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Revista Espanola de Cardiologia... Apr 2019Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart...
Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart transplant and has been associated with an increased risk of sudden cardiac death. Risk stratification in these patients continues to be challenging. The identification of the specific etiology of the disease is very useful for the early detection of mutation carriers. Genetic study often provides prognostic information and can determine the therapeutic approach. Wide phenotypic variability is observed depending on the mutated gene, the type of mutation, and the presence of additional genetic and environmental factors.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Calcium-Binding Proteins; Cardiomyopathy, Dilated; Cytoskeletal Proteins; Desmosomes; Filamins; Genes; Genes, Mitochondrial; Genetic Testing; Humans; Lysosomal-Associated Membrane Protein 2; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Prognosis; RNA-Binding Proteins; Risk Assessment; Sarcomeres
PubMed: 30792015
DOI: 10.1016/j.rec.2018.10.017 -
Journal of B.U.ON. : Official Journal... 2018The purpose of this study was to systematically review the literature of esophageal carcinosarcomas (ECS) and report epidemiologic and clinicopathologic data for this...
PURPOSE
The purpose of this study was to systematically review the literature of esophageal carcinosarcomas (ECS) and report epidemiologic and clinicopathologic data for this rare entity. We also attempted to shed light to the biologic behavior of ECSs with special reference to factors that may affect disease-free (DES) and overall survival (OS).
METHODS
A systematic literature review was performed using MEDLINE, EMBASE and the Cochrane Library databases (Search date: 12 May 2017). The search strategy referred to carcinosarcoma OR pseudosarcoma OR polypoid carcinoma OR sarcomatoid carcinoma OR spindle-cell squamous cell carcinoma OR metaplastic carcinoma OR pseudosarcomatous carcinoma AND esophagus. A total number of 103 ECS patients was identified. Results: ECs most frequently occur in middle-aged as well as elderly men with a history of smoking or drinking. Middle and/or lower esophagus remains the most common location. Imaging plays a pivotal role in the management of ECS by delineating the anatomic extent of the tumor and thereby determining the appropriate therapeutic strategy. Nevertheless, immunohistochemistry is the gold standard for the diagnosis of carcinosarcomas, since it has been demonstrated that CEA, EMA, pancreatin, chromogranin A, CD56 and synaptophysin staining are highly specific markers for the carcinomatous components, while desmin, vimentin and smooth muscle/sarcomeric actin show affinity for the sarcomatous elements. Esophagectomy has been traditionally considered the treatment modality of choice. Endoscopic procedures, including mucosal resection and submucosal dissection have also been proposed. Alternative therapies, such as radio- and chemotherapy proved insufficient.
CONCLUSION
ECS is a rare tumor. Immunohistochemistry is the gold standard for the diagnosis of this disease. Esophagectomy has been traditionally considered the treatment modality of choice. Endoscopic procedures have also been proposed while potential benefit of alternative therapies, such as radiotherapy and chemotherapy remains controversial.
Topics: Carcinosarcoma; Esophageal Neoplasms; Female; Humans; Immunohistochemistry; Male
PubMed: 30570870
DOI: No ID Found -
Pflugers Archiv : European Journal of... May 2019Human-induced pluripotent stem cells (hiPSC) can be differentiated to cardiomyocytes at high efficiency and are increasingly used to study cardiac disease in a human...
Human-induced pluripotent stem cells (hiPSC) can be differentiated to cardiomyocytes at high efficiency and are increasingly used to study cardiac disease in a human context. This review evaluated 38 studies on hypertrophic (HCM) and dilated cardiomyopathy (DCM) of different genetic causes asking to which extent published data allow the definition of an in vitro HCM/DCM hiPSC-CM phenotype. The data are put in context with the prevailing hypotheses on HCM/DCM dysfunction and pathophysiology. Relatively consistent findings in HCM not reported in DCM were larger cell size (156 ± 85%, n = 15), more nuclear localization of nuclear factor of activated T cells (NFAT; 175 ± 65%, n = 3), and higher β-myosin heavy chain gene expression levels (500 ± 547%, n = 8) than respective controls. Conversely, DCM lines showed consistently less force development than controls (47 ± 23%, n = 9), while HCM forces scattered without clear trend. Both HCM and DCM lines often showed sarcomere disorganization, higher NPPA/NPPB expression levels, and arrhythmic beating behaviour. The data have to be taken with the caveat that reporting frequencies of the various parameters (e.g. cell size, NFAT expression) differ widely between HCM and DCM lines, in which data scatter is large and that only 9/38 studies used isogenic controls. Taken together, the current data provide interesting suggestions for disease-specific phenotypes in HCM/DCM hiPSC-CM but indicate that the field is still in its early days. Systematic, quantitative comparisons and robust, high content assays are warranted to advance the field.
Topics: Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Mutation; Myocardial Contraction; Myocytes, Cardiac; Phenotype
PubMed: 30324321
DOI: 10.1007/s00424-018-2214-0 -
Circulation. Genomic and Precision... Jan 2018Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk...
Chemotherapy-related cardiac dysfunction is a significant side effect of anticancer treatment. Risk stratification is based on clinical- and treatment-related risk factors that do not adequately explain individual susceptibility. The addition of genetic variants may improve risk assessment. We conducted a systematic literature search in PubMed and Embase, to identify studies investigating genetic risk factors for chemotherapy-related cardiac dysfunction. Included were articles describing genetic variants in humans altering susceptibility to chemotherapy-related cardiac dysfunction. The validity of identified studies was assessed by 10 criteria, including assessment of population stratification, statistical methodology, and replication of findings. We identified 40 studies: 34 exploring genetic risk factors for anthracycline-induced cardiotoxicity (n=9678) and 6 studies related to trastuzumab-associated cardiotoxicity (n=642). The majority (35/40) of studies had a candidate gene approach, whereas 5 genome-wide association studies have been performed. We identified 25 genetic variants in 20 genes and 2 intergenic variants reported significant at least once. The overall validity of studies was limited, with small cohorts, failure to assess population ancestry and lack of replication. SNPs with the most robust evidence up to this point are rs1786814 (sarcomere structure and function), rs2229774 (topoisomerase-2β expression), rs7853758 (drug transport), rs17863783 (drug metabolism), and 1 intergenic variant (rs28714259). Existing evidence supports the hypothesis that genetic variation contributes to chemotherapy-related cardiac dysfunction. Although many variants identified by this systematic review show potential to improve risk stratification, future studies are necessary for validation and assessment of their value in a diagnostic and prognostic setting.
Topics: Anthracyclines; Antibiotics, Antineoplastic; CELF Proteins; Genetic Variation; Genome-Wide Association Study; Heart Diseases; Humans; Neoplasms; Receptors, Retinoic Acid; Risk; Retinoic Acid Receptor gamma
PubMed: 29557343
DOI: 10.1161/CIRCGEN.117.001753 -
Sports Medicine (Auckland, N.Z.) May 2017Resistance training is an integral component of physical preparation for athletes. A growing body of evidence indicates that eccentric strength training methods induce... (Review)
Review
BACKGROUND
Resistance training is an integral component of physical preparation for athletes. A growing body of evidence indicates that eccentric strength training methods induce novel stimuli for neuromuscular adaptations.
OBJECTIVE
The purpose of this systematic review was to determine the effects of eccentric training in comparison to concentric-only or traditional (i.e. constrained by concentric strength) resistance training.
METHODS
Searches were performed using the electronic databases MEDLINE via EBSCO, PubMed and SPORTDiscus via EBSCO. Full journal articles investigating the long-term (≥4 weeks) effects of eccentric training in healthy (absence of injury or illness during the 4 weeks preceding the training intervention), adult (17-35 years), human participants were selected for the systematic review. A total of 40 studies conformed to these criteria.
RESULTS
Eccentric training elicits greater improvements in muscle strength, although in a largely mode-specific manner. Superior enhancements in power and stretch-shortening cycle (SSC) function have also been reported. Eccentric training is at least as effective as other modalities in increasing muscle cross-sectional area (CSA), while the pattern of hypertrophy appears nuanced and increased CSA may occur longitudinally within muscle (i.e. the addition of sarcomeres in series). There appears to be a preferential increase in the size of type II muscle fibres and the potential to exert a unique effect upon fibre type transitions. Qualitative and quantitative changes in tendon tissue that may be related to the magnitude of strain imposed have also been reported with eccentric training.
CONCLUSIONS
Eccentric training is a potent stimulus for enhancements in muscle mechanical function, and muscle-tendon unit (MTU) morphological and architectural adaptations. The inclusion of eccentric loads not constrained by concentric strength appears to be superior to traditional resistance training in improving variables associated with strength, power and speed performance.
Topics: Adaptation, Physiological; Adolescent; Adult; Exercise; Humans; Muscle Contraction; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Physical Education and Training; Resistance Training
PubMed: 27647157
DOI: 10.1007/s40279-016-0628-4 -
The Canadian Journal of Cardiology Nov 2015Genetic investigations have established that mutations in proteins of the contractile unit of the myocardium, known as the sarcomere, may be associated with hypertrophic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Genetic investigations have established that mutations in proteins of the contractile unit of the myocardium, known as the sarcomere, may be associated with hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and dilated cardiomyopathy (DCM). It has become clinical practice to offer genetic testing in affected individuals to identify causative mutations, which provides the basis for presymptomatic testing of relatives who are at risk of disease development. This ensures adequate clinical follow-up of mutation carriers, whereas noncarriers can be discharged. However, before genetic testing can be used for individual risk assessment and prediction of prognosis, it is important to investigate if there is a relation between the clinical disease expression (phenotype) of the condition and mutations in specific disease genes (genotype).
METHODS
We reviewed the literature in relation to phenotypic features reported to be associated with mutations in cardiac troponin I (cTnI; TNNI3), which is a recognized sarcomeric disease gene in all 3 cardiomyopathies.
RESULTS
The results of this review did not identify specific genotype-phenotype relations in HCM or DCM, and cTnI appeared to be the most frequent disease gene in RCM.
CONCLUSIONS
To further explore if there is a genotype-phenotype relation, long-term follow-up studies are needed. It is essential to investigate the natural history of the condition among affected individuals and to provide clinical follow-up on disease development among healthy mutation carriers. Such information is required to provide evidence-based counselling for affected families and to elucidate if knowledge about specific genotypes can be used in future risk prediction models.
Topics: Cardiomyopathies; DNA; Genetic Testing; Genotype; Humans; Mutation; Phenotype; Troponin I
PubMed: 26440512
DOI: 10.1016/j.cjca.2015.06.015