Personalized medicine最新文献

Colorectal cancer remains a major cause of mortality in the USA, despite advances in prevention and screening. Existing therapies focus primarily on generic treatment such as surgical intervention and chemotherapy, depending on disease severity. As personalized medicine and targeted molecular oncology continue to develop as promising treatment avenues, there has emerged a need for effective targets and biomarkers of colorectal cancer. The transmembrane receptor guanylyl cyclase C (GUCY2C) regulates intestinal homeostasis and has emerged as a tumor suppressor. Further, it is universally expressed in advanced metastatic colorectal tumors, as well as other cancer types that arise through intestinal metaplasia. In this context, GUCY2C satisfies many characteristics of a compelling target and biomarker for gastrointestinal malignancies.

Aim: The COVID-19 pandemic forced medical practices to augment healthcare delivery to remote and virtual services. We describe the results of a nationwide survey of cardiovascular professionals regarding telehealth perspectives. Materials & methods: A 31-question survey was sent early in the pandemic to assess the impact of COVID-19 on telehealth adoption & reimbursement. Results: A total of 342 clinicians across 42 states participated. 77% were using telehealth, with the majority initiating usage 2 months after the COVID-19 shutdown. A variety of video-based systems were used. Telehealth integration requirements differed, with electronic medical record integration being mandated in more urban than rural practices (70 vs 59%; p < 0.005). Many implementation barriers surfaced, with over 75% of respondents emphasizing reimbursement uncertainty and concerns for telehealth generalizability given the complexity of cardiovascular diseases. Conclusion: Substantial variation exists in telehealth practices. Further studies and legislation are needed to improve access, reimbursement and the quality of telehealth-based cardiovascular care.

Aim: To investigate the association of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil (5-FU) related toxicities and patient survival. Materials & methods: A total of 103 colorectal cancer patients prescribed 5-FU were included in the study. Genotyping was conducted for several DPYD, MTHFR and TYMS polymorphisms using a microarray analyzer. Results: DPYD 496A>G polymorphism was found to be significantly associated with 5-FU related grade 0-2, but not severe toxicities (p = 0.02). Furthermore, patients with DPYD 85TC and CC genotypes had longer progression and overall survival times compared to TT genotypes in our study group (log rank = 6.60; p = 0.01 and log rank = 4.40; p = 0.04, respectively). Conclusion: According to our results, DPYD 496AG and GG genotypes might be protective against severe adverse events compared to the AA genotype. Another DPYD polymorphism, 85T>C, may be useful in colorectal cancer prognosis. Further studies for both polymorphisms should be conducted in larger populations to achieve accurate results.

Aim: ALK, ROS1, NTRK and RET gene fusions and MET exon 14 skipping alterations represent novel predictive biomarkers for advanced non-small-cell lung cancer (NSCLC). Therefore, testing patients for these genetic variants is crucial for choosing the best selective treatment. Over the last couple of decades, next-generation sequencing (NGS) platforms have emerged as an extremely useful tool for detecting these variants. Materials & methods: In the present study, we report our NGS molecular records produced during a year of diagnostic activity. Results: Overall, our in-house developed NGS workflow successfully analyzed n = 116/131 (88.5%) NSCLC samples. Of these, eight (6.8%) and five (4.3%) out of 116 patients harbored ALK and RET gene rearrangements, respectively: one case harbored ROS1 gene fusion (0.7%). Conclusion: Our results highlight that an RNA-based NGS analysis can reliably detect gene fusion alterations, thereby playing a pivotal role in the management of NSCLC patients.

