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Aneurysmal lesions are commonly seen in Ehlers-Danlos Syndrome (EDS). To better identify the regional and vessel-specific spectrum of aneurysms in different subtypes of EDS, we performed a systematic review. We searched Medline for relevant studies from 1963 to April 2022. Studies providing a report of any EDS subtype by genetic diagnosis, histologic analysis, or clinical criteria were included. A total of 448 patients from 220 studies were included. 720 vessel-specific aneurysms were reported: 386 in the abdominopelvic area, 165 in the intracranial region, 98 in the thorax, 2 in the extremities, and 6 in the venous system. In 27 out of the 65 patients with ruptured aneurysms, the ruptured aneurysm was the initial presentation. Multiple aneurysms were present in 163 out of 249 patients who had been systematically evaluated for other locations of aneurysms. The head and neck and abdominopelvic regions are two potential foci for aneurysm formation in patients with EDS. The aneurysm development in EDS is not confined to arteries; the venous system and cardiac septa may also be affected. Many patients develop multiple aneurysms, either at the time of the initial presentation or throughout their lifetime and aneurysm formation or rupture may be the first presentation of EDS.
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Aneurisma Roto , Síndrome de Ehlers-Danlos , Humanos , Aneurisma Roto/genética , Artérias/patologia , Síndrome de Ehlers-Danlos/complicações , Síndrome de Ehlers-Danlos/genética , Síndrome de Ehlers-Danlos/diagnósticoRESUMO
BACKGROUND: With an increase in the incidence and prevalence of non-rheumatic valvular heart diseases (NRVHDs), having a proper understanding of the disease current status in terms of quality of care and healthcare access can considerably affect further planning for the healthcare system. OBJECTIVE: In this study, we aimed to evaluate and compare the quality and equity of care concerning NRVHDs in terms of gender and sociodemographic index (SDI) using a newly proposed index. METHODS: We obtained the primary measures (e.g. incidence) from the Global Burden of Disease (GBD) data about NRVHD from 1990 to 2017 to calculate the subsequent secondary indices (e.g. mortality-to-incidence ratio) with close association to quality of care. Then, using principal component analysis (PCA), quality of care index (QCI) was calculated as a novel index from the secondary indices, rescaled to 0-100. QCI was calculated for all age groups and both genders, globally, regionally and nationally between 1990 and 2017. RESULTS: Globally, the QCI for NRVHDs in 2017 was 87.3, and it appears that gender inequity was unremarkable (gender disparity ratio = 1.00, female QCI: 90.2, male QCI: 89.7) in 2017 similar to the past three decades. Among WHO world regions, the Western Pacific Region and Eastern Mediterranean Region showed the highest (90.1) and lowest (74.0) QCI scores. Regarding SDI, the high-middle-SDI quintile with a QCI of 89.4 and the low-SDI quintile with a QCI of 77.8 were the two extremes of healthcare quality in 2017. CONCLUSION: Although global status regarding the NRVHD's quality of care is acceptable, higher attention is required for lower SDI countries.
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Carga Global da Doença , Doenças das Valvas Cardíacas , Feminino , Saúde Global , Acessibilidade aos Serviços de Saúde , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/terapia , Humanos , Incidência , Masculino , Qualidade da Assistência à Saúde , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Neuroblastoma is a complicated pediatric tumor, originating from the neural crest, which is the most prevalent in adrenal glands, but may rarely be seen in some other tissues as well. Studies are focused on developing new strategies through novel chemo- and immuno-therapeutic drug targets. Different types of oncogenes such as MYCN, tumor suppressor genes such as p53, and some structural genes such as vascular endothelial growth factor are considered as targets for neuroblastoma therapy. The individual expression patterns in NB cells make them appropriate for this purpose. The combined effect of nano-drug delivery systems and specific drug targets will result in lower systemic side effects, prolonged therapeutic effects, and improvements in the pharmacokinetic properties of the drugs. Some of these novel drug delivery systems with a focus on liposomes as carriers are also discussed. In this review, genes and protein products that are beneficial as drug targets in the treatment of neuroblastoma have been discussed.
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Nanopartículas/uso terapêutico , Nanotecnologia , Neuroblastoma/terapia , Animais , Ensaios Clínicos como Assunto , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , HumanosRESUMO
BACKGROUND: Given the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)-derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults. METHODS AND FINDINGS: This study was a population-based multiethnic retrospective cohort of 1,744 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with normoglycemia (baseline fasting plasma glucose [FPG] less than 100 mg/dL) from 6 United States of America communities. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years. The intermuscular adipose tissue (IMAT) and SAT areas were measured in baseline chest CT exams and were corrected by height squared (SAT and IMAT indices) using a predefined measurement protocol. T2D incidence, as the main outcome, was based on follow-up FPG, review of hospital records, or self-reported physician diagnoses. Participants' mean age was 69 ± 9 years at baseline, and 977 (56.0%) were women. Over a median of 7 years, 103 (5.9%) participants were diagnosed with T2D, and 147 (8.4%) participants died. The IMAT index (hazard ratio [HR]: 1.27 [95% confidence interval [CI]: 1.15-1.41] per 1-standard deviation [SD] increment) and the SAT index (HR: 1.43 [95% CI: 1.16-1.77] per 1-SD increment) at baseline were associated with T2D incidence over the follow-up. The associations of the IMAT and SAT indices with T2D incidence were attenuated after adjustment for body mass index (BMI) and waist circumference, with HRs of 1.23 (95% CI: 1.09-1.38) and 1.29 (95% CI: 0.96-1.74) per 1-SD increment, respectively. The limitations of this study include unmeasured residual confounders and one-time measurement of adipose tissue biomarkers. CONCLUSIONS: In this study, we observed an association between IMAT at baseline and T2D incidence over the follow-up. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D. TRIAL REGISTRATION: ClinicalTrials.gov NCT00005487.
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Tecido Adiposo/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Gordura Subcutânea/diagnóstico por imagem , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Background Obesity and sarcopenia are associated with mortality in chronic obstructive pulmonary disease (COPD). Routine chest CT examinations may allow assessment of obesity and sarcopenia by soft-tissue markers for predicting risks of mortality. Purpose To investigate associations between soft-tissue markers subcutaneous adipose tissue (SAT), intermuscular adipose tissue (IMAT), and pectoralis muscle (PM) index from chest CT with mortality in participants with COPD. Materials and Methods In this secondary analysis of a prospectively enrolled cohort from the Multi-Ethnic Study of Atherosclerosis, participants with available chest CT in 2010-2012 were included. CT examinations were analyzed to determine SAT, IMAT (within PM), and PM areas. The spirometry evaluations were used to establish COPD diagnosis. Mortality data were extracted from the National Death Index (April 2010 to December 2017). The correlations of the soft-tissue markers with fat mass index were studied. The associations of these markers and risks of mortality in participants with COPD were assessed by using Cox proportional-hazard models adjusted for confounders. Results Among 2994 participants who were included (mean age, 69 years ± 9 [standard deviation]; 1551 women), 265 had COPD (9%; mean age, 72 years ± 9; 162 men) and 49 participants with COPD (18%) died during follow-up. The SAT, IMAT, and PM areas had moderate-to-excellent reliabilities (intraclass correlation coefficient, 0.88-0.99). In the 2994 participants, the SAT (ρ = 0.80; 95% CI: 0.78, 0.81; P < .001) and IMAT indexes (ρ = 0.37; 95% CI: 0.34, 0.41; P < .001) were correlated with fat mass index. Those with COPD and higher SAT index had lower risks of mortality (hazard ratio, 0.2; 95% CI: 0.1, 0.4; P < .001, per doubling), whereas a higher IMAT index was associated with a higher risk of mortality (hazard ratio, 1.4; 95% CI: 1.0, 1.9; P = .04, per doubling). Conclusion Soft-tissue markers were reliably obtained by using chest CT performed for lung assessment. In participants with chronic obstructive pulmonary disease, a high intermuscular adipose tissue index was associated with a higher risk of mortality than was a high subcutaneous adipose tissue index. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sverzellati and Cademartiri in this issue.
