OBJECTIVE: The psychological consequences of being aware of an increased risk of developing abdominal aortic aneurysm as a first-degree relative of a person with abdominal aortic aneurysm are hitherto unexplored. This study investigates the awareness of heritability and anxiety in male and female adult offspring of abdominal aortic aneurysm patients compared to controls. Health-related quality of life among participants with aortic pathology was compared to participants with normal aortic diameters.
METHODS: This was a cross-sectional point prevalence study based on the participants examined in the Detecting Abdominal Aortic Aneurysm in First Degree Relatives Trial (DAAAD; 752 adult offspring, 756 matched controls), 2020-2022. Questionnaires about health-related quality of life and study-specific questions regarding awareness of heritability were collected prior to the aortic ultrasound.
RESULTS: Attendance rate was higher among individuals with heredity compared to controls (67% vs. 52%, p < 0.001). Of 1508 adult offspring examined, 65% reported having a close relative with abdominal aortic aneurysm (6% in controls). Female adult offspring reported higher awareness of heritability than controls (38% vs. 12%, p < 0.001), as did males (32% vs. 8%, p < 0.001). A slight majority of participants with awareness reported anxiety (54% of female offspring; 51% of male). There were no measured differences in health-related quality of life between the groups when standard health-related quality of life instruments were used.
CONCLUSIONS: The higher-than-expected proportion of adult offspring with awareness of heritability and anxiety about such risk indicates that we fail to communicate risk to this group appropriately via the current channels of information within the healthcare system. This calls for the development of dedicated strategies for improved communication of abdominal aortic aneurysm risk to patients and their next of kin.

BACKGROUND: The number of patients with Alzheimer\'s disease (AD) has increased dramatically in Asia.
OBJECTIVE: To update the demographic characteristics of patients with AD and their informants in eight Asian countries and compare them from 12 years prior.
METHODS: The A1-A3 components of the Uniform Dataset (UDS), version 3.0, were administered in Taiwan, Beijing, Hong Kong, Korea, Japan, Philippines, Thailand, and Indonesia. Data were compared with patients with AD in the first registration using the UDS version 1.0 from 2010-2014 in the same regions.
RESULTS: A total of 1885 patients with AD and their informants were recruited from 2022 to 2024 and were compared with 2042 patients recruited a decade prior. Each country had its own unique characteristics that changed between both eras. The mean age of the patients and informants was 79.8±8.2 years and 56.5±12.1 years, respectively. Compared with the first registration, the patients were older (79.8 vs 79.0, p=0.002) and had worse global function (mean CDR-SB scores 6.1 vs 5.8, p<0.001); more informants were children (56 % vs. 48 %, p<0.001), and their frequency of in-person visits increased significantly if not living together. A total of 11 %, 4.5 %, 11 %, and 0.4 % of the patients had a reported history of cognitive impairment in their mothers, fathers, siblings, and children, respectively; all percentages, except children, increased significantly over the past decade.
CONCLUSIONS: The present study reports the heterogeneous characteristics of patients with AD and their informants in Asian countries, and the distinct changes in the past decade. The differences in dementia evaluation and care between developing and developed countries warrant further investigation.

OBJECTIVE: Unaffected first-degree relatives (FDRs) from families with two or more affected FDRs with Crohn\'s disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex versus simplex families and to investigate the risk of future CD onset accounting for potential confounders.
METHODS: We assessed the Crohn\'s and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores (CD-PRS), urinary fractional excretion of lactulose-to-mannitol ratio (LMR), fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset.
RESULTS: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (p=0.026) but not with baseline CD-PRS or LMR. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio 3.65, 95% confidence interval 2.18 - 6.11, p < 0.001).
CONCLUSIONS: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families.

UNASSIGNED: Psoriasis, a chronic inflammatory skin disease, is believed to be influenced by both genetic and environmental factors. Despite this understanding, the clinical epidemiological status of psoriasis patients with a family history of the disease remains uncertain.
UNASSIGNED: In this study, we participated in a multicenter observational epidemiological study involved over 1,000 hospitals and enrolled a total of 5,927 psoriasis patients. These patients were categorized into two groups based on the presence or absence of a family history of psoriasis: family history cases (896) and sporadic cases (5,031). The clinical manifestations of these two groups were analyzed through clinical classification, comorbidities, treatment response, and other relevant factors.
UNASSIGNED: The findings of our study indicate that individuals with a family history of psoriasis predisposition exhibit a notably elevated prevalence of psoriatic arthritis compared to those with sporadic occurrences. Moreover, patients with a family history of psoriasis display a more rapid and efficacious response to secukinumab. Additionally, individuals with moderate to severe psoriasis are at a heightened risk of developing cardiovascular and liver diseases in comparison to those with mild psoriasis, with no discernible impact of familial history on the likelihood of comorbidities.
UNASSIGNED: Our study identified the clinical characteristics of individuals with a familial predisposition to psoriasis, offering novel insights into the management and therapeutic approaches for patients with this condition.

