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PURPOSE: Adolescent and young adult patients occupy a clinically transitional space between pediatric and adult care. Youth with chronic conditions and special healthcare needs may have trouble accessing and receiving appropriate care in this transition, which may lead to patient safety issues and medicolegal risks for physicians. The objectives of this article were to explore patient safety issues and identify medicolegal risks for physicians. METHODS: A national repository was retrospectively searched for medicolegal cases (MLCs) involving complaints from youth. The study included MLCs closed at the Canadian Medical Protective Association between 2013 and 2022 involving youth. The study participants were adolescents and young adults aged ≥ 15 and ≤ 21 years with medical complexity. The frequencies and proportions of patient safety events and medicolegal risks for physicians were calculated by exploring factors that contributed to each incident using established frameworks. RESULTS: A total of 182 eligible MLCs were identified. Of 206 involved physicians, 55 were psychiatrists. The most common reasons for patient complaints were deficient assessment, diagnostic error, and communication breakdown with the patient and/or family. More than half of the cases were related to a harmful incident. Peer experts reviewed the cases and identified factors such as a deficient assessment, a failure to perform a test or intervention, failure to refer the patient, and insufficient provider knowledge/skill as contributing to the patient safety event. DISCUSSION: The impact of our findings is to identify gaps in care delivery to youth that can inform practitioners of ways to mitigate the gaps and improve patient care and health outcomes.
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BACKGROUND: With the rapid evolution of artificial intelligence (AI), particularly large language models (LLMs) such as ChatGPT-4 (OpenAI), there is an increasing interest in their potential to assist in scholarly tasks, including conducting literature reviews. However, the efficacy of AI-generated reviews compared with traditional human-led approaches remains underexplored. OBJECTIVE: This study aims to compare the quality of literature reviews conducted by the ChatGPT-4 model with those conducted by human researchers, focusing on the relational dynamics between physicians and patients. METHODS: We included 2 literature reviews in the study on the same topic, namely, exploring factors affecting relational dynamics between physicians and patients in medicolegal contexts. One review used GPT-4, last updated in September 2021, and the other was conducted by human researchers. The human review involved a comprehensive literature search using medical subject headings and keywords in Ovid MEDLINE, followed by a thematic analysis of the literature to synthesize information from selected articles. The AI-generated review used a new prompt engineering approach, using iterative and sequential prompts to generate results. Comparative analysis was based on qualitative measures such as accuracy, response time, consistency, breadth and depth of knowledge, contextual understanding, and transparency. RESULTS: GPT-4 produced an extensive list of relational factors rapidly. The AI model demonstrated an impressive breadth of knowledge but exhibited limitations in in-depth and contextual understanding, occasionally producing irrelevant or incorrect information. In comparison, human researchers provided a more nuanced and contextually relevant review. The comparative analysis assessed the reviews based on criteria including accuracy, response time, consistency, breadth and depth of knowledge, contextual understanding, and transparency. While GPT-4 showed advantages in response time and breadth of knowledge, human-led reviews excelled in accuracy, depth of knowledge, and contextual understanding. CONCLUSIONS: The study suggests that GPT-4, with structured prompt engineering, can be a valuable tool for conducting preliminary literature reviews by providing a broad overview of topics quickly. However, its limitations necessitate careful expert evaluation and refinement, making it an assistant rather than a substitute for human expertise in comprehensive literature reviews. Moreover, this research highlights the potential and limitations of using AI tools like GPT-4 in academic research, particularly in the fields of health services and medical research. It underscores the necessity of combining AI's rapid information retrieval capabilities with human expertise for more accurate and contextually rich scholarly outputs.
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This review identifes the factors influencing the relationship between physicians and patients that can lead to patients' dissatisfaction and medical complaints. Utilizing a systemic approach 92 studies were retrieved which included quantitative, qualitative, and mixed method studies. Through a thematic analysis of the literature, we identified three interrelated main themes that can influence the relationship between physicians and patients, patients' satisfaction, and the decision to file a medico-legal complaint. The main themes include patient and physician characteristics; the interpersonal relationship between physicians and patients; and the health care system and policies, with relevant subthemes. These themes are demonstrated in a descriptive model. The review suggests areas of focus for physicians who may wish to increase their awareness around the potential sources of relational problems with their patients. Identifying these issues may assist in improvements in the therapeutic relationship with patients, can reduce their medico-legal risk, and enhance the quality of their clinical practice. The findings can also be utilized to support andragogical principles for medical learners. The article can serve as a structured framework to identify potential problems and gaps to design and test effective interventions to mitigate these potential relational problems between physician-patient.
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Satisfação do Paciente , Relações Médico-Paciente , Humanos , Feminino , Masculino , Imperícia/legislação & jurisprudência , AdultoRESUMO
Despite the importance of independent medical examinations (IMEs), there is virtually no literature on the risks to the IME assessor nor the learning needs of psychiatrists in this area. To address this deficit, a retrospective chart review of nearly 38,000 cases from the Canadian Medical Protective Association (CMPA) identified 108 files involving complaints or legal actions against psychiatrists performing IMEs. Most complaints identified by the CMPA were to regulatory bodies, including biased opinion, inadequate assessment, inappropriately relying on a requester's information without independent evaluation, nonadherence to regulatory body policies, cursory documentation lacking relevant details, and communication breakdowns. A survey by the Canadian Academy of Psychiatry and the Law (CAPL) and the Canadian Psychiatric Association (CPA) had 306 Canadian psychiatrist respondents. About 37 percent of psychiatrists completing IMEs reported medico-legal consequences, including complaints to regulatory authorities. Only 40 percent of those doing IMEs and 20 percent of all psychiatrists had formal training in doing IMEs. The studies confirm that despite a low but important risk of medico-legal consequences, many psychiatrists performing IMEs do not have formalized training. Using the new CAPL Canadian Guidelines for Forensic Psychiatry Assessment and Report Writing is a step to reduce the risk of such evaluations.
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Avaliação Médica Independente , Psiquiatria , Humanos , Estudos Retrospectivos , Canadá , Psiquiatria Legal , Psiquiatria/educaçãoRESUMO
Objective: There is little known about the medico-legal risk for infectious disease specialists in Canada. The objective of this study was to identify the causes of these medico-legal risks with the goal of improving patient safety and outcomes. Methods: A 10-year retrospective analysis of Canadian Medical Protective Association (CMPA) closed medico-legal cases from 2012 to 2021 was performed. Peer expert criticism was used to identify factors that contributed to the medico-legal cases at the provider, team, or system level, and were contrasted with the patient complaint. Results: During the study period there were 571 infectious disease physician members of the CMPA. There were 96 patient medico-legal cases: 45 College complaints, 40 civil legal matters, and 11 hospital complaints. Ten cases were associated with severe patient harm or death. Patients were most likely to complain about perceived deficient assessments (54%), diagnostic errors (53%), inadequate monitoring or follow-up (20%), and unprofessional manner (20%). In contrast, peer experts were most critical of the areas of diagnostic assessment (20%), deficient assessment (10%), failure to perform test/intervention (8%), and failure to refer (6%). Conclusion: While infectious disease physicians tend to have lower medico-legal risks compared to other health care providers, these risks still do exist. This descriptive study provides insights into the types of cases, presenting conditions, and patient allegations associated with their practice.
Objectif: On sait peu de choses sur les risques médico-légaux auxquels sont exposés les spécialistes des maladies infectieuses au Canada. L'objectif de cette étude est de cibler les causes qui sous-tendent ces risques et, ce faisant, d'améliorer la sécurité et l'issue clinique des patients. Méthodes: Une analyse rétrospective sur 10 ans des dossiers médico-légaux conclus par l'Association canadienne de protection médicale (ACPM) entre 2012 et 2021 a été effectuée. Des experts ont été consultés pour cerner les facteurs à l'origine des dossiers médico-légaux en question, que ce soit à l'échelle des prestataires de soins, des équipes ou du système, et ces facteurs ont été mis en parallèle avec les plaintes des patients. Résultats: Au cours de la période de l'étude, 571 médecins membres de l'ACPM étaient spécialisés dans le traitement des maladies infectieuses. Quatre-vingt-seize dossiers médico-légaux portant sur des patients ont été recensés : 45 plaintes auprès d'un Collège, 40 poursuites au civil et 11 plaintes intrahospitalières. Un préjudice grave ou un décès a été constaté dans dix dossiers. Les motifs de plainte les plus répandus chez les patients étaient les évaluations perçues comme déficientes (54 %), les erreurs de diagnostic (53 %), une surveillance ou un suivi inadéquats (20 %) et un comportement non professionnel (20 %). En revanche, les experts consultés se sont surtout montrés critiques à l'égard des évaluations diagnostiques (20 %), des évaluations déficientes (10 %), du manquement à faire un test ou une intervention (8 %) et du manquement à orienter quelqu'un vers une ou un collègue (6 %). Conclusion: Les risques médico-légaux des médecins spécialisés dans le traitement des maladies infectieuses sont généralement moindres que ceux d'autres professionnels de la santé. Néanmoins, ces risques existent. Cette étude descriptive jette un éclairage sur le type de dossiers associés à la pratique de ces médecins, sur les motifs de consultation et sur les allégations formulées par les patients. Summary: Infectious disease (ID) physicians play a vital role in managing a broad spectrum of illnesses, from common infections to complex conditions, through rapid disease detection, effective treatment, preventive measures, and appropriate use of antimicrobial agents. ID doctors generally have a lower risk of complaints and lawsuits compared to other types of doctors. However, these risks do still exist and are important to consider.Our research team conducted a review of medico-legal cases over a 10-year period (20122021) involving ID physicians, with the goal of identifying why these problems occurred and how physicians might avoid them in the future. We examined why patients complained, what the types of diseases were, and the extent of patient harm. We also looked at which other types of doctors were most often involved in these cases.Most of the cases were either complaints made to a college (47%) or civil legal cases (42%). The rate of cases remained relatively stable over the study period. Twenty percent of complaints were linked to conditions of the bones, muscles, and connective tissue, such as osteomyelitis and septic arthritis. More than half of the patients who complained specifically mentioned concerns with the physician's assessment or a diagnostic error. In contrast, when expert physicians reviewed these cases, they only identified diagnostic errors in 20% of cases, and deficient assessments in 10% of cases.This research is important for two reasons. First, it may help to create a clearer picture of the current medico-legal landscape within the ID specialty. Second, by identifying areas of potential risk, it can guide the development of strategies to reduce these risks, thereby improving patient safety and trust in health care providers.
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For patients with hypertrophic cardiomyopathy (HCM), a thickened intraventricular septum and systolic anterior motion of the mitral valve (SAM) can contribute to significant left ventricular outflow tract obstruction (LVOTO), mitral regurgitation, and debilitating symptoms. Current guidelines recommend septal reduction therapy through alcohol septal ablation or surgical septal myectomy for patients whose symptoms persist despite medical therapy. Although alcohol septal ablation is a less invasive treatment option, it is not suitable for patients with septal perforator branch anatomy that is not compatible with the procedure, those with midcavitary obstruction, and patients in whom the mechanism of LVOTO is primarily related to SAM. Septal ablation also has a notably higher rate of atrioventricular block requiring permanent pacemaker insertion, and the need for reintervention has been reported to be 15% or more. In contrast, septal myectomy offers direct visualisation and can address thickened septum and mitral valve (MV) anomalies. It can be used to treat a wider variety of anatomies, with lower rates of reoperation. Aside from the more invasive nature of the procedure, a major limitation of septal myectomy, however, is access, because relatively few surgeons specialise in the procedure. This is important because there is a significant correlation between procedural volumes and outcomes. Patients should be evaluated by a multidisciplinary heart team to ensure that they are aware of all treatment options. In this review, we explore the 2 methods of septal reduction therapy and highlight the need for further training of septal myectomy surgeons to ensure access to optimal septal reduction therapies for Canadian patients with HCM.
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Purpose: Recent guidelines provide broader support for the use of less invasive imaging modalities for the evaluation of patients with stable chest pain. Coronary CT angiography (CCTA) uses increasingly sophisticated techniques to improve evaluation of coronary lesions. The purpose of this study is to describe one center's experience implementing AI-assisted advanced imaging techniques to diagnose coronary artery disease. Materials & methods: Retrospective study of patients who had AI-assisted CCTA interpretation, including a subgroup who underwent fractional flow reserve CT (FFR-CT) and invasive coronary angiography. Descriptive statistics summarized baseline characteristics and univariate statistics compared findings between groups of patients with and without anatomically and hemodynamically significant lesions based on FFR-CT. For patients who underwent invasive coronary angiography, concordance between CCTA and angiography was evaluated. Results: Of 532 included patients, AI-assisted CCTA identified statistically significant difference in calcification scores, plaque types and total plaque volume between lesions <50% and ≥50% stenosis. CCTA results were mostly concordant with invasive coronary angiography. Importantly, we identified a subset of patients with less than 50% anatomical stenosis that demonstrated physiologically significant stenosis on FFR-CT and invasive coronary angiography. Conclusions: AI-assisted CCTA and other advanced techniques are a tool to support high quality diagnostic assessment of coronary lesions in a clinical environment. Combined CCTA with FFRCT in mild to moderate coronary stenosis identifies patients with hemodynamically significant stenosis even when quantitative stenosis is <50%. Implementation of AI-assisted coronary CT angiography is feasible in a community hospital setting, but these technologies do not replace the need for expert review and clinical correlation.
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BACKGROUND: During the COVID-19 pandemic, family physicians faced challenges including travel restrictions for patients, lockdowns, diagnostic testing delays, and changing public health guidelines. Given that 95% of Canadian physicians are members of the Canadian Medical Protective Association (CMPA), the CMPA's telephone helpline - which offers peer-to-peer support - provides valuable insights into family physicians' experiences during the pandemic. METHODS: We used a content analysis approach to identify and understand family physicians' questions and concerns related to the COVID-19 pandemic expressed during calls to the Canadian Medical Protective Association (CMPA) telephone helpline. Calls were classified with preliminary codes and subsequently organized into themes. We collected aggregated data on calls, including province, call date, and whether the physician self-identified having hospital-based activities as part of their practice. Findings from the analysis were explored alongside family physician calls per month (call volume). RESULTS: Between 01 and 2020 and 31 December 2021, 2,272 family physician calls related to the pandemic were included for content analysis. We identified six major themes across these calls: challenging patient interactions; COVID-related care; the impact of the pandemic on the healthcare system; virtual care; physician obligations and rights; and public health matters. COVID-related call volumes were highest early in the pandemic especially among physicians without major hospital affiliation when family physicians practiced with little guidance on how to balance patient care and scarce resources in the face of a novel pandemic. CONCLUSIONS: This research provides unique insight on the effects the COVID-19 pandemic had on family medicine in Canada. These results provide insights on the needs and information gaps of family physicians in a public health crisis and can inform preparedness efforts by public health agencies, professional organizations, educators, and practitioners.
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COVID-19 , Médicos de Família , Humanos , Pandemias , COVID-19/epidemiologia , Canadá/epidemiologia , Controle de Doenças TransmissíveisRESUMO
BACKGROUND: Never events (NEs) are patient safety incidents that are preventable and so serious they should never happen. To reduce NEs, several frameworks have been introduced over the past two decades; however, NEs and their harms continue to occur. These frameworks have varying events, terminology and preventability, which hinders collaboration. This systematic review aims to identify the most serious and preventable events for targeted improvement efforts by answering the following questions: Which patient safety events are most frequently classified as never events? Which ones are most commonly described as entirely preventable? METHODS: For this narrative synthesis systematic review we searched Medline, Embase, PsycINFO, Cochrane Central and CINAHL for articles published from 1 January 2001 to 27 October 2021. We included papers of any study design or article type (excluding press releases/announcements) that listed NEs or an existing NE framework. RESULTS: Our analyses included 367 reports identifying 125 unique NEs. Those most frequently reported were surgery on the wrong body part, wrong surgical procedure, unintentionally retained foreign objects and surgery on the wrong patient. Researchers classified 19.4% of NEs as 'wholly preventable'. Those most included in this category were surgery on the wrong body part or patient, wrong surgical procedure, improper administration of a potassium-containing solution and wrong-route administration of medication (excluding chemotherapy). CONCLUSIONS: To improve collaboration and facilitate learning from errors, we need a single list that focuses on the most preventable and serious NEs. Our review shows that surgery on the wrong body part or patient, or the wrong surgical procedure best meet these criteria.
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Erros Médicos , Erros de Medicação , Humanos , Erros Médicos/prevenção & controle , Erros de Medicação/prevenção & controle , Segurança do Paciente , Instalações de Saúde , Atenção à SaúdeRESUMO
Although rapid treatment improves outcomes for patients presenting with sepsis, early detection can be difficult, especially in otherwise healthy adults. OBJECTIVES: Using medico-legal data, we aimed to identify areas of focus to assist with early recognition of sepsis. DESIGN SETTING AND PARTICIPANTS: Retrospective descriptive design. We analyzed closed medico-legal cases involving physicians from a national database repository at the Canadian Medical Protective Association. The study included cases closed between 2011 and 2020 that had documented peer expert criticism of a diagnostic issue related to sepsis or relevant infections. MAIN OUTCOMES AND MEASURES: We used univariate statistics to describe patients and physicians and applied published frameworks to classify contributing factors (provider, team, system) and diagnostic pitfalls based on peer expert criticisms. RESULTS: Of 162 involved patients, the median age was 53 years (interquartile range [IQR], 34-66 yr) and mortality was 49%. Of 218 implicated physicians, 169 (78%) were from family medicine, emergency medicine, or surgical specialties. Eighty patients (49%) made multiple visits to outpatient care leading up to sepsis recognition/hospitalization (median = two visits; IQR, 2-4). Almost 40% of patients were admitted to the ICU. Deficient assessments, such as failing to consider sepsis or not reassessing the patient prior to discharge, contributed to the majority of cases (81%). CONCLUSIONS AND RELEVANCE: Sepsis continues to be a challenging diagnosis for clinicians. Multiple visits to outpatient care may be an early warning sign requiring vigilance in the patient assessment.
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BACKGROUND: With the onset of the COVID-19 pandemic, physicians have had concerns related to the impact of the pandemic on their practice of medicine. Our objective was to evaluate physician questions and concerns related to the COVID-19 pandemic by studying physician calls made to a medico-legal telephone helpline, and explore associations between the pattern of these calls and the temporal progression of the pandemic. METHODS: We conducted a descriptive study of calls related to the COVID-19 pandemic to the Canadian Medical Protective Association (CMPA) from Jan. 1, 2020, to June 30, 2021. Using content analysis, we classified calls into themes. Using a Poisson regression model, we tested for associations between the weekly numbers of physician calls related to COVID-19 and national rates of COVID-19 cases and deaths. RESULTS: We analyzed 3810 COVID-19-related calls. The highest call volume was observed during the pandemic's early months and was widely distributed across the country. Call volume correlated with rates of SARS-CoV-2 infection during the pandemic's first wave (p = 0.002) but not across the entire study period. Call themes included virtual care (826 calls), the pandemic's effect on health care (1160 calls) and challenging patient interactions (1091 calls). INTERPRETATION: We observed high volumes of physician calls to a medico-legal helpline during the first 18 months of the COVID-19 pandemic in Canada. Our data provide insight into the questions and concerns of Canadian physicians, and serve as a contemporaneous account of the adaptability and resilience of physicians during this challenging time.
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COVID-19 , Médicos , COVID-19/epidemiologia , Canadá/epidemiologia , Humanos , Pandemias , SARS-CoV-2Assuntos
Cateterismo Cardíaco , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Reserva Fracionada de Fluxo Miocárdico , Bélgica , Canadá , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Humanos , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: Visual estimation is the most commonly used method to evaluate the degree of coronary artery stenosis prior to coronary artery bypass grafting. In interventional cardiology, the use of fractional flow reserve (FFR) to guide revascularization decisions has become routine. We investigated whether the preoperative FFR measurement of coronary lesions is associated with anastomosis function 6 months after surgical revascularization using a multiarterial grafting strategy. METHODS AND RESULTS: In this prospective double-blind study, 67 patients were enrolled from two institutions in Europe and Canada. From these patients, 199 coronary lesions were assessed visually and with FFR at the time of the preoperative angiogram. All patients received coronary revascularization using multiple arterial grafts. A post-operative 6-month angiogram was performed to assess anastomosis functionality using a described angiographic method. The primary outcome was the association between preoperative FFR values and anastomosis function 6 months after surgery. Preoperative FFR was significantly associated with 6-months anastomotic function for all conduits and for all targets (P < 0.001). An FFR value of ≤0.78 was associated with an anastomotic occlusion rate of 3%. CONCLUSION: We found a significant association between the preoperative FFR measurement of the target vessel and the anastomotic functionality at 6 months, with a cut-off of 0.78. Integration of FFR measurement into the preoperative diagnostic workup before multiarterial coronary surgical revascularization leads to improved anastomotic graft function. CLINICAL TRIALS. GOV IDENTIFIER: NCT02527044.
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Ponte de Artéria Coronária , Reserva Fracionada de Fluxo Miocárdico , Idoso , Angiografia , Angiografia Coronária , Ponte de Artéria Coronária/métodos , Circulação Coronária , Método Duplo-Cego , Humanos , Período Pré-Operatório , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Serotonergic appetite suppressants and ergot-derived dopamine agonists have been associated with drug-induced valvular heart disease. The purpose of this meta-analysis is to synthesise the current evidence of a link between several medications affecting sertonergic pathways and valvular heart disease. METHODS: PubMed was searched to identify studies evaluating an association between medications with serotonergic activity and cardiac valvular pathology. Case reports, uncontrolled studies and in vitro studies were excluded. Relevant studies were assessed for quality and potential bias; those of adequate quality were included in a quantitative synthesis. Sensitivity analyses were conducted, and potential publication bias was examined. RESULTS: There was a consistent, significant relationship between certain medications and heart valve disease, including serotonergic medications (OR 3.30, 95% CI 1.99 to 5.49) and dopaminergic medications (OR 2.56, 95% CI 1.68 to 3.91). Subanalyses, including analyses that limited exposure to a single medication or effects to a single heart valve were also consistently significant. Most studies were retrospective or observational in nature, with a higher risk of selection and presentation biases. There was significant heterogeneity and variability between studies, particularly when it came to dose and duration of exposure. CONCLUSIONS: There was a consistent, significant association between many medications that affect serotonergic pathways and valvular heart disease. Although many of these medications have been withdrawn from the market, some small studies suggest that recreational drug 3,4-methylenedioxyâmethamphetamine and widely prescribed selective serotonin reuptake inhibitors may affect similar pathways.
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Dopaminérgicos/efeitos adversos , Doenças das Valvas Cardíacas/induzido quimicamente , Doenças das Valvas Cardíacas/epidemiologia , Serotoninérgicos/efeitos adversos , HumanosRESUMO
Bilateral internal thoracic artery (BITA) grafting is considered a superior choice for coronary artery bypass grafting (CABG). While the 10-year outcomes of BITA grafting from the recent Arterial Revascularization Trial (ART) are still pending, numerous observational studies have demonstrated the advantages of BITA grafting. These include better long-term graft patency and freedom from arteriosclerosis, in addition to higher survival rate compared to CABG using only the left internal thoracic artery (ITA). The different BITA configurations are in situ and composite-the choice of optimal grafting configuration is challenging. Patient factors such as coronary anatomy, presence of a diseased ascending aorta and the potential need for a future redo sternotomy will influence the choice of the grafting strategy. In situ BITA grafting is associated with excellent clinical outcomes and has been extensively described in the literature. However, uncertainties remain regarding the ideal in situ configuration and design. Composite BITA grafting is the other option that maximizes right ITA (RITA) utilization. In this configuration, the RITA is able to reach the distal circumflex and right coronary artery branches. This approach decreases the need for a third graft conduit.
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Background Aortic valve sclerosis ( AVS c), the early asymptomatic presentation of calcific aortic valve (AV) disease, affects 25% to 30% of patients aged >65 years. In vitro and ex vivo experiments with antioxidant strategies and antagonists of osteogenic differentiation revealed that AVS c is reversible. In this study, we characterized the underlying changes in the extracellular matrix architecture and valve interstitial cell activation in AVSc and tested in vitro and in vivo the activity of a clinically approved SOD (superoxide dismutase) mimic and redox-active drug MnTnBu OE -2-PyP5+ ( BMX -001). Methods and Results After receiving informed consent, samples from patients with AVS c, AV stenosis, and controls were collected. Uniaxial mechanical stimulation and in vitro studies on human valve interstitial cells were performed. An angiotensin II chronic infusion model was used to impose AV thickening and remodeling. We characterized extracellular matrix structures by small-angle light scattering, scanning electron microscopy, histology, and mass spectrometry. Diseased human valves showed altered collagen fiber alignment and ultrastructural changes in AVS c, accumulation of oxidized cross-linking products in AV stenosis, and reversible expression of extracellular matrix regulators ex vivo. We demonstrated that MnTnBu OE -2-PyP5+ inhibits human valve interstitial cell activation and extracellular matrix remodeling in a murine model (C57 BL /6J) of AVS c by electron microscopy and histology. Conclusions AVS c is associated with architectural remodeling despite marginal effects on the mechanical properties in both human and mice. MnTnBu OE -2-PyP5+ controls AV thickening in a murine model of AVS c. Because this compound has been approved recently for clinical use, this work could shift the focus for the treatment of calcific AV disease, moving from AV stenosis to an earlier presentation ( AVS c) that could be more responsive to medical therapies.
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Valva Aórtica/patologia , Fármacos Cardiovasculares/farmacologia , Metaloporfirinas/farmacologia , Idoso , Animais , Valva Aórtica/efeitos dos fármacos , Estenose da Valva Aórtica/prevenção & controle , Calcinose/prevenção & controle , Estudos de Casos e Controles , Colágeno/efeitos dos fármacos , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Esclerose/prevenção & controle , Superóxido Dismutase/antagonistas & inibidores , Remodelação Vascular/efeitos dos fármacosRESUMO
Myocardial revascularization can be achieved through 2 different methods: coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). Clinical trials comparing PCI and CABG generally use the composite end points of death, stroke, myocardial infarction and target vessel revascularization to determine superiority. Other effects of these interventions, including the preservation of normal coronary physiology, the response of the coronary tree to stressors and the response of the vessel wall to the revascularization intervention, are not routinely considered, but these may have significant implications for patients in the medium and long term. For PCI, relatively small differences in clinical outcomes have been reported between bare metal and drug-eluting stents, and the latter seems to have inconsistent and somewhat unpredictable effects on the vascular biology of the coronary arteries. In coronary bypass, the use of arterial conduits is associated with superior clinical outcomes, better long-term patency and the preservation of essentially normal coronary function after intervention. This review assembles the clinical, physiological, angiographic and pathological literature currently available and attempts to provide a more complete picture of the effects of CABG and PCI on coronary arteries.
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Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/fisiopatologia , Intervenção Coronária Percutânea/métodos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , StentsRESUMO
Heart valve diseases (HVDs) arise from a number of different processes that affect both the structure and function of the valve apparatus. Despite diverse aetiologies, treatments for HVDs are limited to percutaneous or surgical interventions. The search for medical therapies to prevent or slow the progression of HVDs has been hampered by our poor understanding of the progression from subclinical to symptomatic phases, and our limited knowledge of the molecular signals that control the susceptibility of valve interstitial cells to pathological remodeling. Clinical evidence has suggested a link between certain neurotransmitters and valvular diseases of the heart. The fenfluramine-phentermine appetite suppressants popular in the 1980s were linked to mitral valve dysfunction, and ergot-derived dopamine agonists for Parkinson's disease have been associated with an increased risk of mitral and aortic valve regurgitation. The effect does not appear to be limited to medications, as valvular pathologies have also been observed in patients with carcinoid tumours of serotonin-producing enterochromaffin cells. The role of neurotransmitter molecules in valve pathology has not been adequately characterized and may represent a target for future medical therapies. Here we present current evidence from both clinical and basic science suggesting a link between neurotransmitters and HVDs, opening the door to future research in this area.
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Catecolaminas/metabolismo , Progressão da Doença , Doenças das Valvas Cardíacas/metabolismo , Neurotransmissores/metabolismo , Serotonina/metabolismo , Animais , Fenfluramina/metabolismo , HumanosRESUMO
PURPOSE OF REVIEW: The publication of the NOBLE and EXCEL trials, with seemingly conflicting results, brought into question whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is better for low-risk patients with left main coronary artery stenosis (LMCAS). This review appraises the methods and results of NOBLE and EXCEL, contextualizes them within the literature, and determines how they may affect clinical practice. RECENT FINDINGS: We appraised the trials and describe differences in methodology and results. NOBLE recruited primarily isolated LMCAS, and found that CABG was superior to PCI. EXCEL's population included patients LMCAS in the context of multivessel CAD, and found PCI and CABG were comparable. Both trials enrolled young patients with few comorbidities, and there was more protocol-mandated consistency in the procedural techniques and medical therapy of patients receiving PCI. SUMMARY: The generalizability of these trials is limited by the use of young, healthy patients at highly skilled centres that rarely reflect typical clinical practice. If these studies are to maintain relevance, trialists must address the lack of protocolization of surgical interventions and inconsistent medical therapies. Unfortunately, the limitations of NOBLE and EXCEL mean that we are no closer to answering the question of what is the optimal treatment for patients with LMCAS.