Sex and gender shape disease presentation, diagnostic accuracy, treatment response and clinical outcomes in rheumatology, yet these dimensions remain insufficiently embedded in clinical practice. Owing to the markedly unbalanced sex prevalence ratios across many rheumatic diseases, the 'minority' sex is consistently under-represented in clinical studies, limiting the interpretation of long-term outcomes and treatment effectiveness. Sex-related differences in pain perception, inflammatory biomarkers and imaging patterns further complicate disease assessment, and treatment allocation and drug persistence also differ between women and men. Gender-related factors - including disparities in care-seeking behaviours, social roles and lifestyle factors - additionally modulate symptom burden and disease trajectories. Evidence remains particularly scarce for transgender, gender-diverse and intersex individuals, who are rarely captured in clinical cohorts, restricting the development of inclusive and generalizable evidence. Embedding sex-aware and gender-aware approaches into diagnostic reasoning, risk assessment and therapeutic decision-making is therefore essential for advancing precision, equity and truly personalized rheumatological care. Such integration enables clinicians to interpret disease signals more accurately, anticipate divergent multimorbidity trajectories and tailor treatment strategies to the biological and sociocultural contexts of each patient.
Rheumatoid arthritis (RA) causes persistent symptoms that limit individuals' ability to engage in meaningful daily occupations. Occupational therapy plays a key role in integrating lifestyle and behavioral strategies into comprehensive RA management. To examine the efficacy of a client-centered, modular lifestyle intervention (LI) on occupational performance and health outcomes of individuals with RA. A randomized controlled trial. Rheumatology outpatient clinic of a university hospital. Forty-five individuals diagnosed with RA were randomly assigned to an LI group (n = 23) or a control group (n = 22). The LI group received an eight-session, occupation-based LI; the control group received twice-weekly well-being check phone calls over 4 wk. The primary outcome was the Canadian Occupational Performance Measure (COPM) Performance score. Secondary outcomes included COPM Satisfaction, Disease Activity Score-28, visual analog scale for pain, Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire, and Rheumatoid Arthritis Quality of Life Scale scores. Assessments were conducted at baseline, postintervention, and 6-mo follow-up. Compared with the control group, the LI group demonstrated significantly greater improvements in the primary outcome (COPM Performance) as well as in secondary outcomes including COPM Satisfaction, pain, fatigue, and quality of life. A delayed reduction in disease activity was observed at the 6-mo follow-up. The LI produced durable improvements in occupational performance and patient-reported outcomes, supporting its integration as a sustainable adjunct to pharmacological care for individuals with RA. Plain-Language Summary: People with rheumatoid arthritis often have difficulty completing daily activities because of pain, fatigue, and limitations in movement. This study explored whether a structured lifestyle program based on occupational therapy principles could help improve these challenges. All participants continued their usual medical treatment throughout the study. In addition, one group received an eight-session lifestyle intervention focused on meaningful daily activities, healthy habits, energy conservation, and participation in social and leisure activities. The control group received their usual medical treatment along with brief well-being check phone calls. Participants who received the lifestyle program showed greater improvements in performing and enjoying daily activities and reported lower fatigue levels than those in the control group. These findings suggest that adding an occupation-based lifestyle program to standard medical care may provide meaningful benefits for people living with rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by progressive joint involvement. The disease is associated with reduced health-related quality of life, functional ability, work productivity, and daily activity, in addition to pain, fatigue, and inflammation-induced structural damage. RA emerges through a complex interplay of multiple factors, including the release of inflammatory cytokines. One such cytokine is tumor necrosis factor (TNF), which is inhibited by golimumab, an approved treatment for the disease. Golimumab is produced using a recombinant cell line that originated from genetically modified mice immunized with human TNF. This narrative review presents the efficacy and safety outcomes from the golimumab pivotal randomized controlled trials (RCTs) that evaluated the subcutaneous and intravenous formulations. Across the RCTs, treatment was associated with an American College of Rheumatology ≥ 20% improvement. A majority of participants reported at least one AE and the most frequent were upper respiratory infection, nasopharyngitis, and bronchitis. The review also presents data from post hoc analyses and real-world studies, which demonstrated benefits that included improvements in health-related quality of life and daily productivity, prolonged drug survival, and reduced fatigue, pain, disease activity, and structural damage. Lastly, data from meta-analyses, including RCTs and real-world studies, demonstrated that golimumab had an adverse event pattern similar to other TNF inhibitors. Collectively, these studies demonstrated that golimumab is an effective and safe treatment for RA when used according to the approved indication.
