Screening Of First-degree Relatives Research Articles

Low Rates of Colorectal Cancer Screening in Our Patients' First-Degree Relatives: Are We Failing Them?

Guidelines recommend screening those with a family history of early-onset colorectal cancer at age 40 or 10 years before the age of their relative's diagnosis. Currently, there is no literature reporting the screening rate in these individuals and no protocols are in place to identify and target this population for screening awareness. Assess adherence to current screening guidelines among FDRs of patients with early-onset colorectal cancer. Retrospective and qualitative study involving a telephone survey where patients were asked about relative's screening status and barriers to screening. Two community-based institutions between January 2018-December 2021. Individuals diagnosed with early-onset colorectal cancer who had undergone surgery at our institutions. Rate of screening in first-degree relatives of our patients with early-onset colorectal cancer. Other factors measured included demographics, clinicopathologic characteristics and screening barriers. Thirty-six patients were identified. Survey response rate was 66.6% (n=24). A total of 88 first-degree relatives who met criteria for screening resulted, with 67.1% (n=59) having a known screening status. Of the 59 with known screening status, it was reported that only 44% (n=26) have undergone screening. Patients of African American race, stage III/IV disease, Medicare/Medicaid and living within Baltimore City County were more likely to have family members with unknown or no screening. Lack of insurance coverage was the most common barrier noted 12.5% (n=3); whereas 54.1% (n=13) reported no barriers to screening. Retrospective design. Most first-degree relatives of patients diagnosed with early-onset colorectal cancer do not undergo colorectal cancer screening. This could be attributed to the lack of protocols that could guarantee these individuals are informed of their elevated risk and the different options available for screening. Furthermore, our study suggests that racial and socioeconomic disparities exist among high-risk patients who should pursue screening. See Video Abstract.

Screening for colorectal cancer by full colonoscopy in first-degree relatives of colorectal cancer patients: a multicentric study by the Italian League for the Fight against Cancer.

Colorectal cancer currently presents the third-highest incidence of cancers worldwide, making secondary prevention through screening programs for colorectal cancer, usually by Fecal Occult Blood Testing, an essential preventive medicine intervention. First-degree relatives of colorectal cancer patients are a particularly at-risk group, with indications to consider direct screening by full colonoscopy. Colonoscopy is considered the gold standard for diagnosing colorectal cancer, as it has high sensitivity and specificity, and is both a diagnostic and therapeutic tool. However, it requires significant organizational and financial resources, and has a small but relatively higher risk of complications as opposed to fecal occult blood testing. The present study aimed to assess the appropriateness of a screening program without age restrictions of CRC by full colonoscopy in asymptomatic, first-degree adult relatives of patients with colorectal cancer, aiming both to actively increase screening coverage and to determine the detection rate of precancerous lesions and colorectal cancer in this population. Uncontrolled interventional study - colorectal cancer screening by full colonoscopy for at-risk population. The Italian League for the Fight against Cancer started a colorectal cancer screening program by full colonoscopy for first-degree relatives of colorectal cancer patients in 1998 in the province of Latina, Lazio Region, Italy. The program was expanded to the provinces of Rieti, Lazio Region, and Sassari, Sardinia Region, in 2014 and 2016 respectively, and was concluded in 2018. Subjects were actively and voluntarily recruited by the study's working group. Subjects that had already been subjected to a full colonoscopy in the preceding 5 years were excluded from this study. Identified neoplastic lesions were treated either directly or referred to the Day Hospital setting, and histologically diagnosed following World Health Organization guidelines. In total, 2,288 subjects (age range 15-88, mean 52.3 yrs, M/F = 946/1,204) were screened by colonoscopy, of which 103 (4.5%) were incomplete and 2,173 (95.0%) complete, with data on colonoscopy performance missing for 12 participants. Out of 468 positive outcomes on colonoscopy, diagnosis for 422 (204M/173F), 19.4% of total subjects, was adenomatous polyps and 46 (20M/20F), 2.1% of total subjects, was colorectal cancer. Female sex was a protective factor against a positive test outcome, with a 35% reduction compared to male sex, with OR=0.64 95%CI (0.52-0.80). On the other hand, being over 50 years of age was found to be a risk factor, making a positive outcome more than twice as likely, with OR=2.3 95%CI (1.8-2.9). Subjects over 50 also had significantly more instances of multiple adenomas being found, however the size distribution of found adenomas was not significantly different between subjects under and over 50, despite size being a predictor of risk of neoplastic progression. Given the high detection rate of precancerous lesions and colorectal cancer in the studied population, it is our opinion that guidelines should continue to recommend earlier and more frequent screening in first-degree relatives of patients with colorectal cancer, and, barring the introduction of more cost-effective and/or lower risk procedures with a similar efficacy profile, maintain the use of colonoscopy as the main screening option.

