Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.

Deep learning to assess right ventricular ejection fraction from two-dimensional echocardiograms in precapillary pulmonary hypertension.

BACKGROUND: Precapillary pulmonary hypertension (PH) is characterized by a sustained increase in right ventricular (RV) afterload, impairing systolic function. Two-dimensional (2D) echocardiography is the most performed cardiac imaging tool to assess RV systolic function; however, an accurate evaluation requires expertise. We aimed to develop a fully automated deep learning (DL)-based tool to estimate the RV ejection fraction (RVEF) from 2D echocardiographic videos of apical four-chamber views in patients with precapillary PH. METHODS: We identified 85 patients with suspected precapillary PH who underwent cardiac magnetic resonance imaging (MRI) and echocardiography. The data was divided into training (80%) and testing (20%) datasets, and a regression model was constructed using 3D-ResNet50. Accuracy was assessed using five-fold cross validation. RESULTS: The DL model predicted the cardiac MRI-derived RVEF with a mean absolute error of 7.67%. The DL model identified severe RV systolic dysfunction (defined as cardiac MRI-derived RVEF < 37%) with an area under the curve (AUC) of .84, which was comparable to the AUC of RV fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) measured by experienced sonographers (.87 and .72, respectively). To detect mild RV systolic dysfunction (defined as RVEF ≤ 45%), the AUC from the DL-predicted RVEF also demonstrated a high discriminatory power of .87, comparable to that of FAC (.90), and significantly higher than that of TAPSE (.67). CONCLUSION: The fully automated DL-based tool using 2D echocardiography could accurately estimate RVEF and exhibited a diagnostic performance for RV systolic dysfunction comparable to that of human readers.

Is There a Learning Curve for the 5-Year Implant Survival Rate of Total Hip Arthroplasty Using the Direct Anterior Approach With a Traction Table? A Prospective Cohort Study.

BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) is attracting attention as a minimally invasive surgery, but the learning curve to master this approach is a concern, and its effect on long-term results is unknown. The purpose of this prospective cohort study was to clarify how the learning curve affects the 5-year results of DAA THA with a traction table. METHODS: Of 402 THA cases using DAA with a mobile traction table and fluoroscopy, 249 cases composed of the first 50 cases for each surgeon were assessed during a learning curve, and 153 cases were evaluated after more than 50 cases of experience. RESULTS: The 5-year-implant survival rate was 99.2% both during and after the learning curve. The 2-year complication rate in the learning curve group was 8.9 versus 5.9%, which was not statistically significant. The 2-to-5-year complication rates also did not differ between the cohorts (0 versus 0.7%). Both groups demonstrated decreased complication rates when comparing 2-year complications to 2-to-5-year complications. Clinical scores significantly improved by 2 years and were maintained at 5 years in both groups. The cup safe-zone success rates were 96.4% during the learning curve and 98.7% after the learning curve. The stem safe-zone success rates were 97.2% during the learning curve and 96.1% after the learning curve. Surgical time was approximately 20 minutes shorter after the first 50 cases than during the learning curve (70.8 versus 90.6 minutes, P = .001). Intraoperative blood loss was significantly less after the learning curve than during the learning curve. CONCLUSIONS: This study implies that the learning curve affects perioperative results such as surgical time and intraoperative blood loss, but has little effect on short-term results up to 2 years after surgery and no effect on mid-term results from 2 to 5 years after surgery.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Fibroblast growth factor receptor 1 as a potential marker of terminal effector peripheral T helper cells in rheumatoid arthritis patients.

OBJECTIVES: RA is an autoimmune disease characterized by destructive polyarthritis. CD4+ T cells are pivotal to its pathogenesis, and our previous study revealed the expression of fibroblast growth factor receptor 1 (FGFR1) is modulated by MTX treatment in CD4+ T cells of RA patients; however, the roles of FGFR1 in CD4+ T cells in the pathogenesis of RA is unclear. Therefore, in this study, we aimed to characterize FGFR1-positive CD4+ T cells in RA patients. METHODS: The abundance of FGFR1-positive CD4+ T cells in peripheral blood and synovium was determined. Single-cell RNA sequencing (scRNA-seq) was performed on synovial CD4+ T cells to characterize FGFR1-positive cells. In addition, T cell activation status and cytokine production were determined using flow cytometry. RESULTS: The percentage of FGFR1-positive CD4+ T cells in the peripheral blood was higher in RA patients than in healthy controls (P =0.0035). They were also present in the synovium of active RA patients. The results of scRNA-seq revealed that peripheral Th (Tph) cells preferentially expressed FGFR1. Additionally, these FGFR1-positive Tph cells displayed a terminal effector cell phenotype. Consistent with this finding, FGFR1-positive CD4+ T cells in peripheral blood expressed IL-21 and IFN-γ. CONCLUSION: Our study provides evidence that FGFR1 marks terminal effector Tph cells in patients with RA.

