A novel endovascular method of atherectomy for calcified common femoral and popliteal disease using the crosser system: Crossbow and Rambow techniques.

OBJECTIVES: This study aims to report the efficacy and safety of new atherectomy methods using the Crosser system for calcified lesions in the common femoral and popliteal artery: the Crosser system supported by bended 0.014 wire (Crossbow) technique and retrograde approach of sheathless Crosser system supported by bended 0.014 wire (Rambow) technique. MATERIALS AND METHODS: This report describes a single-center, retrospective study. A total of 23 patients (mean ± SD age, 73 ± 10 years; 19 men) with symptomatic peripheral artery disease received the Crossbow technique and Rambow technique for treatment of calcified common femoral and popliteal disease; these patients were enrolled between October 2013 and October 2015. The primary efficacy outcome was acute technical success, defined as achievement of residual stenosis < 30% for stenting and < 50% for angioplasty or atherectomy. The primary safety outcome was assessed on the basis of angiographic complications. RESULTS: The Crossbow and Rambow techniques were undertaken in 100% and 17% of the patients, respectively. Acute technical success was achieved in 96% of the patients. There were two embolic events. CONCLUSION: Crossbow and Rambow techniques could be effective atherectomy methods of calcified common femoral and popliteal disease. Regarding safety, embolic protection devices may be needed for our atherectomy methods.

Nation-wide cohort study of remission induction therapy using rituximab in Japanese patients with antineutrophil cytoplasmic antibody-associated vasculitis: Effectiveness and safety in the first 6 months.

OBJECTIVES: The aim of this article is to evaluate the effectiveness and safety of rituximab (RTX) for microscopic polyangiitis and granulomatosis with polyangiitis in Japan. METHODS: In this prospective observational study, all patients with microscopic polyangiitis and granulomatosis with polyangiitis administered RTX were enrolled at each institution. During the observation period of 2 years, data up to 6 months were analysed. Cox proportional hazards analysis was used to assess the factors associated with an outcome. RESULTS: Of the 75 patients who received RTX for remission induction therapy, 53 achieved remission by the sixth month and 50 were in remission at the sixth month. During therapy, 38 serious adverse events were observed in 24 patients, 21 serious infections in 16 patients, and 9 patients died. No factors were associated with remission; however, there was a significant difference between patients with and without remission in serious adverse events (22.6% vs. 54.5%), serious infections (11.3% vs. 45.4%), and death (1.9% vs. 36.4%). The hazard ratio (95% confidence interval) for serious infection was 3.49 (1.29-9.74) for patients aged ≥ 75 years and 3.53 (1.31-9.53) for pulmonary complications. Four patients maintained remission for 6 months. CONCLUSIONS: The effectiveness and safety of RTX for microscopic polyangiitis and granulomatosis with polyangiitis for up to 6 months was demonstrated.

Parallel Wiring Using a Single Intravascular Ultrasound Catheter with Double Rapid Exchange Lumens Technique for Chronic Total Occlusions in Peripheral Artery Disease.

PURPOSE: To describe a parallel wiring using a single intravascular ultrasound catheter with double rapid exchange lumens (PASSABLE) technique for peripheral CTOs. TECHNIQUE: The technique is demonstrated in a 73-year-old patient with CTOs of the superficial femoral and popliteal artery. Intravascular ultrasound (IVUS) examination revealed the first guidewire was advanced to the intramedial space of the popliteal artery. Following insertion of the first guidewire into only the distal rapid exchange lumen of the IVUS catheter and a second guidewire into the proximal rapid exchange lumen, a guidewire torquer was passed over it and tightened close to an exit port of the proximal rapid exchange lumen to prevent it from exiting an entry port while advancing the IVUS catheter. The IVUS catheter was advanced to the intraplaque region using only the distal rapid exchange lumen and the second guidewire was then advanced to the intraplaque region under IVUS guidance. The IVUS-guided wiring using the second guidewire on both the distal and proximal rapid exchange lumen was continued and resulted in a successful guidewire crossing into the distal true lumen. CONCLUSION: This novel technique may prove beneficial in enabling operators to perform IVUS-guided parallel wiring more easily and efficiently.

