Spinopelvic fusion surgery from lower thoracic spine to pelvis increased hip joint moment-motion analysis.

PURPOSE: Spinal fusion surgery is often performed with pelvic fixation to prevent distal junctional kyphosis. The inclusion of spinopelvic fixation has been reported to induce progression of hip joint arthropathy in a radiographic follow-up study. However, its biomechanical mechanism has not yet been elucidated. This study aimed to compare the changes in hip joint moment before and after spinal fusion surgery. METHODS: This study was an observational study and included nine patients (eight women and one man) who were scheduled to undergo spinopelvic fusion surgery. We calculated the three-dimensional external joint moments of the hip during gait, standing, and climbing stairs before and 1 year after surgery. RESULTS: During gait, the maximum extension moment was 0.51 ± 0.29 and 0.63 ± 0.40 before and after spinopelvic fusion surgery (p = 0.011), and maximum abduction moment was 0.60 ± 0.33 and 0.83 ± 0.34 before and after surgery (p = 0.004), respectively. During standing, maximum extension moment was 0.76 ± 0.32 and 1.04 ± 0.21 before and after spinopelvic fusion surgery (p = 0.0026), and maximum abduction moment was 0.12 ± 0.20 and 0.36 ± 0.22 before and after surgery (p = 0.0005), respectively. During climbing stairs, maximum extension moment was - 0.31 ± 0.30 and - 0.48 ± 0.15 before and after spinopelvic fusion surgery (p = 0.040), and maximum abduction moment was 0.023 ± 0.18 and - 0.02 ± 0.13 before and after surgery (p = 0.038), respectively. CONCLUSION: This study revealed that hip joint flexion-extension and abduction-adduction moments increased after spinopelvic fixation surgery in the postures of standing, walking, and climbing stairs. The mechanism was considered to be adjacent joint disease after spinopelvic fusion surgery including sacroiliac joint fixation.

S2 alar-iliac screw loosening as a preventive factor for hip joint osteoarthritis after adult spinal deformity surgery: a case-control study.

PURPOSE: This study aimed to evaluate the progression of hip pathology and risk factors after ASD surgery. METHODS: This case-control study enrolled 123 patients (246 hips); seven hips underwent hip arthroplasty were excluded. We measured the center-edge (CE) angle, joint space width (JSW), and Kellgren-Lawrence (KL) grade. We defined a CE angle˂25° as developmental dysplasia of the hip (DDH). We evaluated S2 alar-iliac (AI) screw loosening at final follow-up. RESULTS: The annual decrease in the JSW was 0.31 mm up to 1 year, and 0.13 mm after 1 year (p = 0.001). KL grade progression occurred in 24 hips (10.0%; group P), while no progression occurred in 215 (90.0%; group N) hips. Nonparametric analysis between groups P and N revealed that significant differences were observed in sex, DDH, KL grade, ratio of S2AI screw fixation at baseline, and ratio of S2AI screw loosening at final follow-up. Multiple logistic regression analysis revealed that DDH (p = 0.018, odds ratio (OR) = 3.0, 95%CI = 1.2-7.3), baseline KL grade (p < 0.0001, OR = 37.7, 95%CI = 7.0-203.2), and S2AI screw fixation (p = 0.035, OR = 3.4, 95%CI = 1.1-10.4) were significant factors. We performed sub-analysis to elucidate the relationship between screw loosening and hip osteoarthritis in 131 hips that underwent S2AI screw fixation. Non-loosening of the S2AI screw was a significant factor for KL grade progression (p < 0.0001, OR = 8.9, 95%CI = 3.0-26.4). CONCLUSION: This study identified the prevalence and risk factors for the progression of hip osteoarthritis after ASD surgery. Physicians need to pay attention to the hip joint pathology after ASD surgery.

Adjacent segment disease on hip joint as a complication of spinal fusion surgery including sacroiliac joint fixation.

PURPOSE: Recently, the number of adult spinal deformity surgeries including sacroiliac joint fixation (SIJF) by using an S2 alar iliac screw or iliac screw has increased to avoid the distal junctional failure. However, we occasionally experienced patients who suffered from hip pain after a long instrumented spinal fusion. We hypothesized that long spinal fusion surgery including SIJF influenced the hip joint as an adjacent joint. The aim of this paper was to evaluate the association between spinal deformity surgery including SIJF and radiographic progression of hip osteoarthritis (OA). METHODS: This study was retrospective cohort study. In total, 118 patients who underwent spinal fusion surgery at single center from January 2013 to August 2018 were included. We measured joint space width (JSW) at central space of the hip joint. We defined reduction of more than 0.5 mm/year in JSW as hip OA progression. The patients were divided into two groups depending on either a progression of hip osteoarthritis (Group P), or no progression (Group N). RESULTS: The number of patients in Group P and Group N was 47 and 71, respectively. Factor that was statistically significant for hip OA was SIJF (p = 0.0065, odds ratio = 7.1, 95% confidence interval = 1.6-31.6). There were no other significant differences by the multiple logistic regression analysis. CONCLUSION: This study identified spinal fixation surgery that includes SIJF as a predictor for radiographic progression of hip OA over 12 months. We should pay attention to hip joint lesions after adult spinal deformity surgery, including SIJF.

Novel 3,4,7-Substituted Benzofuran Derivatives Having Binding Affinity to κ-Opioid Receptor.

A series of novel 3,4,7-trisubstituted benzofuran derivatives were synthesized, and their binding affinity to κ- (KOR) and µ-opioid receptors (MOR) were evaluated. Several aryl ethers showed moderate binding activities to KOR (IC50=3.9-11 µM) without binding to MOR.

Optimal flip angle of Gd-EOB-DTPA-enhanced MRI in patients with hepatocellular carcinoma and liver metastasis.

PURPOSE: To investigate optimal flip angle (FA) of three-dimensional fat-suppressed T1-weighted image on Gd-EOB-DTPA-enhanced MRI. METHODS: Forty-five patients with 35 hepatocellular carcinomas (HCCs) and 16 liver metastases (METs) were investigated. Signal-to-noise ratio (SNR), tumor-to-liver contrast (TLC) of HCC and MET, visual image quality (IQ) and lesion conspicuity (LeCo) were evaluated at hepatobiliary phase with different FAs (FA15°-30°-45°-60° in 13 patients, FA5°-10°-15°-20°-25° in 32 patients). RESULTS: TLC gradually showed better in range from FA15° to FA60° and FA5° to FA25°, but SNRs gradually decreased. SNR and TLC-MET at FA15° were significantly better than those at FA45° and FA60°. SNR at FA10° was significantly higher than at FA5°, FA20°, and FA25°. TLC-HCC and TLC-MET at FA5° were inferior to other FAs. IQs and LeCos at FA15° and FA30° were superior to those at FA45° and FA60°. IQs at FA5° and FA25° were significantly lower than those at FA10°-20°, although LeCos for HCC and MET at FA25° were superior to those at FA5°-20°. CONCLUSIONS: FA ranging from 10° to 20° is suitable for hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI, to image HCC and MET.

Accurate fall risk classification in elderly using one gait cycle data and machine learning.

BACKGROUND: Falls among the elderly are a major societal problem. While observations of medium-distance walking using inertial sensors identified potential fall predictors, classifying individuals at risk based on single gait cycles remains elusive. This challenge stems from individual variability and step-to-step fluctuations, making accurate classification difficult. METHODS: We recruited 44 participants, equally divided into high and low fall-risk groups. A smartphone secured on their second sacral spinous process recorded data during indoor walking. Features were extracted at each gait cycle from a 6-dimensional time series (tri-axial angular velocity and tri-axial acceleration) and classified using the gradient boosting decision tree algorithm. FINDINGS: Mean accuracy across five-fold cross-validation was 0.936. "Age" was the most influential individual feature, while features related to acceleration in the gait direction held the highest total relative importance when aggregated by axis (0.5365). INTERPRETATION: Combining acceleration, angular velocity data, and the gradient boosting decision tree algorithm enabled accurate fall risk classification in the elderly, previously challenging due to lack of discernible features. We reveal the first-ever identification of three-dimensional pelvic motion characteristics during single gait cycles in the high-risk group. This novel method, requiring only one gait cycle, is valuable for individuals with physical limitations hindering repetitive or long-distance walking or for use in spaces with limited walking areas. Additionally, utilizing readily available smartphones instead of dedicated equipment has potential to improve gait analysis accessibility.

The treatment of femoral neck fractures: results using cephalocervical screws with sliding mechanism.

BACKGROUND: A new device for the treatment of femoral neck fractures that uses 2 cephalocervical screws in a sliding mechanism allowing linear intraoperative and postoperative compression has been developed. The purpose of this retrospective study was to determine the results using this device for the treatment of stable and unstable femoral neck fractures. METHODS: Between November 2007 and November 2011, 61 consecutive skeletally mature patients with femoral neck fractures were treated with a new cephalocervical screw (Dual SC screw; KISCO DIR Co., Ltd., Kobe). All contactable patients were followed up for a minimum of 16 weeks postoperatively (range 16-123 weeks). Clinical and radiographic examinations were performed at the final evaluation. Healing and return to activities of daily living were used to evaluate outcomes. RESULTS: There were 51 women and 10 men with a mean age of 80.8 years (range, 41-99). The average of surgical time was 33.1 min (21-66 min). One patient died, one was too infirm for follow-up, and eleven could not be located, leaving 48 patients available for final evaluation (78.7%). The overall incidence of nonunion was 10.4%. Fracture nonunion was less common for undisplaced fractures than for displaced fractures (1 of 21 [4.8%] vs. 4 of 27 [14.8%]). The mean amount of collapse of the neck was 5.45 mm (3.92 mm in undisplaced and 6.64 mm in displaced). Radiographic analysis at final evaluation revealed no implant failures. 62.5% of the patients recovered their prefracture status. CONCLUSION: The Dual SC screw device appears to be a reliable implant for the treatment of femoral neck fractures. Its design contributes to overcome the implant failures such as a medial migration, cut-out, or back-out; besides, the union rate of this implant was considered superior to that of existing systems. If the early shortening of the neck occurs after this surgery, the surgeons should be considered to keep them partially weight bearing or choose a replacement procedure for such patients.

Development of a Novel Rat Knee Osteoarthritis Model Induced by Medial Meniscus Extrusion.

OBJECTIVE: The medial meniscus extrusion (MME) is associated with increased stress on the knee joint, which leads to cartilage degeneration. To evaluate the etiology of knee osteoarthritis, it is extremely important to create animal models of the disease that more closely resemble actual clinical conditions in terms of symptomatology, molecular biology, and histology. This study aimed to create a clinically relevant model of MME in rats. DESIGN: Behavioral, molecular biological, and histological changes in the newly developed rat MME model were compared with those in sham and medial meniscus transection and medial collateral ligament transection (MMT) models to examine the characteristics of this model. RESULTS: In the MME rat model, behavioral evaluation shows abnormalities in gait compared with the other 2 groups, and molecular biological evaluation of the infrapatellar synovia of rats shows that gene expression of inflammatory cytokines, matrix-degrading enzymes, and pain-related nerve growth factor was increased compared with the sham group. Furthermore, histological evaluation reveals that cartilage degeneration was the most severe in the MME group. CONCLUSIONS: The newly developed MME model reproduced the characteristic pathology of MME in clinical practice, such as severe pain, inflammation, and rapid progression of osteoarthritis. The MME model, which might more closely mimic human knee osteoarthritis (OA), could be a useful model for elucidating the pathophysiology and considering therapeutic management for knee OA.

Erratum for Lumbar Fusion including Sacroiliac Joint Fixation Increases the Stress and Angular Motion at the Hip Joint: A Finite Element Study.

[This corrects the article DOI: 10.22603/ssrr.2021-0231.].

Medial meniscus extrusion and varus tilt of joint line convergence angle increase stress in the medial compartment of the knee joint in the knee extension position -finite element analysis.

PURPOSE: Although it has been recognized that the medial meniscus extrusion (MME) leads to progressive cartilage loss and osteoarthritis (OA), about 20% of cases with MME had minor symptoms and poor progression of knee OA. However, it is still unclear which patients will have minimal symptoms or will not progress to degeneration. The purpose of this study is to compare the effect of the relationship between the MME and Joint line convergence angle (JLCA) on knee stress with the finite element (FE) analysis method. METHODS: The 65 year-old female was taken computer tomography (CT) from thigh to ankle. A 3-dimentional nonlinear FE model was constructed from the patient's DICOM data. We made the six models, which was different from JLCA and MME. Contact stresses on the surfaces between femoral and tibial cartilages and both side of meniscus are analyzed. RESULTS: As the JLCA or MME increased, the stress load on the medial compartment increased. The effect of MME was stronger on the femoral side, while the effect of JLCA was stronger for the tibia and meniscus. If the JLCA was tilted valgus, the stress in the medial compartment did not increase even in the presence of MME. CONCLUSIONS: This study revealed that the MME is associated with increased a stress loading on medial compartment structures. Furthermore, this change was enhanced by the varus tilt of the JLCA. In the case of valgus alignment, the contact pressure of the medial compartment did not increase so much even if with the MME. LEVEL OF EVIDENCE: Level V.

Lumbar Fusion including Sacroiliac Joint Fixation Increases the Stress and Angular Motion at the Hip Joint: A Finite Element Study.

Introduction: Adult spinal fusion surgery improves lumbar alignment and patient satisfaction. Adult spinal deformity surgery improves saggital balance not only lumbar lesion, but also at hip joint coverage. It was expected that hip joint coverage rate was improved and joint stress decreased. However, it was reported that adjacent joint disease at hip joint was induced by adult spinal fusion surgery including sacroiliac joint fixation on an X-ray study. The mechanism is still unclear. We aimed to investigate the association between lumbosacral fusion including sacroiliac joint fixation and contact stress of the hip joint. Methods: A 40-year-old woman with intact lumbar vertebrae underwent computed tomography. A three-dimensional nonlinear finite element model was constructed from the L4 vertebra to the femoral bone with triangular shell elements (thickness, 2 mm; size, 3 mm) for the cortical bone's outer surface and 2-mm (lumbar spine) or 3-mm (femoral bone) tetrahedral solid elements for the remaining bone. We constructed the following four models: a non-fusion model (NF), a L4-5 fusion model (L5F), a L4-S1 fusion model (S1F), and a L4-S2 alar iliac screw fixation model (S2F). A compressive load of 400 N was applied vertically to the L4 vertebra and a 10-Nm bending moment was additionally applied to the L4 vertebra to stimulate flexion, extension, left lateral bending, and axial rotation. Each model's hip joint's von Mises stress and angular motion were analyzed. Results: The hip joint's angular motion in NF, L5F, S1F, and S2F gradually increased; the S2F model presented the greatest angular motion. Conclusions: The average and maximum contact stress of the hip joint was the highest in the S2F model. Thus, lumbosacral fusion surgery with sacroiliac joint fixation placed added stress on the hip joint. We propose that this was a consequence of adjacent joint spinopelvic fixation. Lumbar-to-pelvic fixation increases the angular motion and stress at the hip joint.

Feature selection to classify lameness using a smartphone-based inertial measurement unit.

BACKGROUND AND OBJECTIVES: Gait can be severely affected by pain, muscle weakness, and aging resulting in lameness. Despite the high incidence of lameness, there are no studies on the features that are useful for classifying lameness patterns. Therefore, we aimed to identify features of high importance for classifying population differences in lameness patterns using an inertial measurement unit mounted above the sacral region. METHODS: Features computed exhaustively for multidimensional time series consisting of three-axis angular velocities and three-axis acceleration were carefully selected using the Benjamini-Yekutieli procedure, and multiclass classification was performed using LightGBM (Microsoft Corp., Redmond, WA, USA). We calculated the relative importance of the features that contributed to the classification task in machine learning. RESULTS: The most important feature was found to be the absolute value of the Fourier coefficients of the second frequency calculated by the one-dimensional discrete Fourier transform for real input. This was determined by the fast Fourier transformation algorithm using data of a single gait cycle of the yaw angular velocity of the pelvic region. CONCLUSIONS: Using an inertial measurement unit worn over the sacral region, we determined a set of features of high importance for classifying differences in lameness patterns based on different factors. This completely new set of indicators can be used to advance the understanding of lameness.

