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1.
Hum Genomics ; 14(1): 35, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008459

RESUMO

Precision medicine aims to empower clinicians to predict the most appropriate course of action for patients with complex diseases like cancer, diabetes, cardiomyopathy, and COVID-19. With a progressive interpretation of the clinical, molecular, and genomic factors at play in diseases, more effective and personalized medical treatments are anticipated for many disorders. Understanding patient's metabolomics and genetic make-up in conjunction with clinical data will significantly lead to determining predisposition, diagnostic, prognostic, and predictive biomarkers and paths ultimately providing optimal and personalized care for diverse, and targeted chronic and acute diseases. In clinical settings, we need to timely model clinical and multi-omics data to find statistical patterns across millions of features to identify underlying biologic pathways, modifiable risk factors, and actionable information that support early detection and prevention of complex disorders, and development of new therapies for better patient care. It is important to calculate quantitative phenotype measurements, evaluate variants in unique genes and interpret using ACMG guidelines, find frequency of pathogenic and likely pathogenic variants without disease indicators, and observe autosomal recessive carriers with a phenotype manifestation in metabolome. Next, ensuring security to reconcile noise, we need to build and train machine-learning prognostic models to meaningfully process multisource heterogeneous data to identify high-risk rare variants and make medically relevant predictions. The goal, today, is to facilitate implementation of mainstream precision medicine to improve the traditional symptom-driven practice of medicine, and allow earlier interventions using predictive diagnostics and tailoring better-personalized treatments. We strongly recommend automated implementation of cutting-edge technologies, utilizing machine learning (ML) and artificial intelligence (AI) approaches for the multimodal data aggregation, multifactor examination, development of knowledgebase of clinical predictors for decision support, and best strategies for dealing with relevant ethical issues.


Assuntos
Infecções por Coronavirus/genética , Diabetes Mellitus/genética , Neoplasias/genética , Pneumonia Viral/genética , Medicina de Precisão/tendências , Cardiomiopatias , Infecções por Coronavirus/epidemiologia , Análise de Dados , Diabetes Mellitus/epidemiologia , Genômica/tendências , Humanos , Metabolômica/tendências , Neoplasias/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Proteômica/tendências
2.
Rev Med Suisse ; 16(704): 1574-1578, 2020 Sep 02.
Artigo em Francês | MEDLINE | ID: mdl-32880115

RESUMO

Precision medicine aims to tailor prevention and treatment to individual data. Although different markers can be used (e.g. transcriptome or proteome), its rise is closely linked to that of genomics, owing to the henceforth reasonable cost of DNA sequencing. The enormous datasets thus generated can be exploited due to remarkable advances in bioinformatics and information sciences. However, beyond the technological endeavor, humanities and social sciences also play a central role to redefine health and illness. The precision medicine unit at CHUV gathers stakeholders from these various domains in order to demonstrate the utility of precision medicine and catalyze its integration into healthcare, to the benefit of the patient.


Assuntos
Genômica , Ciências Humanas , Informática Médica , Biologia Molecular , Medicina de Precisão/tendências , Humanos
4.
Br J Radiol ; 93(1114): 20200183, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795176

RESUMO

The first hospital-based treatment facilities for particle therapy started operation about thirty years ago. Since then, the clinical experience with protons and carbon ions has grown continuously and more than 200,000 patients have been treated to date. The promising clinical results led to a rapidly increasing number of treatment facilities and many new facilities are planned or under construction all over the world. An inverted depth-dose profile combined with potential radiobiological advantages make charged particles a precious tool for the treatment of tumours that are particularly radioresistant or located nearby sensitive structures. A rising number of trials have already confirmed the benefits of particle therapy in selected clinical situations and further improvements in beam delivery, image guidance and treatment planning are expected. This review summarises some physical and biological characteristics of accelerated charged particles and gives some examples of their clinical application. Furthermore, challenges and future perspectives of particle therapy will be discussed.


Assuntos
Medicina de Precisão/tendências , Radioterapia (Especialidade)/tendências , Radioterapia de Alta Energia/tendências , Humanos , Aceleradores de Partículas , Terapia com Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador
5.
Am J Psychiatry ; 177(8): 671-685, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32741287

RESUMO

Major depressive disorder is a remarkably common and often severe psychiatric disorder associated with high levels of morbidity and mortality. Patients with major depression are prone to several comorbid psychiatric conditions, including posttraumatic stress disorder, anxiety disorders, obsessive-compulsive disorder, and substance use disorders, and medical conditions, including cardiovascular disease, diabetes, stroke, cancer, which, coupled with the risk of suicide, result in a shortened life expectancy. The goal of this review is to provide an overview of our current understanding of major depression, from pathophysiology to treatment. In spite of decades of research, relatively little is known about its pathogenesis, other than that risk is largely defined by a combination of ill-defined genetic and environmental factors. Although we know that female sex, a history of childhood maltreatment, and family history as well as more recent stressors are risk factors, precisely how these environmental influences interact with genetic vulnerability remains obscure. In recent years, considerable advances have been made in beginning to understand the genetic substrates that underlie disease vulnerability, and the interaction of genes, early-life adversity, and the epigenome in influencing gene expression is now being intensively studied. The role of inflammation and other immune system dysfunction in the pathogenesis of major depression is also being intensively investigated. Brain imaging studies have provided a firmer understanding of the circuitry involved in major depression, providing potential new therapeutic targets. Despite a broad armamentarium for major depression, including antidepressants, evidence-based psychotherapies, nonpharmacological somatic treatments, and a host of augmentation strategies, a sizable percentage of patients remain nonresponsive or poorly responsive to available treatments. Investigational agents with novel mechanisms of action are under active study. Personalized medicine in psychiatry provides the hope of escape from the current standard trial-and-error approach to treatment, moving to a more refined method that augurs a new era for patients and clinicians alike.


Assuntos
Transtorno Depressivo Maior , Gerenciamento Clínico , Comorbidade , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/imunologia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Interação Gene-Ambiente , Humanos , Neuroimagem/métodos , Medicina de Precisão/tendências , Fatores de Risco
6.
PLoS One ; 15(7): e0234387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609781

RESUMO

In this article, we studied geographic variation in the use of personalized genetic testing for advanced non-small cell lung cancer (NSCLC) and we evaluated the relationship between genetic testing rates and local socioeconomic and ecological variables. We used data on all advanced NSCLC patients who had a genetic test between April 2012 and April 2013 in France in the frame of the IFCT Biomarqueurs-France study (n = 15814). We computed four established measures of geographic variation of the sex-adjusted rates of genetic testing utilization at the "départment" (the French territory is divided into 94 administrative units called 'départements') level. We also performed a spatial regression model to determine the relationship between département-level sex-adjusted rates of genetic testing utilization and economic and ecological variables. Our results are the following: (i) Overall, 46.87% lung cancer admission patients obtained genetic testing for NSCLC; département-level utilization rates varied over 3.2-fold. Measures of geographic variation indicated a relatively high degree of geographic variation. (ii) there was a statistically significant relationship between genetic testing rates and per capita supply of general practitioners, radiotherapists and surgeons (negative correlation for the latter); lower genetic testing rates were also associated with higher local poverty rates. French policymakers should pursue effort toward deprived areas to obtain equal access to personalized medicine for advanced NSCLC patients.


Assuntos
Acesso aos Serviços de Saúde/tendências , Medicina de Precisão/economia , Medicina de Precisão/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/genética , Bases de Dados Factuais , Feminino , França , Testes Genéticos/tendências , Acesso aos Serviços de Saúde/economia , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade
9.
Mol Cell ; 78(6): 1002-1018, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32559422

RESUMO

We are witnessing several revolutionary technological advances in cancer. These innovations have not only contributed to a growing understanding of the tumor and its microenvironment but also uncovered an increasing array of new therapeutic targets. For most advanced cancers, therapy resistance limits the benefit of single-agent therapies. Therefore, some 5,000 clinical trials are ongoing globally to probe the clinical benefit of new combination treatments. However, the possibilities to combine individual treatments dramatically outnumber the patients available to enroll in clinical trials. This comes at a potential cost of missed opportunities, clinical failure, avoidable toxicity, insufficient patient accrual, and financial loss. A solution may be to design combination therapies more rationally, which are informed by fundamental biological and mechanistic insight. We will discuss some successes and failures of current treatment combinations, as well as interesting emerging preclinical concepts that warrant clinical exploration.


Assuntos
Quimioterapia Combinada/tendências , Neoplasias/terapia , Drogas Desenhadas/uso terapêutico , Humanos , Neoplasias/metabolismo , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Microambiente Tumoral/efeitos dos fármacos
12.
Value Health ; 23(5): 529-539, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32389217

RESUMO

Precision medicine is a dynamic area embracing a diverse and increasing type of approaches that allow the targeting of new medicines, screening programs or preventive healthcare strategies, which include the use of biologic markers or complex tests driven by algorithms also potentially taking account of patient preferences. The International Society for Pharmacoeconomics and Outcome Research expanded its current work around precision medicine to (1) describe the evolving paradigm of precision medicine with examples of current and evolving applications, (2) describe key stakeholders perspectives on the value of precision medicine in their respective domains, and (3) define the core factors that should be considered in a value assessment framework for precision medicine. With the ultimate goal of improving health of well-defined patient groups, precision medicine will affect all stakeholders in the healthcare system at multiple levels spanning the individual perspective to the societal perspective. For an efficient, timely and practical precision medicine value assessment framework, it will be important to address these multiple perspectives through building consensus among the stakeholders for robust procedures and measures of value aspects, including performance of precision mechanism; aligned reimbursement processes of precision mechanism and subsequent treatment; transparent expectations for evidence requirements and study designs adequately matched to the intended use of the precision mechanism and to the smaller target patient populations; recognizing the potential range of value-generation such as ruling-in and ruling-out decisions.


Assuntos
Farmacoeconomia , Medicina de Precisão/tendências , Avaliação da Tecnologia Biomédica , Humanos
13.
Crit Rev Oncol Hematol ; 151: 102977, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32446181

RESUMO

At present, hemato-oncologic diagnostics is facing dynamic changes. This applies to the exploration and introduction of novel technologies such as next-generation sequencing or digital droplet PCR for myeloid and lymphatic malignancies in laboratory routine, or liquid biopsy for patients with lymphoid malignancies. Targeted therapies such as FLT3 or IDH1/IDH2 inhibitors for acute myeloid leukemia are entering clinical practice. Thus, the demand for hematologic precision diagnostics both at initial diagnosis and during the course of the disease are equally increasing, and a short turn-around time becomes crucial. NGS expands the armamentarium for minimal residual disease diagnostics, but novel questions arise relating to sensitivity, the appropriate time points of this analysis, or the thresholds triggering therapeutic interventions. In this review article, we summarize some of the most relevant current changes and subsequent challenges for diagnostics in various myeloid and lymphatic malignancies. Future directions of hemato-oncologic diagnostics in the next 5-10 years are highlighted.


Assuntos
Testes Diagnósticos de Rotina/tendências , Testes Genéticos/tendências , Neoplasias Hematológicas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Mieloide Aguda/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Medicina de Precisão/tendências , Testes Genéticos/métodos , Genômica/métodos , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Síndromes Mielodisplásicas/genética , Neoplasia Residual
14.
Curr Opin Anaesthesiol ; 33(3): 463-474, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371636

RESUMO

PURPOSE OF REVIEW: The present review examines how targeted approaches to care, based on individual variability in patient characteristics, could be applied in the perioperative setting. Such an approach would enhance individualized risk assessment and allow for targeted preventive and therapeutic decision-making in patients at increased risk for adverse perioperative events. RECENT FINDINGS: Prior and current studies highlight valuable lessons on how future investigations attempting to link specific patient-related characteristics or treatment modalities with outcomes and adverse drug responses might be designed in the perioperative setting. SUMMARY: Our review highlights the past, present, and future directions of perioperative precision medicine. Current evidence provides important lessons on how a specific patient and disease tailored approach can help perioperative physicians in delivering the most appropriate and safest perioperative care.


Assuntos
Assistência Perioperatória , Medicina de Precisão , Humanos , Assistência Perioperatória/tendências , Medicina de Precisão/tendências , Medição de Risco
15.
Lancet Neurol ; 19(6): 522-532, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32470424

RESUMO

Advances in DNA sequencing technologies have resulted in a near doubling, in under 10 years, of the number of causal genes identified for inherited neuromuscular disorders. However, around half of patients, whether children or adults, do not receive a molecular diagnosis after initial diagnostic workup. Massively parallel technologies targeting RNA, proteins, and metabolites are being increasingly used to diagnose these unsolved cases. The use of these technologies to delineate pathways, biomarkers, and therapeutic targets has led to new approaches entering the drug development pipeline. However, these technologies might give rise to misleading conclusions if used in isolation, and traditional techniques including comprehensive neurological evaluation, histopathology, and biochemistry continue to have a crucial role in diagnostics. For optimal diagnosis, prognosis, and precision medicine, no single ruling technology exists. Instead, an interdisciplinary approach combining novel and traditional neurological techniques with computer-aided analysis and international data sharing is needed to advance the diagnosis and treatment of neuromuscular disorders.


Assuntos
Pesquisa Interdisciplinar/tendências , Doenças Neuromusculares/diagnóstico , Doenças Neuromusculares/genética , Humanos , Pesquisa Interdisciplinar/métodos , Doenças Neuromusculares/terapia , Medicina de Precisão/tendências , Prognóstico , Análise de Sequência de DNA
16.
Nat Rev Endocrinol ; 16(6): 305-320, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32235875

RESUMO

The specific metabolic contribution of consuming different energy-yielding macronutrients (namely, carbohydrates, protein and lipids) to obesity is a matter of active debate. In this Review, we summarize the current research concerning associations between the intake of different macronutrients and weight gain and adiposity. We discuss insights into possible differential mechanistic pathways where macronutrients might act on either appetite or adipogenesis to cause weight gain. We also explore the role of dietary macronutrient distribution on thermogenesis or energy expenditure for weight loss and maintenance. On the basis of the data discussed, we describe a novel way to manage excessive body weight; namely, prescribing personalized diets with different macronutrient compositions according to the individual's genotype and/or enterotype. In this context, the interplay of macronutrient consumption with obesity incidence involves mechanisms that affect appetite, thermogenesis and metabolism, and the outcomes of these mechanisms are altered by an individual's genotype and microbiota. Indeed, the interactions of the genetic make-up and/or microbiota features of a person with specific macronutrient intakes or dietary pattern consumption help to explain individualized responses to macronutrients and food patterns, which might represent key factors for comprehensive precision nutrition recommendations and personalized obesity management.


Assuntos
Nutrientes/fisiologia , Obesidade/dietoterapia , Obesidade/etiologia , Medicina de Precisão/tendências , Animais , Dieta , Dieta Redutora , Metabolismo Energético/fisiologia , Humanos , Estado Nutricional , Obesidade/epidemiologia , Medicina de Precisão/métodos
17.
Urol Clin North Am ; 47(2): 245-255, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32272996

RESUMO

Personalized medicine gathers the most relevant data involved in human health. Currently, the diagnosis of male infertility is limited to spermiogram, which does not provide information on the male fertile potential. New diagnostic methods are required. The application of omics techniques in the study of male reproductive health renders a huge amount of data providing numerous novel infertility biomarkers, from genes to metabolites, to diagnose the cause of male infertility. Recent studies hold the promise that these biomarkers will allow a noninvasive infertility diagnosis and the improvement of the sperm selection techniques.


Assuntos
Infertilidade Masculina/etiologia , Infertilidade Masculina/terapia , Medicina de Precisão , Biomarcadores/análise , Genômica , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Metabolômica , Medicina de Precisão/tendências , Espermatogênese/fisiologia
18.
Thorac Surg Clin ; 30(2): 121-125, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32327170

RESUMO

Almost a half of patients diagnosed with nonesmall-cell lung cancer (NSCLC) present with incurable disease, and a significant number of patients who are treated with curative intent for early-stage disease will eventually recur. Systemic therapy is selected based on tumor histology, squamous versus nonsquamous NSCLC, molecular testing, and PD-L1 score. Depending on PD-L1 score, patients are eligible for immunotherapy alone or in combination with chemotherapy in the first-line setting. Oncogenic driver mutations can be detected in approximately 50% of patients with nonsquamous NSCLC of which several can be targeted therapeutically with small molecular inhibitors. Continued research is needed for more specific agents with less toxicity and better central nervous system penetration, and agents to treat patients who develop resistance against targeted treatments and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Farmacogenética , Medicina de Precisão/métodos , Medicina de Precisão/tendências
19.
Lancet ; 395(10229): 1078-1088, 2020 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222192

RESUMO

The identification of molecular targets and the growing knowledge of their cellular functions have led to the development of small molecule inhibitors as a major therapeutic class for cancer treatment. Both multitargeted and highly selective kinase inhibitors are used for the treatment of advanced treatment-resistant cancers, and many have also achieved regulatory approval for early clinical settings as adjuvant therapies or as first-line options for recurrent or metastatic disease. Lessons learned from the development of these agents can accelerate the development of next-generation inhibitors to optimise the therapeutic index, overcome drug resistance, and establish combination therapies. The future of small molecule inhibitors is promising as there is the potential to investigate novel difficult-to-drug targets, to apply predictive non-clinical models to select promising drug candidates for human evaluation, and to use dynamic clinical trial interventions with liquid biopsies to deliver precision medicine.


Assuntos
Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular/tendências , Neoplasias/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Quimioterapia Combinada , Previsões , Humanos , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Inibidores de Proteínas Quinases/uso terapêutico
20.
Dig Dis Sci ; 65(3): 874-884, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32026181

RESUMO

The intestinal microbiome encodes vast metabolic potential, and multidisciplinary approaches are enabling a mechanistic understanding of how bacterial enzymes impact the metabolism of diverse pharmaceutical compounds, including chemotherapeutics. Microbiota alter the activity of many drugs and chemotherapeutics via direct and indirect mechanisms; some of these alterations result in changes to the drug's bioactivity and bioavailability, causing toxic gastrointestinal side effects. Gastrointestinal toxicity is one of the leading complications of systemic chemotherapy, with symptoms including nausea, vomiting, diarrhea, and constipation. Patients undergo dose reductions or drug holidays to manage these adverse events, which can significantly harm prognosis, and can result in mortality. Selective and precise targeting of the gut microbiota may alleviate these toxicities. Understanding the composition and function of the microbiota may serve as a biomarker for prognosis, and predict treatment efficacy and potential adverse effects, thereby facilitating personalized medicine strategies for cancer patients.


Assuntos
Antineoplásicos/efeitos adversos , Gastroenteropatias/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Antineoplásicos/administração & dosagem , Gastroenteropatias/microbiologia , Gastroenteropatias/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiopatologia , Humanos , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Probióticos/administração & dosagem
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