Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
1.
Stud Health Technol Inform ; 270: 1061-1065, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32570544

RESUMO

PROMISE (Personal Medical Safe) was a German research project which aimed to provide the responsibility of genomic data to the patient via a mobile app. The patient should accept or decline study requests to use his/her genomic data via the app. In the evaluation of the app the experiences with mobile health as well as the opinion on being the genomic data manager were measured. Furthermore, the test patients were asked about their opinion and their concerns on the PROMISE app. Most of the 19 test patients were aware of the high sensibility of genomic data and thought that the PROMISE app was a suitable solution. The largest part found it good that they were the responsible data owner. However, several participants also found it important to have a permanent contact person when it comes to questions on inquiries or the app.

2.
ESC Heart Fail ; 7(2): 692-696, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31802644

RESUMO

Cardiac sarcoidosis is a chronic inflammatory disease with a large spectrum of symptoms that can mimic diseases such as dilated, hypertrophic, or arrhythmogenic cardiomyopathies. It can be asymptomatic but can also present with ventricular arrhythmias, conduction disease, and heart failure (HF) or even sudden cardiac death (SCD). We present here the case of a patient transplanted due to end-stage arrhythmogenic right ventricular cardiomyopathy (ARVC), fulfilling the task force criteria. A few years after successful heart transplantation (HTX), the patient developed similar symptoms and morphofunctional changes of the heart, which led to critical re-evaluation of his primary diagnosis.

3.
Stud Health Technol Inform ; 267: 101-109, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31483261

RESUMO

One of the major obstacles for research on German medical reports is the lack of de-identified medical corpora. Previous de-identification tasks focused on non-German medical texts, which raised the demand for an in-depth evaluation of de-identification methods on German medical texts. Because of remarkable advancements in natural language processing using supervised machine learning methods on limited training data, we evaluated them for the first time on German medical reports using our annotated data set consisting of 113 medical reports from the cardiology domain. We applied state-of-the-art deep learning methods using pre-trained models as input to a bidirectional LSTM network and well-established conditional random fields for de-identification of German medical reports. We performed an extensive evaluation for de-identification and multiclass named entity recognition. Using rule based and out of domain machine learning methods as a baseline, the conditional random field improved F2-score from 70 to 93% for de-identification, the neural approach reached 96% in F2-score while keeping balanced precision and recall rates. These results show, that state-of-the-art machine learning methods can play a crucial role in de-identification of German medical reports.


Assuntos
Anonimização de Dados , Aprendizado Profundo , Registros Eletrônicos de Saúde , Aprendizado de Máquina , Processamento de Linguagem Natural
4.
Clin Res Cardiol ; 108(11): 1297-1308, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30980206

RESUMO

BACKGROUND: Left ventricular non-compaction has been increasingly diagnosed in recent years. However, it is still debated whether non-compaction is a pathological condition or a physiological trait. In this meta-analysis and systematic review, we compare studies, which investigated these two different perspectives. Furthermore, we provide a comprehensive overview on the clinical outcome as well as genetic background of left ventricular non-compaction cardiomyopathy in adult patients. METHODS AND RESULTS: We retrieved PubMed/Medline literatures in English language from 2000 to 19/09/2018 on clinical outcome and genotype of patients with non-compaction. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Altogether, 35 studies with 2271 non-compaction patients were included in our meta-analysis. The mean age at diagnosis was the mid of their fifth decade. Two-thirds of patients were male. Congenital heart diseases including atrial or ventricular septum defect or Ebstein anomaly were reported in 7% of patients. Twenty-four percent presented with family history of cardiomyopathy. The mean frequency of neuromuscular diseases was 5%. Heart rhythm abnormalities were reported frequently: conduction disease in 26%, supraventricular tachycardia in 17%, and sustained or non-sustained ventricular tachycardia in 18% of patients. Three important outcome measures were reported including systemic thromboembolic events with a mean frequency of 9%, heart transplantation with 4%, and adequate ICD therapy with 15%. Nine studies investigated the genetics of non-compaction cardiomyopathy. The most frequently mutated gene was TTN with a pooled frequency of 11%. The average frequency of MYH7 mutations was 9%, for MYBPC3 mutations 5%, and for CASQ2 and LDB3 3% each. TPM1, MIB1, ACTC1, and LMNA mutations had an average frequency of 2% each. Mutations in PLN, HCN4, TAZ, DTNA, TNNT2, and RBM20 were reported with a frequency of 1% each. We also summarized the results of eight studies investigating the non-compaction in altogether 5327 athletes, pregnant women, patients with sickle cell disease, as well as individuals from population-based cohorts, in which the presence of left ventricular hypertrabeculation ranged from 1.3 to 37%. CONCLUSION: The summarized data indicate that non-compaction may lead to unfavorable outcome in different cardiomyopathy entities. The presence of key features in a multimodal diagnostic approach could distinguish between benign morphological trait and manifest cardiomyopathy.


Assuntos
Miocárdio Ventricular não Compactado Isolado/genética , Humanos , Miocárdio Ventricular não Compactado Isolado/diagnóstico , Miocárdio Ventricular não Compactado Isolado/terapia
5.
J Neurol Surg A Cent Eur Neurosurg ; 80(1): 26-33, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30508865

RESUMO

OBJECTIVES: Ventriculoperitoneal (VP) shunting is commonly used to treat pediatric hydrocephalus, but failure rates are high. VP shunt failure in children is mostly caused by infection and/or proximal/distal shunt obstruction. However, to our knowledge, no previous reviews have discussed this topic using only clinical studies when age-related data could be obtained. This systematic review aimed at reevaluating what is already known as the most common causes of shunt failure and to determine the incidence and causes of VP shunt failure during the first 2 years of life as a step to establish solid evidence-based guidelines to avoid VP shunt failure in infants. METHODS: We performed a search using the search terms "Cerebrospinal Fluid Shunts" (Medical Subject Headings [MeSH]) AND failure [All Fields] AND ("humans" [MeSH] AND English [lang] AND "infant" [MeSH]). Only articles that specifically discussed VP shunt complications in children < 2 years were included. RESULTS: We found that the most common causes of VP shunt failure in children < 2 years were shunt obstruction and infection, both observed in a range. CONCLUSION: VP shunt failure is very common in infants, mostly resulting from obstruction and infection. Future studies should focus on methods designed to avoid these complications or on alternative treatments for hydrocephalus.


Assuntos
Hidrocefalia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Derivação Ventriculoperitoneal/efeitos adversos , Fatores Etários , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino
6.
EMBO Mol Med ; 10(1): 107-120, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29138229

RESUMO

The transcriptome needs to be tightly regulated by mechanisms that include transcription factors, enhancers, and repressors as well as non-coding RNAs. Besides this dynamic regulation, a large part of phenotypic variability of eukaryotes is expressed through changes in gene transcription caused by genetic variation. In this study, we evaluate genome-wide structural genomic variants (SVs) and their association with gene expression in the human heart. We detected 3,898 individual SVs affecting all classes of gene transcripts (e.g., mRNA, miRNA, lncRNA) and regulatory genomic regions (e.g., enhancer or TFBS). In a cohort of patients (n = 50) with dilated cardiomyopathy (DCM), 80,635 non-protein-coding elements of the genome are deleted or duplicated by SVs, containing 3,758 long non-coding RNAs and 1,756 protein-coding transcripts. 65.3% of the SV-eQTLs do not harbor a significant SNV-eQTL, and for the regions with both classes of association, we find similar effect sizes. In case of deleted protein-coding exons, we find downregulation of the associated transcripts, duplication events, however, do not show significant changes over all events. In summary, we are first to describe the genomic variability associated with SVs in heart failure due to DCM and dissect their impact on the transcriptome. Overall, SVs explain up to 7.5% of the variation of cardiac gene expression, underlining the importance to study human myocardial gene expression in the context of the individual genome. This has immediate implications for studies on basic mechanisms of cardiac maladaptation, biomarkers, and (gene) therapeutic studies alike.


