Expected impact of immunomodulatory agents during pregnancy: A newborn's perspective.

The neonatal immune ontogeny begins during pregnancy to ensure that the neonate is well-suited for perinatal life. It prioritizes Th2/M2 and regulatory responses over Th/M1 activity to avoid excessive inflammatory responses and to ensure immune tolerance and homeostasis. Newborns also present increased Th17/Th22 responses providing effective anti-fungal immunity and mucosal protection. Intrauterine exposure to immune modulatory drugs with the placental transfer may influence the natural course of the fetal immune development. The vertical transfer of both biological therapy and small molecules begins during the first trimester through neonatal Fc receptor or placental diffusion, respectively, reaching its maximum transfer potential during the third trimester of pregnancy. Most of the biological therapy have a prolonged half-life in newborn's blood, being detectable in infants up to 12 months after birth (usually 6-9 months). The use of immunomodulators during pregnancy is gaining global interest. Current evidence mainly reports birth-related outcomes without exhaustive analysis of the on-target side effect on the perinatal immune system ontogeny, the infection risk, or the immune dysregulation. The present review will focus on: (1) the main characteristics of the perinatal immune system to understand its specific features and vulnerabilities to immune modulation; (2) the mechanisms of placental transfer of immunomodulators; and (3) the immune changes reported to date in newborns exposed to immunomodulators with emphasis on the current concerns and gaps in knowledge.

Proliferative synovitis, an ultrasound pattern associated with ACPA-positive patients and erosive disease in rheumatoid arthritis.

OBJECTIVES: To analyse ultrasound (US) differences between rheumatoid arthritis (RA) patients according to autoantibody status and characterise the clinical and radiological features associated with the US pattern of seropositive patients. METHODS: We collected demographic and clinical data and bilateral hand US images of RA patients. We defined an extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal, which we called US proliferative synovitis (US PS). To better characterise US PS, MRI of the dominant hand and immunostaining of synovial biopsies were made in subgroups of 42 and 23 patients, respectively. RESULTS: We included 205 RA patients (84.8% seropositive). No significant differences in disease activity were found according to autoantibody status. US PS was found in 55.5% of seropositive and 16.1% of seronegative patients (p=0.0001). In the multivariate analysis, erosions [OR 4.90 95% CI (2.17-11.07), p=0.0001] and ACPA [OR 3.5 95% CI (1.39-10.7), p=0.009] but not RF status [OR 0.74 95% CI (0.31-1.71), p=0.483] were independently associated with US PS. After a mean follow-up of 46 months, US PS was independently associated with changes in therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016). Ninety-four per cent of joints with US PS had RAMRIS synovitis sub-index grade 2-3. US PS was significantly associated with higher synovial vessel density (p=0.042). CONCLUSIONS: In RA patients, US PS was associated with ACPA status, erosive disease and an enhanced need to change disease-modifying anti-rheumatic drug therapy in the long-term. At synovial level, this US pattern was characterised by higher vessel density.

Intra-articular therapies: patient preferences and professional practices in European countries.

To assess patient perspective and professional practice of intraarticular therapies (IATs) across Europe, an expert international multidisciplinary panel designed two open web-based surveys: one targeting people who had experienced at least two IATs (44 items); and one targeting health care providers (HCPs) (160 items). Surveys were disseminated via patient and professional associations and social media. A descriptive analysis was performed. The surveys were answered by 200 patients and 186 HCPs from 26 countries, showing that IAT is routinely performed by rheumatologists (97%) and orthopaedic surgeons (89%), with specific training being compulsory in a few countries. The most frequent indications for IAT are arthritis (76%), osteoarthritis (74%), crystal arthritis (71%) and bursitis (70%); the most frequently injected joints are knee (78%) and shoulder (70%); and the most used compounds are glucocorticoids. The majority of HCPs report informing patients about side-effects (73%), benefits (72%), and the nature of the procedure (72%), which coincides with 27% of patients reporting that they had not been informed about benefits or potential complications of IATs; 73% of patients had not been asked whether they wanted an anaesthetic. Few HCPs (10%) obtain written consent (56% get oral consent, being mandatory for 32%), a procedure deemed necessary by 41% of the patients. 50% of patients reported a clear benefit of IAT and 20% experienced complications including pain, impaired mobility, rashes, or swelling. In summary, the practice of IAT is variable across Europe, and although patients perceive it as relatively safe and usually effective procedure, some gaps were identified.

EULAR recommendations for intra-articular therapies.

OBJECTIVES: To establish evidence-based recommendations to guide health professionals using intra-articular therapies (IAT) in adult patients with peripheral arthropathies. METHODS: A multidisciplinary international task force established the objectives, users and scope and the need for background information, including systematic literature reviews) and two surveys addressed to healthcare providers and patients throughout Europe. The evidence was discussed in a face-to-face meeting, recommendations were formulated and subsequently voted for anonymously in a three-round Delphi process to obtain the final agreement. The level of evidence was assigned to each recommendation with the Oxford levels of evidence. RESULTS: Recommendations focus on practical aspects to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles and 11 recommendations were established, addressing issues related to patient information, procedure and setting, accuracy, routine and special aseptic care, safety issues and precautions to be addressed in special populations, efficacy and safety of repeated joint injections, use of local anaesthetics and aftercare. CONCLUSION: We have developed the first evidence and expert opinion-based recommendations to guide health professionals using IAT. We hope that these recommendations will be included in different educational programmes, used by patient associations and put into practice via scientific societies to help improve uniformity and quality of care when performing IAT in peripheral adult joints.

Biomarkers for treatment change and radiographic progression in patients with rheumatoid arthritis in remission: a 5 year follow-up study.

OBJECTIVE: To identify biomarkers of treatment change and radiographic progression in patients with RA under remission. PATIENTS AND METHODS: RA patients in remission (DAS28-ESR <2.6) were selected and followed up for 5 years. An MRI of the dominant hand and an US assessment of knees/hands and serum levels of inflammation/angiogenesis biomarkers were performed at baseline and at 12th month. Synovial biopsies were obtained in patients with Power Doppler signal. Conventional radiographies of hands/feet were taken at baseline and after 5 years. Radiographic progression was defined as the change in the modified Sharp van der Heijde Score at 5 years >10.47 (small detectable change). RESULTS: Sixty patients were included, 81.6% were ACPA+ and 45% were taking biological DMARDs. At baseline, 66.6% had Power Doppler signal. After 5 years, 73.3% of patients remained in remission. Change of therapy was performed in 20 patients (33.3%) and was associated with BMI [odds ratio (OR) 1.3, 95% CI: 1, 1.7], lack of biological DMARD therapy (OR 24.7, 95% CI: 2.3, 257.2), first-year progression of MRI erosions (OR 1.2, 95% CI: 1, 1.3) and calprotectin serum levels (OR 2.8, 95% CI: 1, 8.2). Radiographic progression occurred in six (10%) patients. These patients had higher first-year progression of MRI erosions (P = 0.03) and bone oedema (P = 0.04). Among 23 patients undergoing synovial biopsy, mast cell density was independently associated with clinical flares. CONCLUSIONS: One-third of RA patients lost clinical remission and changed therapy throughout the 5 years of follow-up, which was independently associated with BMI, lack of biological DMARDs therapy and first-year progression of MRI erosion score and calprotectin serum levels. Significant radiographic progression was uncommon.

Interactions between rheumatoid arthritis antibodies are associated with the response to anti-tumor necrosis factor therapy.

BACKGROUND: Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50-60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. METHODS: For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. RESULTS: The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). CONCLUSIONS: The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA.

Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease.

OBJECTIVE: To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. METHODS: Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies. RESULTS: We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample. CONCLUSIONS: Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

A comparative study on clinical and serological characteristics between patients with rhupus and those with systemic lupus erythematosus and rheumatoid arthritis.

BACKGROUND: The concomitant presence of two autoimmune diseases - systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) - in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus. METHODS: This was a cross-sectional study. We included rhupus patients from 11 different rheumatology departments, and compared them to SLE and RA patients at a ratio of 2:1. All information was recorded following a pre-established protocol. RESULTS: A total of 200 patients were included: 40 rhupus patients and 80 each of SLE and RA patients as controls. Disease duration was similar among SLE and rhupus groups (around 13 years), but the RA group had a significantly lower disease duration. Main clinical manifestations were articular (94.2%), cutaneous (77.5%) and haematological (72.5%). Rhupus patients had articular manifestations similar to those expected in RA. Only 10% of rhupus patients had renal involvement compared with 25% of those with SLE (p < 0.05), while interstitial lung disease was more common in patients affected by RA. The 2019 EULAR/ACR SLE criteria were met in 92.5% of the rhupus patients and in 96.3% of the SLE cohort (p > 0.05). Excluding the joint domain, there were no differences between the numbers of patients who met the classification criteria. CONCLUSION: Rhupus patients follow a particular clinical course, with full expression of both SLE and RA in terms of organ involvement, except for a lower prevalence of kidney affection. The new 2019 EULAR/ACR SLE criteria are not useful for differentiating SLE and rhupus patients. A new way of classifying autoimmune diseases is needed to identify overlapping clusters.

