Crosstalk between Inflammation and Atherosclerosis in Rheumatoid Arthritis and Systemic Lupus Erythematosus: Is There a Common Basis?

Cardiovascular disease is the leading cause of morbidity and mortality in patients with rheumatoid arthritis and systemic lupus erythematosus. Traditional cardiovascular risk factors, although present in lupus and rheumatoid arthritis, do not explain such a high burden of early cardiovascular disease in the context of these systemic connective tissue diseases. Over the past few years, our understanding of the pathophysiology of atherosclerosis has changed from it being a lipid-centric to an inflammation-centric process. In this review, we examine the pathogenesis of atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis, the two most common systemic connective tissue diseases, and consider them as emblematic models of the effect of chronic inflammation on the human body. We explore the roles of the inflammasome, cells of the innate and acquired immune system, neutrophils, macrophages, lymphocytes, chemokines and soluble pro-inflammatory cytokines in rheumatoid arthritis and systemic lupus erythematosus, and the roles of certain autoantigens and autoantibodies, such as oxidized low-density lipoprotein and beta2-glycoprotein, which may play a pathogenetic role in atherosclerosis progression.

ADAMTS13, von Willebrand Factor, Platelet Microparticles, Factor VIII, and Impact of Somatic Mutations in the Pathogenesis of Splanchnic Vein Thrombosis Associated with BCR-ABL-Negative Myeloproliferative Neoplasms.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are often associated with splanchnic vein thrombosis (SVT). Not all the factors involved in the thrombotic tendency are currently known. OBJECTIVES: This study aims to evaluate a possible association between ADAMTS13, von Willebrand factor (VWF), platelet microvesicles (MV), and factor VIII activity (FVIII:C) with thrombotic events in MPN patients. MATERIALS AND METHODS: In total, 36 consecutive MPN patients with SVT were enrolled. The MPNs were diagnosed based on clinical characteristics and one or more gene mutations among JAK-2, CALR, and MPL. As controls, 50 randomly selected patients with MPN without thrombosis, 50 patients with deep vein thrombosis without MPNs, and 50 healthy blood donors were evaluated. Complete blood count, ADAMTS13, VWF, MV, and FVIII:C in plasma were measured in all the subjects. RESULTS: The JAK-2 mutation was found in 94% of the patients with SVT, but none were triple-negative for genetic mutations (JAK2 V617F, CALR, MPL, and exon 12). Compared to the normal subjects, in all the MPN patients (with or without SVT), the levels of ADAMTS13 were found to be significantly lower (p < 0.001) and the MV concentrations were significantly higher (p < 0.001). Among the MPN patients, the VWF and FVIII:C levels were significantly higher in the patients with SVT than those without thrombosis (p = 0.007 and p = 0.04, respectively). Splenomegaly was present in 78% of MPN patients with SVT and in 30% of those without SVT (p < 0.001). The ADAMTS13/VWF ratio was reduced in all the patients, but not in the healthy blood donors (p < 0.001). CONCLUSIONS: The significant increase in circulating MV, VWF, and FVIII:C in the MPN patients and in the patients with thrombosis supports the role of endothelium damage in promoting thrombotic events. In particular, a significant increase in VWF and FVIII:C levels was found in the MPN patients with SVT.

Syncope Time Frames for Adverse Events after Emergency Department Presentation: An Individual Patient Data Meta-Analysis.

Background and Objectives: Knowledge of the incidence and time frames of the adverse events of patients presenting syncope at the ED is essential for developing effective management strategies. The aim of the present study was to perform a meta-analysis of the incidence and time frames of adverse events of syncope patients. Materials and Methods: We combined individual patients' data from prospective observational studies including adult patients who presented syncope at the ED. We assessed the pooled rate of adverse events at 24 h, 72 h, 7-10 days, 1 month and 1 year after ED evaluation. Results: We included nine studies that enrolled 12,269 patients. The mean age varied between 53 and 73 years, with 42% to 57% females. The pooled rate of adverse events was 5.1% (95% CI 3.4% to 7.7%) at 24 h, 7.0% (95% CI 4.9% to 9.9%) at 72 h, 8.4% (95% CI 6.2% to 11.3%) at 7-10 days, 10.3% (95% CI 7.8% to 13.3%) at 1 month and 21.3% (95% CI 15.8% to 28.0%) at 1 year. The pooled death rate was 0.2% (95% CI 0.1% to 0.5%) at 24 h, 0.3% (95% CI 0.1% to 0.7%) at 72 h, 0.5% (95% CI 0.3% to 0.9%) at 7-10 days, 1% (95% CI 0.6% to 1.7%) at 1 month and 5.9% (95% CI 4.5% to 7.7%) at 1 year. The most common adverse event was arrhythmia, for which its rate was 3.1% (95% CI 2.0% to 4.9%) at 24 h, 4.8% (95% CI 3.5% to 6.7%) at 72 h, 5.8% (95% CI 4.2% to 7.9%) at 7-10 days, 6.9% (95% CI 5.3% to 9.1%) at 1 month and 9.9% (95% CI 5.5% to 17) at 1 year. Ventricular arrhythmia was rare. Conclusions: The risk of death or life-threatening adverse event is rare in patients presenting syncope at the ED. The most common adverse events are brady and supraventricular arrhythmias, which occur during the first 3 days. Prolonged ECG monitoring in the ED in a short stay unit with ECG monitoring facilities may, therefore, be beneficial.

Laryngotracheal aspiration test reduce the false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative nasopharyngeal swab.

BACKGROUND: In the emergency department (ED) definitive diagnosis of SARS-COV-2 pneumonia is challenging as nasopharyngeal swab (NPS) can give false negative results. Strategies to reduce false negative rate of NPS have limitations. Serial NPSs (24-48 h from one another) are time-consuming, sputum can not be collected in the majority of patients, and bronchoalveolar lavage (BAL), the most sensitive test, requires specific expertise. Laryngotracheal aspiration (LTA) is easy to perform and showed a similar accuracy to BAL for diagnosis of other pulmonary diseases, however it was not studied to diagnose SARS-COV-2 pneumonia. OBJECTIVE: An observational cross-sectional study was performed to evaluate the negative predictive value of LTA in patients with suspected SARS-COV-2 pneumonia despite a negative NPS. METHODS: In the EDs of two university hospitals, consecutive patients with suspected SARS-COV-2 pneumonia despite a negative NPS underwent LTA performed with a nasotracheal tube connected to a vacuum system. Final diagnosis based on all respiratory specimen tests (NPS, LTA and BAL) and hospital data was established by two reviewers and in case of discordance by a third reviewer. RESULTS: 117 patients were enrolled. LTA was feasible in all patients and no patients experienced adverse events. Fifteen (12.7%) patients were diagnosed with community-acquired SARS-COV-2 pneumonia: 13 LTA positive and only 2 (1.7%) LTA negative. The negative predictive value of NPS and LTA was 87.3% (79.9% - 92.7%) and 98.1% (93.3%99.8%) respectively. CONCLUSIONS: LTA resulted feasible, safe and reduced false negative rate in patients with suspected SARS-COV-2 pneumonia despite a negative NPS.

Short- vs long-course antibiotic therapy for pneumonia: a comparison of systematic reviews and guidelines for the SIMI Choosing Wisely Campaign.

Reduction of the inappropriate use of antibiotics in clinical practice is one of the main goals of the Società Italiana di Medicina Interna (SIMI) choosing wisely campaign. We conducted a systematic review of secondary studies (systematic reviews and guidelines) to verify what evidence is available on the duration of antibiotic treatment in Pneumonia. A literature systematic search was performed to identify all systematic reviews and the three most cited and recent guidelines that address the duration of antibiotic therapy in pneumonia. Moreover, a meta-analysis of non-duplicate data from randomized controlled trials (RCTs) considered in the enrolled systematic reviews was performed together with a trial sequential analysis to identify the need for further studies. Two systematic reviews on antibiotic duration in community-acquired pneumonia (CAP) for a total of 17 RCTs (2764 patients) were enrolled in our study. Meta-analysis of non-duplicate RCTs show a non-significant difference in rate of treatment failure between short (≤ 7 days) and long (> 7 days) antibiotic treatment course: RR 1.05 (95% CI, 0.82-1.36). The trial sequential analysis suggests that further data would not affect current evidence or become clinically relevant. Selected guidelines suggest consideration of a short course, with a low grade of evidence and without citing the already published systematic reviews. Antibiotic treatment of CAP for ≤ 7 days is not associated with a higher rate of treatment failure than longer courses and should thus be taken in consideration. Guidelines should upgrade the evidence on this topic.