Assuntos
Cardiomiopatia Dilatada/genética , Regulação da Expressão Gênica , Variação Estrutural do Genoma , RNA/genética , Transcriptoma , Animais , Estudos de Coortes , Humanos , Masculino , Camundongos , MicroRNAs/genética , Miocárdio/metabolismo , Locos de Características Quantitativas , RNA Longo não Codificante/genética , RNA Mensageiro/genética
7.
Clin Res Cardiol ; 107(1): 30-41, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28840316

RESUMO

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, which goes along with increased risk for sudden cardiac death (SCD). Despite the knowledge about the different causal genes, the relationship between individual genotypes and phenotypes is incomplete. METHODS AND RESULTS: We retrieved PubMed/Medline literatures on genotype-phenotype associations in patients with HCM and mutations in MYBPC3, MYH7, TNNT2, and TNNI3. Altogether, 51 studies with 7675 HCM patients were included in our meta-analysis. The average frequency of mutations in MYBPC3 (20%) and MYH7 (14%) was higher than TNNT2 and TNNI3 (2% each). The mean age of HCM onset for MYH7 mutation positive patients was the beginning of the fourth decade, significantly earlier than patients without sarcomeric mutations. A high male proportion was observed in TNNT2 (69%), MYBPC3 (62%) and mutation negative group (64%). Cardiac conduction disease, ventricular arrhythmia and heart transplantation (HTx) rate were higher in HCM patients with MYH7 mutations in comparison to MYBPC3 (p < 0.05). Furthermore, SCD was significantly higher in patients with sarcomeric mutations (p < 0.01). CONCLUSION: A pooled dataset and a comprehensive genotype-phenotype analysis show that the age at disease onset of HCM patients with MYH7 is earlier and leads to a more severe phenotype than in patient without such mutations. Furthermore, patients with sarcomeric mutations are more susceptible to SCD. The present study further supports the clinical interpretation of sarcomeric mutations in HCM patients.


Assuntos
Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica/genética , Morte Súbita Cardíaca/prevenção & controle , Mutação , Cadeias Pesadas de Miosina/genética , Adulto , Idade de Início , Idoso , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Hipertrófica/terapia , Proteínas de Transporte/genética , Estudos de Casos e Controles , Morte Súbita Cardíaca/etiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Resultado do Tratamento , Troponina I/genética , Troponina T/genética , Adulto Jovem
8.
Eur Heart J ; 38(46): 3449-3460, 2017 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-29029073

RESUMO

Aims: In this study, we aimed to clinically and genetically characterize LVNC patients and investigate the prevalence of variants in known and novel LVNC disease genes. Introduction: Left ventricular non-compaction cardiomyopathy (LVNC) is an increasingly recognized cause of heart failure, arrhythmia, thromboembolism, and sudden cardiac death. We sought here to dissect its genetic causes, phenotypic presentation and outcome. Methods and results: In our registry with follow-up of in the median 61 months, we analysed 95 LVNC patients (68 unrelated index patients and 27 affected relatives; definite familial LVNC = 23.5%) by cardiac phenotyping, molecular biomarkers and exome sequencing. Cardiovascular events were significantly more frequent in LVNC patients compared with an age-matched group of patients with non-ischaemic dilated cardiomyopathy (hazard ratio = 2.481, P = 0.002). Stringent genetic classification according to ACMG guidelines revealed that TTN, LMNA, and MYBPC3 are the most prevalent disease genes (13 patients are carrying a pathogenic truncating TTN variant, odds ratio = 40.7, Confidence interval = 21.6-76.6, P < 0.0001, percent spliced in 76-100%). We also identified novel candidate genes for LVNC. For RBM20, we were able to perform detailed familial, molecular and functional studies. We show that the novel variant p.R634L in the RS domain of RBM20 co-segregates with LVNC, leading to titin mis-splicing as revealed by RNA sequencing of heart tissue in mutation carriers, protein analysis, and functional splice-reporter assays. Conclusion: Our data demonstrate that the clinical course of symptomatic LVNC can be severe. The identified pathogenic variants and distribution of disease genes-a titin-related pathomechanism is found in every fourth patient-should be considered in genetic counselling of patients. Pathogenic variants in the nuclear proteins Lamin A/C and RBM20 were associated with worse outcome.


Assuntos
Hipertrofia Ventricular Esquerda/genética , Mutação/genética , Adulto , Arritmias Cardíacas/genética , Cardiomiopatia Dilatada/genética , Conectina/genética , Morte Súbita Cardíaca/etiologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Lamina Tipo A/genética , Masculino , Linhagem , Proteínas de Ligação a RNA/genética
9.
Circulation ; 136(16): 1528-1544, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-28838933

RESUMO

BACKGROUND: Biochemical DNA modification resembles a crucial regulatory layer among genetic information, environmental factors, and the transcriptome. To identify epigenetic susceptibility regions and novel biomarkers linked to myocardial dysfunction and heart failure, we performed the first multi-omics study in myocardial tissue and blood of patients with dilated cardiomyopathy and controls. METHODS: Infinium human methylation 450 was used for high-density epigenome-wide mapping of DNA methylation in left-ventricular biopsies and whole peripheral blood of living probands. RNA deep sequencing was performed on the same samples in parallel. Whole-genome sequencing of all patients allowed exclusion of promiscuous genotype-induced methylation calls. RESULTS: In the screening stage, we detected 59 epigenetic loci that are significantly associated with dilated cardiomyopathy (false discovery corrected P≤0.05), with 3 of them reaching epigenome-wide significance at P≤5×10-8. Twenty-seven (46%) of these loci could be replicated in independent cohorts, underlining the role of epigenetic regulation of key cardiac transcription regulators. Using a staged multi-omics study design, we link a subset of 517 epigenetic loci with dilated cardiomyopathy and cardiac gene expression. Furthermore, we identified distinct epigenetic methylation patterns that are conserved across tissues, rendering these CpGs novel epigenetic biomarkers for heart failure. CONCLUSIONS: The present study provides to our knowledge the first epigenome-wide association study in living patients with heart failure using a multi-omics approach.


Assuntos
Cardiomiopatia Dilatada/genética , Metilação de DNA , Epigênese Genética , Epigenômica/métodos , Loci Gênicos , Insuficiência Cardíaca/genética , Ventrículos do Coração/química , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Estudos de Casos e Controles , Ilhas de CpG , Perfilação da Expressão Gênica , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo , RNA Mensageiro/genética , Análise de Sequência de RNA
10.
Clin Res Cardiol ; 106(2): 127-139, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27576561

RESUMO

AIMS: Routine genetic testing in Dilated Cardiomyopathy (DCM) has recently become reality using Next-Generation Sequencing. Several studies have explored the relationship between genotypes and clinical phenotypes to support risk estimation and therapeutic decisions, however, most studies are small or restricted to a few genes. This study provides to our knowledge the first systematic meta-analysis on genotype-phenotype associations in DCM. METHODS AND RESULTS: We retrieved PubMed/Medline literature on genotype-phenotype associations in patients with DCM and mutations in LMNA, PLN, RBM20, MYBPC3, MYH7, TNNT2 and TNNI3. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Together, 48 studies with 8097 patients were included. Furthermore, we reviewed recent studies investigating genotype-phenotype associations in DCM patients with TTN mutations. The average frequency of mutations in the investigated genes was between 1 and 5 %. The mean age of DCM onset was the beginning of the fifth decade for all genes. Heart transplantation (HTx) rate was highest in LMNA mutation carriers (27 %), while RBM20 mutation carriers were transplanted at a markedly younger age (mean 28.5 years). While 73 % of DCM patients with LMNA mutations showed cardiac conduction diseases, low voltage was the reported ECG hallmark in PLN mutation carriers. The frequency of ventricular arrhythmia in DCM patients with LMNA (50 %) and PLN (43 %) mutations was significantly higher. The penetrance of DCM phenotype in subjects with TTN truncating variants increased with age and reached 100 % by age of 70. CONCLUSION: A pooled analysis of available genotype-phenotype data shows a higher prevalence of sudden cardiac death (SCD), cardiac transplantation, or ventricular arrhythmias in LMNA and PLN mutation carriers compared to sarcomeric gene mutations. This study will further support the clinical interpretation of genetic findings.


Assuntos
Cardiomiopatia Dilatada/genética , Mutação , Adulto , Fatores Etários , Arritmias Cardíacas/genética , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Morte Súbita Cardíaca/etiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Fatores Sexuais
11.
Genomics Proteomics Bioinformatics ; 14(4): 244-52, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27477449

RESUMO

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau (τ). Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated significantly across the patient population with τ. This study shows that multi-modal cardiac models can successfully capture diastolic (dys) function, a prerequisite for future clinical trials on HF-pEF.


Assuntos
Simulação por Computador , Insuficiência Cardíaca/fisiopatologia , Adulto , Idoso , Fator Natriurético Atrial/análise , Biomarcadores/análise , Pressão Sanguínea , Cateterismo Cardíaco , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/metabolismo , Ecocardiografia , Feminino , Insuficiência Cardíaca/metabolismo , Frequência Cardíaca , Hemodinâmica , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Precursores de Proteínas/análise
12.
Med Image Anal ; 34: 52-64, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27133269

RESUMO

Personalization is the process of fitting a model to patient data, a critical step towards application of multi-physics computational models in clinical practice. Designing robust personalization algorithms is often a tedious, time-consuming, model- and data-specific process. We propose to use artificial intelligence concepts to learn this task, inspired by how human experts manually perform it. The problem is reformulated in terms of reinforcement learning. In an off-line phase, Vito, our self-taught artificial agent, learns a representative decision process model through exploration of the computational model: it learns how the model behaves under change of parameters. The agent then automatically learns an optimal strategy for on-line personalization. The algorithm is model-independent; applying it to a new model requires only adjusting few hyper-parameters of the agent and defining the observations to match. The full knowledge of the model itself is not required. Vito was tested in a synthetic scenario, showing that it could learn how to optimize cost functions generically. Then Vito was applied to the inverse problem of cardiac electrophysiology and the personalization of a whole-body circulation model. The obtained results suggested that Vito could achieve equivalent, if not better goodness of fit than standard methods, while being more robust (up to 11% higher success rates) and with faster (up to seven times) convergence rate. Our artificial intelligence approach could thus make personalization algorithms generalizable and self-adaptable to any patient and any model.


Assuntos
Inteligência Artificial , Simulação por Computador , Medicina de Precisão/métodos , Humanos , Física , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
Clin Chem ; 61(10): 1246-55, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26240298

RESUMO

BACKGROUND: Biomarkers are well established for diagnosis of myocardial infarction [cardiac troponins, high-sensitivity cardiac troponins (hs-cTn)], exclusion of acute and chronic heart failure [B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP)] and venous thromboembolism (d-dimers). Several studies have demonstrated acute increases in cardiac biomarkers and altered cardiac function after strenuous sports that can pretend a cardiovascular emergency and interfere with state-of-the-art clinical assessment. METHODS: We performed a systematic review and metaanalysis of biomarker and cardiovascular imaging changes after endurance exercise. We searched for observational studies published in the English language from 1997 to 2014 that assessed these biomarkers or cardiac function and morphology directly after endurance exercise. Of 1787 identified abstracts, 45 studies were included. RESULTS: Across all studies cardiac troponin T (cTnT) exceeded the cutoff value (0.01 ng/mL) in 51% (95% CI, 37%-64%) of participants. The measured pooled changes from baseline for high-sensitivity cTnT (hs-cTnT) were +26 ng/L (95% CI, 5.2-46.0), for cTnI +40 ng/L (95% CI, 21.4; 58.0), for BNP +10 ng/L (95% CI, 4.3; 16.6), for NT-proBNP +67 ng/L (95% CI, 49.9; 84.7), and for d-dimer +262 ng/mL (95% CI, 165.9; 358.7). Right ventricular end diastolic diameter increased and right ventricular ejection fraction as well as the ratio of the early to late transmitral flow velocities decreased after exercise, while no significant changes were observed in left ventricular ejection fraction. CONCLUSIONS: Current cardiovascular biomarkers (cTnT, hs-cTnT, BNP, NT-proBNP, and d-dimer) that are used in clinical diagnosis of pulmonary embolism, acute coronary syndrome, and heart failure are prone to alterations due to strenuous exercise. Hence, it is necessary to take previous physical exercise into account when a cardiac emergency is suspected.


Assuntos
Síndrome Coronariana Aguda/diagnóstico , Teste de Esforço , Tolerância ao Exercício , Insuficiência Cardíaca/diagnóstico , Embolia Pulmonar/diagnóstico , Síndrome Coronariana Aguda/sangue , Biomarcadores/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Insuficiência Cardíaca/sangue , Humanos , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Embolia Pulmonar/sangue , Troponina T/sangue
14.
PLoS One ; 10(7): e0134869, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26230546

RESUMO

BACKGROUND: Despite modern pharmacotherapy and advanced implantable cardiac devices, overall prognosis and quality of life of HF patients remain poor. This is in part due to insufficient patient stratification and lack of individualized therapy planning, resulting in less effective treatments and a significant number of non-responders. METHODS AND RESULTS: State-of-the-art clinical phenotyping was acquired, including magnetic resonance imaging (MRI) and biomarker assessment. An individualized, multi-scale model of heart function covering cardiac anatomy, electrophysiology, biomechanics and hemodynamics was estimated using a robust framework. The model was computed on n=46 HF patients, showing for the first time that advanced multi-scale models can be fitted consistently on large cohorts. Novel multi-scale parameters derived from the model of all cases were analyzed and compared against clinical parameters, cardiac imaging, lab tests and survival scores to evaluate the explicative power of the model and its potential for better patient stratification. Model validation was pursued by comparing clinical parameters that were not used in the fitting process against model parameters. CONCLUSION: This paper illustrates how advanced multi-scale models can complement cardiovascular imaging and how they could be applied in patient care. Based on obtained results, it becomes conceivable that, after thorough validation, such heart failure models could be applied for patient management and therapy planning in the future, as we illustrate in one patient of our cohort who received CRT-D implantation.


Assuntos
Insuficiência Cardíaca/terapia , Medicina de Precisão , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos
15.
BMC Med Educ ; 15: 106, 2015 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-26084490

RESUMO

BACKGROUND: While the number of international students has increased over the last decade, such students face diverse challenges due to language and cultural barriers. International medical students suffer from personal distress and a lack of support. Their performance is significantly lower than non-international peers in clinical examinations. We investigated whether international students benefit from a peer-led exam preparation course. METHODS: An exam preparation course was designed, and relevant learning objectives were defined. Two evaluations were undertaken: Using a qualitative approach, tutees (N = 10) were asked for their thoughts and comments in a semi-structured interview at the end of the semester. From a quantitative perspective, all participants (N = 22) were asked to complete questionnaires at the end of each course session. RESULTS: International students reported a range of significant benefits from the course as they prepared for upcoming exams. They benefited from technical and didactic, as well as social learning experiences. They also considered aspects of the tutorial's framework helpful. CONCLUSION: Social and cognitive congruence seem to be the key factors to success within international medical students' education. If tutors have a migration background, they can operate as authentic role models. Furthermore, because they are still students themselves, they can offer support using relevant and understandable language.


