Implication of inflammation on Coxsackie virus and Adenovirus receptor expression on cardiomyocytes and the role of platelets in patients with dilated cardiomyopathy.

BACKGROUND: Coxsackie Virus and Adenovirus Receptor (CXADR or CAR) is involved in the pathogenesis of inflammatory dilated cardiomyopathy (DCM). We aimed to examine the relationship of CAR expression on platelets and cardiomyocytes with virus persistence, local and systemic inflammation and platelet activity in patients with DCM. METHODS: Endomyocardial biopsy (EMB) samples of 38 patients (mean age 39.5±11.3 years, 20 male) with DCM were analyzed for CAR expression, local inflammation grade by immunohistochemistry and virus persistence by real-time PCR. Platelet morphology was analyzed in all patients and 30 healthy subjects (HS) using scanning electron microscopy, platelet activity by light transmission aggregation, and CAR persistence by immunofluorescence. Platelets of 20 patients were analyzed for cytomegalovirus and herpes simplex virus 1-2 by immunofluorescence. Serum levels of tumor necrosis factor alpha (TNF α) and Interleukin-6 were assessed using ELISA in all studied subjects. RESULTS: CAR expression in EMB samples was related to the heart failure functional class and the level of IL-6. Platelets from DCM patients showed enhanced spontaneous and ADP induced aggregation. Platelets' CAR expression was >4 fold higher in DCM than HS and was observed predominantly at sites of intercellular communications in microaggregates and leukocyte-platelet aggregates. CAR-positive patients showed significantly higher TNF-α and IL-6 serum levels in CAR-negative patients. Platelets of 6 (30%) DCM patients revealed the mature cytomegalovirus and herpes simplex viruses particles. CONCLUSION: Tight junction protein CAR may serve as a docking pin creating a new type of contact structure that could be responsible for signaling between neighboring cells in pathological conditions.

Enoxaparin dose impacts blood cell phenotypes during mild SARS-CoV-2 infection: the observational single-center study.

Coronavirus disease 2019 (COVID-19) is associated with various hemostatic abnormalities requiring constant search for better delicate antithrombotic management in these high-risk patients. The choice and the optimal dose of anticoagulant is important, but unclear, especially for mild COVID-19. Enoxaparin has been tested in several COVID trials with mixed results regarding hard clinical outcomes including mortality. We analyzed clinical, laboratory data and changes in platelets, erythrocytes and leukocytes by scanning electron microscopy on admission and at hospital discharge in patients with confirmed COVID-19 treated with enoxaparin (n = 31) and matched healthy controls (n = 32) in a retrospective observational study. The data were triaged by enoxaparin dose comparing 40 mg/daily prophylactic enoxaparin dose (PED) with 80 mg/daily therapeutic (TED) regimens. All patients experienced mild disease, none required pulmonary support, and all survived. The impact of enoxaparin dose was prominent for platelets and erythrocytes, but less evident for leukocytes. PED was associated with significant platelet activation, diminished numbers of silent nonactive discoid cells, and increased number and size of platelet microaggregates with leukocyte involvement. In contrast, TED did not cause extra platelet activation, while circulating platelet microaggregates were smaller and lacking leukocytes in their construction. PED caused significant increase of erythrocyte-platelet aggregates formation, and numerically higher proportion of circulating echinocytes. TED was associated with significant decrease of rouleaux sludge formation compared to only some trend after PED. Changes in leukocytes were less dependent on enoxaparin dose. However, PED has been associated with enhanced aggregate formation in 7 out of 10 patients, while trap net formation has been decreased in 17 out of 21 TED patients. We conclude that over hospital stay TED was superior to PED in patients with mild COVID-19. The inability of PED to adequately protect major circulating blood cells is probably due to enhanced clearance or/and diminished bioavailability of enoxaparin during COVID. These retrospective observational small sample size data may be relevant to better understanding of the mixed results in controlled outcome-driven trials exploring optimal COVID-19 anticoagulant strategies.

Impact of olokizumab on platelets, leukocytes and erythrocytes during mild COVID-19.

No abstract present.

Cost-effectiveness of Platelet Function-Guided Strategy with Clopidogrel or Ticagrelor.

Some patients treated with dual antiplatelet therapy (DAPT) following acute coronary syndrome (ACS) can still exhibit heightened residual platelet reactivity (HRPR), which is potentially linked to adverse vascular outcomes. Better tailored DAPT strategies are needed to address this medical need. AIM: To assess the cost-effectiveness of guided DAPT with clopidogrel or ticagrelor in addition to aspirin when using VerifyNow P2Y12 testing in post-ACS patients. METHODS: The costs were calculated per 1,000 patients aged >55 years. It was assumed that all patients received either generic clopidogrel or ticagrelor for 1 year, and underwent VerifyNow P2Y12 assay testing before DAPT maintenance. RESULTS: Guided DAPT will prevent five more MIs and six more deaths per 1,000 patients than a standard prescription of generic clopidogrel. The total predictive value of costs per patient is 32% lower if a guided strategy is used than if ticagrelor is given to all patients. CONCLUSION: Assessment of heightened residual platelet reactivity with P2Y12 assay in triaging DAPT post-ACS patients for 1 year is a cost-effective strategy that would reduce financial burden compared to routine administration of more expensive antiplatelet agents.

Historical overview of studies on inflammation in Russia.

INTRODUCTION: Historical overview of development investigations on inflammation in Russia up to date is presented. MATERIAL AND METHODS: Analysis of modern Russian language literature (1950-2010) on history of medicine and researchers' activity on inflammation, as well as Russian language content of internet on this theme, was made. Many names of Russian researchers are still little known to the English-speaking Western readers. RESULTS: Starting in the eighteenth century, the mystery of the inner workings of the inflammation process attracted the interest of physicians and biologists of the Russian Empire. Accumulated knowledge focused mainly on the etiological factors of inflammation. In the nineteenth century, scientific schools emerged for studying inflammation and established close contacts with leading scientists in other countries. At this time, Ilya Mechnikov formulated his famous biological theory of inflammation, according to which inflammation is a protective adaptation response to an injury. He also developed his teaching on phagocytosis and was awarded the Nobel Prize. In the twentieth century, Russian scientists participated in the discovery of viruses and new bacterial pathogens, and in the investigation of the mechanics of the genesis and development of inflammatory processes. CONCLUSION: Today interest in studies of inflammation in Russia is on the increase; scientists united by the Russian Inflammation Society continue their quest to investigate inflammatory mediators, and study molecular and cellular mechanisms and approaches in the treatment of complications associated with inflammation.