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Aims: Excellent outcomes have been reported following CT-based robotic arm-assisted total hip arthroplasty (rTHA) compared with manual THA; however, its superiority over CT-based navigation THA (nTHA) remains unclear. This study aimed to determine whether a CT-based robotic arm-assisted system helps surgeons perform accurate cup placement, minimizes leg length, and offsets discrepancies more than a CT-based navigation system. Methods: We studied 60 hips from 54 patients who underwent rTHA between April 2021 and August 2023, and 45 hips from 44 patients who underwent nTHA between January 2020 and March 2021 with the same target cup orientation at the Department of Orthopedic Surgery at Ozu Memorial Hospital, Japan. After propensity score matching, each group had 37 hips. Postoperative acetabular component position and orientation were measured using the planning module of the CT-based navigation system. Postoperative leg length and offset discrepancies were evaluated using postoperative CT in patients who have unilateral hip osteoarthritis. Results: The absolute differences in radiological inclination (RI) and radiological anteversion (RA) from the target were significantly smaller in rTHA (RI 1.2° (SD 1.2°), RA 1.4° (SD 1.2°)) than in nTHA (RI 2.7° (SD 1.9°), RA 3.0° (SD 2.6°)) (p = 0.005 for RI, p = 0.002 for RA). The absolute distance of the target’s postoperative centre of rotation was significantly smaller in the mediolateral (ML) and superoinferior (SI) directions in rTHA (ML 1.1 mm (SD 0.8), SI 1.3 mm (SD 0.5)) than in nTHA (ML 1.9 mm (SD 0.9), SI 1.6 mm (SD 0.9)) (p = 0.002 for ML, p = 0.042 for SI). Absolute leg length and absolute discrepancies in the acetabular, femoral, and global offsets were significantly lower in the rTHA group than in the nTHA group (p = 0.042, p = 0.004, p = 0.003, and p = 0.010, respectively). In addition, the percentage of hips significantly differed with an absolute global offset discrepancy of ≤ 5 mm (p < 0.001). Conclusion: rTHA is more accurate in cup orientation and position than nTHA, effectively reducing postoperative leg length and offset discrepancy. Cite this article: Bone Jt Open 2024;6(1):3–11.

Abstract Deep learning-based image segmentation has allowed for the fully automated, accurate, and rapid analysis of musculoskeletal (MSK) structures from medical images. However, current approaches were either applied only to 2D cross-sectional images, addressed few structures, or were validated on small datasets, which limit the application in large-scale databases. This study aimed to validate an improved deep learning model for volumetric MSK segmentation of the hip and thigh with uncertainty estimation from clinical computed tomography (CT) images. Databases of CT images from multiple manufacturers/scanners, disease status, and patient positioning were used. The segmentation accuracy, and accuracy in estimating the structures volume and density, i.e., mean HU, were evaluated. An approach for segmentation failure detection based on predictive uncertainty was also investigated. The model has improved all segmentation accuracy and structure volume/density evaluation metrics compared to a shallower baseline model with a smaller training database (N = 20). The predictive uncertainty yielded large areas under the receiver operating characteristic (AUROC) curves (AUROCs ≥ .95) in detecting inaccurate and failed segmentations. Furthermore, the study has shown an impact of the disease severity status on the model’s predictive uncertainties when applied to a large-scale database. The high segmentation and muscle volume/density estimation accuracy and the high accuracy in failure detection based on the predictive uncertainty exhibited the model’s reliability for analyzing individual MSK structures in large-scale CT databases.

Abstract Our previous cryogenic electron microscopy (cryoEM) analysis showed that the core structures of α-synuclein filaments accumulated in brains of patients diagnosed with dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) patients are different. We analyzed the post-translational modifications (PTMs) in these filaments , and examined their relationship with the core filament structures and pathological features. Besides the common PTMs in MSA and DLB filaments, acetylation, methylation, oxidation and phosphorylation were frequently detected in MSA filaments, but not in DLB filaments. Furthermore, in DLB filament cases, the processing occurred at the C-terminal side of Asp at 119 residue and Asn at 122 residue, while in MSA cases, the processing occurred at multiple sites between residues 109–123. We have previously reported that PTMs in tau filaments depend on the filament core structure. This was considered to apply to α-synuclein filaments as well. As an example, PTMs including processing sites detected in α-synuclein filaments in early-onset DLB (an atypical form, now named juvenile-onset α-synucleinopathy) brain also supported this idea. These suggests that PTMs appeared to be closely related to the specific filament core structures.

Abstract Background CLCN2-related leukoencephalopathy (CC2L) is a rare autosomal recessive disorder caused by biallelic variants of CLCN2, which encodes chloride channel 2. Although CC2L is associated with distinct radiological features, it presents with a wide range of clinical features. Case presentation A 34-year-old woman presented to our hospital with a sudden onset of vertigo with headache. The patient reported intermittent headaches and tingling in both arms since the age of 31 years. On the first visit, the patient was alert and neurologically intact, except for slight hyperreflexia of the limbs without laterality. Head magnetic resonance imaging (MRI) showed high-intensity signals on axial T2-weighted fluid-attenuated inversion recovery and diffusion-weighted images bilaterally in the posterior limbs of the internal capsules, cerebral peduncles, superior and middle cerebellar peduncles, decussation of superior cerebellar peduncles, and central tegmental tract. All the patient’s symptoms were resolved or eased following supportive care. The patient stopped attending our hospital at the age of 46 years. At 51 years of age, the patient revisited our hospital because of the recurrence of vertigo, headache, and nausea. She did not present with any abnormalities by neurological examination. Head MRI showed widespread high-intensity signals similar to those 17 years ago. Genetic testing revealed compound heterozygous variants in CLCN2 (NM_004366.6): a novel variant c.1828 C > T, p.(Arg 610*) from her father and c.61dup, p.(Leu21Profs*27) from her mother. The patient was finally diagnosed with CC2L. She received supportive treatment, which made her symptoms manageable. Conclusions This is a detailed report of a patient with adult-onset CC2L who was successfully diagnosed and followed up with head MRI. This report provides new insights into CC2L and highlights its persistent, distinct, and stable characteristics observed in head MRI over one decade and the difficulty in forming a diagnosis without MRI when patients have minimal and common symptoms, such as in the present case.

