Ethical implications of developing RNA-based therapies for cardiovascular disorders.

The awareness concerning RNA-based therapies was boosted significantly after the successful development of COVID-19 vaccines. However, they can potentially lead to significant advances in other areas of medicine, such as oncology or chronic diseases. In recent years, there has been an exponential increase in the number of RNA-based therapies that were evaluated as potential treatments for cardiovascular disorders. One of the areas that was not explicitly assessed about these therapies is represented by their overall ethical framework. Some studies evaluate ethical issues of RNA-based treatments in general or targeting specific disorders (especially neurodegenerative) or interventions for developing RNA-based vaccines. Much less information is available regarding the ethical issues associated with developing these therapeutic strategies for cardiovascular disorders, which is the main aim of this study. We will focus our analysis on three main topics: risk-benefit analysis (including the management of public awareness about these technologies), and justice (in both research and clinical medicine).

Physician-Patient Relationship in Current Cosmetic Surgery Demands More than Mere Respect for Patient Autonomy-Is It Time for the Anti-Paternalistic Model?

The ethical framework of cosmetic surgery is distinct from the one associated with clinical medicine. This distinctiveness has led to significant difficulties in conceptualizing the physician-patient relationship (PPR), as most models have been developed specifically for the latter. The purpose of this article is to show that the PPR in cosmetic surgery can be better described through a distinct approach that we name the anti-paternalistic model of the PPR, and we will briefly present the differences between it and autonomy-based models. We will analyze the principle of non-interference, the variable degree of autonomy of both the patient and the physician within this relationship, the handling of the relevant information, the principle of beneficence as satisfaction, the difficulties regarding the informed consent, the algorithm allowing for the refusal of the procedure, and children-related issues. Based on this analysis, we will show that an anti-paternalistic model of the PPR is preferable to an autonomy-based one, as it allows for better clarification of the underlying ethical issues involved in cosmetic surgery.

Markers of hyperglycemia in the vitreous humor. A systematic review and meta-analysis.

BACKGROUND: Vitreous humor has been extensively used in forensic practice to assess hyperglycemia after death. The results from different articles, for various hyperglycemia markers are highly variable, and a systematic analysis of the results from studies currently used in forensic practice as landmarks has not yet been performed. Therefore, we aimed to evaluate to usefulness and limits of using the values of vitreous glucose, lactic acid, beta-hydroxybutyrate, and 1,5 Anhydro-d-glucitol to detect postmortem hyperglycemia. MATERIALS AND METHODS: For this purpose, we performed a systematic review and a meta-analysis using the random-effects model to identify the threshold values and average differences for the markers mentioned above in the vitreous humor of diabetic versus nondiabetic subjects. RESULTS: We included eleven studies in the meta-analysis and found the following mean differences between the diabetic and nondiabetic groups: for glucose - 91.4 mg/dl, for lactate - 34.17 mg/dl, for the Traub formula - 111 mg/dl, for fructosamine - 0.71 mmol/L, for beta-hydroxybutyrate - 36.55 mg/dl and 1,5 Anhydro-d-glucitol - -15.2 mg/dl. We also gave practical recommendations, based on the range of values and 95% confidence intervals in normal subjects and controls to identify antemortem hyperglycemia and evaluated, whenever possible, threshold values for fatal diabetes. CONCLUSIONS: Glucose, Traub formula, fructosamine, and beta-hydroxy-butyrate can be used to detect postmortem hyperglycemia with some limitations; 1,5 Anhydro-d-glucitol can only be used to suggest the absence of a hyperglycemic status before death.

Age in the Time of COVID-19: An Ethical Analysis.