Deep generative models for automated muscle segmentation in computed tomography scanning.

Accurate gluteus medius (GMd) volume evaluation may aid in the analysis of muscular atrophy states and help gain an improved understanding of patient recovery via rehabilitation. However, the segmentation of muscle regions in GMd images for cubic muscle volume assessment is time-consuming and labor-intensive. This study automated GMd-region segmentation from the computed tomography (CT) images of patients diagnosed with hip osteoarthritis using deep learning and evaluated the segmentation accuracy. To this end, 5250 augmented pairs of training data were obtained from five participants, and a conditional generative adversarial network was used to identify the relationships between the image pairs. Using the preserved test datasets, the results of automatic segmentation with the trained deep learning model were compared to those of manual segmentation in terms of the dice similarity coefficient (DSC), volume similarity (VS), and shape similarity (MS). As observed, the average DSC values for automatic and manual segmentations were 0.748 and 0.812, respectively, with a significant difference (p < 0.0001); the average VS values were 0.247 and 0.203, respectively, with no significant difference (p = 0.069); and the average MS values were 1.394 and 1.156, respectively, with no significant difference (p = 0.308). The GMd volumes obtained by automatic and manual segmentation were 246.2 cm3 and 282.9 cm3, respectively. The noninferiority of the DSC obtained by automatic segmentation was verified against that obtained by manual segmentation. Accordingly, the proposed GAN-based automatic GMd-segmentation technique is confirmed to be noninferior to manual segmentation. Therefore, the findings of this research confirm that the proposed method not only reduces time and effort but also facilitates accurate assessment of the cubic muscle volume.

Prediction of Pelvic Inclination in the Sitting Position after Corrective Surgery for Adult Spinal Deformity.

INTRODUCTION: Hip dislocation rates in patients with combined total hip arthroplasty (THA) and spinal deformity fixation are significantly higher than those of THA alone. Nevertheless, there are no treatment recommendations for patients who undergo THA and require a spine deformity correction later. METHODS: Twenty-eight patients underwent spinal fixation surgery for adult spinal deformity. Sagittal spinopelvic alignment was analyzed on lateral radiographs taken preoperatively and postoperatively in the sitting and standing positions. Univariate linear regression analysis was conducted to identify the factors affecting the pelvic inclination in the sitting position after spinal fixation. Multiple regression analysis was conducted to determine the most efficient combination of radiographic parameters for predicting postoperative pelvic inclination while sitting. RESULTS: There were significantly weak associations between postoperative sacral slope (SS) in the sitting position and the following factors: the number of vertebral levels fused (ß = 0.30, p = 0.003); the presence of sacral fixation (ß = 0.22, p = 0.01); the presence of sacroiliac joint fixation (ß = 0.24, p = 0.008); and preoperative SS while standing and sitting (ß = 0.21, p = 0.01 and ß = 0.34, p = 0.001). Postoperative lumbar lordosis (LL) while standing was strongly associated with postoperative SS in the sitting position (ß = 0.67, p <.0001). The combination of postoperative LL in the standing position and preoperative SS in the sitting position was the best fit, and the adjusted R-squared was 0.82. CONCLUSIONS: We devised a prediction formula for pelvic inclination while sitting after spinal fixation that has high predictability: postoperative SS while sitting = 11.7+ (0.4 × postoperative planned LL while standing) + (0.16 × preoperative SS while sitting). This study could be the basis for treatment recommendations for patients who have undergone THA and require a spine deformity correction later.

Formal Total Synthesis of (±)-Strictamine Based on a Gold-Catalyzed Cyclization.

A gold-catalyzed cyclization of 1-propargyl-1,2,3,4-tetrahydro-ß-carboline led to formation the D-ring of strictamine. Functional group modifications of the resulting tetracyclic indolenine led to the formal total synthesis of (±)-strictamine.

A ferredoxin Arg-Glu pair important for efficient electron transfer between ferredoxin and ferredoxin-NADP(+) reductase.

In order to elucidate the importance of a ferredoxin (Fd) Arg-Glu pair involved in dynamic exchange from intra- to intermolecular salt bridges upon complex formation with ferredoxin-NADP(+) oxidoreductase (FNR), Equisetum arvense FdI and FdII were investigated as normal and the pair-lacking Fd, respectively. The FdI mutant lacking this pair was unstable and rapidly lost the [2Fe-2S] cluster. The catalytic constant (k(cat)) of the electron transfer for FdI is 5.5 times that for FdII and the introduction of this pair into FdII resulted in the increase of k(cat) to a level comparable to that for FdI, demonstrating directly that the Arg-Glu pair is important for efficient electron transfer between Fd and FNR.

Acute ethanol administration down-regulates toll-like receptor-4 in the murine liver.

Acute ethanol administration temporarily decreases the sensitivity to endotoxin (lipopolysaccharide, LPS) in the liver. The purpose of this study was to investigate the changes of toll-like receptor (TLR)-4, a newly identified LPS receptor in macrophages, in the liver following acute ethanol administration. Male C57BL/6N mice were given a bolus intragastric administration of ethanol (5 mg/g BW) through a gastric canula, and liver samples were obtained 2-48 h later. RAW264.7 macrophages were cultured in the presence of ethanol (100 mM) or LPS (10 ng/ml) for up to 4 h. TLR-4 mRNA in the liver and RAW264.7 cells was detected by RNase protection assay. As expected, TLR-4 mRNA was clearly detected in the control liver; however, it was barely detectable in the liver 2-6 h after ethanol administration, followed by the gradual increase to the basal levels 48 h later. Interestingly, LPS (10 ng/ml), but not ethanol (100 mM), decreased TLR-4 mRNA in RAW264.7 macrophages in 4 h. Indeed, gut-sterilization by oral antibiotics pretreatment prevented the decrease in TLR-4 mRNA caused by acute ethanol administration, supporting the hypothesis that gut-derived endotoxin is involved in the mechanism. These findings clearly indicated that acute ethanol administration in vivo down-regulates TLR-4 expression in the liver. This phenomenon most likely explains the mechanism by which acute ethanol blunts the response of Kupffer cells to LPS transiently.

Lead evaluation of tetrahydroquinolines as nonsteroidal selective androgen receptor modulators for the treatment of osteoporosis.

Tetrahydroquinoline (THQ) was deemed to be a suitable scaffold for our nonsteroidal selective androgen receptor modulator (SARM) concept. We adapted the strategy of switching the antagonist function of cyano-group-containing THQ (CN-THQ) to the agonist function and optimized CN-THQ as an orally available drug candidate with suitable pharmacological and ADME profiles. Based on binding mode analyses and synthetic accessibility, we designed and synthesized a compound that possesses a para-substituted aromatic ring attached through an amide linker. The long-tail THQ derivative 6-acetamido-N-(2-(8-cyano-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl)-2-methylpropyl)nicotinamide (1 d), which bears a para-acetamide-substituted aromatic group, showed an appropriate in vitro biological profile, as expected. We considered that the large conformational change at Trp741 of the androgen receptor (AR) and the hydrogen bond between 1 d and helix 12 of the AR could maintain the structure of the AR in its agonist form; indeed, 1 d displays strong AR agonistic activity. Furthermore, 1 d showed an appropriate in vivo profile for use as an orally available SARM, displaying clear tissue selectivity, with a separation between its desirable osteoanabolic effect on femoral bone mineral density and its undesirable virilizing effects on the uterus and clitoral gland in a female osteoporosis model.

Asymmetric autocatalysis induced by meteoritic amino acids with hydrogen isotope chirality.

Achiral meteoritic amino acids, glycine and alpha-methylalanine, with hydrogen isotope (D/H) chirality, acted as the source of chirality in asymmetric autocatalysis with amplification of ee to afford highly enantioenriched 5-pyrimidyl alkanols.