ABSTRACT
Há muitos anos a cultura celular bidimensional (2D) é utilizada como modelo de estudo de doenças, possuindo grande importância na medicina regenerativa, apesar de ainda conter limitações significativas. A fim de contornar essas limitações, a cultura celular tridimensional (3D) propõe uma organização mais complexa e sustentável que pode ser produzida a partir de células-tronco adultas (ASCs), células-tronco embrionárias (ESCs) ou células-tronco pluripotentes induzidas (iPSCs). A cultura 3D possibilitou o cultivo de células em um ambiente mais próximo do fisiológico, levando à formação de distintos tecidos órgãos-específicos. Em outras palavras, a cultura de células 3D possibilita a criação de estruturas orgânicas muito semelhantes aos órgãos de um ser humano, tanto estruturalmente, quanto funcionalmente. Desse modo, tem-se o que é chamado de organoides. O uso dos organoides tem crescido exponencialmente em ambientes in vitro, permitindo a análise e observação dos diversos fenômenos fisiológicos existentes. Como exemplo, pode-se citar os organoides cerebrais ("mini-brains") reproduzidos in vitro buscando delinear as peculiaridades e complexidades do cérebro humano, com o objetivo de compreender algumas disfunções neurológicas que acometem esse sistema, como as duas principais doenças neurodegenerativas: Doenças de Alzheimer e Parkinson. Portanto, os organoides cerebrais podem permitir notável avanço da medicina regenerativa aplicada a doenças neurodegenerativas, já que esses "mini-brains" podem ser produzidos a partir de células do próprio paciente. Isso permitirá intervenções personalizadas, como testagens farmacológicas, a fim de definir qual seria o melhor tratamento medicamentoso. Consequentemente, essa tecnologia pode permitir terapias mais eficientes e individualizadas - o que é fundamental para a Medicina Personalizada (AU).
For many years, two-dimensional (2D) cell culture has been used as a model to study diseases, having great importance in regenerative medicine, despite still having significant limitations. In order to circumvent these limitations, three-dimensional (3D) cell culture proposes a more complex and sustainable organization that can be produced from adult stem cells (ASCs), embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs). The 3D culture enabled the cultivation of cells in an environment closer to the physiological one, leading to the formation of different organ-specific tissues. In other words, 3D cell culture makes it possible to create organic structures very similar to the organs of a human being, both structurally and functionally. In this way, we have what are called organoids. The use of organoids has grown exponentially in in vitro environments, allowing the analysis and observation of the various existing physiological phenomena. As an example, we can mention the brain organoids ("mini-brains") reproduced in vitro, seeking to delineate the peculiarities and complexities of the human brain, in order to understand some neurological dysfunctions that affect this system, such as the two main neurodegenerative diseases: Alzheimer's and Parkinson's Diseases. Therefore, brain organoids may allow a remarkable advance in regenerative medicine applied to neurodegenerative diseases, as these "mini-brains" can be produced from the patient's own cells. This will allow for personalized interventions, such as drug testing, in order to define what would be the best drug treatment. Consequently, this technology can enable more efficient and individualized therapies - which is fundamental for Personalized Medicine (AU).
Subject(s)
Humans , Parkinson Disease , Organoids , Concierge MedicineABSTRACT
Lymphoma refers to a group of heterogeneous malignancies originating from the reticuloendothelial and lymphatic systems. The clinical manifestations, treatment strategies, and disease outcomes of different types of lymphoma considerably vary. Recent developments in high-throughput sequencing technologies have enhanced understanding of the pathogenesis and molecular stratification of lymphoma. In the era of new drugs, precise stratification and targeted drug selection can not only improve the prognosis of patients with lymphoma but also reduce the toxic side effects of traditional chemotherapy, ultimately achieving the accurate diagnosis and individualized treatment of tumors. This article reviews the research progress of molecular diagnosis and individualized treatment of different lymphoma subtypes and lymphoma-related research in important meetings such as ASCO, EHA, and ICML in 2023.
ABSTRACT
OBJECTIVE@#To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients.@*METHODS@#A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment.@*RESULTS@#Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05).@*CONCLUSION@#Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.
