Personalized medicine最新文献

Background: Validate a novel in vitro resistance platform for breast cancer (BC) by assessing resistance profiles of treatment-naïve and residual tumors after neoadjuvant chemotherapy (NACT) and applying a machine learning algorithm to predict NACT response using clinical biomarkers.

Methods: Tumor cells from primary BC and residual disease (RD) were cultured on the chemoresistance platform with various chemotherapies. Resistance was categorized as low ( < 40%), medium (40-60%), or high ( > 60%) after 72 h based on cell viability. Clinicopathological data from BC samples were analyzed using the XGBoost algorithm and SHAP interpretation to identify NACT-resistant patients.

Results: Patients undergoing upfront surgery (n = 70) exhibited significantly favorable prognosis compared to RD cases (n = 27), which had higher drug resistance and worse outcomes. AI analysis of 1,012 patients achieved 82% accuracy in predicting pathological response and RD, with age, estrogen receptor status, tumor grade and size, axillary status, and HER2 status identified as key predictors. The algorithm predicted NACT resistance with 81.8% accuracy in 11 patient samples.

Conclusion: The chemoresistance platform identified resistance patterns highlighting its utility in precision medicine. Additionally, the XGBoost algorithm accurately predicted NACT response, supporting the integration of AI with functional precision medicine for personalized BC treatment.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has become increasingly utilized in the treatment of appendiceal adenocarcinoma (AA) with peritoneal metastases. There are multiple intraperitoneal chemotherapeutic agents and protocols used at different centers, however there is little data available to guide clinicians on the optimal treatment strategy for individual patients. While it is often treated with paradigms extrapolated from colorectal cancer, AA has been shown to have a distinct mutational profile. Commonly mutated genes in AA such as KRAS and GNAS have been targeted by recently described systemic therapies for various tumors with positive results, suggesting that there may be a role for a patient-centered approach to HIPEC as well. Data specific to AA remains limited, however ongoing research into novel strategies such as next-generation sequencing of tumor samples and in vitro testing of patient-derived organoids for a variety of gastrointestinal cancers with peritoneal metastases has shown promise in personalizingHIPEC regimens.

Background: Personalized medicine (PM) is advancing disease prevention and treatment, but regulatory and clinical concerns persist, requiring evaluation of healthcare professionals' (HPs) knowledge and attitudes.

Methods: His study assessed PM awareness among HPs at Tabriz University of Medical Sciences, Iran. Participants from diverse clinical departments completed a survey covering PM definitions, benefits, ethical concerns, genetic testing knowledge, attitudes, and barriers. A literature review guided question development.

Results: Among 141 HPs (55.3% male, 44.7% female), only 27.7% reported sufficient PM knowledge, though 82.3% acknowledged genetic health influences. Those with adequate knowledge more often endorsed PM tools (92.3% vs. 68.6%, p = 0.01) but expressed greater concern about healthcare disparities (82.1% vs. 67.6%, p = 0.03). Key barriers included cost (17%) and ethical risks, with 72% fearing PM would widen economic gaps and 23.4% anticipating insurance discrimination. Females and married HPs were more concerned about discrimination (p = 0.039 and p = 0.038, respectively). Despite concerns, 80% of physicians supported genome-guided prescribing.

Conclusion: While HPs recognize PM's potential, limited awareness and ethical concerns hinder adoption. Addressing knowledge gaps and equity issues through education is crucial for PM integration in Iran.

Chronic lymphocytic leukemia (CLL) is a common, incurable leukemia. Precision treatment for CLL uses genetic testing to align therapeutic selection with patient characteristics. Insurers are uneven in their reimbursement of precision CLL treatment, partly due to uncertain evidence of cost-effectiveness. This review surveys the current cost-effectiveness evidence for precision CLL treatment and identifies areas for future research. We conducted a scoping review of economic evaluations of precision CLL treatments indexed in PubMed, Embase, and Web of Science and published by October 2024. Eight articles were retrieved. Studies examined heterogeneous patient populations, treatment regimens, and stratification strategies. Four studies (50%) focused on subgroups with del(17p) and/or TP53 mutations only. Three studies (38%) analyzed the costs and outcomes of both treatment and genetic testing, while 62% did not include the cost or outcomes of genetic testing. All studies obtained clinical model parameters from published trials. Five studies (63%) reported that precision CLL treatment was likely cost-effective at willingness to pay thresholds ranging from $26,489/QALY to $130,477/QALY. Future research should focus on generating real-world data, broadening the scope of analysis to include societal perspectives, and exploring distributional impacts to more effectively address the heterogeneity of precision CLL treatments when determining their cost-effectiveness.

Aim: On-aspirin platelet reactivity, wherein patients show sub-optimal or no response to antiplatelet therapy, occurs in 5-60% of subjects. The genetic etiology of such reactivity in patients with vascular diseases, especially ischemic stroke in the Indian population, is unknown. This study aimed to examine the genetic variations in the pathways of platelet aggregation and aspirin metabolism that could predict aspirin response.

Methods: This is a prospective cohort study, which included 293 ischemic stroke patients on 150 mg aspirin for over 7 days. Platelet aggregation was assessed using light transmission aggregometry with 10 µM ADP and 0.5 mM arachidonic acid as agonist. After excluding patients with serum salicylic acid levels < 30 µg/mL, 230 individuals were analyzed. Candidate gene variants in COX1, COX2, GpIIb/IIIa, P2RY1, PEAR1, ITGB3, and UGT1A6, were genotyped using PCR-RFLP or allelic discrimination assays.

Results: The T allele of P2RY1 (rs1371097 C > T) was significantly associated with inadequate platelet response with an odds ratio of 1.71 (95% CI: 1.122-2.61; p = 0.0131). Carriers of this allele had a 3.46-fold increased risk of inadequate response after adjustment for age and gender.

Conclusions: The P2RY1 (rs1371097 C > T) variant may be a potential genetic marker for inadequate response to aspirin in Indian ischemic stroke patients.

The severity of COVID-19 disease can vary greatly, influenced by genetic factors and comorbid conditions that may increase mortality. This study has examined potential genetic influences on the disease for a young adult aged 36 years with T2DM-CAD multi-morbidity with severe COVID-19 disease and in-hospital mortality using whole-exome sequencing. The patient exhibited a constellation of severe symptoms and abnormality in several biochemical markers associated with COVID-19 disease and comorbid conditions. A total of 756 variants were discovered in the patient, including several rare and novel variants associated with immune pathways. A set of 10 unique candidate variants in 10 distinct genes were identified with nine variants located within genes associated with the COVID-19 panel (HLA-DRB1, IL23R, PRKDC, RNF31, SLC37A4, TAP2, TCIRG1, TCN2, and TPP2), while one variant was found in a gene (PAX6) from Diabetes panel. Enrichment analysis showed that the top three enriched GO biological processes were a response to stimulus (n = 23, p = 6.8E-3), immune system process (n = 22, p = 3.6E-12), and regulation of immune system process (n = 19, p = 1.57E-11). The Maximal Clique Centrality algorithm identified HLA-DRB1 as a prominent hub gene and potential loss-of-function mutation in HLA-DRB1, suggests a compromised antigen presentation mechanism within this patient.

Understanding the regional differences in approved gene therapies, clinical trial development, and regulatory frameworks is crucial for ensuring equitable access and addressing justice issues in advanced therapeutics. This review aimed to evaluate the differences between the US, the EU, Japan, and China and offer policy recommendations to promote harmonization between these countries and regions. Gene therapy approvals show significant regional disparities, with the US leading with 23 approved therapies, followed by the EU with 16. Few products are accessible worldwide reflecting challenges in obtaining cross-border approvals. Moreover, access is uneven within regions like the EU, with high-income countries having better accessibility. High costs and complex reimbursement processes exacerbate these issues, with some products being withdrawn from the market due to pricing disputes. Regulatory differences, such as differing data needs, further delay access in countries, like Japan, where gene therapy products are unavailable until years after a product is ready for approval. Clinical trial activity mirrors these disparities, with China's growing number of trials potentially reshaping the landscape. Harmonizing regulations across regions could streamline the approval process for therapies, making them more efficient and reducing disparities. Furthermore, key solutions include incentivizing cost reductions, adopting innovative payment models, and aligning evidence/reimbursement requirements.

Background: Gastric cancer is an aggressive and heterogeneous disease, primarily sporadic, with only 1-3% of cases being hereditary. However, gastric cancer is a component of several hereditary cancer syndromes. The BRCA1 and BRCA2 genes encode key DNA repair proteins involved in homologous recombination. Studies suggest a significantly increased risk of gastric cancer in first-degree relatives of BRCA1/2 mutation carriers.

Methods: We systematically searched PubMed, Scopus, and Web of Science for relevant studies. Risk ratios (RRs) with 95% confidence intervals (CIs) were computed using DerSimonian and Laird random-effect models. Heterogeneity was assessed via I² statistics. Statistical analyses were performed using R (version 4.2.3).

Results: Fourteen studies with 160,551 patients were included, of whom 25,934 had BRCA1/2 mutations (BRCA1: 14322; BRCA2: 11612). BRCA1 and BRCA2 mutations were significantly associated with increased gastric cancer risk (RR 2.30; 95% CI: 1.33-3.97; p = 0.003; I² = 82% and RR 2.45; 95% CI: 1.82-3.28; p < 0.001; I² = 25%). Among the gastric cancer patients, BRCA1 and BRCA2 mutations were associated with RRs of 3.02 (p = 0.101; I² = 65%) and 4.86 (p < 0.001; I² = 0%), respectively.

Conclusions: This meta-analysis suggests that BRCA1/2 mutation carriers have a higher risk of developing gastric cancer.

Aims: This study explored employees' understanding of, and psychosocial responses to, workplace genetic testing (wGT) results.

Materials & methods: Employees of a US healthcare system who underwent wGT (hereditary cancer/heart disease risk, pharmacogenomics) and received results were surveyed. We ascertained pretest education engagement, test understanding, and psychosocial responses. Regression analyses identified predictors of scores on a modified Feelings About genomiC Test Results questionnaire (positive feelings, negative emotions, and uncertainty after wGT).

Results: N = 418 employees (mean age = 44 years; 88.3% female; 80.6% white) completed the survey. Mean scores (out of 12; higher scores indicate a greater extent of each feeling) were 5.2 (SD = 2.9) for positive feelings, 1.2 (SD = 2.2) for negative emotions, and 2.0 (SD = 2.5) for uncertainty. Identifying as non-Hispanic African American/Black and receiving increased risk (cancer/heart disease) wGT results were associated with lower positive feelings and higher negative emotions and uncertainty scores (all p < 0.05). Open-ended responses indicated difficulty interpreting, recalling, and utilizing results.

Conclusions: wGT was associated with low levels of measured psychosocial harm among participants. However, results suggested a greater likelihood of negative psychosocial responses among those with increased risk of cancer/heart disease and non-Hispanic African American/Black employees. Future studies should explore strategies to ensure all employees undergoing wGT have educational and psychosocial support.

Aims: While "tailored communication" and "precision medicine" have been well-defined in medical literature, the concept of "precision communication" in healthcare has yet to be clarified. We sought to review how "precision communication" has been used in the medical literature to date and propose a working definition for this term.

Materials & methods: We searched seven medical literature databases from inception until 22 May 2024, for articles using terms related to "precision communication." Multiple reviewers screened titles/abstracts and full-texts; an initial pool of full-text articles underwent thematic analysis to clarify relevant themes for inclusion. Data regarding the use of the term "precision communication" were manually charted and analyzed descriptively.

Results: Of the 7,648 articles identified, 21 full-text articles were included in the final descriptive analysis. These articles highlighted the personalization of tailored communication to patient characteristics, its impact on clinical outcomes, and the recipients of "precision communication." The latter may distinguish "precision communication" from similar terms: where "tailored communication" was mostly applied to undefined groups, we propose that "precision communication" is precise toward specific patient subpopulations, paralleling the use of genomics in precision medicine.

Conclusions: From this review, we defined precision communication as "the personalization of communication to subpopulations."