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Background Studies comparing the safety of orexin receptor antagonists and other hypnotic types for older patients with heart failure (HF) remain lacking. This study aimed to compare orexin receptor antagonists (suvorexant) with benzodiazepines or Z-drugs for sleep treatment and investigate the risk of acute HF-related rehospitalisation in older patients with HF.Methods This study used a cohort design to analyse data from an administrative claims database from April 2008 to December 2020. The study population was determined based on inclusion and exclusion criteria from a cohort of 1 159 937 patients aged ≥65 years, selected through random sampling. The follow-up period was censored based on multiple criteria, including outcome occurrences and hypnotic classification changes. Kaplan-Meier survival analysis and Cox proportional hazards models were conducted for risk assessment.Results The analysis included 1858 patients, aged ≥65 years and experiencing their first HF-related hospitalisation. These patients were categorised based on the initially prescribed hypnotic classification, including suvorexant, benzodiazepines and Z-drugs in 490, 606 and 762 patients, respectively. The average age and SD were similar across all hypnotic classes at 82.7±7.6 years. Kaplan-Meier curves indicated a higher trend of rehospitalisation risk for benzodiazepines and Z-drugs than for suvorexant. The adjusted HRs were 2.77 (95% CI 1.17 to 6.52) for benzodiazepines and 2.98 (95% CI 1.33 to 6.68) for Z-drugs.Conclusions Suvorexant administration for sleep treatment in older patients with HF shows a potentially reduced risk of acute HF-related rehospitalisation compared with benzodiazepines and Z-drugs. The results of this study provide valuable information for selecting hypnotics in older patients with HF having concurrent sleep disorders.

Abstract To examine the association between hip fracture and associated factors, including polypharmacy, and develop an optimal predictive model, we conducted a population-based matched case–control study using the health insurance claims data on hip fracture among Japanese patients. We included 34,717 hospitalized Japanese patients aged ≥ 65 years with hip fracture and 34,717 age- and sex- matched controls who were matched 1:1. This study included 69,434 participants. Overall, 16 variable comorbidities and 60 variable concomitant medications were used as explanatory variables. The participants were added to early elderly and late elderly categories for further analysis. The odds ratio of hip fracture increased with the number of medications only in the early elderly. AUC was highest for early elderly (AUC, 0.74, 95% CI 0.72–0.76). Use of anti-Parkinson’s drugs had the largest coefficient and was the most influential variable in many categories. This study confirmed the association between risk factors, including polypharmacy and hip fracture. The risk of hip fracture increased with an increase in medication number taken by the early elderly and showed good predictive accuracy, whereas there was no such association in the late elderly. Therefore, the early elderly in Japan should be an active target population for hip fracture prevention.

Abstract Gravity-dependent physical processes strongly affect the ability of elderly people to maintain musculoskeletal health by reducing muscle atrophy and increasing bone mineral density, thereby increasing quality of life. A need therefore exists to identify molecules in the musculoskeletal system that are responsive to gravitational loading and to establish an objective indicator for the maintenance of healthy musculoskeletal systems. Here, we performed an integrated assessment of the results of soleus muscle proteomic analyses in three model mouse experiments under different gravity environments (hypergravity, hindlimb unloading, and spaceflight). Myl6b, Gpd1, Fbp2, Pvalb, and Actn3 were shown to be gravity-responsive muscle proteins, and alterations in the levels of these proteins indicated changes in muscle fiber type to slow-twitch type due to gravity loading. In addition, immunoblotting and enzyme-linked immunosorbent assays revealed that Pvalb levels in the sera of hindlimb-unloaded mice and osteoporosis patients were higher than in control subjects, suggesting that Pvalb levels might be useful to objectively evaluate soleus muscle atrophy and bone loss.

