The Health History of First-Degree Relatives' Dyslipidemia Can Affect Preferences and Intentions following the Return of Genomic Results for Monogenic Familial Hypercholesterolemia.

Genetic testing is key in modern healthcare, particularly for monogenic disorders such as familial hypercholesterolemia. This Tohoku Medical Megabank Project study explored the impact of first-degree relatives' dyslipidemia history on individual responses to familial hypercholesterolemia genomic results. Involving 214 participants and using Japan's 3.5KJPN genome reference panel, the study assessed preferences and intentions regarding familial hypercholesterolemia genetic testing results. The data revealed a significant inclination among participants with a family history of dyslipidemia to share their genetic test results, with more than 80% of participants intending to share positive results with their partners and children and 98.1% acknowledging the usefulness of positive results for personal health management. The study underscores the importance of family health history in genetic-testing perceptions, highlighting the need for family-centered approaches in genetic counseling and healthcare. Notable study limitations include the regional scope and reliance on questionnaire data. The study results emphasize the association between family health history and genetic-testing attitudes and decisions.

Recontact: a survey of current practices and BRCA1/2 testing in Japan.

Genetic testing advances have enabled the provision of previously unavailable information on the pathogenicity of genetic variants, frequently necessitating the recontact of former patients by clinicians. In Japan, national health insurance coverage was extended to BRCA1/2 testing for the diagnosis of hereditary breast and ovarian cancer for patients who meet certain criteria in 2020, and conditions necessitating recontact were expected to increase. Studies and discussions regarding recontact have been conducted in the U.S. and Europe; however, in Japan, the national discussion around recontact remains undeveloped. We conducted a cross-sectional study by interviewing 73 facilities accredited by the Japanese Organization of Hereditary Breast and Ovarian Cancer regarding the practice of recontacting patients at these facilities. Sixty-six facilities responded that they recontact patients, but only 17 facilities had a protocol for this. The most common reason for recontact was that it could benefit the patient. Facilities that did not recontact stated that they lacked the necessary personnel or services. Most facilities indicated that a recontact system should be implemented in their practice. The increased burden on too few medical personnel, unestablished systems, patient confusion, and the right not to know were cited as barriers to implementing recontact. Although developing recommendations on recontact would be useful for providing equitable healthcare in Japan, there is an urgent need to deepen the discussion on recontacting, as negative opinions about recontacting patients were observed.

The return of individual genomic results to research participants: design and pilot study of Tohoku Medical Megabank Project.

Certain large genome cohort studies attempt to return the individual genomic results to the participants; however, the implementation process and psychosocial impacts remain largely unknown. The Tohoku Medical Megabank Project has conducted large genome cohort studies of general residents. To implement the disclosure of individual genomic results, we extracted the potential challenges and obstacles. Major challenges include the determination of genes/disorders based on the current medical system in Japan, the storage of results, prevention of misunderstanding, and collaboration of medical professionals. To overcome these challenges, we plan to conduct multilayer pilot studies, which deal with different disorders/genes. We finally chose familial hypercholesterolemia (FH) as a target disease for the first pilot study. Of the 665 eligible candidates, 33.5% were interested in the pilot study and provided consent after an educational "genetics workshop" on the basic genetics and medical facts of FH. The genetics professionals disclosed the results to the participants. All positive participants were referred to medical care, and a serial questionnaire revealed no significant psychosocial distress after the disclosure. Return of genomic results to research participants was implemented using a well-prepared protocol. To further elucidate the impact of different disorders, we will perform multilayer pilot studies with different disorders, including actionable pharmacogenomics and hereditary tumor syndromes.

Population-based biobank participants' preferences for receiving genetic test results.

There are ongoing debates on issues relating to returning individual research results (IRRs) and incidental findings (IFs) generated by genetic research in population-based biobanks. To understand how to appropriately return genetic results from biobank studies, we surveyed preferences for returning IRRs and IFs among participants of the Tohoku Medical Megabank Project (TMM). We mailed a questionnaire to individuals enrolled in the TMM cohort study (Group 1; n=1031) and a group of Tohoku region residents (Group 2; n=2314). The respondents were required to be over 20 years of age. Nearly 90% of Group 1 participants and over 80% of Group 2 participants expressed a preference for receiving their genetic test results. Furthermore, over 60% of both groups preferred to receive their genetic results 'from a genetic specialist.' A logistic regression analysis revealed that engaging in 'health-conscious behaviors' (such as regular physical activity, having a healthy diet, intentionally reducing alcohol intake and/or smoking and so on) was significant, positively associated with preferring to receive their genetic test results (odds ratio=2.397 (Group 1) and 1.897 (Group 2)). Our findings provided useful information and predictors regarding the return of IRRs and IFs in a population-based biobank.

Intravenous immunoglobulin therapy induces neutrophil apoptosis in Kawasaki disease.

To investigate the effect of high-dose intravenous immunoglobulin (IVIg) on neutrophil apoptosis in Kawasaki disease (KD), we studied the in vitro spontaneous and IVIg-induced apoptosis of neutrophils by analyzing a proportion of annexin V-positive cells and cells with fragmented DNA. The mean number of peripheral neutrophils in the post-IVIg phase decreased significantly (P < 0.01) compared with that in the pre-IVIg phase. The mean proportion of spontaneous apoptotic neutrophils in the post-IVIg phase was significantly higher (P < 0.01) than that in the pre-IVIg phase, and there was a significantly positive correlation (P < 0.01) with the reduction ratio of the circulating neutrophil counts from the pre-IVIg through the post-IVIg phases. IVIg induced a dose-dependent increase in the proportion of apoptotic neutrophils in the pre-IVIg phase. As a result, the present study demonstrated a novel action in which high-dose IVIg therapy decreased the number of circulating neutrophils by accelerating their apoptosis in KD.