Clinical evaluation of a novel drill dilator as the first-line tract dilation technique during EUS-guided biliary drainage by nonexpert hands (with videos).

BACKGROUND AND AIMS: In cases in which tract dilation fails using the initially selected dilation device during EUS-guided hepaticogastrostomy (EUS-HGS), dilation should be re-attempted using another device. However, switching from one device to another during the procedure is often associated with prolonged procedure time and deviation from the correct axis. Therefore, it is highly desired that the initial tract dilation succeeds on the first attempt. Recently, a novel drill dilator has become available in Japan. Because there have been no previous studies comparing this novel device versus others as an initial dilation device, this article reports on the technical feasibility of this novel device for use during EUS-HGS and compares it with a balloon catheter. METHODS: This retrospective study included patients who underwent EUS-HGS using a self-expandable metal stent between October 2021 and October 2022. Excluded from the study were patients who underwent EUS-HGS using a plastic stent or stent deployment without tract dilation. The primary outcome in this study was the technical success rate of initial tract dilation using the drill dilator. This dilator has been available at our hospital since June 2022. Thus, EUS-HGS was performed using this device as the primary dilation device from June 2022 to October 2022. As the control group, we corrected patients who underwent EUS-HGS using a 4-mm balloon catheter as the primary dilation device from October 2021 to May 2022. RESULTS: A total of 49 patients were included: 19 underwent EUS-HGS using the drill dilator and 30 underwent EUS-HGS using a balloon catheter. EUS-HGS using the drill dilator initially was performed mainly by nonexpert hands (n = 19), whereas only some procedures in the balloon catheter group were performed by nonexpert hands (n = 2). Although the initial tract dilation was successful in all patients in the drill dilator group (19 of 19 [100%]) and in 29 (97%) of 30 in the balloon catheter group, additional tract dilation was needed in 73.7% (14 of 19) of the drill dilator group upon insertion of the 8.5F stent delivery system. In contrast, the stent delivery system insertion was successful without additional tract dilation in all patients in the balloon catheter group. CONCLUSIONS: The novel drill dilator might be useful as a dilation device; however, the balloon dilation technique should be selected first upon deploying a dedicated metal stent with an 8.5F stent delivery system.

Association Between the Development of Thrombosis and Worsening of Disease Severity in Patients With Moderate COVID-19 on Admission　- From the CLOT-COVID Study.

BACKGROUND: The worsening of coronavirus disease 2019 (COVID-19) severity is a critical issue in current clinical settings and may be associated with the development of thrombosis.Methods and Results: This study used patient data obtained in the CLOT-COVID study, a retrospective multicenter cohort study. The demographics of patients with moderate COVID-19 on admission with and without worsened severity during hospitalization were compared and predictors were identified. Of 927 patients with moderate COVID-19 on admission, 182 (19.6%) had worsened severity during hospitalization. Patients with worsening of severity were older, more likely to have hypertension, diabetes, heart disease, and active cancer, and more likely to use pharmacological thromboprophylaxis. Patients with worsening of severity had higher D-dimer levels on admission and were more likely to develop thrombosis and major bleeding during hospitalization than those without worsening. Increased age (odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, P=0.005), diabetes (OR: 1.63, 95% CI: 1.11-2.33, P=0.012), D-dimer levels >1.0 µg/mL on admission (OR: 2.10, 95% CI: 1.45-3.03, P<0.001), and thrombosis (OR: 6.28, 95% CI: 2.72-14.53, P<0.001) were independently associated with worsening of COVID-19 severity. CONCLUSIONS: Approximately 20% of patients with moderate COVID-19 had worsened severity during hospitalization. Increased age, diabetes, D-dimer levels >1.0 µg/mL on admission, and the development of thrombosis during hospitalization were significantly associated with worsened COVID-19 severity.

