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1.
Urol Clin North Am ; 47(4): 469-474, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008497

RESUMO

Multiple immunologic platforms have provided minimal impact in patients with metastatic castration-resistant prostate cancer, necessitating that novel approaches continue to be developed. Although checkpoint inhibitors have been largely ineffective, there remain small cohorts of patients who have durable responses but lack the conventional indicators for response to this class of drugs, that is, high mutational burden or significant genomic alterations, as seen in other solid tumors. This article presents an update on the evolution of immunotherapeutics that target a more lethal form of prostate cancer and provides the groundwork for future considerations as to how this field should proceed.


Assuntos
Quinases Ciclina-Dependentes/genética , Regulação Neoplásica da Expressão Gênica , Imunoterapia/métodos , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/terapia , Idoso , Produtos Biológicos/uso terapêutico , Vacinas Anticâncer/administração & dosagem , Quinases Ciclina-Dependentes/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Fenótipo , Medicina de Precisão/métodos , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/efeitos dos fármacos
2.
Urol Clin North Am ; 47(4): 523-536, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008501

RESUMO

Personalized medicine uses a patient's genotype, environment, and lifestyle choices to create a tailored diagnosis and therapy plan, with the goal of minimizing side effects, avoiding lost time with ineffective treatments, and guiding preventative strategies. Although most precision medicine strategies are still within the laboratory phase of development, this article reviews the promising technologies with the greatest potential to improve the diagnosis and treatment options for male infertility, including sperm cell transplantation, genomic editing, and new biomarker assays, based on the latest proteomic and epigenomic studies.


Assuntos
Genômica , Infertilidade Masculina/genética , Infertilidade Masculina/terapia , Medicina de Precisão/métodos , Biomarcadores/sangue , Terapia Combinada , Previsões , Humanos , Infertilidade Masculina/diagnóstico , Masculino , Proteômica , Medição de Risco , Resultado do Tratamento
3.
Viruses ; 12(9)2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32972027

RESUMO

Traditionally, drug discovery utilises a de novo design approach, which requires high cost and many years of drug development before it reaches the market. Novel drug development does not always account for orphan diseases, which have low demand and hence low-profit margins for drug developers. Recently, drug repositioning has gained recognition as an alternative approach that explores new avenues for pre-existing commercially approved or rejected drugs to treat diseases aside from the intended ones. Drug repositioning results in lower overall developmental expenses and risk assessments, as the efficacy and safety of the original drug have already been well accessed and approved by regulatory authorities. The greatest advantage of drug repositioning is that it breathes new life into the novel, rare, orphan, and resistant diseases, such as Cushing's syndrome, HIV infection, and pandemic outbreaks such as COVID-19. Repositioning existing drugs such as Hydroxychloroquine, Remdesivir, Ivermectin and Baricitinib shows good potential for COVID-19 treatment. This can crucially aid in resolving outbreaks in urgent times of need. This review discusses the past success in drug repositioning, the current technological advancement in the field, drug repositioning for personalised medicine and the ongoing research on newly emerging drugs under consideration for the COVID-19 treatment.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Reposicionamento de Medicamentos , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Reposicionamento de Medicamentos/economia , Reposicionamento de Medicamentos/tendências , Humanos , Pandemias , Pesquisa Farmacêutica , Pneumonia Viral/epidemiologia , Medicina de Precisão , Doenças Raras/tratamento farmacológico
4.
Nat Commun ; 11(1): 4719, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948767

RESUMO

A small number of de novo assembled human genomes have been reported to date, and few have been complemented with population-based genetic variation, which is particularly important for North Africa, a region underrepresented in current genome-wide references. Here, we combine long- and short-read whole-genome sequencing data with recent assembly approaches into a de novo assembly of an Egyptian genome. The assembly demonstrates well-balanced quality metrics and is complemented with variant phasing via linked reads into haploblocks, which we associate with gene expression changes in blood. To construct an Egyptian genome reference, we identify genome-wide genetic variation within a cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genome references. Thus, the Egyptian genome reference will be a valuable resource for precision medicine.


Assuntos
Grupos Étnicos/genética , Genética Populacional , Genômica , Egito , Frequência do Gene , Variação Genética , Genoma Humano , Humanos , Desequilíbrio de Ligação , Masculino , Medicina de Precisão , Sequenciamento Completo do Genoma
5.
Pediatr Clin North Am ; 67(5): 995-1009, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32888694

RESUMO

Artificial intelligence (AI) in the last decade centered primarily around digitizing and incorporating the large volumes of patient data from electronic health records. AI is now poised to make the next step in health care integration, with precision medicine, imaging support, and development of individual health trends with the popularization of wearable devices. Future clinical pediatric cardiologists will use AI as an adjunct in delivering optimum patient care, with the help of accurate predictive risk calculators, continual health monitoring from wearables, and precision medicine. Physicians must also protect their patients' health information from monetization or exploitation.


Assuntos
Algoritmos , Inteligência Artificial , Cardiologia/métodos , Medicina de Precisão/métodos , Criança , Registros Eletrônicos de Saúde , Humanos
6.
Emerg Med J ; 37(10): 630-636, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32948623

RESUMO

Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust's COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.


Assuntos
Infecções por Coronavirus/terapia , Etiquetas de Emergência Médica/tendências , Serviço Hospitalar de Emergência/estatística & dados numéricos , Mortalidade Hospitalar/tendências , Equipe de Assistência ao Paciente/organização & administração , Pneumonia Viral/terapia , Tromboembolia/diagnóstico , Adulto , Fatores Etários , Idoso , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Progressão da Doença , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Seleção de Pacientes , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Medicina de Precisão/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Tromboembolia/epidemiologia , Tromboembolia/terapia , Reino Unido
7.
Can J Nurs Res ; 52(3): 199-208, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32893692

RESUMO

Precision health is the integration of personal genomic data with biological, environmental, behavioral, and other information relevant to the care of a patient. Genetics and genomics are essential components of precision health. Genetics is the study of the effects of individual genes, and genomics is the study of all the components of the genome and interactions between genes, environmental factors, and other psychosocial and cultural factors. Knowledge about the role of genetics and genomics on health outcomes has increased substantially since the completion of the human genome project in 2003. Insights about genetics and genomics obtained from bench science are now having positive clinical implications on patient health outcomes. Nurses have the potential to make distinct contributions to precision health due to their unique role in the health care system. In this article, we discuss gaps in the development of precision health in nursing and how nursing can expand the definition of precision health to actualize its potential. Precision health plays a role in nursing practice. Understanding this connection positions nurses to incorporate genetic and genomic knowledge into their nursing practice.


Assuntos
Padrões de Prática em Enfermagem/organização & administração , Medicina de Precisão/enfermagem , Genética , Genômica , Humanos
8.
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
9.
Curr Hypertens Rep ; 22(10): 80, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880739

RESUMO

PURPOSE OF REVIEW: Precision Aging® is a novel concept that we have recently employed to describe how the model of precision medicine can be used to understand and define the multivariate risks that drive age-related cognitive impairment (ARCI). Hypertension and cardiovascular disease are key risk factors for both brain function and cognitive aging. In this review, we will discuss the common mechanisms underlying the risk factors for both hypertension and ARCI and how the convergence of these mechanisms may be amplified in an individual to drive changes in brain health and accelerate cognitive decline. RECENT FINDINGS: Currently, our cognitive health span does not match our life span. Age-related cognitive impairment and preventing and treating ARCI will require an in-depth understanding of the interrelated risk factors, including individual genetic profiles, that affect brain health and brain aging. Hypertension and cardiovascular disease are important risk factors for ARCI. And, many of the risk factors for developing hypertension, such as diabetes, smoking, stress, viral infection, and age, are shared with the development of ARCI. We must first understand the mechanisms common to the converging risk factors in hypertension and ARCI and then design person-specific therapies to optimize individual brain health. The understanding of the convergence of shared risk factors between hypertension and ARCI is required to develop individualized interventions to optimize brain health across the life span. We will conclude with a discussion of possible steps that may be taken to decrease ARCI and optimize an individual's cognitive life span.


Assuntos
Envelhecimento , Encéfalo/fisiopatologia , Disfunção Cognitiva , Hipertensão/complicações , Humanos , Medicina de Precisão , Fatores de Risco
10.
Medicine (Baltimore) ; 99(35): e21942, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871940

RESUMO

RATIONALE: Currently, digital surgical techniques have been widely used in the precise treatment of mandibular resection and reconstruction with fibula flaps. Utilizing these innovative techniques in surgical planning and hardware fabrication before surgery has shown to provide great help. However, it is difficult for even experienced surgeons to place the preformed reconstruction plate in the same position as its preoperative design, causing surgical results to differ from preoperative planning. This study aims to solve these acknowledged challenges by creating newly designed equipment. PATIENT CONCERNS: Two patients suffering from long-term expansion of the mandible were admitted to our department. Case I was a 39-year-old female patient who was concerned about the disease in the middle of the mandible, Case II was a 45-year-old female patient who was concerned about the disease at the left mandibular angle and ramus region. DIAGNOSES: Two patients were diagnosed with the mandibular ameloblastoma based on computed tomography (CT) scan and pathological results. INTERVENTIONS: Personalized 3-dimensional (3D) surgical guides were applied to 2 patients with mandibular ameloblastoma who underwent mandibular resection and reconstruction with vascularized fibula flaps using a specially optimized and designed reconstruction guide plate. OUTCOMES: We achieved precise mandibular repair with such a guide in full accordance with the preoperative plan and ensured the restoration of patient facial symmetry. LESSONS: Optimized reconstruction guide template could accurately locate the preformed reconstruction plate. This component had the ability to ensure that the location of the actual reconstruction plates were highly consistent with preoperative designed models.


Assuntos
Ameloblastoma/cirurgia , Fíbula/transplante , Mandíbula/cirurgia , Neoplasias Mandibulares/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/instrumentação , Adulto , Ameloblastoma/diagnóstico por imagem , Feminino , Fíbula/irrigação sanguínea , Humanos , Mandíbula/diagnóstico por imagem , Neoplasias Mandibulares/diagnóstico por imagem , Pessoa de Meia-Idade , Medicina de Precisão , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/transplante
11.
Adv Exp Med Biol ; 1255: 175-193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32949400

RESUMO

Personalized medicine has been driven by improvements in genomic sequencing and analysis. For several diseases, in particular cancers, it has for nearly a decade been standard clinical practice to analyze the genome and expression of the genes of patients. The results are reflected directly in the treatment plan for the patient, in targeted medical inventions. This specialized mode of diagnostics has been restricted to account for averaged trends in the tumor. The approach sharply contrasts our knowledge on heterogeneity within tumors. Several studies further describe how treatment against one tumor subclone in some cases merely serves to provide space and support for uncontrolled growth of more aggressive subclones. In this chapter, we describe current possibilities for implementation of single cell sequencing of malignomas in clinic, as well as discuss hands-on practical advice for single cell routine diagnostics that allows for full delineation of tumor clonality.


Assuntos
Neoplasias/diagnóstico , Neoplasias/genética , Medicina de Precisão , Análise de Sequência , Análise de Célula Única , Humanos , Neoplasias/patologia
13.
Nat Commun ; 11(1): 4487, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32900998

RESUMO

An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.


Assuntos
Envelhecimento Saudável/metabolismo , Metaboloma , Proteoma/metabolismo , Idoso , Estudos de Coortes , Feminino , Envelhecimento Saudável/genética , Voluntários Saudáveis , Humanos , Lipidômica , Estudos Longitudinais , Masculino , Metabolômica , Pessoa de Meia-Idade , Medicina de Precisão , Estudos Prospectivos , Proteômica , Suécia , Transcriptoma
14.
Nat Commun ; 11(1): 4469, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901013

RESUMO

Dissecting tumor heterogeneity is a key to understanding the complex mechanisms underlying drug resistance in cancers. The rich literature of pioneering studies on tumor heterogeneity analysis spurred a recent community-wide benchmark study that compares diverse modeling algorithms. Here we present FastClone, a top-performing algorithm in accuracy in this benchmark. FastClone improves over existing methods by allowing the deconvolution of subclones that have independent copy number variation events within the same chromosome regions. We characterize the behavior of FastClone in identifying subclones using stage III colon cancer primary tumor samples as well as simulated data. It achieves approximately 100-fold acceleration in computation for both simulated and patient data. The efficacy of FastClone will allow its application to large-scale data and clinical data, and facilitate personalized medicine in cancers.


Assuntos
Algoritmos , Variações do Número de Cópias de DNA , Neoplasias/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Biologia Computacional/métodos , Simulação por Computador , DNA de Neoplasias/genética , Resistencia a Medicamentos Antineoplásicos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Modelos Genéticos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Filogenia , Medicina de Precisão , Análise de Sequência de DNA
19.
Lancet Haematol ; 7(10): e765-e771, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976753

RESUMO

Over the past 30 years, the scientific community has made little progress in changing the natural history of peripheral T-cell lymphomas. Of the haematological malignancies, T-cell lymphomas have an extremely poor prognosis. One reason for this poor outcome has been that no treatment programme has ever been developed specifically for the broader category of the disease-peripheral T-cell lymphoma-let alone any of the specific subtypes, except advances made for patients with CD30-positive anaplastic large cell lymphoma. Decades of effort have focused on retrofitting chemotherapy programmes used for other diseases, such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for diffuse large B-cell lymphoma, which have not been associated with much progress, and have universally produced far more toxicity than benefit. A remarkable heterogeneity, a paucity of cases, and the absence of peripheral T-cell lymphoma-specific drugs, until recently at least, have limited the field's ability to make substantive and innovative advances. Over the past few years, however, it appears the field is beginning to make progress. Lineage and disease-specific novel-to-novel platforms are producing, although perhaps not unsurprisingly, compelling results suggesting that the path to a cure for this rare orphan disease might be heading in a different direction.


Assuntos
Linfoma de Células T Periférico/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Imunoterapia/métodos , Medicina de Precisão/métodos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
20.
Zhonghua Zhong Liu Za Zhi ; 42(8): 624-628, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867452

RESUMO

Small cell lung cancer (SCLC), a special type of lung cancer, is a highly malignant neuroendocrine tumor with strong invasiveness and rapid progression. SCLC is sensitive to radiotherapy and chemotherapy, so radiotherapy and chemotherapy have been the main first-line treatment of SCLC. However, it is easy to develop drug resistance after treatment. Therefore, the study of anti-angiogenic therapy has attracted more and more attention. At present, anti-angiogenic drugs mainly focus on four categories: monoclonal antibodies (such as bevacizumab), endogenous angiogenesis inhibitors (such as endostar), anti-angiogenic fusion protein (such as aflibercept) and small molecular tyrosine kinase inhibitors (such as anlotinib). There are still some bottlenecks in the research and clinical application of antiangiogenic drugs. It is the right direction to explore better combination therapy and effective dual-field and multi-target drugs.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/farmacologia , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Medicina de Precisão , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
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