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2.
J Med Virol ; 96(5): e29653, 2024 May.
Article in English | MEDLINE | ID: mdl-38712746

ABSTRACT

The magnitude of the effect of human T-lymphotropic virus 1 (HTLV-1) infection on uveitis remains unclear. We conducted a cross-sectional study in a highly endemic area of HTLV-1 in Japan. The study included 4265 residents (men, 39.2%), mostly middle-aged and older individuals with a mean age of 69.9 years, who participated in our surveys between April 2016 and September 2022. We identified HTLV-1 carriers by screening using chemiluminescent enzyme immunoassays and confirmatory tests, and the proportion of carriers was 16.1%. Participants with uveitis were determined from the medical records of all hospitals and clinics where certified ophthalmologists practiced. We conducted logistic regression analyses in an age- and sex-adjusted model to compute the odds ratio (OR) and 95% confidence interval (CI) of uveitis according to HTLV-1 infection status. Thirty-two (0.8%) participants had uveitis. For HTLV-1 carriers, the age- and sex-adjusted OR (95% CI) of uveitis was 3.27 (1.57-6.72) compared with noncarriers. In conclusion, HTLV-1 infection was associated with a higher risk of uveitis among mostly middle-aged and older Japanese residents in a highly endemic HTLV-1 area. Our findings suggest that physicians who treat HTLV-1 carriers should assess ocular symptoms, and those who diagnose patients with uveitis should consider HTLV-1 infection.


Subject(s)
Carrier State , HTLV-I Infections , Human T-lymphotropic virus 1 , Uveitis , Humans , Female , Male , Japan/epidemiology , Uveitis/epidemiology , Uveitis/virology , HTLV-I Infections/epidemiology , Cross-Sectional Studies , Aged , Middle Aged , Prevalence , Human T-lymphotropic virus 1/isolation & purification , Carrier State/epidemiology , Carrier State/virology , Adult , Aged, 80 and over , Endemic Diseases , Young Adult
3.
Arthritis Res Ther ; 26(1): 48, 2024 02 12.
Article in English | MEDLINE | ID: mdl-38347556

ABSTRACT

BACKGROUND: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk. METHODS: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history. RESULTS: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66). CONCLUSIONS: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development.


Subject(s)
Lupus Erythematosus, Systemic , Neoplasms , Female , Humans , Adult , Middle Aged , Cohort Studies , Calcineurin Inhibitors/adverse effects , Glucocorticoids/therapeutic use , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Risk Factors , Registries , Neoplasms/chemically induced , Neoplasms/epidemiology , Severity of Illness Index
5.
J Epidemiol ; 2023 Jul 29.
Article in English | MEDLINE | ID: mdl-37517991

ABSTRACT

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.

6.
Front Immunol ; 14: 1124417, 2023.
Article in English | MEDLINE | ID: mdl-36969256

ABSTRACT

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study. Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels. Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63-77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5-59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation. Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels.


Subject(s)
Immunoglobulin G , Humans , Aged , Cohort Studies , Risk Factors
7.
Intern Med ; 62(16): 2329-2334, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-36631087

ABSTRACT

Objective The early diagnosis of rheumatoid arthritis (RA) improves disease outcomes. Using bilateral magnetic resonance imaging (MRI), we investigated whether or not tenosynovitis at the level of the metacarpophalangeal (MCP) and wrist joints, as well as non-symmetrical versus symmetrical involvement, predicts RA development in undifferentiated arthritis (UA) patients. Methods We collected the clinical and serological findings as well as bilateral gadolinium-enhanced 1.5-T MRI data of UA patients after 1 year. A multivariate logistic regression analysis was used to determine the association of tenosynovitis in UA with RA development. Ninety-one UA patients from the Nagasaki Early Arthritis Clinic who did not meet the 2010 European League Against Rheumatism/American College of Rheumatology classification criteria for RA were selected. Tenosynovitis at the MCP and wrist joints was scored according to the RA MRI scoring system. Results Of these 91 UA patients, 29 (31.9%) progressed to RA, with a median disease duration of 3 months, despite only 10.9% being positive for anti-cyclic citrullinated peptide antibody (ACPA). A univariate analysis showed higher MCP tenosynovitis scores, MCP flexor tenosynovitis, and symmetrical MCP tenosynovitis in the RA development group than in the non-development group (p<0.05). A multivariate analysis showed that symmetrical MCP tenosynovitis was independently associated with RA development after adjusting for age, gender, swollen joint count, C-reactive protein level, and ACPA positivity (odds ratio: 4.96). The presence of symmetrical MCP tenosynovitis had low sensitivity (35%) but high specificity (87%) for RA development. Conclusion MRI-detected tenosynovitis, especially symmetrical findings at the MCP joint, is predictive of RA development in a UA population with low ACPA positivity.


Subject(s)
Arthritis, Rheumatoid , Synovitis , Tenosynovitis , Humans , Disease Progression , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Tenosynovitis/diagnostic imaging , Wrist Joint/diagnostic imaging , Wrist Joint/pathology , Magnetic Resonance Imaging/methods , Synovitis/diagnosis
8.
Mod Rheumatol ; 33(4): 708-714, 2023 Jul 04.
Article in English | MEDLINE | ID: mdl-35856575

ABSTRACT

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.


Subject(s)
Arthritis, Rheumatoid , Bone Marrow Diseases , Synovitis , Humans , Bone Marrow , Disease Progression , Magnetic Resonance Imaging/methods , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Synovitis/diagnostic imaging , Synovitis/etiology , Bone Marrow Diseases/etiology , Bone Marrow Diseases/complications , Finger Joint/diagnostic imaging , Finger Joint/pathology , Wrist Joint/diagnostic imaging , Wrist Joint/pathology , Edema/diagnostic imaging , Edema/etiology
9.
Intern Med ; 62(12): 1849-1855, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-36351576

ABSTRACT

We encountered a 78-year-old Japanese man with IgG4-related sialoadenitis complicated with marked eosinophilia. We diagnosed him with IgG4-RD (related disease) with a submandibular gland tumor, serum IgG4 elevation, IgG4-positive plasma cell infiltration, and storiform fibrosis. During follow-up after total incision of the submandibular gland, the peripheral eosinophil count was markedly elevated to 29,480/µL. The differential diagnosis of severe eosinophilia without IgG4-RD was excluded. The patient exhibited a prompt response to corticosteroid therapy. His peripheral blood eosinophil count was the highest ever reported among similar cases. We also review previous cases of IgG4-RD with severe eosinophilia.


Subject(s)
Autoimmune Diseases , Eosinophilia , Immunoglobulin G4-Related Disease , Male , Humans , Aged , Immunoglobulin G4-Related Disease/complications , Immunoglobulin G4-Related Disease/diagnosis , Immunoglobulin G4-Related Disease/pathology , Autoimmune Diseases/complications , Eosinophilia/complications , Eosinophilia/diagnosis , Inflammation/complications , Immunoglobulin G
10.
Arthritis Res Ther ; 24(1): 264, 2022 12 07.
Article in English | MEDLINE | ID: mdl-36476479

ABSTRACT

BACKGROUND: This exploratory study compared the inhibition of bone erosion progression in rheumatoid arthritis (RA) patients treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) plus denosumab versus csDMARD therapy alone and investigated the effects of denosumab on bone micro-architecture and other bone-related parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: In this open-label, randomized, parallel-group study, patients with RA undergoing treatment with a csDMARD were randomly assigned (1:1) to continue csDMARD therapy alone or to continue csDMARDs with denosumab (60-mg subcutaneous injection once every 6 months) for 12 months. The primary endpoint was the change from baseline in the depth of bone erosion, measured by HR-pQCT, in the second and third metacarpal heads at 6 months after starting treatment. Exploratory endpoints were also evaluated, and adverse events (AEs) were monitored for safety. RESULTS: In total, 46 patients were enrolled, and 43 were included in the full analysis set (csDMARDs plus denosumab, N = 21; csDMARD therapy alone, N = 22). Most patients were female (88.4%), and the mean age was 65.3 years. The adjusted mean (95% confidence interval) change from baseline in the depth of bone erosion, measured by HR-pQCT, in the 2-3 metacarpal heads at 6 months was - 0.57 mm (- 1.52, 0.39 mm) in the csDMARDs plus denosumab group vs - 0.22 mm (- 0.97, 0.53 mm) in the csDMARD therapy alone group (between-group difference: - 0.35 mm [- 1.00, 0.31]; P = 0.2716). Similar results were shown for the adjusted mean between-group difference in the width and volume of bone erosion of the 2-3 metacarpal heads. Significant improvements in bone micro-architecture parameters were shown. The incidence of AEs and serious AEs was similar between the csDMARDs plus denosumab and the csDMARD therapy alone groups (AEs: 52.2% vs 56.5%; serious AEs: 4.3% vs 8.7%). CONCLUSIONS: Although the addition of denosumab to csDMARDs did not find statistically significant improvements in bone erosion after 6 months of treatment, numerical improvements in these parameters suggest that the addition of denosumab to csDMARDs may be effective in inhibiting the progression of bone erosion and improving bone micro-architecture. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry, UMIN000030575. Japan Registry for Clinical Trials, jRCTs071180018.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Aged , Female , Humans , Male , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Japan , Tomography
11.
Aging (Albany NY) ; 14(20): 8258-8269, 2022 10 21.
Article in English | MEDLINE | ID: mdl-36279393

ABSTRACT

Reactivation of Epstein-Barr virus (EBV) is associated with the etiopathogenesis of a broad spectrum of diseases. This study aimed to investigate the association between psychological distress and EBV serological reactivation among community-dwelling older people and assess the role of sex differences in this association. This population-based cross-sectional survey was conducted among individuals who underwent annual health checkups (N = 2,821; median age 72.4 years). EBV serological reactivation was defined as elevation of EBV early antigen immunoglobulin G titers, and psychological distress was defined as Kessler 6 scores ≥5. Multivariable logistic regression analysis was performed to calculate odds ratios (OR) and 95% confidence intervals (CI) for EBV serological reactivation and psychological distress. EBV serological reactivation and psychological distress were detected in 16.4% and 8.7% of participants, respectively. Women accounted for 71% (328/463) of those with EBV serological reactivation. Multivariable logistic regression analysis showed psychological distress was not significantly associated with EBV serological reactivation among all participants (OR 1.31, 95% CI: 0.95, 1.82; P = 0.102). A sex-stratified multivariable analysis showed a positive association among women (OR 1.45, 95% CI: 1.01, 2.08; P = 0.043), but no association among men. EBV serological reactivation was independently associated with psychological distress in community-dwelling older women. The sex difference in our results warrants further investigation to clarify the physiological mechanisms underlying the association.


Subject(s)
Epstein-Barr Virus Infections , Herpesvirus 4, Human , Female , Humans , Male , Aged , Epstein-Barr Virus Infections/complications , Cross-Sectional Studies , Independent Living , Antibodies, Viral , Japan/epidemiology , Immunoglobulin G
12.
Sci Rep ; 12(1): 7175, 2022 05 03.
Article in English | MEDLINE | ID: mdl-35504933

ABSTRACT

Height loss starting in middle age is reportedly significantly associated with death due to cardiovascular disease. Impaired blood flow is the main pathology in cardiovascular disease. Hematopoietic stem cells such as CD34-positive cells play an important role in maintaining the microcirculation and preventing impaired blood flow by activating endothelial repair and angiogenesis. Therefore, circulating CD34-positive cell count could be associated with height loss. To clarify the association between circulating CD34-positive cell count and height loss, we conducted a follow-up study of 363 Japanese men aged 60-69 years over 2 years. Height loss was defined as being in the highest quartile of height decrease per year. Independent of known cardiovascular risk factors, circulating CD34-positive cell count was significantly inversely associated with height loss. The fully adjusted odds ratio (OR) and 95% confidence interval (CI) of height loss for circulating CD34-positive cell count (logarithmic values) was 0.49 (0.32, 0.74). This study suggests that a lower capacity to maintain the microcirculation due to a fewer CD34-positive cells might affect height loss.


Subject(s)
Cardiovascular Diseases , Aged , Antigens, CD34 , Cell Count , Cross-Sectional Studies , Follow-Up Studies , Humans , Male , Middle Aged , Risk Factors
14.
Immunol Med ; 45(3): 168-174, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35369853

ABSTRACT

Remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE), a rheumatic disease affecting the elderly, responds well to corticosteroids; however, our RS3PE patients' corticosteroid therapy is longer than expected. Elderly-onset rheumatoid arthritis (EORA) patients are reported to be at a significantly increased risk for steroid-related side effects including cardiovascular diseases (CVDs). To clarify the complications during a 1-year follow-up in corticosteroid-treated RS3PE patients compared to EORA patients. We retrospectively analyzed the records of 47 RS3PE patients (28 men, 19 women, age 78.4 ± 7.5 years) and 46 EORA patients (10 men, 36 women; 77.0 ± 6.8 yrs) to compare the complications over a 1-year follow-up. The RS3PE and EORA groups' average initial PSL doses were 16.5 ± 7.2 mg/day and 7.3 ± 4.6 mg/day, respectively. During the 1-year follow-up after treatment, there was no significant increase in CVDs in both groups. However, infections occurred in nine RS3PE patients, which is a significantly higher incidence compared to the EORA patients with infections (n = 3). The initial PSL dose was the independent variable associated with the incidence of infection. Infections were significantly increased during elderly RS3PE patients' steroid therapy. The initial corticosteroid dose was an infection-risk factor.Key messagesInfections are increased during steroid therapy in elderly patients with RS3PE syndrome.The initial dose of corticosteroids was one of the risk factors for infections.


Subject(s)
Arthritis, Rheumatoid , Synovitis , Aged , Aged, 80 and over , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Edema/drug therapy , Edema/etiology , Female , Follow-Up Studies , Humans , Male , Retrospective Studies , Syndrome , Synovitis/drug therapy
15.
Arthritis Rheumatol ; 74(7): 1147-1158, 2022 07.
Article in English | MEDLINE | ID: mdl-35188715

ABSTRACT

OBJECTIVE: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti-citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N-linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. METHODS: Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new-onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long-term drug-free remission (DFR) during up to 16 years follow-up. RESULTS: IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. CONCLUSION: The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre-disease phase and contributes to disease development.


Subject(s)
Arthritis, Rheumatoid , Immunoglobulin G , Anti-Citrullinated Protein Antibodies , Autoantibodies , Cross-Sectional Studies , Glycosylation , Humans , Myeloblastin
17.
Int J Mol Sci ; 22(21)2021 Oct 26.
Article in English | MEDLINE | ID: mdl-34768991

ABSTRACT

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.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Fibroblasts/drug effects , Gene Expression Regulation/drug effects , Methotrexate/pharmacology , MicroRNAs/genetics , Synoviocytes/drug effects , Arthritis, Rheumatoid/genetics , Cell Proliferation/drug effects , Cells, Cultured , Down-Regulation/drug effects , Down-Regulation/genetics , Gene Expression Regulation/genetics , Humans , Synovial Membrane/drug effects , Synoviocytes/metabolism , Up-Regulation/drug effects
18.
Arthritis Res Ther ; 23(1): 260, 2021 10 15.
Article in English | MEDLINE | ID: mdl-34654467

ABSTRACT

OBJECTIVE: To identify potential biomarkers to distinguish familial Mediterranean fever (FMF) from sepsis. METHOD: We recruited 28 patients diagnosed with typical FMF (according to the Tel Hashomer criteria), 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the FMF and sepsis groups in order to identify specific molecular networks. Multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by importance and determine specific biomarkers for distinguishing FMF from sepsis. RESULTS: Fifteen of the 40 cytokines were found to be suitable for further analysis. Levels of serum granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor 2, vascular endothelial growth factor, macrophage inflammatory protein-1b, and interleukin-17 were significantly elevated, whereas tumor necrosis factor-α (TNF-α) was significantly lower in patients with FMF compared with those with sepsis. Cytokine clustering patterns differed between the two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both GM-CSF and TNF-α could distinguish FMF from sepsis with high accuracy (cut-off values for GM-CSF = 8.3 pg/mL; TNF-α = 16.3 pg/mL; sensitivity, 92.9%; specificity, 94.4%; accuracy, 93.4%). CONCLUSION: Determination of GM-CSF and TNF-α levels in combination may represent a biomarker for the differential diagnosis of FMF from sepsis, based on measurement of multiple cytokines.


Subject(s)
Familial Mediterranean Fever , Sepsis , Biomarkers , Familial Mediterranean Fever/diagnosis , Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Sepsis/diagnosis , Tumor Necrosis Factor-alpha , Vascular Endothelial Growth Factor A
19.
J Gen Fam Med ; 22(5): 271-277, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34484994

ABSTRACT

BACKGROUND: Physical frailty is related to adverse outcomes, and poor oral health has been linked to malnourishment. Subjective measures of oral health-related quality of life (OHRQoL) have been used as indicators of the oral health problems of older adults, and they have been associated with malnourishment. This study aimed to assess OHRQoL's association with physical frailty. METHODS: Cross-sectional study was conducted using data from the Nagasaki Islands Study that enrolled participants aged ≥60 years at Japanese national medical check-ups from 2014 to 2019. Physical frailty phenotype criteria were determined using the modified Fried frailty phenotype model. OHRQoL was assessed using the Geriatric Oral Health Assessment Index (GOHAI). Dentists conducted clinical dental examinations. Simple correlation and linear regression analyses were performed to investigate the associations of number of physical frailty phenotype criteria with GOHAI and other oral health indicators. RESULTS: Among 1341 participants with a mean age of 72 years, GOHAI score was significantly associated with number of physical frailty phenotype criteria (B = -0.01, 95% confidence interval: -0.02 to -0.01, p < 0.001). The association remained significant after adjustment for age, sex, body mass index, history of hypertension, history of diabetes mellitus, smoking status, Kessler-6 score, and number of remaining teeth. CONCLUSIONS: Oral health-related quality of life was associated with physical frailty in Japanese community-dwelling older adults.

20.
Arthritis Res Ther ; 23(1): 197, 2021 07 23.
Article in English | MEDLINE | ID: mdl-34301311

ABSTRACT

OBJECTIVE: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. METHODS: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. RESULTS: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, -0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. CONCLUSIONS: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Azetidines , Humans , Piperidines/adverse effects , Purines , Pyrazoles , Pyrimidines/adverse effects , Pyrroles/adverse effects , Sulfonamides , Treatment Outcome
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