Mortality-associated Risk Factors in Hospitalized COVID-19 Patients in Japan: Findings of the CLOT-COVID Study.

BACKGROUND: Reports of mortality-associated risk factors in patients with the novel coronavirus disease 2019 (COVID-19) are limited. METHODS: We evaluated the clinical features that were associated with mortality among patients who died during hospitalization (n = 158) and those who were alive at discharge (n = 2,736) from the large-scale, multicenter, retrospective, observational cohort CLOT-COVID study, which enrolled consecutively hospitalized COVID-19 patients from 16 centers in Japan from April to September 2021. Data from 2,894 hospitalized COVID-19 participants of the CLOT-COVID study were analyzed in this study. RESULTS: Patients who died were older (71.1 years vs 51.6 years, P < 0.001), had higher median D-dimer values on admission (1.7 µg/mL vs 0.8 µg/mL, P < 0.001), and had more comorbidities. On admission, the patients who died had more severe COVID-19 than did those who survived (mild: 16% vs 63%, moderate: 47% vs 31%, and severe: 37% vs 6.2%, P < 0.001). In patients who died, the incidence of thrombosis and major bleeding during hospitalization was significantly higher than that in those who survived (thrombosis: 8.2% vs 1.5%, P < 0.001; major bleeding: 12.7% vs 1.4%, P < 0.001). Multivariable logistic regression analysis revealed that age >70 years, high D-dimer values on admission, heart disease, active cancer, higher COVID-19 severity on admission, and development of major bleeding during hospitalization were independently associated with a higher mortality risk. CONCLUSION: This large-scale observational study in Japan identified several independent risk factors for mortality in hospitalized patients with COVID-19 that could facilitate appropriate risk stratification of patients with COVID-19.

Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.

Leg position effects on the femoral neurovascular bundle location during a direct anterior approach total hip arthroplasty: a radiographic study.

BACKGROUND: Femoral neurovascular injury is a serious complication in a direct anterior approach (DAA) total hip arthroplasty. However, dynamic neurovascular bundle location changes during the approach were not examined. Thus, this study aimed to analyze the effects of leg position on the femoral neurovascular bundle location using magnetic resonance imaging (MRI). METHODS: This study scanned 30 healthy volunteers (15 males and 15 females) with 3.0T MRI in a supine and 30-degree hip extension position with the left leg in a neutral rotation position and the right leg in a 45-degree external extension position. The minimum distance from the edge of the anterior acetabulum to the femoral nerve (dFN), artery, and vein were measured on axial T1-weighted images at the hip center level, as well as the angle to the horizontal line of the femoral nerve (aFN), artery (aFA), and vein from the anterior acetabulum. RESULTS: The dFN in the supine position with external rotation was significantly larger than supine with neutral and extension with external rotation position (20.7, 19.5, and 19.0; p = 0.031 and 0.012, respectively). The aFA in supine with external rotation was significantly larger than in other postures (52.4°, 34.2°, and 36.2°, p < 0.001, respectively). The aFV in supine with external rotation was significantly larger than in supine with a neutral position (52.3° versus 47.7°, p = 0.037). The aFN in supine and external rotation was significantly larger than other postures (54.6, 38.2, and 33.0, p < 0.001, respectively). CONCLUSIONS: This radiographic study revealed that the leg position affected the neurovascular bundle location. These movements can be the risk of direct neurovascular injury or traction.

Analysis of Light Intensity and Charge Holding Time Dependence of Pinned Photodiode Full Well Capacity.

In this paper, the light intensity and charge holding time dependence of pinned photodiode (PD) full well capacity (FWC) are studied for our pixel structure with a buried overflow path under the transfer gate. The formulae for PDFWC derived from a simple analytical model show that the relation between light intensity and PDFWC is logarithmic because PDFWC is determined by the balance between the photo-generated current and overflow current under the bright condition. Furthermore, with using pulsed light before a charge holding operation in PD, the accumulated charges in PD decrease with the holding time due to the overflow current, and finally, it reaches equilibrium PDFWC. The analytical model has been successfully validated by the technology computer-aided design (TCAD) device simulation and actual device measurement.