Abstract Background Past research has suggested a cross-sectional association between COVID-19-related discrimination and PTSD symptom severity. However, no cohort study has examined the longitudinal association that better supports causal interpretation. Also, even if such an association genuinely exists, the specific pathway remains unclear. Methods We conducted a two-year follow-up study, obtaining data from healthcare workers in a hospital setting. We first evaluated how COVID-19-related discrimination in 2021 was associated with subsequent PTSD symptom severity in 2023. Thereafter, we conducted causal mediation analysis to examine how this association was mediated by psychological distress in 2022, accounting for exposure-mediator interaction. Missing data were handled using random forest imputation. Results A total of 660 hospital staff were included. The fully adjusted model showed greater PTSD symptom severity in individuals who experienced any COVID-19-related discrimination compared with those without such experiences (β, 0.44; 95% CI, 0.04–0.90). Regarding each type of discrimination, perceived discrimination was associated with greater PTSD symptom severity (β, 0.52; 95% CI, 0.08–0.96), whereas verbal discrimination did not reach statistical significance. Psychological distress mediated 28.1%–38.8% of the observed associations. Conclusions COVID-19-related discrimination is associated with subsequent PTSD symptom severity in healthcare workers. Psychological distress may serve as an important mediator, underscoring the potential need for interventions targeting this factor.

Abstract Background In this study, we aimed to investigate the preoperative and postoperative anteroposterior position (AP) of the femur relative to the tibia in total knee arthroplasty (TKA) and assess the influence of change in the AP position on clinical outcomes. Methods We evaluated 49 knees that underwent bi-cruciate-substituted TKA using a navigation system. The preoperative and postoperative AP position of the femur relative to the tibia at maximum extension, 15°, 30°, 45°, 60°, 90°, 105°, and 120° and maximum flexion angles were calculated. The 2011 Knee Society Score was evaluated preoperatively and 1 year postoperatively. The Wilcoxon signed rank and Spearman’s rank correlation tests were performed, with statistical significance set at P

Abstract Purpose This study investigated the tibiofemoral contact point (CP) on standing lateral radiographs in knee osteoarthritis and assessed the relationship between CP and pre‐ and postoperative knee kinematics in total knee arthroplasty (TKA). Methods The intraoperative knee status of 46 knees with varus deformity that underwent bicruciate stabilized TKA using a navigation system was investigated. The intraoperative anteroposterior (AP) position of the femur relative to the tibia at maximum extension, 15°, 30°, 45°, 60° and 90° was evaluated by the navigation system before and after TKA. The CP, defined as the CP between the femur and tibia, was assessed on standing lateral radiographs at the maximum extension of the knee before and 1 year after TKA. CP was expressed as the ratio of tibial plateau distance on a scale of 0–1, with 0 indicating the most anterior position of the femur relative to the tibia. Results The mean CP on standing lateral radiographs was 0.54 ± 0.12 and 0.46 ± 0.08 before and after TKA, respectively. The postoperative CP was significantly more anterior than the preoperative CP (p = 0.0002). The mean AP position of the femur relative to the tibia moved anteriorly during early knee flexion both before and after TKA, representing nonanatomical AP movement. The preoperative posterior CP group (CP > 0.54) showed more nonanatomical AP movement from 15° to 60° before and after TKA compared with the preoperative anterior CP group (CP

Aims: This study aimed to investigate the incidence of ≥ 5 mm asymmetry in lower and whole leg lengths (LLs) in patients with unilateral osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH-OA) and primary hip osteoarthritis (PHOA), and the relationship between lower and whole LL asymmetries and femoral length asymmetry. Methods: In total, 116 patients who underwent unilateral total hip arthroplasty were included in this study. Of these, 93 had DDH-OA and 23 had PHOA. Patients with DDH-OA were categorized into three groups: Crowe grade I, II/III, and IV. Anatomical femoral length, femoral length greater trochanter (GT), femoral length lesser trochanter (LT), tibial length, foot height, lower LL, and whole LL were evaluated using preoperative CT data of the whole leg in the supine position. Asymmetry was evaluated in the Crowe I, II/III, IV, and PHOA groups. Results: The incidences of whole and lower LL asymmetries were 40%, 62.5%, 66.7%, and 26.1%, and 21.7%, 20.8%, 55.6%, and 8.7% in the Crowe I, II/III, and IV, and PHOA groups, respectively. The incidence of tibial length asymmetry was significantly higher in the Crowe IV group (44.4%) than that in the PHOA group (4.4%). In all, 50% of patients with DDH-OA with femoral length GT and LT asymmetries had lower LL asymmetry, and 75% had whole LL asymmetry. The incidences of lower and whole LL asymmetries were 20% and 42.9%, respectively, even in the absence of femoral length GT and LT asymmetries. Conclusion: Overall, 43% of patients with unilateral DDH-OA without femoral length asymmetry had whole LL asymmetry of ≥ 5 mm. Thus, both the femur length and whole LL should be measured to accurately assess LL discrepancy in patients with unilateral DDH-OA. Cite this article: Bone Jt Open 2024;5(2):79–86.

Purpose: Using navigation systems during total hip arthroplasty (THA) has been reported to be useful for preventing acetabular cup malpositioning. However, only few studies have reported on the application of navigation systems to THA at low-volume hospitals owing to cost and usage complexity. Therefore, the aim of this study was to determine whether smartphone-based portable navigation using augmented reality technology would enable low-volume surgeons to perform acetabular cup placement more accurately than with the conventional manual technique. Methods: We retrospectively compared acetabular cup placement between the navigation (n ​= ​28) and conventional (n ​= ​24) groups. The acetabular cup inclination and anteversion angles were measured using computed tomography (CT)-based planning software. Furthermore, the absolute difference between the postoperative and target angles was compared between the groups. Results: The absolute difference between the postoperative and target angles of cup inclination was 2.6° ​± ​2.3° in the navigation group and 5.6° ​± ​5.2° in the conventional group (p ​

Background/Objectives: Sporadic Creutzfeldt–Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann’s criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan. Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann’s criteria were calculated by comparing diagnoses with those made by the JPDS Committee. Results: Of the 786 included cases, Hermann’s criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann’s criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as “definite” by both criteria. Conclusions: The findings suggest that Hermann’s criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.

