Bioethics in medical care rationing during the coronavirus disease-19 pandemic

ABSTRACT Background: Coronavirus (CoV) disease (COVID)-19 poses difficult situations in which the ethical course of action is not clear, or choices are made between equally unacceptable responses. Methods: A web search was performed using the terms “bioethics; COVID-19; ethics; severe acute respiratory syndrome CoV-2; emergent care; pandemic; and public health emergencies.” Results: Protection from COVID-19 has resulted in the cancellation of necessary medical interventions, lengthened suffering, and potential non-COVID-19 deaths. Prolonged lockdown reduced well-being, triggering or aggravating mental illnesses and violence, and escalated medical risks. Collateral damage includes restrictions on visitations to hospitals, alienation from the deceased relative, or lack of warm caring of patients. Finally, in a public health crisis, public health interest overrides individual rights if it results in severe harm to the community. Conclusion: Balancing ethical dilemmas are one more challenge in the COVID-19 pandemic. (REV INVEST CLIN. 2021;73(1):1-5)

Bioethics in the COVID-19 Pandemic Research: Challenges and Strategies

As all other aspects in times of the coronavirus disease (COVID)-19 pandemic, carrying-out quality clinical research has been challenging. Many well-established paradigms have shifted as a consequence of the rapid demand for new knowledge. New treatments are fast-moving, informed consent forms are difficult to obtain, a competitive invitation from researchers to participate in different studies is common, and non-COVID-19 research protocols are suffering continuity. However, these challenges should not imply taking shortcuts or accepting deficiencies in bioethical standards, but rather enhance the alertness for rigorous ethical approaches despite these less than ideal circumstances. In this manuscript, we point out some interrogates in COVID-19 research and outline possible strategies to overcome the difficult task to continue with high-quality research without violating the ethical principles. (REV INVEST CLIN. 2020;72(5):265-70)

Left atrial function and volume by magnetic resonance in patients with hereditary amyloidosis

ABSTRACT Background Left atrial (LA) enlargement is a reliable predictor of adverse cardiovascular events, and reduced atrial function is an independent risk factor for mortality in patients with amyloidosis. The objective of this study was to characterize the LA function in Mexican patients with a confirmed diagnosis of hereditary transthyretin amyloidosis (amyloid transthyretin [ATTR]) Methods All consecutive patients with diagnosis of hereditary ATTR who underwent a cardiac magnetic resonance study in the period from March 2016 to June 2017 were included in the study; the volumes and function of the left atrium were evaluated Results Patients were divided into two groups, one with and one without cardiac amyloidosis. Statistically significant differences were observed between both groups in terms of indexed maximal LA volume, 26 mL versus 35.9mL, p = 0.03; indexed minimal LA volume, 10.7 mL versus 13.6mL, p = 0.03; and indexed LA pre-contraction volume, 17 mL versus 22.4mL, p = 0.03. No statistically significant differences were observed between both groups when comparing neither different ejection volumes nor the different ejection fractions Conclusions Patients with hereditary ATTR with cardiac involvement have remodeling of the left atrium, with increased atrial volumes, without diminishing its function.

III. The role of the Research Ethics Committees in the regulation of Pharma-Sponsored studies

Participants of Pharma-sponsored research are exposed to risks, benefits, and uncertainties that do not occur in other forms of clinical studies. Ethics committees represent the subjects’ first line of protection. This responsibility begins with the study review and ends after all study subjects finish the intervention. The objective of this paper is to review the most common controversial issues found in Pharma-sponsored studies. Potential solutions are proposed to prevent or resolve the polemical aspects. However, different challenges will be faced in the near future (e.g., when new therapies reach their late stage of development). All parties involved in research should work together to guarantee the protection of participants, the paramount principle on which clinical investigation is based. Pharma-sponsored research is a crucial driver to develop and implement innovative approaches to improve the informed consent process and the execution of the studies.

II. The research ethics involving vulnerable groups

Abstract Vulnerability in research occurs when the participant is incapable of protecting his or her interests and therefore, has an increased probability of being intentionally or unintentionally harmed. This manuscript aims to discuss the conditions that make a group vulnerable and the tools and requirements that can be used to reduce the ethical breaches when including them in research protocols. The vulnerability can be due either to an inability to understand and give informed consent or to unequal power relationships that hinder basic rights. Excluding subjects from research for the only reason of belonging to a vulnerable group is unethical and will bias the results of the investigation. To consider a subject or group as vulnerable depends on the context, and the investigator should evaluate each case individually.