Biological insights into systemic lupus erythematosus through an immune cell-specific transcriptome-wide association study.

OBJECTIVE: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis. METHODS: We built gene expression predictive models in blood B cells, CD4+ and CD8+ T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches. RESULTS: TWAS identified 171 genes for SLE (p<1.0×10-5); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10-8). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10-9) around CD83. For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1, and that presence of the SLE risk allele decreased ACAP1 expression. CONCLUSIONS: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations.

Combination therapy with remdesivir and immunomodulators improves respiratory status in COVID-19: A retrospective study.

Immunomodulators (tocilizumab/baricitinib) improve outcomes of coronavirus disease 2019 (COVID-19) patients, but the synergistic effect of remdesivir is unknown. The effect of combination therapy with remdesivir, immunomodulators, and standard treatment in COVID-19 patients was investigated. This retrospective, single-center study included COVID-19 patients who were treated with tocilizumab or baricitinib. The severity of respiratory status in the two groups on Days 14 and 28 and the duration to respiratory recovery in both groups were compared, and the effect of remdesivir use on respiratory status was examined in a multivariate analysis. Ninety-eight patients received tocilizumab or baricitinib; among them, 72 used remdesivir (remdesivir group) and 26 did not (control group). The remdesivir group achieved faster respiratory recovery than the control group (median 11 vs. 21 days, p = 0.033), faster weaning from supplemental oxygen (hazard ratio [HR]: 2.54, 95% confidence interval [CI]: 1.14-5.66, p = 0.021). Age, body mass index, diabetes mellitus, and time from onset to oxygen administration were independent prognostic factors. The remdesivir group achieved better severity level at Days 14 and 28 (p = 0.033 and 0.003, respectively) and greater improvement from baseline severity (p = 0.047 and 0.018, respectively). Remdesivir combination therapy did not prolong survival (HR: 0.31, 95% CI: 0.04-2.16, p = 0.23). Among severely ill COVID-19 patients who received immunomodulator, remdesivir contributed to a shorter respiratory recovery time and better respiratory status at Days 14 and 28. Concomitant remdesivir with immunomodulators and standard treatment may provide additional benefit in improving respiratory status of COVID-19 patients.

Therapeutic-Dose vs. Prophylactic-Dose Anticoagulation Therapy for Critically Ill Patients With COVID-19 in a Practice-Based Observational Study.

BACKGROUND: The potential benefit of therapeutic-dose anticoagulation for critically ill patients with coronavirus disease 2019 (COVID-19) is still controversial.Methods and Results: In the CLOT-COVID study, 225 patients with severe COVID-19 on admission requiring mechanical ventilation or extracorporeal membrane oxygenation were divided into patients with therapeutic-dose anticoagulation (N=110) and those with prophylactic-dose anticoagulation (N=115). There was no significant difference in the incidence of thrombosis between the groups (9.1% vs. 7.8%, P=0.73). CONCLUSIONS: Among a cohort of critically ill patients with COVID-19, approximately half received therapeutic-dose anticoagulation, although it did not show a potential benefit compared with prophylactic-dose anticoagulation.

Incidence, risk factors, and clinical impact of major bleeding in hospitalized patients with COVID-19: a sub-analysis of the CLOT-COVID Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. METHOD: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. RESULTS: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6-14] vs 28 [19-43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). CONCLUSIONS: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19.

