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Objectives To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. Methods We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine–Gray model to assess the association between low IgG (the minimum IgG levels Results Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03–3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. Conclusion Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Background Single leg squat (SLS) tests help predict anterior cruciate ligament injuries. However, the variability in joint movement during this test has not been fully investigated. The aim of this study was to examine the knee frontal plane movement variability during SLS in patients with anterior cruciate ligament (ACL) injury. Methods In this cross-sectional study, we enrolled 56 patients with ACL injury (28 males; 28 females) and 46 healthy subjects (23 males; 23 females). All participants underwent SLS tests. All kinematic variables were joint angle of trunk, pelvis and lower limb, center of gravity (COG), center of pressure (COP). These data were obtained at the frontal plane and the coefficient of variation (CV) were calculated. Multiple comparisons were performed between healthy subjects and the injured leg and uninjured leg of patients with ACL injury. The correlation of the CV in knee varus/valgus range of motion (ROM) with the CV in other kinematic variables were investigated in patients with ACL injury. Results Compared with healthy subjects, patients with ACL injury exhibited significantly larger the CV in knee varus/valgus ROM. A positive correlation was observed between the CV in knee varus/valgus ROM and the CV in pelvic lateral inclination ROM in patients with ACL injury. Conclusions Knee frontal plane movement variability during SLS may help evaluate the risk of ACL injury/re-injury. In addition, pelvic lateral inclination variability during SLS may need to be evaluated in conjunction with knee frontal plane movement variability.

ObjectivesTo visualise the trajectories of pulmonary arterial pressure (PAP) in systemic sclerosis (SSc) and identify the clinical phenotypes for each trajectory, by applying latent trajectory modelling for PAP repeatedly estimated by echocardiography.MethodsThis was a multicentre, retrospective cohort study conducted at four referral hospitals in Kyoto, Japan. Patients with SSc who were treated at study sites between 2008 and 2021 and who had at least three echocardiographic measurements of systolic PAP (sPAP) were included. A group-based trajectory model was applied to the change in sPAP over time, and patients were classified into distinct subgroups that followed similar trajectories. Pulmonary hypertension (PH)-free survival was compared for each trajectory. Multinomial logistic regression analysis was performed for baseline clinical characteristics associated with trajectory assignment.ResultsA total of 236 patients with 1097 sPAP measurements were included. We identified five trajectories: rapid progression (n=9, 3.8%), early elevation (n=30, 12.7%), middle elevation (n=54, 22.9%), late elevation (n=24, 10.2%) and low stable (n=119, 50.4%). The trajectories, in the listed order, showed progressively earlier elevation of sPAP and shorter PH-free survival. In the multinomial logistic regression analysis with the low stable as a reference, cardiac involvement was associated with rapid progression, diffuse cutaneous SSc was associated with early elevation and anti-centromere antibody was associated with middle elevation; older age of onset was associated with all three of these trajectories.ConclusionThe pattern of changes in PAP over time in SSc can be classified into five trajectories with distinctly different clinical characteristics and outcomes.

[Purpose] This study investigated the parameters that characterize the knee, hip, and pelvic kinematics during a single-leg squat in preoperative anterior cruciate ligament rupture injury. [Participants and Methods] Overall, 15 patients with unilateral anterior cruciate ligament deficiency were enrolled in this study. For each single-leg squat, data from two-dimensional video cameras and three-dimensional motion analysis were collected. Measurement indices included the articular angles of the knee, hip, and trunk. The anterior cruciate ligament-injured leg was compared with the uninjured leg. [Results] The maximum knee valgus and flexion angles during a single-leg squat were smaller in the injured leg than in the uninjured leg. During the single-leg squat, the effect of "compensatory mechanisms" appeared as knee valgus and flexion movements. In particular, the knee valgus angle decreased in the anterior cruciate ligament-injured leg compared to that in the uninjured leg. [Conclusion] This phenomenon suggests that it is possible to utilize recurrence prevention training for anterior cruciate ligament injury.

Objective In Para-cycling competitions, cyclists with amputation of one-leg and no prosthesis, i.e., Division Cycle, Sport Class C2, perform pedaling movement on bicycle by unilateral leg. The purpose of this study was to describe neuromuscular activation of lower extremity muscles in two cyclists with single leg amputation and one cyclist with two legs during pedaling. We compared averaged rectified values (ARV) of surface electromyography for lower extremity muscles during crank cycle for two single leg cyclists with one cyclist with two legs at 65%, 80%, and 95% of VO2 max. Results Characteristic features of cyclists with single amputation of leg were increases in ARV for proximal region of the rectus femoris muscle in first half of pulling phase, increases in ARV for the biceps femoris muscle in first half of pulling phase, and increases in ARV for the medial gastrocnemius muscle in pulling phase. These findings in this study suggest that cyclists with single amputation of leg use characteristic neuromuscular coordination in the muscles contributing to hip and knee flexion joint moments during pulling phase and this may be the strategy in cyclists with single amputation of leg to compensate lack of hip and/or knee extension torque from contralateral leg.

