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1.
Front Radiol ; 4: 1335349, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654762

RESUMO

Background: Chronic pulmonary embolism (PE) may result in pulmonary hypertension (CTEPH). Automated CT pulmonary angiography (CTPA) interpretation using artificial intelligence (AI) tools has the potential for improving diagnostic accuracy, reducing delays to diagnosis and yielding novel information of clinical value in CTEPH. This systematic review aimed to identify and appraise existing studies presenting AI tools for CTPA in the context of chronic PE and CTEPH. Methods: MEDLINE and EMBASE databases were searched on 11 September 2023. Journal publications presenting AI tools for CTPA in patients with chronic PE or CTEPH were eligible for inclusion. Information about model design, training and testing was extracted. Study quality was assessed using compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: Five studies were eligible for inclusion, all of which presented deep learning AI models to evaluate PE. First study evaluated the lung parenchymal changes in chronic PE and two studies used an AI model to classify PE, with none directly assessing the pulmonary arteries. In addition, a separate study developed a CNN tool to distinguish chronic PE using 2D maximum intensity projection reconstructions. While another study assessed a novel automated approach to quantify hypoperfusion to help in the severity assessment of CTEPH. While descriptions of model design and training were reliable, descriptions of the datasets used in training and testing were more inconsistent. Conclusion: In contrast to AI tools for evaluation of acute PE, there has been limited investigation of AI-based approaches to characterising chronic PE and CTEPH on CTPA. Existing studies are limited by inconsistent reporting of the data used to train and test their models. This systematic review highlights an area of potential expansion for the field of AI in medical image interpretation.There is limited knowledge of A systematic review of artificial intelligence tools for chronic pulmonary embolism in CT. This systematic review provides an assessment on research that examined deep learning algorithms in detecting CTEPH on CTPA images, the number of studies assessing the utility of deep learning on CTPA in CTEPH was unclear and should be highlighted.

2.
Front Cardiovasc Med ; 11: 1279298, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374997

RESUMO

Introduction: Cardiac magnetic resonance (CMR) is of diagnostic and prognostic value in a range of cardiopulmonary conditions. Current methods for evaluating CMR studies are laborious and time-consuming, contributing to delays for patients. As the demand for CMR increases, there is a growing need to automate this process. The application of artificial intelligence (AI) to CMR is promising, but the evaluation of these tools in clinical practice has been limited. This study assessed the clinical viability of an automatic tool for measuring cardiac volumes on CMR. Methods: Consecutive patients who underwent CMR for any indication between January 2022 and October 2022 at a single tertiary centre were included prospectively. For each case, short-axis CMR images were segmented by the AI tool and manually to yield volume, mass and ejection fraction measurements for both ventricles. Automated and manual measurements were compared for agreement and the quality of the automated contours was assessed visually by cardiac radiologists. Results: 462 CMR studies were included. No statistically significant difference was demonstrated between any automated and manual measurements (p > 0.05; independent T-test). Intraclass correlation coefficient and Bland-Altman analysis showed excellent agreement across all metrics (ICC > 0.85). The automated contours were evaluated visually in 251 cases, with agreement or minor disagreement in 229 cases (91.2%) and failed segmentation in only a single case (0.4%). The AI tool was able to provide automated contours in under 90 s. Conclusions: Automated segmentation of both ventricles on CMR by an automatic tool shows excellent agreement with manual segmentation performed by CMR experts in a retrospective real-world clinical cohort. Implementation of the tool could improve the efficiency of CMR reporting and reduce delays between imaging and diagnosis.

3.
Front Cardiovasc Med ; 11: 1323461, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38317865

RESUMO

Background: Segmentation of cardiac structures is an important step in evaluation of the heart on imaging. There has been growing interest in how artificial intelligence (AI) methods-particularly deep learning (DL)-can be used to automate this process. Existing AI approaches to cardiac segmentation have mostly focused on cardiac MRI. This systematic review aimed to appraise the performance and quality of supervised DL tools for the segmentation of cardiac structures on CT. Methods: Embase and Medline databases were searched to identify related studies from January 1, 2013 to December 4, 2023. Original research studies published in peer-reviewed journals after January 1, 2013 were eligible for inclusion if they presented supervised DL-based tools for the segmentation of cardiac structures and non-coronary great vessels on CT. The data extracted from eligible studies included information about cardiac structure(s) being segmented, study location, DL architectures and reported performance metrics such as the Dice similarity coefficient (DSC). The quality of the included studies was assessed using the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: 18 studies published after 2020 were included. The DSC scores median achieved for the most commonly segmented structures were left atrium (0.88, IQR 0.83-0.91), left ventricle (0.91, IQR 0.89-0.94), left ventricle myocardium (0.83, IQR 0.82-0.92), right atrium (0.88, IQR 0.83-0.90), right ventricle (0.91, IQR 0.85-0.92), and pulmonary artery (0.92, IQR 0.87-0.93). Compliance of studies with CLAIM was variable. In particular, only 58% of studies showed compliance with dataset description criteria and most of the studies did not test or validate their models on external data (81%). Conclusion: Supervised DL has been applied to the segmentation of various cardiac structures on CT. Most showed similar performance as measured by DSC values. Existing studies have been limited by the size and nature of the training datasets, inconsistent descriptions of ground truth annotations and lack of testing in external data or clinical settings. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], PROSPERO [CRD42023431113].

4.
Front Radiol ; 3: 1112841, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492379

RESUMO

Recent years have seen a dramatic increase in studies presenting artificial intelligence (AI) tools for cardiac imaging. Amongst these are AI tools that undertake segmentation of structures on cardiac MRI (CMR), an essential step in obtaining clinically relevant functional information. The quality of reporting of these studies carries significant implications for advancement of the field and the translation of AI tools to clinical practice. We recently undertook a systematic review to evaluate the quality of reporting of studies presenting automated approaches to segmentation in cardiac MRI (Alabed et al. 2022 Quality of reporting in AI cardiac MRI segmentation studies-a systematic review and recommendations for future studies. Frontiers in Cardiovascular Medicine 9:956811). 209 studies were assessed for compliance with the Checklist for AI in Medical Imaging (CLAIM), a framework for reporting. We found variable-and sometimes poor-quality of reporting and identified significant and frequently missing information in publications. Compliance with CLAIM was high for descriptions of models (100%, IQR 80%-100%), but lower than expected for descriptions of study design (71%, IQR 63-86%), datasets used in training and testing (63%, IQR 50%-67%) and model performance (60%, IQR 50%-70%). Here, we present a summary of our key findings, aimed at general readers who may not be experts in AI, and use them as a framework to discuss the factors determining quality of reporting, making recommendations for improving the reporting of research in this field. We aim to assist researchers in presenting their work and readers in their appraisal of evidence. Finally, we emphasise the need for close scrutiny of studies presenting AI tools, even in the face of the excitement surrounding AI in cardiac imaging.

5.
Eur Respir J ; 62(2)2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37414419

RESUMO

BACKGROUND: Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives". METHODS: Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements. RESULTS: 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening. CONCLUSIONS: This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR.


Plain language summaryPulmonary arterial hypertension (PAH) is a disease of the vessels of the lung that causes their narrowing and stiffening. As a result, the heart pumping blood into these diseased lung vessels has to work harder and eventually gets worn out. PAH can affect patients' ability to function in daily activities and impact their quality of life. It also reduces their life expectancy dramatically. Patients are, therefore, often monitored and undergo several investigations to adapt treatment according to their situation. These investigations include a survey of how a patient feels (the emPHasis-10 questionnaire), functions (walking test) and how well the heart is coping with the disease (MRI of the heart). Until now, it is unclear how changes on MRI of the heart reflect changes in how a patient feels and functions. Our study identified patients that had the emPHasis-10 questionnaire, walking test and MRI of the heart at both the time of PAH diagnosis and one year later. This allowed us to compare how the changes in the different tests relate to each other. And because previous research identified thresholds for important changes in the emPHasis-10 questionnaire and the walking tests, we were able to use these tests as a benchmark for changes in the MRI of the heart. Our study identified thresholds for change on heart MRI that might indicate whether a patient has improved or worsened. This finding might have implications for how patients are monitored in clinical practice and future research on PAH treatments.


Assuntos
Hipertensão Arterial Pulmonar , Disfunção Ventricular Direita , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Qualidade de Vida , Imageamento por Ressonância Magnética/métodos , Volume Sistólico/fisiologia , Hipertensão Pulmonar Primária Familiar , Função Ventricular Direita , Valor Preditivo dos Testes
6.
Front Cardiovasc Med ; 9: 956811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911553

RESUMO

Background: There has been a rapid increase in the number of Artificial Intelligence (AI) studies of cardiac MRI (CMR) segmentation aiming to automate image analysis. However, advancement and clinical translation in this field depend on researchers presenting their work in a transparent and reproducible manner. This systematic review aimed to evaluate the quality of reporting in AI studies involving CMR segmentation. Methods: MEDLINE and EMBASE were searched for AI CMR segmentation studies in April 2022. Any fully automated AI method for segmentation of cardiac chambers, myocardium or scar on CMR was considered for inclusion. For each study, compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM) was assessed. The CLAIM criteria were grouped into study, dataset, model and performance description domains. Results: 209 studies published between 2012 and 2022 were included in the analysis. Studies were mainly published in technical journals (58%), with the majority (57%) published since 2019. Studies were from 37 different countries, with most from China (26%), the United States (18%) and the United Kingdom (11%). Short axis CMR images were most frequently used (70%), with the left ventricle the most commonly segmented cardiac structure (49%). Median compliance of studies with CLAIM was 67% (IQR 59-73%). Median compliance was highest for the model description domain (100%, IQR 80-100%) and lower for the study (71%, IQR 63-86%), dataset (63%, IQR 50-67%) and performance (60%, IQR 50-70%) description domains. Conclusion: This systematic review highlights important gaps in the literature of CMR studies using AI. We identified key items missing-most strikingly poor description of patients included in the training and validation of AI models and inadequate model failure analysis-that limit the transparency, reproducibility and hence validity of published AI studies. This review may support closer adherence to established frameworks for reporting standards and presents recommendations for improving the quality of reporting in this field. Systematic Review Registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022279214].

7.
Medicina (Kaunas) ; 58(8)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36013554

RESUMO

Background and Objectives: Interest in artificial intelligence (AI) for outcome prediction has grown substantially in recent years. However, the prognostic role of AI using advanced cardiac magnetic resonance imaging (CMR) remains unclear. This systematic review assesses the existing literature on AI in CMR to predict outcomes in patients with cardiovascular disease. Materials and Methods: Medline and Embase were searched for studies published up to November 2021. Any study assessing outcome prediction using AI in CMR in patients with cardiovascular disease was eligible for inclusion. All studies were assessed for compliance with the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Results: A total of 5 studies were included, with a total of 3679 patients, with 225 deaths and 265 major adverse cardiovascular events. Three methods demonstrated high prognostic accuracy: (1) three-dimensional motion assessment model in pulmonary hypertension (hazard ratio (HR) 2.74, 95%CI 1.73−4.34, p < 0.001), (2) automated perfusion quantification in patients with coronary artery disease (HR 2.14, 95%CI 1.58−2.90, p < 0.001), and (3) automated volumetric, functional, and area assessment in patients with myocardial infarction (HR 0.94, 95%CI 0.92−0.96, p < 0.001). Conclusion: There is emerging evidence of the prognostic role of AI in predicting outcomes for three-dimensional motion assessment in pulmonary hypertension, ischaemia assessment by automated perfusion quantification, and automated functional assessment in myocardial infarction.


Assuntos
Hipertensão Pulmonar , Infarto do Miocárdio , Inteligência Artificial , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Prognóstico , Medição de Risco
8.
Heart ; 108(15): 1224-1246, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831003
9.
BJGP Open ; 6(4)2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35764408

RESUMO

BACKGROUND: The COVID-19 pandemic necessitated an unprecedented implementation of remote consultations in UK primary care services. Specifically, older adults in care homes had a high need for infection prevention owing to their existing health conditions. GP practices in the East Midlands incorporated augmented video consultations (AVC) with the potential to support remote healthcare assessments for older adults at care homes. AIM: To explore GPs' and care home staff's experiences of the use of AVC as a mechanism to perform remote examinations of older adults in care homes. DESIGN & SETTING: Qualitative interviews were conducted with GPs and care home staff in the East Midlands, UK, during May-August 2020. METHOD: A convenience sample of GPs (n = 5), nurses (n = 12), and senior healthcare assistants (n = 3) were recruited using a purposive approach. Data were collected through semi-structured telephone interviews and analysed using framework analysis. RESULTS: Findings from participants indicated that AVC enabled real-time patient examinations to aid diagnosis and promoted person-centred care in meeting the needs of older adults. The participants also discussed the challenges of video consultations for patients with cognitive impairment and those receiving end-of-life care. CONCLUSION: AVCs show great potential in terms of GPs providing primary care services for care homes. However, healthcare staff must be involved in the development of the technology, and consideration should be given to the needs of older adults with cognitive impairment and those receiving end-of-life care. It is also vital that training is available to encourage confidence and competency in implementing the technology.

10.
J Cardiovasc Magn Reson ; 24(1): 25, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35387651

RESUMO

BACKGROUND: Right atrial (RA) area predicts mortality in patients with pulmonary hypertension, and is recommended by the European Society of Cardiology/European Respiratory Society pulmonary hypertension guidelines. The advent of deep learning may allow more reliable measurement of RA areas to improve clinical assessments. The aim of this study was to automate cardiovascular magnetic resonance (CMR) RA area measurements and evaluate the clinical utility by assessing repeatability, correlation with invasive haemodynamics and prognostic value. METHODS: A deep learning RA area CMR contouring model was trained in a multicentre cohort of 365 patients with pulmonary hypertension, left ventricular pathology and healthy subjects. Inter-study repeatability (intraclass correlation coefficient (ICC)) and agreement of contours (DICE similarity coefficient (DSC)) were assessed in a prospective cohort (n = 36). Clinical testing and mortality prediction was performed in n = 400 patients that were not used in the training nor prospective cohort, and the correlation of automatic and manual RA measurements with invasive haemodynamics assessed in n = 212/400. Radiologist quality control (QC) was performed in the ASPIRE registry, n = 3795 patients. The primary QC observer evaluated all the segmentations and recorded them as satisfactory, suboptimal or failure. A second QC observer analysed a random subcohort to assess QC agreement (n = 1018). RESULTS: All deep learning RA measurements showed higher interstudy repeatability (ICC 0.91 to 0.95) compared to manual RA measurements (1st observer ICC 0.82 to 0.88, 2nd observer ICC 0.88 to 0.91). DSC showed high agreement comparing automatic artificial intelligence and manual CMR readers. Maximal RA area mean and standard deviation (SD) DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 is 92.4 ± 3.5 cm2, 91.2 ± 4.5 cm2 and 93.2 ± 3.2 cm2, respectively. Minimal RA area mean and SD DSC metric for observer 1 vs observer 2, automatic measurements vs observer 1 and automatic measurements vs observer 2 was 89.8 ± 3.9 cm2, 87.0 ± 5.8 cm2 and 91.8 ± 4.8 cm2. Automatic RA area measurements all showed moderate correlation with invasive parameters (r = 0.45 to 0.66), manual (r = 0.36 to 0.57). Maximal RA area could accurately predict elevated mean RA pressure low and high-risk thresholds (area under the receiver operating characteristic curve artificial intelligence = 0.82/0.87 vs manual = 0.78/0.83), and predicted mortality similar to manual measurements, both p < 0.01. In the QC evaluation, artificial intelligence segmentations were suboptimal at 108/3795 and a low failure rate of 16/3795. In a subcohort (n = 1018), agreement by two QC observers was excellent, kappa 0.84. CONCLUSION: Automatic artificial intelligence CMR derived RA size and function are accurate, have excellent repeatability, moderate associations with invasive haemodynamics and predict mortality.


Assuntos
Inteligência Artificial , Hipertensão Pulmonar , Ventrículos do Coração , Humanos , Espectroscopia de Ressonância Magnética , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes
11.
BMJ Case Rep ; 15(3)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351764

RESUMO

Coronary sinus thrombosis is a rare phenomenon, most commonly occurring following invasive cardiac procedures. Spontaneous thrombosis is extremely rare and little is known about the natural history or optimal management. We present a case of coronary sinus thrombosis occurring in the context of myocardial infarction with concealed ventricular wall rupture.


Assuntos
Trombose Coronária , Ruptura Cardíaca Pós-Infarto , Infarto do Miocárdio , Trombose dos Seios Intracranianos , Trombose Coronária/complicações , Trombose Coronária/diagnóstico por imagem , Ruptura Cardíaca Pós-Infarto/complicações , Ruptura Cardíaca Pós-Infarto/etiologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Infarto do Miocárdio/complicações , Trombose dos Seios Intracranianos/complicações
12.
Front Cardiovasc Med ; 9: 1037385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684562

RESUMO

Objectives: Right ventricle (RV) mass is an imaging biomarker of mean pulmonary artery pressure (MPAP) and pulmonary vascular resistance (PVR). Some methods of RV mass measurement on cardiac MRI (CMR) exclude RV trabeculation. This study assessed the reproducibility of measurement methods and evaluated whether the inclusion of trabeculation in RV mass affects diagnostic accuracy in suspected pulmonary hypertension (PH). Materials and methods: Two populations were enrolled prospectively. (i) A total of 144 patients with suspected PH who underwent CMR followed by right heart catheterization (RHC). Total RV mass (including trabeculation) and compacted RV mass (excluding trabeculation) were measured on the end-diastolic CMR images using both semi-automated pixel-intensity-based thresholding and manual contouring techniques. (ii) A total of 15 healthy volunteers and 15 patients with known PH. Interobserver agreement and scan-scan reproducibility were evaluated for RV mass measurements using the semi-automated thresholding and manual contouring techniques. Results: Total RV mass correlated more strongly with MPAP and PVR (r = 0.59 and 0.63) than compacted RV mass (r = 0.25 and 0.38). Using a diagnostic threshold of MPAP ≥ 25 mmHg, ROC analysis showed better performance for total RV mass (AUC 0.77 and 0.81) compared to compacted RV mass (AUC 0.61 and 0.66) when both parameters were indexed for LV mass. Semi-automated thresholding was twice as fast as manual contouring (p < 0.001). Conclusion: Using a semi-automated thresholding technique, inclusion of trabecular mass and indexing RV mass for LV mass (ventricular mass index), improves the diagnostic accuracy of CMR measurements in suspected PH.

13.
Respir Med Case Rep ; 34: 101553, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815934

RESUMO

The introduction of Cystic Fibrosis Trans Regulatory modulator (CFTRm) drugs has seen a transformation in Cystic Fibrosis (CF) treatment. This has led to a significant improvement in lung function and quality of life with the potential for a real impact on life expectancy. Transient mild to moderate hepatic transaminitis is a well-known side effect of CFTRm drugs, which often improves on cessation and may not recur following the re-institution of the drug. We describe a case of transaminitis developing nine months after the initiation of Kaftrio, which progressed to liver necrosis despite stopping Kaftrio and took many months to resolve. The patient had experienced significant improvement in lung function and overall health while on Kaftrio and deteriorated when it was stopped. He was keen to restart; however, Kaftrio was not reinstated due to the potential risk of acute liver failure.

14.
BMJ Case Rep ; 14(5)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039546

RESUMO

Whilst meningiomas are common neoplasms of the central nervous system; ectopic meningiomas are very rare. When they do occur, they are typically in the head and neck. Due to their rarity, they propose a diagnostic challenge with interesting pathological findings. To date, only seven ectopic meningiomas arising in the mediastinum have been reported in the literature. We aim to shift the focus on the diagnostic journey of this rare entity which involved various imaging and histopathological techniques. Our patient was successfully treated with no complications after four years through input from specialists and the multidisciplinary team.


Assuntos
Neoplasias Meníngeas , Meningioma , Cabeça , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Pescoço
15.
Nat Genet ; 53(5): 630-637, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33958779

RESUMO

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome. We uncovered kidney targets for 479 (58.3%) BP-GWAS variants and paired 49 BP-GWAS kidney genes with 210 licensed drugs. Our colocalization and Mendelian randomization analyses identified 179 unique kidney genes with evidence of putatively causal effects on BP. Through Mendelian randomization, we also uncovered effects of BP on renal outcomes commonly affecting patients with hypertension. Collectively, our studies identified genetic variants, kidney genes, molecular mechanisms and biological pathways of key relevance to the genetic regulation of BP and inherited susceptibility to hypertension.


Assuntos
Predisposição Genética para Doença , Genômica , Hipertensão/genética , Rim/patologia , Processamento Alternativo/genética , Pressão Sanguínea/genética , Metilação de DNA/genética , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética
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