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.

In addition to the butterfly rash, lupus nephritis is the most specific manifestation of systemic lupus erythematosus (SLE). The perspective on this organ manifestation has fundamentally changed as well as the manifestation of SLE itself 40 years after the first multicenter clinical study on lupus nephritis. Even if there is a faint glimpse of hope of a cure, there is still the fight against the problem of nonresponders and also the progressive loss of organ function. This update gives an overview of the current importance of lupus nephritis in the context of the whole SLE disease, of the special features and on the options provided by the new diagnostic and therapeutic developments.
UNASSIGNED: Neben dem Schmetterlingserythem ist die Lupusnephritis wohl die spezifischste Ausprägung des systemischen Lupus erythematodes (SLE). Vierzig Jahre nach der ersten multizentrischen klinischen Studie zur Lupusnephritis hat sich die Perspektive auf diese Organmanifestation ganz wesentlich verändert wie auch die Erscheinung des SLE selbst. Auch wenn sich ein zarter Schimmer von Hoffnung auf Heilung zeigt, kämpfen wir nach wie vor mit Nonrespondern und gegen den progredienten Organfunktionsverlust. Dieses Update gibt einen Überblick über die aktuelle Bedeutung der Lupusnephritis im Kontext der Gesamterkrankung SLE, über die Besonderheiten, Möglichkeiten und Herausforderungen, die diese Organbeteiligung bietet, und über die Chancen, die uns neue diagnostische und therapeutische Entwicklungen bieten.

Patients with diseases of the musculoskeletal system are confronted with a large quantity of treatment offers based on methods of complementary medicine. Despite a considerable number of publications on this topic, the scientific evidence is still poor. This article focuses on Ayurvedic medicine (AM), traditional Chinese medicine (TCM), mind-body medicine and homeopathy. These procedures have a longstanding tradition of practice and each claims to have its own theoretical concept; however, the application in the field of rheumatology can only be recommended either for specific entities or, in the case of homeopathy, not at all. In addition, this article summarizes the evidence for dietary recommendations, nutritional supplements and herbal medicine in rheumatology. The latter topics are frequently discussed in the popular press and are a much-debated issue between physicians and patients; however, clear-cut recommendations for the application on a scientific basis are the exception and mainly consist of the endorsement to adhere to the principles of a Mediterranean diet.
UNASSIGNED: Für Patienten mit Erkrankungen des muskuloskeletalen Systems existiert eine schwer überschaubare Zahl von Behandlungsangeboten aus dem Bereich komplementärer Heilverfahren. Trotz einer beträchtlichen Zahl von Publikationen zu diesem Thema ist die wissenschaftliche Evidenz nach wie vor gering. Der Beitrag widmet sich der ayurvedischen Medizin (AM), der traditionellen chinesischen Medizin (TCM), der Mind-Body-Medizin und der Homöopathie. Auch wenn es sich dabei um Verfahren handelt, die eine lange Anwendungstradition haben und sich auf ein eigenes theoretisches Konzept berufen, kann ihre Anwendung in der Rheumatologie nur für bestimmte Entitäten oder – im Fall der Homöopathie – nicht empfohlen werden. Zusätzlich wird die Evidenz für Diätverfahren, Nahrungsergänzungsmittel und Phytotherapie vorgestellt. Die Letztgenannten treffen in der Laienpresse auf großes Interesse und beanspruchen in der Sprechstunde einen relevanten Anteil an Beratungszeit. Allerdings sind auch hier Anwendungsempfehlungen auf wissenschaftlicher Grundlage die Ausnahme und fokussieren v. a. auf eine vollwertige, an den Prinzipien der Mittelmeerkost orientierte Ernährung.

UNASSIGNED: This study aimed to explore protective effects and potential mechanism of ectoine, a natural osmoprotectant, on ocular surface mucin production in dry eye disease.
UNASSIGNED: A dry eye model was established in C57BL/6 mice exposed to desiccating stress (DS) with untreated (UT) mice as controls. DS mice were topically treated with 2.0% ectoine or PBS vehicle. Corneal epithelial defects were assessed by Oregon Green Dextran (OGD) fluorescent staining. Conjunctival goblet cells, ocular mucins, and T help (Th) cytokines were evaluated by immunofluorescent staining or ELISA, and RT-qPCR.
UNASSIGNED: Compared with UT mice, corneal epithelial defects were detected as strong punctate OGD fluorescent staining in DS mice with vehicle, whereas ectoine treatment largely reduced OGD staining to near-normal levels. Conjunctival goblet cell density and cell size decreased markedly in DS mice, but was significantly recovered by ectoine treatment. The protein production and mRNA expression of two gel-forming secreted MUC5AC and MUC2, and 4 transmembrane mucins, MUC1, MUC4, MUC16, and MUC15, largely decreased in DS mice, but was restored by ectoine. Furthermore, Th2 cytokine IL-13 was inhibited, whereas Th1 cytokine IFN-γ was stimulated at protein and mRNA levels in conjunctiva and draining cervical lymph nodes (CLNs) of DS mice, leading to decreased IL-13/IFN-γ ratio. Interestingly, 2.0% ectoine reversed their alternations and restored IL-13/IFN-γ balance.
UNASSIGNED: Our findings demonstrate that topical ectoine significantly reduces corneal damage, and enhances goblet cell density and mucin production through restoring imbalanced IL-13/IFN-γ signaling in murine dry eye model. This suggests therapeutic potential of natural osmoprotectant ectoine for dry eye disease.

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.
BACKGROUND: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).
La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.

UNASSIGNED: Gout is a metabolic disorder that leads to elevated serum uric acid levels and deposition of urate crystals in the joints. The disease is usually confined to the joint space and leads to pain and limitation of jaw opening. The case describes a 45-year-old female patient with a chief complaint of \'occasional pain in the left temporal muscle region\'. The case disclosed a gout manifestation in the temporomandibular joint (TMJ) after physical and radiographic findings. Gout manifestation in the TMJ is an unusual presentation and a few reports in the English literature address the subject. Gout in the TMJ should be included as a differential diagnosis for joint disorders because of its rarity. A clinician may overlook gout involving the TMJ in the differential diagnosis of facial pain even when the patient has received a diagnosis of gout in other joints.

OBJECTIVE: To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD).
METHODS: A retrospective analysis was conducted on clinical data of 125 patients with anti-MDA5 + CADM-ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ2 test, Log-rank test, COX and logistic regression analysis.
RESULTS: In this cohort, 125 anti-MDA5 + CADM-ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow-up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C-reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti-MDA5 + CADM-ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016).
CONCLUSIONS: Patients with anti-MDA5 + CADM-ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.

Aberrant epigenetic modifications, particularly DNA methylation, play a critical role in the pathogenesis and progression of human diseases. The current review aims to reveal the role of aberrant DNA methylation in the pathogenesis and progression of diseases and to discuss the original data obtained from international research laboratories on this topic. In the review, we mainly summarize the studies exploring the role of aberrant DNA methylation as diagnostic and prognostic biomarkers in a broad range of human diseases, including monogenic epigenetics, autoimmunity, metabolic disorders, hematologic neoplasms, and solid tumors. The last section provides a general overview of the possibility of the DNA methylation machinery from the perspective of pharmaceutic approaches. In conclusion, the study of DNA methylation machinery is a phenomenal intersection that each of its ways can reveal the mysteries of various diseases, introduce new diagnostic and prognostic biomarkers, and propose a new patient-tailored therapeutic approach for diseases.

UNASSIGNED: The incidence of Crohn\'s disease (CD) and rheumatoid arthritis (RA) co-morbidity, as well as the number of individuals affected, is on the rise due to their shared molecular and cellular factors. This study aimed to identify potential therapeutic targets and medicines for comorbid CD and RA.
UNASSIGNED: We integrated single-cell RNA sequencing, Mendelian randomization, and colocalization analysis results from public databases to analyse immune cell subgroups in CD and RA patients and identify candidate therapeutic targets. We further screened potential medicines for the identified candidate targets using the Comparative Toxicogenomics Database (CTD) and molecular docking and molecular dynamics simulations.
UNASSIGNED: The proportion of CD8 effector memory T cells (Tem) was consistently elevated in the peripheral blood mononuclear cells (PBMCs) of both CD and RA patients. MYBL1 had a causal effect on the onset of both CD (OR = 1.23; 95 % CI, 1.05-1.45; P = 0.046) and RA (OR = 1.45; 95 % CI, 1.14-1.85; P = 0.04). Four potential therapeutic molecules were retrieved from the CTD database, among which tretinoin (docking score: -6.3 kcal/mol) showed the best potential.
UNASSIGNED: Our comprehensive analysis suggests that CD8 Tem cells are a key cell group in comorbid RA and CD and that MYBL1 has a causal effect. Tretinoin was identified as a potential targeted therapeutic drug, which is of great clinical research value.