Despite using a myriad of methods to combat the spread of COVID-19, the healthcare systems (especially the intensive care units) have been overwhelmed, showing an outpaced capacity of available beds and ventilators. Choosing the right criteria to allocate the scarce ICU seems very challenging, being necessary a rapid, uncomplicated and universally accepted tool for patients' triage regarding access to lifesaving resources; one such criterion, which generates intense debates, is age. Under certain circumstances, it might seem appropriate to choose to treat a young over an old patient. The main advantage of this approach is the potential for long-term survival, implying an equal right to reach an advanced age. Many authors have given moral reasons to support it, mainly based on utilitarian ethics or on distributive justice. However, there are numerous counterarguments to this approach, which we will summarize in this article. We will show that age should never be used as a unique criterion for withholding/not initiating life-saving procedures, even in pandemics or cases in which healthcare resources are extremely scarce. This approach is based on fundamental Codes of Ethics, such as the WMA Code of Ethics or the Oath of Hippocrates and all physicians treating patients should obey them.

Changes in disease burden in Poland between 1990-2017 in comparison with other Central European countries: A systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Systematic collection of mortality/morbidity data over time is crucial for monitoring trends in population health, developing health policies, assessing the impact of health programs. In Poland, a comprehensive analysis describing trends in disease burden for major conditions has never been published. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides data on the burden of over 300 diseases in 195 countries since 1990. We used the GBD database to undertake an assessment of disease burden in Poland, evaluate changes in population health between 1990-2017, and compare Poland with other Central European (CE) countries. METHODS: The results of GBD 2017 for 1990 and 2017 for Poland and CE were used to assess rates and trends in years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs). Data came from cause-of-death registration systems, population health surveys, disease registries, hospitalization databases, and the scientific literature. Analytical approaches have been used to adjust for missing data, errors in cause-of-death certification, and differences in data collection methodology. Main estimation strategies were ensemble modelling for mortality and Bayesian meta-regression for disability. RESULTS: Between 1990-2017, age-standardized YLL rates for all causes declined in Poland by 46.0% (95% UI: 43.7-48.2), YLD rates declined by 4.0% (4.2-4.9), DALY rates by 31.7% (29.2-34.4). For both YLLs and YLDs, greater relative declines were observed for females. There was a large decrease in communicable, maternal, neonatal, and nutritional disease DALYs (48.2%; 46.3-50.4). DALYs due to non-communicable diseases (NCDs) decreased slightly (2.0%; 0.1-4.6). In 2017, Poland performed better than CE as a whole (ranked fourth for YLLs, sixth for YLDs, and fifth for DALYs) and achieved greater reductions in YLLs and DALYs than most CE countries. In 2017 and 1990, the leading cause of YLLs and DALYs in Poland and CE was ischaemic heart disease (IHD), and the leading cause of YLDs was low back pain. In 2017, the top 20 causes of YLLs and YLDs in Poland and CE were the same, although in different order. In Poland, age-standardized DALYs from neonatal causes, other cardiovascular and circulatory diseases, and road injuries declined substantially between 1990-2017, while alcohol use disorders and chronic liver diseases increased. The highest observed-to-expected ratios were seen for alcohol use disorders for YLLs, neonatal sepsis for YLDs, and falls for DALYs (3.21, 2.65, and 2.03, respectively). CONCLUSIONS: There was relatively little geographical variation in premature death and disability in CE in 2017, although some between-country differences existed. Health in Poland has been improving since 1990; in 2017 Poland outperformed CE as a whole for YLLs, YLDs, and DALYs. While the health gap between Poland and Western Europe has diminished, it remains substantial. The shift to NCDs and chronic disability, together with marked between-gender health inequalities, poses a challenge for the Polish health-care system. IHD is still the leading cause of disease burden in Poland, but DALYs from IHD are declining. To further reduce disease burden, an integrated response focused on NCDs and population groups with disproportionally high burden is needed.

Retrocaval ureter: a meta-analysis of prevalence.