Background Rapid knee valgus and knee internal rotation motions in the initial phase of landing are the known mechanisms for anterior cruciate ligament injury, and many studies have been investigated on knee joint peak angle during landing. However, the variability in joint movement during landing has not been fully investigated. This study aimed to compare the coefficient of variation of lower extremity range of motion in patients with anterior cruciate ligament reconstruction and healthy subjects during landing. Methods In this cross-sectional study, 54 patients with anterior cruciate ligament reconstruction and 44 healthy subjects were enrolled. All participants underwent six trials of single-leg hop landing for maximum safe horizontal distance. The kinematic variables were the coefficient of variation during two discrete (0.05 after initial contact and maximum knee flexion) time points for selected three-dimensional hip and knee joint range of motion. Comparisons were performed between the two groups. Results Compared with healthy subjects, patients with anterior cruciate ligament reconstruction had greater the coefficient of variation in hip internal/external rotation range of motion (patients with anterior cruciate ligament reconstruction had 41.9%, healthy subjects had 25.5%; P=0.0018; effect size: 0.32) and knee internal/external rotation range of motion (patients with anterior cruciate ligament reconstruction had 68.4%; healthy subjects had 48.1%; P=0.0014; effect size: 0.32) for periods that spanned 0.05 s from the initial contact. Conclusions Patients with anterior cruciate ligament reconstruction could be disadvantageous in ability to control and adapt hip and knee joint rotations when controlling landings.

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease.Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics.Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH.Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.

BackgroundKnee extensor muscle strength and cardiorespiratory fitness (CRF) are major components of physical fitness. Because the interactive association of knee extensor muscle strength and CRF with bone health remains unclear, we aimed to investigate such association in Japanese adults.MethodsAltogether, 8,829 Japanese adults (3,731 men and 5,098 women) aged ≥45 years completed the maximum voluntary knee extension test, submaximal exercise test, medical examination, and a questionnaire on lifestyle habits. Using an osteo-sono assessment index, low bone stiffness tendency was defined as 80% under the young-adults mean. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after confounder adjustment.ResultsOverall, 542 men (14.5%) and 978 women (19.2%) had low bone stiffness tendency. We observed an inverse association between muscle strength and low bone stiffness tendency after adjustment for CRF in both sexes (p for linear trend < 0.001). Compared with the lowest CRF, the multivariable ORs (95% CI) for low bone stiffness tendency in the highest CRF were 0.47 (0.36, 0.62) for men and 1.05 (0.82, 1.35) for post-menopausal women (p < 0.001 and p = 0.704, respectively). No interactive association between muscle strength and CRF for low bone stiffness tendency existed in both sexes and irrespective of menopausal status.ConclusionKnee extensor muscle strength and CRF were associated additively, not synergistically, with bone health. Maintaining high levels of both physical fitness components may improve musculoskeletal health in the cohort. The relationship between physical fitness and bone status should be longitudinally investigated in the future.

Lithium-ion batteries are widely used as a power source for portable equipment. However, the use of highly flammable organic solvents in the liquid electrolyte component in these batteries presents a serious safety concern. In this study, the thermal stability of battery cathodes comprising LiNi1/3Mn1/3Co1/3O2 (NMC) and LiPF6-based electrolyte solutions have been investigated using transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) methods. Ex situ TEM measurements revealed that significant structural change occurred in the charged NMC composite after heating at a temperature above the exothermal peaks. It was found that LiF nanocrystallites precipitated in LiPF6 and that a number of nanoscale stacking faults developed in the $$R\bar{3}m$$ R 3 ¯ m layered structure of NMC. The results suggested that the decomposition reaction of LiPF6 and the structural change of NMC were directly associated with the exothermic reaction in the liquid electrolyte-based NMC electrode composite.