Assuntos
Diversidade Cultural , Educação de Graduação em Medicina/organização & administração , Intercâmbio Educacional Internacional , Mentores , Grupo Associado , Aprendizado Social , Estudantes de Medicina/psicologia , Habilidades para Realização de Testes , Educação de Graduação em Medicina/métodos , Estudos de Avaliação como Assunto , Feminino , Alemanha , Humanos , Entrevistas como Assunto , Masculino , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Inquéritos e Questionários , Voluntários , Adulto Jovem
16.
Anesth Essays Res ; 9(1): 51-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25886421

RESUMO

BACKGROUND: Various sedative and analgesic techniques have been used during shock wave lithotripsy (SWL). AIM: This study aimed at evaluating the efficacy of ultrasound-guided unilateral transversus abdominis plane (TAP) block as an analgesic technique alternative during ureteric SWL. SETTINGS AND DESIGN: Prospective randomized comparative study. MATERIALS AND METHODS: Fifty patients scheduled for ureteric SWL were randomly allocated into two equal groups: Group (F) received 1.5 mcg/kg fentanyl intravenous and group (T) received unilateral TAP block with injection of 25 ml of bupivacaine 0.25% (62.5 mg). STATISTICAL ANALYSIS: Statistical analysis was performed using SPSS program version 19 and EP16 program. RESULTS: The visual analog scale was significantly less in group (T) than in group (F) both intra-operatively (at 10, 20, 30, and 40 min) and postoperatively (at 10 min intervals in the postanesthesia care unit [PACU]) (P < 0.001). Rescue analgesia with pethidine during the procedure and in the PACU was less (P < 0.001) in the group (T) than group (F) with a median of 20 mg versus 55 mg, respectively. The higher sedation scores observed in group (F) at 15, 25, and 35 min during the procedure, and at 20 min during the PACU time were statistically highly significant (P < 0.001), but only significant at 10 min (P = 0.03) and 30 min (P = 0.007) during the PACU time. There was also highly significant decrease (P < 0.001) in the time of PACU stay in group (T) (38.2 ± 6.6 min) compared with group (F) (89.2 ± 13.39 min). We recorded 6 patients in group (F) (24%) who have developed respiratory depression (respiratory rate < 10 breaths/min) compared to 0% in group (T) (P = 0.022). In addition, in group (F) nausea was noted in 8 patients (32%) and vomiting in 6 patients (24%), which was statistically significant when compared to group (T) (0%) (P = 0.01 and 0.022, respectively). CONCLUSION: Ultrasound-guided unilateral TAP block is an effective alternative analgesic technique during ureteric SWL.

17.
Eur Heart J ; 36(18): 1123-35a, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25163546

RESUMO

AIM: Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. METHODS AND RESULTS: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. CONCLUSION: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Análise de Sequência de DNA/métodos , Cardiomiopatia Dilatada/diagnóstico , Europa (Continente) , Estudos de Viabilidade , Feminino , Marcadores Genéticos/genética , Genótipo , Heterozigoto , Humanos , Masculino , Mutação/genética , Fenótipo , Características de Residência
18.
Artigo em Inglês | MEDLINE | ID: mdl-25485357

RESUMO

Clinical applications of computational cardiac models require precise personalization, i.e. fitting model parameters to capture patient's physiology. However, due to parameter non-identifiability, limited data, uncertainty in the clinical measurements, and modeling assumptions, various combinations of parameter values may exist that yield the same quality of fit. Hence, there is a need for quantifying the uncertainty in estimated parameters and to ascertain the uniqueness of the found solution. This paper presents a stochastic method to estimate the parameters of an image-based electromechanical model of the heart and their uncertainty due to noise in measurements. First, Bayesian inference is applied to fully estimate the posterior probability density function (PDF) of the model. To that end, Markov Chain Monte Carlo sampling is used, which is made computationally tractable by employing a fast surrogate model based on Polynomial Chaos Expansion, instead of the true forward model. Then, we use the mean-shift algorithm to automatically find the modes of the PDF and select the most likely one while being robust to noise. The approach is used to estimate global active stress and passive stiffness from invasive pressure and image-based volume quantification. Experiments on eight patients showed that not only our approach yielded goodness of fits equivalent to a well-established deterministic method, but we could also demonstrate the non-uniqueness of the problem and report uncertainty estimates, crucial information for subsequent clinical assessments of the personalized models.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Imagem Cinética por Ressonância Magnética/métodos , Modelos Cardiovasculares , Disfunção Ventricular Esquerda/fisiopatologia , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/diagnóstico , Simulação por Computador , Sistema de Condução Cardíaco/patologia , Ventrículos do Coração/patologia , Humanos , Imageamento Tridimensional/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Razão Sinal-Ruído , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia
19.
J Biol Inorg Chem ; 19(7): 1233-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25064750