Prediction of Technical Failure of Inframalleolar Angioplasty in Patients with Chronic Limb Threatening Ischaemia.

OBJECTIVE: This study sought to: determine anatomically evaluated predictors of the technical failure of inframalleolar angioplasty (IMA), develop a predictive model for unsuccessful IMA, and investigate the effect of IMA on clinical outcomes in patients with chronic limb threatening ischaemia (CLTI). METHODS: This single centre retrospective observational study enrolled 159 patients with CLTI who underwent IMA for de novo occluded lesions between November 2017 and May 2021. These patients were divided into two groups: the Failed IMA group (n = 62) and the Successful IMA group (n = 97). RESULTS: In multivariable analysis, no target vessel outflow (OR 39.8, 95% CI 10.7 - 148, p < .001), medial artery calcification (MAC) grade (OR 4.91, 95% CI 1.40 - 17.3, p = .010), and occluded pedal arch (OR 5.2, 95% CI 1.2 - 22.7, p = .030) were identified as independent predictors of IMA technical failure. The risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.93; after bootstrapping adjustment for optimism, this value represented a corrected AUC of 0.95. The patients in the Successful IMA group had a significantly higher proportion of wound healing at 12 months than those in the Failed IMA group (log rank p = .030). IMA technical failure was associated with a significant change in the proportion of wound healing (HR 0.59, 95% CI 0.37- 0.94, p = .030). CONCLUSION: No target vessel outflow, MAC grade, and occluded pedal arch were independent predictors of IMA technical failure. Additionally, successful IMA was associated with better wound healing outcomes at 12 months. Furthermore, a model incorporating these three predictors precisely predicted IMA technical failure.

Prediction of successful guidewire crossing of below-the-knee chronic total occlusions using a Japanese scoring system.

OBJECTIVE: To develop a scoring system that can adequately predict a successful guidewire crossing (S-GC) of below-the-knee (BTK) chronic total occlusions (CTOs) in angiographic evaluation. METHODS: A retrospective, multicenter, nonrandomized study examined 448 consecutive BTK CTOs in 299 patients treated with endovascular therapy in seven Japanese medical centers from April 2012 to April 2020. The cohort was classified into two groups: an S-GC group and a failed guidewire crossing group. RESULTS: The final logistic regression model created by a backward stepwise multivariate logistic regression model included five variables: "No outflow of the target vessel," "CTO length ≥200 mm," "Reference vessel diameter <2.0 mm," "Calcification at the proximal entry point," and "Blunt type at entry point." Optimisms were adjusted using 1000 bootstrap samples with replacement and candidate's risk score models developed according to optimism-adjusted correlation coefficients of risk factors. Choosing the best model as the Japanese-BTK (J-BTK) CTO score by comparing the optimism-adjusted area under receiver-operating characteristic curves it was decided to assign one point to "Blunt type at the proximal entry point," one point to "Calcification at the proximal entry point," one point to "Reference vessel diameter <2.0 mm," one point to "CTO length ≥200 mm," and two points to "No outflow of the target vessel." This rule was then used to categorize BTK CTOs into four grades with varying probabilities of S-GC: grade A (J-BTK CTO score of 0 and 1), grade B (score of 2 and 3), grade C (score of 4 and 5), and grade D (score of 6). Rates of S-GC in each grade (grades A, B, C, and D) were 97.3%, 76.8%, 19.3%, and 0%, respectively. Lesions categorized as grade C or D have a lower chance of S-GC. Internal validation was performed using the Hosmer-Lemeshow test (P = .99). CONCLUSIONS: The J-BTK CTO score predicts the probability of an S-GC of BTK CTOs and stratifies the difficulty of endovascular therapy for BTK CTOs in angiographic evaluation.

Clinical characteristics and social productivity levels of patients with malignant rheumatoid arthritis based on a nationwide clinical database in Japan: annual survey from 2003 to 2013.

