This single-center retrospective study aimed to evaluate the clinical efficacy of peloid therapy in patients with knee osteoarthritis. Patients diagnosed with knee osteoarthritis according to the criteria of the American College of Rheumatology, with a radiographic grade of at least 2 according to the Kellgren-Lawrence radiographic grading system, and who received at least seven sessions of peloid therapy to the knee were retrospectively analyzed between January 2023 and January 2026. After applying the inclusion and exclusion criteria, a total of 329 patients were included in the analysis. High-organic-content peloid was heated to approximately 47-48 °C and locally applied to the knee area for approximately 20 min per session, with patients receiving a total of 7-15 treatment sessions over 2-3 weeks. The primary endpoint of the study was defined as the change in the WOMAC total score, while the secondary endpoints included WOMAC subscales, VAS pain, VAS global, VAS physician, and HAQ scores. Statistically significant improvement was observed in all post-treatment clinical assessment parameters compared to pre-treatment (p < 0.001). An average decrease of 33.64 points in the WOMAC total score, approximately 38 points in the VAS pain score, and 0.69 points in the HAQ score was observed. Effect size values ranged from 1.00 to 1.57, indicating a very large treatment effect. In the responder analysis, clinically significant improvement was observed in 67.2% of patients. These findings suggest that peloid therapy may provide significant improvement in pain and functional status in patients with knee osteoarthritis and may be an effective complementary treatment option in clinical practice. However, prospective and controlled studies are needed to support these findings with stronger evidence. CLINICAL TRIAL REGISTRATION: Not applicable.
EULAR recommends kidney biopsy in systemic lupus erythematosus (SLE) patients with glomerular hematuria, whereas both ACR and KDIGO require the presence of proteinuria and/or impaired kidney function. We explored the value of hematuria for the diagnosis of new-onset lupus nephritis (LN). Cross-sectional study of SLE patients who underwent diagnostic kidney biopsy in two independent centers. Clinically significant LN was defined as ISN/RPS class III, IV, V, or mixed III/IV + V. Presentation patterns were categorized by glomerular hematuria, proteinuria, and impaired kidney function. Among patients with glomerular hematuria, regression models identified factors associated with clinically significant LN, and a nomogram was constructed. Of 227 biopsies, 181 (79.7%) showed clinically significant LN. Isolated glomerular hematuria was evident in 11 patients, of whom 9 revealed non-LN pathology; the two LN cases (class II and III) both demonstrated concurrent SLE serologic activity. Among patients with glomerular hematuria (n = 137), independent factors associated with clinically significant LN included anti-dsDNA positivity (OR 12.00, 95% CI 3.36-51.40), higher non-renal SLEDAI score (OR 1.20 per point, 95% CI 1.02-1.46), higher proteinuria (OR 3.77 per 1 g/d, 95% CI 2.00-9.03), and younger age (OR 0.96 per year, 95% CI 0.91-1.00). The combined presence of these factors yielded a predicted probability of 97% (95% CI 90-99%) of clinically significant LN, whereas their absence was associated with a probability of only 6% (95% CI 1-23%). When considering the need for kidney biopsy in patients with lupus, hematuria should be evaluated in the context of overall disease activity; extra-renal and serologic activity substantially increase the likelihood of clinically significant LN.
Anaphylaxis is a life-threatening systemic hypersensitivity reaction with highly variable clinical expression and unpredictable severity. Increasing evidence suggests that host-microbiota interactions may contribute to interindividual variability in allergic sensitization and effector responses. This review summarizes current mechanistic, preclinical, and emerging human data supporting a role for the microbiota in modulating anaphylaxis risk and severity. Recent experimental studies demonstrate that gut microbial composition and function influence susceptibility to systemic allergic reactions through effects on immune maturation, epithelial barrier integrity, and mast cell biology. Microbiota-derived metabolites, particularly short-chain fatty acids, can directly suppress mast cell activation and degranulation via epigenetic mechanisms. In parallel, preclinical models indicate that dysbiosis exacerbates anaphylactic responses, whereas microbial restoration attenuates disease severity. Emerging translational evidence further suggests that commensal bacteria may directly metabolize food allergens, reducing IgE-binding capacity and effector cell activation. Human studies, although limited, report associations between microbial signatures, allergen-specific IgE levels, and clinical phenotypes, as well as links between microbiota composition and oral immunotherapy outcomes. Current evidence supports a biologically plausible role for the microbiota in shaping anaphylaxis susceptibility and severity; however, findings remain largely associative. Future longitudinal and mechanistic studies are needed to establish causality and evaluate the translational potential of microbiota-targeted strategies for the prevention and management of anaphylaxis.
Rheumatoid arthritis (RA) is associated with loss of muscle quality and strength, but accessible quantitative tools for detecting these changes remain limited. We evaluated whether shear wave viscoelastic imaging (SWVI), acoustic attenuation imaging (AAI), and isokinetic strength testing could characterize rectus femoris muscle involvement in RA, and used public synovial transcriptomic data to provide hypothesis-generating biological context. Twenty-nine patients with RA (early RA, n = 7; active RA, n = 11; treated low/moderate-activity RA, n = 11) and 27 healthy controls underwent rectus femoris ultrasound and knee isokinetic strength testing. The main ultrasound variables were rectus femoris thickness and cross-sectional area, mean Young's modulus (Emean), viscosity (Vimean), speed of sound (SoS), and AAI. Group differences, Spearman correlations, receiver-operating-characteristic (ROC) curves, and exploratory logistic models were analyzed. Because the RA cohort was small and diabetes was more common in RA than in controls, ROC, nomogram, and multivariable results were interpreted as exploratory rather than confirmatory. Public GSE55235 synovial transcriptome data were reanalyzed to identify inflammatory and extracellular-matrix pathways that may plausibly link synovitis with systemic muscle impairment. Rectus femoris thickness and cross-sectional area showed limited between-group separation, whereas Emean, Vimean, SoS, AAI, and isokinetic strength differed across groups (all p < 0.001). AAI increased from controls to early, active, and treated low/moderate-activity RA groups and correlated with disease duration in the full cohort (Spearman rho = 0.864); this association remained strong in RA-only adjusted sensitivity analyses. SoS decreased across the same gradient (rho =  - 0.875 with duration in the full cohort), whereas Vimean was highest in active RA and correlated with DAS28 in the full cohort (rho = 0.643). Extensor peak torque was lower in RA and correlated inversely with DAS28 in the full cohort (rho =  - 0.844); the corresponding RA-only association was more moderate but remained significant (rho =  - 0.642). In exploratory ROC analyses, AAI, SoS, and extensor peak torque showed high apparent discrimination between RA and controls; however, the small overall and subgroup samples, baseline differences in diabetes and height, and absence of external validation make these estimates potentially unstable and preclude conclusions about clinical applicability. Synovial transcriptomic analysis showed enrichment of TNF, NF-κB, JAK-STAT, cytokine-receptor, and extracellular-matrix remodeling pathways in RA synovium, supporting a plausible inflammatory background rather than direct evidence of muscle pathology. In this exploratory clinical-transcriptomic study, SWVI/AAI and isokinetic strength testing detected rectus femoris muscle-quality and functional differences associated with RA. AAI and SoS may be candidate ultrasound parameters for RA-associated muscle involvement, but their disease specificity, independence from diabetes, and tissue-level interpretation require confirmation in larger, externally validated studies with reference-standard muscle-composition assessment and reliability testing. • This study integrates meta-analysis, Mendelian randomization, and single-cell RNA sequencing to comprehensively evaluate treatment efficacy, genetic influences, and immune alterations in late-onset rheumatoid arthritis (LORA). • LORA patients exhibit distinct treatment responses compared with younger-onset RA, including lower clinical remission rates with biologics/tsDMARDs and higher residual disease activity (DAS28). • Genetic variants in the IL-6R and TYK2 pathways are identified as key modifiers of drug response and disease susceptibility in LORA. • The findings underscore the need for age- and genetics-informed personalized treatment strategies in elderly patients with rheumatoid arthritis.
Cardiovascular disease (CVD) accounts for approximately 40% of deaths among patients with rheumatoid arthritis (RA), yet the burden of heart failure (HF) within this population remains poorly characterized. Using the KURAMA cohort, we aimed to quantify the prevalence of HF among RA outpatients and develop a practical HF screening tool that uses variables readily available to rheumatologists in routine clinical practice. A cross-sectional study of 542 outpatients with RA was conducted. Their HF status was determined using a prespecified multistep algorithm that integrated clinical history, loop diuretic use, N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography, and careful differentiation from interstitial lung disease (ILD). Adaptive LASSO regression was applied to identify independent factors associated with HF and construct a detection score using non-cardiac variables. Heart failure was detected in 26.5% of patients with RA. Older age, lower haemoglobin (Hb) levels, higher serum creatinine (CRE) levels, and higher Simplified Disease Activity Index (SDAI) were identified as independent non-cardiac factors associated with HF. A 4-factor HF detection score was constructed based on adjusted odds ratios. The area under the receiver operating characteristic curve (AUC) for the discrete score based on variables routinely available in rheumatology clinics was 0.793, comparable to that of NT-proBNP ≥ 125 pg/mL alone (AUC = 0.814). HF affects over one in four RA outpatients. A simple 4-factor score may serve as a practical first-line triage tool to identify patients who warrant further cardiac evaluation and cardiology referral.
Fibromyalgia is a heterogeneous chronic condition characterized by variability in pain, psychological distress, central sensitization, and functional impairment. Cross-sectional studies have identified reproducible symptom phenotypes; however, their longitudinal stability remains incompletely understood. Objectives:This study aimed to evaluate the longitudinal stability of data-driven fibromyalgia phenotypes across repeated clinical assessments in a large, harmonized, multi-institutional cohort. We analyzed longitudinal data from 821 adults with fibromyalgia recruited from 2 academic medical centers. Standardized assessments included the Revised Fibromyalgia Impact Questionnaire, Beck Depression Inventory, Central Sensitization Inventory, McGill Pain Questionnaire, and selected SF-36 functional domains. Unsupervised clustering was performed at baseline to derive symptom phenotypes, which were ordered by overall severity. Using baseline-derived model parameters, phenotype membership was assigned at subsequent visits. Phenotype transitions were examined between visit 1 and visit 2 (n = 191) and across visits 1 to 3 (n = 72) using transition matrices and alluvial visualizations. Two clinically interpretable fibromyalgia phenotypes were identified at baseline, representing lower-severity/preserved function and higher-severity/global impairment profiles. Across 6-month follow-up intervals, most participants remained within their baseline phenotype (61.9% from visit 1→2 and 64.8% from visit 2→3). Transitions occurred in a minority of individuals and were primarily between adjacent severity phenotypes. Among participants with 3 or more visits, phenotype membership remained stable across repeated assessments. Data-driven fibromyalgia phenotypes demonstrate substantial longitudinal stability, supporting their validity as enduring clinical constructs rather than transient symptom states. These findings support phenotype-based stratification for longitudinal research and precision treatment approaches in fibromyalgia. Longitudinal analysis shows that fibromyalgia symptom phenotypes are largely stable over time, with infrequent transitions occurring mainly between adjacent severity groups.
Accurate and timely prediction of critical events from longitudinal electronic health record (EHR) data is essential for precision medicine, particularly in complex chronic diseases with heterogeneous and evolving patient trajectories. Despite rapid growth in the number of statistical and machine learning methods, prediction remains challenging, especially for binary outcomes. Many valid approaches either lack transparency, ignore temporal dependence, or are difficult to dynamically update with new data, limiting clinical applicability. Existing dynamic prediction methods are designed primarily for continuous outcomes and do not directly extend to binary settings, which are common in clinical practice. We use a Bayesian generalized linear mixed model approach to develop a cross-validated sequential prediction (CVSP) algorithm for estimating the conditional probability of a binary outcome given all available historical data. The prediction model integrates population-level fixed effects, lagged outcomes to capture shorter-term dependence, and patient-specific random intercepts to account for longer-term dependence due to unobserved heterogeneity. Predictions are cross-validated and generated sequentially at each visit with Monte Carlo integration, without refitting the model as new data accrue. Variable selection via bootstrap LASSO is incorporated to improve model parsimony and prediction validity. The framework is motivated by and applied to systemic sclerosis (SSc) patients with longitudinal assessments of proximal muscle weakness. The proposed method demonstrates superior discriminative performance (cross-validated AUC of 0.86) compared to standard regression and machine learning approaches, while also maintaining good calibration. The CVSP approach allows efficient individualized predictions that incorporate a patient's entire medical history. Variable selection reduces the number of predictors while preserving accuracy. This Bayesian CVSP framework provides a generalizable approach for individualized, visit-by-visit prediction of binary outcomes from longitudinal EHR data. By dynamically updating risk estimates without repeated refitting, it supports real-time clinical decision-making and advances precision medicine for chronic disease management.
To estimate the risk of venous thromboembolism (VTE) in a nationwide cohort of newly diagnosed patients with SLE and in a cohort of established patients with SLE at Karolinska University Hospital compared with the general population. Individuals with SLE were identified from the National Patient Register and matched to general population comparators on age, sex and residence. Follow-up was from diagnosis/matching until incident VTE, death, emigration or study end. The Karolinska cohort was followed from enrolment and additionally stratified by lupus nephritis (LN) and antiphospholipid antibody (aPL) positivity. Incidence rates (IR) of VTE were estimated and adjusted HRs with 95% CIs were estimated using Cox models. Time-dependent adjusted HRs were estimated using flexible parametric survival models. In the nationwide cohort (N=4335), the mean age at inclusion was 49 years, 83% were female and mean follow-up was 7.4 years. The VTE IR was 8.8 per 1000 person-years compared with 2.8 in comparators, corresponding to an HR of 3.3 (95% CI 2.9 to 3.8). In the Karolinska cohort (N=784), the HR was 4.9 (95% CI 3.7 to 6.5). VTE risk was highest in the first few years after SLE diagnosis. LN was not significantly associated with VTE, and aPL positivity was associated with a 60% higher hazard, which was non-significant and attenuated after excluding individuals with prior VTE. SLE is associated with an over threefold increased risk of VTE, in particular soon after SLE diagnosis, underscoring the need for individualised VTE risk assessment.
To evaluate and compare the efficacy of anti-osteoporotic-medications (AOM) for the prevention and treatment of glucocorticoid-induced-osteoporosis (GIOP). Systematic review and network-meta-analysis conducted in accordance with PRISMA-NMA guidelines (ProsperoID:CRD42024502298). MEDLINE, Embase, and Web of Science were searched from inception to December 2025 to identify randomized-controlled-trials and comparative-observational-studies evaluating AOM in adults receiving oral glucocorticoids (GC). Outcomes included percentage change in areal bone- mineral-density (aBMD) at the lumbar-spine (primary), femoral-neck, and total-hip. A random effects network-meta-analysis was performed, integrating direct and indirect comparisons across AOM. Certainty of evidence was assessed using the CINeMA framework. Thirty-one studies (28 randomized-controlled-trials and 3 observational-studies) involving 5,260 participants (age-range:29.6-70.6years, 72.5%females) were included. All AOM were superior to placebo or calcium/vitaminD supplementation in increasing lumbar-spine aBMD. Teriparatide demonstrated the greatest efficacy compared with alendronate (effect-size:3.8;95%CI:2.9-4.6), risedronate (4.0;95%CI:2.9-5.1), denosumab (1.5;95%CI:0.1-2.9), and zoledronate (2.4;95%CI:1.1-3.6), while no significant difference was observed with romosozumab (0.3;95%CI:-2.1 to 1.4). Among antiresorptive-medications, zoledronate and denosumab showed greater efficacy than oral bisphosphonates, which demonstrated modest positive effects. In sensitivity analyses restricted to established GIOP, defined as GC users ≥3months, teriparatide and romosozumab remained superior to antiresorptive-medications. Evidence for total-hip and femoral-neck aBMD outcomes was limited by substantial network inconsistency (mostly missing data). Included studies were underpowered to assess difference in fracture outcomes. This network-meta-analysis demonstrates a clear gradient of efficacy among AOM in GIOP, with anabolic and potent antiresorptive-medications producing the largest gains in lumbar- spine aBMD supporting current ECTS recommendations advocating risk-stratified treatment selection.
To evaluate longitudinal antiphospholipid antibody (aPL) patterns in newly diagnosed systemic lupus erythematosus (SLE) and their association with vascular events, disease activity and organ damage. We conducted a prospective study within the INSPIRE registry including patients with newly diagnosed SLE (median disease duration 232 days [114-484]) with serum at baseline, 6 and 24 months. Anti-cardiolipin (aCL) and anti-beta2 glycoprotein I (anti-β2GPI) IgG/IgM were measured by ELISA; lupus anticoagulant when feasible. aPL positivity was analysed using manufacturer cut-offs and moderate-high titres (>40 U). Patients were classified as persistently negative, positive, fluctuating or negativised. High- and low-risk aPL profiles were defined per EULAR recommendations. Associations with thrombosis, SLEDAI-2K, Physician Global Assessment (PGA) and SLICC/ACR Damage Index (SDI) were assessed. Among 270 patients, 77.1% were aPL-positive at least once, predominantly low-titre. Moderate-high titre aPLs were less frequent and stable. Most patients with baseline negativity or low-titre/single positivity reverted to negative, whereas dual or triple positivity was associated with persistence. A subgroup (3.1%) progressed from negative/low-titre to high-risk profiles. aPL negativisation occurred in 12.5% and was inversely associated with baseline aPL burden. Over two years, 19 (7%) developed thrombosis, with higher risk in high-risk and persistently positive groups; no thrombotic events occurred in persistently aPL-negative patients.aPL titres did not correlate with SLEDAI-2K or PGA, while aCL IgG and anti-β2GPI IgG correlated weakly with anti-dsDNA. SDI remained low across groups. In early SLE, aPLs are largely low-titre and fluctuating, with some patients evolving to higher-risk states, supporting serial aPL testing.
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To test whether ultrasonography of patients with rheumatoid arthritis (RA) in the American College of Rheumatology/the European Alliance of Associations for Rheumatology (ACR/EULAR) remission is useful for prediction of relapse after discontinuation of a biological disease-modifying antirheumatic drug (bDMARD). Prospective trial including patients with RA in persistent ACR/EULAR remission treated with conventional synthetic DMARDs plus bDMARDs. After stopping the bDMARD, nine study visits including clinical examination and ultrasound of 14 joints (blinded to clinical data) were conducted within 52 weeks. The primary hypothesis was that a Power Doppler (PD) score≥1 predicted relapse occurring within week 16 after bDMARD cessation. Relapse was defined as a change from remission to moderate/high disease activity according to the Simplified Disease Activity Score. Inclusion of 110 patients was originally planned; however, the study was terminated after reaching 38 (34.5%) patients due to insufficient recruitment. Relapses till week 16 were numerically more common in patients with PD score≥1 at baseline than in those with PD=0 (9/30 (30.0%) vs 0/7 (0%), p=0.160). Similar observations were made for weeks 24 and 52. PD scores were higher at the time of relapse than at preceding visits (mean PD score difference: 3.2 (±4.5) points, p=0.034). There were trends towards a higher baseline PD score in patients who had a relapse until week 16 as compared with those who remained in remission (5.2±5.8 vs 2.3±3.0, p=0.079). The primary endpoint was not reached. The presented data should be interpreted as hypothesis-generating, serving to stimulate future research on the value of ultrasound in assessing remission and predicting relapse in RA. NCT01602302.
A subset of psoriasis (PsO) patients exhibits subclinical entheseal inflammation and bone remodeling placing them at higher risk of developing psoriatic arthritis (PsA). Whether early pharmacological interventions during this phase can modulate these inflammatory and structural changes remains largely unclear. In this single-arm, open-label trial (EPos, EUDRACT 2018-000335-27) PsO patients with moderate-to-severe psoriasis, arthralgia, subclinical inflammatory and/or structural bone changes assessed by hand MRI and/or HR-pQCT were included. Patients who had current or past signs of PsA or prior b/tsDMARD exposure were excluded. Participants received apremilast 30 mg BID over 24 weeks. The primary endpoint was the change in structural entheseal lesions (SEL) (number, density and structure) at hand joints assessed by HR-pQCT (week 24). Secondary endpoints were change in bone and inflammatory alterations assessed by MRI (PsAMRIS) as well as clinical response.Safety was monitored RESULTS: Twenty patients (50.0±11.6 years;9 women) were included, all with long-standing PsO and frequent nail and scalp involvement. Over 24 weeks no significant progression in the SEL number was detected while entheseal cortical density and cortical thickness also remained stable. No progression in number and volume of erosions was observed. Total PsAMRIS as marker of inflammation remained stable. Significant improvements in skin disease activity (PASI: 10.9±6.7 vs. 5.2±6.6,p=0.013) and tender joint count (3.2±3.4 vs. 0.8±1.8,p=0.006) was seen. No new safety signals emerged. In PsO patients at increased risk of PsA, no significant change in subclinical entheseal bone or inflammatory imaging was observed over 24 weeks of apremilast treatment, while skin disease activity and pain outcomes improved. These findings support further investigation of disease-interception strategies in early psoriatic disease.
Rehabilitation is rarely integrated into routine rheumatology care, despite high rates of functional limitation in adults with rheumatoid arthritis (RA). The Preserving Valued Activities in Life (PREVAIL) model of care proposes a function-focused screening survey administered during routine rheumatology visits to guide referrals to rehabilitation and facilitate integration into standard RA care. This study aimed to assess the perceived feasibility and acceptability of the PREVAIL model and inform modifications for pilot testing. We used a multimethod approach including (1) a cross-sectional survey of 309 adults with RA to assess the feasibility and validity of a proposed screening tool to identify functional limitations for referral and (2) semistructured interviews with 24 adults with RA, 6 rheumatology clinicians, and 6 physical therapists to evaluate the perceived acceptability and feasibility of the PREVAIL model of care. The proposed screening tool demonstrated moderate correlations with established measures of functional status and disease activity but identified 90% of participants for rehabilitation referral based on proposed disability risk criteria, necessitating refinement. Interview data revealed broad support for the PREVAIL model across key vested parties. Participants emphasized the value of proactively addressing function, identified patient and clinician knowledge gaps regarding rehabilitation, and highlighted the model's potential to enhance patient-clinician communication. Modifications to improve feasibility included remote survey completion, educational materials for key vested parties, and an interim physical therapy consultation call to better prioritize referrals. The PREVAIL model of care was perceived to be both feasible and acceptable. Study findings directly inform refinements to support real-world implementation in a pilot clinical trial.
Early and accurate prediction of rheumatoid arthritis (RA) is critical for improving patient prognosis; however, existing approaches rely excessively on single autoantibody markers, neglect the systematic predictive value of routine hematological parameters, and lack mechanistic interpretability. In this study, 500 patients attending a rheumatology outpatient clinic were enrolled, and 29 routine laboratory features were collected. Anti-CCP positivity and early RA onset within 12 months were defined as dual binary prediction targets. Five traditional machine learning models (logistic regression, random forest, gradient boosting, SVM, and KNN) and five deep learning models (MLP, ResNet, Transformer, AE-Classifier, and TCN) were systematically compared using six evaluation metrics: accuracy, AUC-ROC, F1-score, precision, recall, and Matthews correlation coefficient (MCC). A four-dimensional SHAP explainability analysis was subsequently applied to the best-performing deep learning model. Logistic regression achieved the best overall performance (Accuracy = 0.848, AUC = 0.857, F1 = 0.910, MCC = 0.441). Among deep learning models, the Transformer performed relatively well (AUC = 0.812), whereas ResNet and TCN exhibited severe class collapse (MCC ≈ 0). SHAP analysis identified ESR (Mean|SHAP| = 0.097) and CRP (0.090) as the most important positive predictive drivers, and albumin (ALB, 0.062) as the key protective factor, together forming a core biomarker triad for early RA risk prediction. Dependence plots further revealed the synergistic interaction between ESR and CRP, as well as a non-linear protective threshold effect of ALB. Individual waterfall plots confirmed close alignment between model decisions and clinical pathological mechanisms. The proposed machine learning pipeline based on routine laboratory parameters can effectively predict early RA risk, and the SHAP explainability analysis transforms the model "black box" into clinically readable decision rationale, providing evidence-based support for optimizing early screening strategies in rheumatology.
Mild and moderate asthma are the most common forms of asthma, but they often remain poorly controlled due to inappropriate treatment strategies and low adherence. Formal consensus on best practices for managing mild-to-moderate asthma is still lacking. To achieve formal consensus on the management of mild-to-moderate asthma and validate the appropriateness and clinical feasibility of the recommendations in clinical practice. A modified Delphi process involving a panel of respiratory experts was employed to formulate consensus statements across the following key domains identified through a cross-sectional survey administered to Italian allergists and immunologists: definition of asthma control, tools for assessment of asthma control, patient phenotyping, personalized treatment, and patient education and empowerment. The appropriateness and clinical feasibility of the agreed statements were validated with a RAND/UCLA method. Full consensus was reached on asthma control in mild-to-moderate asthma, defined as the absence of symptoms, exacerbations, limitation of daily activities, and oral corticosteroids, and the optimization of lung function. Assessment of control, future risk, and phenotype should be performed with appropriate tools and timing, to implement proactive management especially in patients at risk of exacerbations and disease progression. This study provides a comprehensive, expert-driven consensus for the management of mild-to-moderate asthma, formally validated for appropriateness despite variability in real-world implementation. The findings support a patient-centric, proactive approach and offer practical recommendations to bridge the gap between guidelines and clinical practice.
Patients with rheumatoid arthritis (RA) face an elevated risk of sepsis and its associated neurological complications, most notably sepsis-associated encephalopathy (SAE). Nonetheless, early identification of SAE in this population remains a substantial clinical challenge. To address this gap, we aimed to develop and validate a predictive model that incorporates the neutrophil-to-albumin ratio (NAR) to estimate SAE risk in RA patients with sepsis. This retrospective multicenter cohort study included a derivation cohort of 89 patients with RA and sepsis from two centers and an independent external validation cohort of 37 patients from a third center. Patients in the derivation cohort were classified into SAE and non-SAE groups. Three machine learning algorithms (LASSO, random forest, and XGBoost) were applied for feature selection, and the optimal model was selected based on area under the receiver operating characteristic curve (AUC). Model performance was evaluated using bootstrap resampling, calibration curves, and decision curve analysis. The final XGBoost model was subsequently evaluated in the external validation cohort. A web-based dynamic prediction tool was developed for clinical application. Kaplan-Meier analysis and Cox regression were performed to evaluate 28-day survival. SAE occurred in 23.6% of patients and was associated with significantly higher 28-day mortality (61.9% vs. 33.8%, p = 0.04). Six