This is the official English summary of the Japanese 2025 guide. The first edition of the guide for the diagnosis and management of connective tissue disease (CTD) associated with interstitial lung disease (ILD) was published in 2020 as a joint initiative by the Japanese Respiratory Society and the Japanese College of Rheumatology. This updated edition reflects major advances over the past five years, incorporating the latest international guidelines, consensus statements, and considerations unique to the Japanese healthcare reimbursement system. The guide is structured to facilitate timely clinical decision-making by highlighting key diagnostic and therapeutic milestones. The newly added content includes a conceptual framework for understanding ILD in CTD, practical clinical flowcharts, screening strategies, and risk factors, an overview of acute exacerbations, and a comprehensive approach to rehabilitation. Notably, treatment algorithms for ILD associated with polymyositis/dermatomyositis and systemic sclerosis have been revised to align with the most recent evidence and disease-specific recommendations, thereby enhancing their relevance to real-world practice. In addition, a provisional algorithm was proposed for the management of rheumatoid arthritis-associated ILD. The updated guide aims to standardize the multidisciplinary management of CTD-associated ILD and offers future perspectives to guide research and improve patient outcomes.
AimTo evaluate the factors associated with changes in self-efficacy in systemic lupus erythematosus (SLE) patients from a prevalent cohort.MethodsMembers of the Almenara Lupus Cohort who had entered it between 2018 and 2024 were included. Sociodemographic variables were collected. Self-efficacy was examined with the five domains of the PROMIS self-efficacy for the management of chronic conditions' instrument and general self-efficacy. The Short Form (SF)-36 health questionnaire' [physical and mental component summary measures (PCS and MCS)] was obtained. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and damage with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Therapeutic variables included the use of antimalarials and of immunosuppressants as well as the daily prednisone dose. Generalized estimating equations were performed using general self-efficacy and the five domains for chronic disease management as outcomes.Results331 patients were included; their mean age at diagnosis was 35.1 (SD = 13.7) years and 91.5% their disease duration at baseline was 10.3 (SD = 7.49) years; (n = 303) were women; 97.9% were Mestizo. Factors associated with a better general self-efficacy were White ethnicity (β = 7.09, SE = 1.14, p < 0.001), being currently employed (β = 1.09, SE = 0.53, p = 0.038), PCS (β = 0.08, SE = 0.02, p < 0.001), and previous general self-efficacy (β = 0.39, SE = 0.05, p < 0.001). In contrast, Black ethnicity (β = -2.06, SE = 0.56, p < 0.001 and daily prednisone dose (β = -0.13, SE = 0.02, p < 0.001) were negatively associated with general self-efficacy.ConclusionsFactors associated with general self-efficacy improvement were higher previous self-efficacy, White ethnicity, being currently employed and having a better HRQoL In contrast, Black ethnicity and higher daily prednisone dose predisposed to general self-efficacy worsening.
People with rheumatoid arthritis (RA) are at increased risk of serious infection, but less is known about nonserious infections. Our prospective cohort study evaluated associations between medications for RA and the risk of nonserious infections. We remotely recruited adults with RA in a community rheumatology practice-based research network. Participants joined the ArthritisPower Registry (now PatientSpot) and completed a baseline and up to six monthly follow-up surveys. Using data from consecutive monthly surveys, we assessed associations between medication use at the prior survey and infection report at the subsequent survey, adjusting for confounders. We recruited 351 people with RA (mean age 60, 84% female) who reported 439 infections (330 infections per 100 patient-years). Associations between medication use and infection were assessed among 1,075 qualifying observations with 289 (27%) total infections and 146 (14%) infections with health care encounters or antibiotic use. Compared to those receiving conventional synthetic disease-modifying antirheumatic drugs who were biologic or JAK inhibitor (JAKi) naïve, current biologic or JAKi use was not associated with either infection outcome. Infections were numerically more common with glucocorticoids ≥10 mg/day (odds ratio 1.94, 95% confidence interval 0.89-4.24). Season, previous infection, poorer function, and rural residence were significantly associated with one or both infection outcomes. Biologics and JAKi were not associated with greater risk for nonserious infections compared to conventional therapies. Given that nonserious infection risk may be due more to exposures and general health status, future studies should assess whether the common practice of interrupting medications in people with infection improves or worsens outcomes.