Sudden death in young South European population: a cross-sectional study of postmortem cases

To describe the annual incidence and the leading causes of sudden non-cardiac and cardiac death (SCD) in children and young adult Portuguese population. We retrospectively reviewed autopsy of sudden unexpected deaths reports from the Portuguese National Institute of Legal Medicine and Forensic Sciences’ database, between 2012 and 2016, for the central region of Portugal, Azores and Madeira (ages 1–40: 26% of the total population). During a 5-year period, 159 SD were identified, corresponding to an annual incidence of 2,4 (95%confidence interval, 1,5–3,6) per 100.000 people-years. Victims had a mean age of 32 ± 7 years-old, and 72,3% were male. There were 70,4% cardiac, 16,4% respiratory and 7,5% neurologic causes of SD. The most frequent cardiac anatomopathological diagnosis was atherosclerotic coronary artery disease (CAD) (33,0%). There were 15,2% victims with left ventricular hypertrophy, with a diagnosis of hypertrophic cardiomyopathy only possible in 2,7%. The prevalence of cardiac pathological findings of uncertain significance was 30,4%. In conclusion, the annual incidence of SD was low. Atherosclerotic CAD was diagnosed in 33,0% victims, suggesting the need to intensify primary prevention measures in the young. The high prevalence of pathological findings of uncertain significance emphasizes the importance of molecular autopsy and screening of first-degree relatives.

Challenges and Applications of Genetic Testing in Dilated Cardiomyopathy: Genotype, Phenotype and Clinical Implications.

Genetic tests for dilated cardiomyopathy (DCM) have a diagnostic yield of up to 40%, but there is significant genetic heterogeneity and other challenges, such as variable expressivity and incomplete penetrance. Pedigree analysis is essential for distinguishing between sporadic and familial DCM cases by assessing family history. Familial DCM yields higher results in genetic testing, but sporadic DCM does not rule out the possibility of a genetic cause. Some genes have specific phenotypes, with the Lamin gene ( LMNA ) being associated with a phenotype of malignant arrhythmias and advanced heart failure (HF). The presence of a causal genetic variant can also aid in prognostic evaluation, identifying more severe cases with lower rates of reverse remodeling (RR) compared to individuals with a negative genotype. Current guidelines recommend genetic evaluation and counseling for individuals with DCM, along with cascade screening in first-degree relatives in cases where one or more variants are identified, offering an opportunity for early diagnosis and treatment. Relatives with a positive genotype and negative phenotype are candidates for serial evaluation, with frequency varying by age. Genotype also assists in individualized recommendations for implantable cardioverter-defibrillator (ICD) placement and advice regarding physical activity and family planning. Ongoing studies are progressively elucidating the details of genotype/phenotype relationships for a large number of variants, making molecular genetics increasingly integrated into clinical practice.

Predictive factors based on the health belief model on cancer screening behaviour in first degree relatives of patients with Lynch syndrome-associated colorectal cancer

ObjectivesThis study aimed to investigate colorectal cancer-related knowledge, health beliefs, and screening behaviour in first-degree relatives (FDRs) of patients with Lynch syndrome-associated colorectal cancer (CRC) and explore the predictive factors of screening behaviour based on a health belief model. MethodsThis cross-sectional study was conducted in the colorectal department of a Class A tertiary hospital in Guangzhou from December 2017 to December 2019. A total of 265 FDRs of 96 patients with Lynch syndrome-related CRC were selected. The study was conducted in the colorectal department of a tertiary cancer centre in Guangzhou. The demographic questionnaire, the simplified CRC knowledge questionnaire, and the Champion’s Health Belief Model Scale were used for evaluation. Data were analyzed using statistical description, between-group comparisons, and binary logistic regression. ResultsA total of 160 (60.4%), 61 (23.0%), and 44 (16.6%) of the participants had high, medium, and low levels of knowledge about CRC, respectively; the average overall score of health belief was 121.36 ± 13.02. Sixty-one participants (23.0%) underwent Lynch syndrome-associated cancer screening. The predictive factors of screening behaviour included sex (male), age (older), married status (married), multiple primary cancers of the index patients, and high levels of knowledge and health beliefs (P < 0.05). ConclusionsThe knowledge and health beliefs of cancer and cancer screening in FDRs of patients with Lynch syndrome-associated CRC should be improved. Both knowledge and beliefs are critical in promoting their cancer screening behaviour. Interventions should focus on health education and enhance health beliefs of the FDRs for better screening behaviour.