Aims: This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods: The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm3). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results: CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm2. Conclusion: Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):589–596.

Introduction: Some patients who have not been diagnosed with diffuse idiopathic skeletal hyperostosis (DISH) (patients in the preclinical stage of DISH [pre-DISH]) may develop DISH in the future. However, there are currently no clearly defined diagnostic criteria for pre-DISH. This study aims to define pre-DISH by analyzing the change in the ossification extent in each intervertebral space in the thoracic and lumbar spines over time using computed tomography (CT). Methods: Of the patients who underwent CT of the thoracic to pelvic region at least twice from 2009 to 2018, 188 who underwent CT at an interval of 5 years to 5 years and 2 months were enrolled. The prevalence of DISH during the first and second CT scans was investigated. The pre-DISH feature was defined, and the prevalence of pre-DISH on the first CT and the change after 5 years in patients with pre-DISH was investigated. Results: Of the 188 patients, 37 (19.7%) and 48 (25.5%) were diagnosed with DISH on the first and second CT scans, respectively. Pre-DISH was defined as the ossification characterized by the modified Mata score of three contiguous intervertebral spaces with a score of 2 points (222; 2 points, ligament ossification of half or more of the intervertebral disc height but incomplete fusion), and 52 patients were diagnosed with pre-DISH. Of the 52 patients with a score of (222), 11 (21.2%) were diagnosed with DISH 5 years later. Conclusions: Patients who have three contiguous intervertebral spaces with a modified Mata score of 2 or 3 points should be considered pre-DISH.

Objectives This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity.Design Retrospective observational study of a nationwide database.Setting The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint.Participants This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018.Main outcome measure The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis.Results The median time to surgery was 9 months (IQR 4–22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p

BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with progressive impairment of spinal motor neurons. Continuous research endeavor is underway to fully understand the molecular mechanisms associating with this disorder. Although several studies have implied the involvement of inositol pyrophosphate IP7 in ALS, there is no direct experimental evidence proving this notion. In this study, we analyzed inositol pyrophosphate IP7 and its precursor IP6 in the mouse and human ALS biological samples to directly assess whether IP7 level and/or its metabolism are altered in ALS disease state.MethodsWe used a liquid chromatography-mass spectrometry (LC-MS) protocol originally-designed for mammalian IP6 and IP7 analysis. We measured the abundance of these molecules in the central nervous system (CNS) of ALS mouse model SOD1(G93A) transgenic (TG) mice as well as postmortem spinal cord of ALS patients. Cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) from ALS patients were also analyzed to assess if IP7 status in these biofluids is associated with ALS disease state.ResultsSOD1(G93A) TG mice showed significant increase of IP7 level in the spinal cord compared with control mice at the late stage of disease progression, while its level in cerebrum and cerebellum remains constant. We also observed significantly elevated IP7 level and its product-to-precursor ratio (IP7/IP6) in the postmortem spinal cord of ALS patients, suggesting enhanced enzymatic activity of IP7-synthesizing kinases in the human ALS spinal cord. In contrast, human CSF did not contain detectable level of IP6 and IP7, and neither the IP7 level nor the IP7/IP6 ratio in human PBMCs differentiated ALS patients from age-matched healthy individuals.ConclusionBy directly analyzing IP7 in the CNS of ALS mice and humans, the findings of this study provide direct evidence that IP7 level and/or the enzymatic activity of IP7-generating kinases IP6Ks are elevated in ALS spinal cord. On the other hand, this study also showed that IP7 is not suitable for biofluid-based ALS diagnosis. Further investigation is required to elucidate a role of IP7 in ALS pathology and utilize IP7 metabolism on the diagnostic application of ALS.

Background: The characteristics of functional limb weakness (FLW) as one of the manifestations of functional neurological disorder after vaccination against coronavirus disease 2019 (COVID-19) remain controversial. Methods: In this descriptive case series, we aimed to elucidate the characteristics of Japanese patients with FLW who claimed muscle weakness after COVID-19 vaccination among patients who visited our outpatient clinic between 1 June 2021 and 31 December 2022. Results: Nine patients were diagnosed with FLW (mean age: 30.8 years), including two men and seven women. Seven patients were vaccinated with the BioNTech/Pfizer vaccine and two with the mRNA-1273 Moderna vaccine. All patients demonstrated various positive signs for FLW. Magnetic resonance imaging or computed tomography indicated no abnormality that could explain their symptoms. At the time of the clinic visit, five patients were treated for psychiatric disorders, including depression, insomnia, attention-deficit hyperactivity disorder, and Asperger's syndrome. Muscle weakness spread to the limbs beyond the vaccinated arm in seven patients. Conclusions: We describe the basic characteristics of FLW in Japanese patients after COVID-19 vaccination. Further recognition of these characteristics could aid the diagnosis of FLW by physicians allowing them to support these patients effectively.

Background: Osteophyte formation is attracting attention as an early-stage pathology of knee osteoarthritis (OA). Although osteophyte formation is understood as a defense response to joint instability, its role and impact on OA remain largely unknown. Many studies have been conducted using the surgical destabilization of the medial meniscus (DMM) mouse model, but there are few standard evaluation methods, especially in the histological evaluation of early-stage osteophytes. The purpose of this study was to establish a reproducible and uniform method for histological evaluation of characteristics of early osteophyte formation in the DMM mouse model. Methods: Male mice were operated with DMM at 12 weeks old and histologically evaluated at 4 days and 1, 2 and 4 weeks after DMM. Osteophyte Width, Osteophyte Area, and Original and Modified Maturity Scores were used to evaluate osteophytes for all sections. Results: Osteophyte Width, Osteophyte Area and Maturity Scores were all greater anteriorly than posteriorly in the knee joint. The Modified Maturity Score was more strongly correlated with position than the Original Maturity Score, and could be used to evaluate early-stage osteophyte formation. Conclusion: The Modified Maturity Score as well as Osteophyte Width and Area at the section of the anterior cruciate ligament (ACL) attachment site can provide a reproducible evaluation method to histologically assess the early-stage osteophyte formation in the DMM mouse model.