OBJECTIVES: Malignant rheumatoid arthritis (MRA) is defined as rheumatoid arthritis (RA) with systemic vasculitis or other severe extra-articular manifestations. Japan has a nationwide database for MRA. We analyzed the characteristics of Japanese patients with MRA based on data from the Ministry of Health, Labour and Welfare (MHLW). METHODS: We were permitted to use data on 43,108 patients who were registered in the MHLW database from 2003 to 2013. RESULTS: Median age was 65 (interquartile range, 57-72) years. Patients consisted of 71% females. Proportions of patients who had or had experienced interstitial pneumonia and pleuritis were increased, episcleritis was stable, and other MRA manifestations were decreased over time. The number of positive symptoms per patient also decreased over time. The median dose of glucocorticoid, percentage of patients undergoing surgery, and use of non-steroidal anti-inflammatory drugs and apheresis decreased year by year. Steinbrocker stage and class improved over time. Median C-reactive protein levels and erythrocyte sedimentation rate also decreased. Regarding social productivity levels of patients with MRA, the proportion of patients who were working or working from home increased and the proportion of patients recuperating or hospitalized decreased. CONCLUSION: In patients with MRA, disease activity decreased and social productivity improved from 2003 to 2013.

Impact of adding tacrolimus to initial treatment of interstitial pneumonitis in polymyositis/dermatomyositis: a single-arm clinical trial.

OBJECTIVE: Interstitial pneumonia is common and has high short-term mortality in patients with PM and DM despite glucocorticoid (GC) treatment. Retrospective studies suggested that the early use of immunosuppressive drugs with GCs might improve its short-term mortality. METHODS: A multicentre, single-arm, 52-week-long clinical trial was performed to test whether the initial combination treatment with tacrolimus (0.075 mg/kg/day, adjusted for the target whole-blood trough levels between 5 and 10 ng/ml) and GCs (0.6-1.0 mg/kg/day of prednisolone followed by a slow taper) improves short-term mortality of PM/DM-interstitial pneumonia patients. The primary outcome was overall survival. We originally intended to compare, by using propensity-score matching, the outcome data of clinical trial patients with that of historical control patients who were initially treated with GCs alone. RESULTS: The 52-week survival rate with the combination treatment (N = 26) was 88.0% (95% CI, 67.3, 96.0). Safety profiles of the combination treatment were consistent with those known for tacrolimus and high-dose GCs individually. Serious adverse events occurred in 11 patients (44.0%), which included four opportunistic infections. Only 16 patients, including only 1 deceased patient, were registered as historical controls, which precluded meaningful comparative analysis against the clinical trial patients. CONCLUSION: Our study provided findings which suggest that initial treatment with tacrolimus and GCs may improve short-term mortality of PM/DM-interstitial pneumonia patients with manageable safety profiles. This was the first prospective clinical investigation conducted according to the Good Clinical Practice Guideline of the International Conference on Harmonization for the treatment of this potentially life-threatening disease. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT00504348.

Diastolic Intra-Left Ventricular Pressure Difference During Exercise: Strong Determinant and Predictor of Exercise Capacity in Patients With Heart Failure.

BACKGROUND: Although the enhancement of early-diastolic intra-left ventricular pressure difference (IVPD) during exercise is considered to maintain exercise capacity, little is known about their relationship in heart failure (HF). METHODS AND RESULTS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 50 HF patients (left ventricular [LV] ejection fraction 39 ± 15%). Echocardiographic images were obtained at rest and submaximal and peak exercise. Color M-mode Doppler images of LV inflow were used to determine IVPD. Thirty-five patients had preserved exercise capacity (peak oxygen consumption [VO2] ≥14 mL·kg-1·min-1; group 1) and 15 patients had reduced exercise capacity (group 2). During exercise, IVPD increased only in group 1 (group 1: 1.9 ± 0.9 mm Hg at rest, 4.1 ± 2.0 mm Hg at submaximum, 4.7 ± 2.1 mm Hg at peak; group 2: 1.9 ± 0.8 mm Hg at rest, 2.1 ± 0.9 mm Hg at submaximum, 2.1 ± 0.9 mm Hg at peak). Submaximal IVPD (r = 0.54) and peak IVPD (r = 0.69) were significantly correlated with peak VO2. Peak IVPD determined peak VO2 independently of LV ejection fraction. Moreover, submaximal IVPD could well predict the reduced exercise capacity. CONCLUSION: Early-diastolic IVPD during exercise was closely associated with exercise capacity in HF. In addition, submaximal IVPD could be a useful predictor of exercise capacity without peak exercise in HF patients.