OR04-4 Loss of KDM1A in Bilateral Macronodular Adrenal Hyperplasia With GIP-Dependent Cushing's Syndrome and in Acromegaly With Paradoxical GH Response to Oral Glucose

Abstract Context Primary bilateral macronodular adrenal hyperplasia (PBMAH) with glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome is caused by ectopic expression of GIP receptor (GIPR) in the adrenal lesions. Such ectopic expression of GIPR was also reported in other endocrine neoplasm, notably in somatotroph pituitary adenomas from acromegalic patients with paradoxical increase of GH after oral glucose load, suggesting a common molecular pathogenesis. We aimed to identify the driver event responsible for GIP-dependent PBMAH with Cushing's syndrome and ectopic GIPR expression in somatotropinomas. Methods We conducted an international, multicenter, cohort study. We collected blood and adrenal samples from patients who had undergone unilateral or bilateral adrenalectomy for GIP-dependent PBMAH with Cushing's syndrome. Adrenal samples from patients with PBMAH and Cushing's syndrome without food-dependent cortisol production were used as controls. We further collected somatotropinoma specimens from acromegaly patients followed at two expert endocrine centers in France. Results 17 patients with familial or sporadic GIP-dependent PBMAH with Cushing's syndrome were studied. We identified germline heterozygous mutations in the lysine demethylase 1A (KDM1A) gene in all 17 patients. We further identified a recurrent deletion of the short arm of chromosome 1 harboring the KDM1A locus in the adrenal lesions of affected patients. None of the 25 patients in the control group had KDM1A germline or somatic alterations. Concomitant genetic inactivation of both KDM1A alleles resulted in loss of KDM1A expression in the adrenal lesions. RNA-sequencing revealed the global impact of KDM1A loss in adrenal tissue on gene transcription and identified differentially regulated genes including those encoding for GIPR and other G-Protein-Coupled Receptors that may be involved in adrenal tumorigenesis and regulation of steroidogenesis. In vitro pharmacologic inhibition, silencing and knock-out by CRISPR-Cas9 genome editing of KDM1A led to an increase in GIPR transcripts and protein in human adrenocortical H295R cells. Somatotropinoma samples from 78 patients with acromegaly were studied. 24% of these patients presented with a paradoxical rise of GH after oral glucose load and expressed ectopically GIP-receptor in their somatotropinoma. None of the somatotropinomas harbored KDM1A pathogenic variants, but those from patients with paradoxical GH response displayed a recurrent chromosome 1p loss. Discussion We identified germline inactivating KDM1A mutations and loss of heterozygosity as a genetic predisposition to GIP-dependent PBMAH with Cushing's syndrome following a tumor suppressor gene model of tumorigenesis. We currently perform genetic screening in first-degree relatives of patients with GIP-dependent PBMAH with Cushing's syndrome and clinical examination with biochemical testing in asymptomatic KDM1A variant carriers. We did not identify somatic KDM1A mutations in somatotropinomas expressing GIPR ectopically, however their recurrent 1p chromosome loss suggests that KDM1A haploinsufficiency may contribute to GIPR expression in those tumors. Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.

Highly malignant disease in early-onset arrhythmogenic cardiomyopathy

Abstract Background Arrhythmogenic cardiomyopathy (AC) is an inheritable and progressive cardiomyopathy characterized by high risk of ventricular tachyarrhythmias and sudden cardiac death. Pediatric patients are underrepresented in AC publications, and the AC penetrance and incidence of cardiac events in children have yet to be determined. Current guidelines recommend initiating family screening in first-degree relatives after age 10–12 years, but the clinical value of this approach has not been systematically evaluated. Purpose We aimed to explore the incidence of severe cardiac events in pediatric patients with AC and to describe the phenotype in early-onset AC. Furthermore, we wanted to estimate the penetrance of AC disease in genotype positive pediatric family members. Methods In a single-center follow-up study, we included consecutive AC pediatric patients and genotype positive family members ≤18 years of age. The patients were followed regularly with electrocardiographic, structural and arrhythmic characteristics according to the AC 2010 Task Force Criteria (TFC). Penetrance of AC disease was defined as fulfilling definite AC diagnosis by the 2010 TFC. We defined severe cardiac events as cardiac death, heart transplantation (HTx) or severe ventricular arrhythmias (VAs) (sustained ventricular tachycardia or aborted cardiac arrest). Results We included 62 individuals (11 probands, 51 family members). Fourteen events (5 HTx, 9 VAs) occurred during 6±4 years of follow-up, giving a cumulative incidence of 23% and a yearly incidence rate of 4%. Seven (50%) events occurred in patients ≤12 years of age (Figure 1). All children who underwent heart transplantation were ≤12 years. At inclusion, 13 patients (21%) fulfilled definite AC diagnosis (10 probands, 3 family members). At end of follow-up, AC diagnosis were fulfilled in 20 (32%) patients (11 probands, 9 family members), indicating progression of disease in 7 patients. Mean age at definite AC diagnosis was 13±4 years and 8 patients (40%) were ≤12 years old (Figure 1). All patients diagnosed with AC &amp;lt;12 years of age had biventricular disease with mean LVEF 30±9% and right ventricular fractional area change 21±5% at end of follow-up. Among the family members, 5 (10%) had signs of AC disease at the time of genetic diagnosis. At end of follow-up, AC penetrance was 18% and 3 (6%) experienced severe cardiac events at a mean age of 13±6 years. Conclusion In a pediatric AC cohort of probands and genotype positive family members, we found a high incidence of VA and HTx. Half of the events occurred in children ≤12 years of age, supporting a markedly severe phenotype in early-onset AC. AC penetrance among pediatric family members identified by screening was high, with a significant incident of events. Our findings emphasize the high risk features of early-onset AC disease and indicate a need to start AC family screening in children at an younger age than recommended by current guidelines. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Norwegian Research Council

