Binding and Activation of LRP1-Dependent Cell Signaling in Schwann Cells Using a Peptide Derived from the Hemopexin Domain of MMP-9.

Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following a peripheral nervous system injury. The low-density lipoprotein receptor-related protein-1 (LRP1) is significantly upregulated in SCs in response to acute injury, activating cJun and promoting SC survival. Matrix-metalloproteinase-9 (MMP-9) is an LRP1 ligand that binds LRP1 through its hemopexin domain (PEX) and activates SC survival signaling and migration. To identify novel peptide mimetics within the hemopexin domain of MMP-9, we examined the crystal structure of PEX, synthesized four peptides, and examined their potential to bind and activate LRP1. We demonstrate that a 22 amino acid peptide, peptide 2, was the only peptide that activated Akt and ERK1/2 signaling in SCs, similar to a glutathione s-transferase (GST)-fused holoprotein, GST-PEX. Intraneural injection of peptide 2, but not vehicle, into crush-injured sciatic nerves activated cJun greater than 2.5-fold in wild-type mice, supporting that peptide 2 can activate the SC repair signaling in vivo. Peptide 2 also bound to Fc-fusion proteins containing the ligand-binding motifs of LRP1, clusters of complement-like repeats (CCRII and CCRIV). Pulldown and computational studies of alanine mutants of peptide 2 showed that positively charged lysine and arginine amino acids within the peptide are critical for stability and binding to CCRII. Collectively, these studies demonstrate that a novel peptide derived from PEX can serve as an LRP1 agonist and possesses qualities previously associated with LRP1 binding and SC signaling in vitro and in vivo.

Axon-derived PACSIN1 binds to the Schwann cell survival receptor, LRP1, and transactivates TrkC to promote gliatrophic activities.

Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following PNS injury. The ligands and receptors that activate and sustain SC transformation remain incompletely understood. Proteins released by injured axons represent important candidates for activating the SC Repair Program. The low-density lipoprotein receptor-related protein-1 (LRP1) is acutely up-regulated in SCs in response to injury, activating c-Jun, and promoting SC survival. To identify novel LRP1 ligands released in PNS injury, we applied a discovery-based approach in which extracellular proteins in the injured nerve were captured using Fc-fusion proteins containing the ligand-binding motifs of LRP1 (CCR2 and CCR4). An intracellular neuron-specific protein, Protein Kinase C and Casein Kinase Substrate in Neurons (PACSIN1) was identified and validated as an LRP1 ligand. Recombinant PACSIN1 activated c-Jun and ERK1/2 in cultured SCs. Silencing Lrp1 or inhibiting the LRP1 cell-signaling co-receptor, the NMDA-R, blocked the effects of PACSIN1 on c-Jun and ERK1/2 phosphorylation. Intraneural injection of PACSIN1 into crush-injured sciatic nerves activated c-Jun in wild-type mice, but not in mice in which Lrp1 is conditionally deleted in SCs. Transcriptome profiling of SCs revealed that PACSIN1 mediates gene expression events consistent with transformation to the repair phenotype. PACSIN1 promoted SC migration and viability following the TNFα challenge. When Src family kinases were pharmacologically inhibited or the receptor tyrosine kinase, TrkC, was genetically silenced or pharmacologically inhibited, PACSIN1 failed to induce cell signaling and prevent SC death. Collectively, these studies demonstrate that PACSIN1 is a novel axon-derived LRP1 ligand that activates SC repair signaling by transactivating TrkC.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Postoperative change in lumbopelvic alignment after short-segment transforaminal lumbar interbody fusion is related to preoperative postural difference in lumbar lordosis.