consensus predictors (SOFA score, procalcitonin, platelet count, length of stay, NAR, and age) were identified. The XGBoost model achieved a bootstrap-corrected AUC of 0.859 (95% CI: 0.751-0.946) in the derivation cohort. In the independent external validation cohort, the final XGBoost model achieved an AUC of 0.849 (95% CI: 0.674-1.000). SHAP analysis demonstrated that higher SOFA, procalcitonin, length of stay, age, and NAR values increased SAE risk, whereas higher platelet count was protective. Kaplan-Meier analysis showed significantly lower 28-day survival in the high NAR group (p = 0.023), and elevated NAR was associated with increased mortality risk (HR = 2.178, 95% CI: 1.095-4.332). The NAR-integrated XGBoost model provides a robust and interpretable tool for early SAE prediction in RA patients with sepsis, showing potential clinical utility for bedside risk stratification.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder associated with accelerated atherosclerosis and increased cardiovascular morbidity. Atherogenic indices derived from routine lipid parameters have emerged as potential markers of cardiovascular risk; however, their relationship with disease activity in RA remains incompletely understood, particularly in Indian populations. To evaluate the association between atherogenic indices and disease activity in patients with rheumatoid arthritis and to assess their potential utility as biomarkers of inflammatory burden and cardiometabolic risk. This cross-sectional observational study included 100 patients with rheumatoid arthritis (RA) who met the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and 50 years of age- and sex-frequency-matched control participants without rheumatoid arthritis or other inflammatory rheumatic diseases. Clinical, anthropometric, laboratory, and lipid profile data were collected. Disease activity was assessed using the Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP). Atherogenic indices, including Castelli's Risk Index-I (CRI-I), Castelli's Risk Index-II (CRI-II), Atherogenic Index of Plasma (AIP), Atherogenic Coefficient (AC), and non-high-density lipoprotein cholesterol (non-HDL-C), were calculated and analyzed in relation to disease activity measures. Patients with RA exhibited significantly higher triglycerides, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), Castelli's Risk Index-I (CRI-I), Castelli's Risk Index-II (CRI-II), Atherogenic Index of Plasma (AIP), and Atherogenic Coefficient (AC), together with lower HDL-C levels compared with healthy controls (all p<0.05). Atherogenic indices increased progressively across disease activity categories, with the highest values observed among patients with high disease activity (all p≤0.001). Among the evaluated indices, AIP demonstrated the strongest correlation with Disease Activity Score in 28 joints with C-reactive protein (DAS28-CRP) (r=0.45, p<0.001), followed by CRI-II (r=0.38, p<0.001). In multivariable logistic regression analysis, AIP remained independently associated with high disease activity (odds ratio (OR)=3.12, 95% CI: 1.42-6.85, p=0.004), together with erythrocyte sedimentation rate (ESR) and BMI. Atherogenic indices are significantly associated with disease activity in rheumatoid arthritis, with AIP demonstrating the strongest relationship with inflammatory burden. These findings suggest that AIP may serve as a simple, inexpensive, and readily available marker for the integrated assessment of disease activity and cardiometabolic risk in patients with RA. Prospective multicenter studies are warranted to validate its clinical utility and prognostic significance.
Systemic autoimmune diseases can adversely affect the health of childbearing women and pregnancy outcomes. Additionally, some of theadministered medications are teratogenic, prompting international rheumatological societies to recommend effective contraception and preconception counselling. Given the limited structured education in this field, this study aimed to assess reproductive health awareness and perceptions of family planning among women with systemic autoimmune diseases. A survey-based study was conducted at the Division of Clinical Immunology and Rheumatology, University Hospital Centre Zagreb, Zagreb, Croatia. The sample included 165 women aged 18-50 years who completed the ReproKnow questionnaire assessing reproductive health knowledge, while sociodemographic and clinical data were obtained through interviews and medical records. The median ReproKnow score was 5/10 correct answers indicating moderate knowledge of the studied topic. Greater reproductive health awareness was observed among patients with higher education levels and those diagnosed with SLE or vasculitis. Although one-third of participants stated that their diagnosis affected family planning, only one-fifth reported consistent contraception use, even among those receiving teratogenic medications. Knowledge of contraception efficacy was low (25%), but associated with consistent use. Substantial gaps remain in contraception knowledge and use, highlighting the need for targeted educational interventions and further research to improve reproductive health counselling and contraception practice.