Research advances of various omics analyses in chronic refractory wounds on body surface / 中华烧伤杂志

The diagnosis and treatment of chronic refractory wounds on body surface has always been full of challenges, and it also poses a huge burden on medical care and society. High-throughput sequencing combined with omics analysis can reveal potential mechanisms of chronic wound formation, and identify potential biomarkers related to diagnosis, prognosis, and screening of chronic wound. Combined with multiple levels of omics analysis, the detailed molecular mechanism of chronic wound development can be further explored and understood, so as to provide clues for the formulation of personalized treatment methods and lay a solid foundation for the precision medicine of chronic wounds. Therefore, this review addresses the recent progress of various omics analyses in chronic refractory wounds on body surface.

Research progress on genome-guided precision oncology and development ideas of antitumor Chinese medicine / 中国中药杂志

Genome-guided oncology refers to a new treatment concept that transcends histological classification and pathological ty-ping and uses drugs according to the genetic characteristics of tumors. New drug development technology and clinical trial design based on this concept provide new ideas for the clinical application of precision oncology. The multi-component and multi-target characteristics of Chinese medicine provide rich resources for the development of tumor-targeting drugs from natural products, and the design of the master protocol trial aiming at the characteristics of precision oncology supports the rapid clinical screening of effective tumor-targeting drugs. The emergence of the synthetic lethality strategy breaks through the bottleneck that the drug can only target the oncogene but cannot do anything to the tumor suppressor gene with the loss-of-function mutation in the past. With the rapid development of high-throughput sequencing technology, the cost of sequencing is also decreasing. For the development of tumor-targeting drugs, how to keep up with the update speed of target information is a difficult problem of concern. Based on the integration of innovative ideas and me-thods of precision oncology, network pharmacology, and synthetic lethality strategy on synthetic lethal interaction network of antitumor Chinese medicine compatibility formula design, and the combination of improvement of innovative clinical trial methods, such as master protocol trial, basket trial, and umbrella trial, unique advantages of Chinese medicine are expected to be exerted beyond the antibody-based drugs and small molecule-based drugs and corresponding targeted drugs are potentially developed for clinical application.

Guiding opioid-free intravenous antinociception with the Analgesia Nociception Index: a case report / Antinocicepção intravenosa sem opioides orientada pelo Índice de Analgesia/Nocicepção: relato de caso

Abstract Background: Opioid-free anesthesia decreases the incidence of opioid adverse events, but its optimal antinociceptive depth has not been clearly defined. Personalizing intraoperative opioid-free infusions with a nociception monitor may be the solution. Case report: We describe the feasibility and potential limitations of titrating opioid-free antinociception during major abdominal surgery using the Analgesia Nociception Index (Mdoloris, Lille, France) in an obese patient. After stabilizing the patient's nociception-antinociception balance intraoperatively we quickly reversed anesthesia and the patient did not require postoperative opioids. Conclusion: Personalizing opioid-free antinociception with a nociception monitor is feasible. It may optimize intraoperative antinociception and improve postoperative comfort.

Resumo Introdução A anestesia sem opioides diminui a incidência de eventos adversos associados aos opioides, mas a profundidade antinociceptiva ideal dessa abordagem não está claramente definida. Personalizar a infusão intraoperatória sem opioides com o uso de monitor de nocicepção pode ser a solução. Relato de caso Descrevemos a viabilidade e as eventuais limitações da titulação da antinocicepção sem opioides por meio do uso do Índice de Analgesia/Nocicepção (Mdoloris, Lille, França) durante cirurgia abdominal de grande porte em paciente com obesidade. Depois de estabilizar o equilíbrio nocicepção-antinocicepção da paciente no intraoperatório, revertemos rapidamente a anestesia e a paciente não precisou de opioides no pós-operatório. Conclusão A personalização da antinocicepção sem opioides por meio do emprego de monitor de nocicepção é factível. A abordagem pode otimizar a antinocicepção intraoperatória e melhorar o conforto pós-operatório.

Extensión tumoral intraoperatoria radioguiada en cáncer gastrointestinal con alta expresión de receptor del factor de crecimiento epidérmico / Tumor Extent during Radioguided Surgery in Gastrointestinal Cancer with High Expression of Epidermal Growth Factor Receptor

RESUMEN Con el auge contemporáneo de novedosos paradigmas en las ciencias médicas, como la Medicina personalizada, se busca una resección oncológica más eficaz, con nuevos márgenes quirúrgicos de acuerdo al estadio tumoral. Para alcanzar estos resultados, se abren paso técnicas como la cirugía radioinmunoguiada. En Cuba, los adelantos biotecnológicos han permitido el desarrollo de fármacos líderes en el mundo, como el Nimotuzumab, un anticuerpo monoclonal dirigido contra el receptor del factor de crecimiento epidérmico, sobrexpresado en múltiples tumores malignos de origen epitelial. Al marcarlo con un radioisótopo puede auxiliar al cirujano en la determinación precisa de la extensión tumoral (radioguiada) de estas neoplasias durante el acto quirúrgico(AU)

ABSTRACT The contemporary rise of new paradigms within medical sciences, such as personalized medicine, a more effective oncological resection is pursued, with new surgical margins based on tumor stage. To achieve these outcomes, some techniques, such as radioimmunoguided surgery, are expanding. In Cuba, biotechnological advances have allowed the development of world-leading drugs, such as nimotuzumab, a monoclonal antibody directed against the epidermal growth factor receptor, overexpressed in multiple malignant tumors of epithelial origin. Marking it with a radioisotope can help the surgeon in the precise determination of tumor extent (radioguided) of these malignancies during the surgical act(AU)

Individualized treatment for allergic rhinitis based on key nasal clinical manifestations combined with histamine and leukotriene D4 levels / Tratamento individualizado para a rinite alérgica baseado nas principais manifestações clínicas nasais e dos níveis de histamina e leucotrieno D4

Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.

Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.

Deriving primary cancer cell cultures for personalized therapy

ABSTRACT Cancer is the second-leading cause of death in the world, accounting for one out of six deaths. Consequently, there is an urgent need for new and more effective therapeutic options as well as drug screening methods. Immortal, “stable” cancer cell lines have been employed since the past century to assess drug response but face several disadvantages. They often accumulate new genetic aberrations due to long-term culture and lack the indisputable heterogeneity of solid tumors, therefore, compromising the recapitulation of molecular features from parental tumors. Primary cancer cells have emerged as an attractive alternative to commercial cell lines since they can preserve such properties more closely. Here, we provide an overview of the basic concepts underlying generation and characterization of primary cell cultures from tumor samples. We emphasize the advantages and disadvantages of using these types of cancer cell cultures, and we make a comparison with other types of cultures used for personalized therapy. Finally, we consider the use of primary cancer cell cultures in personalized therapy as a means to improve drug response prediction and therapeutic outcomes.

Inteligência artificial e diagnóstico por imagem - o futuro chegou? / Artificial intelligence and diagnostic imaging - has the future come?

Na nova era da Medicina de Precisão, a inteligência artificial (IA) - um conjunto de sistemas e programas que permitem às máquinas serem capazes de executar tarefas que habitual mente exigiriam a participação humana - emerge como ferramenta capaz de criar novas maneiras de analisar as imagens médicas além dos parâmetros morfológicos convencionais. Embora ainda não estejam completamente disponíveis para o uso clínico, essa nova abordagem tem grande potencial de aplicação na prática clínica e de pesquisa médica. A discussão dos conceitos básicos, potenciais aplicações e limitações das novas técnicas de IA no diagnóstico por imagem é importante para a interpretação adequada do potencial efeito que essa tecnologia teria na medicina, contrapondo-se à excessiva ansiedade despertada por abordagens superficiais e apressadas. Este artigo tem por objetivo apresentar uma visão equilibrada e atual sobre o tema, com especial foco no presente e no futuro da imagenologia cardíaca

In the new era of Precision Medicine, artificial intelligence (AI) - a set of systems and programs that enable machines to be able to perform cognitive tasks that would usually require human participation emerges as a tool that can create new ways of analyzing images beyond the conventional morphological parameters. Although not yet ready for clinical use, these tools have a potential effect on clinical and research practice. The discussion of the basic concepts, potential applications and limitations of new AI techniques in imaging diagnosis is important for a balanced interpretation of their results, as opposed to the excessive anxiety recently observed among professionals dealing with the subject. In this brief article, we aim to take a balanced and attentive look on this subject, with special focus on the horizon of modern cardiac imaging

Precision Medicine: Changing the way we think about healthcare

Health care has changed since the decline in mortality caused by infectious diseases as well as chronic and non-contagious diseases, with a direct impact on the cost of public health and individual health care. We must now transition from traditional reactive medicine based on symptoms, diagnosis and treatment to a system that targets the disease before it occurs and, if it cannot be avoided, treats the disease in a personalized manner. Precision Medicine is that new way of thinking about medicine. In this paper, we performed a thorough review of the literature to present an updated review on the subject, discussing the impact of the use of genetics and genomics in the care process as well as medical education, clinical research and ethical issues. The Precision Medicine model is expanded upon in this article to include its principles of prediction, prevention, personalization and participation. Finally, we discuss Precision Medicine in various specialty fields and how it has been implemented in developing countries and its effects on public health and medical education.

Next-generation Sequencing-based genomic profiling: Fostering innovation in cancer care?

OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.

Omics techniques and biobanks to find new biomarkers for the early detection of acute lymphoblastic leukemia in middle-income countries: a perspective from Mexico / Técnicas ómicas y biobancos para el hallazgo de nuevos biomarcadores para la detección temprana de leucemia linfoblástica aguda en países de ingresos medios: una perspectiva mexicana

Abstract: Acute lymphoblastic leukemia (ALL) affects the quality of life of many children in the world and particularly in Mexico, where a high incidence has been reported. With a proper financial investment and with well-organized institutions caring for those patients, together with solid platforms to perform high-throughput analyses, we propose the creation of a Mexican repository system of serum and cells from bone marrow and blood samples derived from tissues of pediatric patients with ALL diagnosis. This resource, in combination with omics technologies, particularly proteomics and metabolomics, would allow longitudinal studies, offering an opportunity to design and apply personalized ALL treatments. Importantly, it would accelerate the development of translational science and will lead us to further discoveries, including the identification of new biomarkers for the early detection of leukemia.

Resumen: La leucemia linfoblástica aguda (LLA) afecta la calidad de vida de una gran cantidad de individuos en edad pediátrica en todo el mundo; particularmente en México, donde se ha reportado una alta incidencia. Con un apropiado fondo de inversión financiera, así como instituciones adecuadamente organizadas al cuidado de los pacientes con LLA, en conjunto con plataformas sólidas para llevar a cabo análisis globales y de alto rendimiento, se propone la creación de un repositorio para la conservación de suero y células provenientes de médula ósea y sangre derivadas de pacientes pediátricos con LLA al diagnóstico. Estos recursos, en combinación con las tecnologías ómicas, en particular la proteómica y la metabolómica, podrían permitir el establecimiento de estudios longitudinales y ofrecer una oportunidad para el diseño y aplicación de tratamientos personalizados para la LLA. Esta estrategia permitiría acelerar el desarrollo de la ciencia traslacional, favoreciendo el hallazgo de importantes descubrimientos, incluyendo la identificación de nuevos biomarcadores para la detección temprana de la leucemia.

Future directions in overactive bladder treatment: Personalized medicine can be applied?

No abstract available.

Personalized medicine and the clinical laboratory / Medicina personalizada e o laboratório clínico

Personalized medicine is the use of biomarkers, most of them molecular markers, for detection of specific genetic traits to guide various approaches for preventing and treating different conditions. The identification of several genes related to heredity, oncology and infectious diseases lead to the detection of genetic polymorphisms that are involved not only in different clinical progression of these diseases but also in variations in treatment response. Currently, it is possible to detect these polymorphisms using several methodologies: detection of single nucleotide polymorphisms using polymerase chain reaction methods; nucleic acid microarray detection; and nucleic acid sequencing with automatized DNA sequencers using Sanger-derived methods and new generation sequencing. Personalized medicine assays are directed towards detecting genetic variations that alter interactions of drugs with targets or the metabolic pathways of drugs (upstream and downstream) and can be utilized for the selection of drug formulations and detect different immunogenicities of the drug. Personalized medicine applications have already been described in different areas of Medicine and allow specific treatment approaches to be applied to each patient and pathology according to the results of these assays. The application of such a protocol demands an increasing interaction between the clinical laboratory and the clinical staff. For its implementation, a coordinated team composed of basic researchers and physicians highly specialized in their areas supported by a highly specialized team of clinical analysts particularly trained in molecular biology assays is necessary.

Medicina personalizada é o uso de biomarcadores, em sua maioria marcadores moleculares, para a detecção de traços genéticos específicos, a fim de orientar diversas abordagens para a prevenção e o tratamento de diferentes doenças. A identificação de vários genes relacionados a doenças hereditárias, oncológicas e infecciosas permite a detecção de polimorfismos genéticos que estão envolvidos em diferentes evoluções clínicas dessas doenças, bem como com variações na resposta ao tratamento. Atualmente, já é possível detectar esses polimorfismos utilizando diversas metodologias: a detecção de polimorfismos de nucleotídeo único pela reação de polimerização em cadeia; a detecção de microarranjos de ácidos nucleicos; e o sequenciamento de ácidos nucleicos com sequenciadores de DNA automatizados usando métodos derivados de sequenciamento Sanger ou de nova geração. Os ensaios de medicina personalizada são dirigidos para detectar variações genéticas que alteram interações de fármacos com alvos ou vias metabólicas de fármacos (anabólicas e catabólicas), podendo ser utilizados para a seleção de formulações farmacêuticas e para detectar diferentes imunogenicidades da droga. As aplicações de medicina personalizada já foram descritas em várias áreas da Medicina e permitem que abordagens de tratamento específicas sejam aplicadas para cada paciente e para cada doença, de acordo com os resultados dos ensaios utilizados. A aplicação de um protocolo desse tipo exige uma relação intensa entre o laboratório e o corpo clínico. Para sua execução, é necessária uma equipe coordenada, composta por investigadores de pesquisa básica e médicos altamente especializados em suas áreas, apoiada por um time bastante especializado de analistas clínicos treinados em testes de biologia molecular.

Lesionalized Therapy beyond Personalized Therapy in Cancer Management

No abstract available.

Role of biomarkers in risk stratification of acute coronary syndrome.

Diagnosis of acute coronary syndrome (ACS) encompasses a wide spectrum of myocardial ischaemia varying from assuredly benign to potentially fatal. Cardiac biomarkers have had a major impact on the management of this disease and are now the cornerstone in its diagnosis and prognosis. In this review we discuss both the established and the newer emerging biomarkers in ACS and their role in highlighting not only myocardial necrosis but also different facets of the pathophysiology of ACS. The future of cardiac biomarker testing may be in multimarker testing to better characterize each patient of ACS and thus tailor both short-term and long-term therapy accordingly. This novel concept, however, needs to be tested in clinical trials for its incremental value and cost-effectiveness.