Effect of isometric quadriceps exercise on local microcirculation of the infrapatellar fat pad in female patients with knee osteoarthritis.

OBJECTIVE: To elucidate the local microcirculation of the infrapatellar fat pad (IFP) in patients with knee osteoarthritis (KOA) by determining the changes in IFP hardness and hemoglobin concentration during isometric quadriceps exercise (IQE). DESIGN: In this observational cross-sectional study, patients diagnosed with bilateral KOA were included in the KOA group (30 knees), healthy older adults in the control group (20 knees), and younger adults in the young group (20 knees). Ultrasonography was performed at rest and during IQE to measure IFP hardness based on shear wave velocity. Near-infrared spectroscopy was performed to measure oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), and total hemoglobin (cHb) in the IFP before (Baseline), during (IQE task), and after IQE (Post). IFP hardness and O2Hb, HHb, and cHb concentration were analyzed using a linear mixed model for the groups and measurement points. RESULTS: During IQE, IFP hardness changes were significantly less in the KOA group than in the other groups (KOA: 95 % confidence intervals (CIs) [-0.854, 0.028]; control: 95 % CI [-0.941, -0.341]; and young: 95 % CI [-2.305, -1.706]). In the KOA group, O2Hb concentration exhibited no significant changes at Post compared with Baseline; however, significant changes were observed in the other groups (KOA: 95 % CI [-1.176, 0.423]; control: 95 % CI [-1.452, -0.276]; and young: 95 % CI [-4.062, -2.102]). CONCLUSIONS: During IQE, changes in hardness and hemoglobin concentration in the IFP were not significant in the KOA group, suggesting impaired local microcirculation of the IFP.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

2023 Japan Society of clinical oncology clinical practice guidelines update for antiemesis.

BACKGROUND: The Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis 2023 was extensively revised to reflect the latest advances in antineoplastic agents, antiemetics, and antineoplastic regimens. This update provides new evidence on the efficacy of antiemetic regimens. METHODS: Guided by the Minds Clinical Practice Guideline Development Manual of 2017, a rigorous approach was used to update the guidelines; a thorough literature search was conducted from January 1, 1990, to December 31, 2020. RESULTS: Comprehensive process resulted in the creation of 13 background questions (BQs), 12 clinical questions (CQs), and three future research questions (FQs). Moreover, the emetic risk classification was also updated. CONCLUSIONS: The primary goal of the present guidelines is to provide comprehensive information and facilitate informed decision-making, regarding antiemetic therapy, for both patients and healthcare providers.

Non-pharmacological treatments for anticipatory nausea and vomiting during chemotherapy: a systematic review and meta-analysis of the Clinical Practice Guidelines for Antiemesis 2023.

BACKGROUND: Anticipatory chemotherapy-induced nausea and vomiting (CINV) is a conditioned response influenced by the severity and duration of previous emetic responses to chemotherapy. We aimed to evaluate the efficacy of non-pharmacologic interventions for anticipatory CINV among patients with cancer. METHODS: We conducted a systematic search in databases, including PubMed, the Cochrane Library, CINAHL, and Ichushi-Web, from January 1, 1990, to December 31, 2020. Randomized controlled trials, non-randomized designs, observational studies, or case-control studies that utilized non-pharmacological therapies were included. The primary outcomes were anticipatory CINV, with an additional investigation into adverse events and the costs of therapies. The risk-of-bias for each study was assessed using the Cochrane risk-of-bias tool, and meta-analysis was performed using Revman 5.4 software. RESULTS: Of the 107 studies identified, six met the inclusion criteria. Three types of non-pharmacological treatments were identified: systematic desensitization (n = 2), hypnotherapy (n = 2), and yoga therapy (n = 2). Among them, systematic desensitization significantly improved anticipatory CINV as compared to that in the control group (nausea: risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.49-0.72, p < 0.00001; vomiting: RR = 0.54, 95% CI = 0.32-0.91, p = 0.02). However, heterogeneity in outcome measures precluded meta-analysis for hypnotherapy and yoga. Additionally, most selected studies had a high or unclear risk of bias, and adverse events were not consistently reported. CONCLUSIONS: Our findings suggest that systematic desensitization may effectively reduce anticipatory CINV. However, further research is warranted before implementation in clinical settings.

Use of accelerometry to detect varus thrust of osteoarthritic knees before and one year after high tibial osteotomy.

BACKGROUND: The purpose of this study was to determine the effects of high tibial osteotomy (HTO) on varus thrust during gait in patients with medial compartment knee osteoarthritis (KOA), and to identify factors that influence thrust before and one year after surgery. METHODS: HTO was performed in 60 KOA patients (70 knees, including 56 knees by open wedge and 14 by closed wedge). The control group comprised 28 normal, control subjects. Several parameters were evaluated before surgery and one year thereafter. Varus thrust was defined as acceleration of the thigh relative to the lower leg in the coronal plane. Knee-injury-and-osteoarthritis-outcome scores (KOOSs), knee joint angles, radiography, and mediolateral knee acceleration during free speed gait were measured and analyzed. RESULTS: One-year after HTO, KOOSs, knee extension angles, and range of knee motion were improved (p < 0.001). The hip-knee-ankle angle and joint-line-convergent angle (JLCA) had decreased (p < 0.001), and walking speed had increased (p < 0.001). Preoperatively, patient acceleration was significantly (p < 0.05) higher than that of controls, and it did not change after HTO. However, it was reduced significantly (p < 0.05) after adjusting for walking speed. Walking speed correlated significantly with acceleration preoperatively, postoperatively, and among controls. Surgical methods (open-wedge/closed-wedge HTO) and correction angle did not affect postoperative acceleration. There was a low correlation between acceleration and KOOSs (KOOSa, KOOSp), knee joint angles, or JLCA postoperatively, but no relationship was found between acceleration and these parameters in the preoperative or the control group. CONCLUSIONS: Walking speed correlated significantly with acceleration preoperatively, postoperatively, and with those of controls. Mediolateral acceleration of the thigh relative to the lower leg in patients with KOA was significantly higher than that of normal controls before surgery, and it did not change after HTO. However, after surgery it was reduced significantly after adjusting for walking speed.

Association between early immunophenotypic changes and therapeutic response of belimumab in patients with systemic lupus erythematosus.

Belimumab is a therapeutic medication that inhibits the B-cell-activating factor (BAFF) used for systemic lupus erythematosus (SLE); however, the response sometimes varies among individuals, even when patients are stratified based on general clinical characteristics. Therefore, we focused on immunological phenotypic changes with belimumab, investigated their association with subsequent clinical courses, and sought to identify relevant immunological indicators to stratify patients who would benefit from belimumab. We assessed changes in B and T cell phenotypes, as well as BAFF-related factors, such as levels of BAFF and a proliferation-inducing ligand, and expression of three BAFF receptors: BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), transmembrane activator and cyclophilin ligand interactor (TACI), in 19 patients with SLE who were treated with belimumab before and 3 months after treatment. First, to visualize patterns in complex and diverse data, we summarized B cell changes such as subsets and BAFF receptor expressions into two axes, the first and second principal components (PC1 and PC2), and characterized broad phenotypic changes by cluster analysis. Next, we evaluated whether the B cell changes represented by PC1 and PC2 were associated with other concurrent phenotypic changes, baseline factors, and treatment response at 6 months. We found that lower PC2, indicating increased BAFF-R expression and decreased percentage of naïve B cells, was associated with a subsequent therapeutic response at 6 months (odds ratio 5.3, 95% confidence interval 1.2-24, p = .031). Furthermore, higher percentages of effector memory CD3+CD4+ T cells at baseline were associated with lower PC2 and therapeutic response. Further analysis revealed that increased PC1, as reflected by increased BCMA and TACI expression and an increase in the percentage of class-switched memory B cells, was associated with both T and B cell activation. Although belimumab is a B-cell targeted therapy, it can also influence T-cell phenotypes. Thus, early B cell changes could be used to predict treatment response, and their changes could be predicted from baseline T cell phenotypes, indicating the importance of B and T cell interactions.

Optimal Dose of Intravenous Cyclophosphamide during remission induction therapy in ANCA-associated vasculitis: a retrospective cohort study of J-CANVAS.

OBJECTIVES: To identify the optimal dose of intravenous cyclophosphamide (IVCY) for induction therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We retrospectively assessed patients with AAV who received IVCY every 2-3 weeks during the remission induction phase. The associations of the IVCY dose with infection-free survival and relapse-free survival were analysed using a Cox regression model. We compared patients in three categories: very low-dose (VLD), low-dose (LD), and conventional dose (CD) (<7.5 mg/kg, 7.5-12.5 mg/kg, and >12.5 mg/kg, respectively). The non-linear association between IVCY dose and the outcomes were also evaluated. RESULTS: Of the 80 patients (median age 72 years), 12, 42, and 26 underwent the VLD, LD, and CD regimens, respectively, of whom 4, 3, and 7 developed infection or died. The adjusted hazard ratios for infection or death were 4.3 (95% confidence interval (CI) 0.94-19.8) for VLD and 5.1 (95% CI 1.21-21.3) for CD, compared with LD. We found the hazard ratio for infection or death increased when the initial IVCY dose exceeded 9 mg/kg. Relapse-free survival did not differ clearly. CONCLUSION: Low-dose IVCY (7.5-12.5 mg/kg) may result in fewer infections and similar relapse rates compared with the conventional regimen (>12.5 mg/kg).

The relationship between the effect of hand visibility on visuotactile temporal resolution and autistic traits.

Individuals with autism spectrum disorder (ASD) have atypical sensory processing, particularly when sensory stimuli are delivered from different modalities with a temporal lag of subseconds. Previous studies have suggested that individuals with ASD require a longer temporal lag to judge temporal orders of successive audiovisual stimuli than neurotypical individuals; however, it remains unclear whether a lower temporal resolution in the visuotactile domain is associated with an individual's autistic traits. In addition, a previous study demonstrated that visuotactile temporal resolution degraded when the participants saw a hand image on a display. In this study, we investigated whether the temporal resolution of the visuotactile stimuli degrades when the participant's own hand or rubber hands are visible, and whether the effect of the hand's visibility on the temporal resolution decreases according to an individual's autistic traits. We used the temporal order judgment (TOJ) of the vibrotactile stimulus delivered to the participant's index finger and an LED attached above their own hand or rubber hand. Our findings suggest that when participants could not see their hand, temporal order judgment tended to be coarser in participants with higher autistic traits. However, this tendency was not observed when they could see both their own or the rubber hands. Moreover, temporal resolution degraded when the participants could see their own hands. These results indicate that autistic traits influence the temporal resolution of visuotactile stimuli if they are delivered as external signals in TOJ.

Relationships between autistic traits, taste preference, taste perception, and eating behaviour.

Individuals with autism spectrum disorder exhibit atypical taste perception and eating behaviours. However, little is known about the effect of autistic traits on eating behaviours in the general population. This study explored the relationships between autistic traits, taste preferences, taste perceptions, and eating behaviours among Japanese population using an online questionnaire survey. The results showed significant effect of autistic traits on eating behaviours, that people with higher autistic traits tended to have higher selective eating behaviours, such as increased sensitivity to food texture and mixed flavours. Moreover, selective eating behaviours were correlated with the preference for sour taste and aftertaste sensitivity. Those results suggest that eating behaviours can be influenced by the relationship between autistic traits, taste perceptions, and taste preferences. We discuss these results in the context of previous findings, and future investigations into the possibility of solving selective eating problems in individuals with autism.

Risk of adrenal insufficiency in patients with polymyalgia rheumatica versus patients with rheumatoid arthritis: A cross-sectional study.

OBJECTIVE: To determine whether patients with polymyalgia rheumatica (PMR) are more susceptible to glucocorticoid-induced adrenal insufficiency, one of the barriers to glucocorticoid tapering strategies, compared to patients with rheumatoid arthritis (RA). METHODS: This cross-sectional study included PMR and RA patients who underwent adrenocorticotropic hormone (ACTH) tests to assess adrenal function. The eligibility criteria were as follows: previous use of prednisolone (PSL) ≥ 5 mg/day, use of PSL for six consecutive months before ACTH test, and current use of PSL at 5 mg/day or less. The association between disease type (PMR vs. RA) and insufficient adrenal response was assessed using logistic regression models. RESULTS: Twenty-six of 34 (76.5%) patients with PMR and 13 of 37 (35.1%) patients with RA had insufficient adrenal response. Compared to patients with RA, patients with PMR were more likely to have insufficient adrenal response, even after adjusting for age, sex, and PSL dose (adjusted odds ratio, 6.75; 95% confidence interval, 1.78-25.60). CONCLUSION: Patients with PMR have a higher risk of glucocorticoid-induced adrenal insufficiency than patients with RA. Assessing the adrenal function in patients with PMR will contribute to establishing a more appropriate glucocorticoid reduction strategy.

CG223, a novel BET inhibitor, exerts TGF-ß1-mediated antifibrotic effects in a murine model of bleomycin-induced pulmonary fibrosis.

Pulmonary fibrosis is a progressive disease with poor prognosis and limited therapeutic options. In this study, we evaluated the potential therapeutic effects of CG223, a novel inhibitor of bromodomain and extra-terminal motif (BET) proteins, on pulmonary fibrosis by focusing on the transforming growth factor-ß1 (TGF-ß1) pathway. In a murine model of bleomycin-induced pulmonary fibrosis, CG223 attenuated fibrosis while reducing the infiltration of inflammatory cells into the lungs. Fibroblasts expressing BRD4, a member of the BET protein family, were enriched in the tissue regions corresponding to bleomycin-induced fibrotic lesions. Additionally, pulmonary fibroblasts isolated from bleomycin-instilled mice showed a significantly increased association of BRD4 with the promoters of two pro-fibrotic genes linked to the entry into the TGF-ß1 autocrine/paracrine loop, thrombospondin 1 (Thbs1) and integrin ß3 (Itgb3), as well as with the promoter of a myofibroblast marker gene, actin alpha 2 (Acta2). Subsequent in vitro studies with murine primary lung fibroblasts showed that the mRNA induction of Thbs1, Itgb3, and Acta2 by TGF-ß1 can be inhibited by CG223 in a dose-dependent manner. Taken together, CG223-induced BRD4 inhibition suppressed lung fibrogenesis by affecting multiple genes, including those involved in the triggering of the TGF-ß1 autocrine/paracrine loop.

Optimizing antiemetic treatment for chemotherapy-induced nausea and vomiting in Japan: Update summary of the 2015 Japan Society of Clinical Oncology Clinical Practice Guidelines for Antiemesis.

Patients with cancer should appropriately receive antiemetic therapies against chemotherapy-induced nausea and vomiting (CINV). Antiemetic guidelines play an important role in managing CINV. Accordingly, the first Japanese antiemetic guideline published in 2010 by the Japan Society of Clinical Oncology (JSCO) has considerably aided Japanese medical staff in providing antiemetic therapies across chemotherapy clinics. With the yearly advancements in antiemetic therapies, the Japanese antiemetic guidelines require revisions according to published evidence regarding antiemetic management worldwide. A revised version of the first antiemetic guideline that considered several upcoming evidences had been published online in 2014 (version 1.2), in which several updated descriptions were included. The 2015 JSCO clinical practice guideline for antiemesis (version 2.0) (in Japanese) has addressed clinical antiemetic concerns and includes four major revisions regarding (1) changes in emetogenic risk categorization for anti-cancer agents, (2) olanzapine usage as an antiemetic drug, (3) the steroid-sparing method, and (4) adverse drug reactions of antiemetic agents. We herein present an English update summary for the 2015 JSCO clinical practice guideline for antiemesis (version 2.0).

Can the loco-check be used as a self-check tool for evaluating fall risk among older subjects? A prospective study.

BACKGROUND: Japan has now become a super-aged society. Notably, as the Japanese society ages, the prevalence of falls, which represent an aging-related problem, has increased. Locomotive syndrome (LS) is a condition of decreased mobility due to locomotive organ disorder. The loco-check is simple tool to detect early-stage LS. The loco-check comprises seven items relating to daily activities. Higher numbers of affirmative answers in the loco-check are negatively associated with physical functions. The purpose of this study was to examine the potential correlation between the number of affirmative answers given on the "loco-check" survey and the likelihood of experiencing at least one fall during the following one-year period. METHODS: This prospective study included 154 cases (35 men, 119 women), all aged 65 years or older, answered the loco-check at baseline. As part of their normal treatment process, the participants made monthly visits to the out-patient department; thus, at each of these visits for the following 12 months a medical doctor interviewed each patient to determine whether they had experienced a fall during the previous month. RESULTS: The mean age of the sample was 77.3 years, and the median number of affirmative answers given was 2.0. The number of affirmative answers significantly correlated with the cases which had a fall event within the follow-up period. Specifically, an increase in one "yes" answer on the loco-check increased the relative risk of fall (odds ratio: 1.32; 95% Confidence interval (CI): 1.03-1.70). In addition, the risk of fall was high in cases which showed the number of affirmative answers given on the loco-check ≥4 (odds ratio: 9.26; 95% CI: 1.05-81.7). CONCLUSION: The number of affirmative answers given on the loco-check is positively correlated with a fall event within the following year.

CD163-positive macrophage infiltration predicts systemic involvement in sarcoidosis.

BACKGROUND: Sarcoidosis is a chronic and systemic inflammatory disease, in which patients present with noncaseating epithelioid granulomas. Cutaneous lesions of sarcoidosis develop in 9% to 35% of all sarcoidosis patients and comprise various clinical subtypes. It usually affects multiple organs and has a variable clinical course; this is called systemic sarcoidosis (SS). However, occasionally, it only affects the skin and is then called cutaneous sarcoidosis (CS). Recent observations suggest that serum levels of soluble CD163 correlate with immune cell activity in sarcoidosis patients; however, the contribution of M1 and M2 macrophages toward disease progression remains unclear. METHODS: We evaluated macrophage phenotypes histopathologically using skin biopsy samples obtained from patients with CS (n = 8) and SS (n = 31) and performed immunostaining with CD68, iNOS (M1 macrophages), PD-L1, and CD163 (M2 macrophages). RESULTS: The density of CD163-positive cells in the SS group was significantly higher than that in the CS group. There was no significant correlation between the CD163 (+) cell density and serum angiotensin-converting enzyme level, serum calcium, or tuberculin reaction. CONCLUSIONS: Immunostaining for CD163 may be a novel and useful marker to predict systemic involvement in patients with cutaneous lesions of epithelioid granulomas.

Risk factors for cytomegalovirus disease with cytomegalovirus re-activation in patients with rheumatic disease.

Objective: To assess risk factors for cytomegalovirus (CMV) disease with CMV re-activation in patients with rheumatic disease.Methods: The clinical data of consecutive patients with rheumatic disease who experienced CMV re-activation were examined. We evaluated the difference in various baseline factors at the first detection of CMV pp65 antigenemia on the development of CMV disease using logistic regression models. The changes of laboratory data in the 4 weeks before CMV re-activation were also assessed.Results: We identified 80 patients (median age [interquartile range] = 65.0 years [51.5-74.0]) with CMV re-activation. Oral candidiasis, serum albumin ≤30 g/L, and CMV pp65-positive cell count >5.6/105 polymorphonuclear leukocyte cells were found to be associated with CMV disease (odds ratio [OR] [95% CI] = 9.99 [2.02-49.50], 11.4 [1.94-67.40] and 6.80 [1.63-28.30], respectively). Moreover, decreases in serum albumin level and blood lymphocyte count in the 4 weeks before CMV re-activation also predicted CMV disease (OR [95% CI] = 2.02 [1.07-3.8] and 1.96 [1.09-3.54], respectively).Conclusion: In CMV re-activation patients with rheumatic disease, the presence of oral candidiasis, high CMV pp65 positive cell count, and hypoalbuminemia are possible risk factors for CMV disease.

Association between preexisting lung involvements and the risk of diffuse alveolar hemorrhage in patients with microscopic polyangiitis: A multi-center retrospective cohort study.

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.

Effectiveness and safety of chronic hepatitis C treatment with direct-acting antivirals in patients with rheumatic diseases: A case-series.

Objectives: To assess the effectiveness and safety of interferon-free direct-acting antiviral (DAA) therapy for patients with concomitant hepatitis C virus (HCV) infection and rheumatic diseases (RDs), including rheumatoid arthritis (RA).Methods: This was a single-center observational case-series study conducted in Japan from 2014 to 2018. The primary endpoint was the sustained virological response (SVR) rate 24 weeks after the end of therapy (EoT24). We also evaluated hepatological and rheumatological outcomes and adverse events.Results: Of the 2314 patients with RDs, 18 received DAA therapy (RA = 11, other RDs = 7). The SVR rate for the initial DAA therapy was 89% (16/18). The remaining two achieved SVR with secondary DAA therapy. Along with HCV elimination, hepatological parameters improved significantly from baseline to EoT24. During the study period, no patients newly developed cirrhosis or HCC after HCV elimination. Several patients showed improvement in RDs activity. In RA patients, the simplified disease activity index decreased significantly from baseline to EoT24 (median [interquartile range]: 11.53 [5.14-14.89] vs. 4.06 [2.08-9.05], respectively). On-treatment adverse events were minimal, while two patients experienced tuberculosis reactivation after EoT.Conclusion: DAA therapy was effective and safe, providing hepatological and rheumatological benefits in HCV-infected patients with RDs. Immune reconstitution following HCV elimination should be noted.

Utility of Coagulation Markers for the Prediction of Rapidly Progressive Interstitial Lung Disease in Patients with Dermatomyositis.

We aimed to evaluate the utility of coagulation markers for the prediction of rapidly progressive interstitial lung disease (RP-ILD) in patients with dermatomyositis (DM). In this retrospective study, 29 patients with DM-associated ILD were analyzed. The number of patients with RP-ILD was 15 (52%). The baseline clinical and demographic data and laboratory markers were analyzed to identify predictive factors for RP-ILD.The univariate logistic regression analysis demonstrated that in addition to well-known laboratory markers, such as serum ferritin, KL-6, and lymphocyte counts, a prolonged activated partial thromboplastin time (aPTT) ratio at the time of DM-associated ILD diagnosis was useful for predicting RP-ILD. Moreover, the logistic regression model and receiver operating characteristic curve analysis showed that combinations of the aPTT ratio and well-known laboratory markers were significantly effective in predicting RP-ILD. This study suggested that an association between RP-ILD and the coagulation system exists.

Roles of high-mobility group box 1 and thrombin in murine pulmonary fibrosis and the therapeutic potential of thrombomodulin.

Cross talk between inflammation and coagulation plays important roles in acute or subacute progressive pulmonary fibrosis characterized by diffuse alveolar damage. Thrombomodulin is a physiological inhibitor of high-mobility group box 1 (HMGB1), and thrombin and may be effective for this condition. This study investigated the roles of HMGB1 and thrombin in the pathophysiology of bleomycin-induced pulmonary fibrosis and the efficacy of recombinant human soluble thrombomodulin (rhTM). Pulmonary fibrosis was induced in wild-type C57BL/6 mice by intratracheal instillation of bleomycin. We first assessed HMGB1, thrombin, transforming growth factor (TGF)-ß1, and α-smooth muscle actin (SMA) levels in bronchoalveolar lavage fluid and lung tissue sections over time. Expression of HMGB1 and thrombin was elevated before that of TGF-ß1 and α-SMA and remained high during the fibrotic phase after bleomycin instillation. We next examined whether in vitro stimulation with HMGB1 and thrombin induced expression of TGF-ß1 and α-SMA in cultured alveolar macrophages and lung fibroblasts, respectively, by performing quantitative PCR, enzyme-linked immunosorbent assay, Western blot, and immunofluorescence analyses. HMGB1 and thrombin stimulation induced TGF-ß1 production by alveolar macrophages, and thrombin stimulation also induced α-SMA expression in lung fibroblasts. Finally, we evaluated the effect of rhTM on bleomycin-induced pulmonary fibrosis. Compared with the vehicle control, both early and late-phase administration of rhTM suppressed the fibrotic process. Our results suggest that HMGB1 and thrombin were involved in the pathophysiology of pulmonary fibrosis via production of profibrotic proteins and that rhTM attenuated bleomycin-induced pulmonary fibrosis. rhTM may be a therapeutic option for acute or subacute pulmonary fibrosis.

The Rubber Tail Illusion as Evidence of Body Ownership in Mice.

The ownership of one's body parts represents a fundamental aspect of self-consciousness. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it is unclear whether nonprimate mammals experience similar feelings. Therefore, the present study used rubber tails to investigate body ownership in rodents. When the real tails and rubber tails were synchronously stroked, the mice responded as if their own tails were touched when the rubber tails were grasped. In contrast, when the stimuli were delivered asynchronously, there was a significantly lower mean response rate when the rubber tail was grasped. These findings suggest that mice may experience body ownership of their tails, suggestive of the rubber hand illusion in humans. SIGNIFICANCE STATEMENT: To explore the manner in which the ownership of body parts is experienced, this study specifically used the rubber hand illusion (RHI), in which self-consciousness can be extended out of one's own body. Accumulating empirical evidence supports the existence of this concept in humans and nonhuman primates, but it remains unclear whether nonprimate mammals experience similar feelings. This study demonstrated for the first time that mice may experience body ownership of their tails, which is suggestive of the RHI in humans and provides evidence that may highlight how humans experience the ownership of body parts.