Acute generalized exanthematous pustulosis and polyarthritis associated with a novel CARD14 mutation.

Acute generalised exanthematous pustulosis (AGEP) is a rare toxicoderma characterised by an acute onset rash, with many sterile pustules on the surface, high fever and increased acute phase reactants. We report the case of a patient who presented to the dermatology department with an AGEP and polyarthritis, in which a novel CARD14 mutation was identified. The pathophysiological mechanism of AGEP remains unclear, although mutations in the IL36RN gene have been identified in a small subset of AGEP patients. Similarly, mutations in the CARD14 gene have been linked to pustular types of psoriasis and familiar cases of pityriasis rubra pilaris; however, there are no reports associating mutations in the CARD14 gene with AGEP.

Clinical and Microbiological Profile of Bacterial Microbial Keratitis in a Portuguese Tertiary Referral Center-Where Are We in 2015?

OBJECTIVES: To study the microbial profile, antibiotic susceptibility pattern, risk factors, therapeutic trends, and clinical outcomes for microbial keratitis (MK) in a tertiary health care center. METHODS: All cases with suspected bacterial keratitis that were followed at consultation from September 2007 to August 2015 were included. Microbial cultures were obtained and patients were managed following an internal protocol. RESULTS: Two hundred thirty-five patients were included, with a mean age of 50.01±20.73 years. We obtained a 38.4% culture-positive rate, with higher proportion of gram-positives (70.8%). The commonest agents were Staphylococcus aureus (23.1%), Corynebacterium macginleyi (20.0%), and Pseudomonas aeruginosa (13.8%). Fluoroquinolone susceptibility was 97%, with no trend toward its decrease. A total of 95.7% had local risk factors, being trauma and contact lens wear the most common (28.9% each), with different age and pathogens distributions (P<0.001). Topical fluoroquinolones were first-line treatment in 99%, in association with aminoglycosides in 81.6%. Good initial response was registered in 95.9%, but 4.1% needed to step up treatment to fortified antibiotics, mainly if Pseudomonas (P=0.021). Good outcome was achieved in 81.8%, negatively affected by exposure and herpetic keratitis (P<0.001), central location (P=0.01), presence of Tyndall (P<0.001), corneal edema (P<0.001), and worse initial best-corrected visual acuity (P<0.001), but not Pseudomonas isolate (P=0.724). CONCLUSIONS: Gram-positives are the most frequent pathogens and shifting trends in the isolate distribution or emergence of resistant strains were not demonstrated. The susceptibility to first-line antibiotic agents remained high. We suggest a more aggressive approach to P. aeruginosa cases or MK presenting with poor outcome variables.

Transepithelial Accelerated Crosslinking for Progressive Keratoconus: A Critical Analysis of Medium-Term Treatment Outcomes.

Purpose: To report the 4-year outcomes of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) in the treatment of eyes with progressive keratoconus (KC). Methods: Eyes of patients who underwent TE-ACXL (6mW/cm2 for 15 minutes) for progressive KC and presented 48 months of follow-up were included. Corrected distance visual acuity (CDVA), keratometry measurements (Kmax, maximum keratometry, Kmean, mean keratometry and Astg, corneal astigmatism), thinnest corneal thickness (PachyMin), and topographic, and tomographic indices (specifically the posterior radius of curvature from the 3.0 mm centered on the thinnest point of the cornea (PRC), and the D-index) were analysed preoperatively and every 12 months after TE-ACXL, up to 48 months. Progression after TE-ACXL was considered when eyes presented ≥1 criteria: (1) increase of ≥1D in Kmax or increase of ≥0.75D in Kmean or increase of ≥1D in Astg; (2) reduction of ≥0.085 mm in PRC; (3) decrease ≥5% in PachyMin. Results: 41 eyes from 30 patients were included, with a mean age at crosslinking of 20.90±4.69 years. There was a significant increase in Kmean (+0.64±1.04 D, p<0.001; +0.98 ± 1.49 D, p<0.001; +1.27±2.01 D, p<0.001; +1.13±2.00 D, p=0.006) and a significant decrease in PRC throughout follow-up (-0.12±0.22, p=0.002; -0.15±0.24, p<0.001; -0.17±0.43, p=0.021; -0.16±0.43, p=0.027). PachyMin decreased significantly at 36 and 48 months (-8.50±15.93 µm, p=0.004; -7.82±18.37, p=0.033). According to our progression criteria, there was a major progression rate throughout follow-up (57.1%, 61.1%, 58.8%, and 67.9%, respectively). Surgery and follow-up were uneventful in all subjects. Eleven eyes (26.8%) required further procedures, ≥36 months after the initial TE-ACXL, due to persistent progressive disease. Conclusion: TE-ACXL proved to be a safe therapeutic option for progressive KC. However, its efficacy is deemed unsatisfactory, as a notable proportion of affected eyes may continue to advance within a 4-year timeframe, necessitating additional procedures to halt the disease's course.

