Application of the TIMI risk score for ST-elevation MI in the National Registry of Myocardial Infarction 3

CONTEXT: The Thrombolysis in Myocardial Infarction (TIMI) risk score for ST-elevation myocardial infarction (STEMI) is a simple integer score for bedside risk assessment of patients with STEMI. Developed and validated in multiple clinical trials of fibrinolysis, the risk score has not been validated in a community-based population. OBJECTIVE: To validate the TIMI risk score in a population of STEMI patients reflective of contemporary practice. DESIGN, SETTING, AND PARTICIPANTS: The risk score was evaluated among 84 029 patients with STEMI from the National Registry of Myocardial Infarction 3 (NRMI 3), which collected data on consecutive patients with myocardial infarction (MI) from 1529 US hospitals between April 1998 and June 2000. MAIN OUTCOME MEASURES: Ability of the TIMI risk score to correctly predict risk of death in terms of model discrimination (c statistic) and calibration (agreement of predicted and observed death rates). RESULTS: Patients in NRMI 3 tended to be older, to be more often female, and to have a history of coronary disease more often than those in the derivation set. Forty-eight percent received reperfusion therapy. The TIMI risk score revealed a significant graded increase in mortality with rising score (range, 1.1%-30.0%; P<.001 for trend). The risk score showed strong prognostic capacity overall (c = 0.74 vs 0.78 in derivation set) and among patients receiving acute reperfusion therapy (c = 0.79). Predictive behavior of the risk score was similar between fibrinolytic-treated patients (n = 23 960; c = 0.79) and primary percutaneous coronary intervention patients (n = 15 348; c = 0.80). In contrast, among patients not receiving reperfusion therapy, the risk score underestimated death rates and offered lower discriminatory capacity (c = 0.65). CONCLUSIONS: Sufficiently simple to be practical at the bedside and effective for risk assessment across a spectrum of patients, the TIMI risk score may be useful in triage and treatment of patients with STEMI who are treated with reperfusion therapy.     

Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis

Aim of the study

In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis.

Material and methods

The anti-ulcer assays were performed using the following protocols: nonsteroidal-antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated.

Results

It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastric juice and total acidity and significantly increased the gastric pH (p < 0.05), compared with the control group, with the exception of the group treated with 50 mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2000 mg/kg.

Conclusions

In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity.     

Factors associated with severe maternal outcomes in patients with eclampsia in an obstetric intensive care unit: A cohort study

To describe the clinical profile, management, maternal outcomes and factors associated with severe maternal outcome (SMO) in patients admitted for eclampsia.A retrospective cohort study was carried out. All women admitted to the Obstetric Intensive Care Unit (ICU) at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Recife, Northeast of Brazil, from April 2012 to December 2019 were considered for inclusion and patients with the diagnosis of eclampsia were selected. Patients who, after reviewing their medical records, did not present a diagnosis of eclampsia were excluded from the study. Severe maternal outcome (SMO) was defined as all cases of near miss maternal mortality (MNM) plus all maternal deaths during the study period. The Risk Ratio (RR) and its 95% confidence interval (95% CI) were calculated as a measure of the relative risk. Multiple logistic regression analysis was performed to control confounding variables. The institute''s internal review board and the board waived the need of the informed consent.Among 284 patients with eclampsia admitted during the study period, 67 were classified as SMO (23.6%), 63 of whom had MNM (22.2%) and 5 died (1.8%). In the bivariate analysis, the following factors were associated with SMO: age 19 years or less (RR = 0.57 95% CI 0.37–0.89, P = .012), age 35 years or more (RR = 199 95% CI 1.18–3.34, P = .019), the presence of associated complications such as acute kidney injury (RR = 3.85 95% CI 2.69–5.51, P < .001), HELLP syndrome (RR = 1.81 95% CI 1.20–2.75, P = .005), puerperal hemorrhage (PPH) (RR = 2.15 95% CI 1.36–3.40, P = .003) and acute pulmonary edema (RR = 2.78 95% CI 1.55–4.96, P = .008). After hierarchical multiple logistic regression analysis, the factors that persisted associated with SMO were age less than or equal to 19 years (ORa = 0.46) and having had PPH (ORa = 3.33).Younger age was a protective factor for developing SMO, while those with PPH are more likely to have SMO.     

The Role of Invasive Therapies in Elderly Patients with Acute Myocardial Infarction

INTRODUCTION:

In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies - IT), especially in the context of long-term outcomes after hospital discharge.

METHODS:

We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were ≥70 years old (elderly group - EG), and 1040 were <70 years of age (younger group - YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy - CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models.

RESULTS:

By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG.

CONCLUSION:

Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.     

Facilitation of endocannabinoid effects in the ventral hippocampus modulates anxiety-like behaviors depending on previous stress experience

Although several pieces of evidence indicate that the endocannabinoid system modulates anxiety-like behaviors and stress adaptation, few studies have investigated the brain sites of these effects. The ventral hippocampus (VHC) has been related to anxiety behaviors and has a high expression of cannabinoid-1 (CB1) receptors. Moreover, endocannabinoid signaling in the hippocampus is proposed to regulate stress adaptation. In the present study we investigated the role of previous stressful experience on the effects of AM404, an anandamide uptake inhibitor, microinjected into the VHC of rats submitted to the elevated plus maze (EPM), a widely used animal model of anxiety. Stressed animals were forced restrained for two h 24 h before the test. AM404 (5–50 pmol) microinjection promoted an anxiogenic-like effect in non-stressed rats but decreased anxiety in stressed animals. AM251 (0.01 to 1000 pmol), a CB1 receptor antagonist, failed to change behavior in the EPM over a wide dose range but prevented the effects of AM404. Anxiolytic-like effects of AM404 (5 pmol) intra-VHC injection were also observed in the Vogel conflict test (VCT), another model of anxiety that involves previous exposure to stressful situations (48 h of water deprivation). These results suggest that facilitation of endocannabinoid system neurotransmission in the ventral hippocampus modulates anxiety-like behaviors and that this effect depends on previous stress experience.     

Kinesthetic motor imagery modulates body sway

The aim of this study was to investigate the effect of imagining an action implicating the body axis in the kinesthetic and visual motor imagery modalities upon the balance control system. Body sway analysis (measurement of center of pressure, CoP) together with electromyography (EMG) recording and verbal evaluation of imagery abilities were obtained from subjects during four tasks, performed in the upright position: to execute bilateral plantar flexions; to imagine themselves executing bilateral plantar flexions (kinesthetic modality); to imagine someone else executing the same movement (visual modality), and to imagine themselves singing a song (as a control imagery task). Body sway analysis revealed that kinesthetic imagery leads to a general increase in CoP oscillation, as reflected by an enhanced area of displacement. This effect was also verified for the CoP standard deviation in the medial–lateral direction. An increase in the trembling displacement (equivalent to center of pressure minus center of gravity) restricted to the anterior–posterior direction was also observed to occur during kinesthetic imagery. The visual imagery task did not differ from the control (sing) task for any of the analyzed parameters. No difference in the subjects' ability to perform the imagery tasks was found. No modulation of EMG data were observed across imagery tasks, indicating that there was no actual execution during motor imagination. These results suggest that motor imagery performed in the kinesthetic modality evokes motor representations involved in balance control.     

Amino acid catabolism: a pivotal regulator of innate and adaptive immunity

Enhanced amino acid catabolism is a common response to inflammation, but the immunologic significance of altered amino acid consumption remains unclear. The finding that tryptophan catabolism helped maintain fetal tolerance during pregnancy provided novel insights into the significance of amino acid metabolism in controlling immunity. Recent advances in identifying molecular pathways that enhance amino acid catabolism and downstream mechanisms that affect immune cells in response to inflammatory cues support the notion that amino acid catabolism regulates innate and adaptive immune cells in pathologic settings. Cells expressing enzymes that degrade amino acids modulate antigen-presenting cell and lymphocyte functions and reveal critical roles for amino acid- and catabolite-sensing pathways in controlling gene expression, functions, and survival of immune cells. Basal amino acid catabolism may contribute to immune homeostasis that prevents autoimmunity, whereas elevated amino acid catalytic activity may reinforce immune suppression to promote tumorigenesis and persistence of some pathogens that cause chronic infections. For these reasons, there is considerable interest in generating novel drugs that inhibit or induce amino acid consumption and target downstream molecular pathways that control immunity. In this review, we summarize recent developments and highlight novel concepts and key outstanding questions in this active research field.     

Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998-2003

Viral hepatitis ranks as the fifth cause of morbidity for infectious diseases in Cuba. Epidemics are observed frequently in the population, the hepatitis A virus being the main agent responsible for such epidemics. Previous reports also confirmed the circulation of the hepatitis E virus. From 1998 to 2003, 258 serum samples were collected by the Reference Laboratory on Viral Hepatitis during 33 outbreaks of acute viral hepatitis as well as from 39 sporadic clinical cases. Sera were tested for anti-HAV and anti-HEV IgM by EIA. Overall of the 33 outbreaks studied sera from 12 (36.4%) were positive for anti-HAV IgM only, from 7 (21.2%) were positive for anti-HEV IgM only, and from 14 (42.4%) were positive for antibodies to both viruses. Individually of the 258 sera collected, 137 (53.1%) were positives for anti-HAV IgM, 20 (7.8%) were positives for anti-HEV IgM, 33 (12.8%) were positives for both markers and 68 (26.4%) were negative to both. Of the clinical cases, 4 (10.3%) were positives for anti-HAV IgM, 13 (33.3%) were positives for anti-HEV IgM and 5 (12.8%) were positives for both markers. Seventeen (43.6%) sera were negatives for all viral hepatitis markers available (A-E). A high positivity for HEV was found in outbreaks tested with the kit produced by CIGB. In particular HEV seems to infect individuals of all ages. The results demonstrate the co-circulation of and co-infection with two enterically transmitted viruses; however a higher positivity was observed for anti-HAV than to anti-HEV (53.1% vs. 7.8%) in outbreaks.     

Inhibition of platelet activation by quinones isolated from Auxemma oncocalyx Taub

The present work explored the anti-platelet effect produced by the quinone fractions (17.8, 35.7 and 71.4 microg/ml) isolated from the heartwood of Auxemma oncocalyx Taub. Our results show that the quinone fraction (QF) is a reversible and concentration-dependent inhibitor of human platelet aggregation induced by ADP, arachidonic acid (AA), collagen and thrombin. Besides, the QF effect was significantly potentiated after its association with aspirin or imidazole, and in this case, the AA-induced platelet aggregation was completely blocked. The addition of QF to L-arginine caused a small but significant increase in the percentage of platelet inhibition (13%) only when compared to QF alone. Finally, the addition of QF to pentoxifylline, a known phosphodiesterase inhibitor, resulted in significant potentiation (43% inhibition) of the antiplatelet effects seen with QF (9.7%) or PTX (10%) alone. Although QF presented an antiplatelet effect, it caused a significant decrease in bleeding time, manifested 3 h after oral (100 or 200 mg/Kg) or 1 and 3 h after intraperitonial (30 mg/Kg) administration. In conclusion. QF possibly acts through a combined cyclo-oxygenase and TxA2 synthase inhibition. Besides, QF also increases platelets cAMP levels which also contributes to its anti-aggregatory effects.