RISK SCORE MODEL FOR PREDICTING CARDIOTOXICITY IN BREAST CANCER: DIAGNOSTIC VALUE OF HIGH-SENSITIVITY CARDIAC TROPONIN T. / ШКАЛА РИЗИКУ КАРДІОТОКСИЧНОСТІ У ХВОРИХ НА РАК ГРУДНОЇ ЗАЛОЗИ: ДІАГНОСТИЧНЕ ЗНАЧЕННЯ ВИСОКОЧУТЛИВОГО СЕРЦЕВОГО ТРОПОНІНУ Т.

Cardiovascular diseases are the second leading cause of death among breast cancer (BC) patients. Prediction of cardiovascular toxicity (CT) is an important part of the successful treatment and survival of patients. OBJECTIVE: to develop a risk score model for cardiovascular toxicity (CT) predicting, based on cardiovascular risk factors (RFs), RFs associated with cancer therapy, and troponin levels. MATERIAL AND METHODS: The study included 76 BC patients with a prospective analysis of their clinical and treatment data, RFs, echocardiographic indicators before the start of treatment and after 6 months, and an increase in troponin level. Among all RFs, the most significant RFs of CT were: radiation therapy, treatment with anthracyclines, and cardiovascular diseases. Based on the obtained results, a combined CT risk score was developed and proposed.According to the sum of points, patients were divided into groups: group 1 - with a low risk of CT development, the sum of points < 5; group 2 - moderate risk, 6-7 points; group 3 - high risk, > 8 points. RESULTS: In a pilot prospective study, an analysis of the RFs of CT was provided, compared to echocardiography data and the degree of troponin increase in dynamic observation; the risk score model for the CT prediction was developed for BC patients stratification. According to the developed score, BC patients with a total of > 8 points are considered to have a high risk of CT complications. CONCLUSIONS: The use of the proposed risk model score with calculation of the RFs of CT along with high-sensitivity troponin increase during cancer treatment allows predicting the risk of CT developing at the early stages - before the onset of clinical manifestations. Accordingly, these BC patients have a high risk of CT, and the use of personalized cardiac monitoring together with cardioprotective therapy can prevent cardiovascular complications.

Serial Measurement of Global Longitudinal Strain Among Women With Breast Cancer Treated With Proton Radiation Therapy: A Prospective Trial for 70 Patients.

PURPOSE: Conventional photon radiation therapy (RT) for breast cancer is associated with a reduction in global longitudinal strain (GLS) and an increase in troponin, N-terminal pro hormone B-type natriuretic peptide (NT-proBNP), and incident heart failure. The cardiac radiation exposure with proton-RT is much reduced and thus may be associated with less cardiotoxicity. The objective was to test the effect of proton-RT on GLS, troponin, and NT-proBNP. METHODS AND MATERIALS: We conducted a prospective, observational, single-center study of 70 women being treated with proton-RT for breast cancer. Serial measurements of GLS, high-sensitivity troponin I, and NT-proBNP were performed at prespecified intervals (before proton-RT, 4 weeks after completion of proton-RT, and again at 2 months after proton-RT). RESULTS: The mean age of the patients was 46 ± 11 years, and the mean body mass index was 25.6 ± 5.2 kg/m2; 32% of patients had hypertension, and the mean radiation doses to the heart and the left ventricle (LV) were 0.44 Gy and 0.12 Gy, respectively. There was no change in left ventricular ejection fraction (65 ± 5 vs 66 ± 5 vs 64 ± 4%; P = .15), global GLS (-21.7 ± 2.7 vs -22.7 ± 2.3 vs -22.8 ± 2.1%; P = .24), or segmental GLS from before to after proton-RT. Similarly, there was no change in either high-sensitivity troponin or NT-proBNP with proton-RT. However, in a post hoc subset analysis, women with hypertension had a greater decrease in GLS after proton-RT compared with women without hypertension (-21.3 ± 3.5 vs -24.0 ± 2.4%; P = .006). CONCLUSIONS: Proton-RT did not affect LV function and was not associated with an increase in biomarkers. These data support the potential cardiac benefits of proton-RT compared with conventional RT.

Relaxin-3 Ameliorates Diabetic Cardiomyopathy by Inhibiting Endoplasmic Reticulum Stress.

Background: This study is aimed at investigating whether relaxin-3 exhibits protective effects against cardiomyopathy in diabetic rats by suppressing ERS. Methods: Eighty male SD rats were randomly divided into two groups: controls (n = 20) and diabetes (n = 60). The streptozotocin-treated rats were randomly divided into three groups: diabetic group (DM), low-dose relaxin-3 group (0.2 µg/kg/d), and high-dose relaxin-3 group (2 µg/kg/d). The myocardial tissues and collagen fiber were observed by hematoxylin and eosin (H&E) and Masson staining. Serum brain natriuretic peptide (BNP), troponin (TNI), myoglobin, interleukin (IL-17), interleukin (IL)-1α, and tumor necrosis factor (TNF)-α were determined by ELISA. The protein expression of glucose regulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the heart tissue of each group was detected by Western blot analysis. Results: (1) HE and Masson staining indicated that relaxin-3 could attenuate myocardial lesions and myocardial collagen volume fraction. (2) BNP, TnI, and myoglobin in the DM group at four and eight weeks were significantly higher than in the controls (P < 0.01). The relaxin-3-treated groups showed significantly reduced serum BNP, TnI, and myoglobin levels compared with the DM group (P < 0.05). (3) IL-17, IL-1α, and TNF-α levels in the DM rats at 4 weeks were higher than in the controls (P < 0.05). Low or high dose of relaxin-3-treated groups showed reduced serum IL-17 and TNF-α levels compared with the DM group at four and eight weeks (P < 0.05). (4) CHOP and GRP78 protein expression was increased in the DM group at four and eight weeks compared with the controls (P < 0.01), and small and large doses of relaxin-3 significantly reduced GRP78 and CHOP protein expression. Conclusions: Exogenous relaxin-3 ameliorates diabetic cardiomyopathy by inhibiting ERS in diabetic rats.

Computed tomography coronary angiography in non-ST-segment elevation myocardial infarction.

Electrocardiography and high-sensitivity cardiac troponin testing are routinely applied as the initial step for clinical evaluation of patients with suspected non-ST-segment elevation myocardial infarction. Once diagnosed, patients with non-ST-segment elevation myocardial infarction are commenced on antithrombotic and secondary preventative therapies before undergoing invasive coronary angiography to determine the strategy of coronary revascularisation. However, this clinical pathway is imperfect and can lead to challenges in the diagnosis, management, and clinical outcomes of these patients. Computed tomography coronary angiography (CTCA) has increasingly been utilised in the setting of patients with suspected non-ST-segment elevation myocardial infarction, where it has an important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia. CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory. In addition, CTCA provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease and highlights alternative or incidental diagnoses for those with cardiac troponin elevation. However, the routine application of CTCA has yet to demonstrate an impact on subsequent major adverse cardiovascular events. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction. We here review the current evidence relating to the clinical application of CTCA in patients with non-ST-segment elevation myocardial infarction and highlight the areas where CTCA is likely to have an increasing important role and impact for our patients.

A Newly Synthesized Derivative and a Natural Parent Molecule: Which Would Be More Beneficial as a Future Antitumor Candidate? Docking and In Vivo Study.

Seeking for new effectual anticancer drugs is of great importance. In this study, a newly synthesized and well-characterized chromene derivative (ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate) "C" was prepared. Molecular docking studies were done. The new compound "C" in compare to the natural parent Quercetin "Q," as a well-known natural chromene derivative with antioxidant and antitumor activities, were tested for their antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing mice. Both reduced ascites volume, decreased viable EAC cells, and prolonged EAC-bearing mice life span. They normalized troponin, creatine kinase-MB, lactate dehydrogenase, and urea levels, reversed liver enzyme activities towards normal, and increased antioxidant levels while reduced tumor necrosis factor-alpha (TNF-α) levels. Compared to each other, the new synthetic derivative "C" showed stronger antineoplastic effects than the natural parent "Q" may via the anti-inflammatory activities. Therefore, the newly synthesized chromene derivative is more promising as a future antitumor candidate than the natural parent molecule "Quercetin." Finally, our results encourage researchers to pay more attention to developing more novel natural-based derivatives that would be more beneficial as future therapeutics than their natural parents.

