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BackgroundDifficult-to-treat rheumatoid arthritis (D2T RA) refers to a subset of patients who fail to achieve adequate disease control after the use of two or more biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with different mechanisms of action, while maintaining active inflammatory disease. This presents a therapeutic challenge and highlights the need to explore contributing factors such as the potential role of the gut microbiota. Therefore, the aim of this study was to analyze the gut microbiota and inflammation in patients with D2T RA in comparison to patients with easy-to-treat RA (E2T RA).ObjectiveTo analyze the gut microbiota and inflammation in patients with D2T RA.MethodsWe performed an observational study of a prospective cohort between 2007 and 2011 and analyzed the gut microbiota. In 2022, we identified 2 extreme patient phenotypes: (1) D2T RA, which was defined as failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (with different mechanisms of action) plus signs of active disease; and (2) easy-to-treat RA (E2T RA), i.e., stable disease managed with a single treatment. The gut microbiota was analyzed using 16S rRNA gene sequencing; bioinformatics analysis was performed using QIIME2, and its functionality was inferred through PICRUSt. We recorded data on clinical findings, inflammation, and cytokines. A Cox multivariate analysis was performed to identify factors related to D2T RA.ResultsThe study population comprised 39 patients: 13 (33%) with D2T RA and 26 (66%) with E2T RA. The families Lachnospiraceae and Pasteurellaceae, and their genera Coprococcus and Haemophilus were more abundant in E2T RA patients, while the genus Megasphaera was more abundant in D2T RA patients. The Firmicutes/Bacteroidetes ratio decreased in D2T RA patients. The metabolic profile of the gut microbiota was characterized by differences in Degradation/Utilization/Assimilation pathway and the Biosynthesis pathway. The factors associated with D2T RA were inflammatory activity according to DAS28-ESR (HR, 2.649; p = 0.013), prednisone (HR, 3.794; p = 0.008), and the Firmicutes/Bacteroidetes ratio (HR, 0.288; p = 0.033).ConclusionThe composition of the gut microbiota of patients with D2T RA differed from that of E2T RA patients, as did the metabolic pathways.

Objective To evaluate cognitive function in patients with rheumatoid arthritis (RA) and inflammatory activity.Patients and methods We performed a cross-sectional study of a cohort of patients with RA initiating their first biological treatment due to moderate-to-high inflammation and a healthy control group (no inflammatory diseases) matched for age, sex and educational level. All participants underwent a comprehensive neuropsychological assessment, with cognitive impairment defined as a Montreal Cognitive Assessment (MoCA) score

Objective: To evaluate sleep disorders and associated factors in patients with rheumatoid-arthritis-associated interstitial lung disease (RA-ILD). Methods: We performed an observational study of 35 patients with RA-ILD (cases) and 35 age- and sex-matched RA patients without ILD (controls). We evaluated sleep disorders (Oviedo Sleep Questionnaire), positive psychological factors (resilience using the Wagnild and Young Resilience Scale, emotional intelligence using the 24-item Trait Meta-Mood Scale), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (36-item short-form survey), and fatigue (Functional Assessment of Chronic Illness Therapy Questionnaire). Other variables studied included the Charlson Comorbidity Index (CCI) and RA activity according to the DAS28-ESR. Results: Compared to the controls, the cases were characterized by poorer sleep quality with a higher prevalence of insomnia (42% vs. 20%; p = 0.039), greater severity of insomnia (p = 0.001), and lower sleep satisfaction (p = 0.033). They also had poorer resilience and emotional recovery and more severe anxiety and depression. A diagnosis of ILD was the only factor independently associated with the three dimensions of sleep quality. The predictors of poorer sleep satisfaction in patients with RA-ILD were age (β = −0.379), DAS28-ESR (β = −0.331), and usual interstitial pneumonia pattern (β = −0.438). The predictors of insomnia were DAS28-ESR (β = 0.294), resilience (β = −0.352), and CCI (β = 0.377). Conclusions: RA-ILD is associated with significant sleep disorders. RA-ILD seems to be an independent risk factor for sleep alterations, with a greater impact on insomnia. Age, disease activity, and comorbidity also play a role in sleep disorders in patients with RA-ILD.