S257 Improving Adherence to Colorectal Cancer Screening Recommendations for First-Degree Relatives of Patients With Advanced Adenomas

Introduction: Advanced adenoma (AA), defined as polyp size ≥1 cm or histologic features with villous or high-grade dysplasia, is common and confers an increased risk of colorectal cancer (CRC) to affected individuals and their first-degree relatives (FDR). Patients are unaware of this associated risk leading to inadequate screening of FDR. Also, practice variation regarding screening age/interval results in inconsistent recommendations. In this quality improvement study, we aimed to improve adherence to CRC screening recommendations for FDR of patients with a multifaceted intervention. Methods: A pre-post study was conducted at a single academic center between 7/2020-5/2022 including adults undergoing outpatient screening/surveillance colonoscopy. Interventions included (1) surveying faculty/fellows on barriers to adhering to guidelines, (2) creating patient education materials in various languages on AA and importance of FDR screening, (3) standardizing screening recommendations with an automated prescriptive template in the endoscopy report, (4) educating providers and nurses, and (5) sharing quarterly compliance reports. The primary outcome was adherence to CRC screening recommendations for FDR of patients with AAs. Data were collected by chart review of the endoscopy report and post-procedure pathology follow up letters. Results: Prior to the intervention, only 7% (11 of 166) with AA received appropriate CRC screening recommendations for their FDR. On the pre-intervention survey (n=38), suboptimal adherence was due to low familiarity with guidelines (47%), variability in delivery of screening recommendations (5% in endoscopy report; 18% spoke to patient; 13% communicated to primary provider; 47% no recommendation), and limited time available to communicate recommendations and provide patient education. Development of an automated template to standardize recommendations was implemented on 12/2021, followed by improved monthly rates of adherence to recommendations, from a baseline of 7% to 50%, 56%, 74%, 77% and 80%, respectively (Figure). Conclusion: Earlier and more intensive screening of FDRs in those with AA is considered an untapped opportunity with the potential to substantially reduce the burden of CRC. This project utilizes stakeholder/patient education and automation of the process to improve compliance with the recommendations. Such novel workflows can play a key role in reducing the burden of CRC by targeting high-risk individuals for CRC screening.Figure 1.: Adherence rate of recommendations for colorectal cancer screening in first-degree relatives of patients with advanced adenomas

S299 How Often Do We Provide Recommendations to Patients With Colorectal Cancer or Advanced Colonic Adenomas on When Their First-Degree Relatives Should Begin Colorectal Cancer Screening?