Tick-borne encephalitis (TBE) is an infection of the central nervous system caused by the tick-borne encephalitis virus (TBEV). TBE is endemic in parts of Europe and Asia. TBEV is transmitted to humans primarily by Ixodes ticks. There have been 5 TBE cases identified in Japan, all on the northern island of Hokkaido. Rodents with TBEV antibodies and Ixodes ticks have been identified throughout Japan, indicating that TBEV infection might be undiagnosed in Japan. Residual serum and cerebrospinal fluid (CSF) collected in 2010–2021 from 520 patients ≥1 year-of-age previously hospitalized with encephalitis or meningitis of unknown etiology at 15 hospitals (including 13 hospitals outside of Hokkaido) were screened by ELISA for TBEV IgG and IgM antibodies; TBEV infection was confirmed by the gold standard neutralization test. Residual serum was available from 331 (63.6%) patients and CSF from 430 (82.6%) patients; both serum and CSF were available from 189 (36.3%). Two patients were TBE cases: a female aged 61 years hospitalized for 104 days in Oita (2000 km south of Hokkaido) and a male aged 24 years hospitalized for 11 days in Tokyo (1200 km south of Hokkaido). Retrospective testing also identified a previous TBEV infection in a female aged 45 years hospitalized for 12 days in Okayama (1700 km south of Hokkaido). TBEV infection should be considered as a potential cause of encephalitis or meningitis in Japan. TBE cases are likely undiagnosed in Japan, including outside of Hokkaido, due to limited clinical awareness and lack of availability of TBE diagnostic tests.

Abstract Background Cerebral amyloid angiopathy is a common cause of subcortical hemorrhage in older adults. Although open hematoma removal may be performed for severe subcortical hemorrhage, its safety in patients with cerebral amyloid angiopathy has not been established, and postoperative rebleeding may occur. Therefore, this study aimed to investigate factors associated with postoperative rebleeding. Methods Out of 145 consecutive patients who had undergone craniotomy for surgical removal of subcortical intracerebral hemorrhage between April 2010 and August 2019 at a single institution in Japan, we examined 109 patients with subcortical hemorrhage who met the inclusion criteria. After excluding 30 patients whose tissue samples were unsuitable for the study, the final study cohort comprised 79 patients. Results Of the 79 patients, 50 (63%) were diagnosed with cerebral amyloid angiopathy (cerebral amyloid angiopathy group) and 29 (37%) were not diagnosed with noncerebral amyloid angiopathy (noncerebral amyloid angiopathy group). Postoperative rebleeding occurred in 12 patients (24%) in the cerebral amyloid angiopathy group and in 2 patients (7%) in the noncerebral amyloid angiopathy group. Preoperative prothrombin time–international normalized ratio and intraoperative bleeding volume were significantly associated with postoperative rebleeding in the cerebral amyloid angiopathy group (odds ratio = 42.4, 95% confidence interval = 1.14–1578; p = 0.042 and odds ratio = 1.005, 95% confidence interval = 1.001–1.008; p = 0.007, respectively). Conclusions Patients with cerebral amyloid angiopathy-related cerebral hemorrhage who are receiving antithrombotic therapy, particularly warfarin therapy, are at a high risk of postoperative rebleeding. Trial registration Registry and Registration Number of the study: 19–220, 2019/12/23, retrospectively registered.

Abstract Subacute sclerosing panencephalitis (SSPE) occurs in some individuals after measles infection, following a symptom-free period of several years. It resembles chronic traumatic encephalopathy (CTE), which happens after repetitive head impacts or exposure to blast waves, following a symptom-free period. As in CTE, the neurofibrillary changes of SSPE are concentrated in superficial cortical layers. Here we used electron cryo-microscopy (cryo-EM) of tau filaments from two cases of SSPE to show that the tau folds of SSPE and CTE are identical. Two types of filaments were each made of two identical protofilaments with an extra density in the β-helix region. Like in CTE, the vast majority of tau filaments were Type I, with a minority of Type II filaments. These findings suggest that the CTE tau fold can be caused by different environmental insults, which may be linked by inflammatory changes.

Abstract This paper presents methods of decomposition of musculoskeletal structures from radiographs into multiple individual muscle and bone structures. While existing solutions require dual-energy scan for the training dataset and are mainly applied to structures with high-intensity contrast, such as bones, we focused on multiple superimposed muscles with subtle contrast in addition to bones. The decomposition problem is formulated as an image translation problem between (1) a real X-ray image and (2) multiple digitally reconstructed radiographs, each of which contains a single muscle or bone structure, and solved using unpaired training based on the CycleGAN framework. The training dataset was created via automatic computed tomography (CT) segmentation of muscle/bone regions and virtually projecting them with geometric parameters similar to the real X-ray images. Two additional features were incorporated into the CycleGAN framework to achieve a high-resolution and accurate decomposition: hierarchical learning and reconstruction loss with the gradient correlation similarity metric. Furthermore, we introduced a new diagnostic metric for muscle asymmetry directly measured from a plain X-ray image to validate the proposed method. Our simulation and real-image experiments using real X-ray and CT images of 475 patients with hip diseases suggested that each additional feature significantly enhanced the decomposition accuracy. The experiments also evaluated the accuracy of muscle volume ratio measurement, which suggested a potential application to muscle asymmetry assessment from an X-ray image for diagnostic and therapeutic assistance. The improved CycleGAN framework can be applied for investigating the decomposition of musculoskeletal structures from single radiographs.