INTRODUCTION: Retrocaval ureter is a congenital abnormality of the right ureter, which has been shown, in rare cases to cause clinical symptoms, mainly due to the development of ureterohydronephrosis. PURPOSE: The purpose of this article is to identify the prevalence of the retrocaval ureter, and to emphasize its clinical and surgical importance. DESIGN: A meta-analysis of prevalence, on cases obtained from PubMed, Web of Science, and Scopus databases. RESULTS: A total number of 13 studies contained data that allowed us to estimate the prevalence of the retrocaval ureter, which was identified overall in 9 cases, out of 18,493 subjects. The overall prevalence of retrocaval ureter was 0.13%, with a 95% confidence interval between 0.06 and 0.27%. There was no publication bias, all studies being under the funnel. CONCLUSIONS: The overall prevalence of retrocaval ureter is 0.13%. Even if this is obviously a rare condition, its presence must be suspected by practitioners, especially in the presence of urological symptoms without a clear cause.

Duplication and transposition of inferior vena cava: A meta-analysis of prevalence.

OBJECTIVE: The primary aim of this article was to establish the actual prevalence of transposition and duplication of the inferior vena cava and to increase awareness about them. METHODS: A meta-analysis of prevalence was conducted of cases obtained from PubMed, Web of Science, and Scopus databases. RESULTS: A total of 48 studies contained data that allowed us to estimate the prevalence of these variants (39 for duplication and 32 for transposition). The overall prevalence of duplication was 0.7%, with a 95% confidence interval between 0.5% and 0.9%; for transposition, the prevalence was 0.3%, with a 95% confidence interval between 0.2% and 0.5%. The publication bias was minimal. Duplication prevalence was significantly higher in anatomy studies compared with imaging and surgery studies; for transposition, there were no statistically significant differences by detection technique. CONCLUSIONS: The overall prevalence of duplication of the inferior vena cava is 0.7%; for transposition, it is 0.3%. Even if they are obviously rare conditions, their presence must be suspected by practitioners as they can have important clinical consequences, may require changes in the surgery protocol, or can be associated with other congenital abnormalities.

Patient autonomy and disclosure of material information about hospital-acquired infections.

Hospital-acquired infections are nowadays a major health care problem worldwide. The morbidity and mortality associated with them are highest in intensive care units, but their effects are identifiable in virtually any medical department. Information about hospital-acquired infections, especially about their preventive measures, are rarely presented nowadays in a correct fashion to patients. This article aims to present, in a structured manner, the theoretical and practical aspects related to disclosure of hospital-acquired infections-related information to patients and its importance in preventing their spread. We will analyze both the conceptual framework for disclosing medical information related to nosocomial infections (autonomy, veracity, social justice, the principle of double effect, the precautionary principle, and nonmaleficence) and the practicalities regarding the disclosure of proper information to patients.

Myocardial Bridging: A Meta-Analysis of Prevalence.

The main objective of this article was to analyze prevalence data about myocardial bridging (MB) in published studies. To this purpose, we performed a meta-analysis of studies published in English literature that contained data about the prevalence of MB and its anatomical characteristics. The overall prevalence was 19% (CI: 17-21%); autopsy studies revealed an overall prevalence of 42% (CI: 30-55%), CT studies 22% (CI: 18-25%), and coronary angiography 6% (CI: 5-8%). Most bridges were located on the left anterior descending artery (82% overall, 63% on autopsy studies), had a mean thickness of 2.47 mm and a mean length of 19.3 mm. In conclusion, autopsy studies should be the gold standard in evaluating the actual prevalence of myocardial bridges, while in vivo high-resolution CT scanning should be preferred to coronary angiography studies.

Cardiovascular consequences of myocardial bridging: A meta-analysis and meta-regression.

Myocardial bridging, a congenital abnormality in which a coronary artery tunnels through the myocardial fibres was usually considered a benign condition. Many studies suggested a potential hemodynamic significance of myocardial bridging and some, usually case reports, implied a possible correlation between it and various cardiovascular pathologies like acute myocardial infarction, ventricular rupture, life-threatening arrhythmias, hypertrophic cardiomyopathy, apical ballooning syndrome or sudden death. The main objective of this article is to evaluate whether myocardial bridging may be associated with significant cardiac effects or if it is strictly a benign anatomical variation. To this purpose, we performed a meta-analysis (performed using the inverse variance heterogeneity model) and meta-regression, on scientific articles selected from three main databases (Scopus, Web of Science, Pubmed). The study included 21 articles. MB was associated with major adverse cardiac events - OR = 1.52 (1.01-2.30), and myocardial ischemia OR = 3.00 (1.02-8.82) but not with acute myocardial infarction, cardiovascular death, ischemia identified using imaging techniques, or positive exercise stress testing. Overall, myocardial bridging may have significant cardiovascular consequences (MACE, myocardial ischemia). More studies are needed to reveal/refute a clear association with MI, sudden death or other cardiovascular pathologies.

Illicit Drugs and their Impact on Cardiovascular Pathology.

The use of illicit drugs has dramatically increased during the past years. Consequently, the number of presentations at the emergency departments due to the adverse effects of the illicit drugs has also increased. This review discusses the cardiovascular effects of cocaine, opiates and opioids, cannabinoids, amphetamines, methamphetamines and hallucinogens as we consider that it is essential for a clinician to be aware of them and understand their mechanisms in order to optimize the therapeutic management.

New technologies in biomedicine. Opinions of young Romanian physicians / Nuevas tecnologías en biomedicina. Opiniones de médicos jóvenes de Rumania / Novas tecnologias em biomedicina. Opiniões de jovens médicos romenos

Aim. The purpose of this article is to summarize the way young medical professionals view these modern biomedical procedures and their moral acceptability. Materials and methods. A survey, filled in online, analyzing items in four main areas: genetic techniques, cloning, stem cell research, and assisted reproduction. Results. Genetics related items. Most subjects agreed that the right to the genetic material should be a fundamental human right and that genetic engineering should be used if it could lead to the elimination os severe genetic diseases like cystic fibrosis and thalassemia. The least acceptance rate was obtained for techniques that would either change physical traits (like eye or hair color) or augment them. Assisted reproductive techniques. Most subjects agreed that the prenatal screening should be mandatory, and if the screening detects a severe congenital malformation the physician should recommend therapeutic abortion. Cloning. Most subjects disagreed that cloning of any type, either therapeutic or reproductive, using human, animal, or vegetal genetic material. Stem cell research. Most subjects agreed with the collection and storage of cord blood stem cells and the use of adult stem cells, and most of them disagreed with the creation of embryos specifically for obtaining stem cells. Conclusions. Even if the national legislation in this area is very scarce, the responses have usually identified the highly controversial techniques. If however the national legislation has elements similar to the items from the survey, they tended to take the respective items as morally acceptable without trying to analyze them critically.

Objetivo. El propósito de este artículo es recoger la forma en que jóvenes profesionales médicos ven los procedimientos biomédicos modernos y su aceptabilidad moral. Materiales y métodos: Una encuesta, rellenada online, que analiza elementos en cuatro áreas principales: técnicas genéticas, clonación, investigación con células madre y reproducción asistida. Resultados: Elementos relacionados con la genética: La mayoría de los sujetos acepta que el derecho a material genético debería ser un derecho humano fundamental y que la ingeniería genética debería usarse si pudiese eliminar enfermedades genéticas severas como la fibrosis quística y la talasemia. Se obtuvo una frecuencia de aceptación menor para técnicas que pudieran o cambiar características físicas (como el color de los ojos o del pelo) o aumentarlas. Técnicas de reproducción asistida: La mayoría de los sujetos acepta que el examen de detección prenatal debiera ser mandatorio y si se detecta una deformación congénita severa, el médico debería recomendar aborto terapéutico. Clonación: La mayoría de los sujetos no acepta clonación de ningún tipo, terapéutica o reproductiva, usando material genético humano, animal o vegetal. Investigación con células madre: La mayoría de los sujetos acepta recoger y almacenar células madre del cordón umbilical y el uso de células madre adultas y está en desacuerdo con la creación de embriones específicamente para obtener células madre. Conclusiones: aunque la legislación nacional en esta área es muy escasa, las respuestas por lo general han identificado las técnicas altamente controversiales. Sin embargo, si la legislación nacional tiene elementos similares a los temas de la encuesta, se tiende a tomarlos respectivamente como moralmente aceptables sin tratar de analizarlos críticamente.