This study aimed to determine the risk of developing interstitial lung disease (ILD) as a major post-COVID outcome in individuals with autoimmune diseases. This retrospective cohort study utilized data from the TriNetX U.S. Collaborative Network. The case group comprised individuals with autoimmune rheumatic diseases who contracted COVID-19, whereas the control group included those who remained uninfected during the follow-up period. Patient baseline characteristics were balanced using propensity score matching (PSM). The primary outcome was newly diagnosed ILD. A Cox proportional hazards regression model was employed to calculate PSM-adjusted hazard ratios (HRs). Kaplan-Meier curves and log-rank tests were used to evaluate survival differences. The study included 174 256 individuals (26 768 COVID-19 cases and 147 488 controls) from January 1, 2020, to December 31, 2022. After propensity score matching, two cohorts of 26 763 individuals were identified, both with balanced baseline characteristics. During the follow-up period, the COVID-19 group exhibited a significantly higher risk of ILD (HR: 1.23; 95% CI: 1.10-1.36). Subgroup analyses by age, sex, and autoimmune disease consistently revealed higher risks in the COVID-19 group than in the control group. COVID-19 infection was identified as a risk factor for the development of ILD in patients with autoimmune diseases, highlighting the importance of vigilant pulmonary surveillance in this population. Nevertheless, these findings should be interpreted with caution due to potential residual confounding, diagnostic misclassification, and the heterogeneity of autoimmune diseases, which may mask disease-specific risk variations and lead to potential misattribution of ILD risk across different autoimmune conditions.
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Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) associated with systemic autoimmune rheumatic diseases (SARDs). Its clinical characteristics and outcomes in SARDs remain poorly defined. To describe demographics, imaging patterns, and outcomes in SARD-associated PPFE. Patients diagnosed with PPFE and SARDs at Mayo Clinic (2000-2024) were included. PPFE diagnosis was confirmed by high-resolution computed tomography, and SARD diagnoses were established by rheumatologists. Fifteen of 62 patients with PPFE had SARDs with majority having systemic sclerosis (SSc)(n= 7, 46%). Median age at PPFE diagnosis was 57.2 years; 80% were female; 40% were ever-smokers; 40% required supplemental oxygen; 5 had pulmonary hypertension. Coexisting ILD patterns included UIP (26.7%) and NSIP (20%). Coexisting ILD patterns included usual interstitial pneumonia (26.7%) and nonspecific interstitial pneumonia (20%). Three patients died, including two with SSc. Systemic sclerosis was the most frequently observed SARD among patients with PPFE, and may coexist with other ILD patterns; recognition may inform risk stratification, multidisciplinary evaluation, and longitudinal follow-up. Pleuroparenchymal Fibroelastosis and Rheumatic Disorders: What We Know So FarPleuroparenchymal fibroelastosis (PPFE) is an uncommon type of lung scarring that mainly affects the upper parts of the lungs and the thin membrane covering them (the pleura). While PPFE can occur after lung transplants or infections, it is now being recognized in people with autoimmune diseases that also affect the lungs. These conditions are known as systemic autoimmune rheumatic diseases (SARDs) and include illnesses such as scleroderma, rheumatoid arthritis, lupus, and myositis. This study looked at patients diagnosed with PPFE at Mayo Clinic between 2000 and 2023 to better understand how PPFE appears in people with autoimmune diseases. Researchers reviewed medical records and imaging studies (CT scans) and confirmed each case through both lung and rheumatology specialists. Out of 62 people with PPFE, 15 also had an autoimmune disease. The most common condition linked to PPFE was systemic sclerosis, followed by dermatomyositis, rheumatoid arthritis, systemic lupus erythematosus, and mixed connective tissue disease. Most of the affected patients were women in their fifties. Nearly half of them needed oxygen therapy, and some developed pulmonary hypertension. The study found that PPFE can occur across several autoimmune diseases, not just scleroderma. Recognizing this connection can help doctors identify lung scarring earlier and provide more personalized care for people with autoimmune diseases who develop breathing problems.
This review examines enhancements to the U-Net's ability to represent complex spatial structures for segmentation through attention mechanisms. The study surveys applications across both medical and non-medical domains, focusing on cSAM, cCAM, CBAM, and their associated serial (sfSCAM) and parallel (pfSCAM) fusion architectures. Beyond accuracy, the analysis also considers backbone design, diversity of evaluation metrics, pruning strategies, and potential sources of bias. Following PRISMA guidelines, we systematically searched major academic databases using U-Net- and attention-related keywords. The final corpus was constructed through stepwise exclusions (E1-E3) from an initial set of 1807 retrieved records. Spatial, channel, and hybrid attention modules were taxonomized; their placement within encoder, decoder, skip, and bottleneck blocks was identified; and application trends across domains such as liver, brain, skin, and retinal imaging were summarized. Attention-augmented U-Net models consistently improved the segmentation of subtle, scale-dependent structures across modalities, including CT, MRI, ultrasound, dermoscopy, fundus, and satellite imaging. Spatial attention in skip connections and decoders reduced noise while preserving boundaries, whereas encoder-level channel attention improved semantic weighting; CBAM combined both effects. Parallel fusion (pfSCAM) balanced accuracy and efficiency, while serial fusion (sfSCAM) enabled stable feature refinement. Attention placement strongly influenced global-local fusion and noise suppression. Pruning reduced computational cost with minimal performance loss, although evaluation remained focused on Dice and cross-entropy, with limited use of IoU, Hausdorff distance, and F1-score. Spatial and channel attention, along with their serial and parallel fusion variants, function as structural design principles within the U-Net. Effective practice integrates careful module placement, pruning or quantization strategies, and explicit bias auditing.
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Primary Sjögren's disease (pSjD) is one of the most common autoimmune connective tissue diseases. Sicca symptoms are a hallmark of pSjD. Up to 80% of patients have immunoglobulin G (IgG) anti-Ro52 autoantibodies in their plasma. This study investigates the frequency of IgG and IgA anti-Ro52 autoantibodies in plasma and saliva from pSjD patients, and assess the associations between disease activity and autoantibody titers. The study was conducted on a Norwegian cross-sectional SjD cohort (n = 113). IgA and IgG anti-Ro52 autoantibodies were measured in plasma and saliva by an indirect in-house enzyme-linked immunosorbent assay (ELISA). ELISA results were correlated with clinical data using relative risk and Spearman's correlation coefficients. Measuring plasma, 73% of the cohort were positive for IgG anti-Ro52 and 47% for IgA anti-Ro52 autoantibodies. In saliva, 34% were positive for IgA anti-Ro52 and 17% for IgG anti-Ro52 autoantibodies. We observed an inverse correlation between plasma IgG anti-Ro52 autoantibodies and disease activity. Patients with a low plasma titre of IgG anti-Ro52 autoantibodies had a higher probability of reporting pain, as indicated by the EULAR Sjögren's Syndrome Patient Reported Index score (relative risk = 0.48, 95% confidence interval 0.29-0.80, p = 0.002). Furthermore, plasma IgA anti-Ro52 correlated significantly with the focus score. IgA and IgG anti-Ro52 autoantibodies in saliva and plasma showed an inverse correlation with disease activity but significant positive association with immune activity in patients with SjD. Our findings do not support the use of salivary IgA and IgG anti-Ro52 autoantibodies as biomarkers of disease activity in SjD.
