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Three-dimensional (3D) imaging using computed tomography (CT) has made it possible to accurately evaluate ossification of the posterior longitudinal ligament (OPLL). Recently, we developed a novel technique to measure ossification volume using the 3D analysis. The purpose of this study was to investigate the natural course of OPLL and the risk factors for volume progression. Forty-one patients (22 males and 19 females) diagnosed with cervical OPLL who had been non-surgically treated were included in this study. We evaluated clinical examination, radiological findings, and the volume of ossified lesions during at least 1-year intervals. Furthermore, we performed risk factor analysis for OPLL volume progression. The mean ossification volume was 2047.4 ± 1437.3 mm3 in the first examination and 2201.0 ± 1524.1 mm3 in the final examination, indicating a significant increase during the follow-up period (p

Transcranial motor evoked potential (TcMEP) monitoring is the gold standard for intra-operative neurological monitoring (IOM) of motor pathways during complex spine surgery because of its high sensitivity and specificity. However, although it is very low, the rate of false-negatives in TcMEP monitoring is not zero. Therefore, over-reliance on TcMEP monitoring can cause potentially preventable motor deficits. We report a case of motor deficits due to nerve root stretch after surgical correction of a congenital lumbar kyphoscoliosis in a 56-year-old woman. TcMEPs did not show any significant changes during surgery, whereas free-run electromyography (EMG) demonstrated a long-lasting train activity in the left quadriceps femoris muscle (QF) after correction at the osteotomy area. According to the normal findings on TcMEP monitoring, we did not release the correction. Postoperatively, a significant decrease (grade 2-) in the manual muscle test for the left QF and iliopsoas muscle and hypesthesia of the left anterior thigh was revealed. Fortunately, muscle strength was fully recovered without revision surgery at 6 months postoperatively; however, numbness in the left anterior thigh persisted at 2 years after surgery. Our report suggests that the possibility of false-negative TcMEPs should be kept in mind, especially during surgery with a risk of nerve root injury. When abnormal findings in the free-run EMG, including long-lasting train activity, are observed, surgeons should consider performing appropriate responses, such as the release of the correction, even when no substantial changes are seen in the TcMEPs.

Abnormalities of lower extremity alignment (LEA) in recurrent patella dislocation (RPD) have been studied mostly by two-dimensional (2D) procedures leaving three-dimensional (3D) factors unknown. This study aimed to three-dimensionally examine risk factors for RPD in lower extremity alignment under the weight-bearing conditions. The alignment of 21 limbs in 15 RPD subjects was compared to the alignment of 24 limbs of 12 healthy young control subjects by an our previously reported 2D–3D image-matching technique. The sagittal, coronal, and transverse alignment in full extension as well as the torsional position of the femur (anteversion) and tibia (tibial torsion) under weight-bearing standing conditions were assessed by our previously reported 3D technique. The correlations between lower extremity alignment and RPD were assessed using multiple logistic regression analysis. The difference of lower extremity alignment in RPD between under the weight-bearing conditions and under the non-weight-bearing conditions was assessed. In the sagittal and coronal planes, there was no relationship (statistically or by clinically important difference) between lower extremity alignment angle and RPD. However, in the transverse plane, increased external tibial rotation [odds ratio (OR) 1.819; 95% confidence interval (CI) 1.282–2.581], increased femoral anteversion (OR 1.183; 95% CI 1.029–1.360), and increased external tibial torsion (OR 0.880; 95% CI 0.782–0.991) were all correlated with RPD. The tibia was more rotated relative to femur at the knee joint in the RPD group under the weight-bearing conditions compared to under the non-weight-bearing conditions (p

Background A solitary fibrous tumour (SFT) is an unusual neoplasm typically found in soft tissues. Although SFTs can arise in the bones, they very rarely arise in the vertebral arch. Here, we describe a case of a SFT that arose in the vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked osteosarcoma. Case presentation A 49-year-old woman presented with a 2-month history of lower back pain and a lumbar region mass. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The patient received neoadjuvant chemotherapy, followed by a surgical procedure comprising an anterior spinal fusion and en bloc resection. Histologically, our initial diagnosis was osteosarcoma. The postoperative course was uneventful, and the patient received adjuvant chemotherapy. However, the tumour metastasised to the lung 5 years after the first surgery, and a second surgery was performed for lung tumour resection. The histology of the metastatic lung tumour appeared similar to that of the malignant SFT, and the specimen from the first surgery was re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus confirming our final diagnosis of malignant SFT. The patient died of disease progression 8 years after the first surgery; however, there was no evidence of local recurrence. Conclusions Malignant SFT in the vertebral arch is extremely rare and very difficult to distinguish histologically an osteoid from lace-like collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from other neoplasms. Although it is difficult to completely resect a SFT arising from the spine, we demonstrated the feasibility of an en bloc resection of spinal tumours arising from posterior elements, without local recurrence.

Bone leiomyosarcoma is a rare primary osseous malignant tumor with a high metastatic potential. Similar to other bone sarcomas, high histological grade and tumor stage are predictive of a poor outcome. We herein present our experience with treating a 64-year-old woman with bone leiomyosarcoma accompanied by multiple bone metastases. A biopsy revealed occasional osteoclast-like giant cells. In addition to radiation therapy, the osteoclastogenesis inhibitor denosumab was administered but the patient did not undergo adjuvant chemotherapy or surgery. Good clinical and short-term radiological responses to denosumab have been observed for 2 years. Therefore, denosumab may represent a viable treatment option without the need for adjuvant chemotherapy.

