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1.
Trials ; 25(1): 308, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715118

RESUMEN

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).


Asunto(s)
Pulmón , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial , Síndrome de Dificultad Respiratoria , Ultrasonografía Intervencional , Humanos , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/mortalidad , Respiración Artificial/métodos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Resultado del Tratamiento , Ultrasonografía Intervencional/métodos , Factores de Tiempo , Estudios Multicéntricos como Asunto , Valor Predictivo de las Pruebas , Medicina de Precisión/métodos
2.
Cancer Med ; 13(9): e7209, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38716651

RESUMEN

OBJECTIVE: Precision medicine is transforming cancer treatment, yet the perspectives of surgeons who often play a critical role in the delivery of precision medicine remain understudied. METHODS: We conducted semi-structured interviews with 13 surgeons involved in a precision medicine trial for children with poor prognosis cancer. We explored knowledge of genetics, confidence with somatic and germline results, ratings of benefit to stakeholders and willingness to undertake surgical procedures. RESULTS: Surgeons generally had positive attitudes towards precision medicine but expressed concerns about families' unrealistic expectations, mixed opinions on the benefits and the use of research-only biopsies. Most surgeons rated their genetics knowledge as 'good' (69%) and felt 'very confident' in identifying genetic specialists (66%), but 'not confident' (66.6%) in making treatment recommendations. Surgeons' willingness to undertake a procedure was influenced by potential patient benefit. CONCLUSIONS: Our findings support the need for more workforce and training support for surgeons to fully engage with precision medicine.


Asunto(s)
Actitud del Personal de Salud , Neoplasias , Medicina de Precisión , Cirujanos , Humanos , Medicina de Precisión/métodos , Neoplasias/terapia , Neoplasias/genética , Neoplasias/psicología , Femenino , Masculino , Pronóstico , Niño , Conocimientos, Actitudes y Práctica en Salud , Adulto , Familia/psicología
3.
JCO Clin Cancer Inform ; 8: e2300205, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38723213

RESUMEN

PURPOSE: Decision about the optimal timing of a treatment procedure in patients with hematologic neoplasms is critical, especially for cellular therapies (most including allogeneic hematopoietic stem-cell transplantation [HSCT]). In the absence of evidence from randomized trials, real-world observational data become beneficial to study the effect of the treatment timing. In this study, a framework to estimate the expected outcome after an intervention in a time-to-event scenario is developed, with the aim of optimizing the timing in a personalized manner. METHODS: Retrospective real-world data are leveraged to emulate a target trial for treatment timing using multistate modeling and microsimulation. This case study focuses on myelodysplastic syndromes, serving as a prototype for rare cancers characterized by a heterogeneous clinical course and complex genomic background. A cohort of 7,118 patients treated according to conventional available treatments/evidence across Europe and United States is analyzed. The primary clinical objective is to determine the ideal timing for HSCT, the only curative option for these patients. RESULTS: This analysis enabled us to identify the most appropriate time frames for HSCT on the basis of each patient's unique profile, defined by a combination relevant patients' characteristics. CONCLUSION: The developed methodology offers a structured framework to address a relevant clinical issue in the field of hematology. It makes several valuable contributions: (1) novel insights into how to develop decision models to identify the most favorable HSCT timing, (2) evidence to inform clinical decisions in a real-world context, and (3) the incorporation of complex information into decision making. This framework can be applied to provide medical insights for clinical issues that cannot be adequately addressed through randomized clinical trials.


Asunto(s)
Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Medicina de Precisión , Trasplante Homólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias Hematológicas/terapia , Trasplante Homólogo/métodos , Masculino , Persona de Mediana Edad , Femenino , Medicina de Precisión/métodos , Adulto , Anciano , Estudios Retrospectivos , Síndromes Mielodisplásicos/terapia , Adulto Joven
4.
Cien Saude Colet ; 29(5): e17652022, 2024 May.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-38747779

RESUMEN

The complexities referred to in the search for "accuracy" in the diagnosis of cystic fibrosis (CF) point to reflections around "what is needed" in the current situation of "precision medicine". We analyzed the discourses of 19 social actors belonging to the community of specialists in cystic fibrosis, exploring the semantic meanings of the word "precision", and the barriers to diagnosis and innovations in therapeutics. We adopted the critical discourse analysis (CDA) of Norman Fairclough in order to achieve the discursive constructions around the integrality of care, the guarantee and equitable supply of basic social needs. Access was identified as an emic category when in the social arenas of dispute are health needs and the right to life.


As complexidades referidas na busca pela "exatidão" no diagnóstico da fibrose cística (FC) apontam para reflexões em torno de "o que é preciso" na atual conjuntura da "medicina de precisão". Analisamos os discursos de 19 atores sociais pertencentes à comunidade de especialistas na fibrose cística, explorando as acepções semânticas do vocábulo "precisão" e as barreiras ao diagnóstico e às inovações na terapêutica. Adotamos a análise crítica do discurso de Norman Fairclough a fim de alcançar as construções discursivas em torno da integralidade do cuidado, da garantia e oferta equitativa dos básicos sociais. O acesso foi identificado como categoria êmica quando nas arenas sociais de disputa estão as necessidades de saúde e o direito à vida.


Asunto(s)
Fibrosis Quística , Accesibilidad a los Servicios de Salud , Fibrosis Quística/diagnóstico , Fibrosis Quística/terapia , Humanos , Medicina de Precisión/métodos , Necesidades y Demandas de Servicios de Salud , Derecho a la Salud
5.
J Biomed Sci ; 31(1): 47, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724973

RESUMEN

The field of regenerative medicine has witnessed remarkable advancements with the emergence of induced pluripotent stem cells (iPSCs) derived from a variety of sources. Among these, urine-derived induced pluripotent stem cells (u-iPSCs) have garnered substantial attention due to their non-invasive and patient-friendly acquisition method. This review manuscript delves into the potential and application of u-iPSCs in advancing precision medicine, particularly in the realms of drug testing, disease modeling, and cell therapy. U-iPSCs are generated through the reprogramming of somatic cells found in urine samples, offering a unique and renewable source of patient-specific pluripotent cells. Their utility in drug testing has revolutionized the pharmaceutical industry by providing personalized platforms for drug screening, toxicity assessment, and efficacy evaluation. The availability of u-iPSCs with diverse genetic backgrounds facilitates the development of tailored therapeutic approaches, minimizing adverse effects and optimizing treatment outcomes. Furthermore, u-iPSCs have demonstrated remarkable efficacy in disease modeling, allowing researchers to recapitulate patient-specific pathologies in vitro. This not only enhances our understanding of disease mechanisms but also serves as a valuable tool for drug discovery and development. In addition, u-iPSC-based disease models offer a platform for studying rare and genetically complex diseases, often underserved by traditional research methods. The versatility of u-iPSCs extends to cell therapy applications, where they hold immense promise for regenerative medicine. Their potential to differentiate into various cell types, including neurons, cardiomyocytes, and hepatocytes, enables the development of patient-specific cell replacement therapies. This personalized approach can revolutionize the treatment of degenerative diseases, organ failure, and tissue damage by minimizing immune rejection and optimizing therapeutic outcomes. However, several challenges and considerations, such as standardization of reprogramming protocols, genomic stability, and scalability, must be addressed to fully exploit u-iPSCs' potential in precision medicine. In conclusion, this review underscores the transformative impact of u-iPSCs on advancing precision medicine and highlights the future prospects and challenges in harnessing this innovative technology for improved healthcare outcomes.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Células Madre Pluripotentes Inducidas , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Células Madre Pluripotentes Inducidas/citología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Evaluación Preclínica de Medicamentos/métodos , Orina/citología , Medicina Regenerativa/métodos
6.
Br J Anaesth ; 132(6): 1187-1189, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729743

RESUMEN

Viscoelastic haemostatic testing (VHT) has been used to determine hyperfibrinolysis and hypofibrinolysis. When modified by addition of tissue plasminogen activator (tPA), VHT has been suggested to assess responses to antifibrinolytic therapy and to estimate the concentration of tranexamic acid in patients undergoing cardiac surgery. Despite some evidence that tPA-modified VHT might allow individualisation of antifibrinolytic therapy, further studies are warranted to prove its clinical benefit for postsurgical bleeding, transfusion of blood products, and thromboembolic events.