Abstract Chronic myeloid leukemia (CML) is a form of myeloproliferative neoplasm caused by the oncogenic tyrosine kinase BCR-ABL. Although tyrosine kinase inhibitors have dramatically improved the prognosis of patients with CML, several problems such as resistance and recurrence still exist. Immunological control may contribute to solving these problems, and it is important to understand why CML patients fail to spontaneously develop anti-tumor immunity. Here, we show that differentiation of conventional dendritic cells (cDCs), which are vital for anti-tumor immunity, is restricted from an early stage of hematopoiesis in CML. In addition, we found that monocytes and basophils, which are increased in CML patients, express high levels of PD-L1, an immune checkpoint molecule that inhibits T cell responses. Moreover, RNA-sequencing analysis revealed that basophils express genes related to poor prognosis in CML. Our data suggest that BCR-ABL not only disrupts the “accelerator” (i.e., cDCs) but also applies the “brake” (i.e., monocytes and basophils) of anti-tumor immunity, compromising the defense against CML cells.

Abstract Background Patients with diabetes are at higher risk of developing polypharmacy because of the high frequency of comorbidities. There have been several reports on the hypoglycemic risk of the combination of hypoglycemic agents and other medications. This study aimed to investigate the hypoglycemic risk of drug-drug interaction between sitagliptin and other oral hypoglycemic agents or antihypertensive agents in Japanese patients with type 2 diabetes. Methods From January 2010 to March 2012, a total of 3247 patients were recruited and evaluated at outpatient clinics at Juntendo University Hospital, other satellite hospitals, and private clinics. This study was a sub-analysis of the Sitagliptin Registration Type 2 Diabetes-Juntendo Collaborating Project. Participants were limited to those treated with oral hypoglycemic agents, excluding insulin users, to investigate the association of the first hypoglycemic events with oral hypoglycemic agents or other medications within 6 months after starting sitagliptin. The factors related to the first hypoglycemic event were analyzed using Cox regression analysis. Results In total, 2956 patients with a mean age of 65.1 ± 11.3 years were included. A total of 46 hypoglycemic events (1.6%) were observed. One patient had severe hypoglycemia followed by emergency transport to the hospital. Sitagliptin was not associated with hypoglycemia, but its combination with sulfonylurea (hazard ratio: 4.42, 95% confidential interval: 1.36–14.42) or β-blocker (hazard ratio, 3.50, 95% confidential interval: 1.54–7.96) was significantly associated with hypoglycemia. Conclusions The drug-drug interactions between sitagliptin and sulfonylurea or β-blocker likely increases the hypoglycemic risk in Japanese patients with type 2 diabetes. Pharmacists should consider potential adverse events from drug-drug interaction in type 2 diabetes with polypharmacy, particularly those who are managed by several doctors or clinics.

Abstract Background Although a high number of wet compresses are prescribed daily in medical institutions in Japan, our understanding of the national burden of the cost of wet compresses and the details regarding their prescription is far from complete. We investigated the national burden of the annual pharmaceutical cost of wet compresses prescribed in Japan and estimated the predictors of this cost using nationwide health insurance claims data. Methods We extracted the records on wet compress products from summary table files obtained from the second version of the “NDB Open Data Japan” website and calculated the annual pharmaceutical cost of wet compresses by patients’ 5-year age group, sex, and prefecture. We also conducted an ecological study treating each prefecture as an individual unit and multiple linear regression analyses using the age-standardized cost of wet compresses per resident as a dependent variable. Results The annual pharmaceutical cost of wet compresses prescribed in Japan in fiscal year 2015 was 149.0 billion Japanese yen (1.18 billion euros; 1.33 billion USD). Multiple linear regression analyses showed that the number of orthopedists and rehabilitation physicians per 100,000 residents were significantly positively associated with the annual pharmaceutical cost of wet compresses per resident (P = 0.042 and P = 0.008, respectively). Conclusions The annual pharmaceutical cost of wet compresses prescribed in Japan has a considerable impact on the nation’s limited healthcare resources. The number of orthopedists and rehabilitation physicians per 100,000 residents may be independent predictors of the wet compress cost in Japan.