Subject(s)
Humans , Autoantibodies , Cyclosporine/therapeutic use , Glomerulonephritis, Membranous/diagnosis , Homozygote , Immunosuppressive Agents/therapeutic use , Pharmacogenomic Testing , Receptors, Phospholipase A2 , Sequence Deletion , Serum Albumin , Tacrolimus/therapeutic useABSTRACT
@#With the rapid advancement of science and technology, the application of 3D printing technology for personalized drug manufacturing is becoming increasingly sophisticated.Compared to traditional manufacturing technology, 3D printing can easily customize preparations with specific sizes, shapes and release behaviors for personalized drug use.This review summarizes the principles of several 3D printing technologies commonly used in drug manufacturing, lists the unique advantages and application examples of 3D printing technology for pharmaceutical preparation, analyses the current research status and development trends of the global industry of drug 3D printing, and summarizes the current problems and challenges facing drug 3D printing, aiming to provide some guidance for researchers of 3D printed drugs.
ABSTRACT
Resumen El adenocarcinoma pancreático es una enfermedad heterogénea. Sin dudas la aparición y la acumulación de mutaciones genéticas promueven el desarrollo del adenocarcinoma pancreático. Sin embargo, de manera contra-intuitiva, los análisis genéticos, por más precisos y profundos que sean, no permi ten la estratificación de los pacientes para predecir la evolución clínica ni para seleccionar el tratamiento más eficaz para cada paciente. Esto es debido a que la evolución clínica y la sensibilidad a los tratamientos están asociadas con su fenotipo, el que, a su vez, está determinado por la expresión global de los genes, es decir están regulados a nivel transcriptómico. Por lo tanto, la estratificación de esos pacientes debe hacerse a través de la lectura transcriptómica y no a través de su análisis genético. Los datos obtenidos sobre grandes cohortes de pacientes indican que el estudio de un conjunto de transcriptos seleccionados podría predecir la evolución clínica y ayudar a decidir el tratamiento más apropiado. Se está avanzando rápidamente hacia una medicina personalizada para esta enfermedad, que de por sí tiene un mal pronóstico, pero que es aún peor si la deci sión terapéutica no es la más adaptada a cada paciente. Estamos convencidos de que en un futuro próximo el tratamiento de los cánceres estará precedido por una caracterización transcriptómica extensa con el fin de seleccionar los tratamientos "a la carta" más adecuados.
Abstract Pancreatic adenocarcinoma is a heterogeneous disease. Undeniably, the appearance and accumulation of genetic muta tions promote the development of pancreatic adenocarcinoma. However, counterintuitively, genetic analyzes, no matter how precise and in-depth they may be, do not allow stratification of patients to predict their clinical evolution or to select the most effective treatment in each case. This is due to the fact that the clinical evolution and sensitivity to treatments are associated with the tumoral phenotype, which, in turn, is determined by the global expression of genes that is regulated at the transcriptomic level. Therefore, the stratification of these patients must be done by analysis at the transcriptomic level and not by genetic analysis. The data obtained from large cohorts of patients indicate that studying the transcription of a selected set of genes could predict the clinical outcome and can help to decide about the most appropriate treatment. We are moving very rapidly towards a personalized medicine for this disease, which in itself has a poor prognosis, even worse if the therapeutic deci sion is not the most adapted to each patient. We are convinced that in the near future the treatment of cancers will be preceded by an extensive transcriptomic characterization in order to select the most suitable "à la carte" treatments.