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Tecido Adiposo/diagnóstico por imagem , Obesidade/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/mortalidade , Sarcopenia/complicações , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Obesidade/diagnóstico por imagem , Estudos Prospectivos , Sarcopenia/diagnóstico por imagem , EspirometriaRESUMO
Hypertension has been listed in several case series and retrospective cohorts as a potential risk factor for the incidence and severity of the new coronavirus (SARS-CoV-2)-associated disease (COVID-19). The debate is noteworthy because almost one billion people around the globe are estimated to have hypertensive diseases, according to the Global Burden of Disease study. Considering the SARS-CoV-2's high infectivity rates, a possible interaction between COVID-19 and hypertension is worrisome. Additionally, antihypertensive drugs, especially the renin-angiotensin-aldosterone system (RAAS) inhibitors, could also influence the natural course of COVID-19 infection. Not only can these associations hold from an epidemiologic standpoint, a mechanistic scenario possibly exists. Hypertension and antihypertensive drugs can increase the expression of transmembrane angiotensin-converting enzyme (ACE)-2 receptors, the entry target of the viruses, thus facilitating infectivity. On the other hand, an increase in ACE-2 could be protective considering the anti-inflammatory, antithrombotic effects of the ACE-2-angiotensin 1-7/Mas pathway. So far, little is known about the whole picture. Observational studies appear to indicate at least a twofold increased risk of mortality for hypertensive patients with COVID-19; however, the previous and continued use of RAAS inhibitors may be protective in this subgroup of patients. The scarcity of randomized clinical trials precludes evidence-based decision-making. At least one randomized study in a non-specified sub-analysis demonstrated no relationship between an angiotensin-converting enzyme inhibitor and incidence or severity of the disease. It is reflected mainly by observational studies and, therefore, by international cardiology societies' guidelines, which state that antihypertensive drugs, particularly RAAS inhibitors, should not be discontinued unless necessary on a case-by-case basis.
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COVID-19 , Hipertensão , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Sistema Renina-Angiotensina , Estudos Retrospectivos , SARS-CoV-2Assuntos
Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico , Fenótipo , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/etiologia , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Doença Granulomatosa Crônica/etiologia , Humanos , Imuno-Histoquímica , Masculino , Mutação , NADPH Oxidases/genética , Radiografia Torácica , Avaliação de Sintomas , Tomografia Computadorizada por Raios XAssuntos
Mycobacterium tuberculosis/genética , Doenças da Imunodeficiência Primária/genética , Receptores de Interferon/genética , Medula Óssea , Pré-Escolar , Evolução Fatal , Predisposição Genética para Doença , Humanos , Masculino , Mutação , Receptores de Interferon/deficiência , Receptor de Interferon gamaAssuntos
Artrite Juvenil/genética , Artrite Juvenil/patologia , Mutação , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/deficiência , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Pré-Escolar , Família , Feminino , Humanos , Lactente , Masculino , Fenótipo , PrognósticoRESUMO
BACKGROUND: Sex hormone (SH) imbalances have been linked to a higher risk of heart failure in both sexes. However, mechanisms that underlie this relationship remain unclear. We examined the association of baseline SH with interstitial and replacement myocardial fibrosis in the MESA (Multi-Ethnic Study of Atherosclerosis) using cardiac magnetic resonance (CMR) T1 mapping and late gadolinium enhancement (LGE). OBJECTIVES: The purpose of this study was to assess the link between baseline sex hormone levels and myocardial fibrosis in the MESA cohort using CMR. METHODS: A total of 2,324 participants (men and postmenopausal women [PMW]) were included in the MESA with SH measured at baseline and had underwent CMR 10 years later. All analyses were stratified by sex and age. Regression models were constructed to assess the associations of baseline SH with extracellular volume (ECV)% and native T1 time and with LGE. Higher native T1 time and ECV% are interpreted as evidence of increasing interstitial myocardial fibrosis (IMF). Given the limited number of myocardial scars present in PMW, analysis of LGE was limited to men. RESULTS: Among older men (age ≥65 years), a 1-SD increment higher free testosterone was significantly associated with 2.45% lower ECV% and 21.5% lower native T1 time, while a 1-SD increment higher bioavailable testosterone was associated with 12.5% lower native T1 time. A 1-SD increment greater sex hormone-binding globulin level was associated with 1% higher ECV%. Among PMW of 55 to 64 years, a 1-SD increment higher total testosterone was associated with 9.5% lower native T1 time. Higher levels of estradiol in older men were independently associated with higher odds of having a myocardial scar (OR: 4.10; 95% CI: 1.35-12.40; P = 0.01). CONCLUSIONS: Among older men, SH imbalances at initial evaluation were independently associated with CMR defined IMF and replacement fibrosis, respectively; while increasing total testosterone in middle-aged PMW was associated with lesser marker of IMF. (JACC Adv 2023;2:100320) Published by Elsevier on behalf of the American College of Cardiology Foundation.
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BACKGROUND: Common genetic variants are associated with risk for hypertrophic cardiomyopathy and dilated cardiomyopathy and with left ventricular (LV) traits. Whether these variants are associated with myocardial fibrosis, an important pathophysiological mediator of cardiomyopathy, is unknown. METHODS: Multi-Ethnic Study of Atherosclerosis participants with T1-mapping cardiac magnetic resonance imaging in-whom extracellular volume was assessed, and genotyping information was available were included (N=1255). Log extracellular volume (%) was regressed on 50 candidate single nucleotide polymorphisms (previously identified to be associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and LV traits) adjusting for age, sex, diabetes, blood pressure, and principal components of ancestry. Ancestry-specific results were pooled by fixed-effect meta-analyses. Gene knockdown experiments were performed in human cardiac fibroblasts. RESULTS: The SMARCB1 rs2186370 intronic variant (minor allele frequency: 0.18 in White and 0.50 in Black participants), previously identified as a risk variant for dilated cardiomyopathy and hypertrophic cardiomyopathy, was significantly associated with increased extracellular volume (P=0.0002) after adjusting for confounding clinical variables. The SMARCB1 rs2070458 locus previously associated with increased LV wall thickness and mass was similarly significantly associated with increased extracellular volume (P=0.0002). The direction of effect was similar in all 4 ancestry groups, but the effect was strongest in Black participants. The variants are strong expression quantitative loci in human LV tissue and associated with genotype-dependent decreased expression of SMARCB1 (P=7.3×10-22). SMARCB1 knockdown in human cardiac fibroblasts resulted in increased TGF (transforming growth factor)-ß1-mediated α-smooth muscle actin and collagen expression. CONCLUSIONS: Common genetic variation in SMARCB1 previously associated with risk for cardiomyopathies and increased LV wall thickness is associated with increased cardiac magnetic resonance imaging-based myocardial fibrosis and increased TGF-ß1 mediated myocardial fibrosis in vitro. Whether these findings suggest a pathophysiologic link between myocardial fibrosis and cardiomyopathy risk remains to be proven.
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Cardiomiopatias , Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Humanos , Cardiomiopatia Dilatada/patologia , Imagem Cinética por Ressonância Magnética , Insuficiência Cardíaca/patologia , Cardiomiopatias/genética , Cardiomiopatias/patologia , Miocárdio/patologia , Cardiomiopatia Hipertrófica/genética , Fibrose , Meios de Contraste , Função Ventricular EsquerdaRESUMO
Microvascular angina (MVA), historically called cardiac syndrome X, refers to angina with nonobstructive coronary artery disease. This female-predominant cardiovascular disorder adds considerable health-related costs due to repeated diagnostic angiography and frequent hospital admissions. Despite the high prevalence of this diagnosis in patients undergoing coronary angiography, it is still a therapeutic challenge for cardiologists. Unlike obstructive coronary artery disease, with multiple evidence-based therapies and management guidelines, little is known regarding the management of MVA. During the last decade, many therapeutic interventions have been suggested for the treatment of MVA. However, there is a lack of summarization tab and update of current knowledge about pharmacologic management of MVA, mostly due to unclear pathophysiology. In this article, we have reviewed the underlying mechanisms of MVA and the outcomes of various medications in patients with this disease. Contrary to vasospastic angina in which normal angiogram is observed as well, nitrates are not effective in the treatment of MVA. Beta-blockers and calcium channel blockers have the strongest evidence of improving the symptoms. Moreover, the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, estrogen, and novel antianginal drugs has had promising outcomes. Investigations are still ongoing for vitamin D, omega-3, incretins, and n-acetyl cysteine, which have resulted in beneficial initial outcomes. We believe that the employment of the available results and results of the future large-scale trials into cardiac care guidelines would help reduce the global cost of cardiac care tremendously.
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Doença da Artéria Coronariana , Angina Microvascular , Humanos , Feminino , Angina Microvascular/diagnóstico , Angina Microvascular/tratamento farmacológico , Angiografia Coronária , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêuticoRESUMO
AIMS: By 2030, we seek to reduce premature deaths from non-communicable diseases, including ischaemic heart disease (IHD), by one-third to reach the sustainable development goal (SDG) target 3.4. We aimed to investigate the quality of care of IHD across countries, genders, age groups, and time using the Global Burden of Diseases Study (GBD) 2017 estimates. METHODS AND RESULTS: We did a principal component analysis on IHD mortality to incidence ratio, disability-adjusted life-years (DALYs) to prevalence ratio, and years of life lost to years lived with disability ratio using the results of the GBD 2017. The first principal component was scaled from 0 to 100 and designated as the quality of care index (QCI). We evaluated gender inequity by the gender disparity ratio (GDR), defined as female to male QCI. From 1990 to 2017, the QCI and GDR increased from 71.2 to 76.4 and from 1.04 to 1.08, respectively, worldwide. In the study period, countries of Western Europe, Scandinavia, and Australasia had the highest QCIs and a GDR of 1 to 1.2; however, African and South Asian countries had the lowest QCIs and a GDR of 0.8 to 1. Moreover, the young population experienced more significant improvements in the QCI compared to the elderly in 2017. CONCLUSION: From 1990 to 2017, the QCI of IHD has improved; nonetheless, there are remarkable disparities between countries, genders, and age groups that should be addressed. These findings may guide policymakers in monitoring and modifying our path to achieve SDGs.
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Isquemia Miocárdica , Doenças não Transmissíveis , Idoso , Feminino , Carga Global da Doença , Saúde Global , Humanos , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/terapia , Qualidade da Assistência à Saúde , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Background: There are multiple predictive factors for cardiovascular (CV) mortality measured at, or after heart failure (HF) diagnosis. However, the predictive role of long-term exposure to these predictors prior to HF diagnosis is unknown. Objectives: We aim to identify predictive factors of CV mortality in participants with HF, using cumulative exposure to risk factors before HF development. Methods: Participants of Multi-Ethnic Study of Atherosclerosis (MESA) with incident HF were included. We used stepwise Akaike Information Criterion to select CV mortality predictors among clinical, biochemical, and imaging markers collected prior to HF. Using the AUC of B-spline-corrected curves, we estimated cumulative exposure to predictive factors from baseline to the last exam before HF. The prognostic performance for CV mortality after HF was evaluated using competing risk regression with non-CV mortality as the competing risk. Results: Overall, 375 participants had new HF events (42.9% female, mean age: 74). Over an average follow-up of 4.7 years, there was no difference in the hazard of CV death for HF with reduced versus preserved ejection fraction (HR = 1.27, p = 0.23). The selected predictors of CV mortality in models with the least prediction error were age, cardiac arrest, myocardial infarction, and diabetes, QRS duration, HDL, cumulative exposure to total cholesterol and glucose, NT-proBNP, left ventricular mass, and statin use. The AUC of the models were 0.72 when including the latest exposure to predictive factors and 0.79 when including cumulative prior exposure to predictive factors (p = 0.20). Conclusion: In HF patients, besides age and diagnosed diabetes or CVD, prior lipid profile, NT-proBNP, LV mass, and QRS duration available at the diagnosis time strongly predict CV mortality. Implementing cumulative exposure to cholesterol and glucose, instead of latest measures, improves predictive accuracy for HF mortality, though not reaching statistical significance.
