Shuntaro Sato

Association of distinct clinical subsets with myositis-specific autoantibodies towards anti-155/140-kDa polypeptides, anti-140-kDa polypeptides, and anti-aminoacyl tRNA synthetases in Japanese patients with dermatomyositis: a single-centre, cross-sectional study.

Objective: To determine the association of distinct clinical subsets with myositis‐specific autoantibodies (MSAs) towards anti‐155/140‐kDa polypeptides [anti‐155/140 antibodies (Abs)], anti‐140‐kDa polypeptides (anti‐140 Abs), and anti‐aminoacyl tRNA synthetases (ARS Abs) in Japanese patients with dermatomyositis (DM). Methods: We compared the clinical features and short‐term prognoses of 30 DM patients whose serological status included these MSAs. The MSAs were determined by immunoprecipitation. Results: Anti‐155/140 Abs (n = 5), anti‐140 Abs (n = 8), and anti‐ARS Abs (n = 7) did not overlap each other. All of the anti‐155/140 Ab‐positive patients (n = 5) were complicated by malignancies, as were all of the anti‐140 Ab‐positive patients (n = 8), who showed rapidly progressive interstitial lung disease (ILD). The survival rate at 6 months from the diagnosis of DM was significantly lower in the anti‐140 Ab‐positive patients than in the other patients. Conclusion: This is the first study to report, in a single cohort of DM patients, that distinct clinical subsets are distributed in an anti‐155/140 Ab‐positive group, an anti‐140 Ab‐positive group, or an anti‐ARS Ab‐positive group. Our data also confirm previous evidence that anti‐155/140 Abs are involved in malignancies and that anti‐140 Abs are involved in rapidly progressive ILD.

Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever

AbstractThe precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients.We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in “attack” or “remission” was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine.Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines’ serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%).Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks.

Total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer: Comparative analysis after propensity score matching: A multicenter study

BACKGROUND In patients with papillary thyroid carcinoma (PTC), the role of total thyroidectomy (TT) versus that of thyroid lobectomy (TL) has been controversial. METHODS This retrospective study was approved by our institutional review board, and the requirement to obtain informed consent was waived. In total, 173 patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by curative surgery from 1994 to 2008 were evaluated. Clinicopathologic features and adverse events were compared between patients who underwent TT and those who underwent TL. After adjustment for differences in baseline clinicopathologic factors using propensity score matching, we compared recurrence-free survival (RFS) and OS. RESULTS TL was performed in 120 patients and TT in 53 patients. Patients who underwent TT were older; had larger tumors; more frequently had nodal metastasis, multifocal tumors, and extracapsular invasion; and more frequently underwent radioactive iodine ablation than patients who underwent TL. Hypocalcemia requiring medication and recurrent laryngeal nerve paralysis were more frequent in TT than TL. The 10-year RFS and OS of all patients were 93.3% and 96.7%, respectively. There was no significant difference in RFS (90.6% vs 93.0% in TT and TL groups, respectively) or OS (96.2% vs 96.9% in TT and TL groups, respectively) according to the extent of surgical resection after propensity score matching. CONCLUSION Equivalent prognoses were observed for patients with 1- to 5-cm stage cN0 and cM0 PTC tumors treated by TL or TT after propensity score matching. Adverse events occurred less frequently in patients who underwent TL than TT.

Salivary gland ultrasonography as a primary imaging tool for predicting efficacy of xerostomia treatment in patients with Sjögren’s syndrome

OBJECTIVE To evaluate ultrasonography (US) grading of salivary gland disease as a predictor of treatment efficacy for impaired salivary function in xerostomia patients with or without Sjögrens syndrome (SS). METHODS We retrospectively analysed the prognostic importance of salivary US grading in 317 patients (168 with SS and 149 without SS). US images of the parotid and submandibular glands in each patient were individually categorized into grades 0-4 based on the extent of damage to the gland; and the sum total grade of the two gland types on either side was assigned a US score of 0-8 for each patient. The relative importance of US score and demographic and clinical variables was assessed using stepwise multiple regression analysis after various durations of xerostomia treatment. RESULTS Multiple regression analysis indicated that the baseline US score before treatment was the most important factor [standardized regression coefficient (β) = -0.523, t-statistic (t) = -7.967, P < 0.001] in predicting negative outcomes in SS patients. Treatment duration (β = 0.277, t = 4.225, P < 0.001) was also a significant but less important positive variable. On the other hand, US grading did not effectively predict treatment outcomes in non-SS patients, with treatment duration (β = 0.199, t = 2.486, P = 0.014) and baseline salivary flow rate before treatment (β = -0.172, t = -2.159, P = 0.032) being significant but weak predictors of positive and negative outcome, respectively. CONCLUSION Salivary gland US grading may help to predict outcomes of treatment for impaired salivary function in patients with SS.

Antineutrophilic cytoplasmic antibody-associated vasculitis with hypocomplementemia has a higher incidence of serious organ damage and a poor prognosis.