Introduction: Hashimoto's thyroiditis, which is characterized by anti-thyroid antibodies such as the anti-thyroglobulin (Tg) antibody and anti-thyroid peroxidase (TPO) antibody, is one of the autoimmune diseases associated with psychiatric illnesses. We previously reported a high prevalence of antibodies to N-terminals of N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN1-NT and GluN2B-NT2) among psychiatric patients with anti-thyroid antibodies. However, it remains unclear whether the presence of anti-thyroid antibodies influences antibodies to GluN1-NT or GluN2B-NT2 among psychiatric patients. The present study aims to examine antibodies to GluN1-NT and GluN2B-NT2 in psychiatric patients with anti-thyroid antibodies (PPATs) and in those without (non-PPATs). Material and methods: We recruited psychiatric inpatients aged 20–60 years. Patients were excluded if they had a history of neurological diseases, dementia, developmental disorders, tumors, or autoimmune diseases except autoimmune thyroiditis. The rest of the participants were divided into two groups according to the presence of serum anti-Tg and anti-TPO antibodies. We investigated serum and cerebrospinal fluid (CSF) antibodies to GluN1-NT and GluN2B-NT2 using an enzyme-linked immunosorbent assay (ELISA). Results: We initially recruited seventy-three psychiatric inpatients. Forty-six patients were excluded because of the exclusion criteria. Eighteen PPATs and nine non-PPATs were ultimately enrolled. We also collected stored sera of eighteen healthy controls (HCs) who were age- and sex-matched with PPATs. The optical densities (ODs) of serum antibodies to GluN1-NT (p = 0.0020) and GluN2B-NT2 (p = 0.039) were significantly higher in PPATs than in HCs. The ODs of CSF antibodies to GluN1-NT (p = 0.030) and GluN2B-NT2 (p = 0.017) as well as the positive ratios of those antibodies were significantly higher in PPATs than in non-PPATs. Conclusion: Our finding indicates that detecting anti-thyroid antibodies in psychiatric patients would be a clue to consider psychiatric conditions related to antibodies to GluN1-NT/GluN2B-NT2. Further studies focusing on the relationship between PPATs and antibodies to GluN1-NT/GluN2B-NT2 are needed.

Study Design Retrospective study. Purpose To evaluate the efficacy of the Spinal Instability Neoplastic Score (SINS) in predicting surgical outcomes and survival. Patients were categorized into two groups according to the SINS, and their surgical outcomes and survival following decompression and stabilization were assessed. Overview of Literature Palliative surgery in patients with a life expectancy ≥3 months may effectively improve their overall condition in the long term. Currently, the effectiveness of the SINS for predicting surgical results and survival remains controversial. Methods This study included 44 patients who underwent decompression and stabilization for spinal metastases at Yokosuka Kyosai Hospital between 2008 and 2017. The patients were divided into two groups: stable (SINS ≤12) and unstable (SINS ≥13). Changes in the Frankel score and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) were compared between the two groups, and patient survival was evaluated according to the SINS, Tokuhashi score, and Katagiri score. Results The stable group (SINS range, 7–12) included 24 patients while the unstable group (SINS range, 13–16) included 20 patients. The Frankel score significantly improved from 2.8 to 3.6 in the stable group (p

Abstract Background A postoperative change in femoral rotation following total hip arthroplasty (THA) might be the cause of dislocation due to the change in combined anteversion. However, very few studies have evaluated the femoral rotation angle following THA, or the factors that influence femoral rotation. We aimed to evaluate changes in femoral rotation after THA, and to investigate preoperative patient factors that influence femoral rotation after THA. Methods This study involved 211 hips treated with primary THA. We used computed tomography to measure the femoral rotation angle before and one week after THA. In addition, multiple regression analysis was performed to evaluate preoperative patient factors that could influence femoral rotation after THA. Results The femoral rotation angle was 0.2 ± 14° externally before surgery and 4.4 ± 12° internally after surgery (p

Introduction: To assess the bone fusion rates and clinical results of two surgical methods (pedicle screw claw-hook fixation and pedicle screw hook fixation) of lumbar spondylolysis repair. Methods: A multicenter database of surgical patients with lumbar spondylolysis was reviewed. All patients < 20 years old with a minimum of 6 months of follow-up and computed tomography images were included. Operation time and blood loss amount were investigated. Visual analogue scale (VAS; 0-10) scores for lower back pain were evaluated to assess clinical results. Results: A total of 17 patients met the inclusion criteria. Pedicle screw hook fixation was performed in five patients (the hook group), and pedicle screw claw-hook fixation was performed in 13 patients (the claw-hook group). One patient was included in both groups because each method was performed at different lumbar levels (L4 and L5). The bone fusion rates at 3, 6, and 9 months after surgery were significantly higher in the claw-hook group than those in the hook group. Operation time and blood loss amount were not significantly different between the groups. VAS scores improved in the claw-hook group but not in the hook group because of a small number of patients. Conclusions: Pedicle screw claw-hook fixation was more effective than pedicle screw hook fixation in terms of bone fusion rates.

Abstract Background The gluteus medius (GMED) affects hip function as an abductor. We evaluated muscle volume and degeneration of the GMED by using CT-based analysis and assessed factors that affect hip abductor strength in patients with unilateral hip osteoarthritis (OA). Methods We examined clinical and imaging findings associated with hip abductor strength in consecutive 50 patients with unilateral hip OA. Hip abductor muscle strength and Harris hip score (HHS) were assessed. Leg length discrepancy (LLD) and femoral offset were assessed using X-ray; CT assessment was employed for volumetric and qualitative GMED analysis. Volumetric analysis involved measurement of cross sectional area (CSA) and three-dimensional (3D) muscle volume. CT density was measured for the qualitative assessment of GMED degeneration with or without adjustment using a bone mineral reference phantom. Results Hip abductor muscle strength on the affected side was significantly lower than that on the contralateral healthy side and positively correlated with overall score and score for limping of gait of HHS, demonstrating the importance of hip abductor strength for normal hip function. A significant correlation was found between CSA and 3D muscle volume, unadjusted CT density and adjusted CT density, and hip abductor strength and these CT measurements. Multiple linear regression analysis demonstrated that 3D muscle volume, adjusted CT density, and LLD are independent factors affecting hip abduction. Conclusions 3D measurement of muscle volume and adjusted CT density more accurately reflect quantity and the GMED quality than do conventional assessments. Increase in muscle volume, recovery of muscle degeneration, and correction of LLD are important for improving limping in patients with hip OA.

Abstract Background While cam resection is essential to achieve a good clinical result with respect to femoroacetabular impingement (FAI), it is unclear whether it should also be performed in cases of borderline developmental dysplasia of the hip (DDH) with a cam deformity. The aim of this study was to evaluate improvements in range of motion (ROM) in cases of cam-type FAI and borderline DDH after virtual osteochondroplasty using a computer impingement simulation. Methods Thirty-eight symptomatic hips in 31 patients (11male and 20 female) diagnosed with cam-type FAI or borderline DDH were analyzed. There were divided into a cam-type FAI group (cam-FAI group: 15 hips), borderline DDH without cam group (DDH W/O cam group: 12 hips), and borderline DDH with cam group (DDH W/ cam group: 11 hips). The bony impingement point on the femoral head-neck junction at 90° flexion and maximum internal rotation of the hip joint was identified using ZedHip® software. Virtual osteochondroplasty of the impingement point was then performed in all cases. The maximum flexion angle and maximum internal rotation angle at 90° flexion were measured before and after virtual osteochondroplasty at two resection ranges (i.e., slight and sufficient). Results The mean improvement in the internal rotation angle in the DDH W/ cam group after slight resection was significantly greater than that in the DDH W/O cam group (P = 0.046). Furthermore, the mean improvement in the internal rotation angle in the DDH W/ cam and cam-FAI groups after sufficient resection was significantly greater than that in the DDH W/O cam group (DDH W/ cam vs DDH W/O cam: P = 0.002, cam-FAI vs DDH W/O cam: P = 0.043). Conclusion Virtual osteochondroplasty resulted in a significant improvement in internal rotation angle in DDH W/ cam group but not in DDH W/O cam group. Thus, borderline DDH cases with cam deformity may be better to consider performing osteochondroplasty.

Introduction: This study aimed to assess treatment outcomes and caregivers' satisfaction regarding scoliosis surgery for handicapped children. Methods: Handicapped children are, by definition, noncommunicatory and/or nonambulatory. We recruited 26 handicapped children who were followed-up for >1 year after a scoliosis surgery. We recruited 40 patients with adolescent idiopathic scoliosis (AIS) who underwent a surgery during the same period as controls. We used a posterior approach in all the children. We determined preoperative body mass index (BMI), main Cobb angle, Cincinnati correction index (CCI), and fusion level; intraoperative time and blood loss per level; and postoperative complications. We also assessed caregivers' satisfaction with surgical treatments for these patients using the modified Bridwell's questionnaire. Results: We have described the results as handicapped children/AIS. Median preoperative BMI was 16.1/18.6 kg/m2. Preoperative and final Cobb angles were 94.2°/59.7° and 39.7°/17.0°, respectively and CCI was 2.0/1.7. The number of fusion levels was 14.6/9.0. The operative time and blood loss per level were 40.1/44.1 minutes and 264/138 ml, respectively. Postoperative complications in handicapped children were adynamic ileus in 8 cases, dysphagia in 5, pneumonia in 3, urinary tract infection in 2, and superior mesenteric artery syndrome (SMA), surgical site deep infection, infectious enteritis, agitation, and liver dysfunction in 1 each. However, in the AIS group, there was only 1 case of SMA. Median caregivers' satisfaction score on the 0-10 visual analog scale was 9. Caregivers for 19 of the 26 handicapped cases (73%) recommended surgical treatment to caregivers of other children with the same disease. Conclusions: Surgical treatment for neuromuscular and syndromic scoliosis was associated with a high rate of postoperative complications. However, the caregivers' satisfaction score after surgery was high.

Objective: The aim of this study was to analyse the optimal trajectories for sacral alar iliac screws (SAISs) in a Japanese patient population and the clinical assessment of insertion accuracies. Methods: The ideal trajectories of SAISs, starting from 2 mm medial to the apex of the lateral sacral crest on the midline between S1 and S2 dorsal foramina, were measured in 80 consecutive spinal disease patients (40 males and 40 females; average age: 67.4 ± 8.1 years) using three-dimensional computed tomographic image software. Following these anatomic analyses, accuracies of 32 inserted SAISs in consecutive patients, who underwent long spinal posterior fusion, were investigated clinically. Results: Lateral angulations of optimal SAIS trajectories in males (left: 37.9; right: 37.7) were significantly larger than those than in females (left: 32.8; right: 32.4). Caudal SAIS angulations for females (left: 33.4; right: 33.9) were significantly larger than those in males (left: 27.5; right: 28.0). The 32 SAISs (100 mm long and 9 mm in diameter) assessed clinically were accurately inserted on optimal trajectories. Conclusion: The optimal trajectories of SAISs in a Japanese patient population are more lateral in males and more caudal in females. This study examines the clinical safety and accuracy of SAIS insertion on these optimal trajectories. Keywords: Sacral alar iliac screw, Optimal entry point, Optimal trajectory, Accuracy, 3D CT

Abstract Background Chronic nonbacterial osteomyelitis (CNO) is a multifocal autoinflammatory disease that often impairs daily life in children. This study aimed to investigate the bone metabolic and inflammatory characteristics of patients with CNO, and to assess the differences between responders and nonresponders to conservative treatment. Methods We investigated the clinical symptoms; laboratory data including inflammatory and bone metabolic biomarkers; and imaging findings from plain radiography, magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), and dual-energy x-ray absorption (DEXA) in 14 patients with CNO. All patients underwent first-line treatment comprising systemic nonsteroidal anti-inflammatory drugs with or without bisphosphonate. According to the response to the first-line treatment, the patients were divided into the clinical remission/partial response group and the no response group. The differences in bone metabolic and inflammatory characteristics between the two groups were assessed. Results All patients had low bone mineral density assessed with DEXA. The bone metabolic biomarkers (bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b) were increased in boys of all ages and in young girls. Multiple inflammatory regions were detected in all patients by using FDG-PET including asymptomatic regions. The no response group had higher immunoglobulin G (IgG) and a greater number of bone inflammatory lesions detected on MRI than the clinical remission/partial response group. Conclusion Our data indicate the involvement of abnormal bone turnover, necessity of whole-body scanning, and association of higher serum IgG levels and greater numbers of inflammatory lesions with prolonged disease activity in patients with CNO.

Abstract Background Rotational acetabular osteotomy (RAO) is an effective joint-preserving surgical treatment for adulthood hip dysplasia (AHD). Despite sufficient correction of acetabular dysplasia, some patients still experience osteoarthritis (OA) progression and require total hip arthroplasty (THA). The purposes of the current study were to investigate the survival rate and the risk factors for OA progression or THA requirement after RAO and to explore whether acetabular overcorrection relates to OA progression. Methods Fifty-six patients (65 hips, mean age: 36.5 ± 11.7 years) with AHD who underwent RAO and were followed up for >10 years (mean: 15.0 ± 3.2 years) were enrolled in this study. A Kaplan-Meier survival analysis was performed to assess the non-OA progression rate and THA-free survival rate of RAO during the 10-year follow-up. To analyze the risk factors for OA progression and THA requirement, the Cox proportional hazards regression analysis was performed. Results No OA progression was found in 76.7% of the patients, and THA was not required in 92.3% during the 10-year follow-up. By multivariate regression analysis, older age at the time of surgery was a risk factor for both OA progression (hazard ratio [HR] = 1.047, 95% confidence interval [CI] = 1.005–1.091) and THA requirement (HR = 1.293, 95% CI = 1.041–1.606). Conclusion RAO is an effective surgical procedure for symptomatic patients with AHD that prevents OA progression and protects the hips from undergoing THA. However, older patients have a higher risk for both OA progression and THA requirement.

Abstract. Objectives:. To investigate the mortality rate following cervical spinal cord injury (SCI) injury and analyze the associated risk factors. Design:. Retrospective cohort study. Setting:. One Level 1 trauma center. Patients/participants:. A cohort of 76 patients with traumatic cervical SCI was reviewed between January 2010 and May 2015, of which 54 patients were selected for the present retrospective study. Intervention:. Operative or conservative treatment. Main outcome measurements:. The following patient parameters were analyzed; age, sex, American Spinal Injury Association (ASIA) impairment scale, neurological impairment level, injury mechanism, radiological findings, treatment, tracheostomy rate, and mortality. Results:. The mean age of the patient cohort was 65 ± 17 years, with 11 females (20%) and 43 males (80%). A total of 16 (30%), 4 (7%), 22 (41%), and 12 patients (22%) were scored A, B, C, and D, respectively, on the ASIA impairment scale. Most of the injuries were at the C4 (30%) and C5 (33%) levels. Falls from standing (35%) and heights (39%) were the most common injury mechanisms. SCI in 40 patients (74%) occurred without major fracture or dislocation. Surgery was performed on 26 patients. The overall mortality was 19%. Patients in the deceased group were significantly older at the time of injury, compared with those who survived. Paralysis had been more severe in the deceased group. A significantly high number of patients in the deceased group received a tracheostomy. When analyzed using a multivariate logistic regression model, an ASIA impairment scale of A was a significant risk factor for mortality. Conclusions:. The risk factors associated with mortality were age, tracheostomy, and an ASIA impairment scale of A, the latter had the highest risk. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Precise osteochondroplasty is key for success in hip arthroscopic surgery, especially for femoroacetabular impingement (FAI) caused by cam or pincer morphology. In this Technical Note, we present computer-assisted hip arthroscopic surgery for FAI, including preoperative planning by virtual osteochondroplasty and intraoperative computer navigation assistance. The important concept of this technique is that navigation assistance for osteochondroplasty is based on planning made by computer simulation analysis. The navigation assistance allows us to perform neither too much nor too little osteochondroplasty. Specifically, computer simulation was used to identify the impingement point. Virtual osteochondroplasty was then performed to determine the maneuvers that would improve range of motion. Thereafter, the planning data were transported to a computed tomography-based computer navigation system that directly provided intraoperative assistance. Thus, computer-assisted technology including preoperative simulation, virtual osteochondroplasty planning, and intraoperative navigation assistance may promote precise hip arthroscopic surgery for FAI.

Recent studies have shown an association between osteopenia and adolescent idiopathic scoliosis (AIS) and implied that osteopenia plays a causative role in AIS development. This study aimed to determine if minodronate (MIN) treatment could prevent curve progression by increasing bone mass in a thoracic restraint (TR) mouse model, which develops causes the development of thoracic scoliosis similar to human AIS. A total of 100 young female C57BL6J mice were divided into four groups: (1) control with vehicle (CON/VEH; n = 20), (2) control with MIN (CON/MIN; n = 20), (3) TR with vehicle (TR/VEH; n = 30), or (4) TR with MIN (TR/MIN; n = 30). MIN (0.01 mg/kg/week) and vehicle were administered intraperitoneally to their respective groups. TR was performed at age 4 weeks, and the mice were sacrificed at age 9 weeks. Body weights, spine radiographs, femoral bone mineral density (BMD), serum bone marker levels, and histomorphometry of the cancellous bone of the thoracic vertebrae were analyzed. TR significantly reduced weight gain in the TR/VEH group relative to the CON/VEH group. TR also induced osteoporosis with accelerated bone resorption, as indicated by decreases in femoral BMDs and thoracic cancellous bone volume and increases in serum bone resorption marker levels and histomorphometric resorption parameters in the TR/VEH group. MIN partially improved body weight gain and improved poor bone structure relative to the TR/VEH group by suppressing high bone resorption in the TR/MIN mice. MIN significantly reduced the curve magnitudes, as indicated by a 43% lower curve magnitude in the TR/MIN mice than in the TR/VEH mice (17.9 ± 8.9° vs. 31.5 ± 13.1°; p< 0.001). The administration of MIN increased bone mass and reduced the severity of scoliosis in the TR mice. MIN was suggested as a possible inhibitor of scoliosis development.

Sclerostin is a potent inhibitor of the canonical Wnt signaling pathway. Wnt signaling pathways have multiple roles in the regulation of cartilage development, growth, and maintenance. This study focused on the role of sclerostin in the process of chondrogenic differentiation. We hypothesized that sclerostin is essential to induce chondrogenic differentiation and regulate endochondral ossification. ATDC5 cells were used to investigate chondrogenic differentiation and terminal calcification. During chondrogenic differentiation, intrinsic sclerostin was upregulated in the early stage, but downregulated in the late stage. Addition of sclerostin elevated expressions of Sox9 and Col2a1 (P

For opening wedge high tibial osteotomy (OWHTO), it is recommended that the osteotomy line is parallel to the medial tibial posterior slope (TPS) in the sagittal view and that the alignments are simultaneously controlled in the coronal and sagittal views. Here combined computed tomography (CT)-based and image-free navigation systems were used for intraoperative reference during OWHTO. Using the CT-based navigation, 2 entry points for insertion of Kirschner wires were preoperatively set up and an accurate osteotomy plane was intraoperatively duplicated. Preoperative planning anticipated a femorotibial angle of 170°, representing a weight-bearing ratio of 62.5%, on the whole-leg radiograph. The original TPS in the sagittal view was aimed to be preserved postoperatively. The hip-knee-ankle (HKA) correction angle was preoperatively measured on the whole-leg radiograph, and the HKA angle and flexion angle were intraoperatively monitored in real time using the image-free navigation. We have introduced an operative technique for OWHTO using CT-based and image-free navigation systems. We expect that this method, with the osteotomy plane parallel to the tibial plateau plane in the sagittal view and simultaneous control of coronal and sagittal alignments, will enable actuation of accurate alignment in the 2 planes and lead to improvements in patient activity in future.

Displaced tibial intercondylar eminence fractures require early reduction and stable fixation to prevent nonunion, knee instability, and a lack of extension. Many types of surgical procedure are recommended including arthrotomy or an arthroscopic technique to stabilize the fracture segment using Kirschner wire, screws, staples, and suture fixation. However, contemporary arthroscopic techniques and devices can facilitate intra-articular surgery and have been applied to the treatment of this fracture. In our current report, we describe a simple suture fixation method under arthroscopy for the treatment of tibial intercondylar eminence fractures. We treated eight knees of eight patients. One patient had a Type II fracture and seven patients had a Type III fracture according to Meyer's classification. Following the arthroscopic inspection of concomitant injuries, debridement of hematoma, and reduction of the fragment, two nonabsorbable sutures (Ethibond No. 2, Johnson & Johnson, Somerville, NJ, USA) were advanced through the suture passer device, which is used to penetrate the anterior cruciate ligament (ACL) near to the insertion site of the displaced fragment. Two surgical sutures were pulled out by the suture retriever from the anterior proximal tibia hole and were fixed to the tibia cortex bone with a double-spike plate. At follow-up, radiographic examinations showed that bone union was achieved in all cases. All but one patient could resume normal activities with no restrictions and no ligamentous instability. All knees had a negative Lachman's test and showed a gain of stable ligament function by KT2000 arthrometer evaluation. One patient had an insignificant extension limitation and experienced slight pain after walking but these symptoms were minimal. In conclusion current arthroscopic surgery techniques for tibial intercondylar fractures can be easily performed and reproducibly achieve secure fixation and early mobilization of the knee.