BACKGROUND: Postoperative changes in lumbar lordosis (LL) after transforaminal lumbar interbody fusion (TLIF) and the related factors are not well-understood. Recently, the preoperative difference in LL between standing and supine positions (DiLL) was proposed as a factor for predicting postoperative radiologic outcomes after short-segment TLIF. This study investigated the influence of DiLL on mid-term radiological outcomes after short-segment TLIF. METHODS: Sixty-six patients with lumbar degenerative disease treated with short-segment TLIF (1-2 levels) who underwent lumbar spine standing radiographs at 3 months, 6 months, 1 year, 2 years, 3 years, 4 years, and 5 years postoperatively were divided into DiLL (+) and DiLL (-) groups (preoperative DiLL ≥0° and <0°, respectively). Associations between the postoperative change in LL and DiLL and clinical outcomes (Oswestry disability index (ODI) and Nakai score) were evaluated. RESULTS: Temporary restoration of LL (+4.5°) until 1 year postoperatively and a subsequent decrease in LL from 1 to 5 years postoperatively (-5.3°) was observed in the DiLL (+) group. No postoperative change in LL was observed in the DiLL (-) group. Postoperative changes in LL were mainly observed in non-fused segments. The postoperative change in LL (ΔLL) until 1 year postoperatively had a significant positive association with DiLL (p = 0.00028), whereas ΔLL from 1 to 5 years postoperatively showed a significant negative association with DiLL (p = 0.010) and a positive association with Nakai score (p = 0.028). ΔLL until 5 years postoperatively showed a significant positive association with postoperative ODI improvement (p = 0.011). CONCLUSIONS: DiLL (+) patients showed a specific time course with temporary LL restoration until 1 year postoperatively and a subsequent decrease in LL from 1 to 5 years postoperatively. Patients with larger postoperative increase in LL until 5 years postoperatively and lesser decrease in LL from 1 to 5 years postoperatively tended to show better mid-term clinical outcomes.

Three-year clinical and radiological results of a cruciate-retaining type of the knee prosthesis with anatomical geometry developed in Japan.

BACKGROUND: The FINE total knee was developed in Japan and clinical use began in 2001. It has unique design features, including an oblique 3o femorotibial joint line that reproduces anatomical geometry. Although 20 years have passed since the FINE knee was clinically used for the first time in Japan, a formal clinical evaluation including patient-reported and radiographic outcomes has not been undertaken. METHODS: A total of 175 consecutive primary cruciate-retaining (CR)-FINE total knee arthroplasties (TKAs) at our hospital between February 2015 and March 2017 were included in this study. Three years postoperatively, range of motion (ROM), Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Forgotten Joint Score (FJS) were recorded and compared with preoperative scores. Radiographic analyses including mechanical alignment, component alignment, and incidence of radiolucent lines also were undertaken based on the radiographs 3 years postoperatively. RESULTS: One-hundred twenty-two knees (70%) were available for 3-year follow-up data using KOOS, except for the sports subscale. Postoperative KOOS-symptom, -pain and -ADL were > 85 points, but KOOS-sports, -QOL and FJS were less satisfactory. ROM, KSS and all the subscales of KOOS were significantly improved compared with preoperative scores. Postoperative mean FJS was 66 and was significantly correlated with all the subscales of KOOS, but not with postoperative ROM. Radiolucent lines ≧1 mm wide were detected in five knees (4.1%). There were no major complications needing revision surgeries. CONCLUSIONS: Patient-reported outcomes (PROs) for symptoms, pain and ADL after the CR-FINE TKA were generally improved, but those for sports, QOL and FJS were improved less. The incidence of radiolucent lines was rare but detected around the femoral components. With the mid- to long-term follow-up, improvements of surgical technique will be necessary to achieve better PROs from patients receiving the FINE knee.

Advanced glycation end products are associated with sarcopenia in older women: aging marker dynamics.

The aim of this study was to determine whether advanced glycation end products (AGEs) revealed by skin autofluorescence (SAF), serum and urine pentosidine level, and serum homocysteine level can serve as a biomarker for sarcopenia in older women. The participants were 70 elderly women. The AGEs pentosidine, homocysteine, and SAF were measured as aging markers. This study shows that among the biomarkers for aging, serum pentosidine correlates with a loss of appendicular lean mass and can serve as a biomarker for sarcopenia. Moreover, SAF and homocysteine values exhibited a positive correlation with age and correlated with each other.Abbreviations: AGEs: advanced glycation end products; BIA: bioelectrical impedance analyzer; BMD: bone mineral density; DLS: degenerative lumbar scoliosis; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunoassay; HHcy: hyperhomocysteinemia; RIA: radioimmunoassay; SAF: skin autofluorescence; SMI: skeletal muscle mass index; T2DM: type 2 diabetes patients.