BACKGROUND: We assessed whether familial colorectal cancer (FCRC) surveillance in individuals without hereditary CRC can be optimized METHODS: The ASCCA-FCRC model simulates CRC development in individuals with a family history of CRC at 2-fold and 4-fold increased CRC risk compared to the general population. We simulated a strategy without surveillance, the current Dutch guideline (5-yearly colonoscopy between 45-75), and three sets of alternative strategies; colonoscopy surveillance, surveillance combining colonoscopy and fecal immunochemical test (FIT) and FIT-based surveillance. Each set included a range of strategies differing in age range and test interval. The optimal strategy was defined as the strategy with highest quality-adjusted life years (QALYs) satisfying all criteria: 1) in the (near-)efficiency area of the cost-effectiveness frontier, and compared to current surveillance 2) non-inferior effectiveness, 3) no substantial increase in colonoscopy burden and, 4) not more expensive.
RESULTS: The optimal strategy was 10-yearly colonoscopy with 2-yearly FIT between colonoscopies from age 40 to 80 for both 2- and 4-fold increased CRC risk. At 2-fold risk, this strategy prevented 0.8 more CRC deaths, gained 15.8 more QALYs at 731 fewer colonoscopies and saved €98k over the lifetime of 1,000 individuals compared to current surveillance. At 4-fold risk, figures were 2.1 more CRC deaths prevented, 37.0 more QALYs gained at 567 fewer colonoscopies and €127k lower costs. Current surveillance was not (near-)efficient.
CONCLUSIONS: FIT could play an important role in FCRC surveillance. Surveillance with 10-yearly colonoscopy and 2-yearly FIT between colonoscopies from age 40 to 80 increases QALYs and reduces colonoscopy burden and costs compared to current FCRC surveillance.

OBJECTIVE: Family history of premature cardiovascular disease is a strong predictor of individual cardiovascular risk. However, family history is not always available and not always reliable. Roughly 80% of health outcomes are influenced not by genetic risk but by societal factors, including adverse health behaviors and environment. Furthermore, in the present age of genetic testing, laboratory evaluations, and imaging, a key question remains: What is the contemporary relevance of family history screening in the management of cardiovascular disease in youth?
RESULTS: Knowledge of an individual\'s family history can help clinicians identify not only inherited risk but also familial clustering of unhealthy behaviors and environmental adversity contributing to enhanced cardiovascular disease risk in youth. For those at greatest risk, prevention strategies can be applied sooner and more conservatively. Integrating family history into clinical practice is crucial for cardiovascular risk assessment and for optimizing outcomes, but, in some cases, is more reflective of social factors.

UNASSIGNED: Although family history of psychiatric disorders has often been considered potentially useful in understanding clinical presentations in patients, it is less clear what a positive gambling family history means for people with gambling disorder. We sought to understand the clinical impact of having a first-degree relative with gambling disorder in a sample of adults with gambling disorder.
UNASSIGNED: Data from 455 participants (aged 18-65 years) who had participated in previous pharmacological and psychotherapeutic clinical trials for gambling disorder were pooled in a secondary analysis. Demographic and clinical variables were compared between those who did versus did not have one or more first-degree relative(s) with gambling disorder. Additionally, we examined whether a family history of gambling disorder was associated with treatment outcome.
UNASSIGNED: 223 (49.0%) participants had at least one first-degree family member(s) with gambling disorder. In terms of clinical variables, family history of gambling disorder was significantly associated with being female, having an earlier age of gambling onset, longer duration of untreated gambling illness, a greater likelihood of developing legal problems secondary to gambling, and higher rates of alcohol use disorder in family members. Family history of gambling disorder was also associated with a greater gambling symptom improvement from pharmacotherapy.
UNASSIGNED: These results indicate that gamblers with a first-degree family member with a gambling disorder may have a unique clinical presentation and better response to treatment interventions.

