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ObjectivePatients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE).MethodsThis was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one’s physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit.ResultsA total of 362 patients with SLE were included. Trust in one’s physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference −6.88, 95% CI −11.72 to −2.04, respectively). Longer internet use was associated with both higher communicative and critical HL.ConclusionThe findings suggest that rheumatologists need to improve their communication to match each patient’s HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.

ObjectiveProviding appropriate health information to patients with systemic lupus erythematosus (SLE) is advantageous in the treatment decision-making process. We aimed to investigate how online health information-seeking behavior affects shared decision-making (SDM) in patients with SLE.MethodsThis cross-sectional study included 464 patients with SLE from five institutions. The main exposure was time spent on the Internet per day, which was divided into four categories (none, ResultsCompared with no Internet use, longer internet use was associated with a higher SDM-Q-9 score: ConclusionsThe present study suggests that SDM between physicians and patients is positively (rather than adversely) associated with online information-seeking behavior, with no negative influence associated with accessing the Internet prior to visits to a rheumatologist. Rheumatologists may need to introduce their patients to websites offering high-quality health information to establish a productive physician–patient relationship for SDM.

Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL among patients with systemic lupus erythematosus (SLE).This was a cross-sectional study using baseline data from the TRUMPA total of 362 SLE patients were included. Trust in one's physician increased with higher functional and communicative HL (per 1-pt increase, 3.21 [95%CI 0.61, 5.81], 5.8 [95%CI 1.96, 9.63]). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-pt increase, 7.01 [95%CI 2.27, 11.76], -6.83 [95%CI -11.67, -1.99]). Longer internet use was associated with both higher communicative and critical HL.The findings suggest that rheumatologists need to improve their communication to match each patient's health literacy, which may foster trust and lead to improved self-management and outcome in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust.

ObjectivePoor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one’s physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians.MethodsThis cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one’s physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications.ResultsAltogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one’s physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence.ConclusionsThis study demonstrated that patients’ health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE.

Objectives Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE. Methods This cross-sectional study was conducted at five referral hospitals. The main exposure was ‘consistency of interest’ and ‘perseverance of effort’ of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians’ grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders. Results The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9–3.6), 3.3 (2.8–3.8) and 3.3 (3.0–3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question ‘I often set a goal but later choose to pursue a different one’ was significantly higher in patients achieving LLDAS. Conclusions Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE.

ObjectivesPoor medication adherence among patients with systemic lupus erythematosus (SLE) is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one’s physician and goal-oriented thinking, hope, and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians.MethodsThis cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centers. Patients with SLE who were prescribed oral medications were included. The main exposure was trust in one’s physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. The outcome was medication adherence measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects, and concerns regarding lupus medications.ResultsAltogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years, and among them, 329 (88.2%) were women. Both trust in one’s physician (per 10-point increase: 0.88, 95% confidence interval [95%CI]: 0.53 to 1.24) and the Health-related Hope score (per 10-point increase: 0.64, 95%CI: 0.33 to 0.95) were associated with better medication adherence.ConclusionsPhysician communication to build trust and coaching on self-management to maintain or achieve what is important in the patient’s life and to enhance hope may lead to better medication adherence.Key messagesWhat is already known on this topicThe possible association of loss of trust in the attending physician with medication adherence in systemic lupus erythematosus has been conflicting in previous research, in which the effect of physician–patient racial mismatch has not been considered. The protective role of hope and goal-oriented thinking for mental symptoms has been suggested among patients with SLE.What this study addsThis study revealed that both trust in one’s physician and health-related hope were associated with better medication adherence in Japanese patients who were ethnically matched to their physicians.How this study may affect research, practice, or policyThe results indicated that physician communication to build trust and coaching on self-management to maintain or achieve what is important in the patient’s life may lead to better medication adherence.