Does the increased motion probing gradient directional diffusion tensor imaging of lumbar nerves using multi-band SENSE improve the visualization and accuracy of FA values?

PURPOSE: Diffusion tensor imaging (DTI) is useful to evaluate lumbar nerves visually and quantitatively. Multi-band sensitivity encoding (MB-SENSE) is a technique to reduce the scan time. This study aimed to investigate if super-multi-gradient DTI with multi-band sensitivity encoding (MB-SENSE) is better in evaluating lumbar nerves than the conventional method. METHODS: The participants were 12 healthy volunteers (mean age 33.6 years). In all subjects, DTI was performed using echo planar imaging with different motion probing gradient (MPG) directions (15 without MB, and 15, 32, 64, and 128 with MB) and the lumbar nerve roots were visualized with tractography. In the five groups, we evaluated the resultant DTI both visually and quantitatively. For visual measures, we counted the number of fluffs and disruptions of the nerve fibers. For quantitative measures, the fractional anisotropy (FA) and standard deviation of the fractional anisotropy (FA-SD) values at two regions (proximal and distal) of the lumbar nerve roots were quantified and compared. RESULTS: Among the five groups, the number of fluffs decreased as the number of MPG directions increased. However, the number of disruptions showed no significant differences. The FA-SD values decreased as the number of MPG directions increased, indicating that the signal variation was reduced with multi-gradient directional DTI. CONCLUSION: High-resolution multi-directional DTI with MB-SENSE may be useful to visualize nerve entrapments and may allow for more accurate DTI parameter quantification with opportunities for clinical diagnostic applications.

Objective evaluation of postoperative changes in real-life activity levels in the postoperative course of lumbar spinal surgery using wearable trackers.

BACKGROUND: Lumbar spinal disease causes disabilities in performing daily activities. Operative treatments are aimed at pain relief and rapid return to routine activity. Patient-based outcome measures are used to evaluate pathologies and therapeutic effects associated with lumbar spinal disease. Nevertheless, it remains unknown as to how much such treatment improves activity levels. The purpose of the current study was to measure changes in activity levels before and after lumbar spinal surgery using a wearable activity tracker and to analyze the differences between results and patient-based outcomes. METHODS: Sixty patients who underwent lumbar surgery were studied. The physical activity of participants was objectively evaluated using a wearable Micro-Motion logger system (Actigraph). We measured the amount of activity before and at 1, 3, 6, and 12 months after the surgery to evaluate postoperative changes. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, Roland-Morris Disability Questionnaire and visual analog scale were used to assess patient-based outcomes of pain and activities of daily living-related scores; we analyzed the relationships between scores and actual activity levels. RESULTS: The amount of actual activity decreased significantly 1 month after the surgery compared to that during the preoperative period, which then improved after 3 months postoperatively (p < 0.01). Furthermore, there was a significant improvement 6 months after the surgery compared to that during the preoperative period (p < 0.05). The changes in activity for each period were strongly correlated, regardless of the period. In contrast, a significant improvement was observed at 1 month after the surgery in almost all items of the patient-based questionnaires (p < 0.05). CONCLUSIONS: The objective activity tracker demonstrated that lumbar surgery results in the amount of activity decreasing 1 month just after surgery followed by gradual postoperative recovery within 3 months. By contrast, patient-based outcomes showed improvement in 1 month that was significantly different from the change in actual activity, indicating a gap between patient-oriented clinical scores and their actual activities.

Relationship between patient-based scoring systems and the activity level of patients measured by wearable activity trackers in lumbar spine disease.

PURPOSES: To evaluate whether a relationship exists between patient-based scoring systems and the activity level of patients with low back pain (LBP) by using wearable activity trackers, and to determine whether activity level was affected by patient factors. METHODS: The subjects were 66 patients with LBP. The physical activity of participants was objectively evaluated using the Micro-Motion logger (Actigraph). The activity level was analyzed with the mean active count of the proportional-integrating mode (PMAC) and zero-crossing mode. Clinical symptoms were evaluated using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire, the Oswestry Disability Index, and visual analog scale (VAS). The relationships between each item of the patient-based questionnaire and activity level, and the influence of individual factors (age, sex, body mass index [BMI], low back pain, and muscle mass) on the activity level were evaluated. RESULTS: In each domain of the JOABPEQ, lumbar spine dysfunction and social life dysfunction were correlated with PMAC (r = 0.327 and 0.321, respectively). The low back pain VAS scores were correlated with PMAC (r = - 0.246). Multiple regression analysis shows that individual factors affecting the activity level of patients with LBP were sex, BMI, low back pain, and muscle mass in PMAC (p < 0.01). CONCLUSIONS: Some domains of the questionnaires were correlated with activity level, but others were not. Additionally, the activity level of patients with LBP was affected by sex, BMI, LBP, and skeletal muscle mass index. These slides can be retrieved under Electronic Supplementary Material.

Analysis of skeletal muscle mass in women over 40 with degenerative lumbar scoliosis.

PURPOSE: We investigated the involvement of sarcopenia in middle-aged and elderly women with degenerative lumbar scoliosis (DLS). METHODS: A total of 971 women (mean age 70.4 years) were included in our study. These included 87 cases of DLS (mean 73.8 years) and 884 controls (69.8). Lumbar and femur BMD was measured for all participants using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index (SMI; appendicular lean mass (kg)/(height (m))2. We determined bone density and skeletal muscle mass in both groups and determined the prevalence of sarcopenia. We examined the correlation between bone density and appendicular muscle mass in both groups. We also examined factors related to scoliosis using logistic regression analysis. RESULTS: The DLS group showed significantly higher lumbar BMD, lower femur BMD, lower lean mass arm, and lower lean mass leg, and lower lean mass trunk (p < 0.05). Sarcopenia prevalence (SMI < 5.75) was 59.8% in DLS subjects and 42.8% in controls, revealing a high prevalence in DLS (p < 0.05). In both groups, lumbar and femur BMD were positively correlated with appendicular muscle mass. By logistic regression analysis, trunk muscle mass was detected as a risk factor for DLS independent of age (p < 0.05). CONCLUSIONS: In middle-aged and elderly women, prevalence of sarcopenia was 59.8% in DLS cases and 42.8% in controls, which revealed a high prevalence in DLS. A decrease in trunk muscle was a significant risk factor for DLS that was independent of age. These slides can be retrieved under Electronic Supplementary Material.

Pentosidine concentration is associated with degenerative lumbar scoliosis in older women: preliminary results.

PURPOSE: Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. The objective of the study was to investigate the prevalence of sarcopenia in degenerative lumbar scoliosis (DLS), and the relationship between biochemical markers including major AGEs, pentosidine, and DLS in older women. METHODS: Our study participants were 20 elderly women with idiopathic DLS (mean age 76.4 years, range 56-88). Nineteen age- and sex-matched volunteers (mean age 74.0 years, range 62-86) served as controls. Spinal and femoral BMD of all participants was measured using dual-energy X-ray absorptiometry. We used a bioelectrical impedance analyzer to analyze body composition, including appendicular skeletal muscle mass index [SMI; appendicular lean mass (kg)/(height (m)]2. SMI < 5.75 was considered diagnostic for sarcopenia. Coronal and sagittal spinal alignments were measured. The following biochemical markers were measured: serum and urinary pentosidine, serum homocysteine, 1,25(OA)2D, and 25(OH)D. The level of each variable was compared between DLS and controls. The relationship between biochemical markers including pentosidine and DLS was examined. RESULTS: Sarcopenia was observed at a high prevalence in participants with DLS: 50% compared with 15.8% of healthy controls. Height, weight, femoral BMI, appendicular lean mass, total lean mass, and SMI all had significantly lower values in the DLS group. Serum pentosidine was significantly higher for the DLS group compared with controls. Correlations with serum pentosidine revealed a significant positive correlation between lumbar scoliosis, pelvic tilt, and pelvic incidence-lumbar lordosis mismatch, and a significantly negative correlation between thoracic kyphosis (P < 0.05). CONCLUSIONS: We found that sarcopenia was involved in DLS, and high serum pentosidine levels are associated with severity of coronal and sagittal malalignment in older women, suggesting that high levels of AGEs are a potential biomarker for the progression of lumbar scoliosis and kyphotic deformity. Further studies are needed to clarify the pathogenesis of DLS.

The impact of postoperative inclination of the joint line on clinical outcomes in total knee arthroplasty using a prosthesis with anatomical geometry.

The goal of this study was to investigate the impact of postoperative inclination of the joint line on clinical results after total knee arthroplasty (TKA) using a prosthesis with anatomical geometry. This study included 145 primary cruciate-retaining type of knee prosthesis with anatomical geometry. Three years postoperatively, clinical outcomes including the patient-reported outcomes (PROs) were recorded. Limb alignment was evaluated by the hip-knee-ankle (HKA) axis and inclination of the joint line was assessed by the joint line orientation angle (JLOA). Knees were divided into two groups according to the HKA: in-range (- 3 to 3°) and outlier group (< - 3° or > 3°) or the JLOA: in-range (2-4°) and outlier group (< 2° or > 4°), and clinical outcomes were compared between the groups. Postoperative Knee Society Function Score (KS-FS) was significantly higher in the HKA in-range group than the outlier group (p = 0.01). The Knee Society Knee Score and all subscales of the Knee injury Osteoarthritis Outcome Score were comparable between the groups. A multivariate analysis revealed a significant association between age at operation and postoperative KS-FS > of 80 points. Neither HKA in-range nor JLOA in-range were associated with the higher knee function. In conclusion, TKA-postoperative inclination of the joint line was not relevant to the short-term PROs. Treatment strategies that attempt to make joint line inclination in order to improve postoperative PROs should be avoided, and alignment goals such as kinematic alignment should be considered carefully.

Objective Assessment of Sleep Disorders in Patients with Lumbar Spinal Stenosis Using Wearable Trackers.

Introduction: Low-back pain causes sleep disorders, which impairs the quality of life (QOL) of patients. Sleep disorders are associated with lumbar spinal stenosis (LSS); however, the postoperative effects of LSS surgery on sleep disorders are unknown. This study aimed to assess sleep disorders in patients with LSS using wearable activity trackers and determine whether surgery improves sleep quality. Methods: A total of 39 patients scheduled for LSS surgery (mean age 71.1±8.7 years; 22 men and 17 women) were studied. Sleep disorders in the participants were objectively evaluated using a wearable Motionlogger Micro system. Sleep efficiency (SEf), mean active count (MAC), and wake after sleep onset (WASO) were measured before and 6 months following surgery. Furthermore, the patient-based outcomes of pain and QOL-related scores were measured and compared with those of healthy participants. The group with improved SEf following surgery was designated as "nonpoor sleepers," whereas the group that did not exhibit improvements was designated as "poor sleepers." The two groups were compared based on patient factors, patient-based questionnaires, and sleep disorder measurements. Results: The SEf and WASO were significantly worse in patients with LSS compared with healthy participants (P<0.05). Furthermore, the SEf in patients with LSS was associated with the Oswestry Disability Index scores. No improvement was observed in the SEf, MAC, and WASO before and after surgery. Evaluation of each case revealed 21 and 12 cases of nonpoor and poor sleepers, respectively. Preoperative low-back pain was significantly associated with improvement in postoperative sleep quality. Conclusions: Sleep disorders in patients with LSS were evaluated, and improvement in sleep disorders following surgery was associated with the intensity of preoperative low-back pain. Sleep disorders are associated with QOL disorders, suggesting that focusing on the treatment of sleep disorders is important in the management of patients with LSS.

Nerve Growth Factor in Breast Cancer Cells Promotes Axonal Growth and Expression of Calcitonin Gene-related Peptide in a Rat Model of Spinal Metastasis.

BACKGROUND/AIM: Bone metastasis commonly causes severe pain. Nerve growth factor (NGF) contributes to pain, and promotes the production of pain-associated neuropeptides, such as calcitonin gene-related peptide (CGRP), from sensory nerve endings. We hypothesized that breast cancer cells have NGF levels that promote axonal growth from dorsal root ganglia (DRGs) neurons, and increase their CGRP production associated with pain from spinal metastases. MATERIALS AND METHODS: Expression of NGF by the cultured rat breast adenocarcinoma cell line CRL-1666 was determined using an enzyme-linked immunosorbent assay (ELISA). We constructed a rat model of spinal metastasis by implanting CRL-1666 into L6 vertebrae and determined the change in CGRP expression in DRG neurons innervating vertebrae immunohistochemically. RESULTS: NGF was expressed by CRL-1666. When DRG cells were co-cultured with CRL-1666, there were more CGRP-ir neurons and with a greater average length of axon growth than in cultures without CRL-1666 (p<0.05). In the rat model of metastasis, there were more CGRP-ir DRG neurons innervating vertebra treated with CRL-1666 than in vertebrae from sham surgery control rats (p<0.05). CONCLUSION: NGF from breast cancer may mediate spinal bone pain from metastasis via axonal growth and up-regulation of pain-associated neuropeptides.

Lateral shift of the femoral condyle after total knee arthroplasty: simulation using 2D-templates of the medial pivot design on knee radiographs of young Japanese patients.

BACKGROUND: Total knee arthroplasty (TKA) is an established surgical treatment for advanced knee osteoarthritis by which patients can expect improvement of knee pain and function. Although many surgeons have investigated limb alignment after TKA, changes in coronal positional relation between the femur and tibia are not known well. METHODS: Radiographs of 105 knees of young Japanese patients between 20 and 49 years-old (60 men and 45 women) without osteoarthritic changes who received arthroscopic surgeries at our hospital were used in this study. Using 2D-templates of the medial pivot design (the FINE total knee), we simulated TKA on a SYNAPSE-PACS software. First, the femoral component was placed in normal knee alignment and then was merged to the medial concave of the insert where the tibial component was placed in neutral alignment. The length of the mediolateral shift of the femoral component was measured as an estimate of lateral shift of the femoral condyle, of which association with radiographic parameters including the femorotibial angle (FTA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) was analyzed. Subjects were classified into three groups according to the femoral component size that was chosen in simulation of TKA, and the lateral shift of the femoral condyle was compared between groups. RESULTS: The estimated mean lateral shift of the femoral condyle was 5.99 ± 1.98 mm and was greater in males than females (p < 0.05). Also, it was most highly correlated with the medial proximal tibial angle (MPTA) (r = - 0.553, p < 0.01). A group receiving larger component sizes significantly shifted more laterally compared with a group receiving smaller component sizes (p < 0.01). CONCLUSIONS: These results suggest that the coronal positional relation between the femur and tibia is altered and subsequent ligament imbalance may occur after mechanically aligned TKA using the medial pivot design.

Comparison of pain and discomfort in supine and lateral positions after surgery for lumbar degenerative disease: A prospective randomized controlled study.

INTRODUCTION: To compare postoperative pain and discomfort between supine and lateral positions after lumbar surgery, a prospective randomized controlled study was performed. METHODS: Forty-three patients with lumbar degenerative disease, treated by decompression (n = 23) or fusion surgery (n = 20), were randomly assigned to be placed in either the supine (supine group: n = 21) or lateral (lateral group: n = 22) position postoperatively, and asked to maintain their position until a day after the surgery. Postoperative back pain and discomfort (visual analog scale [VAS], 0-100 mm) and the number of patients who could maintain their position were examined. RESULTS: The VAS scores for back pain (supine: 64.9 ± 22.0, lateral: 55.7 ± 21.4) showed no significant difference between the positions. However, the supine group showed significantly more severe discomfort (75.6 ± 15.7) than the lateral group (64.9 ± 15.7, p = 0.039). Significantly fewer patients maintained their position in the supine group (28.2%) than in the lateral group (68.2%; p = 0.022). Among patients who underwent fusion surgery, significantly fewer patients maintained their position in the supine group (10.0%) than those in the lateral group (60.0%, p = 0.029). CONCLUSION: Postoperative discomfort was significantly reduced in the lateral position than in the supine position; thus, the lateral position is more suitable after lumbar surgery in terms of postoperative discomfort.

Association Between the Accumulation of Pentosidine at the Sciatic Nerve and Cutaneous Hindpaw Hypersensitivity in a Rat Ovariectomy Model.