Introduction: First-degree relatives of patients found to have colorectal cancer (CRC) or advanced adenomas (AA) are advised to undergo colonoscopy starting at age 40, 10 years prior to time of CRC diagnosis in their first-degree relative, or at age of onset of AA in their first-degree relative; whichever comes first. Current guidelines recommend written communication to patients with CRC or AAs advising screening in first-degree relatives, which is particularly important in light of increased rates of early-onset CRC. We aimed to analyze the rate at which we provided guidance to patients found to have CRC or AAs on advising their first-degree relatives on timing of colonoscopy. Methods: We analyzed patients at our institution who underwent outpatient colonoscopies from November 29, 2021 to April 30, 2022. AAs were defined as adenomas ≥ 1 centimeter (cm) in size with tubulovillous, villous, high-grade dysplasia or traditional serrated features on histology, or sessile serrated lesions (SSLs) either ≥ 1 cm or with dysplasia. Patients with prior history of CRC or AA were excluded. We assessed how often appropriate screening recommendations were provided to patients with CRC or AAs for first-degree relatives based on documentation within 3 months of colonoscopy. Results: A total of 1332 colonoscopies were reviewed, with 47 patients meeting criteria for a new diagnosis of CRC or AA. Of these patients, 53.2% were African American and 57.4% were females (Table). The mean patient age was 56.9 years (± 10.6 years). Of these 47 patients, 3 patients (6.4%) were provided with specific written screening recommendations for first-degree relatives within 3 months of colonoscopy. Conclusion: In this retrospective analysis of patients found to have CRC or AAs on colonoscopy, only 6.4% were provided written guidance to advise first-degree relatives on appropriate timing for colonoscopy within three months after procedure. While verbal recommendations to patients may occur, patients may not recall specifics post-procedure or via telephone. Furthermore, guidelines call for recommendations for family members to be included in endoscopy reports, or through a letter meant to be shared with first-degree relatives. Considering these findings, we aim to provide an education intervention and templates for post-colonoscopy pathology letters and/or clinic visits to facilitate communication to patients with CRC or AAs on appropriately advising CRC screening in family members. Table 1. - Demographic information of patients found to have newly diagnosed colorectal cancer (CRC) or advanced adenoma (AA) on colonoscopy Number of patients (%) Known Family History of CRC or AA 6 (12.8%) Gender Male 20 (42.5%) Female 27 (57.4%) Ethnicity White 14 (29.8%) African American 25 (53.2%) Asian 3 (6.4%) Hispanic 2 (4.3%) Other 3 (6.4%) Age (mean) 56.9 years (± 10.6)

Gastric Cancer Screening in First-Degree Relatives: A Pilot Study in a Diverse Integrated Healthcare System.

Family history of gastric cancer has been shown as an independent risk factor of gastric cancer development and is associated with increased risk of progression to gastric cancer among patients with gastric intestinal metaplasia (GIM). Between 2017 and 2020, we conducted a prospective pilot screening program of patients with a confirmed first-degree relative with gastric cancer to evaluate the feasibility of screening and prevalence of precursor lesions (e.g., GIM or dysplasia) on biopsy. A total of 61 patients completed screening by upper endoscopy with a mapping biopsy protocol: 27 (44%) were found to have GIM and 4 (7%) were found with low-grade dysplasia. Our pilot screening program identified a high prevalence of precursor lesions for gastric cancer among asymptomatic patients with a first-degree relative with gastric cancer. Careful endoscopic inspection and standardized biopsy protocols may aid in prompt identification of these precursor lesions in those at risk of gastric cancer.

Glaucoma Cascade Screening in a High Risk Afro-Caribbean Haitian Population: A Pilot Study.

Précis:Glaucoma cascade screening in first-degree relatives (FDRs) of young Haitian glaucoma patients had high yield for diagnosing manifest and suspected glaucoma in 30.8% of those screened despite modest participation.Purpose:To evaluate the outcomes of glaucoma cascade screening in FDRs (parents, siblings, and offspring) of Haitian juvenile open-angle glaucoma (JOAG) patients.Patients and Methods:Consecutive index patients (Haitians with JOAG) were identified, and the number/type of FDRs residing in South Florida were recorded. These FDRs were invited for free glaucoma screening, which included a comprehensive ophthalmic exam, gonioscopy, automated visual field testing and optical coherence tomographic analysis of the retinal nerve fiber layers. FDR characteristics and clinical findings from screening are reported.Results:A total of 77 FDRs were invited, 26 (33.8%) agreed to undergo screening (18 females, 9 males), which revealed 2 (7.7%) with manifest glaucoma (mean age 77.5 y; one of whom was previously unaware of his glaucoma diagnosis), 6 (23.1%) with suspected glaucoma (mean age 29.8±18.3 y), and 18 (69.2%) without manifest or suspected glaucoma (mean age 37.2±21.8 y). Siblings of index patients were least likely to participate in cascade glaucoma screening when compared with index patients’ parents or offspring. FDR eyes with manifest glaucoma had significantly worse best-corrected visual acuities, higher intraocular pressures, thinner central corneal thicknesses, and thinner circumferential papillary retinal nerve fiber layer thicknesses than those without glaucoma.Conclusion:Glaucoma cascade screening of Haitian JOAG patients’ FDRs revealed that 30.8% had suspected or manifest glaucoma. Future efforts centered on provider-initiated recruitment and improving public glaucoma awareness and education may increase screening participation.