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Background: Sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in women, but the association of menopause status with left atrioventricular coupling is not established. Aim: To assess the prognostic value of a left atrioventricular coupling index (LACI) in peri-menopausal women without a history of cardiovascular disease (CVD). Materials and methods: In all women participating in MESA study with baseline cardiovascular MRI, the LACI was measured as the ratio of the LA end-diastolic volume to the LV end-diastolic volume. Cox models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), coronary heart disease (CHD) death, and hard CVD. Results: Among the 2,087 women participants (61 ± 10 years), 485 cardiovascular events occurred (mean follow-up: 13.2 ± 3.3 years). A higher LACI was independently associated with AF (HR 1.70; 95%CI [1.51-1.90]), HF (HR 1.62; [1.33-1.97]), CHD death (HR 1.36; [1.10-1.68]), and hard CVD (HR 1.30; [1.13-1.51], all p < 0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to traditional models to predict: incident AF (C-statistic: 0.82 vs. 0.79; NRI = 0.325; IDI = 0.036), HF (C-statistic: 0.84 vs. 0.81; NRI = 0.571; IDI = 0.023), CHD death (C-statistic: 0.87 vs. 0.85; NRI = 0.506; IDI = 0.012), hard CVD (C-statistic: 0.78 vs. 0.76; NRI = 0.229; IDI = 0.012). The prognostic value of the LACI had a better discrimination and reclassification than individual LA or LV parameters. Conclusion: In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, CHD death, and hard CVD. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT00005487].
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Background: Rare pathogenic variants in cardiomyopathy (CM) genes can predispose to cardiac remodeling or fibrosis. We studied the carrier status for such variants in adults without clinical cardiovascular disease (CVD) in whom cardiac MRI (CMR)-derived measures of myocardial fibrosis were obtained in the Multi-Ethnic Study of Atherosclerosis (MESA). Objectives: To identify CM-associated pathogenic variants and assess their relative prevalence in participants with extensive myocardial fibrosis by CMR. Methods: MESA whole-genome sequencing data was evaluated to capture variants in CM-associated genes (n = 82). Coding variants with a frequency of <0.1% in gnomAD and 1,000 Genomes Project databases and damaging/deleterious effects based on in-silico scoring tools were assessed by ClinVar database and ACMG curation guidelines for evidence of pathogenicity. Cases were participants with high myocardial fibrosis defined as highest quartile of extracellular volume (ECV) or native T1 time in T1-mapping CMR and controls were the remainder of participants. Results: A total of 1,135 MESA participants had available genetic data and phenotypic measures and were free of clinical CVD at the time of CMR. We identified 6,349 rare variants in CM-associated genes in the overall MESA population, of which six pathogenic/likely pathogenic (P/LP) variants were present in the phenotyped subpopulation. The genes harboring P/LP variants in the case group were MYH7, CRYAB, and SCN5A. The prevalence of P/LP rare variants in cases was higher than controls (5 in 420 [1.1%] vs. 1 in 715 [0.1%], p = 0.03). We identified two MYBPC3 Variants of Unknown Significance (VUS)s with borderline pathogenicity in the case group. The left ventricle (LV) volume, mass, ejection fraction (EF), and longitudinal and circumferential strain in participants with the variants were not different compared to the overall cohort. Conclusions: We observed a higher prevalence of rare potentially pathogenic CM associated genetic variants in participants with significant myocardial fibrosis quantified in CMR as compared to controls without significant fibrosis. No cardiac structural or functional differences were found between participants with or without P/LP variants.
