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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.

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.

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 ​

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.

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.

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 (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.

Background: Polycythemia is a rare disease that can cause hypertension. Secondary polycythemia with increased production of erythropoietin (EPO) is associated with several kidney diseases, including hydronephrosis and cystic disease. However, there have been no reports of a case presenting with polycythemia secondary to bilateral nephromegaly caused by renal infiltration of T-cell acute lymphoblastic leukemia (T-ALL). Case presentation: A 32-year-old Japanese man presented with marked hypertension (215/150 mmHg) with renal insufficiency (creatinine 3.7 mg/dL), proteinuria, hematuria, bilateral nephromegaly, polycythemia (hemoglobin 20.2 g/dL), and increased serum EPO (38.7 mIU/mL, range 4.2–23.7 mIU/mL). Based on renal and bone marrow biopsy findings, he was diagnosed with T-ALL and bilaterally enlarged kidneys caused by renal infiltration of leukemic cells. There was no evidence of endocrine hypertension or fluid retention. Remission induction chemotherapy led to a decrease in kidney size, hemoglobin levels, and serum EPO levels, and allowed dose reductions of most hypertensive drugs, suggesting that hypertension was secondary to polycythemia. The patient's renal function gradually improved and hemodialysis was discontinued after 1 month of chemotherapy. Conclusions: We report a case of marked hypertension and secondary polycythemia induced by severe renal infiltration of T-ALL at diagnosis, which were synchronically improved with induction chemotherapy. This case history suggests the importance of considering lymphoproliferative diseases in the differential diagnosis of secondary polycythemia, leading to severe hypertension. [ABSTRACT FROM AUTHOR]