Membrane protein structure determination by SAD, SIR, or SIRAS phasing in serial femtosecond crystallography using an iododetergent.

The 3D structure determination of biological macromolecules by X-ray crystallography suffers from a phase problem: to perform Fourier transformation to calculate real space density maps, both intensities and phases of structure factors are necessary; however, measured diffraction patterns give only intensities. Although serial femtosecond crystallography (SFX) using X-ray free electron lasers (XFELs) has been steadily developed since 2009, experimental phasing still remains challenging. Here, using 7.0-keV (1.771 Å) X-ray pulses from the SPring-8 Angstrom Compact Free Electron Laser (SACLA), iodine single-wavelength anomalous diffraction (SAD), single isomorphous replacement (SIR), and single isomorphous replacement with anomalous scattering (SIRAS) phasing were performed in an SFX regime for a model membrane protein bacteriorhodopsin (bR). The crystals grown in bicelles were derivatized with an iodine-labeled detergent heavy-atom additive 13a (HAD13a), which contains the magic triangle, I3C head group with three iodine atoms. The alkyl tail was essential for binding of the detergent to the surface of bR. Strong anomalous and isomorphous difference signals from HAD13a enabled successful phasing using reflections up to 2.1-Å resolution from only 3,000 and 4,000 indexed images from native and derivative crystals, respectively. When more images were merged, structure solution was possible with data truncated at 3.3-Å resolution, which is the lowest resolution among the reported cases of SFX phasing. Moreover, preliminary SFX experiment showed that HAD13a successfully derivatized the G protein-coupled A2a adenosine receptor crystallized in lipidic cubic phases. These results pave the way for de novo structure determination of membrane proteins, which often diffract poorly, even with the brightest XFEL beams.

Systematic review and meta-analysis for 2017 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVES: To provide evidence for the revision of clinical practice guideline (CPG) for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the Japan Research Committee for Intractable Vasculitis. METHODS: PubMed, CENTRAL, and the Japan Medical Abstracts Society were searched for articles published between January 1994 and January 2015 to conduct systematic review (SR), and the quality of evidence was assessed with GRADE approach. RESULTS: Nine randomized controlled trials (RCTs) and two non-RCTs were adopted for remission induction therapy, three RCTs and two non-RCTs for plasma exchange, and five RCTs and one non-RCT for remission maintenance therapy. A significant difference was found in efficacy and safety for the following comparisons. In the non-RCT adopted for remission induction therapy, glucocorticoid (GC) + cyclophosphamide (CY) was significantly superior to GC monotherapy regarding remission. GC + intravenous CY for remission induction therapy was superior to GC + oral CY regarding death at one year, serious adverse events, and serious infection. Concomitant use of plasma exchange for remission induction therapy of AAV with severe renal dysfunction reduced risk of end-stage renal disease versus non-users at month 3. CONCLUSION: This SR provided necessary evidence for developing CPG for the management of ANCA-associated vasculitis.

Left Ventricular Mass Influences Relationship Between Filling Pressure and Early-Diastolic Ratio of Inflow Velocity to Mitral Annular Velocity (E/e').

