Incident psoriasis under treatment with tumor necrosis factor-α inhibitors in juvenile idiopathic arthritis patients-analysis of the BiKeR registry.

The efficacy of tumor necrosis factor inhibitors (TNFi) for the treatment of psoriasis is well established, but patients may develop psoriasis for the first time while on TNFi as a paradoxical effect. Limited data on this association in patients with juvenile idiopathic arthritis (JIA) are available. Safety data from patients registered to the German Biologics registry (BiKeR) were analyzed. Patients were grouped by treatment regime: single TNFi, multiple TNFi, non-TNFi biologics or bDMARD-naïve control group receiving methotrexate. TNFi-associated psoriasis was defined as incident diagnosis of psoriasis after starting TNFi treatment. Patients with a history of psoriasis or psoriasis arthritis prior to TNFi therapy were excluded. Event rates using AEs reported after first dose were compared by Wald's test. A total of 4149 patients were treated with a TNFi (etanercept, adalimumab, golimumab, infliximab), 676 with a non-TNFi biologic (tocilizumab, abatacept, anakinra, canakinumab) and 1692 with methotrexate only. A total of 31 patients were diagnosed with incident psoriasis while on one of the above treatments. Compared with methotrexate, psoriasis was more frequent in the TNFi cohorts (RR 10.8, p = 0.019), specifically in the subgroup of TNF antibodies (RR 29.8, p = 0.0009), whereas no significant signal was observed with etanercept. Also, non-TNFi-treated patients presented high incident psoriasis rates (RR 25.0, p = 0.003). Our findings indicate a higher rate of incident psoriasis in JIA patients treated with TNFi monoclonal antibodies or non-TNFi biologic treatment. JIA patients receiving monoclonal antibody TNFi or non-TNFi bDMARD should be monitored for incident psoriasis. Medication change, if topical skin treatment remains insufficient, may be considered.

3D-speckle-tracking echocardiography correlates with cardiovascular magnetic resonance imaging diagnosis of acute myocarditis - An observational study.

Background: The diagnostic importance of three-dimensional (3D) speckle-tracking strain-imaging echocardiography in patients with acute myocarditis remains unclear. The aim of this study was to test the diagnostic performance of 3D-speckle-tracking echocardiography compared to CMR (cardiovascular magnetic resonance imaging) for the diagnosis of acute myocarditis. Methods and results: 45 patients with clinically suspected myocarditis were enrolled in our study (29% female, mean age: 43.9 ± 16.3 years, peak troponin I level: 1.38 ± 3.51 ng/ml). 3D full-volume echocardiographic images were obtained and offline 2D as well as 3D speckle-tracking analysis of regional and global LV deformation was performed. All patients received CMR scans and myocarditis was diagnosed in 29 subjects based on original Lake-Louise criteria. The 16 patients, in whom myocarditis was excluded by CMR, served as controls. Regional changes in myocardial texture (diagnosed by CMR) were significantly associated with regional impairment of circumferential, longitudinal, and radial strain, as well as regional 3D displacement and total 3D strain. Interestingly, the 2D and 3D global longitudinal strain (GLS) showed higher diagnostic performance than well-known parameters associated with myocarditis, such as LVEF (as obtained by echocardiography and CMR) and LVEDV (as obtained by CMR). Conclusions: In this study, we examined the use of 3D-speckle-tracking echocardiography in patients with acute myocarditis. Global longitudinal strain was significantly impaired in patients with acute myocarditis and correlated with CMR findings. Therefore, 3D echocardiography could become a useful diagnostic tool in the primary diagnosis of myocarditis.

Effects of Medical Face Masks on Physical Performance in Patients With Coronary Artery Disease or Hypertension.

In this randomized, prospective monocentric study, 40 subjects with coronary artery disease or hypertension (cardiovascular disease [CVD] group) were assigned to either surgical mask (SM) or class 2 filtering facepiece mask (FFP2). They performed cycle ergometry exercise tests with progressive intensity until exhaustion with the assigned mask and another test with no mask (NM) in random order. A control group of 10 healthy subjects randomly performed 3 exercise tests with NM, SM, and FFP2, respectively. Blood pressure, heart rate, 12-lead electrocardiogram, exertion, shortness of breath, and capillary blood gases from the earlobe were documented. Across all groups, exercise testing with face masks resulted in a significantly reduced peak power output in watts compared with testing with NM (CVD group: SM vs NM: -5.0 ± 7.0%, p = 0.005; FFP2 vs NM: -4.7 ± 14%, p = 0.03; control group: SM vs NM: -6.8 ± 4.4%, p = 0.008; FFP2 vs NM: -8.9 ± 6.3%; p = 0.01) without differences in hemodynamic parameters, such as maximum heart rate and systolic blood pressure. Wearing an FFP2 compared with NM resulted in significant higher carbon dioxide partial pressure (CVD group: FFP2: 36.0 ± 3.2 mm Hg vs NM: 33.3 ± 4.4 mm Hg, p = 0.019; control group: FFP2: 32.6 ± 2.8 mm Hg vs NM: 28.1 ± 1.7 mm Hg, p <0.001) with corresponding differences in hydrogen carbonate and base excess, but not to a clinically critical extent. In conclusion, exercise testing with SM and FFP2 resulted in a significant reduction of peak power output without differences in hemodynamic parameters in subjects with preexisting CVD and in healthy subjects.

Effects of face masks on performance and cardiorespiratory response in well-trained athletes.

BACKGROUND: During the COVID-19 pandemic, compulsory masks became an integral part of outdoor sports such as jogging in crowded areas (e.g. city parks) as well as indoor sports in gyms and sports centers. This study, therefore, aimed to investigate the effects of medical face masks on performance and cardiorespiratory parameters in athletes. METHODS: In a randomized, cross-over design, 16 well-trained athletes (age 27 ± 7 years, peak oxygen consumption 56.2 ± 5.6 ml kg-1 min-1, maximum performance 5.1 ± 0.5 Watt kg-1) underwent three stepwise incremental exercise tests to exhaustion without mask (NM), with surgical mask (SM) and FFP2 mask (FFP2). Cardiorespiratory and metabolic responses were monitored by spiroergometry and blood lactate (BLa) testing throughout the tests. RESULTS: There was a large effect of masks on performance with a significant reduction of maximum performance with SM (355 ± 41 Watt) and FFP2 (364 ± 43 Watt) compared to NM (377 ± 40 Watt), respectively (p < 0.001; ηp2 = 0.50). A large interaction effect with a reduction of both oxygen consumption (p < 0.001; ηp2 = 0.34) and minute ventilation (p < 0.001; ηp2 = 0.39) was observed. At the termination of the test with SM 11 of 16 subjects reported acute dyspnea from the suction of the wet and deformed mask. No difference in performance was observed at the individual anaerobic threshold (p = 0.90). CONCLUSION: Both SM and to a lesser extent FFP2 were associated with reduced maximum performance, minute ventilation, and oxygen consumption. For strenuous anaerobic exercise, an FFP2 mask may be preferred over an SM.

HDAC4 controls histone methylation in response to elevated cardiac load.

In patients with heart failure, reactivation of a fetal gene program, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), is a hallmark for maladaptive remodeling of the LV. The mechanisms that regulate this reactivation are incompletely understood. Histone acetylation and methylation affect the conformation of chromatin, which in turn governs the accessibility of DNA for transcription factors. Using human LV myocardium, we found that, despite nuclear export of histone deacetylase 4 (HDAC4), upregulation of ANP and BNP in failing hearts did not require increased histone acetylation in the promoter regions of these genes. In contrast, di- and trimethylation of lysine 9 of histone 3 (H3K9) and binding of heterochromatin protein 1 (HP1) in the promoter regions of these genes were substantially reduced. In isolated working murine hearts, an acute increase of cardiac preload induced HDAC4 nuclear export, H3K9 demethylation, HP1 dissociation from the promoter region, and activation of the ANP gene. These processes were reversed in hearts with myocyte-specific deletion of Hdac4. We conclude that HDAC4 plays a central role for rapid modifications of histone methylation in response to variations in cardiac load and may represent a target for pharmacological interventions to prevent maladaptive remodeling in patients with heart failure.