The sharp increase in prevalence of atopic disease suggests a role for environmental factors, such as the microbiome. Here, we study the impact of immunoglobulin A (IgA) coating of gut bacteria in infancy on allergic outcomes in two distinct populations: (1) an urbanized cohort of Rochester infants (ROC) enriched for allergies (prevalence of 40%) and (2) infants from a traditional, agrarian Old Order Mennonite (OOM) community with a low prevalence of allergies (less than 2%). We performed immunoglobulin A sequencing (IgA-SEQ) on stool samples collected at an average of 6 months of life to assess gut microbiome IgA coating levels in 9 OOM and 21 ROC infants. Atopic outcomes were diagnosed throughout the first 2 years; 10 of the ROC infants were diagnosed with atopic dermatitis and/or food allergy, while none of the OOM infants were allergic. We also assessed human milk IgA-binding of taxa-derived protein antigens, as well as IgA binding to live bacterial cell cultures. Gut microbiome composition was dominated by Bifidobacterium, followed by Ruminococcus, Enterobacteriaceae, and Blautia. Higher IgA coating of P. melaninogenica and Pasteurellaceae were associated with allergic outcomes and higher coating of R. gnavus was observed in non-allergic infants. IgA coating levels of Atopobium, Bifidobacterium, and Coprococcus were positively associated with infant age, and coating levels of Corynebacterium associated negatively with infant age. In non-allergic infants, IgA coating of Clostridium was decreased, while in allergic infants, IgA coating of Corynebacterium was decreased. Furthermore, breastfeeding was associated with higher levels of fecal IgA in infancy, and IgA-binding capacity to B. infantis, a keystone infant commensal, was subsequently assessed using in vitro experiments. Compared to the ROC cohort, milk from OOM mothers exhibited a higher level of IgA response to B. infantis and several other commensals. Surprisingly, IgA-binding to B. infantis was partially mediated by Fab-independent interactions through binding to glycosylated regions of immunoglobulins. Differential gut microbial IgA coating may play a role in development of allergic diseases in infancy. Human milk from communities with low rates of allergic diseases exhibit higher IgA responses to infant commensals, including B. infantis.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with fluctuating disease activity and heterogeneous clinical manifestations. While DNA methylation changes have been implicated in SLE pathogenesis, their relationship to disease activity remains unclear. This study aimed to identify epigenetic correlates of disease activity in women with SLE using genome-wide DNA methylation profiling. Whole blood DNA from 48 women with established SLE was analyzed using Illumina EPIC arrays. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Differentially methylated positions (DMPs) and regions (DMRs) associated with disease activity were identified using linear modeling and region-level analyses, adjusting for age, ethnicity, smoking status, body mass index (BMI), and cell composition. Gene ontology enrichment and motif analyses were also performed. No individual CpGs reached FDR-corrected significance, therefore, a hypothesis-generating approach using a raw p-value < 0.01 was applied. Over 4,500 suggestive DMPs (p < 0.01) were identified and further analyzed for DMRs and pathway mapping. Thirty-six significant DMRs (at 1% false discovery rate) were detected, with several genes involved in neuroimmune regulation and systemic inflammation. Motif analysis identified REST, a transcriptional repressor that silences neuronal genes in non-neuronal tissues, as a common motif among several DMRs. Semantic analysis of the affected loci revealed five major biological domains relevant to SLE: immune signaling, neuroimmune and neural processes, organ developmental morphogenesis, metabolic regulation, and epigenetic control. This exploratory study identified potential epigenome-wide methylation changes linked to disease activity in a well-controlled cohort of women with SLE. Region-level analysis revealed DMRs mapping to immune and neuroimmune pathways and showed enrichment of the REST binding motif. Although these findings are preliminary and require independent validation, they suggest subtle epigenetic alterations that may be associated with SLE activity and points to candidate pathways for further investigation.
