosis, additional dome screw fixation, composition and size of each cup, and acetabular design were examined in multivariate analysis. Acetabular component designs were categorized as true hemispheric, peripheral self-locking, and elliptical; during the period in question the indications for each cup design were based on the brand of stem used. Comparison between preoperative and postoperative CT images was done to detect the fractures. Patients with fractures identified during surgery were treated with additional dome screw fixation and a 3-week period of nonweightbearing. Patients with occult fractures in this series did not receive additional treatment as we had confirmed secure fixation of the cup during surgery. Occult fractures occurred in 41 hips (8.4%); periprosthetic fractures of the acetabulum were seen during surgery in an additional two hips (0.4%). The superolateral wall was the most frequent location for occult fractures of the acetabulum. After controlling for relevant confounding variables, only the use of peripheral self-locking cups was associated with an increased risk of occult fracture (odds ratio [OR], 2.6 compared with hemispheric cups; 95% CI, 1.2–5.6; p < 0.05). All patients with occult fractures showed bone ingrowth fixation at the final followup, without any additional surgical intervention. Periprosthetic occult fractures of the acetabulum may occur relatively frequently during press-fit impaction. We observed a higher rate of fractures associated with the use of peripheral self-locking components. Occult acetabular fractures not detected on routine postoperative plain films may be ignored if secure fixation of the cup has been confirmed during the operation. Level III, therapeutic study.

Purpose: This study aimed to investigate radiographic outcomes after posterior spinal fusion (PSF) for pediatric patients younger than 10 years with upper cervical disorders. Methods: Thirteen patients (mean age at surgery, 5.9 years; range, 1 to 9 years) who underwent PSF with a minimum of 2 years of follow-up (mean, 5.8 years) were included. Diagnoses were atlanto-axial instability due to congenital disorders for 11 patients and atlanto-axial rotatory fixation for 2 patients. The fusion area was occipito-cervical for 7 patients and C1/2 for 6 patients. PSF was performed using rigid screw-rod constructs for 6 patients and conventional techniques for 7 patients. Ten patients required halo immobilization after surgery. Fusion status, perioperative complications, radiographic alignment, and range of motion (ROM) from C2 to C7 were evaluated. Results: Twelve patients successfully achieved bony fusion (fusion rate, 92%), but complications occurred in 5 patients. Regarding radiographic measures (preoperative/postoperative/final follow-up), the mean atlanto-dental interval was significantly reduced (8.0 mm/2.7 mm/3.5 mm) and the C2-7 ROM was increased (from 49.4 degrees to 66.0 degrees) at the final follow-up (both comparisons, p

Background While the Trendelenburg test has been used for 120 years to detect hip abductor muscle weakness, the methodology has not been standardised. Purposes This study undertook to quantitatively analyze the relation between abductor muscle activity and pelvic tilt angle in the Trendelenburg one-leg stance, examine the pitfalls associated with performing the T-test, and develop a modified method that will produce reliable results. Methods A convenience sample of 15 healthy males was asked to assume a one-leg stance in ten different postures, five with mild flexion on the unsupported side, and five with severe flexion. Trunk sway angle, pelvic tilt angle, and the pelvic on femur (POF) angle were measured for each posture. Statistical analysis was used to assess differences in hip abductor activity and public tilt angle between the control posture and the test postures. Results With minimum trunk sway, hip abductor muscle activity increases when the pelvis is elevated and decreases when it is dropped. With trunk sway toward the test side, abductor muscle activity decreased when the pelvis was elevated; with trunk sway toward the non-test side, muscle activity stayed approximately constant when the pelvis was dropped. Conclusions Based on the results we developed a modified T-test methodology that would improve reliability. This test should be performed with minimum trunk sway and severe flexion on the non-test side. The assessment of muscle weakness is based on whether the patient can keep the single-leg standing posture when forced to elevate the pelvis, not simply on the pelvic drop. In future research, we will perform the modified T-test on patients with a suspected hip abductor deficiency, and assess the usefulness of the modified test. © 2016 The Japanese Orthopaedic Association

Diabetic nephropathy (DN) is accompanied by characteristic changes in the glomerulus, but little is known about the effect of diabetes on parietal epithelial cells (PECs). In this study, a descriptive analysis of PECs was undertaken in diabetic db/db mice and in diabetic patients. PEC hypertrophy was significantly more prominent in diabetic mice than in nondiabetic mice, and this was evident even at the early stage. Additionally, the number of vacuoles in PECs was markedly increased in diabetic mice, suggesting the presence of cellular injury in PECs in DN. Although rare, binuclear cells were observed in mice with early diabetes. In cultured PECs, a high glucose condition, compared with normal glucose condition, induced cellular hypertrophy and apoptosis. Flow cytometry showed that some PECs in the G0 phase reentered the cell cycle but got arrested in the S phase. Finally, in human diabetic subjects, hypertrophy and vacuolization were observed in the PECs. Our data showed that PECs undergo substantial changes in DN and may participate in rearrangement for differentiation into podocytes.

Background: Cyst infection is a complication sometimes seen in patients with autosomal dominant polycystic kidney disease (ADPKD) and often shows through a positive blood culture. However, there have been no reports of ADPKD patients whose cyst infection propagate to peritoneal fluid leading to positive peritoneal fluid culture. Case presentation: A 74-year-old Japanese man with ADPKD under peritoneal dialysis (PD) was presented with left flank pain, fever, and chills at our hospital. He did not show any symptoms or signs suggestive of peritonitis. There were no elevated cell counts or polymorphonuclear leucocytes in his PD fluid. There were some complicated cysts found in computed tomography and magnetic resonance imaging examinations. We clinically diagnosed him as having a renal cyst infection rather than PD-related peritonitis. We initiated treatment by administering ceftriaxone with an immediate favorable response. As the possibility of accompanying prostatitis still remained, we switched to intravenous levofloxacin on the second day. On the 10th day, Helicobacter cinaedi was detected in 2 sets of blood culture as well as in PD fluid. We switched back to ceftriaxone and this treatment was entirely successful. Conclusions: This is the first report of H cinaedi cyst infection which propagates to peritoneal fluid in a patient with ADPKD.

Sporadic cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular amyloid-β (Aβ) deposition, which leads to lobar hemorrhage and dementia. Biological molecules affecting the development of CAA have not been fully characterized. In this study, we performed proteome analysis of biopsied leptomeningeal and cortical vessels obtained from 6 CAA patients and 5 non-CAA patients who underwent surgery for large lobar hemorrhages. We found that 6 proteins, including Aβ, apolipoprotein E (apoE), clusterin (CLU), albumin, complement C4 and vitronectin were significantly upregulated in the vessels of CAA patients as compared to non-CAA patients. ApoE and CLU were found in all CAA patients. We next examined the effects of apoE and CLU on the early phase of Aβ aggregation, using a simple yet powerful in vitro model of CAA, which recapitulates the intramural periarterial drainage pathway model. We found that physiological concentrations of apoE and CLU delayed the initiation time of amyloid growth kinetics in a concentration-dependent manner. These data indicate that apoE and CLU may act as extracellular chaperones to inhibit Aβ amyloid deposition in CAA.

Background Implantation of Kerboull acetabular reinforcement cross-plates (Kerboull plate) carries a risk for injury to vascular structures and pelvic organs. To our knowledge, there is no study assessing anatomical assessment related to this risk with this specific design. Therefore, we performed a prospective study to answer the following four questions: 1) What is the minimum distance and angle between the plate and iliac vessels? 2) What is the distance between the plate and the inner cortex of the ilium? 3) What is the ratio of views with muscle tissue present on the inner surface of the ilium? 4) What are the boundaries of the safe zone for transacetabular screw fixation for a Kerboull plate? Hypothesis A safe zone for fixation screws would be defined by a narrow range of insertion angles. Materials and methods This is a CT-based 3D templating prospective study. Simulations were performed for 18 patients fitted with a Kerboull plate. An original Kerboull plate (Stryker, Mahwah, NJ, USA) was placed at a 45° abduction angle relative to the X-axis (alignment A) and the palette was placed vertically to the X-axis (alignment B). We measured the distance from the centre of the plate to the inner surface of the cortex of the ilium, the shortest distance to vessels and the angle of existing vessels, and the ratio of muscles on the inner surface of the ilium. Results The shortest distance to the vascular structures increased with increasing angle of insertion of the fixation screws, 85.8 ± 12.1 mm for A and 111.4 ± 12.0 mm for B at 45°. The distance to the inner cortex was further increased for screws inserted in posterior direction. At insertion angles ≥ 40°, the screws passed through muscle before invading the pelvis in most cases. However, at anterior-posterior angle (AP angles) ≤ −10°, the risk of direct insertion of screws into the sacroiliac joint increased. Discussion The safe zone for transacetabular screws would be insertion at an angle ≥ 40°, with an AP angle between 0° and −10° (slight posterior direction). Level of evidence Level IV prospective diagnostic study.

