BACKGROUND: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset.
METHODS: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use.
RESULTS: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)].
CONCLUSIONS: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

OBJECTIVE: Rheumatoid Arthritis (RA) has a point prevalence of around 20 million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal.
METHODS: Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5 h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids.
RESULTS: No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein.
CONCLUSIONS: Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources.

Background: Lung ultrasound (LUS) is a tool of growing interest in Rheumatoid Arthritis (RA) oligo- symptomatic ILD to avoid. Objective: We aimed to evaluate (i) the prevalence of pleural (PLUS) and parenchymal (PAUS) abnormalities in LUS in the RA population and their possible correlation to biomarkers; (ii) the predictivity of gender, smoking habits, previous infections (past COVID-19 tuberculosis), and treatments; (iii) the differences in LUS between sexes. Methods: We collected the data of 155 (15 early and 140 late) RA patients with mild respiratory symptoms, evaluating PLUS and PAUS, in fourteen lung areas and also summing the scores (LUS-T). Results: Only 13/155 (8.4%) were completely negative; LUS correlated to age (all parameters p 0.0001), rheumatoid factor IgM (PLUS p 0.0006, PAUS p 0.02, LUS-T p 0.001) and ACPA (p 0.001, 0.006, 0.001, respectively), and PLUS also correlated to IL6 (p 0.02). The male gender was predictive of all LUS evaluations (p 0.001, 0.05, 0.001, respectively), which were higher than in women (p 0.001, 0.01, 0.001, respectively). Other potential risk factors were independent, except biological treatments, which showed a low predictivity to PLUS (p < 0.05). Conclusions: We can conclude that LUS is a useful technique in RA low respiratory symptoms and correlates with age, the most important RA biomarkers, and male sex.

Objectives: The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with active treatments and comorbidities, and its impact on daily clinical practice in adults with systemic autoimmune diseases (SADs). Methods: This cross-sectional single-center study was conducted in a tertiary hospital between January 2021 and March 2022. A sample of adult patients followed up in the SAD Unit with a diagnosis of a SAD and previously tested for anti-Ro/SSA and anti-La/SSB were recruited. All of them underwent a 12-lead electrocardiogram. Results: 167 patients were included. 90 (53.9%) were positive for anti-Ro60, 101 (60.5%) for anti-Ro52, and 45 (26.9%) for anti-La/SSB; 52 (31.3%) were triple-negative. 84% were women, and the mean age was 59 years (standard deviation 12.8). The most common SAD was primary Sjögren\'s syndrome (34.8%), followed by systemic lupus erythematosus (24.6%) and rheumatoid arthritis (22.8%). A statistically significant relationship was found between anti-Ro52 positivity and cardiac rhythm disorders (relative risk = 2.007 [1.197-3.366]), specifically QTc prolongation (relative risk = 4.248 [1.553-11.615]). Multivariate regressions showed a significant association, with diabetes mellitus being the most related comorbidity. The association between anti-Ro52 antibodies and atrioventricular conduction disorders was not significant. Conclusions: The presence of anti-Ro52 antibodies in adult patients with SADs is associated with an increased risk of QTc prolongation. Electrocardiographic screening of patients with SAD, anti-Ro52 antibodies, and other risk factors, like diabetes mellitus or QT-prolonging drugs, seems advisable. Those with baseline electrocardiogram abnormalities or additional risk factors should undergo electrocardiographic monitoring.

Background/Objectives: Calcinosis cutis is the deposition of insoluble calcium salts, which may cause inflammation, ulceration, pain, and restricted joint mobility. It rarely develops in damaged tissues (dystrophic subtype), most frequently in autoimmune connective tissue diseases (CTDs), but there is very limited data on the prevalence. Also, therapy remains an unsolved issue. In this study, we aimed to collect data on the prevalence of calcinosis in CTD patients to highlight that it is a considerable problem. Methods: A retrospective study was conducted in our department to assess the epidemiology of dystrophic calcinosis in CTDs between January 2003 and January 2024. Results: A total of 839 CTD patients were identified, of whom 56 had calcinosis (6.67%). The mean age of the calcinosis patients at diagnosis of underlying CTD was 41.16 ± 19.47 years. The mean time interval from the onset of calcinosis was 5.96 ± 8.62 years. Systemic sclerosis was the most common CTD complicated by calcinosis (n = 22). Conclusions: Our results are comparable to those reported previously in the literature. Although calcinosis is rare in the overall population, it is a present and unsolved problem in CTD patients. Therefore, further studies are needed on the factors involved in the development and progression of calcinosis as well as its treatment.

Background and Objectives: Coadministration of natural products to enhance the potency of conventional antirheumatic treatment is of high interest. This study aimed to assess the impact of administration of silymarin (a nutritional supplement) in patients with active rheumatoid arthritis under treatment with conventional disease-modifying antirheumatic drugs. Materials and Methods: One-hundred and twenty-two patients diagnosed with active rheumatoid arthritis and treated with conventional disease-modifying antirheumatic drugs were randomly assigned to either control or intervention groups; the latter was supplemented with silymarin (300 mg/day) for 8 weeks. Indicators of disease activity, inflammatory markers, disease activity and disability indices, European League Against Rheumatism responses, fatigue, depression, and anxiety scores were determined at baseline and week 8. Results: Silymarin supplementation significantly reduced the number of tender and swollen joints, duration of morning stiffness, severity of pain, disease activity and disability indices, European League Against Rheumatism responses, levels of fatigue, depression, and anxiety. According to our results, silymarin substantially improved patients\' general condition. Conclusions: Our study provides evidence for the benefits of silymarin supplementation to disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis.

Background and Objectives: Dry Eye Disease (DED) is a chronic condition characterised by tear film instability and ocular surface disruption, significantly impacting patients\' quality of life. This study aimed to provide top-level clinical evidence for the long-term efficacy of dehydrated amniotic membrane (dAM, Omnigen®) delivered via a specialised bandage contact lens (sBCL, OmniLenz) for managing moderate-to-severe DED. Materials and Methods: This randomised controlled trial (NCT04553432) involved 93 participants with moderate-to-severe DED, randomised to receive a 1-week bilateral treatment of either dAM (17 mm diameter with 6 mm central \'window\') applied under a sBCL or sBCL alone. Participants were assessed at baseline and followed up at 1, 3, and 6 months post-treatment. Outcomes included changes in symptomatology, tear film and ocular surface measurements, and in vivo confocal microscopy imaging of corneal nerve parameters and corneal dendritic cell (CDC) counts. Results: The dAM-sBCL group demonstrated a 65% reduction in OSDI scores at 6 months (p < 0.001), with 88% of participants showing improvement at 1 month. Corneal staining was significantly reduced in both groups. dAM-sBCL provided significant improvements in corneal nerve parameters at 1 month, with sustained positive trends at 3 months. Additionally, dAM-sBCL significantly reduced mature CDC counts, suggesting an anti-inflammatory effect. Conclusions: Treatment with dAM-sBCL for just 1 week significantly and rapidly improved dry eye symptoms as well as ocular surface signs for at least 3 months. It also enhanced corneal nerve health while reducing activated/mature corneal inflammatory cell numbers, presenting a safe and promising new treatment for moderate-to-severe DED.

Optical coherence tomography (OCT) is a non-invasive imaging technique based on the principle of low-coherence interferometry that captures detailed images of ocular structures. Multiple sclerosis (MS) is a neurodegenerative disease that can lead to damage of the optic nerve and retina, which can be depicted by OCT. The purpose of this pilot study is to determine whether macular OCT can be used as a biomarker in the detection of retrochiasmal lesions of the visual pathway in MS patients. We conducted a prospective study in which we included 52 MS patients and 27 healthy controls. All participants underwent brain MRI, visual field testing, and OCT evaluation of the thicknesses of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (GCL), and macular inner plexiform layer (IPL). OCT measurements were adjusted for optic neuritis (ON). VF demonstrated poor capability to depict a retrochiasmal lesion identified by brain MRI (PPV 0.50). In conclusion, the OCT analysis of the macula appears to excel in identifying retrochiasmal MS lesions compared to VF changes. The alterations in the GCL and IPL demonstrate the most accurate detection of retrochiasmal visual pathway changes in MS patients.

This study presents a trial analysis that uses brain activity information obtained from mice to detect rheumatoid arthritis (RA) in its presymptomatic stages. Specifically, we confirmed that F759 mice, serving as a mouse model of RA that is dependent on the inflammatory cytokine IL-6, and healthy wild-type mice can be classified on the basis of brain activity information. We clarified which brain regions are useful for the presymptomatic detection of RA. We introduced a matrix completion-based approach to handle missing brain activity information to perform the aforementioned analysis. In addition, we implemented a canonical correlation-based method capable of analyzing the relationship between various types of brain activity information. This method allowed us to accurately classify F759 and wild-type mice, thereby identifying essential features, including crucial brain regions, for the presymptomatic detection of RA. Our experiment obtained brain activity information from 15 F759 and 10 wild-type mice and analyzed the acquired data. By employing four types of classifiers, our experimental results show that the thalamus and periaqueductal gray are effective for the classification task. Furthermore, we confirmed that classification performance was maximized when seven brain regions were used, excluding the electromyogram and nucleus accumbens.

BACKGROUND: Glucocorticoids (GCs) play a crucial role in the treatment of many rheumatic diseases regarding their anti-inflammatory and immunosuppressive effects. Inappropriate use of GCs can exacerbate GC-related problems besides complex treatment regimens and miscellaneous well-established adverse events. Although several guidelines exist for managing these problems, there is lack of real-life studies evaluating the problems at the patient level. This study aims to identify GC-related problems among patients with rheumatic diseases and address how they have been solved.
METHODS: This prospective follow-up study was conducted between January 2021 and June 2022 at a university rheumatology outpatient clinic and included patients using GCs. A clinical pharmacist assessed patients for possible GC-related problems at baseline, 3 months, and 6 months. Identified problems, their causes, interventions to address these problems, and their outcomes were categorized using the Pharmaceutical Care Network Europe (PCNE v9.1) classification system. The resolution of the problems was evaluated at the patient\'s next follow-up visit.
RESULTS: A total of 156 patients were included, and 236 GC-related problems were identified in 66% of the patients. Adverse drug events (possible) accounted for the highest proportion of GC-related problems (94.1%), and the most common causes were lack of laboratory monitoring of GC-related adverse events (41.5%) and lack of drug treatment despite existing indications (39.8%). The median cumulative prednisolone dose was higher in patients with GC-related problems (3115 vs. 5455 mg, p = 0.007). The clinical pharmacist suggested 381 interventions: 47.7% (n = 182) at the \'prescriber level\', 31.8% (n = 121) at the \'patient level\', and 20.5% (n = 78) at the \'drug level\'. Of those interventions, 98% were accepted, and 80.1% of the problems were solved.
CONCLUSIONS: This study showed that the prevalence of GC-related problems is high in patients with rheumatic diseases. Integrating clinical pharmacists into the multidisciplinary rheumatology team provides an advantage in effectively identifying and managing GC-related problems at an early stage.