Patients with autoimmune inflammatory rheumatic diseases are particularly vulnerable to infectious diseases. Accordingly, a broader range of vaccines and, in some cases, additional doses are recommended for these patients compared with the general population. This study investigated the vaccination status of adult patients with non-rheumatoid arthritis rheumatic diseases (NRRDs). This retrospective study was conducted in the rheumatology outpatient department of a tertiary care hospital and included adult patients (aged ≥19 years) with NRRDs who received glucocorticoids and/or disease-modifying antirheumatic drugs from January 2023 to March 2023. Among these patients, we compared vaccination rates between high-level immunosuppression (HLI) and non-HLI groups. HLI was defined as current biologic use or prednisolone equivalent at a dose of ≥20 mg/day for ≥14 days. Of the 4,070 patients with NRRDs, 1,522 (37.4%) were in the HLI group. Overall vaccination rates (complete plus partial vaccination) were significantly lower in the HLI group than in the non-HLI group for influenza (20.2% vs. 31.0%, p<0.001), hepatitis B (59.5% vs. 68.8%, p<0.001), pneumococcal disease (12.9% vs. 26.9%, p<0.001), and herpes zoster (4.3% vs. 10.8%, p<0.001). Overall, vaccination rates were low among patients with NRRDs, with especially low rates in the HLI group. These findings highlight the need for systematic vaccination strategies.
Systemic sclerosis (SSc) is a heterogeneous autoimmune disease in which interstitial lung disease (ILD) is a major determinant of mortality. Given that certain chemokines and adhesion molecules may be involved in the inflammation, subsequent vascular injury, and fibrosis observed in SSc, their circulating levels in peripheral blood may reflect the disease processes ranging from inflammation to vascular damage and fibrotic remodeling. However, the potential of these biomarkers to identify patient subgroups with divergent pulmonary trajectories remains to be elucidated. We performed a retrospective analysis of prospectively collected data from patients with early severe SSc (diffuse cutaneous SSc irrespective of ILD status or limited cutaneous SSc with ILD; disease duration <5 years) who were enrolled in a multicenter cohort. Serum levels of five chemokines and four soluble adhesion molecules were quantified at baseline. Patients were classified based on these biomarker profiles using k-means clustering. Changes in pulmonary function were compared among clusters using relative changes in percent vital capacity (%VC). Patients (n = 92) were classified into three clusters: Cluster 1 (n = 37) with elevated sICAM-1 and sE-selectin; Cluster 2 (n = 13) with elevated CCL2, CXCL8, and sP-selectin; and Cluster 3 (n = 42) with no distinctive biomarker pattern. Cluster 3 showed stable %VC and served as the reference group. Cluster 1 showed early decline (one-year difference: -8.41%; 95% CI: -12.62 to -4.20; p < 0.001) that attenuated by year two. In contrast, Cluster 2 showed progressive decline (two-year difference: -7.77%; 95% CI: -15.25 to -0.29; p = 0.042). These biomarker-defined patterns were consistent with a vasculopathic-fibrotic profile in Cluster 1 and an inflammatory-vascular profile in Cluster 2. Serum chemokine and adhesion molecule profiles may help stratify early severe SSc into biologically distinct subgroups with different pulmonary trajectories, supporting their potential utility for early risk stratification in SSc-ILD.
The present study aimed to explore, in patients with rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis, the direct effects of coping strategies on fatigue and the role of depression and anxiety as mediators. It also investigates how moderators, including diagnosis, disease activity, disease duration, and sex, affect the pathways. This observational cross-sectional study examined a sample of 807 patients receiving outpatient care, who were assessed with the following self-report validated questionnaires: the Coping Orientation to the Problems Experienced, the Chalder Fatigue Questionnaire, the Quick Inventory of Depressive Symptomatology, and the State-Trait Anxiety Inventory. While the effect of problem-focused and emotion-focused coping did not seem to be related to fatigue, dysfunctional coping significantly was. Once depression and anxiety were considered as mediators, the direct effect of dysfunctional coping on fatigue lost its significance. When examining the diagnostic category as a moderator, dysfunctional coping has a more significant relationship with fatigue in axial spondyloarthritis compared to rheumatoid arthritis or psoriatic arthritis. When considering sex as a moderator, the association between dysfunctional coping and depression appeared stronger in females than in males. Disease activity and disease duration do not appear to moderate the paths. Maladaptive coping in rheumatic diseases appears to contribute to higher fatigue levels, a relationship mediated by anxiety and depression symptoms, while diagnosis and sex moderate specific paths.