Objetivo. A proposta deste artigo é sumarizar o modo de ver dos jovens profissionais médicos sobre procedimentos biomédicos modernos e sua aceitação moral. Materiais e métodos. Uma pesquisa de opinião realizada online, analisou ítens de quatro principais áreas: técnicas genéticas, clonagem, pesquisa com células-tronco, e reprodução assistida. Resultados. Itens relacionados à Genética. A maioria dos sujeitos concordaram que o direito ao material genético deveria ser um direito humano fundamental e que a engenharia genética poderia ser usada se puder levar à eliminação de doenças genéticas severas como a fibrose cística e a talassemia. A menor taxa de aceitação foi obtida para técnicas que pudessem modificar o aspecto físico individual (como olho e cor do cabelo) ou aumentá-los. Técnicas de reprodução assistida. A maioria dos sujeitos concordaram que a seleção pré-natal (screening) deverá ser impositiva, e que se o "screening" detetar uma severa malformação congênita o médico deveria recomendar o aborto terapêutico. Clonagem. A maioria dos sujeitos discordaram da clonagem de qualquer tipo, terapêutica ou reprodutiva, com material genético de uso humano, animal, ou vegetal. Pesquisa com células-tronco. A maioria dos sujeitos concordaram com a obtenção e estocagem de células-tronco de sangue do cordão umbilical e a utilização de células-tronco adultas , e a maioria deles discordaram da criação de embriões especificamente para a obtenção de células-tronco. Conclusões. Mesmo que a legislação nacional na área seja muito escassa, as respostas usualmente identificaram as técnicas como altamente controversas. Quando a legislação nacional oferece elementos semelhantes aos ítens obtidos pela pesquisa de opinião, eles tenderiam a tomar os respectivos ítens como moralmente aceitáveis sem tentar analisá-los criticamente.

Lethal pulmonary thromboembolism associated with decreased thyroid hormone levels.

Thyroid pathology is rarely involved in the pathogenesis of sudden death in young people. We report here the cases of two young patients with decreased levels of thyroid hormones whose death was caused by an increased thrombotic status, with venous thrombosis and pulmonary thromboembolism. In both cases the thyroid pathology was not considered as the underlying cause of death as the association between this condition and venous thrombosis is still debatable. However its presence may be considered a circumstantial factor, which could increase the severity of the disease and subsequently the lethality rate in pulmonary thromboembolism. An increased awareness for hypothyroidism or subclinical hypothyroidism in clinical practice may lead to a decrease in mortality secondary to thromboembolic disease. Also, increased awareness for thyroid pathology during forensic autopsy in sudden deaths may lead to potentially significant results, that could explain some of the sudden death with an unknown cause, and decrease the number of the so called blank autopsies.

Lethal pulmonary thromboembolism associated with decreased thyroid hormone levels

Thyroid pathology is rarely involved in the pathogenesis of sudden death in young people. We report here the cases of two young patients with decreased levels of thyroid hormones whose death was caused by an increased thrombotic status, with venous thrombosis and pulmonary thromboembolism. In both cases the thyroid pathology was not considered as the underlying cause of death as the association between this condition and venous thrombosis is still debatable. However its presence may be considered a circumstantial factor, which could increase the severity of the disease and subsequently the lethality rate in pulmonary thromboembolism. An increased awareness for hypothyroidism or subclinical hypothyroidism in clinical practice may lead to a decrease in mortality secondary to thromboembolic disease. Also, increased awareness for thyroid pathology during forensic autopsy in sudden deaths may lead to potentially significant results, that could explain some of the sudden death with an unknown cause, and decrease the number of the so called blank autopsies.