Risk of bleeding associated with transbronchial biopsy using flexible bronchoscopy in patients with echocardiographic or chest CT evidence of pulmonary hypertension.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) facilitates the diagnosis of various respiratory diseases. The safety of performing EBUS-guided TBB in patients with a finding of pulmonary hypertension (PH) is controversial. Little is known about the relationship between the risk of bleeding associated with EBUS-guided TBB in the presence of PH suspected on echocardiography or chest CT. METHODS: To assess the risk of bleeding associated with EBUS-guided TBB in patients with presumed PH per echocardiography or chest CT, we retrospectively reviewed the medical records of 314 consecutive patients who underwent EBUS-guided TBB using a guide sheath (GS), as well as echocardiography and chest CT. Bleeding complication was defined as over one minute of suctioning; repeated wedging of the bronchoscope; instillation of cold saline, diluted vasoactive substances, or thrombin due to persistent bleeding. Findings of suspected PH were defined as peak tricuspid regurgitation velocity (TRV) > 2.8 m/s on echocardiography or pulmonary artery to aorta ratio (PA:A ratio) > 0.9 on chest CT. RESULTS: In total, 35 (11.1%) patients developed bleeding, and all cases were managed safely. Furthermore, 17 (5.4%) and 59 (18.8%) patients were suspected to have PH based on echocardiography and chest CT, respectively. Among the patients suspected to have PH on echocardiography, five (5/17 = 29.4%) patients developed bleeding. Among the patients suspected to have PH on chest CT, 11 (11/59 = 18.6%) patients developed bleeding. Univariate analysis revealed that long diameter (≥ 30 mm) of the lesion, lesion location (the biopsy site was inner than the segmental bronchus), bronchoscopic diagnosis of malignancy, and additional biopsy were potential predictive factors for bleeding. The finding of suspected PH on echocardiography correlated significantly with bleeding (p = 0.03). On multivariate analysis, long diameter (≥ 30 mm) of the lesion (p = .021) and findings of suspected PH on echocardiography (p = .049) were significantly associated with bleeding. CONCLUSION: All cases of bleeding in the present study were managed safely. The risk of bleeding is moderately elevated when PH is suspected by echocardiography in patients undergoing EBUS-guided TBB using a GS.

A 2-year longitudinal study of skeletal muscle mass in women over 40 years of age with degenerative lumbar scoliosis.

PURPOSE: We investigated changes in skeletal muscle mass and bone mineral density in degenerative lumbar scoliosis (DLS) patients during a 2-year follow-up following diagnosis. METHOD: This study included 418 Japanese women, identifying 50 patients for the DLS group (mean age 76.4 years) and 368 patients for the control group (mean age 73.4 years). Whole-body skeletal muscle mass was measured using a Bioelectrical Impedance Analyzer. Bone mineral density (BMD) was measured using DXA. Skin autofluorescence (SAF), a marker of advanced glycation end products in the skin, was measured using a spectroscope. Spinal alignment, skeletal muscle mass, BMD, grip strength, and SAF were examined and the amount of change 1 and 2 years from the initial examination for each item was compared between groups. RESULTS: Height, body fat mass, grip strength, upper limb muscle mass, and trunk muscle mass in the DLS group were significantly lower, and lumbar spine BMD was significantly greater compared to controls at the first visit (p < 0.05). There was no significant difference in spinal alignment in the DLS group after 2 years compared with baseline. Trunk muscle mass also decreased significantly more in the DLS group (-2.7%) than in the control group (-1.1%) over the 2-year follow-up (p < 0.05). DISCUSSION: In this study, trunk muscle mass in the DLS group decreased about 2.4 times more in 2 years compared with the control group (p < 0.05). It may be possible to clarify the mechanism of kyphoscoliosis progression in the future with large-scale longitudinal studies.

MRI T2-mapping of lumbar facet joints is effective for quantitative evaluation of lumbar instability in patients with degenerative lumbar disorders.

PURPOSES: To analyze T2 relaxation times of the facet joint by MRI T2-mapping in patients with degenerative lumbar disorders (DLD), and to determine the correlation with lumbar instability in radiographs. METHODS: We conducted a T2-mapping of the lumbar facet joint using a 1.5 T MRI system. We classified patients with degenerative lumbar disorders scheduled to undergo decompression surgery into groups with stability and instability using radiographs, and compared the T2 relaxation times of the lumbar facet. Lumbar instability was defined as the presence of anterior translation ratio > 5% or disk range of motion (ROM) > 5° in the sagittal plane of SLFE radiographs. RESULTS: Inclusion criteria were met by 22 patients (45 levels, mean age 64.3 years). Facet effusions had high sensitivity (90%) but had low specificity (28%) for diagnosis of lumbar instability. Mean T2 relaxation times of right and left facet joints are significantly longer (98.4 ms) in the instability group than they are (87.6 ms) in the stability group (p < 0.001). Anterior translation ratio was positively correlated with mean T2 relaxation times of facet joint (R2 = 0.493, p < 0.05). From a ROC analysis, the cutoff value of T2 relaxation times for lumbar instability was 98.65 ms (sensitivity 60.0%, specificity 95.7%, AUC 0.763). CONCLUSIONS: The T2 relaxation times were positively correlated with lumbar instability. This new quantitative evaluation of lumbar facet joint using MRI T2-mapping might be useful to determine lumbar instability.

