Risk of motor vehicle accidents with profound injuries in patients with ankylosing spondylitis: a nationwide, population-based cohort study.

Background: Patients with ankylosing spondylitis (AS) suffer from impaired physical activity and are prone to motor vehicle accidents (MVA), but definite instruction regarding the relationship between disease evolvement and MVA and potential risk factors is lacking. Objectives: To explore the risk factors and their impact on recorded MVA with profound injuries in AS patients with prescriptions. Design: Nationwide, population-based, matched retrospective cohort study. Methods: Using Taiwanese administrative healthcare databases, with available claims data from 2003 to 2013, we selected 30,911 newly diagnosed adult AS patients with concurrent prescriptions from 2006 to 2012 as AS patients, along with 309,110 non-AS individuals as the control group, matched in gender, age at index date and year of the index date. The risk of recorded MVA with profound injuries was compared between the two groups in terms of incidence rate ratio (IRR) and log-rank test p-value. Using Cox regression analysis, we studied associations between the risk and AS diagnosis. Results: The risk of recorded MVA with profound injuries in AS patients was significantly higher than in non-AS individuals, specifically 2 years after AS diagnosis (IRR, 2.00; 95% confidence interval (CI), 1.42-2.81). For patients with follow-up periods >2 years, the adjusted risk was positively associated with suburban residence (adjusted hazard ratio (aHR), 2.18; 95% CI, 1.55-3.06), rural residence (aHR, 1.89; 95% CI, 1.27-2.80), lower insured income (aHR, 1.35; 95% CI, 1.01-1.81) and recorded MVA with profound injuries before AS diagnosis (aHR, 6.16; 95% CI, 2.53-14.96). AS diagnosis (aHR, 1.81; 95% CI, 1.27-2.59) and frequency of ambulatory visits (aHR, 1.01; 95% CI, 1.004--1.02) were specific associated factors for them compared with those with follow-up periods ⩽2 years. Conclusion: For adult AS patients in Taiwan, factors such as AS disease evolution and frequent ambulatory visits for disease control in the second year of the disease course may significantly increase the risk of recorded MVA with profound injuries beyond 2 years after AS diagnosis.

Characterisation and outcomes of different subsets of low disease activity states in patients with systemic lupus erythematosus.

OBJECTIVES: The lupus low disease activity state (LLDAS) allows for certain clinical and/or serological activity of SLE, provided overall disease activity does not exceed predefined cut-offs. This study aimed to evaluate the outcomes of patients who achieved LLDAS with clinical activity, serological activity only or neither clinical nor serological activity. METHODS: Patients with SLE enrolled in a prospective multinational cohort from March 2013 to December 2020 who were in LLDAS at least once were included. Visits that fulfilled both LLDAS and Definition of Remission in SLE (DORIS) criteria were excluded. RESULTS: 2099 patients were included, with median follow-up of 3.5 (IQR 1.3-5.8) years. At 6150 visits, patients were in LLDAS but not DORIS criteria; of these 1280 (20.8%) had some clinical activity, 3102 (50.4%) visits had serological activity only and 1768 (28.8%) visits had neither clinical nor serological activity. Multivariable regression analysis showed that compared with non-LLDAS, all three subsets of LLDAS had a protective association with flares in the ensuing 6 months and damage accrual in the ensuing 36 months. LLDAS with no clinical or serological activity had a significantly stronger protective association with severe flares in the ensuing 6 months compared with LLDAS with clinical activity (HR 0.47, 95% CI (0.27 to 0.82), p=0.007). CONCLUSIONS: LLDAS without any clinical activity accounted for almost 80% of LLDAS visits. This study confirms that all subsets of LLDAS are associated with reduced flare and damage accrual. However, LLDAS without any clinical or serological activity has the strongest protective association with severe flares.

Correction: Therapeutic DNA vaccine attenuates itching and allergic inflammation in mice with established biting midge allergy.

[This corrects the article DOI: 10.1371/journal.pone.0232042.].

Salivary Gland Sonography in Patients with Primary Fibromyalgia-A Pilot Study.

Primary Sjogren's syndrome (pSS) is often concomitant with fibromyalgia (FM). Salivary gland sonography aids in the diagnosis of pSS. We aimed to discover, in primary FM patients, the presence of pSS in undiagnosed patients through salivary gland sonography. We prospectively recruited 42 primary FM patients. FM symptoms were evaluated based on the revised Fibromyalgia Impact Questionnaire (FIQR). Salivary gland sonography was performed. Patients with positive findings underwent salivary gland biopsy. Comparisons were undertaken using the Mann-Whitney U tests and Chi-squared test. In primary FM patients, the prevalence of dry eye was 83%, and dry mouth was 90%. The salivary gland sonographic score did not differ between patients with and without dry eye/mouth. One patient with a positive finding at salivary gland sonography had a positive result of salivary gland biopsy. In the other four patients who received salivary gland biopsy, despite negative findings in salivary gland sonography, only one had a positive result of salivary gland biopsy. To be noted, scores evaluated by salivary gland sonography were negatively associated with levels of pain (rho = -0.360, p= 0.023) and levels of sleep quality (rho = -0.447, p = 0.004). Our pilot study demonstrated the potential of salivary gland biopsy in detecting undiagnosed pSS in primary FM patients.

Exposure to Volatile Organic Compounds May Contribute to Atopic Dermatitis in Adults.

BACKGROUND: Volatile organic compounds (VOC) are major indoor air pollutants. Previous studies reported an association between VOC exposure and allergic diseases. Here, we aimed to explore the relationship between VOC exposure and atopic dermatitis (AD) in adults. METHODS: We prospectively enrolled 31 adult AD patients and 11 healthy subjects as controls. Urine metabolite levels of VOCs, including 1.3-butadiene, acrylamide, benzene, toluene, and xylene, were all determined with liquid chromatography-mass spectrometry. The relationship between AD and log-transformed urine levels of VOC metabolites were examined using a multivariate linear regression model adjusted for age and sex. We also treated mouse bone marrow-derived cells (BMMCs) with 1,3-butadiene and toluene and measured the release of ß-hexosaminidase. RESULTS: Our results demonstrated that creatinine-corrected urine levels of N-Acetyl-S- (3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-Acetyl-S-(benzyl)-L-cysteine (BMA) were all elevated in AD patients compared with controls. In a multivariate linear regression model, creatinine-corrected urine levels of BMA (a toluene metabolite) and DHBMA (a 1,3-butadiene metabolite) appeared elevated in AD patients, although statistical significance was not reached after correction for multiple comparisons. In addition, 1,3-butadiene and toluene could stimulate BMMCs to degranulate as much as compound 48/80. CONCLUSIONS: Some VOCs, such as 1,3-butadiene and toluene, might be associated with AD pathogenesis in adults.

Association of sustained lupus low disease activity state with improved outcomes in systemic lupus erythematosus: a multinational prospective cohort study.

BACKGROUND: Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials. We assessed long-term protective associations of LLDAS and remission, and specifically examined protective thresholds of sustained LLDAS and remission. METHODS: Patients aged 18 years or older with SLE were followed up from May 1, 2013, to Dec 31, 2020 in a prospective, multinational, longitudinal cohort study. Patients were recruited from 25 centres in 12 countries. Multi-failure time-to-event analyses were used to assess the effect of sustained LLDAS on irreversible damage accrual (primary outcome; measured with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and flare (key secondary outcome; measured with the SELENA Flare Index), with dose exposure and threshold effects studied. Sustained LLDAS or remission were defined as two or more consecutive visits over at least 3 months in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941. FINDINGS: 3449 patients were followed up for a median of 2·8 years (IQR 1·1-5·6), totalling 37 662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) patients had sustained LLDAS at least once. Any duration of sustained LLDAS or remission longer than 3 months was associated with reduced damage accrual (LLDAS: hazard ratio 0·60 [95% CI 0·51-0·71], p<0·0001; remission: 0·66 [0·57-0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51-0·63], p<0·0001; remission: 0·66 [0·60-0·73], p<0·0001), and increasing durations of sustained LLDAS corresponded to increased protective associations. Sustained DORIS remission or steroid-free remission were less attainable than LLDAS. INTERPRETATION: We observed significant protective associations of LLDAS and remission against damage accrual and flare, establish a threshold of 3 months sustained LLDAS or remission as protective, and demonstrate deepening protection with longer durations of sustained LLDAS or remission. FUNDING: The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Opportunities and challenges of lupus care in Latin America, the Middle East, and Asia-Pacific: A call to action.

Lupus remains a disease with a low prioritisation in the national agendas of many countries in Latin America, the Middle East, and Asia-Pacific, where there is a dearth of rheumatologists and limited access to new or even standard lupus treatments. There is thus an important need for education, advocacy, and outreach to prioritise lupus in these regions to ensure that patients receive the care they need. This article reviews some of the specific challenges facing the care and management of people with lupus in these regions and suggests strategies for improving patient outcomes. Specifically, we review and discuss (with a focus on the aforementioned regions) the epidemiology of lupus; economic costs, disease burden, and effects on quality of life; barriers to care related to disease assessment; barriers to effective treatment, including limitations of standard treatments, high glucocorticoid use, inadequate access to new treatments, and low adherence to medications; and strategies to improve lupus management and patient outcomes. We hope that this represents a call to action to come together and act now for the lupus community, policymakers, health authorities, and healthcare professionals to improve lupus management and patient outcomes in Latin America, the Middle East, and Asia-Pacific.

Comparison of Attainment and Protective Effects of Lupus Low Disease Activity State in Patients With Newly Diagnosed Versus Established Systemic Lupus Erythematosus.

OBJECTIVE: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE). METHODS: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare. RESULTS: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up. CONCLUSION: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941).

Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study.

OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE). METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred. RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day. CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.

Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.

Association of atypical anti-neutrophil cytoplasmic antibody with comorbidities and outcome in a hospital-based population.

Introduction: Atypical anti-neutrophil cytoplasmic antibody (a-ANCA) is characterized by a positive fluorescence staining other than typical cytoplasmic or perinuclear ANCA. ANCA is associated with increased risk of dialysis and mortality in patients with ANCA vasculitis. However, comorbidities related to a-ANCA and whether a-ANCA exhibits an increased risk for renal failure and mortality remain unclear. This study aimed to explore the comorbidities and outcome associated with a-ANCA. Materials and methods: This retrospective study enrolled 164 and 170 patients with typical ANCA and a-ANCA positivity, respectively, who visited Taichung Veterans General Hospital, Taiwan from January 2016 to March 2021. Logistic regression analysis was used to determine risk factors and the rheumatological diagnosis associated with a-ANCA. Cox proportional hazard regression and Kaplan-Meier curves were employed to identify variables associated with 5-year renal survival and mortality. Results: Patients with a-ANCA had lower chance of ANCA-associated vasculitis (OR: 0.02, 95 % CI: 0.01-0.07 p < 0.001), and systemic lupus erythematosus (OR: 0.23, 95 % CI: 0.11-0.48, p < 0.001), but a higher risk of rheumatoid arthritis (OR: 2.99, 95 % CI: 1.15-7.83, p = 0.025) and ulcerative colitis (OR: 5.50, 95 % CI: 1.20-25.29, p = 0.028). Patients with a-ANCA had a better renal survival (OR: 0.14, 95 % CI: 0.08-0.24, p < 0.001) and lower mortality (OR: 0.31, 95 % CI: 0.16-0.60, p = 0.001) than patents in the typical ANCA group. The 5-year renal survival and mortality was 89.3 % and 8.8 %, respectively, in patients with a-ANCA. Conclusion: Patients with a-ANCA had better renal survival and lower mortality rates compared to patients with typical ANCA. These real-world data provide evidence of the long-term outcome and shed light on avenues for the strategic management of patients with a-ANCA.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients. METHODS: From December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction. RESULTS: We enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80-0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73-0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71-0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67-0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03-2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11-10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis. CONCLUSION: The clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

The Fracture Risk of Elderly Patients With Atopic Dermatitis.

Background: A higher fracture risk has been reported previously in patients with atopic Dermatitis (AD). The bone mineral density (BMD) was not accounted for in these studies. Objective: To investigate the fracture risk in AD patients after adjustment for factors including BMD. Methods: We retrospectively analyzed AD patients (≥45 years) who underwent BMD examination at our hospital from July 2010 to February 2023. Individuals who received BMD examinations during a health checkup were identified as the controls. We documented their clinical characteristics, BMD, 10-year risk for a major fracture based on FRAX (Fracture Risk Assessment Tool), and development of osteoporotic fractures. Patients were followed until development of new onset fracture or the end of the study period. A cross-sectional comparison of BMD between AD patients and controls at baseline was performed using the Mann-Whitney U test after propensity score matching (PSM). Their fracture risks were compared using the multivariate Cox regression model. BMD and fracture risk were also compared between AD patients who received systemic therapy and those who did not. Results: A total of 50 AD patients and 386 controls were enrolled. The median age was older in AD patients when compared with controls (70 years vs 60 years). Their BMD at all sites was similar after PSM. After a median follow-up of 1.7-2.0 years, 13 osteoporotic fractures were identified. In the multivariate Cox regression analysis, AD was not associated with new onset fractures of all sites (adjusted hazard ratio [aHR] 2.55, 95% confidence interval [CI] 0.72-9.01) but was significantly associated with new onset vertebral fractures (aHR 6.80, 95% CI 1.77-26.17). The BMD and incidence of fractures were similar between AD who received systemic therapy and those who did not. Conclusions: Elderly AD patients had similar BMD but a higher short-term risk for vertebral fractures when compared with the controls.

Traumatic brain injury-induced disruption of the circadian clock.

Disturbances in the circadian rhythm have been reported in patients following traumatic brain injury (TBI). However, the rhythmic expression of circadian genes in peripheral blood leukocytes (PBL) following TBI has not yet been studied. The messenger ribonucleic acid (mRNA) expression of period 1 (Per1), Per2, Per3, cryptochrome 1 (Cry1), Cry2, brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1), and circadian locomotor output cycles kaput (Clock) was quantified in PBLs from sham-operated rats and rats with acute subdural hematoma (ASDH) over a 48-h period. The rectal temperature of the animals was measured every 4 h over 2 days. The mesor, rhythm, amplitude, and acrophase were estimated using cosinor analysis. Cosinor analysis revealed that Per2, Cry1, and Bmal1 mRNAs were rhythmically expressed in the PBLs of sham-operated rats. In contrast, fluctuations in rhythmic expression were not observed following ASDH. The rectal temperature of sham-operated rats also exhibited rhythmicity. ASDH rats had a disrupted rectal temperature rhythm, a diminished amplitude, and an acrophase shift. TBI with ASDH results in dysregulated expression of some circadian genes and changes in body temperature rhythm. Further research is required to understand the pathophysiology of altered circadian networks following TBI. KEY MESSAGES: First to investigate the mRNA expression of circadian genes in PBLs of ASDH rats. ASDH rats had disrupted rhythmicity of Per2, Cry1, and Bmal1 mRNA expression. Cosinor analysis showed that ASDH rats had a disrupted rectal temperature rhythm.

Factors influencing long-term outcomes in fibrotic interstitial lung disease (F-ILD) diagnosed through multidisciplinary discussion (MDD): a prospective cohort study.

BACKGROUND: The diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: We included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender-age-physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model. RESULTS: We enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0-2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28-85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07-15.5; p = 0.039) were significantly associated with overall mortality. CONCLUSION: The long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients.

Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. METHODS: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. RESULTS: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). CONCLUSION: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

Antirheumatic drugs and the risk of nonalcoholic fatty liver disease in patients with rheumatoid arthritis: A nationwide, population-based cohort study.

OBJECTIVES: To assess the association between antirheumatic drugs and of the risk of nonalcoholic fatty liver disease (NAFLD) in a nationwide rheumatoid arthritis (RA) cohort. METHODS: Using claim data from the 2000-2020 National Health Insurance Research Database, we identified 21 457 incident patients with RA from 2002 to 2020 without prior liver diseases. A time-varying multivariable Cox regression model was applied to estimate for the association of NAFLD with the use of antirheumatic drugs after adjusting potential confounders, show as adjusted hazard ratios (aHRs) with 95% confidence interval (CIs). Subgroup analyses were conducted based on age-, sex-, and obesity-related comorbidities. RESULTS: Multivariable time-dependent Cox regression analyses showed that defined daily dose (DDD) of NSAID (aHR, 1.03; 95% CI: 1.02-1.05) and prednisolone equivalent dose >5 mg/day (aHR, 2.39; 95% CI: 1.85-3.09) were risk factors of NAFLD in patients with RA, while prednisolone equivalent dose ≤5 mg/day (aHR of 0.53; 95% CI: 0.40-0.71) and HCQ use (aHR of 0.75; 95% CI: 0.60-0.93) were associated with a decreased risk of NAFLD. In addition, a history of hospitalizations, number of outpatient visits, age, male, and leflunomide use were associated with the development of NAFLD in some subgroups. CONCLUSION: This study reveals that NSAID use and prednisolone equivalent dose >5 mg/day were associated with an increased risk of NAFLD in patients with RA, while the use of HCQ and prednisolone equivalent dose ≤5 mg/day decreased the risk of NAFLD.