Introduction Advanced glycation end-products (AGEs) have the potential to serve as biomarkers of aging and metabolic diseases; however, how their expression relates to clinical symptoms is not well defined. In this study, we sought to determine whether the accumulation of pentosidine, one type of AGE, at the peripheral nerve is associated with cutaneous pain or hypersensitivity caused by ovariectomy (OVX). Methods We assigned 12-week-old female Sprague Dawley rats into either the OVX group (n = 6) or the sham group (n = 6). Cutaneous hindpaw sensitivity to mechanical stimuli was measured with von Frey filaments, using Chaplan's adapted method, and the 50% withdrawal threshold was calculated. Then, the accumulation of pentosidine, which represents AGEs, was measured in sciatic nerve fibers after staining with an anti-pentosidine antibody. Results OVX rats showed significantly increased plantar hypersensitivity to mechanical stimuli compared to sham rats 8 weeks after OVX (P = 0.017). Pentosidine-positive sciatic nerves were detected at a higher rate in OVX rats than in sham rats (P = 0.035). The pentosidine positivity rate in sciatic nerve fibers showed a negative correlation with withdrawal threshold (P < 0.001). Conclusions This study showed that higher levels of pentosidine in sciatic nerve fibers are associated with higher plantar hypersensitivity. Accumulation of pentosidine at the sciatic nerve, caused by OVX, may result in cutaneous hindpaw hypersensitivity.

Changes in lumbar lordosis and predicted minimum 5-year surgical outcomes after short-segment transforaminal lumbar interbody fusion.

Although most patients who undergo transforaminal lumbar interbody fusion (TLIF) show favorable surgical results, some still have unfavorable results for various reasons. This study aimed to investigate the influence of differences in lumbar lordosis (LL) between the standing and supine positions (DiLL: supine LL-standing LL) on minimum 5-year surgical outcomes after short-segment TLIF. Ninety-one patients with lumbar degenerative disease who underwent short-segment TLIF (1-2 levels) were categorized based on preoperative differences in LL as DiLL (+) and DiLL (-). Comparison and correlation analyses were performed. The incidence of adjacent segment disease (ASD) by radiology (R-ASD) and symptomatic ASD (S-ASD), bony fusion rates, and pre- and postoperative clinical scores (visual analog scale [VAS]; Japanese Orthopaedic Association [JOA] score; Oswestry disability index (ODI); and Nakai's score) were evaluated. Postoperatively, VAS for low back pain (LBP) in the sitting position, JOA scores for LBP, lower leg pain, intermittent claudication, ODI, and Nakai's score were significantly worse in the DiLL (+) group than in the DiLL (-) group. DiLL values were significantly correlated with VAS for LBP, ODI, and Nakai's score, postoperatively. Positive DiLL values were associated with poorer postoperative outcomes. DiLL is a simple and useful method for predicting mid-term outcomes after TLIF.

Efficacy and Safety of Condoliase Disc Administration as a New Treatment for Lumbar Disc Herniation.

INTRODUCTION: Condoliase is a newly approved drug that improves symptoms associated with lumbar disk herniation (LDH) by intradiscal administration. This study aimed to evaluate the mid-term outcomes of condoliase injection, examine the adverse events, including cases that required surgery after condoliase administration, and verify cases in which condoliase could be effective. METHODS: We enrolled patients with LDH who were treated conservatively for at least six weeks and received condoliase. We assessed the visual analog scale (VAS) score, Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, Oswestry Disability Index, disk height, and disk degeneration for up to 6 months, and we examined the complications. Furthermore, a 50% or more improvement in leg pain VAS score was considered effective. Factors related to symptom improvement were investigated by determining whether lower limb pain improved in six months. RESULTS: In total, 84 patients were recruited (52 men, 32 women; mean age, 44.2 ± 17.1 [16-86 years]). The duration of illness was 6.7 ± 6.8 (1.5-30) months. All patient-based outcomes significantly improved at 4 weeks after the administration compared with pretreatment. The intervertebral disc height decreased significantly at four weeks after condoliase administration compared with that before administration. Progression of intervertebral disc degeneration occurred in 50% of the patients. Eleven patients underwent herniotomy due to poor treatment effects. Moreover, treatment in 77.4% of the patients was considered effective. A logistic regression analysis revealed that L5/S1 disk administration (p = 0.029; odds ratio, 5.94; 95% confidence interval, 1.20-29.45) were significantly associated with clinical effectiveness. CONCLUSIONS: Condoliase disk administration improved pain and quality of life over time. Condoliase disk administration was more effective in L5/S1 intervertebral administration.