BACKGROUND: Early-diastolic mitral annular velocity (e') and the ratio of early-diastolic left ventricular (LV) inflow velocity (E) to e' (E/e') have been widely used as indexes of LV relaxation and filling pressure, respectively. However, many recent studies have demonstrated that they are not reliable in various clinical settings. We thus investigated the factors influencing these echocardiographic parameters in a multicenter study.Methods and Results:The study group comprised 69 patients, referred for cardiac catheterization, and enrolled in 5 university hospitals. Time constant (τ) and LV mean diastolic pressure (LVMDP) were measured using a micromanometer-tipped catheter. Although e' only weakly correlated with τ (r=-0.35, P<0.01), E/e' modestly correlated with LVMDP (r=0.48, P<0.001). Multivariable analysis revealed that hypertension (ß=-0.33, P<0.01) and LV ejection fraction (LVEF) (ß=0.44, P<0.001) were the independent determinants of e', and LV mass index (LVMI) (ß=0.37, P<0.001) and LVMDP (ß=0.47, P<0.001) were those of E/e'. Additionally, E/e' significantly correlated with LVMDP in patients with normal LVMI (r=0.74, P<0.001) but not in those with increased LVMI. CONCLUSIONS: The coincidence of hypertension and LVEF affected the relationship between LV relaxation and e', whereas LVMI altered the relationship between LV filling pressure and E/e'. Thus, clinical conditions associated with an increase in LVMI, such as LV hypertrophy and LV dilatation, should be considered when estimating the filling pressure from E/e'.

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Relationships of left ventricular strain and strain rate to wall stress and their afterload dependency.

Whether and how left ventricular (LV) strain and strain rate correlate with wall stress is not known. Furthermore, it is not determined whether strain or strain rate is less dependent on the afterload. In 41 healthy young adults, LV global peak strain and systolic peak strain rate in the longitudinal direction (LS and LSR, respectively) and circumferential direction (CS and CSR, respectively) were measured layer-specifically using speckle tracking echocardiography (STE) before and during a handgrip exercise. Among all the points before and during the exercise, all the STE parameters significantly correlated linearly with wall stress (LS: r = -0.53, p < 0.01, LSR: r = -0.28, p < 0.05, CS in the inner layer: r = -0.72, p < 0.01, CSR in the inner layer: r = -0.47, p < 0.01). Strain more strongly correlated with wall stress than strain rate (r = -0.53 for LS vs. r = -0.28 for LSR, p < 0.05; r = -0.72 for CS vs. r = -0.47 for CSR in the inner layer, p < 0.05), whereas the interobserver variability was similar between strain and strain rate (longitudinal 6.2 vs. 5.2 %, inner circumferential 4.8 vs. 4.7 %, mid-circumferential 7.9 vs. 6.9 %, outer circumferential 10.4 vs. 9.7 %), indicating that the differences in correlation coefficients reflect those in afterload dependency. It was thus concluded that LV strain and strain rate linearly and inversely correlated with wall stress in the longitudinal and circumferential directions, and strain more strongly depended on afterload than did strain rate. Myocardial shortening should be evaluated based on the relationships between these parameters and wall stress.

Characteristic systolic waveform of left ventricular longitudinal strain rate in patients with hypertrophic cardiomyopathy.

We analyzed the waveform of systolic strain and strain-rate curves to find a characteristic left ventricular (LV) myocardial contraction pattern in patients with hypertrophic cardiomyopathy (HCM), and evaluated the utility of these parameters for the differentiation of HCM and LV hypertrophy secondary to hypertension (HT). From global strain and strain-rate curves in the longitudinal and circumferential directions, the time from mitral valve closure to the peak strains (T-LS and T-CS, respectively) and the peak systolic strain rates (T-LSSR and T-CSSR, respectively) were measured in 34 patients with HCM, 30 patients with HT, and 25 control subjects. The systolic strain-rate waveform was classified into 3 patterns ("V", "W", and "√" pattern). In the HCM group, T-LS was prolonged, but T-LSSR was shortened; consequently, T-LSSR/T-LS ratio was distinctly lower than in the HT and control groups. The "√" pattern of longitudinal strain-rate waveform was more frequently seen in the HCM group (74 %) than in the control (4 %) and HT (20 %) groups. Similar but less distinct results were obtained in the circumferential direction. To differentiate HCM from HT, the sensitivity and specificity of the T-LSSR/T-LS ratio <0.34 and the "√"-shaped longitudinal strain-rate waveform were 85 and 63 %, and 74 and 80 %, respectively. In conclusion, in patients with HCM, a reduced T-LSSR/T-LS ratio and a characteristic "√"-shaped waveform of LV systolic strain rate was seen, especially in the longitudinal direction. The timing and waveform analyses of systolic strain rate may be useful to distinguish between HCM and HT.

Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequent good functional and structural outcomes in a real-world clinical setting under a treat-to-target strategy.

OBJECTIVE: To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T). METHODS: In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS)

Left Ventricular Global Strain for Estimating Relaxation and Filling Pressure　- A Multicenter Study.

BACKGROUND: Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure. METHODS AND RESULTS: We conducted a prospective multicenter study and compared the correlation of tissue Doppler- and STE-derived parameters with the time constant of LV pressure decay (τ) and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e´) with τ was weak (r=-0.32, P<0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e´ (E/e´) (r=0.50, P<0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e´ (P<0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e´ 0.74, E/A 0.67). CONCLUSIONS: STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e´ for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).

Myocardial shortening in 3 orthogonal directions and its transmural variation in patients with nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: Although longitudinal strain (LS) is known to be reduced in patients with hypertrophic cardiomyopathy (HCM), it has not been elucidated whether or not circumferential strain (CS) is reduced. We aimed to determine whether multidirectional and layer-specific myocardial strain is reduced in patients with nonobstructive HCM. METHODS AND RESULTS: Speckle-tracking echocardiography was performed in 41 HCM patients and 27 control subjects. Segmental and global LS and CS were measured in the inner, mid, and outer layers. Global LS was significantly lower in the HCM group than in controls in the inner (-10.3±2.9 vs. -14.8±2.0%, P<0.001), mid (-8.7±2.6 vs. -13.8±1.9%, P<0.001), and outer (-7.2±2.6 vs. -11.9±1.9%, P<0.001) layers. Global CS was preserved in the inner layer (-23.8±4.7 vs. -24.3±3.3%, P=0.69) but reduced in the mid (-10.3±3.1 vs. -13.3±2.5%, P<0.001) and outer layers (-6.7±2.3 vs. -8.6±2.3%, P=0.002). Differences in CS between the inner and outer layers correlated with segmental relative wall thickness (r=-0.20, P=0.002). Furthermore, only the absolute value of global CS in the inner layer positively correlated with left ventricular ejection fraction (r=0.32, P<0.01) among these multidirectional and layer-specific strains. CONCLUSIONS: In patients with HCM, not only the LS in all layers but also CS in the mid and outer layers was reduced, presumably reflecting impaired myocardial function. In contrast, CS in the inner layer was preserved, being associated with maintenance of chamber function.

Assessment of the Birmingham vasculitis activity score in patients with MPO-ANCA-associated vasculitis: sub-analysis from a study by the Japanese Study Group for MPO-ANCA-associated vasculitis.

OBJECTIVES: In the study cohort enrolled in a prospective open-label, multicenter trial conducted by the Japanese Study Group for MPO-ANCA-associated vasculitis (JMAAV), we conducted this sub-analysis to establish the validity of the Birminghan vasculitis activity score (BVAS) for Japanese patients with MPO-ANCA-associated vasculitis. METHODS: We recorded the BVAS at the time of diagnosis, at 6 weeks after the diagnosis, and at 3, 6, 9, 12, 15 and 18 months after the diagnosis in this study. RESULTS: The most frequently involved organs in the patients were the lungs, kidneys and the nervous system. The kidney (BVAS; new/worse 69.2 %, persistent 40.4 %), general (BVAS; new/worse 67.3 %, persistent 53.8 %), chest (BVAS; new/worse 36.5 %, persistent 46.2 %) and nervous system (BVAS; new/worse 38.5 %, persistent 25.0 %) were the organ systems most frequently involved by the disease at the baseline. The BVAS for new/worse disease decreased immediately after induction therapy, while improvement of the BVAS for persistent disease after therapy differed among the organ systems. CONCLUSIONS: BVAS was demonstrated to be a valuable guide for selection of the optimal treatment. Thus, BVAS was also found to be a useful tool in Japanese patients for the assessment of disease activity and degree of organ damage in patients with MPO-ANCA-associated vasculitis.

