Acute myocardial infarction (AMI) is the leading cause of death worldwide. Its associated mortality, morbidity and complications have significantly decreased with the development of interventional cardiology and percutaneous coronary angioplasty (PCA) treatment, which quickly and effectively restore the blood flow to the area previously subjected to ischemia. Paradoxically, the restoration of blood flow to the ischemic zone leads to a massive production of reactive oxygen species (ROS) which generate rapid and severe damage to biomolecules, generating a phenomenon called myocardial reperfusion injury (MRI). In the clinical setting, MRI is associated with multiple complications such as lethal reperfusion, no-reflow, myocardial stunning, and reperfusion arrhythmias. Despite significant advances in the understanding of the mechanisms accounting for the myocardial ischemia reperfusion injury, it remains an unsolved problem. Although promising results have been obtained in experimental studies (mainly in animal models), these benefits have not been translated into clinical settings. Thus, clinical trials have failed to find benefits from any therapy to prevent MRI. There is major evidence with respect to the contribution of oxidative stress to MRI in cardiovascular diseases. The lack of consistency between basic studies and clinical trials is not solely based on the diversity inherent in epidemiology but is also a result of the methodological weaknesses of some studies. It is quite possible that pharmacological issues, such as doses, active ingredients, bioavailability, routes of administration, co-therapies, startup time of the drug intervention, and its continuity may also have some responsibility for the lack of consistency between different studies. Furthermore, the administration of high ascorbate doses prior to reperfusion appears to be a safe and rational therapy against the development of oxidative damage associated with myocardial reperfusion. In addition, the association with N-acetylcysteine (a glutathione donor) and deferoxamine (an iron chelator) could improve the antioxidant cardioprotection by ascorbate, making it even more effective in preventing myocardial reperfusion damage associated with PCA following AMI.
IntroductionThis study was designed to test the hypothesis that high-dose ascorbate prior to reperfusion followed by low chronic oral doses ameliorate myocardial reperfusion injury (MRI) in acute myocardial infarction patients subjected to primary percutaneous coronary angioplasty (PCA).Material and methodsA randomized double-blind placebo-controlled and multicenter clinical trial was performed on acute myocardial infarction (AMI) patients who underwent PCA. Sodium ascorbate (320 mmol/l, n = 53) or placebo (n = 46) was infused 30 min prior to PCA. Blood samples were drawn at enrolment (M1), after balloon deflation (M2), 6–8 h after M2 (M3) and at discharge (M4). Total antioxidant capacity of plasma (ferric reducing ability of plasma – FRAP), erythrocyte reduced glutathione (GSH) and plasma ascorbate levels were determined in blood samples. Cardiac magnetic resonance (CMR) was performed at 7–15 days and 2–3 months following PCA. Ninety-nine patients were enrolled. In 67 patients, the first CMR was performed, and 40 patients completed follow-up.ResultsThe ascorbate group showed significantly higher ascorbate and FRAP levels and a decrease in the GSH levels at M2 and M3 (p < 0.05). There were no significant differences in the infarct size, indexed end-systolic volume and ejection fraction at both CMRs. There was a significant amelioration in the decreased ejection fraction between the first and second CMR in the ascorbate group (p < 0.05).ConclusionsAscorbate given prior to reperfusion did not show a significant difference in infarct size or ejection fraction. However, it improved the change in ejection fraction determined between 7–15 days and 2–3 months. This result hints at a possible functional effect of ascorbate to ameliorate MRI.
Cancer patient care requires a multi-disciplinary approach and multiple medical and ethical considerations. Clinical care during a pandemic health crisis requires prioritising the use of resources for patients with a greater chance of survival, especially in developing countries. The coronavirus disease 2019 crisis has generated new challenges given that cancer patients are normally not prioritised for admission in critical care units. Nevertheless, the development of new cancer drugs and novel adjuvant/neoadjuvant protocols has dramatically improved the prognosis of cancer patients, resulting in a more complex decision-making when prioritising intensive care in pandemic times. In this context, it is essential to establish an effective and transparent communication between the oncology team, critical care, and emergency units to make the best decisions, considering the principles of justice and charity. Concurrently, cancer treatment protocols must be adapted to prioritise according to oncologic response and prognosis. Communication technologies are powerful tools to optimise cancer care during pandemics, and we must adapt quickly to this new scenario of clinical care and teaching. In this new challenging pandemic scenario, multi-disciplinary work and effective communication between clinics, technology, science, and ethics is the key to optimising clinical care of cancer patients.
The identification of several genetic mutations in colorectal cancer (CRC) has allowed a better comprehension of the prognosis and response to different antineoplastic treatments. Recently, through a systematic process, consensus molecular subtypes (CMS) have been described to characterize genetic and molecular mutations in CRC patients. Through CMS, CRC patients can be categorized into four molecular subtypes of CRC by wide transcriptional genome analysis. CMS1 has microsatellite instability and mutations in CIMP and BRAF pathways. CMS2, distinguished by mutations in specific pathways linked to cellular metabolism, also has a better prognosis. CMS3 has a KRAS mutation as a hallmark. CMS4 presents mutations in fibrogenesis pathways and mesenchymal-epithelial transition, associated with a worse prognosis. CMS classification can be a meaningful step in providing possible answers to important issues in CRC, such as the use of adjuvant chemotherapy in stage II, personalized first-line chemotherapy for metastasic CRC, and possible new target treatments that address specific pathways in each molecular subtype. Understanding CMS is a crucial step in personalized medicine, although prospective clinical trials selecting patients by CMS are required to pass proof-of-concept before becoming a routine clinical tool in oncology routine care.
Reactive oxygen species (ROS) play a physiological role in the modulation of several functions of the vascular wall; however, increased ROS have detrimental effects. Hence, oxidative stress has pathophysiological impacts on the control of the vascular tone and cardiac functions. Recent experimental studies reported the involvement of increased ROS in the mechanism of hypertension, as this disorder associates with increased production of pro-oxidants and decreased bioavailability of antioxidants. In addition, increased ROS exposure is found in ischemia-reperfusion, occurring in acute myocardial infarction and cardiac surgery with extracorporeal circulation, among other settings. Although these effects cause major heart damage, at present, there is no available treatment. Therefore, it should be expected that antioxidants counteract the oxidative processes, thereby being suitable against cardiovascular disease. Nevertheless, although numerous experimental studies agree with this notion, interventional trials have provided mixed results. A better knowledge of ROS modulation and their specific interaction with the molecular targets should contribute to the development of novel multitarget antioxidant effective therapeutic strategies. The complex multifactorial nature of hypertension, acute myocardial infarction, and postoperative atrial fibrillation needs a multitarget antioxidant strategy, which may give rise to additive or synergic protective effects to achieve optimal cardioprotection.
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