Serological short-chain fatty acid and trimethylamine N-oxide microbial metabolite imbalances in young adults with acute myocardial infarction.

Acute myocardial infarction (AMI) is associated with systemic inflammatory processes and metabolic alterations. Microbial-derived metabolites, such as short-chain fatty acids and trimethylamine N-oxide (TMAO), have emerged in recent years as key players in the modulation of inflammation, with potential implications for cardiovascular diseases. We performed a prospective observational study that monitored the serological concentration of bacterial metabolites in 45 young patients (<55 years) without cardiovascular risk factors but with AMI, at hospital admission and at 3 months of follow-up, and compared them with a control group. TMAO and acetate levels were significantly higher in AMI, whereas butyrate and propionate were significantly lower. The acetate/propionate ratio showed the most discrimination between AMI and controls by receiver operating characteristic analysis (area under the curve 0.769, P < 0.0001). A multivariate logistic regression model revealed that this ratio was independently associated with AMI. Short-chain fatty acid concentrations, but not TMAO, exhibited significant correlations with inflammatory and coagulation parameters. Three months after the acute AMI event, all metabolite levels returned to those observed in healthy controls except butyrate. In conclusion, our study reveals disturbances of the serological concentration of microbiota-derived metabolites in AMI that are also related to inflammatory and coagulation parameters. These findings highlight an interesting field of study in the potential role of microbial metabolites from gut in cardiovascular disease.

What to Expect When Systemic Treatment in Juvenile Idiopathic Arthritis Is Withdrawn?

OBJECTIVE: The goal of juvenile idiopathic arthritis (JIA) treatment is to maintain clinical remission. It is also important to reduce drug exposure, whenever possible, in order to avoid or decrease potential side effects. We aimed to analyze remission survival after systemic treatment withdrawal and to determine which factors can influence it. METHODS: We conducted a multicenter, observational, longitudinal study. All patients included had a diagnosis of JIA. We analyzed remission survival using Kaplan-Meier curves according to the systemic treatment received (methotrexate [MTX] alone or in combination with biologic disease-modifying antirheumatic drugs [bDMARDs]) and JIA subgroups (oligoarticular and polyarticular course, juvenile spondyloarthritis, and systemic JIA). In addition, risk factors were examined using multivariate analysis. RESULTS: We included 404 patients with JIA; 370 of them (92%) had received systemic treatment at some point and half of them (185 patients) had withdrawn on at least 1 occasion. There were 110 patients who flared (59%) with a median time of 2.3 years. There were no differences in remission survival between JIA subcategories. Twenty-nine percent of patients with JIA who received MTX and bDMARDs, in which MTX alone was withdrawn, flared; median time to flare of 6.3 years. However, if only the bDMARD was withdrawn, flares occurred 57% of the time; median time to flare of 1.1 years. CONCLUSION: Flares are frequent when systemic treatment is withdrawn, and uveitis or joint injections could be related risk factors. In MTX and biologic-naïve patients, the frequency of flares occurred in more than half of patients, although they were less frequent when clinical remission lasted for > 1 year.

Stopping bDMARDs at the beginning of pregnancy is associated with disease flares and preterm delivery in women with rheumatoid arthritis.

Objectives: Women with Rheumatoid Arthritis (RA) can experience flares during pregnancy that might influence pregnancy outcomes. We aimed at assessing the disease course during pregnancy and identifying risk factors for flares. Methods: Data about prospectively-followed pregnancies in RA were retrospectively collected before conception, during each trimester and in the post-partum period. Clinical characteristics, disease activity (DAS28-CRP3), medication use, and pregnancy outcomes were analysed with regard to disease flares. Results: Among 73 women who had a live birth, 64 (88%) were in remission/low disease activity before conception. During pregnancy, a flare occurred in 27 (37%) patients, mainly during first and second trimester. Flares during pregnancy were associated with the discontinuation of bDMARDs at positive pregnancy test (55% of patients with flare vs. 30% of patients with no flare, p 0.034, OR 2.857, 95% CI 1.112-8.323) and a previous use of >1 bDMARDs (33% of patients with flare vs. 10% of patients with no flare, p 0.019, OR 4.1, 95%CI 1.204-13.966). Preterm pregnancies were characterised by higher values of CRP [10 mg/L (5-11) vs. 3 mg/L (2.5-5), p 0.01] and DAS28-CRP3 [4.2 (1.9-4.5) vs. 1.9 (1.7-2.6), p 0.01] during the first trimester as compared with pregnancies at term. Preterm delivery was associated with the occurrence of flare during pregnancy (flare 27% vs. no-flare 7%, p 0.034, OR 4.625, 95%CI 1.027-20.829). Conclusion: Preterm delivery in RA patients was associated with flares during pregnancy. Flares occurred more frequently after the discontinuation of bDMARDs at positive pregnancy test. Women with aggressive RA on treatment with bDMARDs should be considered as candidates for continuing bDMARDs during pregnancy in order to reduce the risk of flare and adverse pregnancy outcomes.

Evaluation of flare rate and reduction strategies for bDMARDs in juvenile idiopathic arthritis: real world data from a single-centre cohort.

This study aimed to determine the flare rate (FR) in a cohort of Juvenile Idiopathic Arthritis (JIA) patients with tapered or abruptly discontinued biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify predictors of flare. This retrospective observational study included 191 bDMARD dose-reduction events in patients with JIA followed-up at a referral hospital during the period 2000-2019. FR was analysed according to reduction strategies. To identify predictors of flare, Kaplan-Meier and Cox-regression models were plotted at 6 months (6 m), 12 months (12 m) and 24 months (24 m) following tapering (TP) or withdrawal (WD). 165 episodes of TP and 71 episodes of WD were included; 45 episodes where treatment was withdrawn after TP were included in both strategies. FR after TP was 13.4% at 6 m and increased up to 26.6% at 12 m and 51.4% at 24 m. After WD, FR was higher, 52.1% of events had a flare at 6 m and 67.6% at 12 m. Previous TP did not increase time in remission after WD of bDMARDs in the Kaplan-Meier analysis. Factors associated with flares were identified after TP at 6 m: female sex, higher number of previous bDMARDs and longer time on bDMARD treatment were positively associated with flares. Polyarticular subtype and younger age at diagnosis were associated with flares at 12 and 24 m after TP. No factors were identified in multivariable analysis after WD. TP is a successful strategy to maintain remission with lower bDMARD doses. Previous TP of bDMARDs does not seem to increase time in remission after WD.

Disease course and obstetric outcomes of pregnancies in juvenile idiopathic arthritis: are there any differences among disease subtypes? A single-centre retrospective study of prospectively followed pregnancies in a dedicated pregnancy clinic.

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.

Antisynthetase syndrome and pulmonary hypertension: report of two cases and review of the literature.

Antisynthetase Syndrome (ASS) is a subset of idiopathic inflammatory myopathies characterised by specific clinical features such as interstitial lung disease (ILD), fever, myositis, Raynaud's phenomenon, cutaneous involvement and arthritis related to the presence of anti-aminoacyl-tRNA-synthetase (anti-ARS) autoantibodies. Moreover, Pulmonary arterial hypertension (PAH) is a life-threatening complication associated with connective tissue diseases mainly systemic sclerosis (SSc-PAH). It has been suggested that PAH can complicate ASS patients but little is known about the prevalence and risk factors to develop this complication. Here we report on two patients with ASS and PH. The first one represents a complete picture of ASS anti-Jo-1 positive, the second an amyophatic ASS anti-PL-12 positive. In one of our ASS-PAH patients, specific treatment lead to improvement of PAH. There are no specific recommendations on current guidelines regarding either PAH screening or treatment in ASS, but performing echocardiogram, ECG, pulmonary function test and prompt initiation of specific therapies seems to improve right heart catheterisation (RHC) parameters and survival.

High rates of severe disease and death due to SARS-CoV-2 infection in rheumatic disease patients treated with rituximab: a descriptive study.

The objective of this study is to describe the characteristics and outcomes of rheumatic and musculoskeletal disease (RMD) patients who were treated with rituximab and had suspected or confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this descriptive study, RMD patients who were treated with rituximab in the last 12 months at the Rheumatology Department of our hospital were screened for SARS-CoV-2 infection via telephone interview and a comprehensive review of clinical health records (01/02/2020-26/05/2020). Those with probable or confirmed SARS-CoV-2 infection were included. In total, 76 patients were screened. Of these, 13 (17.1%) had suspected or confirmed SARS-CoV-2 infection. With regard to these 13 patients, the median age at coronavirus disease (COVID-19) diagnosis was 68 years (range 28-76 years) and 8 (61.5%) were female. Five patients had rheumatoid arthritis, three had systemic vasculitis, two had Sjögren syndrome, and two had systemic lupus erythematosus. Additionally, seven patients (53.8%) had pulmonary involvement secondary to RMD. Eight patients (61.5%) developed severe disease leading to hospitalization, and seven developed bilateral pneumonia and respiratory insufficiency. Of the eight hospitalized patients, five (62.5%) fulfilled the acute respiratory distress syndrome criteria and three developed a critical disease and died. Our cohort had a high rate of severe disease requiring hospitalization (61.5%), with bilateral pneumonia and hyperinflammation leading to a high mortality rate (23.1%). Treatment with rituximab should be considered a possible risk factor for unfavorable outcomes in COVID-19 patients with RMD. However, further study is required to confirm this association.

The Course of Rheumatic Diseases During Pregnancy.

BACKGROUND: Rheumatic diseases commonly affect women of childbearing age, when women may be contemplating pregnancy or they discover an unplanned pregnancy. Therefore, specific issues about pregnancy planning and management are commonly encountered in patients during these times. Knowledge of the effect of pregnancy on disease activity is important for counseling. This review summarizes recent data on the course of different rheumatic diseases during pregnancy and the postpartum period. Rheumatoid arthritis and systemic lupus erythematosus are the most commonly investigated diseases. Data are increasing about spondyloarthritis. Sparse data are available for other rheumatic diseases. Despite the differences in these diseases and the various courses these disease take during pregnancy, a common feature is that active maternal disease in the months prior to conception increases the risk of flares during pregnancy, which in turn can lead to adverse pregnancy outcomes. Therefore, maternal and fetal health can be optimized if conception is planned when disease is inactive so that a treatment regimen can be maintained throughout pregnancy.