I. The role of research ethics committees in observational studies: epidemiological registries, case reports, interviews, and retrospective studies

Abstract It is often unclear to the clinical investigator whether observational studies should be submitted to a research ethics committee (REC), mostly because, in general, no active or additional interventions are performed. Moreover, obtaining an informed consent under these circumstances may be challenging, either because these are very large epidemiological registries, or the subject may no longer be alive, is too ill to consent, or is impossible to contact after being discharged. Although observational studies do not involve interventions, they entail ethical concerns, including threats such as breaches in confidentiality and autonomy, and respect for basic rights of the research subjects according to the good clinical practices. In this context, in addition to their main function as evaluators from an ethical, methodological, and regulatory point of view, the RECs serve as mediators between the research subjects, looking after their basic rights, and the investigator or institution, safeguarding them from both legal and unethical perils that the investigation could engage, by ensuring that all procedures are performed following the international standards of care for research. The aim of this manuscript is to provide information on each type of study and its risks, along with actions to prevent such risks, and the function of RECs in each type of study.

Prevalencia del polimorfismo del nucleótido simple rs4704963 (T > C) del gen Early B-Cell Factor 1 en una población de pacientes diabéticos tipo 2 con obesidad / Prevalence of Early B-Cell Factor 1 Gene rs4704963 Single Nudeotide Polymorphism (T>C) in a Population of Type 2 Diabetic Patients with Obesity

RESUMEN Introducción: En estudios previos, se determinó para una población con agravamiento de la diabetes tipo 2 con obesidad (DBT+Ob) que sufría estrés una prevalencia del polimorfismo de nucleótido único (SNP) rs4704963 (T > C) del gen Early B-Cell Factor 1 (EBF1) del 16,5%. Objetivos: Determinar la prevalencia de este SNP en pacientes con DBT+ Ob que acuden al Hospital Ramos Mejía de la Ciudad Autónoma de Buenos .Aires y establecer si dicho polimorfismo se asocia con el estrés o la ocurrencia de eventos coronarios agudos. Material y métodos: Se llevó a cabo un estudio observacional, prospectivo, sobre prevalencia del polimorfismo en 53 pacientes con DBT+Ob e índice de masa corporal (IMC) entre 28 y 41, atendidos en el citado hospital en un período de 15 meses. A cada paciente se le computó una escala de estrés percibido, además de evaluarlo mediante la escala de acontecimientos vitales estresantes. Para el análisis estadístico, se realizaron las pruebas de Chi cuadrado y se calcularon los odds ratio (OR). Resultados: La población evaluada (53 pacientes) tuvo una media de edad de 60,2 ±9,77 años; 47,2% fueron hombres. De ellos, 8 individuos (15,1%) presentaron el SNP y todos fueron heterocigotas. Quince sujetos (28,3%) tuvieron síndrome isquémico agudo (SIA) y de estos solo uno (6,6%) tenía el SNP No se halló relación estadísticamente significativa entre la presencia del SNP y la aparición de SIA (p = 0,282). Catorce pacientes (26,4%) presentaron estrés crónico moderado o grave, y no hubo relación entre este hallazgo y la presencia del SNP (p = 0,979). Conclusiones: La prevalencia del SNP rs4704963 (T > C) del gen EBF1 en la población de DBT+Ob estudiada fue del 15,1% y no se halló relación estadísticamente significativa del SNP con el estrés ni con el SIA.

ABSTRACT Background: Previous studies established that in a population with exacerbation of type 2 diabetes with obesity (DBT+Ob) suffering from stress, the prevalence of early B-Cell Factor 1 (EBF1) gene rs4704963 single nucleotide polymorphism (SNP) (T>C) is 16.5%. Objectives: The aim of this study was to determine the prevalence of this SNP in patients with DBT+Ob attending Hospital Ramos Mejía of the Autonomous City of Buenos Aires and to ascertain whether this polymorphism is associated with stress or acute coronary events. Methods: An observational, prospective study on the prevalence of rs4704963 SNP was performed in 53 patients with DBT+Ob and body mass index between 28 and 41, seen in Hospital Ramos Mejía for a period of 15 months. Each patient was evaluated with a stressful life events scale and a perceived stress scale. The chisquare test and odds ratio (OR) were used for statistical analysis. Results: A total of 53 patients were included in the study. Mean population age was 60.2±9.77 years and 47.2% were men. Among these patients, 8 (15.1%) presented SNP and all were heterozygous. Fifteen patients (28.3%) had acute ischemic syndrome (AIS), and among these, only one (6.6%) had SNP No statistically significant relationship was found between the presence of SNP and AIS (p=0.282). Fourteen patients (26.4%) presented moderate or severe chronic stress, and there was no relationship between this finding and the presence of SNP (p=0.979). Conclusions: The prevalence of EBF1 gene rs4704963 SNP (T>C) in the DBT+Ob population was 15.1%. No statistically significant association was found between SNP and stress or AIS.