Aim: The effects of variants in IMPDH, UGT1A9, UGT1A8, UGT2B7 and SLCO1B1 genes on the efficacy and safety of mycophenolate mofetil (MMF) in the Tunisian population were investigated. Materials & methods: A total of 245 kidney transplant patients being treated with MMF were recruited and cotreated with cyclosporine or tacrolimus. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. MMF, cyclosporine and tacrolimus trough levels were measured by immunoassay. The AUC (AUC_0-12hMPA) was estimated by a Bayesian method. Results: In the tacrolimus-treated group, anemia and diarrhea were associated with the UGT1A9-98C and UGT1A9-275T alleles, respectively (p < 0.05). In the cyclosporine-treated group, leukopenia was associated with the SLCO1B1-521T allele (p < 0.05). Both groups had an increased risk of rejection (p < 0.05) associated with the variant alleles of IMPDH2-3757T>C, UGT1A9-2152C>T and UGT1A9-275C>A and the common allele of SLCO1B1-388A>G. However, no significant association was found between the studied genotypes and AUC_0-12hMPA or cotreatment levels. Conclusion: The results constitute preliminary evidence for the inclusion of the pharmacogenetics of MMF in kidney pretransplantation evaluations.

Aim: Our study aimed to screen the genotype frequencies of very important pharmacogenomic (VIP) mutations and identify their differences between Bai and other populations. Materials & methods: We selected 66 VIP variants from PharmGKB (www.pharmgkb.org/) for genotyping. χ2 test was used to identify differences in loci between these populations and FST values of Bai and the other 26 populations were analyzed. Results: Our study showed that the frequencies of SNPs of CYP3A5, ACE, PTGS2 and NAT2 differed significantly from those of the other 26 populations. At the same time, we found that some VIP variants may affect the metabolism of drugs and the genetic relationship between the Bai population and East Asian populations was found to be the closest. Conclusion: By comparing the genotype frequencies of different populations, the loci with significant differences were identified and discussed, providing a theoretical basis for individualized drug use in the Bai ethnic population.

Aim: To evaluate clinicians' and patients' perceptions of pharmacogenetic testing in a clinical setting. Materials & methods: This is a pragmatic mixed-method prospective observational study. Hospital pharmacists and neurologists participated in focus groups regarding pharmacogenetic testing; patients who received pharmacogenetic testing and their community pharmacists completed surveys to assess their perception of these tests. Results: Most study participants had a positive view of pharmacogenetic testing. Three major themes were identified from the focus groups: receptiveness to pharmacogenetic testing, pharmacogenetic test characteristics and integrating pharmacogenetic tests into practice. Conclusion: The views reported are encouraging for the eventual implementation of pharmacogenetics in practice. Local integration of these tests is an essential step to improve patient care through personalized medicine.

The application of artificial intelligence (AI) to healthcare has garnered significant enthusiasm in recent years. Despite the adoption of new analytic approaches, medical education on AI is lacking. We aim to create a usable AI primer for medical education. We discuss how to generate a clinical question involving AI, what data are suitable for AI research, how to prepare a dataset for training and how to determine if the output has clinical utility. To illustrate this process, we focused on an example of how medical imaging is employed in designing a machine learning model. Our proposed medical education curriculum addresses AI's potential and limitations for enhancing clinicians' skills in research, applied statistics and care delivery.

The increase in the use of genome-based screening and diagnostic tests adds to the overall costs of oncologic care for colorectal cancer. This, in turn, has resulted in an increase in published economic analyses. Aim: To perform a systematic literature review of the available economic evidence evaluating the value of genomic testing for colorectal cancer and appraise the quality of the economic studies conducted to date. Methods: A systematic review of the literature for economic studies of colorectal cancer genomics from January 2006 through October 2020, and evaluation of study quality using the Quality of Health Economic Studies (QHES) instrument was conducted. The validated QHES was then applied to a final set of articles that met eligibility criteria. Results: Our search of the literature initially yielded 12,859 records. A final set of 49 articles met our inclusion criteria. The QHES score ranged from 24 to 100, with an average score of 82. Most of the studies (n = 40, 82%) scored above 75 and were considered of good quality. Conclusion: Our analysis revealed that most of the economic analyses of colorectal cancer genomic molecular diagnostics in the literature may be of good quality. There is, however, some variation in methodological rigor between the articles.