Amyloidosis refers to a group of diseases with amyloid fibrils deposited in various organs and is classified into more than 30 diseases in humans based on the kind of amyloid protein. In order to elucidate the molecular pathogenesis of human amyloidosis, we studied the molecular mechanism of amyloid fibril formation in vitro. We first developed a novel fluorometric method to determine amyloid fibrils in vitro based on the unique characteristics of thioflavin T. We next proposed a nucleation-dependent polymerization model to explain the general mechanism of amyloid fibril formation in vitro. Based on this model, we characterized the biological molecular interactions that promote or inhibit amyloid fibril formation in vitro and developed models of pathological molecular environment for inducing human β2-microglobulin-related amyloidosis in long-term hemodialysis patients. We also proposed a novel and attractive cytotoxic mechanism of β2-microglobulin amyloid fibrils, that is, the disruption of endosomal/lysosomal membranes by endocytosed amyloid fibrils. These findings may be useful to elucidate the molecular pathogenesis of other kinds of human amyloidosis.

Myositis ossificans (MO) is an extraskeletal tumor-like lesion with bone formation, and is relatively rare in the head and neck region. We report herein a clinicopathological analysis of MO associated with a muscle of mastication. The patient was a 70-year-old Japanese woman who presented with a tumorous mass in the right parotid area and no history of trauma. The surgically excised tumorous lesion consisted of proliferating fibroblastic cells with no atypia in the central portion, and a formation of trabecular osteoid and/or bony tissue in the peripheral portion as the so-called “zonal phenomenon”. The final histological diagnosis was MO, and the lesion was located in the posterior belly of the digastric muscle on computer tomography. A review of the literature showed that many cases of MO predominantly affected the medial pterygoid and masseter muscle and showed a history of previous trauma. The present case represents a rare case of nontraumatic MO in the uncommon location of the posterior belly of the digastric muscle.

Summary: Nicotinamide adenine dinucleotide (NAD+) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of a NAD+ precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated the role of NMN-producing enzyme nicotinamide phosphoribosyltransferase (Nampt) in diabetic nephropathy. The expression of Nampt in PTs was downregulated in streptozotocin (STZ)-treated diabetic mice when they exhibited albuminuria. This albuminuria was ameliorated in PT-specific Nampt-overexpressing transgenic (TG) mice. PT-specific Nampt-conditional knockout (Nampt CKO) mice exhibited TBM thickening and collagen deposition, which were associated with the upregulation of the profibrogenic gene TIMP-1. Nampt CKO mice also exhibited the downregulation of sirtuins, particularly in Sirt6. PT-specific Sirt6-knockout mice exhibited enhanced fibrotic phenotype resembling that of Nampt CKO mice with increased Timp1 expression. In conclusion, the Nampt-Sirt6 axis in PTs serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy. : Muraoka et al. reveal that the Nampt-Sirt6 axis in proximal tubules serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy. Keywords: NAD, Nampt, Sirt6, metabo-fibrosis, NMN, TBM thickening, diabetic nephropathy

Diabetic nephropathy (DN) is the leading cause for end-stage renal disease, whose main pathological changes were traditionally believed to reside in the glomerulus, although tubulointerstitial and vascular lesions are also well documented. This chapter focuses on the metabolic abnormalities of proximal tubules in the pathogenesis of DN since diabetes is a metabolic as well as a vascular disease, partly resulting from glucose toxicity. Sirt1 is an isoform of sirtuin, a NAD+-dependent deacetylase, and is a key molecule in glucose, lipid, and energy metabolism. Sirt1 has a protective role against diabetic renal damage through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms in affected cells including mesangial cells, podocytes, and tubular cells under diabetic conditions. In diabetes, Sirt1 in the proximal tubule is downregulated before the onset of albuminuria. This downregulation is believed to disrupt the metabolism of NAD+, diminishing the replenishment of the glomerulus with nicotinamide mononucleotide (NMN) from the proximal tubule; this results in Sirt1 downregulation and tight junction protein claudin-1 upregulation in glomerular podocytes. Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) regulation may be an important new therapeutic target for diabetic nephropathy. This tubuloglomerular communication forms a novel target for the treatment of DN. The typical example is the inhibition of SGLT2 in proximal tubules, which inhibits glomerular hyperfiltration and subsequent glomerular damage. The significance of these effects is clinically demonstrated in large trials such as the EMPA-REG OUTCOME study using empagliflozin and the CANVAS Program using canagliflozin. The regulation of proximal tubular cell function is becoming an increasingly important therapeutic strategy for DN.

Study Design A retrospective cohort study. Objectives To investigate the relationship between skeletal muscle status of the trunk and the progression of adolescent idiopathic scoliosis (AIS) during adulthood. Summary of Background Data To date, studies evaluating the risk factors for progression of AIS have principally focused on radiographic parameters. Methods Eighty-two women with AIS managed conservatively, who had a major curve ≥30° at skeletal maturity (Risser grade ≥4), were enrolled. Patients had been followed-up, on average, over 23.5 years (range, 12–37 years) after skeletal maturity, and were ≥30-years-old at the time of the survey (mean, 40.1 years). The ratio of the cross-sectional area (CSA) and signal intensity (SI) of muscles (multifidus [MF], erector spinae [ES], and psoas major [PM]) were evaluated using axial T2-weighted magnetic resonance images at the level of L4. Results The mean progression of the main thoracic and thoracolumbar/lumbar (TL/L) curves after skeletal maturity was 8.2° (mean annual rate of 0.4°) and 7.2° (mean annual rate of 0.3°), respectively. The mean CSA ratio was as follows: MF, 23.3%; ES, 79.6%; and PM, 40.5%. The mean SI ratio was as follows: MF, 34.9%; ES, 31.7%; and PM, 20.9%. On multivariate logistic regression, a higher SI ratio of the MF was predictive of a progression of the Cobb angle and translation of the apical vertebra, with a lower CSA ratio of the ES contributing to the progression of the Cobb angle for the TL/L curve. Conclusions In patients with AIS who have a major curve ≥30° at skeletal maturity, patients with greater TL/L curve progression have lower skeletal muscle volume and higher fatty degeneration of the lumbar extensor muscles in adulthood. However, further longitudinal or prospective studies are necessary to clarify the causal relationship between scoliosis progression and trunk muscular status. Level of Evidence Level III, retrospective cohort study.

Background The lipodystrophy-like phenotype has been suggested in early chronic kidney disease (CKD). It includes adipose tissue atrophy, systemic insulin resistance (IR), dyslipidemia and ectopic lipid accumulation. To elucidate its pathogenesis, we investigated the role of two uremic toxins that affect insulin sensitivity: an endogenous nitric oxide synthase inhibitor, and asymmetric dimethylarginine (ADMA) and indoxyl sulfate (IS). Methods Six-week-old Sprague-Dawley rats were rendered CKD by subtotal nephrectomy (Nx) and compared with sham-operated rats. Cultured 3T3-L1 fibroblasts were differentiated into mature adipocytes with or without ADMA. Transgenic (Tg) mice overexpressing each isoform of ADMA degrading enzyme, dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2 were subject to Nx and their phenotypes were investigated. Results In Nx rats, IR was evident and insulin stimulation failed to activate insulin signaling in adipose tissues. Adipose tissue weight, adipocyte size and adipocyte differentiation marker expressions decreased as a consequence of IR in Nx. Tissue lipid content in the liver and muscle increased in Nx rats. Tissue levels of ADMA, IS and oxidative stress increased in the adipose tissue of Nx rats. Both DDAH1 and DDAH2 expressions decreased, and a putative IS receptor, aryl hydrocarbon receptor, expression increased in the adipose tissue of Nx rats. ADMA inhibited adipocyte differentiation, triglyceride accumulation and insulin signaling, which were reversed by pretreatment with cGMP. In each type of Tg mice overexpressing DDAH1 or DDAH2, all lipodystrophy-like phenotypes induced by Nx were reversed. Conclusions In mild CKD, dysregulation of the ADMA/DDAH pathway in adipose tissue triggers lipodystrophy-like phenotype changes, including ectopic fat depositions.