Asunto(s)
Antifibrinolíticos , Humanos , Antifibrinolíticos/uso terapéutico , Hemorragia Posoperatoria/prevención & control , Medicina de Precisión/métodos , Tromboelastografía/métodos , Activador de Tejido Plasminógeno/uso terapéutico , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/administración & dosificación , Resultado del Tratamiento
7.
J Cell Mol Med ; 28(9): e18374, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38722288

RESUMEN

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.


Asunto(s)
Neoplasias de la Mama , Organoides , Medicina de Precisión , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Femenino , Organoides/efectos de los fármacos , Organoides/patología , Organoides/metabolismo , Medicina de Precisión/métodos , Animales , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones , Resistencia a Antineoplásicos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Persona de Mediana Edad
8.
Support Care Cancer ; 32(5): 323, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695938

RESUMEN

PURPOSE: Breast cancer follow-up (surveillance and aftercare) varies from one-size-fits-all to more personalised approaches. A systematic review was performed to get insight in existing evidence on (cost-)effectiveness of personalised follow-up. METHODS: PubMed, Scopus and Cochrane were searched between 01-01-2010 and 10-10-2022 (review registered in PROSPERO:CRD42022375770). The inclusion population comprised nonmetastatic breast cancer patients ≥ 18 years, after completing curative treatment. All intervention-control studies studying personalised surveillance and/or aftercare designed for use during the entire follow-up period were included. All review processes including risk of bias assessment were performed by two reviewers. Characteristics of included studies were described. RESULTS: Overall, 3708 publications were identified, 64 full-text publications were read and 16 were included for data extraction. One study evaluated personalised surveillance. Various personalised aftercare interventions and outcomes were studied. Most common elements included in personalised aftercare plans were treatment summaries (75%), follow-up guidelines (56%), lists of available supportive care resources (38%) and PROs (25%). Control conditions mostly comprised usual care. Four out of seven (57%) studies reported improvements in quality of life following personalisation. Six studies (38%) found no personalisation effect, for multiple outcomes assessed (e.g. distress, satisfaction). One (6.3%) study was judged as low, four (25%) as high risk of bias and 11 (68.8%) as with concerns. CONCLUSION: The included studies varied in interventions, measurement instruments and outcomes, making it impossible to draw conclusions on the effectiveness of personalised follow-up. There is a need for a definition of both personalised surveillance and aftercare, whereafter outcomes can be measured according to uniform standards.


Asunto(s)
Cuidados Posteriores , Neoplasias de la Mama , Femenino , Humanos , Cuidados Posteriores/métodos , Neoplasias de la Mama/terapia , Análisis Costo-Beneficio , Estudios de Seguimiento , Medicina de Precisión/métodos
9.
J Intern Med ; 295(6): 785-803, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38698538

RESUMEN

In the last decades, the development of high-throughput molecular assays has revolutionised cancer diagnostics, paving the way for the concept of personalised cancer medicine. This progress has been driven by the introduction of such technologies through biomarker-driven oncology trials. In this review, strengths and limitations of various state-of-the-art sequencing technologies, including gene panel sequencing (DNA and RNA), whole-exome/whole-genome sequencing and whole-transcriptome sequencing, are explored, focusing on their ability to identify clinically relevant biomarkers with diagnostic, prognostic and/or predictive impact. This includes the need to assess complex biomarkers, for example microsatellite instability, tumour mutation burden and homologous recombination deficiency, to identify patients suitable for specific therapies, including immunotherapy. Furthermore, the crucial role of biomarker analysis and multidisciplinary molecular tumour boards in selecting patients for trial inclusion is discussed in relation to various trial concepts, including drug repurposing. Recognising that today's exploratory techniques will evolve into tomorrow's routine diagnostics and clinical study inclusion assays, the importance of emerging technologies for multimodal diagnostics, such as proteomics and in vivo drug sensitivity testing, is also discussed. In addition, key regulatory aspects and the importance of patient engagement in all phases of a clinical trial are described. Finally, we propose a set of recommendations for consideration when planning a new precision cancer medicine trial.


Asunto(s)
Biomarcadores de Tumor , Neoplasias , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Neoplasias/genética , Neoplasias/terapia , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Secuenciación de Nucleótidos de Alto Rendimiento , Ensayos Clínicos como Asunto , Oncología Médica/métodos , Oncología Médica/tendencias
10.
Am Soc Clin Oncol Educ Book ; 44(3): e431060, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38771996

RESUMEN

Gastroesophageal cancers (GECs) represent a significant clinical challenge. For early resectable GEC, the integration of immune checkpoint inhibitors into the perioperative chemotherapy and chemoradiation treatment paradigms are being explored and showing promising results. Frontline management of metastatic GEC is exploring the role of targeted therapies beyond PD-1 inhibitors, including anti-human epidermal growth factor receptor 2 agents, Claudin 18.2 inhibitors, and FGFR2 inhibitors, which have shown considerable efficacy in recent trials. Looking ahead, ongoing trials and emerging technologies such as bispecific antibodies, antibody-drug conjugates, and adoptive cell therapies like chimeric antigen receptor T cells are expected to define the future of GEC management. These advancements signify a paradigm shift toward personalized and immunotherapy-based approaches, offering the potential for improved outcomes and reduced toxicity for patients with GEC.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Esofágicas , Medicina de Precisión , Neoplasias Gástricas , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Gástricas/terapia , Medicina de Precisión/métodos , Terapia Molecular Dirigida , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Terapia Combinada
11.
Int J Mol Sci ; 25(9)2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38732242

RESUMEN

Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor and inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond the ability for surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors and targeted therapies. Acquired resistance to these therapies and treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized for specific patients and/or populations. Here, we review the current landscape and progress of standard therapies and explore what personalized oncology techniques may entail in the scope of melanoma. Our purpose is to provide an up-to-date summary of the tools at our disposal that work to circumvent the common barriers faced when battling melanoma.


Asunto(s)
Melanoma , Medicina de Precisión , Neoplasias Cutáneas , Humanos , Melanoma/genética , Melanoma/terapia , Melanoma/patología , Medicina de Precisión/métodos , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Terapia Molecular Dirigida/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Mutación
12.
Nutrients ; 16(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732608

RESUMEN

Flavonoids exert vasculoprotective effects in humans, but interindividual variability in their action has also been reported. This study aims to identify genes that are associated with vascular health effects of flavonoids and whose polymorphisms could explain interindividual variability in response to their intake. Applying the predetermined literature search criteria, we identified five human intervention studies reporting positive effects of flavonoids on vascular function together with global genomic changes analyzed using microarray methods. Genes involved in vascular dysfunction were identified from genome-wide association studies (GWAS). By extracting data from the eligible human intervention studies, we obtained 5807 differentially expressed genes (DEGs). The number of identified upstream regulators (URs) varied across the studies, from 227 to 1407. The search of the GWAS Catalog revealed 493 genes associated with vascular dysfunction. An integrative analysis of transcriptomic data with GWAS genes identified 106 candidate DEGs and 42 candidate URs, while subsequent functional analyses and a search of the literature identified 20 top priority candidate genes: ALDH2, APOE, CAPZA1, CYP11B2, GNA13, IL6, IRF5, LDLR, LPL, LSP1, MKNK1, MMP3, MTHFR, MYO6, NCR3, PPARG, SARM1, TCF20, TCF7L2, and TNF. In conclusion, this integrated analysis identifies important genes to design future nutrigenetic studies for development of precision nutrition for polyphenols.


Asunto(s)
Flavonoides , Estudio de Asociación del Genoma Completo , Nutrigenómica , Humanos , Nutrigenómica/métodos , Flavonoides/farmacología , Flavonoides/administración & dosificación , Polifenoles/farmacología , Polifenoles/administración & dosificación , Medicina de Precisión/métodos , Genómica/métodos
14.
Med Oncol ; 41(6): 145, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38727885

RESUMEN

Polyelectrolytes represent a unique class of polymers abundant in ionizable functional groups. In a solution, ionized polyelectrolytes can intricately bond with oppositely charged counterparts, giving rise to a fascinating phenomenon known as a polyelectrolyte complex. These complexes arise from the interaction between oppositely charged entities, such as polymers, drugs, and combinations thereof. The polyelectrolyte complexes are highly appealing in cancer management, play an indispensable role in chemotherapy, crafting biodegradable, biocompatible 3D membranes, microcapsules, and nano-sized formulations. These versatile complexes are pivotal in designing controlled and targeted release drug delivery systems. The present review emphasizes on classification of polyelectrolyte complex along with their formation mechanisms. This review comprehensively explores the applications of polyelectrolyte complex, highlighting their efficacy in targeted drug delivery strategies for combating different forms of cancer. The innovative use of polyelectrolyte complex presents a potential breakthrough in cancer therapeutics, demonstrating their role in enhancing treatment precision and effectiveness.


Asunto(s)
Antineoplásicos , Sistemas de Liberación de Medicamentos , Neoplasias , Polielectrolitos , Humanos , Polielectrolitos/química , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Medicina de Precisión/métodos
15.
Med Sci Monit ; 30: e943240, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38711247

RESUMEN

Behçet uveitis poses significant management challenges, owing to its intricate pathogenesis and the severe prognosis it harbors, frequently culminating in irreversible visual impairment and an elevated risk of blindness. This review synthesizes contemporary insights into personalized immunosuppressive strategies for Behçet uveitis, emphasizing the necessity for a customized approach in recognition of the disease's heterogeneity and the variable responsiveness to treatment. This discourse elaborates on the application, efficacy, and safety profiles of traditional immunosuppressants, highlighting a paradigm shift toward integrative combination therapies aimed at diminishing reliance on glucocorticoids and mitigating their associated adverse effects. This thorough evaluation seeks to enlighten clinical practices and spearhead future investigations aimed at refining the management of Behçet uveitis, championing a personalized, multidisciplinary strategy to amplify therapeutic efficacy and enhance patient quality of life.


Asunto(s)
Síndrome de Behçet , Inmunosupresores , Uveítis , Humanos , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Behçet/terapia , Síndrome de Behçet/inmunología , Uveítis/inmunología , Uveítis/tratamiento farmacológico , Uveítis/terapia , Inmunosupresores/uso terapéutico , Medicina de Precisión/métodos , Calidad de Vida
16.
Cancer Epidemiol Biomarkers Prev ; 33(5): 635-637, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38689576

RESUMEN

The Oncotype DX (ODX) assay predicts recurrence risk and demonstrates the benefits of adjuvant therapy in patients with early-stage, hormone receptor (HR)-positive/HER2-negative breast cancer. ODX uptake varies by patients' racial/ethnic backgrounds and socioeconomic status (SES). However, community-level variability remains unknown, and research regarding the association between testing status and receipt of adjuvant chemotherapy is limited. To fill these knowledge gaps, Van Alsten and colleagues found a 6% lower prevalence of ODX uptake among patients residing in high SES-deprived areas than among those residing in low SES-deprived areas. Among patients with low and median ODX recurrence scores, those who underwent testing were 28% and 21% less likely to receive adjuvant chemotherapy than those who did not, respectively. The findings emphasize the role of social determinants of health. However, to further reduce or eliminate racial/ethnic disparities and SES inequities, we would need sufficient and effective multi-level approaches. These involve lower ODX testing costs, health insurance coverage expansion, re-classification and validation of ODX recurrence scores in patients of minority ancestry, and the development of a faster, more accurate, and affordable test. See related article by Van Alsten et al., p. 654.


Asunto(s)
Neoplasias de la Mama , Disparidades en Atención de Salud , Medicina de Precisión , Determinantes Sociales de la Salud , Humanos , Neoplasias de la Mama/etnología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/genética , Femenino , Medicina de Precisión/métodos , Disparidades en Atención de Salud/estadística & datos numéricos
17.
BMC Cancer ; 24(1): 574, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724991

RESUMEN

BACKGROUND: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. METHODS: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. DISCUSSION: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. TRIAL REGISTRATION: NCT05525858.


Asunto(s)
Terapia Molecular Dirigida , Neoplasias , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , República de Corea , Terapia Molecular Dirigida/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biomarcadores de Tumor/genética , Genómica/métodos , Mutación , Estudios Observacionales como Asunto
18.
Am Soc Clin Oncol Educ Book ; 44(3): e438466, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38768405

RESUMEN

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Manejo de la Enfermedad , Pronóstico , Medicina de Precisión/métodos , Biomarcadores de Tumor , Terapia Molecular Dirigida
19.
OMICS ; 28(5): 211-212, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38709543

RESUMEN

How we choose to respond to uncertainty matters for robust and responsible science. New laws and consensus reports are popular instruments for global governance of emerging technology and attendant uncertainty. However, the sociologist Pierre Bourdieu noted that "[t]he judicial situation operates like a neutral space that neutralizes the stakes in any conflict through the de-realization and distancing implicit in the conversion of a direct struggle between parties into a dialogue between mediators." Put in other words, while law and legal modes of reasoning are certainly useful for conflict resolution and closure, their overprivileging in emerging technology and uncertainty governance can potentially bring about depoliticization by transforming the struggles and dissent necessary for democratic governance into a "dialogue between mediators." Hence, the critical sociological gaze offered by Bourdieu is particularly relevant for democratization of global governance of multiomics technologies and timely with the current uptake of personalized medicine. For example, in May 2023, the Romanian government introduced a law to give patients the right to personalized medicine. Personalized medicine is related to the larger umbrella concept and field of theranostics, the fusion of therapeutics and diagnostics. It is therefore timely to reflect on a "right for theranostics in planetary health," considering the potential for future pandemics and ecological crises in the 21st century. Rather than forcing consensus or convergence in an innovation ecosystem, dissent grounded in rigorous political theory, sociology of law and critical legal studies can strengthen democratization and global governance for personalized medicine and multiomics technologies.


Asunto(s)
Política , Medicina de Precisión , Medicina de Precisión/métodos , Humanos , Incertidumbre , COVID-19/epidemiología
20.
Zhongguo Fei Ai Za Zhi ; 27(4): 276-282, 2024 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-38769830

RESUMEN

The continuous advancement of molecular detection technology has greatly propelled the development of precision medicine for lung cancer. However, tumor heterogeneity is closely associated with tumor metastasis, recurrence, and drug resistance. Additionally, different lung cancer patients with the same genetic mutation may exhibit varying treatment responses to different therapeutic strategies. Therefore, the development of modern precision medicine urgently requires the precise formulation of personalized treatment strategies through personalized tumor models. Lung cancer organoid (LCO) can highly simulate the biological characteristics of tumor in vivo, facilitating the application of innovative drugs such as antibody-drug conjugate in precision medicine for lung cancer. With the development of co-culture model of LCO with tumor microenvironment and tissue engineering technology such as microfluidic chip, LCO can better preserve the biological characteristics and functions of tumor tissue, further improving high-throughput and automated drug sensitivity experiment. In this review, we combine the latest research progress to summarize the application progress and challenges of LCO in precision medicine for lung cancer.
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Asunto(s)
Neoplasias Pulmonares , Organoides , Medicina de Precisión , Humanos , Medicina de Precisión/métodos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Organoides/efectos de los fármacos , Animales
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