This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer ...(31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.
The present study aims to establish the Japanese Cancer Genome Atlas (JCGA) by analyzing fresh frozen tumor tissues obtained from 5143 Japanese cancer patients. Somatic driver and druggable alterations were detected in 72.2% and 11.3% of samples, respectively, and germline pathogenic mutations in hereditary cancer genes were identified in 9.2% of samples. The JCGA dataset and analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients.
Personalized Telehealth in the Future: A Global Research Agenda Dinesen, Birthe; Nonnecke, Brandie; Lindeman, David ...
JMIR. Journal of medical internet research/Journal of medical internet research,
2016-Mar-01, 2016-03-01, 20160301, Letnik:
18, Številka:
3
Journal Article
Recenzirano
Odprti dostop
As telehealth plays an even greater role in global health care delivery, it will be increasingly important to develop a strong evidence base of successful, innovative telehealth solutions that can ...lead to scalable and sustainable telehealth programs. This paper has two aims: (1) to describe the challenges of promoting telehealth implementation to advance adoption and (2) to present a global research agenda for personalized telehealth within chronic disease management. Using evidence from the United States and the European Union, this paper provides a global overview of the current state of telehealth services and benefits, presents fundamental principles that must be addressed to advance the status quo, and provides a framework for current and future research initiatives within telehealth for personalized care, treatment, and prevention. A broad, multinational research agenda can provide a uniform framework for identifying and rapidly replicating best practices, while concurrently fostering global collaboration in the development and rigorous testing of new and emerging telehealth technologies. In this paper, the members of the Transatlantic Telehealth Research Network offer a 12-point research agenda for future telehealth applications within chronic disease management.
...there is a need to validate these composite SPs in large observational and prospective studies, to avoid the biases inherent to retrospective studies. ...we suggest that a prompt identification of ...different SPs could facilitate the patient stratification in the era of individualized medicine. Authors Sample size (n.) Population Type of SPs Classification Findings Shald4 et al. 320 ICU septic patients Clinical presentation SP 1: MOF SP 2: ND SP 3: RD SP 4: other patients SP 1 showed higher mortality rate Bhavani6et al. 12,473 Patients with sepsis/suspected infection Clinical presentation SP A: higher temperature, HR, RR SP B: lower temperature, HR, RR SP C: older patients SP D: older patients, high doses of vasopressors SP A and D showed higher mortality rate Seymour5 et al. 20,189 Septic patients Clinical presentation SP α: low doses of vasopressors SP β: older patients SP γ: higher rate of inflammation and RD SP δ: LD and septic shock SP δ showed higher mortality rate Seymour1 et al. 191 Animal study Inflammatory status/laboratory alterations Class 1:hypoinflamatory profile Class 2:hyperinflammatory profile Class 2 showed a rapid clinical deterioration Carcillo2 et al. 100 Pediatric study Inflammatory status/laboratory alterations Type 1. immune paralysis + MOF Type 2: thrombocytopenia + MOF Type 3: LD + MOF Type 2 showed higher mortality rate Kudo3 et al. 3696 ICU septic shock patients Inflammatory status/laboratory alterations Cluster dA: severe coagulopathy Cluster dB: moderate coagulopathy Cluster dC: mixed cases Cluster dD: mixed cases Treatment with rhTM lower mortality rate in clusters with severe coagulopathy Table 1 Classification of septic phenotypes based on current literature.
Abstract
Monitoring and modeling biomedical, health care and wellness data from individuals and converging data on a population scale have tremendous potential to improve understanding of the ...transition to the healthy state of human physiology to disease setting. Wellness monitoring devices and companion software applications capable of generating alerts and sharing data with health care providers or social networks are now available. The accessibility and clinical utility of such data for disease or wellness research are currently limited. Designing methods for streaming data capture, real-time data aggregation, machine learning, predictive analytics and visualization solutions to integrate wellness or health monitoring data elements with the electronic medical records (EMRs) maintained by health care providers permits better utilization. Integration of population-scale biomedical, health care and wellness data would help to stratify patients for active health management and to understand clinically asymptomatic patients and underlying illness trajectories. In this article, we discuss various health-monitoring devices, their ability to capture the unique state of health represented in a patient and their application in individualized diagnostics, prognosis, clinical or wellness intervention. We also discuss examples of translational bioinformatics approaches to integrating patient-generated data with existing EMRs, personal health records, patient portals and clinical data repositories. Briefly, translational bioinformatics methods, tools and resources are at the center of these advances in implementing real-time biomedical and health care analytics in the clinical setting. Furthermore, these advances are poised to play a significant role in clinical decision-making and implementation of data-driven medicine and wellness care.