ObjectivesAccessing the Internet has increased the gap in patient health literacy (HL), impacting patient-doctor trust. We examined how trust in physicians is affected by functional HL (the ability to read and write) and by broader concepts of HL, including communicative HL (the ability to extract information from communication to use) and critical HL (the ability to analyze and use information) among patients with systemic lupus erythematosus (SLE).MethodsThis cross-sectional study enrolled 362 SLE patients at five academic centers between June 2020 and August 2021. The 14-item Functional Communicative Critical Health Literacy Scale assessed the three dimensions of HL (range: 1-4 points). Outcomes were trust in one’s physician and physicians generally using the 5-item Wake Forest Physician Trust Scale (range: 0-100 points). General linear models adjusted for age, sex, education, income, disease activity, disease duration, depression, and time using the Internet.ResultsTrust in one’s physician increased with higher functional and communicative HL (per 1-pt increase, 3.21 [95%CI 0.61, 5.81], 5.8 [95%CI 1.96, 9.63]). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-pt increase, 7.01 [95%CI 2.27, 11.76], -6.83 [95%CI -11.67, -1.99]). Longer Internet use was associated with both higher communicative and critical HL.ConclusionsOur findings suggest that rheumatologists can help patients build trust by encouraging dialogue about their health issues with their doctors and family members, rather than trying to improve their ability to discern health information.Key messagesWhat is already known on this topicFactors affecting trust in one’s physician among chronic diseases including SLE are economic status, misdiagnosis experience, and the duration of the physician-patient relationship.In the general population, higher trust in physicians generally was associated with functional HL as patients’ external factors.What this study addsThis is the first study to reveal an association between trust in one’s own physician and HL among patients with SLE. In addition, we were able to expand the correlates of HL by measuring broader concepts of HL dimensions, such as communicative and critical HL.How this study may affect research, practice, or policyThis study suggests the importance of rheumatologists’ encouragement of patients to communicate, share their concerns, and resolve their misunderstandings to develop a trusting relationship. This study recommends that communictive HL (ability to obtain useful health information) should be the focus and not critical HL (ability to discern health information).

Disseminated nontuberculous mycobacterial infection (DNTM) is typically observed in immunocompromised hosts. Recently, it has been reported that healthy individuals with serum neutralizing autoantibodies for interferon (IFN)-γ can also develop DNTM. We herein report a case of anti-IFN-γ antibody-seropositive DNTM caused by Mycobacterium kansasii with symptoms mimicking TAFRO or POEMS syndrome, including anasarca, organomegaly, skin pigmentation, polyneuropathy, osteosclerotic change, thrombocytopenia, serum M protein, high C-reactive protein level, and reticulin fibrosis. The combination of antimicrobial chemotherapy with glucocorticoid and intravenous immunoglobulin improved his symptoms. Glucocorticoids may be an effective method of suppressing the production of anti-IFN-γ antibodies in DNTM.

Optic perineuritis (OPN), which is an inflammatory disorder affecting the optic nerve sheath, is one of the rare complications in granulomatosis with polyangiitis (GPA). Although several groups have reported that immunosuppressive therapies are generally effective against GPA-associated OPN, so far, there is little information as to other options for refractory cases. Here we demonstrate a case of GPA-associated OPN, which is refractory to potent immunosuppressive therapy including high-dose glucocorticoid, intravenous cyclophosphamide and rituximab therapy, and effective application of therapeutic plasma exchange. We also report here that CSF IL-6 levels may serve as a new biomarker for GPA-associated OPN.

Cell polarity is essential for various asymmetric cellular events, where the partitioning defective (PAR) protein, PAR3, plays a unique role as a cellular landmark to establish polarity. In epithelial cells, PAR3 localizes at the subapical border such as the tight junction in vertebrates and functions as an apical determinant. Although there is much information about the regulators of PAR3 localization, the mechanism involved in PAR3 concentration and localization to the specific membrane domain remains an important question to be clarified. In this study, we demonstrate that ASPP2, a stimulator of PAR3 localization, can link PAR3 and protein phosphatase 1 (PP1). The ASPP2–PP1 complex dephosphorylates a novel phosphorylation site, Ser852, of PAR3. Furthermore, Ser852- or Ser889-unphosphorylatable PAR3 mutants form protein clusters and ectopically localize to the lateral membrane. Concomitance of clustering and ectopic localization suggests that PAR3 localization is a consequence of local clustering. We also demonstrate that unphosphorylatable forms of PAR3 are static in molecular turnover and fail to coordinate rapid reconstruction of the tight junction, supporting that both phosphorylated and dephosphorylated states are essential for the functional integrity of PAR3.Summary statementWe show that phosphorylation and dephosphorylation regulate clustering of PAR-3, a cell polarity-regulating factor, and how the clustering regulation affects localization of PAR-3 and cell-cell junction formation.

Cell polarity is essential for various asymmetric cellular events, and the partitioning defective (PAR) protein PAR3 (encoded by PARD3 in mammals) plays a unique role as a cellular landmark to establish polarity. In epithelial cells, PAR3 localizes at the subapical border, such as the tight junction in vertebrates, and functions as an apical determinant. Although we know a great deal about the regulators of PAR3 localization, how PAR3 is concentrated and localized to a specific membrane domain remains an important question to be clarified. In this study, we demonstrate that ASPP2 (also known as TP53BP2), which controls PAR3 localization, links PAR3 and protein phosphatase 1 (PP1). The ASPP2-PP1 complex dephosphorylates a novel phosphorylation site, Ser852, of PAR3. Furthermore, Ser852- or Ser889-unphosphorylatable PAR3 mutants form protein clusters, and ectopically localize to the lateral membrane. Concomitance of clustering and ectopic localization suggests that PAR3 localization is a consequence of local clustering. We also demonstrate that unphosphorylatable forms of PAR3 exhibited a low molecular turnover and failed to coordinate rapid reconstruction of the tight junction, supporting that both the phosphorylated and dephosphorylated states are essential for the functional integrity of PAR3.

AIM To determine characteristics of rheumatoid arthritis (RA) patients in Japan who received the same biological disease-modifying antirheumatic drugs (bDMARDs) for at least 6 months and to identify factors associated with successful down-titration of bDMARDs dependent on shared decision-making. METHODS We included consecutive RA patients who received the same bDMARD with low disease activity or remission for at least 6 months in our two university hospitals. Patients treated with the bDMARD standard dose were defined as SD, while those treated with bDMARD down-titration were defined as DT. We retrospectively reviewed clinical charts and compared data between the two groups. RESULTS Of 288 patients with RA, 204 (70.8%) and 84 (29.2%) continued standard dose treatment and underwent down-titration treatment, respectively. Sixty-six of 84 (78.6%) down-titration-treated patients continued to show low disease activity or remission, whereas 18 (21.4%) relapsed 18.9 ± 24.4 months after bDMARD down-titration was started. Univariate predictor analysis showed that the probable factors of down-titration were no history of bDMARD treatment (P = .001) and low initial Disease Activity Assessment of 28 joint score (P = .048). Other clinical characteristics had no significant relationship with successful down-titration. CONCLUSIONS Thus, bDMARD-naive patients and those with low initial disease activity are more likely to agree to attempt down-titration. However, the timing and method of down-titration should be made in shared decision-making between patients and rheumatologists.

Background/Purpose TRIM21 is one of the autoantigens which react with anti-SS-A antibody (Ab). Previous studies have shown that TRIM21 dysfunction promotes aberrant B-cell differentiation in systemic lupus erythematosus (SLE). Here we examined the relationship between anti-TRIM21 Ab and clinical and immunological characteristics in SLE patients. Methods Twenty-seven patients with SLE before immunosuppressive therapies and four healthy controls (HC) were enrolled in the study. Serum anti-TRIM21 Ab levels were measured using enzyme-linked immunosorbent assays. The serum levels of cytokines and immunoglobulins were measured using cytometer beads arrays. The protein expression levels of TRIM21 in peripheral blood mononuclear cells (PBMCs) were evaluated by western blotting. Results Nineteen and 8 patients showed seronegativity and seropositivity for anti-TRIM21 Ab, respectively. There were no significant differences in the background parameters, including SLE activity and laboratory data. The serum levels of interferon (IFN)-α2 were significantly higher in patients with anti-TRIM21 Ab as compared with those without anti-TRIM21 Ab (p = 0.03). The levels of IgG1, IgG2, and IgA were significantly higher in patients with anti-TRIM21 Ab as compared with those without anti-TRIM21 Ab (p = 0.005, 0.04 and 0.01, respectively). The PBMCs of patients with anti-TRIM21 Ab showed a significantly higher expression of TRIM21 protein as compared with those of patients without anti-TRIM21 Ab. Conclusion Anti-TRIM21 Ab seropositivity is related to B-cell abnormalities and type I IFN overproduction in SLE patients, which may be due to the inhibitory effect of anti-TRIM21 Ab on TRIM21 functions.

Neurymenolides, α-pyrone macrolides isolated from the Fijian red alga Neurymenia fraxinifolia, are anti-methicillin-resistant Staphylococcus aureus and anti-vancomycin-resistant Enterococcus faecium compounds. In this study, the macrocyclic core of neurymenolide A was constructed in an enantioselective manner by employing Claisen rearrangement as the key step.

Macrophages play crucial roles in host defence and tissue homoeostasis, processes in which both environmental stimuli and intracellularly generated metabolites influence activation of macrophages. Activated macrophages are classified into M1 and M2 macrophages. It remains unclear how intracellular nutrition sufficiency, especially for amino acid, influences on macrophage activation. Here we show that a lysosomal adaptor protein Lamtor1, which forms an amino-acid sensing complex with lysosomal vacuolar-type H+-ATPase (v-ATPase), and is the scaffold for amino acid-activated mTORC1 (mechanistic target of rapamycin complex 1), is critically required for M2 polarization. Lamtor1 deficiency, amino-acid starvation, or inhibition of v-ATPase and mTOR result in defective M2 polarization and enhanced M1 polarization. Furthermore, we identified liver X receptor (LXR) as the downstream target of Lamtor1 and mTORC1. Production of 25-hydroxycholesterol is dependent on Lamtor1 and mTORC1. Our findings demonstrate that Lamtor1 plays an essential role in M2 polarization, coupling immunity and metabolism.