Personalized medicine最新文献

Aim: Patient knowledge and attitudes toward pharmacogenetic (PGx) testing may impact adoption of clinical testing. Methods: Questionnaires regarding knowledge, attitudes and ethics of PGx testing were distributed to 504 patients enrolled in the ADAPT study conducted at two urban hospitals in Philadelphia, Pennsylvania, USA. Responses were assessed using multivariable logistic regression. Results: 311 completed the survey (62% response rate). 74% were unaware of PGx testing, but 79% indicated using PGx results to predict medication efficacy was important. In a multivariable model, higher education level (p = 0.031) and greater genetics knowledge (p < 0.001) were associated with more positive attitudes toward PGx testing. Conclusion: Greater patient knowledge of genetics was associated with a more positive attitude toward PGx testing, indicating that educational strategies aimed at increasing genetics knowledge may enhance adoption of PGx testing in the clinic.

Aim: To determine if interventional cardiologists' knowledge and attitudes toward pharmacogenetic (PGx) testing influenced their antiplatelet prescribing decisions in response to CYP2C19 results. Materials & methods: Surveys were administered prior to participating in a randomized trial of CYP2C19 testing. Associations between baseline knowledge/attitudes and agreement with the genotype-guided antiplatelet recommendations were determined using multivariable logistic regression. Results: 50% believed that PGx testing would be valuable to predict medication toxicity or efficacy. 64% felt well informed about PGx testing and its therapeutic application. However, PGx experience, knowledge, nor attitudes were significantly associated with agreement to genotype-guided antiplatelet recommendations. Conclusion: Cardiologists' knowledge and attitudes were not associated with CYP2C19-guided antiplatelet prescribing, but larger studies should be done to confirm this finding.

Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.

Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.

Aim:HER2 is a proto-oncogene expressed in 10-30% of gastric adenocarcinomas and is an ideal target for inhibition in malignancy with high recurrence and dismal survival rates. Materials & methods: A systematic search was conducted via PubMed, Google Scholar and the clinicaltrials.gov database to report the results of ongoing and past studies investigating HER2 inhibitors in gastric cancer. Results: Twenty-five studies were included; ToGA trial is the pivotal trial approving the use of trastuzumab in metastatic gastric cancer, followed by more studies investigating other HER2 inhibitors in this setting, as well as in local and locoregional malignancy. Conclusion: Anti-HER2 molecules are proving efficacy and safety in gastric cancer; the evidence is growing and association with other cancer agents is under investigation.

Aim: Characterize current perceptions, practices, preferences and barriers to integrating pharmacogenomics into patient care at an institution with an established pharmacogenomics clinic. Materials & methods: A 16-item anonymous survey was sent to healthcare professionals practicing at Tampa General Hospital and the University of South Florida Health. Results: Survey participants consisted of nine advanced practice providers, 41 pharmacists and 64 physicians. Majority of survey participants did not feel confident in their ability to interpret and apply pharmacogenomic results. In the past 12 months, 27% of physicians reported ordering a pharmacogenomic test. The greatest reported barrier to integrating pharmacogenomics was the absence of established guidelines or protocols. Conclusion: Most clinicians believed pharmacogenomics would be useful in their clinical practice but do not feel prepared to interpret pharmacogenomic results.

Although immunotherapy has recently revolutionized standard of care in different cancer types, prostate cancer has generally failed to show dramatic responses to immune checkpoint inhibitors. As in other tumors, the goal in prostate cancer is now to target treatments more precisely on patient's individual characteristics through precision medicine. Defects in mismatch repair, mutations in the exonuclease domain of the DNA polymerase epsilon (POLE), high tumor mutational burden and the presence of biallelic loss of CDK12 among others, are predictive biomarkers of response to immunotherapy. In the present review, we summarize the evolving landscape of immunotherapy in prostate cancer, including precision approaches and strategies to define classes of responsive patients and scale up resistance to immune checkpoint inhibitors.