Clinical and radiological testing for subclinical atherosclerosis in first-degree relatives of patients with premature coronary artery disease: feasibility and diagnostic yield

Abstract Background Premature atherosclerotic cardiovascular disease (ASCVD) is highly heritable. The screening of first-degree relatives (FDR) of patients with premature ASCVD is recommended but not routinely performed, and the diagnostic yield of different approaches to such screening is unknown. Purpose To determine the feasibility and diagnostic yield of clinical and radiological screening of FDRs of patients with premature coronary artery disease (CAD) in clinical setting. Method We recruited FDRs of patients with angiographically-proven CAD with stenosis of ≥50% who presented at the age of ≤50 years for males and ≤55 years for females. After clinical and laboratory assessment, patients with no personal history of cardiovascular disease underwent either coronary computed tomography angiography (CCTA), coronary calcium scoring assessment (CAC), or carotid ultrasound (CUS). Subclinical atherosclerosis was defined as 1) CAC score &amp;gt;100 Agatston units or &amp;gt;75% percentile for age and sex; 2) Stenosis &amp;gt;50% in at least one coronary artery or segment involvement scores &amp;gt;50th percentile in males and &amp;gt;75th in females; or, 3) Carotid plaque on ultrasonography. Results We enrolled 220 FDRs between 2017 and 2020, 129 completed clinical assessment (Figure 1). Of them, 28 (21.7%) had a personal history of ASCVD and 101 were tested for subclinical atherosclerosis. The characteristics of these patients are shown in Table 1. The most prevalent cardiovascular risk factors were dyslipidemia (40.6%), hypertension (22.8%), and obesity (21.8%). When assessed with the Framingham risk score calculator without adjustment for family history, only 5.1% and 28.6%, of patients had high or moderate cardiovascular risk, respectively. After adjusting for family history and the presence of statin-indicated conditions, 39.6% and 14.9% of patients were placed in high and moderate risk groups, respectively. Subclinical atherosclerosis was found in 43.6% of all patients (Figure 1) and 57.7% of patients over 40 years of age. The diagnostic yield of procedures was 29.6% for CUS, 37.8% for CCTA and 61.1% for CAC scoring. After the radiological assessment, 13.9% of patients were reclassified to a higher risk group (Table 1). Conclusion Non-invasive cardiovascular imaging detected subclinical atherosclerosis in 43.6% of healthy patients with a family history of premature ASCVD, moving 1 in 7 patients to a higher risk group and suggesting that this screening approach may improve risk prediction in this population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research.St. Paul's Hospital Foundation and the Vancouver General Hospital Foundation. Figure 1Table 1

Cost-effectiveness analysis of screening for first-degree relatives of patients with bicuspid aortic valve

Abstract Introduction Bicuspid aortic valve (BAV) is the commonest congenital heart valve defect, found in 1% to 2% of the general population and associated with life-threatening complications. Given the high heritability index of BAV, many experts recommend echocardiography for first-degree relatives (FDRs) of an index patient. However, the cost-effectiveness of such cascade screening for BAV has not been fully evaluated. Materials and methods Using a decision-analytic model, we performed a cost-effectiveness analysis of echocardiographic screening of FDRs of BAV index cases. Data on BAV probabilities and BAV complications among FDRs were derived from our institution's BAV familial cohort and from the relevant literature on population-based BAV cohorts with long-term follow-up. Health gain was measured as quality-adjusted life years (QALYs). Cost inputs were based on list prices and literature data. One-way and probabilistic sensitivity analyses were performed to account for uncertainty in the model's variables. Results and disscusion Screening of FDRs was found to be the dominant strategy, being more effective and less costly than no screening, with savings of €208 and gains of 1.6 QALYs. Results were sensitive to the full range of reported BAV rates among FDRs across the literature, with the benefit gradually decreasing from the screening age of 55 years, with trend shifting at the age of 69. Conclusions This economic evaluation model revealed that echocardiographic screening of FDRs of BAV index case is not only clinically important but also highly cost effective and cost-saving. Health gains could be achieved from initiating screening program, along with costs saving. Sensitivity analysis supported the model's robustness, suggesting its generalization. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Center for Interdisciplinary Data Science Research fellowships grant

Factors Affecting Cancer Prevention Behaviors and Cancer Screening in First-Degree Relatives of Breast and Colorectal Cancer Patients in Korea: A Cross-Sectional Study.

First-degree relatives (FDRs) of cancer patients have a high risk of cancer due to a similar lifestyle and genetic predisposition. However, previous studies rarely examined the level of cancer prevention behaviors and screening and affecting factors in cancer patients' FDRs. This study aimed to describe the levels of cancer knowledge, attitudes toward cancer, cancer worry, perceived cancer risk, and cancer prevention behaviors and cancer screening in FDRs of breast and colorectal cancer patients. Moreover, it sought to identify factors affecting cancer prevention behavior and cancer screening. A cross-sectional, descriptive correlational design was used. The study enrolled 138 FDRs of breast and colorectal cancer patients. Participants completed self-administered questionnaires at a tertiary hospital in Seoul, Korea. Descriptive statistics, frequencies, chi-square test, independent t test, one-way analysis of variance (ANOVA), Pearson's correlation, multiple regression, and logistic regression were performed for data analysis. The levels of perceived cancer risk, cancer knowledge, attitude toward cancer, and cancer prevention behaviors were moderate, while the level of cancer worry was high. Ninety-two participants reported having undergone cancer screenings, but the types of screening were not associated with their family history. Age, gender, and attitude toward cancer affected cancer prevention behaviors. The cancer screening rate was higher in older participants, in women, and in patients' FDRs with a longer cancer diagnosis. Attitude was the modifiable factor for cancer prevention behaviors. Nurse-led educational and counseling interventions should be developed to improve attitude toward cancer among FDRs of cancer patients.

The prevention of gastric cancer by Helicobacter pylori eradication.

Gastric cancer remains one of the most common causes of death globally. Increasing evidence suggests that many gastric cancer cases can be prevented by eradicating its most important etiological agent, Helicobacter pylori. Using the search terms 'H. pylori' and 'gastric cancer' we reviewed the scientific literature regarding the association between H. pylori and gastric cancer published from 1 January 2020 to 30 May 2021. We review the most important articles relevant to the clinical issues regarding H. pylori eradication for gastric cancer prevention. In randomized trials, eradication of H. pylori is associated with an approximately 50% reduction in sporadic gastric cancer. A similar benefit was observed when screening first-degree relatives of gastric cancer cases, after resection of early gastric cancer to prevent metachronous neoplasia, and in population-based screen and treatment programs in areas of high H. pylori and gastric cancer prevalence. Even in relatively low gastric cancer countries such as the United States, gastric cancer may potentially be avoided by screening for H. pylori, especially among minority groups who are at greatest risk. Gastric cancer is preventable, at least in part, by H. pylori eradication. Ongoing screening trials will help determine whether population-based H. pylori screening programs are feasible and cost-effective. Their results are likely to differ according to H. pylori and gastric cancer prevalence rates.

Systematic review with meta-analysis: the effects of family history on the risk of Barrett's oesophagus and oesophageal adenocarcinoma.

SummaryBackgroundCurrent guidelines recommend different screening approaches for individuals with a family history of Barrett's oesophagus (BO) or oesophageal adenocarcinoma (OAC), varying from no screening to screening all individuals with a positive family history.AimsTo determine evidence‐based risk estimates for individuals with a family history of BO or OACMethodsWe systematically searched Pubmed, Embase and Cochrane Library until October 2020 to identify all studies that reported on the association between family history and the risk of BO and OAC. Pooled summary estimates of adjusted relative risks and prevalence of familial BO/OAC with 95% confidence intervals (CIs) were calculated using a random effects model.ResultsFourteen studies comprising 16 189 BO/OAC patients were analysed. Familial clustering was seen in 8.84% (95% CI: 5.54‐13.82) and 4.37% (95% CI: 2.15‐8.69) of patients with BO and OAC, respectively (nine studies). Screening first‐degree relatives of BO patients had a diagnostic yield between 12% and 44% for BO (four studies). However, the yield for high‐grade dysplasia and OAC was low (<2%). Individuals with a positive family history had a higher risk of having BO (aRR 3.26; 95% CI 1.43‐7.40; I 2 = 46%; three studies) and OAC (aRR 2.19; 95% CI 1.14‐4.21; I 2 = 48%; five studies) compared to individuals without a family history.ConclusionsA verified family history of BO or OAC is a strong risk factor for both BO and OAC. A positive family history could be a clinically meaningful way to identify high‐risk individuals who may benefit from early detection strategies.

Next-Generation Sequencing Reveals Novel Genetic Variants for Dilated Cardiomyopathy in Pediatric Chinese Patients.

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by bilateral or left ventricular cardiac dilation and systolic dysfunction that can lead to heart failure and sudden cardiac death in children. Many studies have focused on genetic variation in DCM-related genes in adult populations; however, the mutational landscape in pediatric DCM patients remains undetermined, especially in the Chinese population. We applied next-generation sequencing (NGS) technology to genetically analyze 46 pediatric DCM patients to reveal genotype-phenotype correlations. Our results indicated DCM-associated pathogenic mutations in 10 genes related to the structure or function of the sarcomere, desmosome, and cytoskeleton. We also identified 6 pathogenic mutations (5 novel) in the Titin (TTN) gene that resulted in truncated TTN variants in 6 (13%) out of 46 patients. Correlations between TTN mutations and clinical outcomes were assessed. Our data indicate that one-third of pediatric DCM cases are caused by genetic mutations. The role of TTN variants should not be underestimated in pediatric DCM and age-dependent pathogenic penetrance of these mutations should be considered for familial DCM cases. We argue that genetic testing of DCM cases is valuable for predicting disease severity, prognosis, and recurrence risk, and for screening first-degree relatives.

Screening first-degree relatives of glaucoma patients reveals barriers to participation

PurposeTo report the results of a glaucoma screening campaign targeting first-degree relatives of glaucoma patients in South India.Methods1598 glaucoma patients were contacted via letter or letter and phone call and...

Family screening in patients with isolated bicuspid aortic valve in a general hospital, yield and subgroup analysis

Abstract Background Bicuspid aortic valve (BAV) may frequently lead to aortic dilatation with risk of aortic dissection. In patients with BAV both familial clustering and aortic dilatation in first-degree relatives (FDR) without BAV has been demonstrated. Based on these findings the ESC Aortic Guidelines recommend to consider screening of FDR, while the ACC/AHA Guidelines on Valvular Heart Diseases consider screening of FDR only if the index patient has associated aortopathy. Currently, no data about the effectiveness of screening is available. Purpose To investigate the yield of screening FDR of patients with isolated BAV and to explore subgroups with FDR of patients who had needed surgery or of patients with aortic dilatation. We hypothesized that aortic dilatation (&amp;gt;40mm) in the index patient is not a risk factor for BAV in FDR. Methods From 2012, patients with BAV visiting the outpatient clinic of a teaching hospital, received information advising cardiac screening of FDR. FDR of patients with isolated BAV who were referred, were included. From the 10 index patients from other hospitals, information was retrieved. [Fig.1] Results Referred were FDR from 118 index patients (mean age 60 years, standard deviation [SD] 14, range 15–90 years, 82 males [70%]). Of all index patients 63 (53%) had undergone aortic valve replacement, including concomitant ascending aorta replacement in 25 (21%). In the non-operated index patients, 31 (26%) had dilatation (&amp;gt;40mm) of sinus of Valsalva and/or tubular ascending aorta. Screened were 257 FDR (median 2 per index patient) comprising 20 parents (8%), 103 siblings (40%) and 134 offspring (52%). Mean age of FDR was 48 years (SD16, range 4–83 years) and 89 subjects (42%) were male. The diagnostic imaging modality was echocardiography in 240 cases (93%) and MRI in 17 cases. Ten FDR had an already known BAV and were not included in the screening. Among the 257 FDR, we diagnosed 12 new BAV (4.7%, 95% confidence interval [CI]2.9–8.0%) (mean age 44 years, 50% male). Additionally, we diagnosed 23 new isolated aorta dilatations (8.9%; 95% CI 6.0–13%) at level of sinus of Valsalva and/or tubular ascending aorta (mean age 57 years, 18 [78%] were male) [Fig. 1]. Among them, 11 had hypertension. FDR (n=147) of index patients with BAV and previous aortic valve surgery (n=63), had a risk ratio (RR) of 2.25 (95% CI 0.62–8.10) of having a BAV. FDR (n=126) of index patients with BAV and repaired or unrepaired aortic dilatation (n=56) had RR 0.35 (95% CI 0.10–1.25) of having a BAV. Conclusions Screening FDR of patients with isolated BAV resulted in a reasonable yield of 14% new cases with BAV or isolated aortic dilatation. The RR of the subgroup with aorta dilatation did not justify the limitation of the FDR as suggested in the ACC/AHA Guidelines. Figure 1. Flowchart of screening and result Funding Acknowledgement Type of funding source: None

Patterns of changes in serum lipid profiles in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients

BackgroundLipid abnormality pervasively is associated with the risk of type 2 diabetes mellitus. To the best of our knowledge, there is no study that has examined the longitudinal changes in a wide range of serum lipid profiles in prediabetic subjects in association with the risk of developing type 2 diabetes mellitus in the future. This study aimed to identify the patterns of changes in lipid profiles over time in prediabetic patients and to classify these subjects in order to highlight which patients are at high risk for future diabetes.MethodsThis prospective 16-year (2003–2019) cohort study was conducted among 1228 prediabetic subjects. The study subjects were followed, and the changes in their lipid profiles, including triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, were evaluated. The latent Markov model was used for data analysis.ResultsThe mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The latent Markov model identified two latent states of subjects in terms of changes in lipid profiles: a low tendency to progress diabetes / high tendency to progress diabetes (74, 26%). The latent Markov model showed that the transition probability from a “low tendency to progress diabetic” state to a “high tendency to progress diabetic” state was lower than the transition probability from “high tendency to progress diabetic” state to “low tendency to progress diabetic” state.ConclusionsThe present study showed that more than half of the first-degree relatives of T2DM had approximately normal lipid profiles and that these patients are more inclined to transition from a higher- to a lower-tendency diabetic state. These findings confirm the value of regular screening of first-degree relatives of T2DM. Moreover, preventive intervention strategies are recommended to reduce their risk of developing T2DM.