Abstract A relationship between antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and complement has been shown, and complement has an important role in the pathogenesis of AAV. The clinical characteristics of AAV with hypocomplementemia still remain unclear. We conducted an observational study of 81 patients with AAV (median onset age 71 years; 58% female). Using medical records, we analyzed the patients’ baseline variables, laboratory data, clinical symptoms, and therapeutic outcomes after treatments including episodes of relapses, initiation of dialysis, and death. We defined hypocomplementemia as the state in which at least one of the following was lower than the lower limit of the normal range: complement 3 (C3), complement 4 (C4), and total complement activity (CH50). Sixteen patients (20%) had hypocomplementemia at their diagnosis of AAV. Compared to the AAV patients without hypocomplementemia (n = 65), those with hypocomplementemia had significantly higher rates of the occurrence of skin lesions (8 [50%] vs. 8 [12%], P = 0.002), diffuse alveolar hemorrhage (DAH) (6 [38%] vs. 5 [8%], P = 0.006), and thrombotic microangiopathy (TMA) (3 [19%] vs. 0 [0%], P = 0.007). The AAV patients with hypocomplementemia had significantly lower platelet levels (16.5 × 104 vs. 24.9 × 104 cells/&mgr;L, P = 0.023) compared to those without hypocomplementemia. More positive immune complex deposits in renal biopsy specimens were seen in the AAV patients with hypocomplementemia than in those without hypocomplementemia (4 [80%] vs. 2 [18%], P = 0.036). Assessed by a log-rank test, hypocomplementemia at disease onset was significantly associated with death (P = 0.033). Hypocomplementemia in AAV at the disease onset was a risk factor for the serious organ damage, and a life prognostic factor. It is thus very important to pay attention to the levels of complement at the diagnosis of AAV.

Soluble α-klotho is a potential biomarker associated with neuropsychiatric systemic lupus erythematosus.

A reduced level of the single-pass transmembrane protein α-Klotho is known to be associated with neuronal damage. We investigated whether α-Klotho in cerebrospinal fluid (CSF) could be a candidate marker for the diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE). We analyzed the laboratory data, symptoms and radiological image findings of 34 NPSLE patients. Patients with SLE without neuropsychiatric manifestations (SLE) (n=25), and patients with viral meningitis (VM) (n=19), multiple sclerosis (MS) (n=20) or neuromyelitis optica (NMO) (n=20) were included as controls. The multivariable analyses revealed that lower CSF α-Klotho level, lower serum anti-Smith antibodies (U/mL) and higher serum C3 (mg/dL) were significant factors for predicting NPSLE. The CSF α-Klotho levels of the NPSLE patients were inversely correlated with the level of granulocyte/macrophage-colony stimulating factor. Our data suggested that the determination of CSF α-Klotho levels will contribute to the diagnosis of NPSLE and help elucidate the mechanisms underlying this disease.

Whole-slide imaging at primary pathological diagnosis: Validation of whole-slide imaging-based primary pathological diagnosis at twelve Japanese academic institutes: Validating whole-slide imaging in Japan

Several reports have demonstrated the use of whole‐slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy‐ and WSI‐based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI‐ and microscopy‐based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy‐based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI‐based primary diagnosis of biopsies and small surgeries in routine daily practice.

Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice: A Japanese Multicenter, Prospective Longitudinal Cohort Study for Achieving a Treat-to-Target Strategy

AbstractTo determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice.We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis.CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01–1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17–2.59), RA typical erosion at baseline (95%CI 1.56–21.1), and the introduction of bDMARDs (95%CI 0.06–0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years.We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients’ disease durations.

Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan

Objectives To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) achieving remission or low disease activity (LDA) in clinical practice. Methods Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD)-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs). CRRP was defined as the yearly progression of modified total Sharp score (mTSS) >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for predicting CRRP. Results The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA) positivity at baseline (OR = 15.2, 95%CI 2.64–299), time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03–3.45), and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06–1.42). Conclusions ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

Frequency of cerebral infarction after pulmonary resection: a multicenter, retrospective study in Japan

Cerebral infarction is a relatively rare complication of thoracic surgery, generally related to risk factors such as hypertension, hyperlipidemia, and a history of vascular diseases including cerebral infarction and ischemic heart disease [1, 2]. As even older patients can be candidates for pulmonary surgery now, if they have an acceptable performance status, the number of pulmonary resections being performed for elderly patients is increasing [3]. Accordingly, the frequency of cerebral infarction is also increasing. On the other hand, some reports have noted that there may be a relationship between the type of pulmonary resection and postoperative cerebral infarction. Regardless of the cause, it is necessary to quantify the incidence of cerebral infarction after pulmonary resection. Data from patients with cerebral infarction after pulmonary resection and the total number of all types of pulmonary resection for malignant diseases; namely, pneumonectomy, lobectomy, segmentectomy, and partial resection by standard thoracotomy or video-assisted thoracoscopic surgery (VATS), were collected, retrospectively, from 188 institutes belonging to the Japanese Association for Chest Surgery, from January, 2004 to December, 2013. Ethical approval for the present study was obtained from the institutional review boards of each institution (Approval number, 14062386-2). The total number of pulmonary resections for malignant diseases was 129,394, with 1124 cases of cerebral infarction after pulmonary resection; therefore, the rate of postoperative cerebral infarction was 0.868%. These included patients with early and late-onset cerebral infarction and those with risk factors for cerebral infarction. The data showed that the number of cerebral infarctions has increased from that documented in previous reports [1, 2]. The reasons for this increasing trend may be correlated, in part, to the growing number of elderly patients, who inherently present with higher risk factors for infarction, as well as the longer survival after surgery. However, the rate of All authors are in: Committee for Patient Safety and Quality Management of Japanese Association for Chest Surgery.