Background The role of gut microbiota in the progression of chronic kidney disease (CKD) has not been fully elucidated. Methods Renal failure was induced in 6-week-old spontaneously hypertensive rats by 5/6 nephrectomy (Nx). We analyzed the gut microbiota population to identify the relevant species potentially involved in inducing renal damage. Human colon Caco-2 cells were used to delineate the mechanism involved in the molecular changes in the gut of Nx rats. Results Nx rats showed an increase in Bacteroides (Bact) and a decrease in Lactobacillus (Lact) species compared with sham-operated rats. Lact, but not Bact, populations were significantly associated with urinary protein excretion. Treatment of Nx rats with 1 × 10(10) CFU/kg/day Lact ameliorated increased urinary protein excretion and higher serum levels of the uremic toxins, indoxyl sulfate and p-cresyl sulfate, and serum urea nitrogen levels. Lact also attenuated systemic inflammation in Nx rats, as evaluated by serum lipopolysaccharide, interleukin-6 and C-reactive protein levels. Histologically, renal sclerosis in Nx rats was restored by Lact treatment. A reduction in the expression of tight junction proteins and the Toll-like receptor 2 (TLR2), a putative Lact receptor, in the colons of Nx rats were mitigated by Lact. Treatment of Caco-2 cells with indole downregulated tight junction protein expression, which was abolished by exposure to Lact. The effects of Lact were reversed by treatment with OxPAPC, a TLR inhibitor. Similarly, the increase in the permeability of the Caco-2 cell monolayer was reversed by the administration of Lact. Lact upregulated TLR2 expression in Caco-2 cells. Lact also attenuated the increase in serum indoxyl sulfate and urea levels and urinary protein excretion in Nx rats even in the pseudogerm-free environment. Conclusions Lact supplementation mitigated the systemic inflammation and proteinuria associated with renal failure, suggesting that in the gut microbiota, Lact plays a protective role against the progression of CKD.

In this study, we examined the association between chronic kidney disease (CKD) and insulin resistance. In a patient cohort with nondiabetic stages 2-5 CKD, estimated glomerular filtration rate (eGFR) was negatively correlated and the plasma aldosterone concentration was independently associated with the homeostasis model assessment of insulin resistance. Treatment with the mineralocorticoid receptor blocker spironolactone ameliorated insulin resistance in patients, and impaired glucose tolerance was partially reversed in fifth/sixth nephrectomized rats. In these rats, insulin-induced signal transduction was attenuated, especially in the adipose tissue. In the adipose tissue of nephrectomized rats, nuclear mineralocorticoid receptor expression, expression of the mineralocorticoid receptor target molecule SGK-1, tissue aldosterone content, and expression of the aldosterone-producing enzyme CYP11B2 increased. Mineralocorticoid receptor activation in the adipose tissue was reversed by spironolactone. In the adipose tissue of nephrectomized rats, asymmetric dimethylarginine (ADMA; an uremic substance linking uremia and insulin resistance) increased, the expression of the ADMA-degrading enzymes DDAH1 and DDAH2 decreased, and the oxidative stress increased. All of these changes were reversed by spironolactone. In mature adipocytes, aldosterone downregulated both DDAH1 and DDAH2 expression, and ADMA inhibited the insulin-induced cellular signaling. Thus, activation of mineralocorticoid receptor and resultant ADMA accumulation in adipose tissue has, in part, a relevant role in the development of insulin resistance in CKD.

Preoperative planning with computed tomography (CT)-based three-dimensional templating has been expanded to achieve more precise placement of hip components. However, few reports have addressed the utility of three-dimensional surgical planning software for secondary osteoarthritis cases. This study therefore investigated the value of CT-based three-dimensional templating software for preoperative planning in primary total hip arthroplasty (THA), with an emphasis on developmental dysplasia of the hip. We performed a retrospective review of 65 hips in 57 patients who underwent cementless primary THA. The preoperative diagnosis was secondary osteoarthritis in all cases due to developmental dysplasia of the hip. All preoperative planning and postoperative evaluations were completed using CT-based three-dimensional templating software. We analyzed the accuracy of stem size prediction and cup size prediction, the reproducibility of preoperative and postoperative stem anteversion, and the absolute error in preoperative and postoperative stem anteversion using CT-based three-dimensional templating software. The sizes of 65 % of the femoral stems (42/65) were estimated exactly, and 98 % (63/65) were accurately estimated to within one stem size. The final acetabular cup sizes corresponded exactly to the preoperatively planned size in 92 % of all cases (62/65). 100 % of the cup size estimates were accurate to within one cup size. There was strong reproducibility of preoperative and postoperative stem anteversion (r = 0.88, P

We investigated the various impingement angles (including both bony and prosthetic impingement) and impingement types that can occur after THA, even when the same combined anteversion parameter is used. We also investigated the relationship between impingement angle and acetabular morphology or femoral anteversion. We evaluated 83 patients with no hip arthritis. We divided them into six groups according to acetabular CE angle (≤15°, >15–≤25°, and >25°) and femoral anteversion (≤20° and >20°). Using three-dimensional templating software, we changed stem and cup anteversion to satisfy a combined anteversion (CA) of 50° in each hip (stem anteversion + cup anteversion = 50°) and investigated the resulting impingement angles. Even with the same CA, differences in impingement angle occurred: 18.3° ± 7.2° with flexion, 30.2° ± 9.7° with internal rotation at 90° flexion, 20.2° ± 12.5° with extension, and 26.2° ± 7.8° with external rotation. As stem anteversion increased, the impingement type changed from prosthetic impingement to bony impingement in flexion and internal rotation and from bony impingement to prosthetic impingement in extension and external rotation. The flexion angle and internal rotation angle at 90° flexion increased (p

Objective To clarify the clinical features and risk factors of cervicogenic headache (CEH; as diagnosed according to the International Classification of Headache Disorders-Third Edition beta) in patients with cervical spine disorders requiring surgery. Background CEH is caused by cervical spine disorders. The pathogenic mechanism of CEH is hypothesized to involve a convergence of the upper cervical afferents from the C1, C2, and C3 spinal nerves and the trigeminal afferents in the trigeminocervical nucleus of the upper cervical cord. According to this hypothesis, functional convergence of the upper cervical and trigeminal sensory pathways allows the bidirectional (afferent and efferent) referral of pain to the occipital, frontal, temporal, and/or orbital regions. Previous prospective studies have reported an 86-88% prevalence of headache in patients with cervical myelopathy or radiculopathy requiring anterior cervical surgery; however, these studies did not diagnose headache according to the International Classification of Headache Disorders criteria. Therefore, a better understanding of the prevalence rate, clinical features, risk factors, and treatment responsiveness of CEH in patients with cervical spine disorders requiring surgery is necessary. Methods We performed a single hospital-based prospective cross-sectional study and enrolled 70 consecutive patients with cervical spine disorders such as cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, cervical spondylotic radiculopathy, and cervical spondylotic myeloradiculopathy who had been scheduled to undergo anterior cervical fusion or dorsal cervical laminoplasty between June 2014 and December 2015. Headache was diagnosed preoperatively according to the International Classification of Headache Disorders-Third Edition beta. The Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, Neck Disability Index, and a 0-100 mm visual analog scale (VAS) were used to evaluate clinical features, and scores were compared between baseline (ie, preoperatively) and 3, 6, and 12 months post-surgery. Results The prevalence of CEH in our population was 15/70 (21.4%, 95%CI: 11.8% to 31.0%). The main clinical features were dull and tightening/pressing headache sensations in the occipital region. Headache severity was mild (VAS, 32 ± 11 mm) and only one patient reported use of an oral analgesic. Compared to patients without CEH, patients with CEH had higher frequencies of neck pain (86.7% vs. 50.9%; P = .017), cervical range of motion limitation (ROM) (66.7% vs. 38.2%; P = .049), and higher Neck Disability Index scores (14 vs. 3; P