Background The prophylaxis for hepatitis B virus (HBV) reactivation assumes that hepatic injury after reactivation is often rapidly progressive and can evoke fulminant hepatitis. The incidence and prognosis of reactivation in patients with rheumatoid arthritis (RA) may be different from those receiving organ transplantation and cancer chemotherapy. This study aimed to investigate the incidence, risk factors, and clinical course of HBV reactivation and develop a scoring system for risk stratification in RA patients with resolved infection. Methods HBV DNA was measured using real-time polymerase chain reaction, and patient data were collected for 4 years in RA patients with resolved HBV infection who were treated with steroids or synthetic or biologic immunosuppressive drugs. Results Among 1127 patients, HBV DNA was detected in 57 patients (1.65/100 person-years); none of the reactivated patients exhibited worsening of hepatic function. Multivariate logistical analysis revealed that age > 70 years and HB core antibody (HBcAb) positivity alone were independent risk factors for HBV reactivation. HBV DNA ≥ 2.1 log copies/mL was observed in 15 patients (0.43/100 person-years); seven patients were treated with nucleic acid analogs (NAAs), whereas the remaining eight were observed without treatment. Among reactivated cases, 15 cases changed to HBV DNA-negative status spontaneously, whereas 24 cases remained HBV DNA positive 70 years) + 2 × (HBcAb positivity alone) + 1 × (treatment other than methotrexate monotherapy). This revealed that patients with the highest score had an odds ratio of 13.01 for HBV reactivation, compared to those with the lowest score. Conclusions Rapid progression and poor outcomes after HBV reactivation were not frequent in RA patients with resolved infection. Our new risk scoring system might be useful for screening and optimization of prophylactic treatment by distinguishing patients with significantly lower reactivation risk.

Objectives Home blood pressure control can reduce the risk of increased urinary albumin excretion in patients with diabetes mellitus. However, the optimal home blood pressure targets to prevent the onset or progression of diabetic nephropathy are not well defined. Methods We performed a retrospective cohort study of 851 patients with type 2 diabetes mellitus. Logistic regression models were used to evaluate the correlations of home SBP levels with progression of diabetic nephropathy. Results During the follow-up of 2 years, 86 patients had progression of diabetic nephropathy. Adjusted odds ratios (95% confidence interval) for progression of diabetic nephropathy in patients with morning SBP of 120-129 mmHg [2.725 (1.074-6.917), P = 0.035], 130-139 mmHg [3.703 (1.519-9.031), P = 0.004] and in those with morning SBP equal or more than 140 mmHg [2.994 (1.182-7.581), P = 0.021] were significantly higher than that in those with morning SBP less than 120 mmHg in multiple logistic analyses. Conclusion The preferable morning SBP targets might be less than 120 mmHg for preventing the onset or progression of diabetic nephropathy in patients with type 2 diabetes mellitus.

The purpose is to develop a new image toggle tool with automatic density normalization (ADN) and automatic alignment (AA) for comparing serial digital mammograms (DMGs).We developed an ADN and AA process to compare the images of serial DMGs. In image density normalization, a linear interpolation was applied by taking two points of high- and low-brightness areas. The alignment was calculated by determining the point of the greatest correlation while shifting the alignment between the current and prior images. These processes were performed on a PC with a 3.20-GHz Xeon processor and 8 GB of main memory. We selected 12 suspected breast cancer patients who had undergone screening DMGs in the past. Automatic processing was retrospectively performed on these images. Two radiologists subjectively evaluated them.The process of the developed algorithm took approximately 1 s per image. In our preliminary experience, two images could not be aligned approximately. When they were aligned, image toggling allowed detection of differences between examinations easily.We developed a new tool to facilitate comparative reading of DMGs on a mammography viewing system. Using this tool for toggling comparisons might improve the interpretation efficiency of serial DMGs.

BackgroundAlthough the reactivation of hepatitis B virus (HBV) is recognised as a serious complication in patients with rheumatic disease (RD) receiving immunosuppressive drugs (ISDs), the incidence and risk factors for reactivation remain controversial.ObjectivesTo investigate the incidence and risk factors for HBV reactivation in patients with RD.MethodsWe performed a multicentre, observational, prospective study over 2 years in patients with resolved HBV infection. Patients with RD treated with a dose of ≥5 mg/day prednisolone and/or synthetic or biological ISDs with negative HB virus surface antigen and positive anti-HB virus surface antibody (HBsAb) and/or anti-HB virus core antibody (HBcAb) were enrolled. Quantitative HBV DNA results and related data were regularly recorded.ResultsAmong 1042 patients, including 959 with rheumatoid arthritis, HBV DNA was detected in 35 (1.93/100 person-years), with >2.1 log copies/mL observed in 10 patients (0.55/100 person-years). None of the reactivated patients, including seven treated with a nucleic acid analogue, showed overt hepatitis. Low HBsAb titres and advanced age seemed to be risk factors for HBV reactivation; however, reactivation was observed in three patients with positive HBsAb and negative HBcAb test results. The risk of reactivation was lower with methotrexate but higher with prednisolone among the different types of ISDs. The intervals from the start of ISD to reactivation were relatively long (3–182 months; median, 66 months).ConclusionsThe incidence of HBV reactivation with ISD use was 1.93/100 person-years in patients with RD with resolved HBV infection. No overt hepatitis was observed in the reactivated patients.

To investigate the influence of biologics on mortality and risk factors for death in rheumatoid arthritis (RA) patients. RA patients treated with at least one dose of biologics in daily practice in six large rheumatology institutes (“biologics cohort”) were observed until 15 May 2010 or death, whichever occurred first. Mortality of the biologics cohort and the “comparator cohort” (comprising patients among the IORRA cohort who had never been treated with biologics) was compared to that of the Japanese general population. Factors associated with mortality were assessed by a Cox model. Among 2683 patients with 6913.0 patient-years of observation, 38 deaths were identified in the biologics cohort. The probability of death in patients lost to follow-up, calculated using the weighted standardized mortality ratio (SMR), was 1.08 [95 % confidence interval (CI) 0.77–1.47] in the biologics cohort and 1.28 (95 % CI 1.17–1.41) in the comparator cohort. Pulmonary involvement was the main cause of death (47.4 %), and the disease-specific SMR of pneumonia was 4.19 (95 % CI 1.81–8.25). Risk factors for death included male gender [hazard ratio (HR) 2.78 (95 % CI 1.24–6.22)], advanced age (HR 1.07, 95 % CI 1.03–1.11), and corticosteroid dose (HR 1.08, 95 % CI 1.01–1.17). Mortality in RA patients exposed to biologics did not exceed that in patients not exposed to biologics, but death from pulmonary manifestations was proportionally increased in RA patients exposed to biologics.

The purposes of this study were to investigate the state of blood pressure control level and to investigate the relationship between blood pressure control level and nephropathy in Japanese type 2 diabetes. We measured clinic and home blood pressure in 923 type 2 diabetic patients. According to the criteria for hypertension in the Japanese Society of Hypertension Guidelines 2009, patients were classified into four groups by clinic systolic blood pressure (130 mmHg) and morning systolic blood pressure (125 mmHg), as follows: controlled hypertension (CH), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH). Of all patients, 13.9, 12.6, 13.3, and 60.2% were identified as having CH, WCH, MH, and SH, respectively. The average number of drugs prescribed was 1.8. We assessed the association between blood pressure control level and nephropathy in diabetic patients. The degree of urinary albumin excretion and the prevalence of nephropathy in diabetic patients were higher in MH and SH groups than those in the CH group. The majority of patients had poor blood pressure control, regardless of ongoing conventional antihypertensive therapy, and diabetic patients with MH and SH were associated with nephropathy. It is suggested that more aggressive antihypertensive treatment is recommended to prevent nephropathy in diabetic patients.

This cross-sectional study was done to show how nutritional indices influence each other and the contributions made by inflammation to the development of rheumatoid cachexia. We studied 295 female patients with rheumatoid arthritis (RA). We chose five nutritional indices: body mass index (BMI), arm muscle area (AMA), triceps skinfold thickness (TSF), which were obtained via anthropometric measurements, and serum albumin and cholesterol. Clinical indicators of RA included disease duration, C-reactive protein (CRP) and Disease Activity Score 28 (DAS28). We performed a bivariate correlation test between the nutritional indices and multiple regression analysis for each nutritional index. Mean AMA was low, 87.3% of the normal value, whereas TSF was not different. Muscle protein expressed by AMA decreased according to RA duration, whereas visceral protein indicated by serum albumin decreased with an increase in RA activity. The continuation of inflammation appears to be essential for a decrease in muscle protein in rheumatoid cachexia. DAS28 showed a positive contribution to BMI in the regression model, and the increase in RA disease activity causes an increase in BMI via an accumulation of tissue fat.

Superresolution is an image processing technique that estimates an original high-resolution image from its low-resolution and degraded observations. In superresolution tasks, there have been problems regarding the computational cost for the estimation of high-dimensional variables. These problems are now being overcome by the recent development of fast computers and the development of powerful computational techniques such as variational Bayesian approximation. This paper reviews a Bayesian treatment of the superresolution problem and presents its extensions based on hierarchical modeling by employing hidden variables.