Influences of advanced age in rheumatoid arthritis: A multicentre ultrasonography cohort study.

OBJECTIVES: We aimed to evaluate the effects of age on clinical characteristics and outcomes in biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD)-naïve patients with rheumatoid arthritis (RA). METHODS: We analysed the cases of 234 Japanese b/tsDMARD-naïve RA patients who underwent b/tsDMARD treatment in a multicentre ultrasound prospective observational cohort. We compared the clinical characteristics at baseline and outcomes at 12 months between those aged ≥60 years and those <60 years. RESULTS: Compared to the <60-year-old group (n = 78), the ≥60-year-old group (n = 156) had higher inflammatory marker values and ultrasound combined scores, especially wrist joints, at baseline. Age at baseline positively correlated significantly with the ultrasound scores at baseline; however, age was not a significant variable by the multiple regression analysis. The patients treated with different MOAs in the ≥60-year-old group had comparable outcomes and multiple regression analysis revealed that mechanism of action (MOA) was not a significant contributor to the Clinical Disease Activity Index at 12 months. CONCLUSIONS: RA patients with advanced age demonstrated distinctive clinical characteristics. The MOAs were not associated with clinical outcomes and ultrasound outcomes in RA patients with advanced age.

Profile of Nagasaki Islands Study (NaIS): A Population-Based Prospective Cohort Study on Multi-disease.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow-up with them for vital status (death), migration, and occurrence of diseases such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1) -associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014-2016, secondary surveys during 2017-2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed-up; and 3,594 and 3,364 residents (aged 27-96 and 28-98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Prediction of radiographic progression during a treat-to-target strategy by the sequential application of MRI-proven bone marrow oedema and power-Doppler grade ≥2 articular synovitis in rheumatoid arthritis: Retrospective observational study.

OBJECTIVES: To investigate the appropriate timing, useful findings and combination of magnetic resonance imaging (MRI) and ultrasound (US) for predicting the radiographic progression in early rheumatoid arthritis (RA). METHODS: Forty-four active RA patients, who examined by both of MRI and US in the symptomatic wrist and finger joints, were recruited in Nagasaki University Hospital from 2010 to 2017 and treated by the treat-to-target therapeutic strategy for 1 year. MRI was evaluated by RA MRI scoring and US by Outcomes Measures in Rheumatology Clinical Trial, respectively. Plain radiographs were assessed by the Genant-modified Sharp score for the symptomatic side in the same manner as MRI and US. Radiographic progression was defined as an annual increase ≥0.75 at 1 year. Factors associated with radiographic progression were analysed. Also, the optimal combination of MRI and US at each timepoint was considered. RESULTS: Logistic regression model revealed that MRI-proven bone marrow oedema at baseline and 6 months and joint counts of power-Doppler grade ≥2 articular synovitis at 3 or 6 months were significantly associated with radiographic progression at 1 year. CONCLUSION: This study may suggest the favourable timing and combination of MRI and US at each point to predict radiographic progression in patients with early-stage RA.

Life prognosis and renal relapse after induction therapy in Japanese patients with proliferative and pure membranous lupus nephritis.

OBJECTIVE: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN). METHODS: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V. RESULTS: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN. CONCLUSIONS: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.

Comparison of the quantitative measurement of 18F-FDG PET/CT and histopathological findings in IgG4-related disease.

OBJECTIVES: To investigate the utility of 18F-FDG PET/CT in the diagnostic procedure of IgG4-related disease (IgG4-RD), we analysed the association between quantitative method of 18F-FDG PET/CT and histological findings. METHODS: Twenty-one patients with IgG4-RD in whom 18F-FDG PET/CT was performed at the time of diagnosis were enrolled. Tissue biopsy was performed at 24 sites in 21 patients. To perform quantitative analysis of 18F-FDG PET/CT imaging, the highest standardised uptake value (SUV) of the pixels (SUVmax) and the average SUV (SUVmean) within the biopsied lesion were measured. The SUVmean of the liver was also measured as a reference. RESULTS: The mean age at diagnosis was 64.6±11.9 years, and the median serum IgG4 level was 650 mg/dl. Histological findings were consistent with IgG4-RD (histopathology-positive) at 19 out of 24 sites. Although there was no significant difference in the values of SUVmax between histopathology-positive and histopathology-negative tissues, the values of SUVmean were significantly higher in the histopathology-positive tissue (4.98 and 3.54, respectively p<0.05). The values of SUVmean/liver were also higher in the histopathology-positive tissue (2.17 and 1.52, respectively p<0.05). To establish a cut-off value of SUVmean to determine which of multiple lesions should be biopsied, a ROC curve was constructed. ROC curve analysis indicated SUVmean=4.07 or SUVmean/liver=1.66 as a cut-off value. CONCLUSIONS: Our present study suggested that quantitative analysis of 18F-FDG-PET/CT imaging might be useful for selecting the biopsy site in IgG4-RD. The calculation of SUVmean, not of SUVmax, is important for evaluating IgG4-RD-related lesions in 18F-FDG PET/CT imaging.

Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan.

BACKGROUND: To evaluate the effect of treatment on serum bone biomarkers and explore whether serum bone biomarkers are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with abatacept. METHODS: We enrolled 59 RA patients treated with abatacept from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients' clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of five bone biomarkers were evaluated (dickkopf-1 [Dkk-1], sclerostin [SOST], osteocalcin [OC], osteopontin [OPN], and osteoprotegerin [OPG]) by multiplex bead assays at baseline, 3, and 6 months: the change over 6 months was defined as the Δ value. 'Power Doppler (PD) responder' was defined as a patient whose Δtotal PD score over 6 months was greater than the median change. RESULTS: Abatacept significantly improved the clinical disease activity and MSUS score over 6 months. Serum OPG was significantly elevated at 6 months after the abatacept introduction (p = 0.016). The ΔSOST and ΔOPG were significantly greater in the PD responders versus the non-PD responders (p = 0.0041 and 0.0073, respectively). The serum Dkk-1 at baseline was significantly lower in the PD responders (n = 30) vs. the non-PD responders (n = 29) (p = 0.026). A multivariate logistic regression analysis showed that the serum Dkk-1 at baseline (odds ratio 0.50, 95% confidence interval [CI] 0.23-0.91, p = 0.043) was an independent predictor of PD responder status. CONCLUSION: Serum levels of bone biomarkers may be useful for predicting RA patients' therapeutic responses to abatacept. TRIAL REGISTRATION: Name of the registry: Assessment of therapeutic responsiveness by imaging of the joints in patients with rheumatoid arthritis; A observational cohort study Trial registration number: UMIN000012524 Date of registration: 12/9/2013 URL of trial registry record: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000014657.

Methotrexate Alters the Expression of microRNA in Fibroblast-like Synovial Cells in Rheumatoid Arthritis.

We aimed to investigate the effect of methotrexate (MTX) on microRNA modulation in rheumatoid arthritis fibroblast-like synovial cells (RA-FLS). RA-FLS were treated with MTX for 48 h. We then performed miRNA array analysis to investigate differentially expressed miRNAs. Transfection with miR-877-3p precursor and inhibitor were used to investigate the functional role of miR-877-3p in RA-FLS. Gene ontology analysis was used to investigate the cellular processes involving miR-877-3p. The production of cytokines/chemokines was screened by multiplex cytokine/chemokine bead assay and confirmed by ELISA and quantitative real-time PCR. The migratory and proliferative activities of RA-FLS were analyzed by wound healing assay and MKI-67 expression. MTX treatment altered the expression of 13 miRNAs (seven were upregulated and six were downregulated). Among them, quantitative real-time PCR confirmed that miR-877-3p was upregulated in response to MTX (1.79 ± 0.46-fold, p < 0.05). The possible target genes of miR-877-3p in RA-FLS revealed by the microarray analysis were correlated with biological processes. The overexpression of miR-877-3p decreased the production of GM-CSF and CCL3, and the overexpression of miR-877-3p inhibited migratory and proliferative activity. MTX altered the miR-877-3p expression on RA-FLS, and this alteration of miR-877-3p attenuated the abundant production of cytokines/chemokines and proliferative property of RA-FLS.

Associations between handgrip strength and hypertension in relation to circulating CD34-positive cell levels among Japanese older men: a cross-sectional study.

BACKGROUND: A positive association between handgrip strength and blood pressure has been reported. Since these factors are linked to the condition of the endothelium, the activity of endothelial repair might influence the association between handgrip strength and hypertension. METHODS: A cross-sectional study was conducted with 257 Japanese men aged 60-69 years who underwent an annual health checkup. As individuals with high level of circulating CD34-positive cells might show active endothelial repair, which plays an important role in vascular homeostasis, participants were stratified by circulating CD34-positive cell levels, using the median value of this population (0.96 cells/µL) as the cutoff. RESULTS: Independent of known cardiovascular risk factors, for participants with a high CD34-positive cell, handgrip strength is significantly positively associated with hypertension (odds ratio and 95% confidence interval of hypertension for 1 standard deviation increment of handgrip strength were 1.85 (1.19, 2.88) but not for participants with a low CD34-positive cell (0.91 (0.61, 1.37)). CONCLUSION: The positive association between handgrip strength and hypertension is limited to high CD34-positive cells. This result may help clarify the role of vascular homeostasis in maintaining muscle strength.

Association between height-related polymorphism rs17081935 and reduced handgrip strength in relation to status of atherosclerosis: a cross-sectional study.

BACKGROUND: Aging is a process that increases oxidative stress. Increased oxidative stress leads to the development of atherosclerosis and mitochondrial dysfunction. Mitochondria contribute to energy production that might have a beneficial influence on maintaining muscle strength. Therefore, the height-related single nucleotide polymorphism (SNP) rs17081935, which is also reported to be associated with mitochondrial metabolism, might be associated with reduced muscle strength and this association might be affected by atherosclerosis status. To clarify those associations, a cross-sectional study of 1374 elderly Japanese individuals aged 60-89 years was conducted. METHODS: Logistic regression was used to clarify the association between rs17081935 and reduced handgrip strength. Since atherosclerosis might affect handgrip strength, participants were stratified by atherosclerosis status. Reduced handgrip strength was defined as being in the lowest quintile of handgrip strength (< 25.6 kg for men and < 16.1 kg for women). RESULTS: No significant associations were found between a minor allele of rs17081935 and reduced handgrip strength among elderly participants without atherosclerosis. A significant inverse association was observed among elderly participants with atherosclerosis. After adjusting for known cardiovascular risk factors and height, the adjusted odd ratio (OR) and 95% confidence interval (CI) for reduced handgrip strength and a minor allele of rs17081935 were 1.13 (0.86, 1.43) for elderly participants without atherosclerosis and 0.55 (0.36, 0.86) for those with atherosclerosis, respectively. CONCLUSION: A minor allele of the height-related SNP rs17081935 was significantly inversely associated with reduced handgrip strength among older individuals with atherosclerosis, but not among those without atherosclerosis.

Possible mechanisms underlying the association between human T-cell leukemia virus type 1 (HTLV-1) and hypertension in elderly Japanese population.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1) activates inflammatory cascades by activating the NF-κB pathway. The minor allele of single nucleotide polymorphism (SNP) in breast cancer suppressor BRCA1-associated protein (BRAP), which has a common etiology with HTLV-1 infection, has been reported to be positively associated with carotid atherosclerosis, but inversely associated with hypertension. Therefore, HTLV-1 infection may be inversely associated with hypertension by activating endothelial maintenance, including atherosclerosis. To clarify these associations, a cross-sectional study was conducted using 2989 Japanese individuals aged 60-99 years participating in a general health check-up. METHODS: Logistic regression models were used to clarify the association between HTLV-1 and hypertension. Platelet levels stratified analyses were also performed since platelet production, which plays a crucial role in endothelium maintenance, can be stimulated by activating the NF-κB pathway. RESULTS: HTLV-1 infection was found to be significantly inversely associated with hypertension, particularly in subjects with high platelet levels (≥ second tertiles of platelet levels); the fully adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 0.75 (0.62, 0.92) for total and 0.64 (0.50, 0.82) for high platelet levels, respectively. Further analysis of the non-hypertensive subjects demonstrated that HTLV-1 infection was significantly positively associated with atherosclerosis in subjects with the highest tertile of platelet levels (2.11 [1.15, 3.86]) but not in subjects with low platelet levels (first and second tertiles of platelet level) (0.89 [0.57, 1.39]). CONCLUSION: Asymptomatic HTLV-1 infection is inversely associated with hypertension, possibly by activating endothelial maintenance, including atherosclerosis progression.

Contributing factors of clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis patients with tightly controlled disease activity in clinical practice: a retrospective study.

OBJECTIVES: To determine whether specific parameters contribute to clinical outcomes at 1 year post-diagnosis in early rheumatoid arthritis (RA) patients under the 'treat-to-target' strategy in clinical practice. METHODS: We retrospectively analyzed 125 RA patients selected according to the following criteria; the patients' symptom duration was ≤6 months, and none had experience with DMARDs. We evaluated the patients' clinical disease activity at baseline and 1 year of treatment and the musculoskeletal ultrasound (MSUS)-detected synovitis activity at baseline. We performed an analysis to identify parameters that contribute to SDAI remission and the use of biologic/targeted synthetic (b/ts) DMARDs at 1 year post-diagnosis. RESULTS: Forty-seven patients received b/tsDMARDs therapy, and 58 patients achieved SDAI remission at 1 year post-diagnosis. Rheumatoid factor positivity, low patient's/evaluator's global assessment at baseline, and methotrexate use at 1 year post-diagnosis were associated with SDAI remission. The baseline clinical disease activity and MSUS scores were not associated with SDAI remission. Anti-cyclic citrullinated peptide antibody positivity/high titer and high swollen joint counts or the presence of severe synovial hypertrophy at baseline were associated with the use of b/tsDMARDs therapy. CONCLUSION: The value of the expected poor-prognosis factors may be diminished by intensive therapy within the 'windows of opportunity'.

Effectiveness and safety of non-tumor necrosis factor inhibitor therapy for anti-human T-cell leukemia virus type 1 antibody-positive rheumatoid arthritis.

OBJECTIVES: Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. METHODS: We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. RESULTS: A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. CONCLUSION: Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients.

Next-generation sequencing of the whole MEFV gene in Japanese patients with familial Mediterranean fever: a case-control association study.

OBJECTIVES: We aimed to identify the whole nucleotide sequence of the Mediterranean fever (MEFV) gene in familial Mediterranean fever (FMF) and reveal novel single nucleotide variants (SNVs) associated with the susceptibility of FMF. METHODS: SeqCap capturing technique followed by Illumina next-generation sequencing have been used to assess two hundred SNVs in the whole region of MEFV in 266 Japanese patients with FMF and 288 ethnically matched controls. We performed an association analysis using these SNVs to identify genetic variants that predispose to FMF. RESULTS: We identified the two most significant SNVs [rs28940578; M694I in exon 10, odds ratio (OR) = 153, p=2.47×10-21 and rs3743930; E148Q in exon 2, OR = 1.65, p<0.0005]. Stratified analysis identified rs28940578 as a risk allele in typical FMF. Haplotype AG, defined by rs401298 and rs28940578, was the most significant and prevalent among patients with typical FMF compared with controls (22.4% vs. 0%, respectively; OR = 137, p=1.44×10-31). Haplotype GTC, defined by rs11466018, rs224231, and rs401877, was the most significant among patients with typical FMF without the rs28940578 mutation compared with controls (15.9% vs. 6%, respectively; OR = 12.4, p=0.004). CONCLUSIONS: rs28940578 is associated with the highest risk in typical FMF cases. This is consistent with results from previous studies in Japan. We found a novel MEFV gene haplotype that confers susceptibility of FMF among typical FMF without the rs28940578 mutation. There were no relevant SNVs identified in MEFV among the atypical FMF group.

Rheumatoid arthritis patients with low baseline Health Assessment Questionnaire scores have a risk of functional disability progression: a post hoc analysis of a nationwide longitudinal cohort in Japan.

OBJECTIVES: To determine prognostic factors for the Health Assessment Questionnaire-Disability Index (HAQ-DI) progression in patients with rheumatoid arthritis (RA) in clinical practice. METHODS: We evaluated 388 biological disease-modifying anti-rheumatic drug (bDMARD)-naïve Japanese patients with RA with moderate to high disease activity at study entry after being treated with conventional synthetic DMARDs. These patients were treated according to a treat-to-target (T2T) strategy for one year. The Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) and the HAQ-DI were assessed every three months. We also evaluated joint destruction using a modified total Sharp score at baseline and at one year. HAQ-DI progression was defined as the yearly progression of HAQ-DI >0.1. We performed a multiple logistic regression analysis to explore the factors predicting HAQ-DI progression at one year. RESULTS: HAQ-DI progression was observed in 18% of the patients. The multiple logistic regression analysis revealed the independent variables associated with HAQ-DI progression were: DAS28-ESR >5.1 at baseline (odds ratio [OR] 0.31, 95% con dence interval [CI] 0.13-0.74, p=0.0083); HAQ-DI score at baseline <0.5 (OR 2.27, 95% CI 1.22-4.26, p=0.0102); and achievement of low disease activity at 12 weeks (OR 0.42, 95% CI 0.21-0.82, p=0.0112). CONCLUSIONS: Our data suggest that maintaining clinical improvement according to T2T and initiating the treatment at an early stage are important for functional improvement after one year and that patients with low baseline HAQ scores have a higher risk of HAQ disability progression.

Association between self-reported walking speed and calcaneal stiffness index in postmenopausal Japanese women.

BACKGROUND: Osteoporosis and related fractures, a worldwide public health issue of growing concern, is characterized by compromised bone strength and an increased risk of fracture. Here we show an association between self-reported walking speed and bone mass among community-dwelling postmenopausal Japanese women aged 50 years and older. DESIGN; CROSS-SECTIONAL STUDY: Setting and Participants; The survey population included 1008 postmenopausal women 50-92 years of age residing in rural communities. METHODS: Self-reported walking speed was ascertained by asking the participants: "Is your walking speed faster than others of the same age and sex?" to which participants responded "yes (faster)" or "no (moderate/slower)." Calcaneal stiffness index was measured. RESULTS: Women with a faster self-reported walking speed were younger and had a lower BMI, higher stiffness index, and higher grip strength than women with a slower walking speed. Multiple linear regression analysis adjusted for age, BMI, grip strength, comorbidity, current smoking, and alcohol drinking status showed a significant association between faster self-reported walking speed and higher calcaneal stiffness index (p <  0.001). CONCLUSIONS: Our findings suggest that questionnaires of walking speed may be useful for predicting bone mass and that a fast self-reported walking may benefit bone health in postmenopausal women.

Insulin-Like Growth Factor-1 (IGF-1) and Reduced Tongue Pressure in Relation to Atherosclerosis Among Community-Dwelling Elderly Japanese Men: A Cross-Sectional Study.

Even though higher serum insulin-like growth factor-1 (IGF-1) levels have a positive effect on preventing reduction in muscle strength, a U-shaped association between IGF-1 and mortality has been reported. Since a recent experimental study revealed that IGF-1 is associated with atherosclerotic lesion formation, the inflammatory status of atherosclerosis could act as a confounding factor on the association between IGF-1 levels and reduced muscle strength. This study aimed to clarify the atherosclerosis-specific association between IGF-1 levels and reduced muscle strength. We conducted a cross-sectional study of 410 elderly men aged 60-89 years. Since a reduction in maximum voluntary tongue pressure against the palate (MTP) is reportedly associated with sarcopenia, we evaluated muscle strength by using MTP and defined reduced MTP as the lowest tertiles of the study population. Among study population, 295 showed no atherosclerosis (carotid intima-media thickness < 1.1 mm). Even though a significant inverse association between IGF-1 and reduced MTP was observed for subjects without atherosclerosis, no such association was detected for subjects with atherosclerosis. The known cardiovascular risk-factor adjusted odds ratio (OR) of a one-standard deviation (SD) increment (28.1 ng/mL) of IGF-1 for reduced MTP was 0.69 (0.51, 0.95) for subjects without atherosclerosis and 1.93 (1.05, 3.52) for subjects with atherosclerosis. IGF-1 was found to be inversely associated with a reduced MTP among elderly men without atherosclerosis but not among those with atherosclerosis. Atherosclerosis can thus act as a powerful confounding factor on the association between IGF-1 levels and a reduced MTP.