Clinical outcomes and prognostic factors in Acanthamoeba keratitis.

PURPOSE: To report clinical findings and prognostic factors for visual and morphological outcomes in patients with Acanthamoeba keratitis (AK). METHODS: Single-center, retrospective, longitudinal study of 51 cases of AK diagnosed by real-time polymerase chain reaction (RT-PCR) between March 2010 and October 2022. The primary outcome was the final best corrected visual acuity (BCVA). Poor visual outcome was defined as a final BCVA ≥ 1 logMAR unit, while good visual outcome was defined as a final BCVA < 1 logMAR unit. Eyes from these two groups were compared, regarding demographic and initial clinical variables, anti-Acanthamoeba treatment used, and complications of the disease. Early diagnosis was defined as ≤ 14 days from symptom onset to diagnostic confirmation and initiation of Acanthamoeba medical treatment. Multivariable logistic regression was used to determine predictors of poor visual outcome. RESULTS: A total of 51 eyes from 46 patients diagnosed with AK, all contact lens (CL) wearers, were included in this study. Average follow-up was 39.0 ± 30.2 [total range 14-120] months. Thirty-one eyes (60.8 %) presented good visual outcome, with a lower baseline age (30.5 ± 9.0 vs. 42.3 ± 15.8; p = 0.020), better initial BCVA (0.8 ± 0.7 logMAR units vs. 1.3 ± 0.9 logMAR units; p = 0.047), higher rate of early diagnosis (45.2 % vs. 5.6 %; p = 0.004), and higher rate of therapeutic epithelial debridement (64.5 % vs. 10 %; p < 0.001). 20 eyes (39.2 %) presented poor visual outcome, with 12 eyes undergoing evisceration/enucleation (23.5 %). These 20 eyes presented a higher rate of complications (90 % vs. 61.3 %; p = 0.031). In multivariable analysis, early diagnosis of AK (OR 19.78; 95 % CI 2.07-189.11; p = 0.010) and therapeutic epithelial debridement (OR 19.02; 95 % CI 3.27-110.57; p = 0.001) were associated with a good visual outcome. CONCLUSIONS: In the present study, poor visual outcome was present in 39 % of affected eyes. Early AK diagnosis (≤14 days from symptom onset) and therapeutic epithelial debridement were associated with good final visual outcome.

Prevalence and clinical characteristics of patients with rheumatoid arthritis with interstitial lung disease using unstructured healthcare data and machine learning.

OBJECTIVES: Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR). METHODS: Observational case-control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared. RESULTS: From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p<0.001), malignancies (15.9% vs 8.5%, p<0.001) and cardiovascular disease (25.8% vs 13.9%, p<0.001) than RAnonILD. RAILD patients also had higher inflammatory burden reflected in more pharmacological prescriptions and higher inflammatory parameters and presented a higher in-hospital mortality with a higher risk of death (HR 2.32; 95% CI 1.59 to 2.81, p<0.001). CONCLUSIONS: We found an estimated age-adjusted prevalence of RA and RAILD by analysing real-world data through NLP. RAILD patients were more vulnerable at the time of inclusion with higher comorbidity and inflammatory burden than RAnonILD, which correlated with higher mortality.

Edgewise Compression and Three-Point Bending Analyses of Repaired Composite Sandwich Panels.

In this work, the fracture behaviour of repaired honeycomb/carbon-epoxy sandwich panels under edgewise compression and three-point bending loading was analysed. Assuming the occurrence of damage resulting from a complete perforation leading to an open hole, the followed repair strategy consists of plug filling the core hole and considering two scarf patches with an angle of 10° in order to repair the damaged skins. Experimental tests were performed on undamaged and repaired situations in order to address the alteration in the failure modes and assess the repair efficiency. It was observed that repair recovers a large part of the mechanical properties of the corresponding undamaged case. Additionally, a three-dimensional finite element analysis incorporating a mixed-mode I + II + III cohesive zone model was performed for the repaired cases. Cohesive elements were considered in the several critical regions prone to damage development. The failure modes and the resultant load-displacement curves obtained numerically were compared with the experimental ones. It was concluded that the numerical model is suitable for estimating the fracture behaviour of sandwich panel repairs.