Superantígenos y neoplasias linfoides / SUPERANTIGENS AND NEOPLASTIC LYMPHOMAS

Los superantígenos (Sags) son proteínas de origen bacteriano o viral capaces de estimular y causar la muerte de un alto numero de linfocitos T o B. normales. Este hecho se debe a que ­ a diferencia de los antígenos convencionales que son reconocidos por todas las regiones variables del receptor de las células T (TCR) o B (BCR) - sólo interactúan con regiones constantes ubicadas dentro de las regiones variables de estos receptores. Los Sags B se unen a sitios constantes de las regiones variables de las cadenas pesadas o livianas de las inmonuglobulinas de superficie (BCR) y causan la muerte por apoptosis de las células B que los reconocen. Los Sags T se unen a los antígenos mayores de histocompatibilidad de clase II en las células presentadoras de antígenos e interactúan con linfocitos T que expresen una región variable particular de su cadena â. Las células T reactivas mueren después de recibir esta fuerte estimulación. No se conocen intentos de investigar si los Sags son capaces de inducir la muerte por apoptosis de células neoplásicas B o T. En el presente trabajo reportamos que diferentes Sags bacterianos o virales son capaces de inducir la apoptosis de celulas de leucemias/linfomas B y T murinos y humanos. Estudiamos los mecanismos de apoptosis involucrados. En el caso de los linfomas T estudiados encontramos que estaban implicadas tanto la vía extrínseca cuanto la intrínseca e incluso un entrecruzamiento de ambas vías. El tratamiento in vivo de ratones inoculados con diferentes linfomas T fue capaz de incrementar muy significativamente la sobrevida libre de enfermedad. Mientras que el 100% de los ratones no tratados o tratados con un Sag control (no interactuante con el receptor T del linfoma) morían en pocos días, el tratamiento con Sags específcos indujo una sobrevida de entre el 40 al 90% de los mismos. Se investigo la capacidad del Sag B PpL secretado por Finegoldia magna y que interactua con celulas B que expresan la cadena liviana κ para inducir la apoptosis in vivo e in vitro. de celulas de linfomas/leucemias B murinas y humanas κ+. El Sag utilizado indujo la apoptosis en estas celulas utilizando solo la via intrinseca. En resumen, se demostro que los Sags B y T inducen la muerte por apoptosis de cèlulas B y T neoplasicas que los reconocen a traves de su receptor para el antigeno. Se discute la posibilidad del uso de los superantígenos para la implementacion de una nueva herramienta terapeutica que tendria la ventaja de afectar solo un numero discreto de linfocitos sin afectar otros tipos de cèlulas normales.

Superantiges are mostly bacterial or viral proteins that stimulate a large number of normal T or B lymphocytes.. This fact is because - unlike conventional antigens that are recognized by all the variable regions of the receptor of these cells - they only interact with constant regions located within the variable regions of the receptors. B-cell superantigens bind to conserved sites of the VH or VL regions of immunoglobulin molecules outside their complementarity-determining regions causing the apoptosis of normal cognate B cells. T cell Superantigens bind to major histocompatibility complex class II molecules in antigen presenting cells and interact with T cells expressing a particular T cell receptor Vß inducing a strong proliferation/deletion response of the superantigen-reactive T cells. No attempts to investigate whether B or T-cell Sags are able to induce the apoptosis of cognate malignant B or T cells were reported. In the present study we show that bacterial and viral-encoded superantigens induce the apoptosis of murine and human cognate lymphoma T cells both in vitro and in vivo. The extrinsic and the intrinsic patway of apoptosis were found to be involved. Besides, a cross-talk between both pathway was also found. In vivo exposure to bacterial superantigens was able to improve the survival of lymphoma bearing mice. Moreover, the permanent expression of a retroviral encoded superantigen induced the complete remission of an aggressive lymphoma in a high percentage of mice. We also studied the ability of a B-cell superantigen (PpL) secreted by Finegoldia magna, which interacts with κ+ bearing cells, to induce the apoptosis of murine and human κ+ lymphoma B cells both in vitro and in vivo. The involvement of the intrinsic but not the extrinsic patway of apoptosis was clearly demonstrated. In summary, herein we show that B and T superantigens are able to induce the apoptosis of cognate B and T malignat cells.The possibility of a therapeutic use of T and B Superantigens in lymphoma/ leukemia B and T cells is discussed. Their possible use would have the advantage of delete only a discrete number of normal lymphocytes without altering other normal cell types.

Antiagregantes plaquetarios en la prevención de la enfermedad vascular cerebral / Antiplatelates cerebral infartion prevention

Los mecanismos productores de isquemia cerebral son múltiples; sin embargo, el tromboembolismo explica una gran proporción de los casos de isquemia cerebral. El papel de los antiagregantes plaquetarios en la prevención secundaria del infarto cerebral esta bien definido. La presente revisión analiza los mecanismos de acción y la eficacia de las tres únicas drogas antiagregantes plaquetarias con efectividad demostrada en la prevención del infarto cerebral. Se analizan las relaciones riesgo-beneficio en cada uno de los agentes farmacológicos, así como también se discuten aspectos en cuanto a la dosis "ideal" de aspirina para esta indicación