Clinical implications of isolated troponinemia following immune checkpoint inhibitor therapy.

Cardiovascular adverse events induced by immune checkpoint inhibitors (ICIs) have gained significant interest over the past decade due to their impact on short- and long-term outcomes. They were initially thought to be rare, but the increasing use of ICIs in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in their incidence. Different guidelines have proposed screening measures for ICI-induced myocarditis by incorporating troponin measurements at baseline and during the first few weeks of treatment. However, no specific guidelines have been developed yet regarding the interpretation of an asymptomatic rise in troponins. This state-of-the art review aims to provide an overview of the clinical relevance of elevated troponins during checkpoint inhibition and recommendations on how to manage elevated troponin levels during ICI therapy.

Reducing avoidable chest pain admissions and implementing high-sensitivity troponin testing.

NHS accident and emergency departments see 0.5 million patients presenting with a cardiac condition each year. The accurate assessment of chest pain and subsequent diagnosis or exclusion of myocardial infarction (MI) represent a significant challenge, with important consequences on patient outcome and healthcare resources. We conducted a cross-sectional analysis of patients admitted with cardiac chest pain to a busy district general hospital in London. The criteria used by physicians to admit patients for further cardiac investigations were measured against national guidance on chest pain assessment and diagnosis of MI. We found that poor adherence to guidance, unsuitable patient pathways and inappropriate diagnostic tools at the point of presentation led to unnecessary inpatient admissions to the hospital. Quality improvement methods were used with the aim to reduce avoidable admissions to hospital in patients presenting with chest pain. We describe a system to implement new high-sensitivity troponin testing into legacy chest pain pathways. This was achieved through local education of National Institute for Health and Care Excellence (NICE) guidance, the use of patient pro formas and the creation of two new chest pain pathway arms to enable physicians to streamline patients for appropriate inpatient or outpatient care. As a result of these changes, we reduced non-compliance with NICE guidance by 83% and achieved a 42% reduction in avoidable chest pain admissions. Overall, the improvements made by this project were sustained over 2 years and saved £21 000 per month in avoidable admissions.

Dor torácica na sala de emergência: quem fica e quem pode ser liberado? / Chest pain in the emergency room: who is left and who can be released?

A dor torácica aguda é um sintoma muito frequente nas unidades de emergência, constituindo-se em um possível sinal de alerta para as doenças com risco iminente de morte. Como a maioria desses pacientes é internada para avaliação de uma possível síndrome coronariana aguda, isso gera um custo hospitalar muito alto por paciente. Por conta dessa possibilidade diagnóstica, muitos emergencistas internam a maioria dos pacientes. Por outro lado, a liberação inapropriada daqueles com infarto agudo do miocárdio representa um risco para o médico e, especialmente, para o paciente. Outro ponto importante é a demora para o atendimento, em que há a influência de fatores relacionados ao paciente, assim como, pontos negativos na logística de atendimento dos serviços de emergência em nosso país. Para excelência no atendimento, é importante uma anamnese detalhada adicionada ao exame físico, a qual permite a elaboração das hipóteses diagnósticas. E para auxiliar os médicos na escolha da hipótese diagnóstica e na tomada rápida de decisão, escores de risco são disponibilizados, os quais, facilmente, identificam a probabilidade de eventos adversos. A conduta imediata de casos com risco de morte imediata tem como principal objetivo reduzir a morbidade e a mortalidade, aumentando, consequentemente, a segurança do profissional da emergência. Sugestões de fluxogramas e algoritmos para o atendimento desses pacientes na sala de emergência definem, de forma objetiva, quem fica e quem pode ser liberado

Acute chest pain is a frequent symptom in emergency units, being a possible war-ning sign of diseases with an imminent risk of death. Since most of these patients are hospitalized to evaluate possible acute coronary syndrome, this generates a very high hospital cost per patient. Because of this diagnostic possibility, emergency professionals admit most patients. In contrast, the inappropriate release of those with acute myocardial infarction poses a risk to the physician and, especially, the patient. Another important point is the delay in care, where there is an influence of patient-related factors, as well as negative points in the logistics of care in the emergency services in our country. For excellence in care, a detailed anamnesis added to the examination is important, allowing the elaboration of diagnostic hypotheses. Moreover, to assist physicians in selecting the diagnostic hypothesis and making fast decisions, there are risk scores that easily identify the likelihood of adverse events. The immediate management of cases with an imminent risk of death is the main objective to reduce morbidity and mortality and, consequently, increase the safety of emergency professionals. Flowcharts and algorithm suggestions targeting patients in the emergency room objectively define who stays and who can be released

[Emergency medicine: updates 2012]. / Médecine d'urgence.

We review some of the most influential papers from 2012 in the different aspects of emergency medicine, such as prehospital medicine, resuscitation, early diagnosis and timely ED discharge and treatment. In particular, intramuscular benzodiazepines have been shown to be efficient in prehospital status epilepticus, epinephrines usefulness in cardiopulmonary resuscitation has been challenged, colloids have been shown to be deleterious in the treatment of severe sepsis and septic shock, the time window for thrombolysis in acute stroke will probably be extended, acute pyelonephritis treatment duration can be decreased, new D-dimers thresholds for older patients may prevent further diagnosis tests, and hs-Troponin may allow earlier discharge of low coronary risk patients.

[Acute dyspnea in the emergency room: the utility of troponin, natriuretic, procalcitonin and D-dimers]. / Dyspnée aiguë aux urgences: utilité des troponines, des peptides natriurétiques, de la procalcitonine et des D-dimères.

In emergency, some "low cost" biological tests are too often systematically performed while others are not prescribed because they are considered "too expensive". Good practices for biological testing are in fact the real means for saving money. Here, in order to help for defining those good practices, we review emergency medical approach and, as an example, specify findings concerning the clinical utility of key blood analyses in patients with acute dyspnea. Emergency laboratory testing is usefull when it contributes to establish the diagnosis or to evaluate comorbidity or to stratify disease severity. In a given emergency context, clinical utility must be anticipated according to a bayesian approach with an estimation of the post-test probabilities using the likelihood ratios (estimated from literature) and the pretest probabilities (established by examination at the bedside). The likelihood ratio is the best criterion for diagnostic accuracy of a biological test. According to this criterion, troponin, natriuretic peptides, procalcitonin and D-dimers are four "costly" markers but which can significantly contribute to the etiologic diagnosis of an acute dyspnea. Troponin, natriuretic peptides and procalcitonin are also prognostic markers and are valuable parameters for stratifying disease severity according to their initial value and their plasmatic kinetic during the clinical course of the disease. In conclusion, it is not only the cost of the test but overall the potential impact of its result on the management of the patient's care which makes the decision of performing the test or not.

Acute myocardial infarction in a patient with normal coronary arteries after an allergic reaction.

The case is described of a man aged 51 years who, one hour after a coronary angiographic examination that showed coronary arteries without lesions, suffered an acute inferior myocardial infarction as the result of an acute allergic reaction, probably to the iodinated contrast agent that was used. Acute myocardial infarction following an allergy is an extremely rare clinical entity that, according to existing data, is due to the local release of vasoconstrictive substances as a result of the allergic reaction.

O papel das troponinas no infarto agudo do miocárdio / The role of troponin in the early diagnosis of acute myocardial infarction

Nos Estados Unidos, em 1997, dentre 550 mil pacientes com suspeita de infarto agudo do miocárdio, aproximadamente metade apresentou eletrocardiograma inalterado. Pesquisas realizadas demonstraram que isso aumenta o risco de morbidade e mortalidade após a alta hospitalar em pacientes com infarto agudo do miocárdio não-diagnosticado. Esse fato estimulou a pesquisa de novos marcadores sorológicos que fossem capazes de fornecer resultados cada vez mais precoces das agressões sofridas pelo organismo decorrentes de necroses das células miocárdicas ocorridas diante do infarto agudo do miocárdio. Uma das descobertas da atualidade foi a troponina, pela sua sensibilidade e especificidade...