ABSTRACT
Though the coronavirus disease is still raging in 2021, clinical research on non-small cell lung cancer (NSCLC) did not stop. However, benefiting from advances in lung cancer treatment modality, NSCLC patients have experienced significant improvements in overall survival and quality of life. Currently, research advances on targeted therapy and immunotherapy have together transformed the status of postoperative adjuvant therapy and established a new standard treatment modality for resectable NSCLC. There are equally important research advances in locally advanced and advanced NSCLC, including new treatment modalities, new therapeutic agents, etc., all of which bringing more options for clinical treatment. These therapies will bring changes to NSCLC and will gradually lead to the chronicity of lung cancer in the foreseeable future. Therefore, this paper reviews important studies that will change clinical practice in NSCLC treatment and noteworthy research advances in 2021. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/surgery , Combined Modality Therapy , Immunotherapy , Lung Neoplasms/surgery , Quality of LifeABSTRACT
Objective:To study the clinical results of personalized surgical treatment for portal hypertension based on portal venous hemodynamics.Methods:A retrospective study was performed on patients with portal hypertension who underwent surgical treatment from January 2016 to December 2020 at the People’s Hospital of Ningxia Hui Autonomous Region and Wuhai People’s Hospital. Of 229 patients included into this study, there were 156 males and 73 females, with age of (4±11) years old. Portal vein CT and ultrasound doppler examination were performed preoperatively and portal vein manometry and ultrasound doppler examination were performed intraoperatively to evaluate portal venous hemodynamics. Based on the evaluation results, different surgical treatments were adopted. Postoperative complications and results of the operations were recorded. Long-term outcomes were evaluated by the rate of recurrence of gastroesophageal varices which was classified as disappearance, mild, moderate and severe according to endoscopic findings.Results:All the 229 patients completed the operations successfully. All together 13 operative treatments were used: (1) simple splenectomy ( n=11); (2) devascularization ( n=176), including 86 patients with splenectomy combined with extensive devascularization, 44 patients with splenectomy combined with selective devascularization and with preservation of paraesophageal veins, 39 patients with splenectomy combined with selective devascularization and reconstruction of spontaneous portosystemic shunt (34 patients with selective devascularization and reconstruction of spontaneous gastrorenal shunt and 5 patients with selective devascularization and reconstruction of spontaneous splenorenal shunt), 4 patients with secondary devascularization for variceal recurrence and 3 patients with devascularization and preservation of spleen; (3) shunt procedures were performed in 42 patients including 21 patients with splenectomy combined with coronary renal shunt, 11 patients with splenectomy combined with coronary-caval shunt, 6 patients with distal splenorenal shunt, 2 patients with proximal splenorenal shunt combined with devascularization, 1 patient with right gastroepiploic vein-inferior vena cava shunt and 1 patient with trans-inferior mesenteric vein coronary renal shunt. There were no operative deaths. The Clavien-Dindo grade 3 and above postoperative complication rate was 6.6% (15/229). Two hundred and eight patients were followed up for 6-60 months, with a median follow-up of 38 months. Severe recurrent varices were found in 21 patients (10.1%, 21/208), with 5 patients (2.4%, 5/208) presented with variceal bleeding. The rate of severe varices after selective shunting and selective devascularization by reconstructing the spontaneous portosystemic shunt (4.2%, 3/72) was significantly lower than that of the other devascularization procedures (13.7%, 17/124)(χ 2=4.53, P=0.033). Conclusion:Better clinical results were achieved by selecting the appropriate surgical procedures based on portal venous hemodynamic characteristics of patients. Selective shunting and selective devascularization by reconstructing the spontaneous portosystemic shunts significantly reduced the recurrence rate of severe varies.
ABSTRACT
Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.
Subject(s)
Solvents , Sertraline/analysis , Precision Medicine , Excipients , Process OptimizationABSTRACT
Tuberculosis is a bacterial infectious illness that is spread mostly by communicable droplets from one person to another. Drug-resistant patients and substandard drug authorization Mycobacterium tuberculosis is one of the two major obstacles to tuberculosis (TB) management in endemic areas, such as India and the rest of the world. Precision medicine, also known as customized medicine, is based on the diversity of systems biology and using predictive techniques to assess health risk and build tailored health plans to assist patients in reducing risk, preventing disease, and treating it with precision. Only active pulmonary tuberculosis is contagious. TB continues to be a significant source of illness and mortality in many low- and middle-income nations, and drug-resistant TB is a major problem in many areas. Furthermore, several novel TB diagnostics methods, such as quick molecular testing, have been developed, and there is a demand for simpler point-of-care tests. Personalized medicine ushers in a new age in healthcare. In the subject of Mycobacteriology, personalized medicine may be used in a variety of ways, including prevention, diagnosis, improved therapy, and prognosis. To change an independent proposition in mycobacterial disorders, a genetic inclination and a protein affliction investigation are presented. Patients' results should be turned into accurate diagnostic tests and focused therapy in order for personalized medicine to be used successfully by the healthcare system.
