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1.
Med Clin North Am ; 103(6): 1005-1019, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582001

RESUMO

Heritable thoracic aortic disease (HTAD) can have life-threatening consequences if not diagnosed early. Affected individuals and at-risk family members benefit from both cardiology and genetic evaluations, including genetic testing. Important information can be obtained through family history, medical history, and genetic testing to help guide management and assess risk. A genetic diagnosis can guide cardiovascular management (type and frequency of vascular imaging, timing of surgical intervention), risk assessment for arterial aneurysm/dissection, evaluation of nonvascular features, and familial testing.


Assuntos
Aorta Torácica/anormalidades , Doenças da Aorta , Testes Genéticos/métodos , Administração dos Cuidados ao Paciente/métodos , Doenças da Aorta/genética , Doenças da Aorta/terapia , Humanos , Medicina de Precisão/métodos
2.
Med Clin North Am ; 103(6): 1077-1092, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582005

RESUMO

Compared to clinicians previously surveyed, primary care providers employed in a health system known for clinical genomics were more likely to have ordered or referred a patient for genetic testing, but had only modestly more genetics training and reported similarly low levels of comfort answering patient questions about genetic risk. Most supported population genomic screening, reported willingness to get screened themselves, and judged a hypothetical patient's decision to be screened favorably relative to a similar patient's decision to decline screening. Stakeholder perceptions of the ethical appropriateness of nudging at-risk patients to discuss testing with counselors were mixed.


Assuntos
Aconselhamento Genético , Testes Genéticos/métodos , Atenção Primária à Saúde , Aconselhamento Genético/ética , Aconselhamento Genético/métodos , Aconselhamento Genético/psicologia , Humanos , Medicina de Precisão/métodos , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/tendências , Sequenciamento Completo do Exoma
3.
Cancer Radiother ; 23(6-7): 773-777, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471250

RESUMO

The conservative treatment of squamous cell carcinoma of anal canal by irradiation is recommended as first indication. Despite its rarity, significant improvements were obtained by retrospective or prospective clinical studies these 20 past years, evaluating concomitant chemotherapy and IMRT. Nevertheless, the individualisation of the treatment, over dose distribution, has poor data available. Fractionation remains classic (1.8-2.0Gy/Fr), but the optimal dose level remains under discussion. The strategy concerning the volumes and doses for the prophylactic volumes remains under discussion. This paper will describe the data published, and the recommendations of working Groups, and the main options under evaluation. To conclude, today only the absence of gap is recommended, the benefit of a one-step schedule reducing the treatment time, then increasing local control and survival, but personalised schedules remain under investigation.


Assuntos
Neoplasias do Ânus/radioterapia , Carcinoma de Células Escamosas/radioterapia , Irradiação Linfática/métodos , Medicina de Precisão/métodos , Neoplasias do Ânus/patologia , Carcinoma de Células Escamosas/patologia , Tratamento Conservador/métodos , Humanos , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos
5.
Expert Opin Drug Saf ; 18(11): 1009-1015, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31478396

RESUMO

Introduction: Therapeutic drug monitoring in oncology is used to prevent major toxicities of selected anticancer agents due to overexposure by individualizing the dose based on a pharmacokinetic target. Areas covered: Numerous studies relating a relation between pharmacokinetic variability and toxicity have been reported since the eighties but very few have been implemented in clinical practice due to a lack of validation and harmonization, logistical constraints and reluctance from oncologists. Following recent recommendations, this paper highlights the current-validated applications of pharmacokinetic monitoring in oncology focusing on the safety of anticancer therapies. Expert opinion: Paradoxically given the oldness of the agents, guidelines of dose adjustment have been recently available for intravenous busulfan, 5-fluorouracil, and high-dose methotrexate. Interestingly, besides the enhancement of tolerability, it applies to potential curative clinical situations. In an era of personalized oncology that integrates complex molecular factors in the treatment of cancer, education is needed for oncologists to show the benefits of this valuable (even old) resource for the safety of patients. Therapeutic drug monitoring for busulfan, 5-fluorouracil and methotrexate will still hold in the future unless more active agents are available in the concerned indications.