Objectives To describe the severity and impact of gastrointestinal involvement in patients with systemic sclerosis (SSc) and identify associated factors.Patients and methods Non-controlled cross-sectional study of patients with SSc (2013 American College of Rheumatology/European League Against Rheumatism criteria). The main variables were severity of gastrointestinal involvement according to the University of California, Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 instrument (UCLA SCTC GIT 2.0) and dysphagia according to the Eating Assessment Tool-10 (EAT-10). We evaluated reflux, distension, diarrhoea, faecal soilage, constipation, emotional well-being and social functioning, as well as dysphagia. Clinical and epidemiological data were collected using the Mini Nutritional Assessment Short Form (MNA-SF) and the EuroQol-5D-3L. The degree of skin fibrosis was assessed using the modified Rodnan skin score (mRSS). Multivariate models were constructed to analyse factors associated with gastrointestinal involvement and dysphagia.Results Of the 75 patients with SSc included, 58.7% had moderate, severe or very severe reflux, 57.4% had constipation according to UCLA SCTC GIT 2.0 and 49.7% had abdominal distension. Gastrointestinal symptoms interfered significantly with social functioning (42.7%) and emotional well-being (40.0%). Dysphagia (EAT-10≥3) was recorded in 52% of patients, and according to MNA-SF poor nutrition in 30.7%, and clear malnutrition requiring a nutritional intervention in 5.3%. Multivariate adjustment revealed an association between severity of gastrointestinal symptoms according to the mRSS (β=0.249; p=0.002) and Visual Analogue Scale 3-Level EuroQol-5D (VAS-EQ-5D-3L) (β=–0.302; p=0.001), whereas presence of dysphagia was associated with the mRSS (OR=2.794; p=0.015), VAS-EQ-5D-3L (OR=0.950; p=0.005) and malnutrition (MNA-SF≤7; OR=3.920; p=0.041).Conclusions Patients with SSc frequently present severe gastrointestinal symptoms. These are associated with poor quality of life, more severe skin involvement and malnutrition.

ObjectiveTo describe severe infection, foci of infection, microorganisms, associated factors, and impact on mortality in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD).Patients and methodsThe study was based on a multicenter prospective cohort of patients with RA-ILD followed up from 2015 to 2023. The main outcome measures were incident severe infection and fatal infection. We evaluated infectious foci, etiologic agents, vaccination status, variables associated with lung function, and clinical-therapeutic variables in RA. The incidence rate (IR) for infection and mortality was calculated per 100 person-years, and 3 multivariate models were constructed to explore factors associated with infection.ResultsWe followed up 148 patients with RA-ILD for a median 56.7 months (699.3 person-years). During this period, 142 patients (96%) had at least 1 infection. A total of 368 infectious episodes were recorded, with an IR of 52.6 per 100 person-years. Of the 48 patients who died, 65% did so from infection. Respiratory infections were the most common first infection (74%), infection overall (74%), and fatal infection (80%) and were caused mostly by SARS CoV-2, Streptococcus pneumoniae, Pseudomonas aeruginosa, and influenza A virus. The factors associated with an increased risk of infection and death in patients with RA-ILD were age, inflammatory activity, and therapy with corticosteroids and immunosuppressants.ConclusionPatients with RA-ILD have a high risk of serious infection, especially respiratory infection. Infection develops early, is recurrent, and is frequently fatal. The presence of associated factors such as advanced age, joint inflammation, and treatment highlight the importance of integrated and preventive medical care.