Violence against physicians in training. A Romanian perspective.

The main purpose of this study was to assess whether there are differences between perceived and actual aggressions directed towards medical trainees from different medical specialties and different stages of medical training, and to characterize various types of aggressions against physicians in training in Romania. A multi-institutional survey was conducted in order to assess the prevalence of perceived and actual violence during medical residents; it included a total number of 384 medical residents from various specialties. Thirty two cases declared perceived physical aggression, most often in psychiatry. Actual physical aggression was 48% higher compared to perceived physical aggression. A similar situation occurred for sexual harassment, with only 9 perceived and 65 actual cases (an increase of 722%). Psychological abuse was the easiest to identify by the physicians in training, as the difference between perceived and actual aggression was minimal (202 and 205 respectively). The degree of perceived violence against physicians in training was much lower than the actual prevalence of the phenomenon, especially for physical and sexual types. This decreased awareness may lead to a failure in taking necessary safety measures and may subsequently increase the severity and consequences of the violent acts directed towards them.

Sudden death due to dissection of the thoracic aorta associated with dissection and rupture of the pulmonary artery: report of two cases.

We present two cases of dissection of the thoracic aorta associated with dissection and rupture of the pulmonary artery. In both cases the initial dissection was hypothesized to occur in the thoracic aorta, with secondary dissection and rupture of the pulmonary artery.

Late abortion. Attitudes amongst young physicians in Romania.

PURPOSE: The main purpose of this article is to analyze the way in which young physicians analyze and address the issue of therapeutic abortion. METHODS: A multi-institutional survey was conducted using an online questionnaire containing 10 items. RESULTS: Most respondents agreed with therapeutic abortion (1) if the fetus is not yet viable and the mother is put at immediate risk by the continuation of the pregnancy, and (2) when the pregnancy is over 14 weeks and the prenatal screening identifies a very severe malformation. The lowest rate of acceptance was obtained by the option to terminate the pregnancy after 14 weeks for a minor malformation (polydactyly). The vast majority agreed that the OG physician should be permitted to refuse an abortion on moral grounds, even if permitted by law. CONCLUSIONS: Our study reveals that the main reasons for conducting therapeutic abortion (TA) in the 2nd or 3rd trimester are: (1) if the mother is put in immediate risk by the continuation of the pregnancy and (2) if the congenital anomaly is extremely severe. Even though the number of respondents considering Down syndrome to be a congenital malformation severe enough to allow TA, the value much lower compared with other low and middle income countries. The main reasons for refusing TA in the 2nd or 3rd trimester are the presence of a minor congenital anomaly or if it is against the moral principles of the physician.

Complex Ebstein's malformation: defining preoperative cardiac anatomy and function.

INTRODUCTION: Ebstein's malformation is a congenital malformation of the tricuspid valve and right ventricle, with a highly variable morphology, and clinical presentation, accounting for less than 1% of all congenital heart diseases, and about 40% of congenital malformations of the tricuspid valve. METHOD: Systematic review of English language literature regarding the morphogenesis and progress of imaging techniques, especially echocardiography and cardiac magnetic resonance imaging, in the preoperative planning of Ebstein's malformation, using the MEDLINE database with the PubMed Entre interface. RESULTS: Technological developments of the recent years, with 3D echocardiographic and cardiac magnetic resonance imaging evolution, have resulted in better understanding of the malformed tricuspid valve and right ventricle in vivo anatomy. Through a better understanding of Ebstein's malformation, there is a continuous trend of surgical techniques favoring tricuspid valve sparing procedures, with a constant decrease in early and late postoperative mortality. CONCLUSIONS: Although imaging methods to investigate Ebstein's malformation have continuously evolved, standardization of assessment protocols by 3D echocardiographic imaging, speckle tracking imaging, and cardiac magnetic resonance imaging is required.