Introduction: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), an autosomal recessive inherited cerebral small vessel disease (CSVD), involves severe leukoaraiosis, multiple lacunar infarcts, early-onset alopecia, and spondylosis deformans. High-temperature requirement serine peptidase A1 (HTRA1) gene mutations cause CARASIL by decreasing HTRA1 protease activity. Although CARASIL is a recessive inherited disease, heterozygous mutations in the HTRA1 gene were recently identified in 11 families with CSVD. Because CSVD is frequently observed in elderly individuals, it is unclear which mutants truly contribute to CSVD pathogenesis. Here, we found heterozygous mutations in the HTRA1 gene in individuals with CSVD and investigated the differences in biochemical characteristics between these mutant HTRA1s and mutant HTRA1s observed in homozygotes. Methods: We recruited 113 unrelated index patients with clinically diagnosed CSVD. The coding sequences of the HTRA1 gene were analyzed. We evaluated HTRA1 protease activities using casein assays and oligomeric HTRA1 formation using gel filtration chromatography. Results: We found 4 heterozygous missense mutations in the HTRA1 gene (p.G283E, p.P285L, p.R302Q, and p.T319I) in 6 patients from 113 unrelated index patients and in 2 siblings in 2 unrelated families with p.R302Q. These mutant HTRA1s showed markedly decreased protease activities and inhibited wild-type HTRA1 activity, whereas 2 of 3 mutant HTRA1s reported in CARASIL (A252T and V297M) did not inhibit wild- type HTRA1 activity. Wild-type HTRA1 forms trimers; however, G283E and T319I HTRA1, observed in manifesting heterozygotes, did not form trimers. P285L and R302Q HTRA1s formed trimers, but their mutations were located in domains that are important for trimer-associated HTRA1 activation; in contrast, A252T and V297M HTRA1s, which have been observed in CARASIL, also formed trimers but had mutations outside the domains important for trimer- associated HTRA1 activation. Conclusions: The mutant HTRA1s observed in manifesting heterozygotes might result in an impaired HTRA1 activation cascade of HTRA1 or be unable to form stable trimers.

Due to the increasing elderly population, the prevalence of osteoporotic hip fractures in Japanese patients continues to rise. It is well established that patients with either hip fracture or both symptomatic and asymptomatic morphometric vertebral compression fracture (VCF) have a poor health prognosis compared with the general population. The purpose of this study was to retrospectively investigate vertebral fracture rates among patients with hip fracture and their influence on mortality. We examined 182 cases of osteoporotic hip fracture in patients admitted to our institution between January 2009 and May 2011. The average age at the time of fracture was 85 years. Radiographs of the lumbar spine were obtained from all of the participants and the lateral spinal radiographs were examined for evidence of VCF. The patients were classified into two groups, those with VCF and those without. A VCF was identified in approximately 78 % of the patients. The mortality rate 1 year after the hip fracture was approximately 22 % and it was significantly higher in patients with VCF. Through multivariate statistics we found that VCF, post-operative complication, loss of ambulation after operation and medication for osteoporosis were statistically significant. In other words, VCF, post-operative complication and loss of ambulation were considered to be poor prognostic factors and medication for osteoporosis was likely to improve the prognosis. We concluded that the risk of mortality after hip fracture is significantly greater in patients who also have VCF compared to patients without VCF, and that medication for osteoporosis is likely to improve prognosis.

The acetabular coverage of the femoral head has been assessed in two-dimensions as the projected covered area or the covered angle on plain radiographs. We present a novel method of the three-dimensional assessment of femoral head coverage obtained by evaluating the covered volume of the femoral head in both normal and dysplastic hips. We also assessed the covered angles on the vertical slices passing through the center of the femoral head. The mean covered volume of the femoral head was 57.4% in normal hips and 26.6% in dysplastic hips. In dysplastic hips, the L-CE, A-CE, and P-CE angles were 7.7°, 21.8°, and 95.8°, respectively, while the acetabular angle was 27.5°. In normal hips, the CE angles were 34.0°, 56.8°, and 109.4°, respectively, while the acetabular angle was 7.2°. Our study suggests the usefulness of a novel 3D assessment for acetabular coverage of the femoral head. This assessment provided the precise 3D information necessary to diagnose hip dysplasia and assess the deficiency of acetabular coverage in these patients. Moreover, we may detect a cut-off between normal and dysplastic hips in the 3D assessment by assessing a large number of dysplastic hips both morphologically and using the new assessment.

The purpose of this study was to investigate the hypothesis that a medial unicompartmental knee arthroplasty might restore the functional flexion axis of a knee to normal. The flexion axis can be indirectly identified by tracking the vertical translation of anatomic landmarks that basically move around the flexion axis during a knee motion. If a unicompartmental knee could help restore the normal flexion axis, the anatomic landmarks after the arthroplasty would show the vertical translation similar to those of normal knees during a knee flexion. While performing a squatting motion, the kinematics of 17 knees were determined before and after a medial unicompartmental arthroplasty to calculate the vertical translation of a clinical epicondylar axis, using a three- to two-dimensional registration technique through a single-plane fluoroscopic system incorporating a biplanar static radiography. The results were compared with a normal data, and a statistical analysis including a two-way repeated-measured analysis of variance was performed. For the medial end, from 10° to 100° knee flexion, normal, osteoarthritic, and unicompartmental knees had the average superior vertical translation of 7.3 ± 4.2, 4.3 ± 7.2, and 2.4 ± 3.1 mm, respectively, with statistical significance between normal and unicompartmental knees (p

Background: Malpositioning during total hip arthroplasty may cause dislocation, pain, and other complications. To evaluate the potential of sacral slope (SS) as a reliable parameter of pelvic flexion. Methods: We developed a model of pelvic flexion to determine the intraobserver and interobserver variability and reliability of SS measurements by lateral radiography by three independent observers. Results: Measurement error was 1.2 and the intraobserver reliability was moderate to substantial (Interclass correlation coefficient: 0.31 to 0.66). Based on the Spearman-Brown formula, the measurement is reliable if it is done at least seven times by two observers, and four times by three observers. Conclusions: The data suggest that measurement of SS of pelvic flexion is a clinically useful parameter for the optimization of THA conditions.