OBJECTIVE: Lung Cancer (LC) is a multifactorial disease for which the role of genetic susceptibility has become increasingly relevant. Our aim was to use artificial intelligence (AI) to analyze differences between patients with LC based on family history of cancer (FHC).
METHODS: From August 2016 to June 2020 clinical information was obtained from Thoracic Tumors Registry (TTR), a nationwide database sponsored by the Spanish Lung Cancer Group. In addition to descriptive statistical analysis, an AI-assisted analysis was performed. The German Technical Information Library supported the merging of data from the electronic medical records and database of the TTR. The results of the AI-assisted analysis were reported using Knowledge Graph, Unified Schema and descriptive and predictive analyses.
RESULTS: Analyses were performed in two phases: first, conventional statistical analysis including 11,684 patients of those 5,806 had FHC. Median overall survival (OS) for the global population was 23 months (CI 95 %: 21.39-24.61) in patients with FHC versus 21 months (CI 95 %: 19.53-22.48) in patients without FHC (NFHC), p < 0.001. The second AI-assisted analysis included 5,788 patients of those 939 had FHC. 58.48 % of women with FHC had LC. 9.53 % of patients had an EGFR or HER2 mutation or ALK translocation and at least one relative with cancer. A family history of LC was associated with an increased risk of smoking-related LC. Non-smokers with a family history of LC were more likely to have an EGFR mutation in NSCLC. In Bayesian network analysis, 55 % of patients with a family history of LC and never-smokers had an EGFR mutation.
CONCLUSIONS: In our population, the incidence of LC in patients with a FHC is higher in women and younger patients. FHC is a risk factor and predictor of LC development, especially in people ≤ 50 years. These results were confirmed by conventional statistics and AI-assisted analysis.

Despite ethical and historical arguments for removing race from clinical algorithms, the consequences of removal remain unclear. Here, we highlight a largely undiscussed consideration in this debate: varying data quality of input features across race groups. For example, family history of cancer is an essential predictor in cancer risk prediction algorithms but is less reliably documented for Black participants and may therefore be less predictive of cancer outcomes. Using data from the Southern Community Cohort Study, we assessed whether race adjustments could allow risk prediction models to capture varying data quality by race, focusing on colorectal cancer risk prediction. We analyzed 77,836 adults with no history of colorectal cancer at baseline. The predictive value of self-reported family history was greater for White participants than for Black participants. We compared two cancer risk prediction algorithms-a race-blind algorithm which included standard colorectal cancer risk factors but not race, and a race-adjusted algorithm which additionally included race. Relative to the race-blind algorithm, the race-adjusted algorithm improved predictive performance, as measured by goodness of fit in a likelihood ratio test (P-value: <0.001) and area under the receiving operating characteristic curve among Black participants (P-value: 0.006). Because the race-blind algorithm underpredicted risk for Black participants, the race-adjusted algorithm increased the fraction of Black participants among the predicted high-risk group, potentially increasing access to screening. More broadly, this study shows that race adjustments may be beneficial when the data quality of key predictors in clinical algorithms differs by race group.

BACKGROUND: Germline breast cancer susceptibility gene (gBRCA) mutation in patients with pancreatic cancer (PC) is not common in clinical practice. Therefore, factors that efficiently show gBRCA mutations and the real-world outcomes of olaparib maintenance therapy have not been fully established. In the present study, we clarified the indicators for the effective detection of gBRCA mutation and the efficacy and safety of olaparib as maintenance therapy.
METHODS: We retrospectively analyzed 84 patients with PC who underwent gBRCA testing (BRACAnalysis, Myriad Genetics, Salt Lake City, UT, USA) at our institute between January 2021 and March 2022. For each patient, clinical data were extracted from medical records.
RESULTS: The median patient age was 64 y (29-85 y), and 41 patients (48.8%) were male. The gBRCA mutations were identified in 10 (11.9%) patients; two patients had BRCA1 mutation and eight had BRCA2 mutation. All patients with gBRCA mutation had a family history of any cancer, and eight of them had a family history of Hereditary Breast and Ovarian Cancer syndrome (HBOC)-related cancer. The gBRCA mutation rate was higher for patients with PC with a family history of HBOC-related cancer compared to that in patients with PC having a family history of other cancers and no family history of cancer (22.9% vs. 4.1%; P = 0.014). In our study, eight out of 10 patients with gBRCA-positive PC received olaparib after platinum-based chemotherapy. The best responses to platinum-based chemotherapy included a complete response in one patient (12.5%) and a partial response in seven patients (87.5%). The median duration of treatment with platinum-based chemotherapy plus olaparib was 17.5 months (8-87 months), and the duration of treatment with olaparib maintenance therapy was 11 months (1-30 months). During olaparib maintenance therapy, three patients showed no disease progression. One of these three patients underwent conversion surgery after receiving olaparib for 12 months.
CONCLUSIONS: The gBRCA testing should be considered proactively, especially in patients with PC with a family history of HBOC-related cancer.