RESUMO

The reaction between nitrite and the oxy forms of globins has complex autocatalytic kinetics with several branching steps and evolves through chain reactions mediated by reactive species (including radicals) such as hydrogen peroxide, ferryl and nitrogen dioxide, starting with a lag phase, after which it proceeds onto an autocatalytic phase. Reported here are UV-Vis spectra collected upon stopped-flow mixing of myoglobin with a supraphysiological excess of nitrite. The best fit to the experimental data follows an A â†’ B â†’ C reaction scheme involving the formation of a short-lived intermediate identified as ferryl. This is consistent with a mechanism where nitrite binds to oxy myoglobin to generate an undetectable ferrous-peroxynitrate intermediate, whose decay leads to nitrate and ferryl. The ferryl is then reduced to met by the excess nitrite. DFT calculations reveal an essentially barrierless reaction between nitrite and the oxy heme, with a notable outer-sphere component; the resulting metastable ferrous-peroxynitrate adduct is found to feature a very low barrier towards nitrate liberation, with ferryl as a final product-in good agreement with experiment.


Assuntos
Ferro/metabolismo , Mioglobina/metabolismo , Nitritos/metabolismo , Ácido Peroxinitroso/metabolismo , Cachalote/metabolismo , Animais , Ferro/química , Modelos Moleculares , Mioglobina/química , Nitritos/química , Oxirredução , Ácido Peroxinitroso/química
20.
Med Image Anal ; 18(8): 1361-76, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24857832

RESUMO

Diagnosis and treatment of dilated cardiomyopathy (DCM) is challenging due to a large variety of causes and disease stages. Computational models of cardiac electrophysiology (EP) can be used to improve the assessment and prognosis of DCM, plan therapies and predict their outcome, but require personalization. In this work, we present a data-driven approach to estimate the electrical diffusivity parameter of an EP model from standard 12-lead electrocardiograms (ECG). An efficient forward model based on a mono-domain, phenomenological Lattice-Boltzmann model of cardiac EP, and a boundary element-based mapping of potentials to the body surface is employed. The electrical diffusivity of myocardium, left ventricle and right ventricle endocardium is then estimated using polynomial regression which takes as input the QRS duration and electrical axis. After validating the forward model, we computed 9500 EP simulations on 19 different DCM patients in just under three seconds each to learn the regression model. Using this database, we quantify the intrinsic uncertainty of electrical diffusion for given ECG features and show in a leave-one-patient-out cross-validation that the regression method is able to predict myocardium diffusion within the uncertainty range. Finally, our approach is tested on the 19 cases using their clinical ECG. 84% of them could be personalized using our method, yielding mean prediction errors of 18.7ms for the QRS duration and 6.5° for the electrical axis, both values being within clinical acceptability. By providing an estimate of diffusion parameters from readily available clinical data, our data-driven approach could therefore constitute a first calibration step toward a more complete personalization of cardiac EP.


Assuntos
Mapeamento Potencial de Superfície Corporal/métodos , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Diagnóstico por Computador/métodos , Eletrocardiografia/métodos , Sistema de Condução Cardíaco/fisiopatologia , Modelos Cardiovasculares , Simulação por Computador , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA