AIMS:Patients with acute pulmonary edema (APE) requiring an urgent heart failure (HF) hospitalization face poor prognosis largely due to pulmonary congestion. We aimed at assessing the patterns and variations of pulmonary congestion associated with different assessments of congestion and prognosis. METHODS:This prospective study included patients with APE who underwent lung ultrasound (8-zone B-lines method) and echocardiography immediately after emergency department visit, with follow-up assessments on days 2, 3, 7, and discharge. B-type natriuretic peptide (BNP) levels were measured at admission, day 7, and discharge. The associations between B-line changes, other congestion marker changes and outcomes were assessed. RESULTS:Among 137 patients (mean age: 77 ± 13 years; 61 % male), 71 % had New York Heart Association IV, 65 % had left ventricular ejection fraction <45 %, and median B-lines were 44 (32-58) on admission. While B-lines showed no association with other congestion markers at admission, they correlated significantly with pulmonary artery systolic pressure (PASP) from day 2 to discharge, and with E/e´ and BNP at day 7 and discharge. Throughout hospitalization, B-line changes consistently correlated with changes in other congestion markers (E/e´, PASP, and BNP) (all-p-values<0.05). Among congestion markers, B-lines showed the most prominent reduction from admission to day 2, and this reduction was associated with a lower risk of all-cause mortality or HF rehospitalization over a median 217-day follow-up (adjusted-HR, 95 %CI = 0.96, 0.94-0.99; p = 0.01). CONCLUSIONS:In APE, B-lines lacked association with other congestion markers immediately after hospitalization. However, B-lines decreased noticeably from admission to day 2, with changes correlating with other markers and prognosis.

Few studies have reported on the validity of a sensor-based lower-limb kinematics evaluation during the timed up and go (TUG) test. This study aimed to determine the validity of a wearable gait sensor system for measuring lower-limb kinematics during the TUG test. Ten young healthy participants were enrolled, and lower-limb kinematics during the TUG test were assessed using a wearable gait sensor system and a standard optical motion analysis system. The angular velocities of the hip, knee, and ankle joints in sit-to-stand and turn-to-sit phases were significantly correlated between the two motion analysis systems (R = 0.612–0.937). The peak angles and ranges of motion of hip, knee, and ankle joints in the walking-out and walking-in phases were also correlated in both systems (R = 0.528–0.924). These results indicate that the wearable gait sensor system is useful for evaluating lower-limb kinematics not only during gait, but also during the TUG test.

Fluid dynamics studies have proposed that coronary flow reserve can be calculated from coronary artery pressure instead of coronary blood flow. We sought to investigate the diagnostic performance of pressure-bounded coronary flow reserve (pb-CFR) compared with CFR measured by conventional thermodilution method (CFRthermo) in the clinical setting. Pressure guidewire was used to measure CFRthermo and fractional flow reserve (FFR) in left anterior descending coronary artery in 62 patients with stable coronary artery disease. Pb-CFR was calculated only with resting distal coronary artery pressure (Pd), resting aortic pressure (Pa) and FFR. Pb-CFR was moderately correlated with CFRthermo (r = 0.54, P < 0.001). Pb-CFR showed a poor agreement with CFRthermo, presenting large values of mean difference and root mean square deviation (1.5 ± 1.4). Pb-CFR < 2.0 predicted CFRthermo < 2.0 with an accuracy of 79

Global longitudinal strain (GLS) is an echocardiographic measure to detect chemotherapy-related cardiovascular dysfunction. However, its limited availability and the needed expertise may restrict its generalization. Artificial intelligence (AI)-based GLS might overcome these challenges. Our aims are to explore the agreements between AI-based GLS and conventional GLS, and to assess whether the agreements were influenced by expertise levels, cardiac remodeling and cardiovascular diseases/risks. Echocardiographic images in the apical four-chamber view of left ventricle were retrospectively analyzed based on AI-based GLS in patients treated with chemotherapy, and correlation between AI-based GLS (Caas Qardia, Pie Medical Imaging) and conventional GLS (Vivid E9/VividE95, GE Healthcare) were assessed. The agreement between unexperienced physicians (“GLS beginner”) and experienced echocardiographer were also assessed. Among 94 patients (mean age 69 ± 12 years, 73

The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.

Few studies have dealt with lower-limb kinematics during the timed up and go (TUG) test in subjects with locomotive syndrome (LS). This study aimed to evaluate the characteristics of lower-limb kinematics during the TUG test in subjects with LS using the wearable sensor-based H-Gait system. A total of 140 participants were divided into the non-LS (n = 28), the LS-stage 1 (n = 78), and LS-stage 2 (n = 34) groups based on the LS risk test. Compared with the non-LS group, the LS-stage 1 and LS-stage 2 groups showed significantly smaller angular velocity of hip and knee extension during the sit-to-stand phase. The LS-stage 2 group showed significantly smaller peak angles of hip extension and flexion during the walking-out phase compared to the non-LS group. These findings indicate that the evaluation of the lower-limb kinematics during the TUG test using the H-Gait system is highly sensitive to detect LS, compared with the evaluation of the lower-limb kinematics when simply walking.

BACKGROUND:Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) have been widely used to assess the functional severity of coronary stenosis. However, their measurement requires using a pressure wire, making their use in all patients difficult. The recently developed vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography, is expected to serve as a surrogate for pressure wire assessment. METHODS:This retrospective study was conducted on patients with intermediate coronary stenosis who underwent FFR and NHPR measurements. The vFFR and NHPR values were compared for diagnosing coronary stenosis as defined by an FFR of ≤0.80, and the number of patients not requiring wire-based assessment was estimated. RESULTS:In a total of 90 lesions from 74 patients (median [SD] age 75 [12] years; men 80%), the median FFR was 0.78 (0.72-0.84), and 57% of these lesions (N = 51) exhibited an FFR of ≤0.80. vFFR provided high discrimination for coronary stenosis (area under the curve 0.80, 95% confidence interval 0.70-0.90), which was comparable to that of NHPRs (p = 0.42). High diagnostic accuracy was consistently observed across a variety of clinical presentations (i.e., old age, diabetes, target coronary artery, and left ventricular hypertrophy) (pinteraction > 0.05). In total, 55 lesions (61%) demonstrated positive or negative likelihood of coronary stenosis when vFFR was <0.73 (specificity 90%) or >0.87 (sensitivity 88%), respectively. CONCLUSION:vFFR demonstrated excellent diagnostic performance for detecting functionally significant coronary stenosis as evaluated by FFR. vFFR may be used as a surrogate for pressure wire assessment.

This study aims to describe the geometrical features of single trabeculae and their network to explain cancellous stiffness as a representative mechanical function from a strength of materials perspective. Compression tests were performed on cancellous bone specimens dissected from a bovine femur as 5-mm cubes to measure cancellous stiffness. The microarchitecture was determined by microfocus X-ray computed tomography, and conventional morphological indicators were analyzed. The length, orientation, and bifurcation characteristics of each trabecula were analyzed by skeletonizing and linearizing the cancellous bone volume. Multiple regression analyses revealed a significant contribution made to cancellous stiffness by the compressive shape factor of the stiffness of single trabeculae, the trabecular orientation, and the bifurcation count, which evaluated the mean number of connected trabeculae at bifurcation points. Bifurcation count made the most significant contribution to cancellous stiffness. The combination of these geometrical indicators expressed the cancellous stiffness (R2 = 0.85), which indicated as high accuracy as that explained by bone volume fraction, in specific bones that were not affected by bone disease or aging. The present study demonstrated mechanically important geometrical features of the microarchitecture and indicated their complex contributions to cancellous stiffness underlying the contribution of bone volume fraction.

Abstract Background Individuals with locomotive syndrome (LS) require nursing care services owing to problems with locomotion and the musculoskeletal system. Individuals with LS generally have a reduced walking speed compared with those without LS. However, differences in lower-limb kinematics and gait between individuals with and without LS are not fully understood. This study aimed to clarify the characteristics of the gait kinematics of individuals with LS using wearable sensors. Methods We assessed 125 participants (mean age 73.0 ± 6.7 years) who used a public health promotion facility. Based on the 25-question Geriatric Locomotive Function Scale (GLFS-25), these participants were grouped into the non-LS (GLFS-25 < 7), LS-stage 1 (GLFS-25 7–16), and LS-stage 2 (GLFS-25 ≥ 16) groups (larger GLFS-25 scores indicate worse locomotive ability). Spatiotemporal parameters and lower-limb kinematics during the 10-m walk test were analyzed by the “H-Gait system”, which is a motion analysis system that was developed by the authors and is based on seven inertial sensors. The peak joint angles during the stance and swing phases, as well as the gait speed, cadence, and step length were compared among all groups. Results There were 69 participants in the non-LS group, 33 in the LS-stage 1 group, and 23 in the LS-stage 2 group. Compared with the non-LS group, the LS-stage 2 group showed significantly smaller peak angles of hip extension (9.5 ± 5.3° vs 4.2 ± 8.2°, P = 0.002), hip flexion (34.2 ± 8.8° vs 28.5 ± 9.5°, P = 0.026), and knee flexion (65.2 ± 18.7° vs 50.6 ± 18.5°, P = 0.005). The LS-stage 1 and LS-stage 2 groups had a significantly slower mean gait speed than the non-LS group (non-LS: 1.3 ± 0.2 m/s, LS-stage 1: 1.2 ± 0.2 m/s, LS-stage 2: 1.1 ± 0.2 m/s, P < 0.001). Conclusions The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2.

Introduction Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. Materials and methods We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). Results Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. Conclusion Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.

Background Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for the prevention and treatment of GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. Methods We analyzed the trabecular microarchitecture, bone metabolism, and material strength of bone biopsy samples from the iliac crest of female patients with rheumatoid arthritis (RA) receiving an average of 6.7 years of BP therapy for GIO (GIOBP group, n = 10), compared with those of age- and bone mineral density (BMD)-matched non-RA postmenopausal women with no history of anti-osteoporosis medication use (reference group, n=10). Results Patients in the GIOBP group had a significantly greater fracture severity index, as calculated by the sum of the Genant visual semiquantitative grading scores of vertebral fractures (T4-L5) compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the BMD-matched reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. Conclusions Our findings indicate that patients with RA receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality.