Journal of clinical medicine
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An outbreak of novel coronavirus-related pneumonia COVID-19, that was identified in December 2019, has expanded rapidly, with cases now confirmed in more than 211 countries or areas. This constant transmission of a novel coronavirus and its ability to spread from human to human have prompted scientists to develop new approaches for treatment of COVID-19. A recent study has shown that remdesivir and chloroquine effectively inhibit the replication and infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCov) in vitro. ⋯ This review should shed light on the fundamental rationale behind inhibition of SARS-CoV-2 enzymes RdRp as new therapeutic approaches for management of patients with COVID-19. In addition, we will discuss the viability and challenges in targeting RdRp and proteinase, and application of natural product quinoline and its analog chloroquine for treatment of coronavirus infection. Finally, determining the structural-functional relationships of the S protein of SARS-CoV-2 will provide new insights into inhibition of interactions between S protein and angiotensin-converting enzyme 2 (ACE2) and enable us to develop novel therapeutic approaches for novel coronavirus SARS-CoV-2.
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Our study aims to perform a meta-analysis of benefits and risks associated with the use of non-vitamin K oral anticoagulants (NOAC) versus vitamin K antagonists (VKA) in patients with a percutaneous coronary intervention (PCI) with a particular focus on the combination type: dual vs. dual antithrombotic therapy (DAT: NOAC + single antiplatelet therapy (SAPT) vs. DAT: VKA + SAPT), dual vs. triple antithrombotic therapy (DAT: NOAC + SAPT vs. TAT: VKA + dual antiplatelet therapy (DAPT)) or triple vs. triple antithrombotic therapy (TAT: NOAC+DAPT vs. TAT: VKA+DAPT). ⋯ Antithrombotic combinations of NOACs (as DAT or TAT) are safer than VKAs with respect to bleeding risk and result in a satisfactory efficacy with no increase of ischemic or thrombotic events in patients undergoing PCI.
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We investigated the prognostic value of standard electroencephalography, a 30-min recording using 21 electrodes on the scalp, during the early post-cardiac arrest period, and evaluated the performance of electroencephalography findings combined with other clinical features for predicting favourable outcomes in comatose out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM). This observational registry-based study was conducted at a tertiary care hospital in Korea using the data of all consecutive adult non-traumatic comatose OHCA survivors who underwent standard electroencephalography during TTM between 2010 and 2018. The primary outcome was a 6-month favourable neurological outcome (Cerebral Performance Category score of 1 or 2). ⋯ After adjusting other clinical characteristics, an electroencephalography background with dominant alpha and theta waves had the highest odds ratio of 13.03 (95% confidence interval, 4.69-36.22) in multivariable logistic analysis. A combination of other clinical features (age < 65 years, initial shockable rhythm, resuscitation duration < 20 min) with an electroencephalography background with dominant alpha and theta waves increased predictive performance for favourable neurologic outcomes with a high specificity of up to 100%. A background with dominant alpha and theta waves in standard electroencephalography during TTM could be a simple and early favourable prognostic finding in comatose OHCA survivors.
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Background: Linezolid is used for the treatment of soft tissue infections in critically ill patients. However, data for characterizing the pharmacokinetics (PK) and assessing whether effective concentrations are reached at the target site are lacking. We hypothesized that current dosing regimens do not lead to effective concentrations in the plasma and interstitial fluid (ISF) of subcutaneous tissue in obese patients. ⋯ PK in obese patients were characterized by lower maximal plasma concentrations (median 3.8 vs. 8.3 mg/L, p < 0.001) and a higher volume of distribution (41.0 vs. 30.8 L, p < 0.001), and the therapeutic target was not reached for MIC ≥ 1 mg/L in ISF and ≥ 2 mg/L in plasma. Conclusions: Increasing the weight led to a decrease of linezolid concentrations in the plasma and subcutaneous tissue. The current dosing regimen does not seem to produce sufficient concentrations to kill bacteria with MIC ≥ 2 mg/L, especially as empirical antimicrobial therapy in critically ill obese patients.
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During veno-arterial extracorporeal membrane oxygenation (VA-ECMO), the increase of left ventricular (LV) afterload can potentially increase the LV stress, exacerbate myocardial ischemia and delay recovery from cardiogenic shock (CS). Several strategies of LV unloading have been proposed. Systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement included adult patients from studies published between January 2000 and March 2019. ⋯ In an analysis stratified by setting, the highest mortality risk benefit was observed in case of acute myocardial infarction: RR 0.75; 95%CI 0.68-0.83; p < 0.0001; I2 = 0%. There were no apparent differences between two techniques in terms of complications. In heterogeneous populations of critically ill adults in CS and supported with VA-ECMO, the adjunct of LV unloading is associated with lower early mortality and higher rate of weaning.