Silicon included in a restructured meat (RM) matrix (Si-RM) as a functional ingredient has been demonstrated to be a potential bioactive antidiabetic compound. However, the jejunal and hepatic molecular mechanisms by which Si-RM exerts its cholesterol-lowering effects remain unclear. Male Wistar rats fed an RM included in a high-saturated-fat high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection were used as late-stage type 2 diabetes mellitus (T2DM) model. Si-RM was included into the HSFHCD as a functional food. An early-stage TD2M group fed a high-saturated-fat diet (HSFD) was taken as reference. Si-RM inhibited the hepatic and intestinal microsomal triglyceride transfer protein (MTP) reducing the apoB-containing lipoprotein assembly and cholesterol absorption. Upregulation of liver X receptor (LXRα/β) by Si-RM turned in a higher low-density lipoprotein receptor (LDLr) and ATP-binding cassette transporters (ABCG5/8, ABCA1) promoting jejunal cholesterol efflux and transintestinal cholesterol excretion (TICE), and facilitating partially reverse cholesterol transport (RCT). Si-RM decreased the jejunal absorptive area and improved mucosal barrier integrity. Consequently, plasma triglycerides and cholesterol levels decreased, as well as the formation of atherogenic lipoprotein particles. Si-RM mitigated the dyslipidemia associated with late-stage T2DM by Improving cholesterol homeostasis. Silicon could be used as an effective nutritional approach in diabetic dyslipidemia management.

ObjectivesTo describe the characteristics of patients between late-onset rheumatoid arthritis (LORA) with young-onset (YORA), and analyze their association with cumulative inflammatory burden.MethodsWe performed a nested cohort study in a prospective cohort comprising 110 patients with rheumatoid arthritis (RA) and 110 age- and sex-matched controls. The main variable was cumulative inflammatory activity according to the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR). High activity was defined as DAS28 ≥ 3.2 and low activity as DAS28 < 3.2. The other variables recorded were inflammatory cytokines, physical function, and comorbid conditions. Two multivariate models were run to identify factors associated with cumulative inflammatory activity.ResultsA total of 22/110 patients (20%) met the criteria for LORA (≥ 60 years). Patients with LORA more frequently had comorbid conditions than patients with YORA and controls. Compared with YORA patients, more LORA patients had cumulative high inflammatory activity from onset [13 (59%) vs. 28 (31%); p = 0.018] and high values for CRP (p = 0.039) and IL-6 (p = 0.045). Cumulative high inflammatory activity in patients with RA was associated with LORA [OR (95% CI) 4.69 (1.49–10.71); p = 0.008], smoking [OR (95% CI) 2.07 (1.13–3.78); p = 0.017], anti–citrullinated peptide antibody [OR (95% CI) 3.24 (1.15–9.13); p = 0.025], average Health Assessment Questionnaire (HAQ) score [OR (95% CI) 2.09 (1.03–14.23); p = 0.034], and physical activity [OR (95% CI) 0.99 (0.99–0.99); p = 0.010]. The second model revealed similar associations with inflammatory activity in patients with LORA.ConclusionControl of inflammation after diagnosis is poorer and comorbidity more frequent in patients with LORA than in YORA patients and healthy controls.

Objective: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD). Methods: We performed a prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. Results: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2–42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR [95% CI], 2.52 [1.03–3.12]; p = 0.041), FVC (OR [95% CI], 0.82 [0.70–0.96]; p = 0.019), and DLCO (OR [95% CI], 0.83 [0.72–0.96]; p = 0.018). Only 10.5% of patients experienced severe adverse effects. Conclusion: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.

This study explores the influence of carboxymethylcelullose (CMC) and methylcelullose (MC), added by simultaneous (sim) and sequential (seq) emulsification methods, on the structure, rheological parameters and in vitro lipid digestibility of pork lard O/W emulsions stabilized by soy protein concentrate (SPC). Five emulsions (SPC, SPC/CMC-sim, SPC/CMC-seq SPC/MC-sim, SPC/MC-seq) were prepared in vitro. The presence of CMC and MC, and the stage of incorporation affected the emulsion microstructure. In the SPC emulsion, lipid droplets were entrapped by a protein layer that was thicker when MC was added, providing greater resistance against environmental stresses during gastrointestinal digestion. At 37 °C, CMC incorporation produced a structural reinforcement of the SPC emulsion, whereas MC addition did not affect the network rigidity, although a delaying effect on the crossover temperature was observed, which was more evident in SPC/MC–seq. The presence and stage of CMC and MC incorporation affected the rate and extent of lipolysis, with SPC/MC-seq presenting an inferior concentration of free fatty acids. The lower extent of lipolysis observed in SPC/MC-seq may be positive in the manufacture of animal fat products in which reduced fatty acid absorption is intended.