Abstract Background The changes in synovial fluid biomarkers after intra‐articular injection of hyarulonic acid (IA HA) remain controversial. We investigate the changes in the properties of synovial fluid (SF) and clinical symptoms before the first and fifth IA HA. Methods A total of 73 patients (73 knees) with symptomatic knee osteoarthritis were treated with five weekly intra‐articular injections of HA and 55 patients (55 knees) were analyzed. The SF total volume, viscosity, and levels of HA, chondroitin 4‐sulfate (C4S), chondroitin 6‐sulfate (C6S), keratin sulfate, and interleukin (IL)‐6 were measured before the first and fifth injections. Clinical evaluations were performed using the American Knee Society score for physician‐based outcome measurements and Knee injury and Osteoarthritis Outcome Score for patient‐based outcome measurements before the first and fifth injections. Results The SF viscosity and levels of HA were significantly increased, and the total SF volume and levels of chondroitin 4‐sulfate, chondroitin 6‐sulfate, and interleukin‐6 were significantly decreased. The physician‐based and patient‐based outcome scores were improved. Conclusions Our findings speculate that HA injections significantly modulate levels of intra articular biomarkers which may indicate beneficial effect for articular cartilage and synovium membrane.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption or a secondary cause of hepatic steatosis. The prevalence of NAFLD is increasing worldwide and its management has become a public health concern. Animal models are traditionally used to elucidate disease mechanisms and identify potential drug targets; however, their translational aspects in human diseases have not been fully established. This study aimed to clarify the utility of animal models for translational research by assessing their relevance to human diseases using gene expression analysis. Weighted gene co-expression network analysis of liver tissues from Western diet (WD)-induced NAFLD mice was performed to identify the modules associated with disease progression. Moreover, the similarity of the gene co-expression network across species was evaluated using module preservation analysis. Nineteen disease-associated modules were identified. The brown module was positively associated with disease severity, and functional analyses indicated that it may be involved in inflammatory responses in immune cells. Moreover, the gene coexpression network of the brown module was highly preserved in human NAFLD liver gene expression datasets. These results indicate that WD-induced NAFLD mice have similar gene coexpression networks (especially genes associated with inflammatory responses) to humans and are thought to be a useful experimental tool for preclinical research on NAFLD. [ABSTRACT FROM AUTHOR]

Background/Aim: Nonalcoholic fatty liver disease (NAFLD) is a wide spectrum of liver disorders ranging from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Recently, the prevalence of NAFLD has dramatically increased, and treatment is urgently needed. Animal models are often used to understand the molecular mechanisms of disease development and progression, but their relevance to human diseases has not been fully understood. This study aimed to establish the usefulness of the animal model for preclinical research, we evaluated its relevance to human disease by gene expression analysis. Materials and Methods: We performed weighted gene co-expression network analysis of liver tissues from a choline-deficient L-amino acid-defined (CDAA) diet-induced NAFLD animal model. In addition, module preservation analysis was conducted to evaluate similarity across species. Results: Several modules were identified to be associated with disease severity, and their gene co-expression network was found to be preserved in the human NAFLD datasets. Of note, module brown (immune cell clusters involved in inflammatory responses) was positively associated with disease severity, and its gene co-expression network was highly preserved in the human datasets. Tyrobp, Laptm5 and Lgals3 were identified as hub genes in the brown module, and their increased expression was confirmed in the human datasets. Conclusion: CDAA diet-induced NAFLD animal model recaptured key aspects of human pathophysiology (especially immune cell functions) and is thought to be a powerful tool for understanding the molecular mechanisms of NAFLD development and progression. [ABSTRACT FROM AUTHOR]