Assuntos
Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/farmacocinética , Relação Dose-Resposta a Droga , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Metotrexato/farmacocinética , Guias de Prática Clínica como Assunto , Medicina de Precisão/métodos
6.
Expert Opin Investig Drugs ; 28(10): 891-902, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31550938

RESUMO

Introduction: Alpha-1 antitrypsin deficiency (AATD) is most often associated with chronic lung disease, early onset emphysema, and liver disease. The standard of care in lung disease due to AATD is alpha-1 antitrypsin augmentation but there are several new and emerging treatment options under investigation for both lung and liver manifestations. Areas covered: We review therapeutic approaches to lung and liver disease in alpha-1 antitrypsin deficiency (AATD) and the agents in clinical development according to their mode of action. The focus is on products in clinical trials, but data from pre-clinical studies are described where relevant, particularly where progression to trials appears likely. Expert opinion: Clinical trials directed at lung and liver disease separately are now taking place. Multimodality treatment may be the future, but this could be limited by treatment costs. The next 5-10 years may reveal new guidance on when to use therapeutics for slowing disease progression with personalized treatment regimes coming to the forefront.


Assuntos
Desenvolvimento de Medicamentos/métodos , Drogas em Investigação/administração & dosagem , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Animais , Progressão da Doença , Drogas em Investigação/farmacologia , Humanos , Hepatopatias/tratamento farmacológico , Hepatopatias/etiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Medicina de Precisão/métodos , Deficiência de alfa 1-Antitripsina/fisiopatologia
7.
Gene ; 718: 144050, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31425740

RESUMO

Individual specific variable drug response against similar drugs raises a significant challenge for the effective and safe treatment of many human diseases. Pharmacogenomics is the branch which try to deal with these challenge by relating drug response to patient specific genome in order to better customize patient treatments. Pharmacogenomics based research focus on the whole genome, but since last few years after realizing the importance, it mainly centralized towards genes of pharmacological importance called pharmacogenes, and try to explore association between their variants and variable drug response in world's different population. This research was initiated with the resulted data from human genome based research projects and later on assisted by exome sequencing projects. Simultaneously, it was boost-up with the participation of various pharmacogenomics groups lead by PGRN. By realizing the significance of pharmacogenes, and their variant related information, in health science, scientific communities are already started to look for genes of pharmacogenomics importance with different aspect. This article aims to provide an inclusive insight on current state of knowledge of pharmacogenes, recent trends and progress in the understanding of the pharmacogenes and the implications for personalized medicine.


Assuntos
Genoma Humano , Farmacogenética/métodos , Farmacogenética/tendências , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Humanos
8.
Lancet ; 394(10198): 604-610, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31395443

RESUMO

Human genomic sequencing has potential diagnostic, prognostic, and therapeutic value across a wide breadth of clinical disciplines. One barrier to widespread adoption is the paucity of evidence for improved outcomes in patients who do not already have an indication for more focused testing. In this Series paper, we review clinical outcome studies in genomic medicine and discuss the important features and key challenges to building evidence for next generation sequencing in the context of routine patient care.


Assuntos
Genômica/métodos , Medicina de Precisão/métodos , Testes Diagnósticos de Rotina , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Avaliação de Resultados da Assistência ao Paciente , Padrão de Cuidado
9.
Clin Exp Rheumatol ; 37 Suppl 118(3): 175-184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464663

RESUMO

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease with diverse clinical picture and outcome. The disease affects primarily middle-aged females and involves the exocrine glands leading to dry mouth and eyes. When the disease extends beyond the exocrine glands (systemic form), certain extraglandular manifestations involving liver, kidney, lungs, peripheral nervous system and the skin may occur. Primary SS is considered the crossroad between autoimmunity and lymphoproliferation, since approximately 5% of patients develop NHL associated lymphomas. As with every chronic disease with complex aetiopathogenesis and clinical heterogeneity, pSS has certain unmet needs that have to be addressed: a) classification and stratification of patients; b) understanding the distinct pathogenetic mechanisms and clinical phenotypes; c) defining and interpreting the real needs of patients regarding the contemporary diagnostic and therapeutic approaches; d) physician and patients' training regarding the wide spectrum of the disease; e) creating common policies across European countries to evaluate and manage SS patients. To achieve these goals, an intense effort is being currently undertaken by the HarmonicSS consortium in order to harmonise and integrate the largest European cohorts of pSS patients. In this review, we present an overview of our perception and vision, as well as new issues arising from this project such as harmonisation protocols and procedures, data sharing principles and various ethical and legal issues originating from these approaches.


Assuntos
Medicina de Precisão/métodos , Síndrome de Sjogren , Xerostomia , Autoimunidade , Europa (Continente) , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/genética
11.
Cancer Radiother ; 23(6-7): 778-783, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31378461

RESUMO

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.


Assuntos
Neoplasias da Mama/radioterapia , Medicina de Precisão/métodos , Lesões por Radiação/etiologia , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Fracionamento da Dose de Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Órgãos em Risco/efeitos da radiação , Tolerância a Radiação , Medição de Risco , Carga Tumoral
12.
Lancet ; 394(10197): 511-520, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31395439

RESUMO

Advances in technologies for assessing genomic variation and an increasing understanding of the effects of genomic variants on health and disease are driving the transition of genomics from the research laboratory into clinical care. Genomic medicine, or the use of an individual's genomic information as part of their clinical care, is increasingly gaining acceptance in routine practice, including in assessing disease risk in individuals and their families, diagnosing rare and undiagnosed diseases, and improving drug safety and efficacy. We describe the major types and measurement tools of genomic variation that are currently of clinical importance, review approaches to interpreting genomic sequence variants, identify publicly available tools and resources for genomic test interpretation, and discuss several key barriers in using genomic information in routine clinical practice.


Assuntos
Genômica/métodos , Medicina de Precisão/métodos , Predisposição Genética para Doença , Humanos , Variantes Farmacogenômicos
13.
Presse Med ; 48(7-8 Pt 1): 859-870, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447331

RESUMO

Non-follicular small cell lymphomas include several entities whose clinical and pathological descriptions have been refined in the last 20 years. MALT lymphoma, developed at the expense of lymphoid tissue associated with the mucosa, is usually localized to a given organ, but can also disseminate. Some patients with MALT lymphoma can be treated by eradicating the associated infectious agent, whereas local treatment should be preferred for other cases ; disseminated forms and relapsed patients are eligible for anti-CD20 antibodies associated with cytotoxic agents. Patients with mantle cell lymphoma have benefited from many advances, including the use of cytarabine and bendamustine, anti-CD20 antibodies, intensive treatments (autograft) and recently targeted therapy (ibrutinib, inhibitor or the Bruton tyrosine kinase). Patients with splenic nodal marginal zone lymphomas should be evaluated for different options, of which immunochemotherapy remains important. For all these entities, the implementation of treatments may be delayed by several years for certain groups of patients. Although considered as incurable, the prognosis of these pathologies has improved significantly and the majority of patients will be able to live for many years with often treatment-free intervals.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Fatores Etários , Idade de Início , Anticorpos Monoclonais/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma de Zona Marginal Tipo Células B/classificação , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/epidemiologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
14.
Presse Med ; 48(7-8 Pt 1): 850-858, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447334

RESUMO

Follicular lymphoma, the second most common lymphoma, is characterized by its slow growth and is often considered incurable in advanced stages. Progresses in biology have contributed to better understand the complex and successive mechanisms of development of this pathology, whose diagnosis is based on a lymph node biopsy. However, the prognosis of the patients is heterogeneous and several indexes have been proposed to identify groups of patients with a similar life expectancy, in order to guide the therapeutic choices. The treatment has been modified in the last 20 years by the emergence of anti-CD20 monoclonal antibodies which constitute, alone or in combination, of the cornerstone of therapeutic management. After staging using, in particular, 18-fluorodeoxyglucose positron emission tomography, the therapeutic strategy will be adapted for each patient, ranging from simple watchful waiting to a combination of chemotherapy and anti-CD20 antibodies. Relapses (which often require a new lymph node biopsy to eliminate a possible histological transformation into an aggressive lymphoma with poorer prognosis) remain common but are still accessible to effective therapeutic interventions. Thanks to these advances, the median life expectancy of patients with follicular lymphoma now exceeds 15 years.


Assuntos
Linfoma Folicular , Biópsia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia/métodos , Imunoterapia/tendências , Expectativa de Vida , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Taxa de Sobrevida , Terapias em Estudo/métodos , Terapias em Estudo/tendências
15.
Vet Clin North Am Small Anim Pract ; 49(5): 809-818, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31256903

RESUMO

We introduce a next phase in the evolution of medicine affecting human and veterinary patients. This evolution, genomic cancer medicine (Pmed), involves expansion of genomic and molecular biology into clinical medicine. The implementation of these new technologies has already begun and is a commercial reality. We introduce the underpinnings for this evolution, and focus on application in complex disease states. Pet owners have begun requesting Pmed technologies. To meet this demand, it is important to be aware of the opportunities and obstacles associated with available Pmed offerings as well as the current state of the field.


Assuntos
Doenças do Gato/genética , Doenças do Gato/terapia , Doenças do Cão/genética , Doenças do Cão/terapia , Neoplasias/veterinária , Medicina de Precisão/veterinária , Animais , Gatos , Cães , Predisposição Genética para Doença , Genômica/métodos , Hemangiossarcoma/genética , Hemangiossarcoma/terapia , Hemangiossarcoma/veterinária , Humanos , Neoplasias/genética , Neoplasias/terapia , Medicina de Precisão/métodos , Análise de Sequência , Medicina Veterinária/métodos
16.
Expert Rev Clin Pharmacol ; 12(9): 885-891, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31305158

RESUMO

Introduction: Secondary loss of response to anti-tumor necrosis factor (TNF) therapy remains a challenge in the clinical management of inflammatory bowel disease (IBD) patients. A frequently observed reason for secondary loss of response to TNF blockers is inadequate drug exposure and sub-therapeutic serum drug concentrations. Areas covered: This review presents an overview of recent research on therapeutic drug monitoring (TDM)-based dosing with anti-TNF agents in IBD. The role of reactive and proactive TDM and different approaches on how to optimize anti-TNF treatment are discussed. Expert opinion: Due to variations within and between patients, the 'one size fits all' theory does not apply to all IBD patients receiving anti-TNF agents. Timing of TDM (i.e. reactive versus proactive) is a matter of debate. Both strategies might optimize anti-TNF treatment, although most trials did not show a clinical benefit compared to conventional dosing up to now. So-called dashboard systems might have an additive value in the optimization of anti-TNF treatment, since these tools enable clinicians to really personalize anti-TNF treatment.


Assuntos
Monitoramento de Medicamentos/métodos , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Relação Dose-Resposta a Droga , Fármacos Gastrointestinais/farmacologia , Humanos , Medicina de Precisão/métodos , Fatores de Tempo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
Nat Commun ; 10(1): 3101, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308377

RESUMO

The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.


Assuntos
Adenocarcinoma/genética , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Esofágicas/genética , Perfilação da Expressão Gênica/métodos , Medicina de Precisão/métodos , Antineoplásicos/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Biologia Computacional/métodos , Conjuntos de Dados como Assunto , Progressão da Doença , Dosagem de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Instabilidade Genômica , Humanos , Aprendizado de Máquina , Modelos Genéticos , Família Multigênica/efeitos dos fármacos , Taxa de Mutação , Polimorfismo de Nucleotídeo Único
20.
Br J Radiol ; 92(1102): 20190209, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31265322

RESUMO

Nasopharyngeal carcinoma (NPC) is a malignancy with unique clinical biological profiles such as associated Epstein-Barr virus infection and high radiosensitivity. Radiotherapy has long been recognized as the mainstay for the treatment of NPC. However, the further efficacy brought by radical radiotherapy has reached the bottleneck in advanced patients, who are prone to develop recurrence and distant metastasis after treatment. The application of photon therapy makes it possible for radiation dose escalation in refractory cases and may provide second chance for recurrent patients with less unrecoverable tissue damage. The concept of adaptive radiotherapy is put forward in consideration of target volume shrinkage during treatment. The replanning procedure offers better protection for the organ at risk. However, the best timing and candidates for adaptive radiotherapy is still under debate. The current tendency of artificial intelligence in NPC mainly focuses on image recognition, auto-segmentation and dose prediction. Although artificial intelligence is still in developmental stage, the future of it is promising.To further improve the efficacy of NPC, multimodality treatment is encouraged. In-depth studies on genetic and epigenetic variations help to explain the great heterogeneity among patients, and could further be applied to precise screening and prediction, personalized radiotherapy and the evolution of targeted drugs. Given the clinical benefit of immunotherapy in other cancers, the application of immunotherapy, especially immune checkpoint inhibitor, in NPC is also of great potential. Results from ongoing clinical trials combining immunotherapy with radiotherapy in NPC are expected.


Assuntos
Inteligência Artificial , Previsões , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Inteligência Artificial/tendências , Humanos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Carcinoma Nasofaríngeo/mortalidade , Neoplasias Nasofaríngeas/mortalidade , Órgãos em Risco/efeitos da radiação , Medicina de Precisão/métodos , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Radioterapia/métodos , Radioterapia de Intensidade Modulada/métodos
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