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In this pandemic of Coronavirus disease 2019 (COVID-19), a vast proportion of healthcare resources, including imaging tools, have been dedicated to the management of affected patients; yet, the frequent reports of unknown presentations and complications of disease over time have been changing the usual standard of care and resource allocation in health centers. As of now, we have witnessed multisystemic symptoms requiring the collaboration of different clinical teams in COVID-19 patients' care. Compared to previous viral pandemics, imaging modalities are now playing an essential role in the diagnosis and management of patients. This widespread utility of imaging modalities calls for a deeper understanding of potential radiologic findings in this disease and identifying the most compatible imaging protocol with safety precautions. Although initially used for respiratory tract evaluation, imaging modalities have also been used for cardiovascular, neurologic, and gastrointestinal evaluation of patients with COVID-19. In this narrative review article, we provide multimodality and multisystemic review of imaging techniques and features that can aid in the diagnosis and management of COVID-19 patients.
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BACKGROUND AND AIMS: The new coronavirus disease (COVID-19) is a systemic disease. Mounting evidence depict signs and symptoms involving multiple organs, most of which supported by pathological data. A plausible link to these manifestations is vascular and endothelial dysfunction/damage. However, much of the current knowledge relies on opinion and incipient evidence. We aim to objectively appraise current evidence on the association between COVID-19 and vascular disease, specifically endotheliitis and vasculitis. METHODS: Two researchers independently entered the search terms COVID-19 OR SARS-CoV-2 AND vasculitis, endotheliitis OR endothelium in the following online platforms: MedRxiv and LitCovid (PubMed). The search period was set from November 1, 2019 to August 28, 2020. Manuscripts with unavailable full texts, not in English, mainly on pre-clinical data, presenting only study designs or not directly related to the topics of this review were excluded. Retrospective and prospective studies, especially longitudinal ones, were given priority to the purpose of this review. Since there was paucity of prospective controlled evidence, case reports/series were also considered. RESULTS: A total of 318 manuscripts were initially found. Sixty-seven (21%) were excluded: 59 (18.5%) met exclusion criteria and 8 (2.5%) were duplicates. One hundred and forty-two manuscripts (44,6%) did not provide original data and were also excluded: 35 (11%) were comments, 108 (33.9%) reviews; 1 (0.3%) position paper. One hundred and seven (33.6%) studies were considered for the present scoping review: 81 (25,5%) case reports/series; 18 (5.7%) prospective; 8 (2.5%) retrospective. Viral inclusions in endothelial cells, mononuclear cell infiltrates in the intima of small vessels and markers of endothelial cell apoptosis were demonstrated. Specificities of COVID-19 may lead to diverse vascular manifestations in different levels of the vascular bed. CONCLUSIONS: Evidence indicates that COVID-19 targets vasculature and endothelium. However, high quality data is still lacking and studies with prospective designs and appropriately matched controls are needed.
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COVID-19/complicações , Endotélio Vascular/patologia , Inflamação/virologia , Vasculite/virologia , Células Endoteliais/virologia , Humanos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Breast cancer is the most common cancer among women, causing considerable burden and mortality. Demographic and lifestyle transitions in low and low-middle income countries have given rise to its increased incidence. The successful management of cancer relies on evidence-based policies taking into account national epidemiologic settings. We aimed to report the national and subnational trends of breast cancer incidence, mortality, years of life lost (YLL) and mortality to incidence ratio (MIR) since 1990. As part of the National and Subnational Burden of Diseases project, we estimated incidence, mortality and YLL of breast cancer by sex, age, province, and year using a two-stage spatio-temporal model, based on the primary dataset of national cancer and death registry. MIR was calculated as a quality of care indicator. Age-period-cohort analysis was used to distinguish the effects of these three collinear factors. A significant threefold increase in age-specific incidence at national and subnational levels along with a twofold extension of provincial disparity was observed. Although mortality has slightly decreased since 2000, a positive mortality annual percent change was detected in patients aged 25-34 years, leading to raised YLLs. A significant declining pattern of MIR and lower provincial MIR disparity was observed. We observed a secular increase of breast cancer incidence. Further evaluation of risk factors and developing national screening policies is recommended. A descending pattern of mortality, YLL and MIR at national and subnational levels reflects improved quality of care, even though mortality among younger age groups should be specifically addressed.