Associations between thyroid-stimulating hormone and hypertension according to thyroid cyst status in the general population: a cross-sectional study.

BACKGROUND: The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone (TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status. METHODS: We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40-74 years who participated in an annual health checkup in 2014. RESULTS: In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = - 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = - 0.03, p = 0.525). CONCLUSIONS: TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid.

Anti-thyroid peroxidase antibody and thyroid cysts among the general Japanese population: a cross-sectional study.

BACKGROUND: Anti-thyroid peroxidase antibody (TPO-Ab) has been shown to cause autoimmune thyroiditis by inducing a deleterious influence on thyroid hormone synthesis. Further, thyroglobulin, which has an important role in thyroid hormone synthesis, is reported to be high in the fluid from thyroid cysts. Therefore, TPO-Ab could be associated with the presence of thyroid cyst, partly by affecting the activity of thyroid hormone synthesis. METHODS: To investigate the association between TPO-Ab and thyroid cysts, we conducted a cross-sectional study of 1432 Japanese with normal thyroid function [i.e., normal range of free triiodothyronine (free T3) and free thyroxine (free T4)] between the ages of 40 and 74 years, who participated in an annual health check-up. RESULTS: In men, the statistical power did not reach a statistical significance value. Additionally, subjects with TPO-Ab showed lower odds ratios (ORs) of thyroid cysts than those without TPO-Ab. In women, subjects with TPO-Ab showed significantly lower ORs of thyroid cysts than those without TPO-Ab. The fully adjusted ORs were 0.68 (0.40, 1.18) for men and 0.40 (0.27, 0.60) for women. When evaluating the association between logarithmic values of TPO-Ab titer and thyroid cysts in both men and women, a notable inverse correlation was observed. The fully adjusted ORs were 0.68 (0.50, 0.92) for men and 0.68 (0.57, 0.81) for women. CONCLUSION: TPO-Ab titer revealed to be inversely associated with thyroid cysts among Japanese with normal thyroid function. The presence of a thyroid cyst could indicate a lower risk of having TPO-Ab among the general population with normal thyroid function.

Association between high psychological distress and poor oral health-related quality of life (OHQoL) in Japanese community-dwelling people: the Nagasaki Islands Study.

BACKGROUND: We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people. METHODS: We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women) has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ≥5 points on the K6 as high psychological distress (high-K6 group). RESULTS: The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (≥ 5) was a substantial contributing factor of the GOHAI (ß = - 0.23, 95% Cl - 2.31 to -1.41, p < 0.0001). CONCLUSIONS: It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population.

Diagnostic efficacy of ultrasound detection of enthesitis in peripheral spondyloarthritis.

Objective: We investigated the diagnostic efficacy of power Doppler ultrasound (PDUS) to detect enthesitis in Japanese patients with peripheral spondyloarthritis (SpA).Methods: This was a single-center cohort study of patients with peripheral symptoms suggestive of SpA. Articular synovia, tendons, and entheses were assessed by PDUS at baseline. Clinical, laboratory, and radiologic findings and classification criteria for SpA were also evaluated.Results: 136 patients were consecutively evaluated. A definite diagnosis was obtained in 111 patients, including 72 with SpA and 39 non-SpA. Among the patients with SpA, PDUS demonstrated articular synovitis in 40 of the 72 patients (56%), tenosynovitis or peritendinitis in 48 (67%), and enthesitis in 63 (88%). Considering PDUS alone, enthesitis in at least one site was the most useful means of differentiating SpA from non-SpA (sensitivity 87.5%; specificity 82.1%; accuracy 85.6%; positive likelihood ratio 4.88). Combining that finding along with fulfillment of Amor, European Spondyloarthropathy Study Group, or Assessment of SpondyloArthritis international Society criteria for peripheral SpA increased the specificity of the diagnosis (92.5%, 92.3%, and 97.4%, respectively).Conclusion: PDUS enthesitis is useful for the diagnosis of SpA with peripheral symptoms. Combining PDUS enthesitis with established SpA classification criteria is beneficial in diagnosing peripheral SpA.