Oxaliplatin-induced peripheral neuropathy (OIPN) is a common and dose-limiting adverse effect of oxaliplatin-based chemotherapy that markedly impairs treatment adherence and long-term quality of life. Despite extensive investigation, effective preventive and therapeutic strategies remain limited, reflecting the complex and multifactorial nature of its pathogenesis. In this review, we revisit the mechanisms underlying OIPN and propose an integrated, stage-dependent mechanistic perspective. Current evidence indicates that OIPN arises from dynamic interactions among multiple pathological processes operating across temporal and anatomical scales. Early oxaliplatin-induced neurotoxicity is primarily expressed as functional and electrophysiological disturbances, which manifest clinically as acute sensory symptoms such as cold hypersensitivity. With sustained exposure, these alterations progressively engage downstream neuroinflammatory and metabolic cascades, ultimately contributing to structural pathology, including axonal degeneration, and to chronic, often persistent, peripheral neuropathy. Importantly, these mechanisms form self-amplifying loops that facilitate the transition from reversible acute symptoms to irreversible structural damage, providing a mechanistic explanation for the limited success of single-target neuroprotective strategies. Emerging complementary mechanisms are briefly discussed to outline future research directions. By reorganizing current evidence into a hierarchical, stage-linked framework that connects upstream neuronal vulnerability, early functional dysfunction, and downstream inflammatory-structural persistence, this review aims to clarify not only the pathophysiological complexity of OIPN but also its implications for stage-specific and combination-based intervention strategies.
Behçet's disease (BD) is a rare, multisystem inflammatory disorder predominantly affecting women during their reproductive years. Its potential impact on pregnancy outcomes makes understanding optimal management strategies crucial. Given the complexity and variability of this disease during pregnancy, there is a compelling need to review current evidence to guide clinical practice and improve maternal and neonatal outcomes. This narrative review consolidates recent literature from database inception to June 2025, focusing on disease course, reproductive implications, and obstetric outcomes in women with BD. It evaluates the safety of immunosuppressive therapies during conception, pregnancy, and lactation. The review highlights key aspects such as preconception planning, disease monitoring, delivery considerations, and postpartum care, drawing from a broad spectrum of clinical research, guidelines, and expert opinions. The current evidence suggests that with personalized, multidisciplinary care and careful medication management, many women with BD can experience successful pregnancies. While existing data support the safety of several therapies and highlight the importance of preconception counseling, significant gaps remain due to limited high-quality prospective studies. Advancements in understanding disease mechanisms, developing standardized protocols, and establishing evidence-based guidelines are necessary to optimize care and further improve reproductive outcomes in this patient population.
Patients' understanding of pain mechanisms is recognized as a significant factor associated with clinical outcomes. However, relatively little research has explored the impact of patients' post-boosting baseline pain knowledge, beliefs and attitudes on subsequent treatment outcomes. Filling this gap could facilitate informed decision-making at an early stage of intervention. This study aims to examine the relationship between baseline pain knowledge, beliefs and attitudes and clinical health outcomes, including kinesiophobia, following a multidisciplinary rehabilitation program. It was hypothesized that baseline understanding more aligned with contemporary scientific understanding would be associated with improved post-treatment health outcomes, even after controlling for initial health status. A total of 330 participants with fibromyalgia were recruited from a Central Sensitivity Syndromes Specialized Unit. Pain knowledge was assessed using the PACKA questionnaire after a brief educational boosting intervention and prior to participation in a three-month multidisciplinary rehabilitation program including physical exercise, psychological intervention, and further pain education. Health-related variables were measured both before and after the intervention to analyze potential associations between post-boosting baseline pain knowledge and post-treatment health outcomes. After controlling for baseline health outcome scores, higher post-boosting baseline pain knowledge was significantly associated with lower post-treatment kinesiophobia (β = -0.23, 95% CI -0.35 to -0.12, p < 0.001). No significant associations were observed between post-boosting baseline pain knowledge and post-treatment fibromyalgia impact, anxiety, depression, or physical functioning (although the association was positive but non-significant). These findings partially support the initial hypothesis, indicating that higher levels of pain-related knowledge at treatment entry are associated with lower post-treatment kinesiophobia following the intervention, while accounting for initial health status, specifically for kinesiophobia.