Abstract Background Cerebral amyloid angiopathy (CAA) occurs in 80% of patients with Alzheimer’s disease (AD) and is mainly caused by the abnormal deposition of Aβ in the walls of cerebral blood vessels. Cerebrovascular molecular mechanisms in CAA were investigated by using comprehensive and accurate quantitative proteomics. Methods Concerning the molecular mechanisms specific to CAA, formalin-fixed paraffin-embedded (FFPE) sections were prepared from patients having AD neuropathologic change (ADNC) with severe cortical Aβ vascular deposition (ADNC +/CAA +), and from patients having ADNC without vascular deposition of Aβ (ADNC +/CAA −; so called, AD). Cerebral cortical vessels were isolated from FFPE sections using laser microdissection (LMD), processed by pressure cycling technology (PCT), and applied to SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Results The protein expression levels of 17 proteins in ADNC +/CAA +/H donors (ADNC +/CAA + donors with highly abundant Aβ in capillaries) were significantly different from those in ADNC +/CAA − and ADNC −/CAA − donors. Furthermore, we identified 56 proteins showing more than a 1.5-fold difference in average expression levels between ADNC +/CAA + and ADNC −/CAA − donors, and were significantly correlated with the levels of Aβ or Collagen alpha-2(VI) chain (COL6A2) (CAA markers) in 11 donors (6 ADNC +/CAA + and 5 ADNC −/CAA −). Over 70% of the 56 proteins showed ADNC +/CAA + specific changes in protein expression. The comparative analysis with brain parenchyma showed that more than 90% of the 56 proteins were vascular-specific pathological changes. A literature-based pathway analysis showed that 42 proteins are associated with fibrosis, oxidative stress and apoptosis. This included the increased expression of Heat shock protein HSP 90-alpha, CD44 antigen and Carbonic anhydrase 1 which are inhibited by potential drugs against CAA. Conclusions The combination of LMD-based isolation of vessels from FFPE sections, PCT-assisted sample processing and SWATH analysis (FFPE-LMD-PCT-SWATH method) revealed for the first time the changes in the expression of many proteins that are involved in fibrosis, ROS production and cell death in ADNC +/CAA + (CAA patients) vessels. The findings reported herein would be useful for developing a better understanding of the pathology of CAA and for promoting the discovery and development of drugs and biomarkers for CAA.

Abstract Purpose The aims of this study were to 1) assess femoral head translation during weight‐bearing in symptomatic developmental dysplasia of the hip (DDH) and 2) compare it between borderline DDH and definite DDH. Methods The study included four individuals with borderline DDH and nine with definite DDH, scheduled for periacetabular osteotomy. Anteroposterior X‐ray images of the hip joint were obtained in the standing position, and computed tomography images of the pelvis were obtained in the supine position. Femoral head translation from the supine to a standing position was measured using 2D/3D X‐ray image registration. Results From a supine to a standing position, the femoral head translated 0.3 mm laterally, 0.5 mm anteriorly, and 0.5 mm superiorly on average. The mean femoral head translation in 3D between the supine and standing positions was 1.5 mm. The 3D femoral head translation in the borderline DDH group was significantly greater than that in the definite DDH group. In the definite DDH group, there was a significant correlation between the center edge (CE) angle and 3D femoral head translation (ρ = ‐0.78, P = 0.012). Conclusions Symptomatic DDH showed femoral head translation in the anterior, lateral, and superior directions during weight‐bearing. In definite DDH, the amount of femoral head translation was negatively correlated with the CE angle. The amount of 3D translation in patients with borderline DDH was larger than that in definite DDH. Dynamic joint instability during weight‐bearing was observed in borderline DDH as well as definite DDH. Treatment to enhance joint stability during weight‐bearing is important in both cases.

Abstract Purpose This study aimed to compare midflexion rotational laxity between two different design concept models of cruciate‐retaining total knee arthroplasty: symmetrical surface design of neutral joint line obliquity and asymmetrical surface design of varus joint line obliquity. Methods Sixty‐three knees that underwent cruciate‐retaining total knee arthroplasty were evaluated. Manual maximum passive rotational stress without acceleration was applied to the knees under navigation monitoring. Pre‐operative and post‐operative internal and external rotational angles were measured at 30°, 45°, 60°, and 90° knee flexion. Results The post‐operative internal rotational laxity was significantly increased compared with pre‐operative levels at 30°, 45°, 60°, and 90° flexion among all subjects (mean 9.7° vs 11.1°, 10.6° vs 11.6°, 11.2° vs 12.9°, and 13.2° vs 14.9°; p = 0.01, 0.04, 0.001, and 0.008, respectively). The post‐operative external rotational laxity was significantly decreased compared to pre‐operative levels at 30°, 45°, 60°, and 90° flexion among all subjects (mean 10.8° vs 6.8°, 12.5° vs 9.4°, 12.8° vs 10.0°, and 11.3° vs 9.5°; p

Background: The clinical course, comorbidity, and management of symptoms after the acute phase of coronavirus disease 2019 (COVID-19) remain controversial. Methods: This was a descriptive case series study, examining the characteristics of patients with longstanding symptoms related to COVID-19 who visited our outpatient clinic between 1 June and 31 December 2021. We analyzed patients’ background, chief complaints, clinical course after COVID-19 onset, and clinical examination results. Results: A total of 90 patients with a mean age of 39.8 years were confirmed as having long COVID. The median time between diagnosis of COVID-19 and visiting our clinic was 66.8 days, and 89 patients (98.9%) were unvaccinated. Depression was the most common comorbidity (nine patients, 10.0%). The most common chief complaint was disturbance of smell and/or taste (35, 38.9%), followed by memory disturbance (22, 24.4%) and fatigue (29, 31.1%). Head MRI was performed for 42 (46.7%) patients, and the most common finding was sinusitis (four patients). Olfactory testing was conducted in 25 patients (27.8%) using a T&T olfactometer, and 14 patients (56%) had mild olfactory impairment. Of the five odors in the T&T, recognition of β-phenylethyl alcohol was most impaired. Conclusions: This study describes the basic characteristics of long COVID in Japan. It suggests that long COVID is complex because it results in a wide range of symptoms.

Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

Introduction JTR-161 is a novel allogeneic human cell product consisting of dental pulp stem cells isolated from the extracted teeth of healthy adults. It is currently under development as a cell-based therapy for ischaemic stroke. The aim of this study is to evaluate the safety and efficacy of JTR-161 in patients with acute ischaemic stroke when given as a single intravenous administration within 48 hours of symptom onset.Methods and analysis This is a first-in-human, randomised, double-blind, placebo-controlled, multicentre, phase 1/2 clinical trial to be conducted in Japan (from January 2019 to July 2021). Patients with a clinical diagnosis of anterior circulation ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS）score of 5–20 at baseline were enrolled. Patients previously treated with recombinant tissue-type plasminogen activator and/or endovascular thrombectomy were allowed to be enrolled. The study consists of three cohorts: cohorts 1 and 2 (each eight patients) and cohort 3 (60 patients). Subjects were randomly assigned to receive either JTR-161 or placebo in a 3:1 ratio in cohorts 1 and 2, and in a 1:1 ratio in cohort 3. The number of cells administered was increased sequentially from 1×108 (cohort 1) to 3 x 108 (cohort 2). In cohort 3, the higher tolerated dose among the two cohorts was administered. The primary endpoint is the proportion of patients who achieve an excellent outcome as defined by all of the following criteria at day 91 in cohort 3: modified Rankin Scale ≤1, NIHSS ≤1 and Barthel Index ≥95.Ethics and dissemination The protocol and informed consent form were approved by the institutional review board at each participating study site. A manuscript with the results of the primary study will be published in a peer-reviewed journal.Trial registration number NCT04608838; JapicCTI-194570 and Clinical Trials. gov.

Abstract. Introduction:. Endoscopic submucosal dissection (ESD) is an advanced therapeutic technique for en bloc resection of superficial gastrointestinal neoplasms. Although gastric ESD is minimally invasive and provides favorable outcomes, it is technically difficult and requires a long procedure time for dissection. The traction-assisted approach overcomes some of the difficulties of gastric ESD, but its ability to reduce the procedure time remains unclear. The traction-assisted approach using dental floss and a clip did not reduce procedure time in the total population, but it reduced procedure time for lesions limited to the greater curvature of the upper or middle of the stomach. Although the traction direction of the clip-with-line method may be limited to the oral side via the cardia, EndoTrac ESD may provide flexible traction at any time during the procedure. This prospective randomized control study has been designed to compare the efficacy and safety of EndoTrac and conventional gastric ESD. Methods/design:. This multicenter, randomized control trial will enroll 150 patients at 2 hospitals in Japan undergoing EndoTrac or conventional ESD for gastric epithelial neoplasia. Patients with a single gastric epithelial neoplasm who meet the inclusion and exclusion criteria will be randomized to EndoTrac or conventional ESD. Patients will be randomized by a computer-generated random sequence with stratification by operator experience, tumor size, tumor location, and institution. The primary endpoint will be ESD procedure time, defined as the time from the start of the submucosal injection to the completion of resection. Other outcomes will include the rates of adverse events and pathological curability Discussion:. The ability of EndoTrac ESD to reduce the long procedure time and/or adverse events observed with conventional ESD can not only reduce physical stress on the patient, but can also reduce length of hospital stay and medical costs. Reduced technical difficulty will contribute to the widespread adoption of this ESD technique worldwide. Trial registration:. University Hospital Medial Information Network Clinical Trials Registry (UMIN-CTR), ID: 000044450; Registered on June 6, 2021. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000050485. Protocol version number:. 1.1, March 1, 2022. Patient enrolment began on June 6, 2021 and is expected to be completed by July 19, 2025.

Progressive multifocal leukoencephalopathy (PML) is a devastating demyelinating disease caused by JC virus (JCV), predominantly affecting patients with impaired cellular immunity. PML is a non-reportable disease with a few exceptions, making national surveillance difficult. In Japan, polymerase chain reaction (PCR) testing for JCV in the cerebrospinal fluid (CSF) is performed at the National Institute of Infectious Diseases to support PML diagnosis. To clarify the overall profile of PML in Japan, patient data provided at the time of CSF-JCV testing over 10 years (FY2011–2020) were analyzed. PCR testing for 1537 new suspected PML cases was conducted, and 288 (18.7%) patients tested positive for CSF-JCV. An analysis of the clinical information on all individuals tested revealed characteristics of PML cases, including the geographic distribution, age and sex patterns, and CSF-JCV-positivity rates among the study subjects for each type of underlying condition. During the last five years of the study period, a surveillance system utilizing ultrasensitive PCR testing and widespread clinical attention to PML led to the detection of CSF-JCV in the earlier stages of the disease. The results of this study will provide valuable information not only for PML diagnosis, but also for the treatment of PML-predisposing conditions.

Background: The neuropathology of sporadic Creutzfeldt–Jakob disease (sCJD) is usually investigated using formalin-fixed and formic acid-treated brain tissue. However, formalin and formic acid treatment can interfere with immunostaining of abnormal prion protein. Therefore, there is a need for biochemical methods other than immunostaining to investigate abnormal prion protein in postmortem tissue. We developed RT-QuIC to quantitate the seeding activity (SD50) of sCJD brain tissue treated with formalin and formic acid. Methods: We used endpoint RT-QuIC assays to analyze SD50 in formalin-fixed brain tissue from 19 sCJD patients (14 MM1 cases, 3 MM2-thalamic form [MM2T] cases and 2 MM2-cortical form [MM2C] cases) diagnosed according to Parchi's classification. We assessed SD50 in brains after incubation in formalin solution for over 1 month, and after treating formalin-fixed brain tissue with formic acid. We also examined how the SD50 values from formalin-fixed brain samples compared with neuropathological and immunohistochemical findings. Results: The SD50 values of formalin-fixed brain samples from 14 MM1 cases, 2 MM2C cases, and 2 MM2T cases were 107.77±0.57/g tissue, 107.44±0.24/g tissue and 106.00±0.77/g tissue, respectively. The average SD50 value in MM1 unfixed brains decreased by 102.04 after formalin fixation for 1 month. In MM1 cases, after combined formalin and formic acid treatment, the SD50 value was reduced by approximately 105.16 compared with that of unfixed tissue. The SD50 values of formalin-fixed tissue showed a consistent pattern with the neuropathological findings in most brain regions examined. Conclusion: RT-QuIC enables the study of formalin-fixed brain tissue from sCJD patients that has not previously been amenable to analysis.

Abstract A previous study reported that a massive cerebral infarct in the territory of the middle cerebral artery (MCA) may be associated with development of neurofibrillary tangles (NFTs) in the ipsilateral basal nucleus of Meynert (BNM). We analyzed 19 cases of an MCA territory infarct and 12 with a putaminal hemorrhage (mean age 82.5 years; female/male ratio 8/23; mean time from stroke onset to autopsy 4182 days). In both groups, 74–100% had a significantly higher rate of phosphorylated tau immunoreactive or Gallyas Braak silver stain-positive neurons on the BNM-affected side than on the BNM-unaffected side. These NFTs were immunoreactive for anti-RD3 and anti-RD4 antibodies, and a triple-band pattern was observed by immunoblot analysis with anti-tau antibody. Most NFTs might be formed within the 5–10 years after stroke onset. There were significantly more TAR DNA-binding protein 43 (TDP43) immunoreactive structures on the BNM-affected side than on the BNM-unaffected side. We showed that many NFTs with TDP43-immunoreactive structures were observed in the ipsilateral BNM associated with a massive cerebral infarct in the MCA territory or a putaminal hemorrhage.

The purpose of the present study was to quantitatively elucidate the levels of protein expression of anti-epileptic-drug (AED) transporters, metabolizing enzymes and tight junction molecules at the blood–brain barrier (BBB) in the focal site of epilepsy patients using accurate SWATH (sequential window acquisition of all theoretical fragment ion spectra) proteomics. Brain capillaries were isolated from focal sites in six epilepsy patients and five normal brains; tryptic digests were produced and subjected to SWATH analysis. MDR1 and BCRP were significantly downregulated in the epilepsy group compared to the normal group. Out of 16 AED-metabolizing enzymes detected, the protein expression levels of GSTP1, GSTO1, CYP2E1, ALDH1A1, ALDH6A1, ALDH7A1, ALDH9A1 and ADH5 were significantly 2.13-, 6.23-, 2.16-, 2.80-, 1.73-, 1.67-, 2.47- and 2.23-fold greater in the brain capillaries of epileptic patients than those of normal brains, respectively. The protein expression levels of Claudin-5, ZO-1, Catenin alpha-1, beta-1 and delta-1 were significantly lower, 1.97-, 2.51-, 2.44-, 1.90- and 1.63-fold, in the brain capillaries of epileptic patients compared to those of normal brains, respectively. Consistent with these observations, leakage of blood proteins was also observed. These results provide for a better understanding of the therapeutic effect of AEDs and molecular mechanisms of AED resistance in epileptic patients.

Human prion diseases are neurodegenerative disorders caused by abnormally folded prion proteins in the central nervous system. These proteins can be detected using the quaking-induced conversion assay. Compared with other bioassays, this assay is extremely sensitive and was used in the present study to determine prion distribution in sporadic Creutzfeldt-Jakob disease patients at autopsy. Although infectivity of the sporadic form is thought to be restricted within the central nervous system, results showed that prion-seeding activities reach 106/g from a 50% seeding dose in non-neuronal tissues, suggesting that prion-seeding activity exists in non-neural organs, and we suggested that non-neural tissues of 106/g SD50 did not exist the infectivity.

Purpose: Pelvic position on the sagittal plane is usually evaluated with the pelvic sagittal inclination (PSI) angle from a single radiograph. However, the reproducibility of pelvic positioning has not been investigated, and thus, the validity of measuring the PSI from a single film/time point is not understood. Herein, the reproducibility of a patient’s pelvic positions in supine and standing postures was analyzed. Methods: A total of 34 patients who underwent either a pelvic osteotomy or total hip arthroplasty were enrolled in this study. Preoperative radiographs in both supine and standing postures were acquired twice (first X-ray and second X-ray) within 6 months; preoperative computed tomography (CT) images of the full pelvis were also acquired in a supine posture (preop-CT). To eliminate measurement variability, each PSI was automatically measured from radiographs and CT images through the use of CT segmentation and landmark localization followed by intensity-based 2D-3D registration. The absolute difference of PSI among each image was calculated and the intra-class correlation coefficient (ICC) in each posture was also analyzed. Results: The median absolute differences of PSI in the supine posture were 1.3° between the first and second X-rays, 1.2° between the first X-ray and preop-CT, and 1.3° between the second X-ray and preop-CT. The median absolute difference of PSI in the standing posture was 1.5°. The ICC was 0.965 (95% CI: 0.939–0.981) in supine and 0.977 (95% CI: 0.954–0.988) during standing. Conclusions: Pelvic positions in supine and standing postures are reproducible. Thus, measuring the PSI from a single radiograph is reliable.

Amyotrophic lateral sclerosis and Parkinsonism-dementia complex (ALS/PDC) is a unique endemic neurodegenerative disease, with high-incidence foci in Kii Peninsula, Japan. To gather new insights into the pathological mechanisms underlying Kii ALS/PDC, we performed transcriptome analyses of patient brains. We prepared frozen brains from three individuals without neurodegenerative diseases, three patients with Alzheimer’s disease, and 21 patients with Kii ALS/PDC, and then acquired microarray data from cerebral gray and white matter tissues. Microarray results revealed that expression levels of genes associated with heat shock proteins, DNA binding/damage, and senescence were significantly altered in patients with ALS/PDC compared with healthy individuals. The RNA expression pattern observed for ALS-type brains was similar to that of PDC-type brains. Additionally, pathway and network analyses indicated that the molecular mechanism underlying ALS/PDC may be associated with oxidative phosphorylation of mitochondria, ribosomes, and the synaptic vesicle cycle; in particular, upstream regulators of these mechanisms may be found in synapses and during synaptic trafficking. Furthermore, phenotypic differences between ALS-type and PDC-type were observed, based on HLA haplotypes. In conclusion, determining the relationship between stress-responsive proteins, synaptic dysfunction, and the pathogenesis of ALS/PDC in the Kii peninsula may provide new understanding of this mysterious disease.

Purpose: Intertrochanteric fractures are usually treated with open reduction and internal fixation, but controversy still remains regarding the proper placement of the lag screw on the anteroposterior view. The stability of the lag screw has been shown to correlate with the bone quality around the screw, but the three-dimensional distribution of the bone mineral density (BMD) in the femoral head has not been studied in detail. Herein, the BMD along the femoral neck axis was measured to clarify the recommended position of the lag screw. Methods: Ten femoral heads acquired from intertrochanteric fractures were evaluated in this study. Each femoral head was scanned with micro computed tomography and the BMD along the femoral neck axis was measured in five regions: center, anterior, posterior, superior, and inferior. The BMD on the anteroposterior view (superior, center, and inferior) and the BMD on the lateral view (anterior, center, and posterior) were compared. Results: The BMD of the center region (173.0 ± 50.6 mg/cm 3 ) was significantly higher than that of the inferior region (139.7 ± 50.1 mg/cm 3 ) on the anteroposterior view ( p < 0.01). On the lateral view, the BMD was lower than the center region in the anterior region (165.7 ± 52.8 mg/cm 3 ) and in the posterior region (157.5 ± 42.3 mg/cm 3 ), but the difference was not significant. Conclusion: The BMD was higher in the center region of the femoral head than in the inferior region. Therefore, lag screws are recommended to be inserted into the center of the femoral head.

Purpose: Diagnosing corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is often difficult due to the wide variety of symptoms and overlaps in the similar clinical courses and neurological findings. The purpose of this study was to evaluate the utility of white matter (WM) atrophy for the diagnosis of patients with clinically diagnosed CBD (corticobasal syndrome, CBS) and PSP (Richardson’s syndrome, RS). Methods: We randomly divided the 3D T1-weighted MR images of 18 CBS patients, 33 RS patients, and 32 age-matched controls into two groups. We obtained segmented WM images in the first group using Voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) based on statistical parametric mapping (SPM) 8 plus diffeomorphic anatomical registration through exponentiated Lie algebra. A target volume of interest (VOI) for disease-specific atrophy was subsequently determined in this group using SPM8 group analyses of WM atrophy between patients groups and controls. We then evaluated the utility of these VOIs for diagnosing CBS and RS patients in the second group. Z score values in these VOIs were used as the determinant in receiver operating characteristic (ROC) analyses. Results: Specific target VOIs were determined in the bilateral frontal subcortical WM for CBS and in the midbrain tegmentum for RS. In ROC analyses, the target VOIs of CBS and RS compared to those of controls exhibited an area under curve (AUC) of 0.99 and 0.84, respectively, which indicated an adequate diagnostic power. The VOI of CBS revealed a higher AUC than that of RS for differentiating between CBS and RS (AUC, 0.75 vs 0.53). Conclusions: Bilateral frontal WM volume reduction demonstrated a higher power for differentiating CBS from RS. This VOI analysis is useful for clinically diagnosing CBS and RS.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1-42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia. We obtained a total of 3498 CSF samples from patients admitted to our hospital during the period from 1996 to 2015. Of these patients, we were able to carry out a brain autopsy in 94 cases. Finally, 78 neuropathologically diagnosed cases (10 AD, six DLB, five DLB with AD, five controls without neurological diseases, and 52 cases with other neurological diseases) were studied. CSF levels of HVA and 5-HIAA were consistently decreased in pathologically advanced Lewy body disorder (LBD; Braak LB stages >3) compared with pathologically incipient LBD (Braak LB stages

The present paper describes a method for 3-dimensional (3D) automated preoperative planning of the femoral component (stem) in total hip arthroplasty (THA). Stem planning is formulated as a problem to determine the optimal parameters of position, rotation, and stem size, based on 3D surface models of host bone reconstructed from CT images, which includes the femur and femoral canal. An objective function that represents the fitness between the femoral canal and stem surfaces is defined. We also defined positional and rotational constraints derived from previous studies on femoral anatomy. Maximization is performed by the Powell method using initial values equally sampled within the possible solution space. We obtained parameters that maximize the objective function by exhaustive adjustment of the parameters. We applied the proposed method to 17 cases, and the proposed method was experimentally evaluated according to differences between planning results of the automated system and those of an experienced surgeon. Preoperative planning was also performed by a surgeon to evaluate performance of the automated system. The difference in stem size was less than 1 size in all cases, and the surgeon agreed with the planning results of the proposed method in 14 cases. In those 14 cases, mean errors of position and orientation were 3.2 mm and 4.6 deg., respectively. The proposed method thus appears applicable in preoperative planning of the stem.

The infectious agents of the transmissible spongiform encephalopathies are composed of amyloidogenic prion protein, PrPSc. Real-time quaking-induced conversion can amplify very small amounts of PrPSc seeds in tissues/body fluids of patients or animals. Using this in vitro PrP-amyloid amplification assay, we quantitated the seeding activity of affected human brains. End-point assay using serially diluted brain homogenates of sporadic Creutzfeldt-Jakob disease patients demonstrated that 50% seeding dose (SD50) is reached approximately 10(10)/g brain (values varies 10(8.79-10.63)/g). A genetic case (GSS-P102L) yielded a similar level of seeding activity in an autopsy brain sample. The range of PrPSc concentrations in the samples, determined by dot-blot assay, was 0.6-5.4 μg/g brain; therefore, we estimated that 1 SD50 unit was equivalent to 0.06-0.27 fg of PrPSc. The SD50 values of the affected brains dropped more than three orders of magnitude after autoclaving at 121°C. This new method for quantitation of human prion activity provides a new way to reduce the risk of iatrogenic prion transmission.