Clinical application of immune checkpoint inhibitors (CPIs) including nivolumab is expanding in the field of oncology treatment. Nivolumab is an anti-programmed death 1 protein (PD-1) antibody designed to augment an immunologic reaction against cancer cells. On the contrary, CPIs are known to cause a unique variety of side effects termed as immune-related adverse events, which can affect any organ including kidney. However, the characteristics of renal disorders by nivolumab treatment are poorly described. We describe two cases of acute kidney injury that were treated with nivolumab. Two patients, one with renal-cell carcinoma and the other with lung cancer, exhibited progressive renal dysfunction after the initiation of nivolumab treatment. By kidney biopsy, each case was diagnosed as acute interstitial nephritis (AIN). Of note, tubular epithelial cells enlarged with hyperchromatic nuclei were focally observed, and this finding was consistent with karyomegalic tubular epithelial cells. In immunostaining, most of the enlarged tubular epithelial cells were positive for Ki-67, which suggested regeneration of tubular epithelial cells. Clinically, in one case, renal function was partially recovered with the discontinuation of nivolumab, while in another case renal function was fully recovered with additional corticosteroid treatment. We presented nivolumab-induced AIN with karyomegalic changes of tubular epithelia. We propose that immunosuppressive therapy may be necessary for the full recovery from renal impairment.

This study investigates the accuracy of a computed tomography (CT)-based navigation system for accurate acetabular component placement during revision total hip arthroplasty (THA).We performed a retrospective review of 30 hips in 26 patients who underwent cementless revision THA using a CT-based navigation system; the control group consisted of 25 hips in 25 patients who underwent cementless primary THA using the same system. We analysed the deviation of anteversion and inclination angles among the pre-operative plan, intra-operative records from the navigation system and data from postoperative CT scans.There were no significant differences between groups (P 0.05) in terms of mean deviation between pre-operative planning and postoperative measurements or between intraoperative records and postoperative measurements.CT-based navigation in revision THA is a useful tool that enables the surgeon to implant the acetabular component at the precise angle determined in pre-operative planning.

Object This study aimed to clarify changes in segmental instability following a unilateral approach for microendoscopic posterior decompression and muscle-preserving interlaminar decompression compared with traditional procedures and destabilized models. Methods An ex vivo experiment was performed using 30 fresh frozen porcine functional spinal units (FSUs). Each intact specimen was initially tested for flexion-extension, lateral bending, and torsion up to 1.5° using a material testing system at an angular velocity of 0.1°/second under a preload of 70 N. Microendoscopic posterior decompression, muscle-preserving interlaminar decompression, bilateral medial facetectomy, left unilateral total facetectomy, and bilateral total facetectomy were then performed, followed by mechanical testing with the same loading conditions, in 6 randomized FSUs from each group. Stiffness and neutral zone were standardized by dividing the experimental values by the baseline values and were then compared among groups. Results Mean standardized stiffness values for all loading modes tended to decrease in the order of muscle-preserving interlaminar decompression, microendoscopic posterior decompression, bilateral medial facetectomy, left unilateral total facetectomy, and bilateral total facetectomy. In contrast, mean standardized neutral zone values tended to increase in the order of muscle-preserving interlaminar decompression, microendoscopic posterior decompression, bilateral medial facetectomy, left unilateral total facetectomy, and bilateral total facetectomy. In flexion, values for standardized stiffness following microendoscopic posterior decompression and muscle-preserving interlaminar decompression were higher and standardized neutral zone following microendoscopic posterior decompression and muscle-preserving interlaminar decompression were lower than the values following left unilateral total facetectomy and bilateral total facetectomy while there was no significant difference among bilateral medial facetectomy, left unilateral total facetectomy, and bilateral total facetectomy. Values of standardized stiffness and standardized neutral zone in left torsion following microendoscopic posterior decompression, muscle-preserving interlaminar decompression, and bilateral medial facetectomy were equally superior to values of the destabilization models (left unilateral total facetectomy and bilateral total facetectomy). Except for standardized stiffness in left bending, the values of the parameters for each bending tended to be the same as in the other loading modes. Conclusions The present biomechanical study showed that overall stability of the FSUs was maintained following microendoscopic posterior decompression, muscle-preserving interlaminar decompression, and bilateral medial facetectomy compared with the destabilization models of left unilateral total facetectomy or bilateral total facetectomy. Comparison of the postoperative stability following microendoscopic posterior decompression, muscle-preserving interlaminar decompression, and bilateral medial facetectomy revealed that muscle-preserving interlaminar decompression tended to be superior, followed by microendoscopic posterior decompression and bilateral medial facetectomy.

Background The surgical depths of approaches for total hip arthroplasty (THA) have not been reported previously. In this study, we investigate the relationships between the distances to the centre of the femoral head in different approaches and body mass index (BMI). Methods The study included patients with normal hip joints who presented to our hospital. We used the pelvic coordinate system relative to the anterior pelvic plane and the femur coordinate system relative to the posterior condylar plane. We assessed the anterior, anterolateral, lateral and posterior approaches, and defined each approach line. We evaluated each distance in terms of BMI and gender. Results 164 hips were assessed. The distance to the centre of the femoral head was the longest in the posterior approach, followed by the lateral, anterolateral, and anterior approaches (pConclusions The distance to the centre of the femoral head is the shortest in the anterior approach, regardless of BMI and gender. The distance in each approach might increase with an increase in BMI. BMI has similar effects in all approaches.

Background Recently, corrective fusion surgery for patients with adult spinal deformity (ASD) has become common in Japan. This study aimed to clarify the status of surgeries for ASD in Japan, focusing on perioperative complications. A nationwide multicenter survey gathering information on surgically treated ASD patients was conducted by the committee for Adult Spinal Deformity of the Japanese Scoliosis Society. Methods This study was a review of retrospectively collected data from 18 spine scoliosis centers belonging to the Japanese Scoliosis Society. Patients who underwent corrective fusion surgery for ASD between 2011 and 2013 were included. Demographics, comorbidities, surgical data, and complications were investigated. Results A total of 1192 patients (mean age, 57.7 years) were included in this study. Of these, 611 patients were aged less than 65 years and 581 patients were aged 65 years or greater. The age distribution had two peaks, in the third and eighth decades. Deformities caused by degeneration represented 67% of the pathology in patients aged over 65 years; however, non-degenerative disease such as adult idiopathic scoliosis and syndromic or congenital deformity represented over 60% of pathology in patients aged less than 65 years. The iatrogenic deformity and reoperation rates were both less than 3%. The mean operation time and estimated blood loss were 370 min and 1642 ml, respectively. Major perioperative complications occurred in 160 patients (14.5%). The incidence of complications was significantly higher in patients aged over 65 years, including neurological deficits, hemorrhagic shock, hematoma, heart failure, and surgical site infection (p Conclusions Older (aged over 65 years) ASD patients showed greater rates of deformity due to the occurrence of degeneration and vertebral fractures, as well as a higher incidence of peri-and postoperative complications. Efforts to reduce perioperative complications are therefore imperative, especially for elderly ASD patients in our aging society.

Diagnosis and treatment are evolving in lumbar spinal stenosis. The lesion is world widely common and becoming more complicated as human life spam is getting longer. Foraminal stenosis is one of examples which are often overlooked, but recent imaging technology, e.g. MRI diffusion-weighted imaging, has been improving precision of the diagnosis. Idiopathic scoliosis with degenerative disc disease and de novo degenerative scoliosis are subject to lumbar canal stenosis. In this lesion, not only the segmental lesion, but also standing spinal alignment should be clarified for the diagnosis and treatment strategy. In this specialized issue of European Journal of Orthopaedic Surgery and Traumatology, ‘‘Foraminal stenosis, the hidden stenosis’’, was reviewed by Dr. Sumihisa Orita et al. (Japan) [1], ‘‘Lumbar spinal stenosis in adult (elderly) spinal deformity’’ was by Dr. Le Huec et al. (France) [2], ‘‘The global alignment in patients with lumbar spinal stenosis: our experience using the EOS full body images’’ was by Dr. Jean-Yves Lazennec et al. (France) [3], ‘‘Surgical and non-surgical treatments for lumbar spinal stenosis’’ was by Dr. Gen Inoue et al. (Japan) [4], and finally ‘‘Minimally invasive surgery for lumbar spinal stenosis’’ including a critical review on interspinous process devices was by Dr. Wouter Moojen and Dr. Niels A. van der Gaag (the Netherlands) [5]. We are privileged with the honour of editing this specialized issue: Lumbar spinal stenosis. The authors in this edition outshine among their counterparts. We are confident that our readers will gain outstanding knowledge on the up-to-date diagnosis, approaches, and techniques in the management of spinal stenosis, for the benefit of their patients. The authors declare no conflict of interest.