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Purpose: To investigate the age-specific normative values of whole-body sagittal alignment (WBSA) including global balance parameters in healthy adults and to clarify the correlations among parameters based on the data from three international multicenter. Methods: Three hundred and seventeen healthy subjects (range: 20–84 y.o., mean: 43.8 ± 14.7 y.o.) were included and underwent whole-body biplanar X-ray imaging system. Spinopelvic parameters and knee flexion (KF), the center of acoustic meatus (CAM)-hip axis (HA), and C2 dentiform apophyse (OD)-HA, the cranial center (Cr)-HA were evaluated radiologically. Sub-analysis for correlation analysis between age and parameters and among parameters was performed to investigate age-specific change and compensatory mechanisms. Results: For age-related change, C2-7 angle (r = .326 for male/.355 for female), KF (r = .427/.429), and SVA (r = .234/.507) increased with age in both male and female group. For global parameters related to the center of the gravity, correlations with age were not significant (r = .120/.161 for OD-HA, r = .163/.275 for Cr-HA, r = .149/.262 for CAM-HA). Knee flexion (KF) has correlation with global parameters (i.e., SVA, OD-HA, Cr-HA, CAM-HA) and does not have correlations with local spinopelvic alignment. Conclusion: While several local alignment changes with age were found, changes in global parameters related to the center of gravity were kept relatively mild by the chain of compensation mechanisms including the lower limbs. We showed the normative values for a comprehensive WBSA in standing posture from large international healthy subjects’ database.

Background Proper identification of lumbosacral transitional vertebrae (LSTV) is important to characterize the relationship between the transitional segment and adjacent levels. Classical classification schemes are inaccurate with respect to the whole spine. We propose a precise vertebral numbering method and investigated the relationship between LSTV and whole-body sagittal alignment. Methods A total of 291 healthy adult volunteers with no history of spinal disease were evaluated with biplanar slot scanning full body stereoradiography to determine the prevalence of LSTV. Vertebrae were counted from the first cervical vertebra using both coronal and sagittal plane images. We then investigated the influence of LSTV on whole-body sagittal alignment in 279 participants. Whole-body key parameters descriptive statistics were compared among groups according to the number of vertebrae (L4, L5, and L6). Statistical analysis was performed between normal and LSTV cases using the Steel-Dwass analysis. Results Of the 291 subjects, 14 (4.8%) had 23 vertebrae and 16 (5.5%) had 25 vertebrae. Eleven (3.8%) had Th11, 3 (1.0%) had L4, and 1 (0.3%) had Th11 + L6, 16 (5.5%) had L6. Compared with the normal group, the sacral base in relation to the pelvis was higher in the L4 group and lower in the L6 group. The C2–C7 angle and lumbar lordosis (LL) were increased in both the L4 and L6 groups. All remaining parameters were decreased in the L4 group and increased in the L6 group. The relationship between LL and PI was similar in the normal and LSTV groups, despite the difference in the sacral base location. Conclusions We propose a precise method for numbering the vertebrae using coronal and sagittal full body images. The spinopelvic parameters of the LSTV population significantly differed from those in the normal spine population due to differences in the sacral base location.

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.

Study Design: A finite element analysis study. Objective: Of proximal junctional failure, upper instrumented vertebra (UIV) fracture can causes severe spinal cord injury. Previously, we reported that higher occupancy rate of pedicle screw (ORPS) at UIV prevented UIV fracture in adult spinal deformity surgery; we had not yet tested this finding using a biomechanical study. The purpose of present study was to measure the differences in loads on the UIV according to the length of PS and ORPS. Methods: We designed an FE model of a lumbar spine (L1-S1) using FE software. The PS was set from L2 to S1 and connected the rod. The FE model simulated flexion (8 Nm) to investigate the loads at UIV (L2) according to the length of the PS. There were 5 screw lengths examined: 40 (ORPS 36.4%), 45 (48.5%), 50 (66.7%), 55 (81.8%), and 60 mm (93.9%). Results: Stress with bending motion was likely to occur at the upper front edge of the vertebral body, the pedicles, and the screw insertion point. The maximum equivalent stress according to screw lengths of 40, 45, 50, 55, and 60 mm were 45.6, 37.2, 21.6, 13.3, and 14.8 MPa, respectively. The longer screw, the less stress was applied to UIV. No remarkable change was observed between the screw lengths of 55 and 60 mm. Conclusions: Increasing ORPS to 81.8% or more reduced the load on the UIV. To prevent UIV fracture, the PS length in the UIV should be more than ORPS 81.8%.

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.

Background Although several radiographic predictors for pulmonary function in adolescent patients have been reported, those in adult patients remain unclear. Therefore, we aimed to investigate the associations between spinal deformity and pulmonary function in nonoperatively treated adult patients with adolescent idiopathic scoliosis (AIS). Methods Of 319 patients treated nonoperatively for AIS, 90 (average age, 40.0 ± 6.5 years) underwent both full-length standing radiographs and pulmonary function test. Standard two-dimensional (2-D) radiographic measurements were performed. Three-dimensional thoracic kyphosis (3-D TK) was calculated from 2-D standing radiograph data using a validated formula: 3-D TK (°) = 18.1 + 0.81 × (2-D TK) + 0.54 × (Cobb angle of thoracic curve). 3-D TK was defined as the sum of segmental kyphosis between T5 and T12, which eliminates the overestimation of TK in 2-D measurements due to rotational deformity. Bivariable correlation analysis, followed by a stepwise multiple linear regression analysis, was performed. Results The average Cobb angle of the thoracic curve at the time of survey was 49.4° ± 14.6° with flexibility of 37.5% ± 18.2%. Thoracic curve magnitude, flexibility, apical vertebral rotation and translation, and 3-D TK were significantly correlated with percent-predicted forced vital capacity (%FVC) and expiratory volume in 1 s (%FEV1.0). Stepwise multiple regression analysis showed that curve flexibility and 3-D TK were significant, independent predictors of %FVC (R2 = 0.358) and %FEV1.0 (R2 = 0.335), curve flexibility having a greater impact (standardized coefficient > 0.45) than 3-D TK ( Conclusions Our results indicate that nonoperatively treated patients with AIS should be recommended to maintain flexibility of the thoracic curve to prevent future pulmonary impairment. Moreover, 3-D TK is another independent predictor of pulmonary function, which suggests that segmental sagittal alignment is a component of deformity correction to focus on.

Fulcrum-bending (FB) correction is considered to provide the best estimation of main thoracic (MT) curve flexibility and postoperative correction in surgical treatment for adolescent idiopathic scoliosis (AIS). However, few studies evaluated the usefulness of FB radiographs for proximal thoracic (PT) curve. We aimed to perform flexibility assessments using both active side-bending (SB) and FB radiographs and evaluate surgical outcomes after posterior spinal fusion (PSF) for Lenke type 2 AIS.This study included 38 consecutive patients with Lenke type 2 AIS who underwent PSF using a pedicle screw construct with a minimum 2-year follow-up. Radiographic parameters, including correction rate, SB and FB flexibility, and FB correction index (FBCI: [correction rate/FB flexibility] × 100), were evaluated preoperatively, immediately after surgery, and at the 2-year follow-up. The clinical outcomes were preoperatively evaluated using the Scoliosis Research Outcomes Instrument-22 and at the follow-up.All scoliosis curves significantly improved and shoulder balance shifted toward left shoulder elevation (all comparisons, p 0.0001). There were significant differences between the SB and FB corrections in the PT and MT curves (p 0.0001). The magnitudes of the discrepancies between the SB and FB corrections in the PT and MT curves were 11.2° ± 5.2° and 11.6° ± 7.2°, respectively. FB correction did not differ from postoperative Cobb angles correction immediately after surgery or at the 2-year follow-up; the mean FBCIs in the PT and MT curves were 98.8% and 105.5%, respectively. The self-image domain SRS-22 scores had significantly increased at the 2-year follow-up (p 0.0001).There were significant differences between the SB and FB corrections, and FB correction tended to approximate the postoperative curve correction (FBCI = 100%) for PT and MT curves in patients with Lenke type 2 AIS. FB flexibility is more reliable than SB flexibility in evaluating actual curve flexibility even for the PT curve.

Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear. We generated NNMT-deficient mice and a unilateral ureter obstruction (UUO) model and conducted two clinical studies on human CKD to investigate the role of NNMT in CKD and fibrosis. In UUO, renal NNMT expression and the degraded metabolites of NAM increased, while NAD + and NAD + precursors decreased. NNMT deficiency ameliorated renal fibrosis; mechanistically, it (1) increased the DNA methylation of connective tissue growth factor (CTGF), and (2) improved renal inflammation by increasing renal NAD + and Sirt1 and decreasing NF-κB acetylation. In humans, along with CKD progression, a trend toward a decrease in serum NAD + precursors was observed, while the final NAD + metabolites were accumulated, and the level of eGFR was an independent variable for serum NAM. In addition, NNMT was highly expressed in fibrotic areas of human kidney tissues. In conclusion, increased renal NNMT expression induces NAD + and methionine metabolism perturbation and contributes to renal fibrosis.

Context Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. Objective Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. Methods Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). Results The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10–5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10–5, OR 5.21, 95% CI 2.76-9.86). Conclusion AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

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.

The gut produces toxins that contribute to the cardiovascular complications of chronic kidney disease. Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor that is used as an anti-diabetic drug, has a weak inhibitory effect against SGLT1 and may affect the gut glucose concentration and environment. Here, we determined the effect of canagliflozin on the gut microbiota and the serum gut-derived uremic toxin concentrations in 5/6th nephrectomized (Nx) rats. Canagliflozin increased the colonic glucose concentration and restored the number of Lactobacillus bacteria, which was low in Nx rats. In addition, the expression of tight junction proteins in the ascending colon was low in Nx rats, and this was partially restored by canagliflozin. Furthermore, the serum concentrations of gut-derived uremic toxins were significantly increased by Nx and reduced by canagliflozin. Finally, the wall of the thoracic aorta was thicker and there was more cardiac interstitial fibrosis in Nx rats, and these defects were ameliorated by canagliflozin. The increases in colonic glucose concentration, Lactobacillus numbers, and tight junction protein expression; and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats.

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.

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.

Under diabetic conditions, sodium–glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+-dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin. We also examined SIRT1 and SGLT2 expression in human kidney biopsies. In db/db mice, SGLT2 expression increased with concomitant decreases in SIRT1, but was inhibited by canagliflozin. For determination of the polarity of SGLT2 and SIRT1 expression, LLC-PK1 cells were seeded into Transwell chambers (pore size, 0.4 µm; Becton Dickinson, Oxford, UK). HG medium was added to either or to both of the upper and lower chambers, which corresponded to the apical and basolateral sides of the cells, respectively. In this system, the lower chamber with HG showed increased SGLT2 and decreased SIRT1 expression. Canagliflozin reversed HG-induced SIRT1 downregulation. Gene silencing and inhibitors for glucose transporter 2 (GLUT2) blocked HG-induced SGLT2 expression upregulation. Gene silencing for the hepatic nuclear factor-1α (HNF-1α), whose nuclear translocation was enhanced by HG, blocked HG-induced SGLT2 expression upregulation. Similarly, gene silencing for importin-α1, a chaperone protein bound to GLUT2, blocked HG-induced HNF-1α nuclear translocation and SGLT2 expression upregulation. In human kidney, SIRT1 immunostaining was negatively correlated with SGLT2 immunostaining. Thus, under diabetic conditions, SIRT1 expression in PTs was downregulated by an increase in SGLT2 expression, which was stimulated by basolateral HG through activation of the GLUT2/importin-α1/HNF-1α pathway.

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.

The functional linkage between pelvis and spine remained long hidden to science. Here, we recount the history of research that led in 1992 to the discovery of the "angle of sacral incidence" by the team of G. Duval-Beaupere. This angle, formed between a ray from the hip joint center to the superior sacral surface and the perpendicular to the sacral surface, was later called pelvic incidence. Specific to each individual, pelvic incidence is tightly correlated with the degree of lumbar lordosis. It is each individual's "signature" for an efficient sagittal balance since it represents the sum of two positional parameters, sacral slope and pelvic tilt. The simultaneous experimental determination of the trunk line of gravity permitted Duval-Beaupere's team to elucidate the conditions of an efficient sagittal balance of the trunk on the lower limbs. We present an in vivo EOS study of eight spino-pelvic parameters describing the sagittal balance in 131 adults. We observe a chain of correlations between the six angular parameters and discuss the functional significance of these results. We show that pelvic incidence increases and lumbar lordosis develops when the infant learns to walk, leading to a correlation between these parameters. This process of association between pelvis and spine might have acquired a solid genetic basis during hominid evolution by natural selection acting on both pelvis and spine. We suggest that this process of functional integration was only possible in the context of bipedal locomotion becoming permanent and stereotyped, expressed by a relatively invariant, periodic walking cycle. Anat Rec, 300:912-931, 2017. © 2017 Wiley Periodicals, Inc.

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.