Intra-articular injection of monoiodoacetate induces diverse hip osteoarthritis in rats, depending on its dose.

BACKGROUND: Monoiodoacetate (MIA)-induced arthritis models are used widely in osteoarthritis (OA) research to develop effective conservative treatments for hip OA, as an alternative to joint replacement surgery. In joint OA models, such as the MIA-induced knee OA model, various doses of MIA are utilized, depending on the purpose of the research. So far, only 2 mg of MIA has been used for MIA-induced hip OA research. We hypothesized that the amount of MIA should be adjusted according to the osteoarthritis model under investigation. We performed radiographic and histological evaluations in rats for hip OA models induced by different doses of MIA. METHODS: One hundred and eighty right hips of six-week-old, male Sprague-Dawley rats (n = 30 rats per group) were treated with either a single intra-articular injection of various doses of MIA (0.25, 0.5, 1.0, 2.0, and 4.0 mg) dissolved in 25 µl of sterile saline (MIA group), or with 25 µl of sterile saline alone (Sham group). Radiographic and histological evaluations of the hip joint were performed at one, two, four, eight, and 12 weeks after administration (n = 6 rats per group per time point). RESULTS: OA changes progressed from 1 week after administration in the 1.0-mg, 2.0-mg, and 4.0-mg MIA groups. The degree of OA changes increased as the dose of MIA increased. The 0.25-mg and 0.5-mg MIA groups presented fewer OA changes than the 2.0-mg and 4.0-mg MIA groups during the entire study period (up to 12 weeks). The administration of 0.25 mg and 0.5 mg of MIA-induced both radiographic and histological OA changes in a time-dependent manner, whereas more than 2 mg of MIA provoked end-stage OA at 8 weeks after injection. Absolute, dose-dependent histopathological OA changes were observed 4 weeks after MIA administration. CONCLUSIONS: Intra-articular MIA injection to the hip joints of rats induced diverse OA changes dose-dependently. Research for developing novel conservative treatments for hip OA and intractable pain should consider the pathological condition when determining the dose of MIA to be employed.

Analgesic effects and arthritic changes following intra-articular injection of diclofenac etalhyaluronate in a rat knee osteoarthritis model.

BACKGROUND: Diclofenac etalhyaluronate (DF-HA) is a recently developed analgesic conjugate of diclofenac and hyaluronic acid that has analgesic and anti-inflammatory effects on acute arthritis. In this study, we investigated its analgesic effect on osteoarthritis, using a rat model of monoiodoacetate (MIA). METHODS: We injected MIA into the right knees of eight 6-weeks-old male Sprague-Dawley rats. Four weeks later, rats were randomly injected with DF-HA or vehicle into the right knee. Seven weeks after the MIA injection, fluorogold (FG) and sterile saline were injected into the right knees of all the rats. We assessed hyperalgesia with weekly von Frey tests for 8 weeks after MIA administration. We took the right knee computed tomography (CT) as radiographical evaluation every 2 weeks. All rats were sacrificed 8 weeks after administration of MIA for histological evaluation of the right knee and immunohistochemical evaluation of the DRG and spinal cord. We also evaluated the number of FG-labeled calcitonin gene-related peptide (CGRP)-immunoreactive(ir) neurons in the dorsal root ganglion (DRG) and ionized calcium-binding adapter molecule 1 (Iba1)-ir microglia in the spinal cord. RESULTS: Administration of DF-HA significantly improved pain sensitivity and reduced CGRP and Iba1 expression in the DRG and spinal cord, respectively. However, computed tomography and histological evaluation of the right knee showed similar levels of joint deformity, despite DF-HA administration. CONCLUSION: DF-HA exerted analgesic effects on osteoarthritic pain, but did not affect joint deformity.