Personalized medicine has been identified as a powerful tool for addressing the myriad of health issues facing different health systems globally. Although recent studies have expanded our ...understanding of how different factors such as genetics and the environment play significant roles in affecting the health of individuals, there are still several other issues affecting their translation into personalizing health interventions globally. Since African populations have demonstrated huge genetic diversity, there is a significant need to apply the concepts of personalized medicine to overcome various African-specific health challenges. Thus, we review the current state, progress, and challenges facing the adoption of personalized medicine in Africa with a view to providing insights to critical stakeholders on the right approach to deploy.
Despite a lower estimated rate of cancer incidence in Iran compared to the global average, the trend is unfortunately increasing. This necessitates the implementation of early detection of cancer and ...targeted therapies to effectively treat various types of cancer. Therefore, the 5th "International Royan Cancer Conference: From Bench to Bedside" was held to focus on critical cancer-related aspects such as gene- and cell therapy, immunotherapy, oligonucleotides in cancer treatment, biosensors for detection, and drug delivery. The 2-day conference took place in February 2024 at the Royan Institute, Tehran. This collaborative effort brought together experts from both basic and clinical research fields. The primary objective of the conference was to address clinical challenges and harness the potential of basic sciences for early cancer diagnosis and treatment, with a robust emphasis on ethical considerations. The conference aimed to ensure optimal patient care while advancing scientific understanding in the field and facilitating effective research collaborations among researchers and enthusiasts dedicated to combating cancer.Despite a lower estimated rate of cancer incidence in Iran compared to the global average, the trend is unfortunately increasing. This necessitates the implementation of early detection of cancer and targeted therapies to effectively treat various types of cancer. Therefore, the 5th "International Royan Cancer Conference: From Bench to Bedside" was held to focus on critical cancer-related aspects such as gene- and cell therapy, immunotherapy, oligonucleotides in cancer treatment, biosensors for detection, and drug delivery. The 2-day conference took place in February 2024 at the Royan Institute, Tehran. This collaborative effort brought together experts from both basic and clinical research fields. The primary objective of the conference was to address clinical challenges and harness the potential of basic sciences for early cancer diagnosis and treatment, with a robust emphasis on ethical considerations. The conference aimed to ensure optimal patient care while advancing scientific understanding in the field and facilitating effective research collaborations among researchers and enthusiasts dedicated to combating cancer.
To assess which improvements and side effects are considered most important by patients with OSA treated with a MAD.
A specific questionnaire consisting of 20 questions, including 10 questions on ...improvements and 10 on side effects, was developed and mailed to all subjects (54).
42 patients, participated in the survey by answering the questionnaire. The results showed that patients placed greater importance on the positive outcomes of treatment, with the most significant being the reduction in snoring and improvement in sleep quality. On the other hand, the side effects of difficulty speaking with the device, tooth mobility, and foreign body sensation were considered important.
The advantages perceived by the patients appear to outweigh the disadvantages, especially the reduction of snoring, increased productivity, and improved social and intellectual life. Most significant side effects are reversible and short-term, while occlusal changes, is not considered important by patients.
Genetic-guided P2Y12 inhibitor selection has been proposed to reduce ischemic events by identifying CYP2C19 loss-of-function (LOF) carriers at increased risk with clopidogrel treatment after ...percutaneous coronary intervention (PCI). A prespecified analysis of TAILOR-PCI (Tailored Antiplatelet Therapy Following PCI) evaluated the effect of genetic-guided P2Y12 inhibitor therapy on cumulative ischemic and bleeding events.
Here, the authors detail a prespecified analysis of cumulative endpoints. The primary endpoint was cumulative incidence rate of ischemic events at 12 months. Cumulative incidence of major and minor bleeding was a secondary endpoint. Cox proportional hazards models as adapted by Wei, Lin, and Weissfeld were used to estimate the effect of this strategy on all observed events.
The TAILOR-PCI trial was a prospective trial including 5,302 post-PCI patients with acute and stable coronary artery disease (CAD) who were randomized to genetic-guided P2Y12 inhibitor or conventional clopidogrel therapy. In the genetic-guided group, LOF carriers were prescribed ticagrelor, whereas noncarriers received clopidogrel. TAILOR-PCI’s primary analysis was time to first event in LOF carriers.
Among 5,276 patients (median age 62 years; 25% women; 82% acute CAD; 18% stable CAD), 1,849 were LOF carriers (903 genetic-guided; 946 conventional therapy). The cumulative primary endpoint was significantly reduced in the genetic-guided group compared with the conventional therapy (HR: 0.61; 95% CI: 0.41-0.89; P = 0.011) with no significant difference in cumulative incidence of major or minor bleeding (HR: 1.36; 95% CI: 0.67-2.76; P = 0.39).
Among CYP2C19 LOF carriers undergoing PCI, a genetic-guided strategy resulted in a statistically significant reduction in cumulative ischemic events without a significant difference in bleeding. (Tailored Antiplatelet Therapy Following PCI TAILOR-PCI; NCT01742117)
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p53 and antiapoptotic B-cell leukemia/lymphoma 2 (BLC2) have been proposed as prognostic markers for early breast cancer (BC), although their relationship with conventional parameters and patient ...prognosis, as well as their distribution within the molecular BC subtypes remains uncertain.
In this observational study, we analyzed the immunohistochemical expression of p53 and BLC2 in 1099 early BC patients surgically treated between 2000 and 2006 and followed for at least 5 years, also considering their association with pathologic factors and molecular subtypes, as well as their influence on disease-free survival.
p53 and BLC2 are distributed differently across molecular subtypes (P < .0001); in particular, p53 positivity and BLC2 negativity seems to be associated with more aggressive conventional tumor phenotypes. Moreover, BLC2 negativity seems to be a significant discriminating factor for disease-free survival (P = .003) according to Kaplan-Meier analysis, while p53 seems to have no discriminating effect. Among patients with discordant p53/BLC2 phenotype, the combination p53+BLC2− seems to be associated with the worst outcomes (P = .007) and significantly influenced the clinical course of node-negative patients treated only with hormone therapy (P = .004).
These two biomarkers, in addition to conventional pathologic factors and molecular subtype, could help define the risk and outcome of BC.
Management of early breast cancer (BC) is complicated by the limited number of clinicopathologic prognostic factors available. We analyzed p53 and antiapoptotic B-cell leukemia/lymphoma 2 (BLC2) immunohistochemistry expression in 1099 early BC patients. p53 and BLC2 are distributed differently across BC molecular subtypes; p53-positive/BLC2-negative BC corresponds to more aggressive phenotypes. p53 and BLC2 could help define the risk and outcome of BC in addition to molecular subtypes.
Inclusion body myositis (IBM) is a progressive muscle disease affecting patients over the age of 40, with distinctive clinical and histopathological features. The typical clinical phenotype is ...characterized by prominent involvement of deep finger flexors and quadriceps muscles. Less common presentations include isolated dysphagia, asymptomatic hyper-CKemia, and axial or limb weakness beyond the typical pattern. IBM is associated with marked morbidity as majority of patients eventually become wheelchair dependent with limited use of their hands and marked dysphagia. Furthermore, IBM mildly affects longevity with aspiration pneumonia and respiratory complications being the most common cause of death. On muscle biopsy, IBM is characterized by a peculiar combination of endomysial inflammation, rimmed vacuoles, and protein aggregation. These histopathological features are reflective of the complexity of underlying disease mechanisms. No pharmacological treatment is yet available for IBM. Monitoring for swallowing and respiratory complications, exercise, and addressing mobility issues are the mainstay of management. Further research is needed to better understand disease pathogenesis and identify novel therapeutic targets.
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