ABSTRACT
Thyroid cancer is the prevalent endocrine cancers, and its incidence is growing all over the world, according to the World Health Organization. About 5–10 per cent of individuals with differentiated thyroid carcinoma may experience destructive behavior and metastasis, and their disease will be refractory to therapeutic techniques such as radiation therapy for an unknown cause, despite the favorable prognosis. Most aggressive, deadly, and unresponsive type of the cancer is thyroid carcinoma. Regrettably, existing treatments are not specific and are thus considered poor in treating thyroid malignancies. Consequently, mortality in this malignancy despite progress in diagnosis and treatment is a prominent issue in medicine. evidence linking cellular, molecular, and genetic to a diagnostic and therapeutic simplification. With the new idea of personalized therapy for thyroid cancer diagnosis, arranging the treatment, discovering the success of the treatment and assessing the visualization has improved in the last ten years. Personalized medicine treatment for thyroid cancer is supported by these studies. According to the findings of this review, cellular and molecular processes of cancer will lay concrete on the way for the development of narrative biomarkers for personalized medicine that take individual variations into account
ABSTRACT
Three-dimensional printing is a technology that prints the products layer-by-layer, in which materials are deposited according to the digital model designed by computer aided design (CAD) software. This technology has competitive advantages regarding product design complexity, product personalization, and on-demand manufacturing. The emergence of 3D technology provides innovative strategies and new ways to develop novel drug delivery systems. This review summarizes the application of 3D printing technologies in the pharmaceutical field, with an emphasis on the advantages of 3D printing technologies for achieving rapid drug delivery, personalized drug delivery, compound drug delivery and customized drug delivery. In addition, this article illustrates the limitations and challenges of 3D printing technologies in the field of pharmaceutical formulation development.
ABSTRACT
BACKGROUND: Organoid models can partially restore the tissue and molecular characteristics of cells in the body, which is a preclinical model with good potential. Compared with precise and regenerative medicine methods, organoids with tissue organ functions can simulate body organs to the greatest extent. Moreover, organoid drug sensitivity data is more accurate than whole-genome sequencing. The technology for organoids can be combined with in vitro gene editing technology to achieve a genetic modification at organ level. OBJECTIVE: To summarize and analyze the research hotpots of organoid models in domestic and foreign databases in the past 10 years. METHODS: A computer search of WanFang, Web of Science, Chinese Clinical Trial Registry, ClinicalTrials.org and SooPAT was performed for articles regarding organoids in the past 10 years, and the research hotspots of organoid models were analyzed and concluded. RESULTS AND CONCLUSION: (1) Retrieval results of WanFang database: A total of 187 articles were included. In 2019, Chinese research on organoids showed an explosive growth. Among them, there were more studies on intestinal organoid models. The main application areas included precision medicine, tumor research and personalized medicine. (2) Retrieval results of the Web of Science Core Collection: A total of 2 450 articles were included. Twenty highly cited articles were analyzed using Histcite software. Among them, five classic original articles of organoids were screened out, and introduced intestinal organoids, pluripotent stem cell-derived three-dimensional brain organoids, prostate cancer organoids cultured from biopsy specimens and circulating tumor cells for a long time, kidney organoids containing nephrons, and three-dimensional organoid models of human stomach tissue, which are the pioneers in various fields and lay the foundation for future research on organoids. (3) Retrieval results of Chinese Clinical Trial Registry and ClinicalTrials.org: There were 13 study protocols related to organoid research in the Chinese Clinical Trial Registry and 23 in the ClinicalTrials.org. Research on clinical application of organoids in the United States is more extensive and develops earlier, but there are mostly cohort studies and single-arm trials. In recent years, China has achieved some results in the field of clinical organoid research, and two high-profile randomized controlled trials are underway. (4) Retrieval results of SooPAT Chinese patent database: There were 55 authorized patents, mainly involving the new culture method of 3D brain organoids, the research and development of high-throughput 3D cell, tissue-like and organoid dynamic culture systems. At present, researchers have successfully constructed a variety of organoid models, such as intestine, brain, kidney and various cancer tissues. However, due to insufficient evidence of clinical randomized controlled trials, the clinical applicability remains to be explored. Tumor organoids that are directly generated by tumor tissues of cancer patients in vitro can be used to analyze potential drug targets, screen anti-cancer drugs and develop new anti-tumor drugs, which will be the main research directions in the field of organoids in the future.
ABSTRACT
Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (
ABSTRACT
Idiosyncratic drug-induced liver injury (iDILI) encompasses the unexpected harms that prescription and non-prescription drugs, herbal and dietary supplements can cause to the liver. iDILI remains a major public health problem and a major cause of drug attrition. Given the lack of biomarkers for iDILI prediction, diagnosis and prognosis, searching new models to predict and study mechanisms of iDILI is necessary. One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI. Thus, major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients. However, there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms. Therefore, there is a need to optimize preclinical human
ABSTRACT
Aim: There are a few studies about the populations' knowledge and perceptions on personalized medicine in Saudi Arabia until now. Therefore, the aim of this study was to assess the knowledge and awareness on personalized medicine amongst health care specialists and university students in health colleges in Saudi Arabia.Methodology: This is a cross-sectional study that include a survey targeting health care specialists. The survey translated to Arabic and after validation, it was converted to an online survey using google forms.Results: About 52.34% of the participants have heard about different terms regarding personalized medicine (personalized medicine, healthcare reform, individualized care and pharmacogenomics). Most of the health care specialists in the present study said that they have poor knowledge about personalized medicine (68.75%). Most of the participants in the present study were interested to learn about personalized medicine and showed a positive attitude about it.Conclusion: The present study found that health care specialists had a poor knowledge about personalized medicine but they are interested to learn more about this field. Therefore, more training and awareness programs about personalized medicine are needed to facilitate its introduction in Saudi Arabia. Moreover, more focus on this field should be introduced into the health colleges’ curricula
ABSTRACT
Ayurveda has a rich history and its significance woven deeply in the Indian culture. The concept of prakriti (a person’s “nature” or constitutional type determined by the proportion of three doshas, namely - vata, pitta and kapha) in Ayurveda is deeply rooted in personalized health management. While the attributes of prakriti has been established to have a genomic basis, there is dearth of elaborate evidences linking prakriti with manifestation of diseases. Next generation sequencing studies have provided a causal link between variation in the gut microbiome and its effect on an individual’s fitness. Separately, reports have identified gut microbial patterns associated with several host variables such as geography, age, diet and extreme prakriti phenotypes. Recently, few reports have identified a “core gut microbiome” consisting of Bacteroides, Faecalibacterium, Prevotella and Ruminococcus prevalent across the Indian population; however, a few bacterial genera were specifically enriched in certain prakritis. Hence, in this review we aim to analyse the role of prakriti variations on dysbiosis of the gut microbiome and concomitantly its effect on human health. We suggest that prakriti phenotyping can function as a potential stratifier of the gut microbiome in a given population and may provide evidence for the conceptual framework of personalized medicine in Ayurvedic system of medicine.
ABSTRACT
El médico en la práctica clínica, asiste con frustración a la ausencia de una metodología uniforme y estandarizada, para procesar la gran avalancha de datos clínicos. Se ve envuelto en un proceso de toma de decisiones en condiciones de incertidumbre. No existen enfermedades sino enfermos. El inconsciente del pensamiento médico, parece querer expresar así la variabilidad extrema individual, que observa en la práctica clínica, así como la incertidumbre que le acompaña frente a la supuesta seguridad de las reglas diagnósticas y terapéuticas. La medicina de precisión y la medicina basada en la evidencia, nacieron con la intención de dar mejores respuestas a espacios de incertidumbre, ante problemas clínicos desde distintos ámbitos de la medicina como la genómica o el big data. Ambas incrementan la capacidad de ofrecer la intervención más adecuada para obtener el mejor resultado en términos de supervivencia, complicaciones y costo-efectividad para cada perfil de paciente en función de sus características biométricas. Los postulados de la medicina de precisión y la medicina basada en la evidencia estarán bajo escrutinio permanente de la comunidad científica en relación a: su racionalidad conceptual y lógica, su sustento empírico, y sobre todo el realismo de sus propuestas finales, por ello se propone como objetivo del artículo defender y argumentar que ambas propuestas metodológicas representan una continuidad y constituyen una inapreciable ayuda para cimentar el juicio clínico de los médicos y favorecer la toma de decisiones de importancia clínica en el contexto de una relación médico-paciente a la altura de las circunstancias científicas y éticas actuales(AU)
The doctor in clinical practice, attends with frustration the absence of a uniform and standardized methodology, to process the great avalanche of clinical data. He is involved in a decision-making process in conditions of uncertainty. There are no illnesses but sick people. The unconscious of the medical thought, seems to want to express the extreme individual variability, which observes in the clinical practice, as well as the uncertainty that accompanies it against the supposed security of the diagnostic and therapeutic rules. Precision medicine and medicine based on evidence, were born with the intention of giving better answers to spaces of uncertainty, to clinical problems from different areas of medicine such as genomics or big data. Both increase the ability to offer the most appropriate intervention to obtain the best result in terms of survival, complications and cost-effectiveness for each patient profile based on their biometric characteristics. The postulates of precision medicine and evidence-based medicine will be under permanent scrutiny of the scientific community in relation to: its conceptual and logical rationality, its empirical sustenance, and above all the realism of its final proposals, for that reason it is proposed as an objective of the article to defend and argue that both methodological proposals represent a continuity and constitute an invaluable aid to base the clinical judgment of physicians and favor the decision making of clinical importance in the context of a doctor-patient relationship at the height of the current scientific and ethical circumstances(AU)
Subject(s)
Humans , Male , Female , Evidence-Based Medicine , Methodology as a Subject , Precision MedicineABSTRACT
Abstract Rheumatoid arthritis (RA) is an autoimmune/inflammatory disease affecting 0.5 to 1% of adults worldwide and frequently leads to joint destruction and disability. Early diagnosis and early and effective therapy may prevent joint damage and lead to better long-term results. Therefore, reliable biomarkers and outcome measures are needed. Refinement of the understanding of molecular pathways involved in disease pathogenesis have been achieved by combining knowledge on RA-associated genes, environmental factors and the presence of serological elements. The presence of autoantibodies is a distinctive feature of RA. Rheumatoid Factor and Anti-Citrullinated Protein Antibodies are the two most remarkable autoantibodies in RA and provide different clinical and pathophysiological information. They precede the onset of disease symptoms and predict a more severe disease course, indicating a pathogenetic role in RA. Therefore, they promote a more accurate prognosis and contribute for a better disease management. Several RA-associated autoantibody systems have been identified: Anti-Carbamylated Antibodies, Anti-BRAF, Anti-Acetylated, Anti-PAD4 antibodies and others. Hopefully, the characterization of a comprehensive array of novel autoantibody systems in RA will provide unique pathogenic insights of relevance for the development of diagnostic and prognostic approaches compatible with an effective personalized medicine.
Subject(s)
Humans , Arthritis, Rheumatoid/diagnosis , Rheumatoid Factor/blood , Autoantibodies/blood , Early Diagnosis , Theranostic NanomedicineABSTRACT
A simple, robust and highly sensitive TB-ARMS method based on qPCR technique was developed to detect kras mutations. The technique was evaluated, and its clinical application was investigated. Mutation specific primers for eight common kras mutations and wild type gene targeted blockers were designed and optimized. Moreover, a mutant-enriched condition was used in to improve the sensitivity and specificity of mutation detection. Constructed plasmids carrying mutant kras genes, as well as confirmed wild type genomic DNA, were used as standard samples for evaluation of the methodology. The performance of our new method was validated by comparing the results of our method with that of a commercial kras kit in testing 40 clinical samples. Preoperative plasma samples, as well as paired tissue samples, were tested in parallel for evaluation of its clinical application. We have developed a new TB-ARMS method for kras mutation detection that can detect minor mutant alleles with a frequency as low as 0.01% in a heterogeneous sample. We have successfully demonstrated its 0.01% detection sensitivity with highly specific mutant amplification in conjunction with selective wild type suppression by blocker under a mutant-enriched reaction condition. We also showed that our TB-ARMS method was more accurate than the commercial kras kit, which is widely used presently. Furthermore, we have validated our method as an efficient liquid biopsy method, and the results of the plasma DNA detection with our TB-ARMS method were in consistent with the sequencing results of paired tissue samples. In conclusion, our TB-ARMS qPCR method could be effectively applied in kras mutation test for clinical tissue samples, as well as for liquid biopsy samples such as plasma.
Subject(s)
Humans , DNA Primers , Diagnostic Techniques and Procedures , Mutation , Neoplasms , Diagnosis , Genetics , Proto-Oncogene Proteins p21(ras) , Genetics , Real-Time Polymerase Chain ReactionABSTRACT
Most treatment strategies for asthma currently include inhaled corticosteroids, with the addition of long-acting beta-2-agonists or leukotriene modifiers, if necessary. However, some patients may not respond to conventional treatment. A better understanding of the pathophysiology of asthma has recently led to the development of biological agents, which have shown promising results for symptom control and future risk reduction in severe asthmatics. This article reviews currently available biologic agents, introduces related studies, and describes the subgroup of patients benefitting from each of biologic agents in the view point of precision medicine.