Objective-Reperfusion therapy for myocardial infarction is limited by a significant reocclusion rate and less optimal myocardial tissue perfusion due to excessive platelet accumulation and recruitment at the sites of vascular injury. We assessed the influence of a selective P2Y 12 -receptor antagonist (AR-C69931MX), in conjunction with thrombolytic therapy, on the prevention of platelet aggregation and thrombus formation. Methods and Results-A canine coronary electrolytic injury thrombosis model was used. Tissue-type plasminogen activator (t-PA; 1 mg/kg in phase I, 0.5 mg/kg in phase II in the AR-C69931MX group, and 1 mg/kg in the placebo group in phase I and II) was administered 30 minutes after thrombus formation; either saline or AR-C69931MX (4 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was given to all animals intravenously 10 minutes before t-PA administration for a total of 2 hours. All animals received heparin (80 U/kg) as an intravenous bolus followed by a continuous infusion of 17 U ⅐ kg Ϫ1 ⅐ h Ϫ1 . Myocardial tissue perfusion was evaluated by use of the colored microsphere technique and real-time myocardial contrast echocardiography. The incidences of reocclusion and cyclic flow variation were significantly decreased in the AR-C69931MX group (PϽ0.05). Myocardial tissue flow with AR-C69931MX treatment improved significantly at 20 and 120 minutes after reflow, whereas tissue flow with placebo remained at a level similar to that during occlusion (PϽ0.05). A lthough much progress has been made in the treatment of ischemic heart disease during the past decades, acute ischemic complications due to excessive platelet accumulation, platelet recruitment, and thrombus formation remain a challenging therapeutic issue. Traditionally, successful reperfusion after acute myocardial infarction has been considered to be restored patency of epicardial coronary arteries. Increasing evidence indicates, however, that an open epicardial coronary artery may not represent "optimal reperfusion" and that adequate myocardial tissue perfusion is at least as important as sustained epicardial coronary patency. Lack of myocardial perfusion at the tissue level, despite restoration of normal anterograde flow in the epicardial infarct-related artery, predicts poor recovery of left ventricular function in acute myocardial infarction. 1 ADP-induced platelet activation plays a pivotal role in thrombus formation and thus, inhibition of this pathway holds promise as a means of significantly reducing clot formation and improving myocardial tissue reperfusion during acute ischemic states. There are 2 subtypes of ADP receptor on platelets: P2Y 1 and P2Y 12 receptor. P2Y 1 is found in other tissues, whereas the P2Y 12 receptor, previously referred to as P 2T , is found only on platelets, megakaryocytes, and astroglial cells of the brain. [2][3][4][5][6] See page 158 Conclusions-TheThe thienopyridines, including ticlopidine and clopidogrel, are platelet ADP receptor antagonists that act at the level of P2Y 12 receptor. 7,8 However, their effects on platelets are slow...
Objectives The majority of available scores to assess mortality risk of coronavirus disease 19 (COVID-19) patients in the emergency department have high risk of bias. Therefore, our aim was to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients, and to compare this score with other existing ones. Methods Consecutive patients (≥18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. Results Median (25th-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO 2 /FiO 2 ratio, platelet count and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829 to 0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833 to 0.885]) and Spanish (0.894 [95% CI 0.870 to 0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). Conclusions We designed and validated an easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation, for early stratification for in-hospital mortality risk of patients with COVID-19.
Introduction: Host colonization by Candida species is an important predisposing factor to candidiasis, which seems to be more frequent in human immunodeficiency virus (HIV)-infected patients. Knowledge about the distribution, antifungal susceptibility, and virulence of oral Candida isolates is important for effective management of candidiasis. Methodology: Oral rinses were collected from 242 HIV-infected patients without clinical evidence of candidiasis seen at the AIDS referral center in Londrina, Brazil. Species were identified by standard phenotypic and molecular methods, and characterized in vitro according to antifungal susceptibility, cell surface hydrophobicity, biofilm formation, and enzyme activities. Results: Oral Candida colonization was detected in 50.4% of patients and combined use of antiretroviral therapy and protease inhibitor had a protective effect against colonization. Candida albicans (75.2%) was the most prevalent species. A high proportion of Candida spp. (39.9%) showed decreased susceptibility to fluconazole. Five isolates were resistant to nystatin. Protease and phospholipase activities were detected in 100% and 36.8% of isolates, respectively. Most isolates displayed a hydrophobic property that was associated with biofilm formation ability. Conclusions: A significant number of oral Candida species exhibiting decreased susceptibility to fluconazole were isolated from colonized HIV-infected individuals. Furthermore, all isolates expressed potential virulence attributes in vitro. Given the high incidence and severity of fungal infections in HIV-infected individuals, the results of this study reinforce the importance of antifungal susceptibility testing, which contributes to therapeutic strategies and highlights the need for continuous surveillance of Candida colonization in this population.
A strategic plan aimed at the rational use of antimicrobials based on educational and interventionist practices can help the infection control professional to adjust the routines to improve healthcare quality.
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