Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is the established standard of care in ACS patients 6 (unstable angina/non ST-segment elevation MI [NSTEMI], 7,8 and STEMI 9 ), especially in those undergoing PCI. 10 Given that evidence-based clinical guidelines for Asian countries often rely on data obtained elsewhere, 11 current clinical practice does not differ largely from that in other regions of the world regarding antiplatelet therapy in ACS patients, except for the lower dose of prasugrel in Japan. 2,3,12, 13 With regard to the use of clopidogrel, poor drug metabolism is more common in Asian populations compared with other international regions, due to the prevalence of CYP2C19 lossn the early 21st century, the annual incidence of acute myocardial infarction (MI) in Japan was reported to be approximately 25% of the incidence in the USA, 1 but registry data indicate that the incidence in Japan has steadily increased between 1979 and 2008. 1 In patients with acute coronary syndrome (ACS), the incidence of ST-segment elevation MI (STEMI) was higher in patients from the Japanese PACIFIC registry 2 than in those from the global GRACE registry. 3 The vast majority (93.5%) of ACS patients in Japan undergo percutaneous coronary intervention (PCI) with angiography or stent implantation, 2 while data from the global registries GRACE and CRUSADE report a lower rate of PCI (50-60%). 3,4 Antiplatelet therapy is used in >90% of ACS patients, both in Japan and worldwide.

Objectives:: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. Methods:: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reactionconfirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. Results:: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. Conclusion:: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.

The innate antiviral response is mediated, at least in part, by Toll-like receptors (TLRs). TLR3 signaling is activated in response to viral infection, and the absence of TLR3 in mice significantly increases mortality after infection with enteroviruses that cause myocarditis and/or dilated cardiomyopathy. We screened TLR3 in patients diagnosed with enteroviral myocarditis/cardiomyopathy and identified a rare variant in one patient as well as a significantly increased occurrence of a common polymorphism compared with controls. Expression of either variant resulted in significantly reduced TLR3-mediated signaling after stimulation with synthetic double-stranded RNA. Furthermore, Coxsackievirus B3 infection of cell lines expressing mutated TLR3 abrogated activation of the type I interferon pathway, leading to increased viral replication. TLR3-mediated type I interferon signaling required cellular autophagy and was suppressed by 3-methyladenine and bafilomycin A1, by inhibitors of lysosomal proteolysis, and by reduced expression of Beclin 1, Atg5, or microtubule-associated protein 1 light chain 3␤ (MAP1LC3␤). However, TLR3-mediated signaling was restored upon exogenous expression of Beclin 1 or a variant MAP1LC3␤ fusion protein refractory to RNA interference. These data suggest that individuals harboring these variants may have a blunted innate immune response to enteroviral infection, leading to reduced viral clearance and an increased risk of cardiac pathology.Virus-induced myocarditis is an important cause of morbidity and mortality (1, 2). The enteroviruses have been considered the most common etiologic agents; however, other viruses, such as the adenoviruses, have also been implicated (3). The advent of molecular hybridization and PCR techniques has directly demonstrated infection of the myocardium with these viruses and has provided evidence of a viral etiology for dilated cardiomyopathy (DCM) 5 (1, 3). These findings further support the hypothesis that DCM is in some cases a long term sequela of acute or chronic myocarditis (4, 5), either due to the pathogenic effect of persistent viral replication or to an ongoing autoimmune process secondary to the viral infection.The recognition of viruses or viral particles by the host triggers the activation of an innate immune response that is characterized by the production of mediators such as tumor necrosis factor-␣, interleukins, interferons, and nitric oxide, all of which are toxic to replicating viruses (6). This initial antiviral response by the host is now known to be mediated at least in part by Toll-like receptors (TLRs) (5, 6). It has been shown that double-stranded (ds) RNA is the primary ligand for TLR3 (7). Although most TLR signaling pathways utilize the adaptor molecule MyD88 (myeloid differentiation primary response gene 88), TLR3 signals through the adaptor molecule called Toll-like receptor adaptor molecule 1 (Ticam1) or Toll/Interleukin 1 receptor domain-containing adapter-inducing interferon ␤ (TRIF) (8, 9). Activation of this pathway triggers produ...

Enterovirus-induced myocardial injury can lead to severe heart failure. To date, little is known about the early innate stress response that contributes to host defense in the heart. Toll-like receptor 3 (TLR3) is important in the initiation of the innate antiviral response. We investigated the involvement of TLR3, which recognizes viral double-stranded RNA, on encephalomyocarditis virus (EMCV) infection. To examine the contribution of TLR3 in protection from EMCV infection, we infected mice deficient in TLR3 with 50 plaque-forming units of EMCV. TLR3-deficient (TLR3−/−) mice were more susceptible to EMCV infection and had a significantly higher viral load in the heart compared with TLR3+/+ mice. Histopathological examination showed that the inflammatory changes of the myocardium were less marked in TLR3−/− than in TLR3+/+mice. TLR3−/− mice had impaired proinflammatory cytokine and chemokine expression in the heart following EMCV infection. However, the expression of interferon-β was not impaired in EMCV-infected TLR3−/− mice. EMCV infection leads to a TLR3-dependent innate stress response, which is involved in mediating protection against virus-induced myocardial injury.

A simple measurement of EAT thickness in the left atrioventricular groove may provide a more accurate assessment of metabolic risk associated with EAT, which could not be accounted for by anthropometric indexes and intraabdominal visceral fat.

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Background-Staphylococcus aureus sepsis is associated with significant myocardial dysfunction. Toll-like receptor 2 (TLR2) mediates the inflammatory response to S aureus and may trigger an innate immune response in the heart. We hypothesized that a TLR2 deficiency would attenuate S aureus-induced cardiac proinflammatory mediator production and the development of cardiac dysfunction. Methods and Results-Wild-type and TLR2-deficient (TLR2D) mice were studied. S aureus challenge significantly increased tumor necrosis factor, interleukin-1␤, and nitric oxide expression in hearts of wild-type mice. This response was significantly blunted in TLR2D mice. Hearts from TLR2D mice had impaired S aureus-induced activation of interleukin-1 receptor-associated kinase, c-Jun NH 2 terminal kinase, nuclear factor-B, and activator protein-1. Moreover, hearts from TLR2D mice were protected against S aureus-induced contractile dysfunction. Conclusions-These results show for the first time that TLR2 signaling contributes to the loss of myocardial contractility and cytokine production in the heart during S aureus sepsis.

Postresuscitation left ventricular dysfunction is correlated with a number of clinical factors, among which past history of myocardial infarction, epinephrine dose, and the cause of cardiac arrest play independent roles. Meanwhile, IVRT 100 ms or longer 6 h postresuscitation predicts poor survival outcomes and serves as a marker of poor prognosis.