Early diagnosis and treatment of steroid-induced diabetes mellitus in patients with rheumatoid arthritis and other connective tissue diseases.

PURPOSE: To reveal how often patients with rheumatoid arthritis (RA) or any of other connective tissue diseases (CTDs) who take prednisolone (PSL) manifest postprandial hyperglycemia, and to evaluate the effects of divided daily dose administration of PSL, and of acarbose and nateglinide, on RA patients. METHOD: The blood sugar (BS) levels of the patients were measured after meals. For in-patients who showed postprandial hyperglycemia, the daily dose of PSL was divided and nateglinide and/or acarbose were/was added if their BS levels did not improve sufficiently. The patients with BS levels that were well controlled for three months were compared with the patients with poorly controlled BS levels. RESULTS: The BS levels of 78 patients, including 16 patients with diabetes mellitus (DM), were measured after meals, and 27 of them were newly diagnosed with DM. Five of 14 patients who took a steady dose of PSL showed high BS levels after lunch (over 200 mg/dl) without elevated HbA1c. The combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia significantly. The period from the start of PSL administration to intervention was significantly longer in patients with good control at three months than the corresponding period in those with poor control. CONCLUSION: The prevalence of postprandial hyperglycemia was high in patients with RA/CTD taking PSL; accordingly, measurement of the BS level after each meal was valuable. Combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia.

Overexpression of T-bet gene regulates murine autoimmune arthritis.

OBJECTIVE: To clarify the role of T-bet in the pathogenesis of collagen-induced arthritis (CIA). METHODS: T-bet-transgenic (Tg) mice under the control of the CD2 promoter were generated. CIA was induced in T-bet-Tg mice and wild-type C57BL/6 (B6) mice. Levels of type II collagen (CII)-reactive T-bet and retinoic acid receptor-related orphan nuclear receptor γt (RORγt) messenger RNA expression were analyzed by real-time polymerase chain reaction. Criss-cross experiments using CD4+ T cells from B6 and T-bet-Tg mice, as well as CD11c+ splenic dendritic cells (DCs) from B6 and T-bet-Tg mice with CII were performed, and interleukin-17 (IL-17) and interferon-γ (IFNγ) in the supernatants were measured by enzyme-linked immunosorbent assay. CD4+ T cells from B6, T-bet-Tg, or T-bet-Tg/IFNγ-/- mice were cultured for Th17 cell differentiation, then the proportions of cells producing IFNγ and IL-17 were analyzed by fluorescence-activated cell sorting. RESULTS: Unlike the B6 mice, the T-bet-Tg mice did not develop CIA. T-bet-Tg mice showed overexpression of Tbx21 and down-regulation of Rorc in CII-reactive T cells. Criss-cross experiments with CD4+ T cells and splenic DCs showed a significant reduction in IL-17 production by CII-reactive CD4+ T cells in T-bet-Tg mice, even upon coculture with DCs from B6 mice, indicating dysfunction of IL-17-producing CD4+ T cells. Inhibition of Th17 cell differentiation under an in vitro condition favoring Th17 cell differentiation was observed in both T-bet-Tg mice and T-bet-Tg/IFNγ-/- mice. CONCLUSION: Overexpression of T-bet in T cells suppressed the development of autoimmune arthritis. The regulatory mechanism of arthritis might involve dysfunction of CII-reactive Th17 cell differentiation by overexpression of T-bet via IFNγ-independent pathways.