The functional flexion axis (FFA) is the principal axis around which the knee moves and thus, by definition, does not move in vertical displacement relative to the tibia. The transepicondylar axis (TEA) has been reported to coincide with the FFA. If that is not true, the TEA should show vertical displacement during motion, and this hypothesis was investigated.Three-dimensional knee kinematics of 20 healthy volunteers were determined during a squatting motion via a 3-dimensional to 2-dimensional image registration technique by calculating the vertical displacement of the clinical epicondylar axis (CEA) through the full range of motion.From 0° to 90° knee flexion, the average vertical displacement of the lateral end of the CEA was3 mm, whereas that of the medial end was large (7.6 mm).The large vertical displacement of the medial end of the CEA suggests that the CEA is not the FFA. This finding implies that the CEA may not be an appropriate axis for a TKA prosthesis having a "single radius" design.Level IV.

Cervical radiculopathy of the C2–4 spinal nerves is a rare condition and is poorly documented in terms of clinical symptoms, hindering its detection during initial patient screening based on imaging diagnostics. The authors describe in detail the clinical symptoms and successful surgical treatment of a patient diagnosed with isolated C-4 radiculopathy. This 41-year-old man suffered from sleep disturbance because of pain behind the right ear, along the right clavicle, and at the back of his neck on the right side. The Jackson and Spurling tests were positive, with pain radiating to the area behind the patient's ear. Unlike in cases of radiculopathy involving the C5–8 spinal nerves, no loss of upper-extremity motor function was seen. Magnetic resonance imaging showed foraminal stenosis at the C3–4 level on the right side, and multiplanar reconstruction CT revealed a beak-type ossification of the posterior longitudinal ligament in the foraminal region at the same level. In the absence of intracranial lesions or spinal cord compressive lesions, the positive Jackson and Spurling tests and the C3–4 foraminal stenosis were indicative of isolated C-4 radiculopathy. Microscopic foraminotomy was performed at the C3–4 vertebral level and the ossified lesion was resected. The patient's symptoms completely resolved immediately after surgery. To the authors' knowledge, this report is the first to describe the symptomatic features of isolated C-4 radiculopathy, in a case in which the diagnosis has been confirmed by both radiological findings and surgical outcome. Based on this case study, the authors conclude that the characteristic symptoms of C-4 radiculopathy are the presence of pain behind the ear and in the clavicular region in the absence of upper-limb involvement.

To assess the usefulness of the urinary crosslinked C-telopeptide of type II collagen (uCTX-II) or crosslinked N-telopeptide of type I collagen (uNTX-I) for evaluating radiological knee osteoarthritis (OA), a cross-sectional study was conducted in the cohorts of the Matsudai knee osteoarthritis survey performed in Niigata, Japan. Urine specimens and standing knee AP X-rays were obtained from 1040 subjects who provided informed consent. The relationship between these markers and gender, age (patients aged 40–59 or 60–79 years), use of bisphosphonates, and OA grades (K–L classification) were analyzed. The diagnostic ability of uCTX-II to detect radiological knee OA was confirmed in the over 60-year-old subjects using a ROC curve. The over 60-year-old men with OA grade 3,4 group had significantly higher uCTX-II levels than the other OA grade groups. In the over 60-year-old women, the uCTX-II levels significantly increased according to the progression of the knee OA grade. No significant difference was observed between the uNTX-I levels in the different OA grade groups. From the standpoint of biomarkers, the higher quartiles of the uCTX-II and uNTX-I levels gradually included higher numbers of grade ≥2 OA subjects in the over 60 year-old women. The area under the curve (AUC) in ROC analysis of uCTX-II exhibited a significant association with the diagnosis of knee OA in women (AUC 0.63), although the accuracy was evaluated to be low in the single measurement of our health checkup-based analysis. This population-based study indicates that the uCTX-II level is strongly correlated with the knee OA grade in women over age 60. A further analysis is needed to clarify its predictive accuracy.

Background: The prognosis of patients with metastatic soft tissue sarcoma (STS) remain poor. Although immunotherapies have been attempted in patients with STS, the prognostic significance of the immune status within the tumor microenvironment in STS is not well understood. The purpose of this study is to investigate the tumor immune microenvironment and evaluate its prognostic impact for patients with STS. Material and Methods: We retrospectively evaluated the tumor immune microenvironment in 116 primary untreated STS patients with five subtypes: synovial sarcoma (SS: n=36), myxoid liposarcoma (MLS: n=32), undifferentiated pleomorphic sarcoma (UPS: n=27), leiomyosarcoma (LMS: n=11), and dedifferentiated liposarcoma (DDLS: n=10). The infiltration of CD8+ and FOXP3+ lymphocytes, CD163+ macrophages, and the expression of HLA class I and PD-L1 in the tumor were evaluated by immunohistochemistry. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Results: UPS had a higher infiltration of CD8+ and FOXP3+ lymphocytes than SS and MLS. Infiltration of CD163 + macrophages were higher in UPS, LMS, and DDLS than in SS and MLS. HLA class I expression was detected in all of UPS, LMS, and DDLS. However, HLA class I was negative in 17% of SS and 69% of MLS. Although no PD-L1 expression was observed in SS and MLS, PD-L1 expression was detected in 36% of UPS, 28% of LMS, and 25% of DDLS. Moreover, PD-L1 expression was associated with poor outcome in these subtypes. Increasing number of CD8+ lymphocytes was associated with a better OS in patients with SS. A higher infiltration of FOXP3+ lymphocytes was associated with an unfavorable OS in patients with MLS but favorable outcome in SS. Moreover, a higher infiltration of CD163+ macrophages showed a significantly worse OS and PFS in patients with SS and MLS. Conclusion: Lymphocytes and macrophages were variably infiltrated across STS subtype. UPS, LMS and DDLS, which have numerous genetic mutations, demonstrated high infiltration of lymphocytes, HLA class I and PD-L1 expression. These suggest that T-cell based immunotherapy such as immune checkpoint inhibitors may be effective in these tumor subtypes. Although the SS and MLS are less mutated and do express cancer-testis antigen NY-ESO-1 in common, expression level of HLA class I is significantly different between SS and MLS. In addition, infiltration of FOXP3+ lymphocytes have opposite effect in these tumors. These suggests different immunotherapeutic strategy might be required in these subtypes. Our results might be useful in the clinical strategy of immunotherapy in STS. Citation Format: Naoki Oike, Hiroyuki Kawashima, Akira Ogose, Hiroshi Hatano, Takashi Ariizumi, Taro Sasaki, Tetsuro Yamagishi, Hajime Umezu, Naoto Endo. Clinical significance of tumor immune microenvironment in soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1501.

We herein report a case of a huge suprascapular arteriovenous malformation (AVM) that was infected after endovascular embolization and then resected to good clinical outcome. The infection occurred after the fourth embolization with N-butyl-cyanoacrylate . The contrast-enhanced CT scan revealed abscesses surrounding the embolized material. The infection was not completely healed by antibiotic treatment, so we performed a resection of the AVM by the circumferential parallel ligation method after preoperative embolization. Fifteen months after the surgery, the patient is healthy without sign of infection. Infection is a rare complication of endovascular embolization. But, once it occurs, it is a very intractable disease.

Magneto-electric (ME) characteristics of the ferromagnetic/ferroelectric Fe 70 Pd 30 /PZT/Fe 70 Pd 30 thin composites were investigated. The ME composites composed of the ferroelectric PZT phase (center layer, t : 260 μm) and the ferromagnetic, magnetostrictive Fe 70 Pd 30 phase ( t : 30–90 μm) glued on both the surfaces of PZT were fabricated. The rapidly solidified Fe 70 Pd 30 ribbon mainly consists of fct martensitic phase with a large magnetostriction and fcc austenite (parent) phase. According to the DC bias magnetic field dependency of the output ME voltage ( V ME ) at an AC magnetic field of 1.0 Oe with an operation frequency of 1 kHz for the composites, the increasing in thickness of magnetostrictive layers showed remarkable improvement of V ME values. For the composite with 90 μm Fe–Pd layers, maximum V ME value of 13.9 mV was obtained at 60 Oe of the DC field, which is about two times higher than that of the composite with 30 μm Fe–Pd layers. Additionally the V ME value of the serial circuit was monotonically enhanced by the serial circuit connection, and the composites exhibited a very large peak at a resonant frequency of 61–68 kHz.

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10(-68); rs9388451, P = 5.1 × 10(-17)) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10(-14)). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (Ptrend = 6.1 × 10(-81)). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases.

Study design A retrospective analysis using prospectively collected data from 3-dimensional computed tomography angiography (3D-CTA). Objective To investigate the frequency of anomalous vertebral arteries (VA) and variations of the posterior portion of the circle of Willis (PPCW) using 3D-CTA for preventing perioperative iatrogenic vascular complications. Summary of background data Some studies have reported that preoperative 3D-CTA is useful for determining the VA blood flow in the cervical spine. However, preoperative 3D-CTA has not been used for evaluating PPCW, which functions as vessels collateral to the basilar artery in the case of iatrogenic VA injury. Methods The study included 100 consecutive patients (61 males and 39 females; mean age, 60.4 ± 15.4 yr; range, 11-86 yr) who underwent cervical decompression and/or instrumentation between April 2008 and May 2012. We measured the diameters of the VA (VAD), posterior communicating artery (PCOMD), first segment of the posterior cerebral artery (P1D), and basilar artery (BAD) twice and determined the frequency of anomalous VA and PPCW variations. Results Hypoplastic VA, hypoplastic PCOM, and hypoplastic P1 were detected in 11 (11.0%), 81 (81.0%), and 13 patients (13.0%), respectively. Hypoplastic PCOM-P1 and hypoplastic basilar artery were observed in 87 (87.0%) and 3 patients (3.0%), respectively. Overall, 47 patients (47.0%) possessed some degree of abnormal VA blood flow.There were 7 patients (7.0%) with both unilaterally hypoplastic VA and bilaterally hypoplastic PCOM-P1s, in whom iatrogenic VA injury on the dominant side could have caused lethal vascular complications. We termed the hypoplastic VA of the contralateral side without collateral vessels as "critical VA." Conclusion The VAs and PPCW vary considerably. Preoperative 3D-CTA provides important information for preventing tragic vascular complications caused by iatrogenic VA injury. Taking the risk of radiation into consideration, we recommend this method for patients at the highest risk for iatrogenic VA injury.

This study investigated the pathway underlying the antitumor activity of telomelysin, a telomerase‐dependent, replication‐selective oncolytic adenovirus, in soft tissue sarcoma cells. Treatment with telomelysin alone resulted in simultaneous induction of apoptosis and autophagy, whereas cotreatment with telomelysin and 3‐methyladenine significantly reduced cell viability and increased apoptosis and the cellular ATP level compared to treatment with telomelysin alone, indicating that telomelysin‐mediated autophagy is a death‐protective but not death‐promoting process. Cotreatment with Z‐Val‐Ala‐Asp‐CH2F significantly increased cellular ATP depletion compared to telomelysin‐alone treatment while inhibiting telomelysin‐induced apoptosis and having no significant effect on cell viability, indicating that it promotes transition from apoptotic to necrotic cell death.

In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese Society for Bone and Mineral Research) established the Osteoporosis Diagnostic Criteria Review Committee. Following discussion held at the 13th scientific meeting of the Society in 1996, the Committee, with the consensus of its members, proposed diagnostic criteria for primary osteoporosis. The Committee revised those criteria in 1998 and again in 2000. The Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society Joint Review Committee for the Revision of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining international consistency and made a revised edition based on the new findings in 2012.

A 17-year-old female patient (a basketball player) suffered from recurrent pelvic abscesses from methicillin-resistant Staphylococcus aureus (MRSA). The first episode, from strain NN12, occurred in October 2004. Her cutaneous abscesses complicated into systemic progression to osteomyelitis and multifocal pelvic abscesses, adjacent to the sacroiliac joint. The second episode, abscesses at tissues adjacent to the sacroiliac joint from strain NN31A, occurred late in February 2005. The third episode, from strain NN31B, occurred on July 30, 2005, repeating the second episode. Three MRSA strains were identical in terms of genotypes (belonging to Panton-Valentine leukocidin [PVL]-positive ST30 community-acquired MRSA, CA-MRSA), pulsed-field gel electrophoresis patterns, and peptide cytolysin gene (psmα) expression levels. The three MRSA strains exhibited superior THP-1 cell invasion ability over hospital-acquired MRSA (New York/Japan clone). The data suggest that PVL-positive ST30 CA-MRSA, with high levels of cell invasion and peptide cytolysins, causes recurrence of pelvic abscesses in a healthy adolescent.

Porous β-tricalcium phosphate (TCP) displays osteoinductivity in certain animals in the absence of osteoinductive agents. We evaluated whether the microstructure may be an important determinant of osteoinduction, and also investigated how bone formation was promoted using β-TCP combined with bone marrow aspirates. We prepared two types of β-TCP, namely, β-TCP A, which possessed interconnected macropores and micropores, and β-TCP B, which possessed macropores but had less detectable micropores. These were implanted with or without marrow in canine muscles. Bone formation and the resorption of each β-TCP implant were evaluated histologically. Newly formed bone began to appear at day 42 in the implants of β-TCP A alone, but the implants of β-TCP B alone did not show any bone formation by day 42. Meanwhile, bone formation was already evident on day 14 by loading with bone marrow aspirates with or without micropores. By immunohistochemistry, the number of cathepsin K-positive cells (osteoclasts) increased as time passed in the implants of β-TCP A alone, while the number of the osteoclasts did not change obviously in the implants of β-TCP B alone from day 14 to 56. Reticular fibrils were evident within the β-TCP A, and were barely observed in the β-TCP B in the silver impregnation. The present result would bring about the possible role to enhance the importance of the surface microstructure for the better osteoinductivity. Our findings suggest that the combination of porous β-TCP and bone marrow facilitates bone formation.

In this study, we have investigated the rotation of the pre-operative and post-operative femur, and stem anteversion to prevent impingement and dislocation. We studied 126 patients who had undergone primary total hip arthroplasty (THA) for the treatment of osteoarthritis. We compared preoperative tilt of anterior pelvic plane (APP), posterior condylar axis of the femur (PCA) relative to APP (APP-PCA) with those of postoperative ones in supine position. There was a moderate correlation between the preand post-operative APP-PCA values (r = 0.71). The postoperative APP-PCA decreased by approximately 6°. However, there was poor correlation between the stem anteversion and the postoperative APP-PCA (r = －0.27). A greater reduction in APP-PCA was observed among patients who exhibited greater external rotation of femur compared to those who showed less external rotation in supine position before THA. We also observed that the post-operative rotation of the femur was dependent on the pre-operative rotation of the femur while it was independent of the stem anteversion.

Background: Several researchers consider the clinical epicondylar axis (CEA) as the functional flexion-extension axis of the knee. The anterior pelvic plane (APP) is commonly used as an anatomical reference plane of the pelvis. However, no study has investigated the relationship of the APP with the CEA and PCA. In this study, we aimed to investigate the relationship of the APP with the CEA and posterior condylar axis (PCA) in the standing and supine positions. Methods: We recruited 77 healthy Japanese subjects for this study, and carried out measurements using the Hip CAS?system, a 3D system used for the assessment of lower extremity alignment. Results: The mean femoral neck anteversion was 16.33°. There was an approximate discrepancy of 6° between the male and the female in anatomy (15.73° and 21.15° in the male and female subjects, respectively). The mean condylar twist angle (CTA) was 6.86° and the mean APP-PCA value in the standing position was ﹣6.88°. The mean APP-CEA value in the standing position was 0.02°, and the discrepancy between males and females was only 0.21° (0.09° and ﹣0.13° for the male and female subjects, respectively). This meant that Xp axis of APP and CEA were almost parallel. On the other hand, the mean APP-CEA value in the supine position was 7.07° (male subjects = 9.48°; female subjects = 5.62°). Here, the CEA was approximately parallel to the horizontal axis of the APP, which was compatible with the neutral position of the knee and hip joint, and anatomically and kinesiologically justified in normal subjects. Conclusion: CEA was approximately parallel to the horizontal axis of the APP. These results are compatible with regard to the neutral position of the knee and hip joints, and anatomically and kinesiologically justified in normal subjects. Moreover, CEA is a potential reference axis for the insertion of the femoral component in THA.

Background: Postoperative pubic or ischial stress fracture may be a complication after curved periacetabular osteotomy (CPO). The discontinuity of the superior pubic rami is a risk factor for this complication. We investigated the stress field differences in standing and sitting positions after CPO. Methods: We used finite element analysis to assess the effects of inferior pubic rami and ischial fractures with or without discontinuity of superior pubic rami. We used the “union model”, obtained from a bony union at the osteotomy site of the superior pubic rami from 38-year-old woman who had undergone CPO for left hip dysplasia. We deleted the bony union region and created a discontinuity in the superior pubic rami equal to the non-union, creating the “discontinuity model”. We compared the stress field and stress value in the simulated standing and half weight-bearing positions on the operative side, one-legged standing position on the non-operative side, and the sitting position. Findings: In 4 cases, the inferior rami experienced the highest stress. Stress values in the discontinuity model were higher than those in the union model: 1.7 times in the case of one-legged standing on the operative side, 2.4 times in the case of half weight-bearing on the operative side, 3.8 times in the case of one-legged standing on the non-operative side, and 2.0 times in the sitting position, respectively. Interpretation: We recommend patients delay weight bearing on the operative side, avoid the sitting position as long as possible, and sit down slowly to prevent inferior pubic rami and ischial fractures after CPO.

Background Venous thromboembolism is one of the general complications following total hip arthroplasty, wherein various preventive treatments have been recommended. Several studies reported that venous thromboembolism incidence after total hip arthroplasty was similar in patients who were administered prophylaxis with a conventional mechanical procedure alone, and those who were administered pharmacological anticoagulation therapy. Therefore, the optimum methods of prophylaxis are still controversial. The purpose of this study was to investigate whether manual calf massage and passive ankle motion could lower the risk for venous thromboembolism after total hip arthroplasty. Methods We retrospectively reviewed the data of 126 consecutive patients undergoing elective primary unilateral total hip arthroplasty wherein manual calf massage and passive ankle motion were performed after the surgery at our hospitals between January and October 2014. The 138 patients of the control group underwent total hip arthroplasty using the same surgical approach and pre- and postoperative protocols without this mechanical prophylaxis between January and December 2013. This mechanical prophylaxis was performed simultaneously 30 times during approximately 10 s; these procedures were repeated thrice immediately after total hip arthroplasty. Duplex ultrasonography was performed to observe the veins of both legs in all the patients on postoperative day 7. Results The incidence of deep vein thrombosis was 6.52% and 0.79% in the control and manual calf massage and passive ankle motion groups, respectively. The odds ratio for the manual calf massage and passive ankle motion groups was 8.72. Performing this mechanical prophylaxis reduced the incidence of venous thromboembolism after total hip arthroplasty. This mechanical prophylaxis is not only simple and easy, but is also safe and inexpensive. Conclusions We therefore recommend that manual calf massage and passive ankle motion be performed in patients who will undergo total hip arthroplasty, if deep vein thrombosis does not exist before the surgery.

We aimed to clarify sex- and age-specific differences in three-dimensional and anatomic characteristics of femoral head coverage and acetabular morphology in healthy subjects. The study included 120 healthy subjects (57 male, 63 female), stratified into groups according to age and sex. We used computed tomography data to measure various anatomic alignment parameters describing femoral head coverage and acetabular morphology. The lateral sector angle in the coronal plane, anterior sector angle in the sagittal plane, and posterior sector angles in the axial plane, which characterize femoral head coverage, did not differ significantly between males and females. However, the Sharp angle in the coronal plane and acetabular anteversion in both the sagittal and axial planes were significantly larger in females than in males. Overall, the age-specific trends were similar between male and female subjects. Specifically, for both males and females, the values for parameters of femoral head coverage were significantly lower in younger subjects (

We investigated the incidence of hip fracture in patients aged ≥50 years in 2015 in Niigata Prefecture, Japan. We also determined the long-term trend in hip fracture incidence from 1985 to 2015. In 2015, 3214 hip fractures occurred in Niigata Prefecture. The crude incidence rate of hip fracture was 282.7 per 100,000 persons per year (122.9 in men and 416.4 in women). The incidence of hip fracture decreased from 2010 to 2015 in all age groups except in men aged 65–69 years and women aged 60–64 years. The percentage of patients who took anti-osteoporotic medication before their hip fractures increased from 10.2% in 2010 to 14.9% in 2015. The age-specific incidence in women tended to increase until 2010, but significantly decreased from 2010 to 2015 (p

Plasma D-dimer level is clinically useful for diagnosing patients with suspected deep vein thrombosis (DVT). However, the cut-off value for the D-dimer level remains controversial and undetermined with regard to total hip arthroplasty (THA). The objective of this study was to estimate the efficacy of an age- and D-dimer-based index for diagnosing DVTs in asymptomatic cases before THA. We enrolled 224 patients with no symptoms associated with DVT before THA. All the patients underwent ultrasonography, and the plasma D-dimer level was recorded about 1 month preoperatively. The optimal cut-off value was calculated using multiple logistic regression and receiver operating curve analyses. DVTs were detected in 13 patients (5.8%) using ultrasonography. Multiple logistic regression analysis demonstrated that age (odds ratio [OR]: 1.13; p = 0.007) and D-dimer value (OR: 1.74; p = 0.003) were related to the existence of preoperative DVT. A DVT index (0.12 × age + 0.45 × the D-dimer value) of 8.15 was the most reasonable cut-off value according to the receiver operating curve analysis. This value caused 100% sensitivity and 70.1% specificity, with an area under the curve (AUC) of 0.905 (range, 0.836–0.975). For age and D-dimer value, the AUCs were 0.828 (0.749–0.907) and 0.716 (0.522–0.910), respectively. This study demonstrated that age and D-dimer index can be useful in screening patients for DVTs before THA. This DVT index is also easy to calculate and may be clinically significant.

Background: The purpose of the study was to investigate the longitudinal time course of quality of life (QOL) in patients under conservative care and patients who received total hip arthroplasty (THA) by comparing their QOL scores along with the rehabilitation and life style parameters. Methods: Sixty-three female patients (age 58.7±7.1 years) of hip osteoarthritis under continuous conservative treatment were surveyed 4 times in two years by SF-36v2 (a modified version of rating scale SF-36) and an additional questionnaire developed by us. Results: Six patients that received THA during period of survey were designated as the THA group. Among the remaining 57 patients, 37 patients answered all four subsequent questionnaires were designated as non-THA group. The non-THA group was further divided into the rehabilitation continuing group in the hospital (RC group; n=8) and the discontinuing group (non-RC group; n=29) from the results of the questionnaire. The scores of physical functioning at the time of the first survey were significantly lower in the THA group compared to the non-THA group (p

Flexion instability following total knee arthroplasty (TKA) is a common indication of early revision. The association between the objective anteroposterior (AP) laxity direction in mid-range flexion and the subjective healing of instability remains unclear; thus, this study aimed to clarify this association. In this study, 110 knees (74 females, 92 knees; 16 males, 18 knees) with medial pivot implants were examined with a median age of 79 (range 60–92) years for a median follow-up duration of 22 (range 6–125) months. AP laxity was measured using a KT-1000 arthrometer. Self-reported knee instability score was used for the subjective healing of instability. Eighty-seven knees did not feel unstable (Group 0), whereas 23 knees felt unstable (Group 1). There was a significant difference in AP displacement [Group 0: median 6 mm; range 2–15 mm and Group 1: median 8 mm; range 4–14; p

The relative torsional angle of the distal tibia is dependent on a deformity of the proximal tibia, and it is a commonly used torsional parameter to describe deformities of the tibia; however, this parameter cannot show the location and direction of the torsional deformity in the entire tibia. This study aimed to identify the detailed deformity in the entire tibia via a coordinate system based on the diaphysis of the tibia by comparing varus osteoarthritic knees to healthy knees.In total, 61 limbs in 58 healthy subjects (age: 54 ± 18 years) and 55 limbs in 50 varus osteoarthritis (OA) subjects (age: 72 ± 7 years) were evaluated. The original coordinate system based on anatomic points only from the tibial diaphysis was established. The evaluation parameters were 1) the relative torsion in the distal tibia to the proximal tibia, 2) the proximal tibial torsion relative to the tibial diaphysis, and 3) the distal tibial torsion relative to the tibial diaphysis.The relative torsion in the distal tibia to the proximal tibia showed external torsion in both groups, while the external torsion was lower in the OA group than in the healthy group (p 0.0001). The proximal tibial torsion relative to the tibial diaphysis had a higher external torsion in the OA group (p = 0.012), and the distal tibial torsion relative to the tibial diaphysis had a higher internal torsion in the OA group (p = 0.004) in comparison to the healthy group.The reverse torsional deformity, showing a higher external torsion in the proximal tibia and a higher internal torsion in the distal tibia, occurred independently in the OA group in comparison to the healthy group. Clinically, this finding may prove to be a pathogenic factor in varus osteoarthritic knees.Level Ⅲ.

Background While navigation systems have been developed to increase implantation accuracy in total hip arthroplasty (THA), they are not yet sufficiently versatile or commonly used. Therefore, to elevate the appeal of such systems, we have developed HipCOMPASS, a simple and effective mechanical angle indicator for use in supine THA. Questions/purposes How accurate is the mean cup orientation [in terms of errors in radiographic anteversion (RA) and inclination (RI)] in cases where HipCOMPASS is used for intraoperative support? Does HipCOMPASS increase this cup orientation accuracy compared to THA cases without it? Does HipCOMPASS increase mean operation time? Methods We measured cup orientation in 97 THA cases with HipCOMPASS and in 80 cases without it. Then we compared the angles determined in preoperative planning with the angles revealed by postoperative computed tomography (CT) for both groups. The discrepancy between them was defined as an error. Errors greater than 10° were considered outliers. Additionally, mean operative time with and without the Hip COMPASS were compared. Results With the use of HipCOMPASS, the mean absolute error values in radiographic anteversion and inclination were 2.9° ± 2.3° (range 0°–12.8°) and 2.9° ± 2.1° (0.1°–7.7°), respectively. In contrast, without the use of HipCOMPASS, radiographic anteversion and inclination error values were 8.8° ± 5.8° (0.1°–25.4°) and 6.1° ± 4.5° (0.2°–21.0°), respectively. Outlier occurrence rates were 1.0 % with HipCOMPASS and 48.8 % without it. Mean operative times with and without HipCOMPASS use were 109.2 ± 23.8 min (74–199 min) and 137.6 ± 40.6 min (71–298 min), respectively. Conclusions The study has found that HipCOMPASS dramatically increases implantation accuracy and it is also a simple and highly versatile tool that can be implemented quickly. Given its low cost in addition to its favourable accuracy, simple implementation, and short operative time, HipCOMPASS can be regarded as a very useful and effective THA support device. Level of evidence Retrospective comparative study, Level 3.

Hydrogen peroxide (H2O2), a reactive oxygen species, is an important signaling molecule for synaptic and neuronal activity in the central nervous system; it is produced excessively in brain ischemia and spinal cord injury. Although H2O2-mediated modulations of synaptic transmission have been reported in ventral horn (VH) neurons of the rat spinal cord, the effects of H2O2 on neuronal excitability and membrane properties remain poorly understood. Accordingly, the present study investigated such effects using a whole-cell patch-clamp technique. The bath-application of H2O2 decreased neuronal excitability accompanied by decreased input resistance, firing frequency, and action potential amplitude and by increased rheobase. These H2O2-mediated changes were induced by activation of extrasynaptic, but not synaptic, GABAA receptors. Indeed, GABAergic tonic currents were enhanced by H2O2. On the other hand, the amplitude of medium and slow afterhyperpolarization (mAHP and sAHP), which plays important roles in controlling neuronal excitability and is mediated by small-conductance calcium-activated potassium (SK) channels, was significantly decreased by H2O2. When extrasynaptic GABAA receptors were completely blocked, these decreases of mAHP and sAHP persisted, and H2O2 increased excitability, suggesting that H2O2 per se might have the potential to increase neuronal excitability via decreased SK channel conductance. These findings indicate that activating extrasynaptic GABAA receptors or SK channels may attenuate acute neuronal damage caused by H2O2-induced hyperexcitability and therefore represent a novel therapeutic target for the prevention and treatment of H2O2-induced motor neuron disorders.

The study aimed to investigate the clinical outcomes and limitations after vertebroplasty with posterior spinal fusion (VP+PSF) without neural decompression for osteoporotic vertebral collapse.We conducted a prospective multicenter study including 45 patients (12 men and 33 women, mean age: 77.0 years) evaluated between 2008 and 2012. Operation time, blood loss, visual analog scale (VAS) of back pain, neurological status, kyphosis angle in the fused area, and vertebral union of the collapsed vertebra were evaluated.The mean operation time was 162 min and blood loss was 381 mL. The postoperative VAS score significantly improved, and the neurological status improved in 35 patients (83 %), and none of the remaining patients demonstrated a deteriorating neurological status at two years post-operatively. The mean kyphosis angle pre-operatively, immediately post-operatively, and two years post-operatively was 23.8°, 10.7°, and 24.3°, respectively, and there was no significant difference between the angles pre-operatively and two years post-operatively. The extensive correction of kyphosis16° was a risk factor for a higher correction loss and subsequent fracture. Union of the collapsed vertebra was observed in 43 patients (95 %) at two years post-operatively.The present study suggests that spinal stabilization rather than neural decompression is essential to treat OVC. Short-segment VP+PSF can achieve a high union rate of collapsed vertebra and provide a significant improvement in back pain or neurological status with less invasive surgery, but has a limit of kyphosis correction more than 16°.

The characteristics and pathogenesis of spinopelvic alignment in Parkinsons's disease (PD) patients-including differences compared to non-PD subjects and their relationships with the severity of PD-have not been clarified. The aim of this study was to investigate the characteristics of spinopelvic alignment in patients with PD.Forty-eight PD patients complaining of chronic low back pain were included (PD group). The PD condition, determined using the Hoehn and Yahr (HY) stage and Unified Parkinson Disease Rating Scale (UPDRS) score; radiographic spinopelvic alignment; lumbar range of motion (ROM); and low back pain-related quality of life assessments were evaluated. Fifty age- and sex-matched patients with adult spinal deformities were included as controls (ASD group).The spinopelvic alignments of the PD/ASD groups demonstrated sagittal vertical axes of 120.9/106.3 mm and pelvic incidences of 49.7/52.9°, with no significant differences. Conversely, there were significant differences in the thoracic kyphosis (TK; 27.6/16.7°), lumbar lordosis (-22.7/-7.9°), and pelvic tilt (25.3/34.4°) (all, p 0.05). With regard to correlations with the PD condition, the HY stage demonstrated significant correlations with the sagittal vertical axis, thoracolumbar kyphosis, and lumbar ROM (all, p 0.05), and the UPDRS score tended to correlate with the TK and thoracolumbar kyphosis (both, p 0.01).Characteristic spinal conditions in PD exist, with progressed PD condition causing stooped posture with increased thoracic or thoracolumbar kyphosis and decreased lumbar ROM; moreover, global sagittal malalignment progresses without sufficient compensatory mechanisms such as loss of TK and pelvic retroversion.

Evidence for the association between dialysis treatment and cognitive decline is limited. The present study aimed to determine whether dialysis treatment is associated with cognitive decline in adult outpatients of a general hospital in Japan.This was a cross-sectional substudy of the Project in Sado for Total Health (PROST). Total Health PROST targeted adult outpatients of a general hospital in Sado City, Niigata, Japan. Among 753 patients (mean age 68.1 ± 11.6 years) analyzed, 66 received dialysis. Cognitive state was evaluated using the Mini-Mental State Examination, and those with a Mini-Mental State Examination score24 were considered "cognitively declined." The prevalence of cognitive decline was compared by odds ratios calculated with multiple logistic regression analysis. Variables included in the analyses were dialysis, age, sex and self-reported histories of hypertension, diabetes, stroke and ischemic heart disease.Of the 66 dialysis patients, 24 (36.4%) showed cognitive decline, whereas 172 (25.0%) of 687 non-dialysis patients showed cognitive decline. The age and sex-adjusted odds ratio for cognitive decline in dialysis patients was 2.57 (95% confidence interval 1.43-4.61), relative to non-dialysis patients. The odds ratio remained significant (odds ratio 2.69, 95% confidence interval 1.49-4.88) even after adjusting for all covariates.The prevalence of cognitive decline was high in dialysis patients relative to non-dialysis patients among outpatients of a general hospital in Japan. Geriatr Gerontol Int 2017; 17: 1584-1587.

Background Mutations in the coding sequence of SCN 5A , which encodes the cardiac Na + channel α subunit, have been associated with inherited susceptibility to various arrhythmias. Variable expression of SCN 5A is a possible mechanism responsible for this pleiotropic effect; however, it is unknown whether variants in the promoter and regulatory regions of SCN 5A also modulate the risk of arrhythmias. Methods and Results We resequenced the core promoter region of SCN 5A and the regulatory regions of SCN 5A transcription in 1298 patients with arrhythmia phenotypes (atrial fibrillation, n=444; sinus node dysfunction, n=49; conduction disease, n=133; Brugada syndrome, n=583; and idiopathic ventricular fibrillation, n=89). We identified 26 novel rare variants in the SCN 5A promoter in 29 patients affected by various arrhythmias (atrial fibrillation, n=6; sinus node dysfunction, n=1; conduction disease, n=3; Brugada syndrome, n=14; idiopathic ventricular fibrillation, n=5). The frequency of rare variants was higher in patients with arrhythmias than in controls. In the alignment with chromatin immunoprecipitation sequencing data, the majority of variants were located at regions bound by transcription factors. Using a luciferase reporter assay, 6 variants (Brugada syndrome, n=3; idiopathic ventricular fibrillation, n=2; conduction disease, n=1) were functionally characterized, and each displayed decreased promoter activity compared with the wild‐type sequences. We also identified rare variants in the regulatory region that were associated with atrial fibrillation, and the variant decreased promoter activity. Conclusions Variants in the core promoter region and the transcription regulatory region of SCN 5A were identified in multiple arrhythmia phenotypes, consistent with the idea that altered SCN 5A transcription levels modulate susceptibility to arrhythmias.

Aim Evidence for the association between dialysis treatment and cognitive decline is limited. The present study aimed to determine whether dialysis treatment is associated with cognitive decline in adult outpatients of a general hospital in Japan. Methods This was a cross-sectional substudy of the Project in Sado for Total Health (PROST). Total Health PROST targeted adult outpatients of a general hospital in Sado City, Niigata, Japan. Among 753 patients (mean age 68.1 ± 11.6 years) analyzed, 66 received dialysis. Cognitive state was evaluated using the Mini-Mental State Examination, and those with a Mini-Mental State Examination score

Background Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism. Methods This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged