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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.
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
5.
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
6.
Curr Opin Ophthalmol ; 31(5): 329-336, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32740060

RESUMO

PURPOSE OF REVIEW: To review the current status of artificial intelligence systems in ophthalmology and highlight the steps required for clinical translation of artificial intelligence into personalized health care (PHC) in retinal disease. RECENT FINDINGS: Artificial intelligence systems for ophthalmological application have made rapid advances, but are yet to attain a state of technical maturity that allows their adoption into real-world settings. There remains an 'artificial intelligence chasm' in the spheres of validation, regulation, safe implementation, and demonstration of clinical impact that needs to be bridged before the full potential of artificial intelligence to deliver PHC can be realized. SUMMARY: Ophthalmology is currently in a stage between the demonstration of the potential of artificial intelligence and widespread deployment. Next stages include aggregating and curating datasets, training and validating artificial intelligence systems, establishing the regulatory framework, implementation and adoption with ongoing evaluation and model adjustment, and finally, meaningful human-artificial intelligence interaction with clinically validated tools that have demonstrated measurable impact on patient and healthcare system outcomes. Ophthalmologists should leverage the ability of artificial intelligence systems to glean insights from large volumes of multivariate data, and to interpret artificial intelligence recommendations in a clinical context. In doing so, the field will be well positioned to lead the transformation of health care in a personalized direction. VIDEO ABSTRACT: http://links.lww.com/COOP/A35.


Assuntos
Algoritmos , Inteligência Artificial , Assistência à Saúde/métodos , Oftalmologia/métodos , Medicina de Precisão/métodos , Doenças Retinianas/terapia , Humanos
7.
Nat Commun ; 11(1): 3872, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32747627

RESUMO

The optimal post-treatment surveillance strategy that can detect early recurrence of a cancer within limited visits remains unexplored. Here we adopt nasopharyngeal carcinoma as the study model to establish an approach to surveillance that balances the effectiveness of disease detection versus costs. A total of 7,043 newly-diagnosed patients are grouped according to a clinic-molecular risk grouping system. We use a random survival forest model to simulate the monthly probability of disease recurrence, and thereby establish risk-based surveillance arrangements that can maximize the efficacy of recurrence detection per visit. Markov decision-analytic models further validate that the risk-based surveillance outperforms the control strategies and is the most cost-effective. These results are confirmed in an external validation cohort. Finally, we recommend the risk-based surveillance arrangement which requires 10, 11, 13 and 14 visits for group I to IV. Our surveillance strategies might pave the way for individualized and economic surveillance for cancer survivors.


Assuntos
Sobreviventes de Câncer , Monitorização Fisiológica/métodos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Adulto , Análise Custo-Benefício , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Monitorização Fisiológica/economia , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/economia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/economia , Recidiva Local de Neoplasia , Medicina de Precisão/economia , Medicina de Precisão/métodos , Fatores de Risco
8.
Int J Mol Sci ; 21(14)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708334

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), also known as coronavirus disease 2019 (COVID-19)-induced infection, is strongly associated with various coagulopathies that may result in either bleeding and thrombocytopenia or hypercoagulation and thrombosis. Thrombotic and bleeding or thrombotic pathologies are significant accompaniments to acute respiratory syndrome and lung complications in COVID-19. Thrombotic events and bleeding often occur in subjects with weak constitutions, multiple risk factors and comorbidities. Of particular interest are the various circulating inflammatory coagulation biomarkers involved directly in clotting, with specific focus on fibrin(ogen), D-dimer, P-selectin and von Willebrand Factor (VWF). Central to the activity of these biomarkers are their receptors and signalling pathways on endothelial cells, platelets and erythrocytes. In this review, we discuss vascular implications of COVID-19 and relate this to circulating biomarker, endothelial, erythrocyte and platelet dysfunction. During the progression of the disease, these markers may either be within healthy levels, upregulated or eventually depleted. Most significant is that patients need to be treated early in the disease progression, when high levels of VWF, P-selectin and fibrinogen are present, with normal or slightly increased levels of D-dimer (however, D-dimer levels will rapidly increase as the disease progresses). Progression to VWF and fibrinogen depletion with high D-dimer levels and even higher P-selectin levels, followed by the cytokine storm, will be indicative of a poor prognosis. We conclude by looking at point-of-care devices and methodologies in COVID-19 management and suggest that a personalized medicine approach should be considered in the treatment of patients.


Assuntos
Plaquetas/metabolismo , Infecções por Coronavirus/patologia , Células Endoteliais/metabolismo , Eritrócitos/metabolismo , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Selectina-P/metabolismo , Pneumonia Viral/patologia , Fator de von Willebrand/metabolismo , Betacoronavirus , Síndrome da Liberação de Citocina/patologia , Humanos , Pandemias , Sistemas Automatizados de Assistência Junto ao Leito , Medicina de Precisão/métodos , Trombocitopenia/patologia , Trombose/patologia
9.
Eur J Endocrinol ; 183(4): 419-426, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32688338

RESUMO

Objective: The need for personalization of the reference values of thyroid function tests has been previously suggested. We aimed at determining TSH reference values in a large cohort of children according to age, sex, BMI, and ethnicity. Design: A population-based cohort study. Methods: The study cohort included 75 549 healthy children aged 5-18 years. Data analyzed included age, gender, TSH, FT4 levels, BMI and ethnicity. Multivariate logistic regression analysis examined the associations between the study parameters. Results: TSH in the Jewish population is lower than in the non-Jewish population (median: 2.1 IU/L (IQR: 1.5) vs 2.2 IU/L (IQR: 1.5), P < 0.0001). TSH is significantly affected by BMI for children defined as underweight, normal weight, overweight or obese, levels increased as weight diverged from the normal range (median levels: 2.1 IU/L (IQR: 1.4), 2.0 IU/L (IQR: 1.3), 2.1 IU/L (IQR: 1.4), 2.4 (IQR: 1.5), respectively, P < 0.001). The 2.5 percentile is affected by gender and BMI (P < 0.02 and P < 0.001, respectively), while the 97.5 percentile is affected by ethnic origin and BMI (P < 0.001 for both). New TSH reference intervals (RI) adjusted according to BMI and ethnicity are suggested. Comparison of the old and new RI demonstrate the significance of RI personalization: 25.1% of the children with TSH levels above the old RI are within the new RI, while 2.3% of the children who were in the old RI are below the new RI. Conclusions: TSH reference values in children are affected by BMI and ethnicity. Reference values should be individualized accordingly to improve future clinical decision-making and treatment.


Assuntos
Índice de Massa Corporal , Grupos Étnicos , Medicina de Precisão/métodos , Testes de Função Tireóidea/normas , Tireotropina/sangue , Adolescente , Análise Química do Sangue/normas , Criança , Pré-Escolar , Técnicas de Diagnóstico Endócrino/normas , Feminino , Humanos , Judeus , Masculino , Pediatria/métodos , Pediatria/normas , Medicina de Precisão/normas , Valores de Referência , Estudos Retrospectivos , Tireotropina/normas , Tiroxina/sangue
10.
Nat Commun ; 11(1): 3296, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620799

RESUMO

Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. We also find strong predictive biomarkers for the sensitivity to 31 compounds, including BCL2 and microtubule inhibitors (MTIs). Lastly, we show that Bcl-xL inhibition can modulate the activity of a predictive biomarker pathway and re-sensitize lung cancer cells and tumors to MTI therapy. Overall, our results support the use of pathways in helping to achieve the goal of precision medicine by uncovering dozens of predictive biomarkers.


Assuntos
Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Transdução de Sinais/genética , Animais , Antineoplásicos/farmacologia , Proteína BRCA1/genética , Proteína BRCA1/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Medicina de Precisão/métodos , Interferência de RNA , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
11.
PLoS One ; 15(7): e0234962, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32609747

RESUMO

The All of Us Research Program (All of Us) is a national effort to accelerate health research by exploring the relationship between lifestyle, environment, and genetics. It is set to become one of the largest research efforts in U.S. history, aiming to build a national resource of data from at least one million participants. All of Us aims to address the need for more diversity in research and set the stage for that diversity to be leveraged in precision medicine research to come. This paper describes how the program assessed demographic characteristics of participants who have enrolled in other U.S. biomedical research cohorts to better understand which groups are traditionally represented or underrepresented in biomedical research. We 1) reviewed the enrollment characteristics of national cohort studies like All of Us, and 2) surveyed the literature, focusing on key diversity categories essential to the program's enrollment aims. Based on these efforts, All of Us emphasizes enrollment of racial and ethnic minorities, and has formally designated the following additional groups as historically underrepresented: individuals-with inadequate access to medical care; under the age of 18 or over 65; with an annual household income at or below 200% of the federal poverty level; who have a cognitive or physical disability; have less than a high school education or equivalent; are intersex; identify as a sexual or gender minority; or live in rural or non-metropolitan areas. Research accounting for wider demographic variability is critical. Only by ensuring diversity and by addressing the very barriers that limit it, can we position All of Us to better understand and tackle health disparities.


Assuntos
Pesquisa Biomédica/métodos , Diversidade Cultural , Demografia/métodos , Pesquisa Biomédica/ética , Estudos de Coortes , Grupos de Populações Continentais , Grupos Étnicos , Feminino , Humanos , Masculino , Grupos Minoritários , Saúde da População , Medicina de Precisão/métodos , Estados Unidos
12.
J Am Med Dir Assoc ; 21(7): 937-938, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32674823

RESUMO

On February 20, 2020, a man living in the north of Italy was admitted to the emergency room with an atypical pneumonia that later proved to be COVID-19. This was the trigger of one of the most serious clusters of COVID-19 in the world, outside of China. Despite aggressive restraint and inhibition efforts, COVID-19 continues to increase, and the total number of infected patients in Italy is growing daily. After 6 weeks, the total number of patients reached 128,948 cases (April 5, 2020), with the higher case-fatality rate (15,887 deaths) dominated by old and very old patients. This sudden health emergency severely challenged the Italian Health System, in particular acute care hospitals and intensive care units. In 1 hospital, geriatric observation units were created, the experience of which can be extremely useful for European countries, the United States, and all countries that in the coming days will face a similar situation.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Surtos de Doenças/estatística & dados numéricos , Avaliação Geriátrica/métodos , Geriatras/estatística & dados numéricos , Controle de Infecções/organização & administração , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Idoso , Idoso de 80 Anos ou mais , Surtos de Doenças/prevenção & controle , Serviço Hospitalar de Emergência/organização & administração , Feminino , Serviços de Saúde para Idosos/organização & administração , Hospitalização/estatística & dados numéricos , Hospitais de Ensino , Humanos , Unidades de Terapia Intensiva/organização & administração , Itália/epidemiologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Papel do Médico , Medicina de Precisão/métodos , Medição de Risco
13.
Medicine (Baltimore) ; 99(29): e21141, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702867

RESUMO

BACKGROUND: Toxoplasma encephalitis (TE) is one of the main opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients, and represents a social burden due to its high prevalence and morbidity. Concomitant antiretroviral therapy (ART), together with effective anti- toxoplasma combination therapy, is an effective strategy to treat AIDS-associated TE (AIDS/TE) patients. However, the timing for the initiation of ART after diagnosis of TE remains controversial. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS/TE patients. METHODS/DESIGN: This trial is a 17-center, randomized, prospective clinical study with 2 parallel arms. A total of 200 participants will be randomized at a 1:1 ratio into the 2 arms: the early ART initiation (≤14 days after TE diagnosis) arm and the deferred ART (>14 days after TE diagnosis) arm. The primary outcome will be the difference of mortality between the 2 arms at 48 weeks. The secondary outcomes will be the differences between the 2 arms in the changes of CD4+ counts from baseline to week 48, the rate of virologic suppression (HIV ribonucleic acid <50 copies/mL) from baseline to week 48, the incidence of TE-associated immune reconstitution inflammatory syndrome during the study period, and the incidence of adverse effects during the study period. DISCUSSION: This present trial aims to evaluate the optimal timing for ART initiation in AIDS/TE patients, and will provide strong evidence for AIDS/TE treatment should it be successful. TRIAL REGISTRATION: This trial was registered as one of the 12 trials under the name of a general project at the chictr.gov (http://www.chictr.org.cn/showproj.aspx?proj=35362) on February 1, 2019, and the registration number of the general project is ChiCTR1900021195.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Antirretrovirais/uso terapêutico , Protocolos Clínicos , Fatores de Tempo , Toxoplasmose Cerebral/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Adulto , Infecções por HIV/complicações , Infecções por HIV/fisiopatologia , Humanos , Medicina de Precisão/métodos , Estudos Prospectivos , Toxoplasmose Cerebral/fisiopatologia
14.
J Neuromuscul Dis ; 7(3): 361-364, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-609089

RESUMO

This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Pneumonia Viral/complicações , Adulto , Doença Crônica , Feminino , Humanos , Miastenia Gravis/complicações , Pandemias , Medicina de Precisão/métodos , Fatores de Risco , Resultado do Tratamento
16.
J Allergy Clin Immunol ; 146(2): 300-306, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561389

RESUMO

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Mastocitose Cutânea/tratamento farmacológico , Mastocitose Sistêmica/tratamento farmacológico , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Difosfonatos/uso terapêutico , Prova Pericial , Glucocorticoides/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/patologia , Agonistas Mieloablativos/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Medicina de Precisão/métodos , Fatores de Risco , Vitamina D/uso terapêutico
17.
Lancet Respir Med ; 8(6): 631-643, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32526190

RESUMO

Despite progress in the supportive care available for critically ill patients, few advances have been made in the search for effective disease-modifying therapeutic options. The fact that many trials in critical care medicine have not identified a treatment benefit is probably due, in part, to the underlying heterogeneity of critical care syndromes. Numerous approaches have been proposed to divide populations of critically ill patients into more meaningful subgroups (subphenotypes), some of which might be more useful than others. Subclassification systems driven by clinical features and biomarkers have been proposed for acute respiratory distress syndrome, sepsis, acute kidney injury, and pancreatitis. Identifying the systems that are most useful and biologically meaningful could lead to a better understanding of the pathophysiology of critical care syndromes and the discovery of new treatment targets, and allow recruitment in future therapeutic trials to focus on predicted responders. This Review discusses proposed subphenotypes of critical illness syndromes and highlights the issues that will need to be addressed to translate subphenotypes into clinical practice.


Assuntos
Cuidados Críticos/métodos , Estado Terminal/classificação , Fenótipo , Medicina de Precisão/métodos , Lesão Renal Aguda/classificação , Lesão Renal Aguda/patologia , Lesão Renal Aguda/terapia , Estado Terminal/terapia , Humanos , Síndrome do Desconforto Respiratório do Adulto/classificação , Síndrome do Desconforto Respiratório do Adulto/patologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Pesquisa Médica Translacional
18.
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
19.
J Neuromuscul Dis ; 7(3): 361-364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508329

RESUMO

This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Imunossupressores/uso terapêutico , Miastenia Gravis/tratamento farmacológico , Pneumonia Viral/complicações , Adulto , Doença Crônica , Feminino , Humanos , Miastenia Gravis/complicações , Pandemias , Medicina de Precisão/métodos , Fatores de Risco , Resultado do Tratamento
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