Asymptomatic High-risk Individuals Research Articles

Multilevel approaches to address disparities in lung cancer screening: a study protocol

BackgroundLow-dose computed tomography (lung cancer screening) can reduce lung cancer-specific mortality by 20–24%. Based on this evidence, the United States Preventive Services Task Force recommends annual lung cancer screening for asymptomatic high-risk individuals. Despite this recommendation, utilization is low (3–20%). Lung cancer screening may be particularly beneficial for African American patients because they are more likely to have advanced disease, lower survival, and lower screening rates compared to White individuals. Evidence points to multilevel approaches that simultaneously address multiple determinants to increase screening rates and decrease lung cancer burden in minoritized populations. This study will test the effects of provider- and patient-level strategies for promoting equitable lung cancer screening utilization.MethodsGuided by the Health Disparities Research Framework and the Practical, Robust Implementation and Sustainability Model, we will conduct a quasi-experimental study with four primary care clinics within a large health system (MedStar Health). Individuals eligible for lung cancer screening, defined as 50–80 years old, ≥ 20 pack-years, currently smoking, or quit < 15 years, no history of lung cancer, who have an appointment scheduled with their provider, and who are non-adherent to screening will be identified via the EHR, contacted, and enrolled (N = 184 for implementation clinics, N = 184 for comparison clinics; total N = 368). Provider participants will include those practicing at the partner clinics (N = 26). To increase provider-prompted discussions about lung screening, an electronic health record (EHR) clinician reminder will be sent to providers prior to scheduled visits with the screening-eligible participants. To increase patient-level knowledge and patient activation about screening, an inreach specialist will conduct a pre-visit phone-based educational session with participants. Patient participants will be assessed at baseline and 1-week post-visit to measure provider-patient discussion, screening intentions, and knowledge. Screening referrals and screening completion rates will be assessed via the EHR at 6 months. We will use mixed methods and multilevel assessments of patients and providers to evaluate the implementation outcomes (adoption, feasibility, acceptability, and fidelity).DiscussionThe study will inform future work designed to measure the independent and overlapping contributions of the multilevel implementation strategies to advance equity in lung screening rates.Trial registrationClinicalTrials.gov, NCT04675476. Registered December 19, 2020.

Prognostic Value of Coronary Artery Calcium in the Intermediate-Risk Population of Developing Coronary Artery Disease

Background: The present study was designed to estimate the coronary artery calcium score (CACS) and its association with the incidence of major adverse cardiovascular events (MACE) in asymptomatic patients who are at risk of coronary artery disease (CAD). Objective: To estimate the CACS and its association with the incidence of MACE in asymptomatic patients. Methods: In this prospective cross-sectional observational study, 108 consecutive patients were enrolled. Demographic details and clinical data including lipid profile, systolic blood pressure, electrocardiography, 2D echocardiography, and routine blood investigations were reported. CACS was derived from computed tomography using a 256-slice scanner with a rotation time of 270 milliseconds. MACE was recorded at a one-year follow-up. Results: The mean age was 54.55 ± 7.7 years with male predominance (62%). CACS categories 0, 1-99, 10-399, 400-999, and more than 1000 constituted 43.5%, 28.7%, 18.52%, 8.33%, and 0.93% respectively. The correlation between the groups of positive and negative CACS and the presence or absence of standard risk factors was found to be statistically significant in diabetes mellitus (P=&lt;0.001), hypertension (P=&lt;0.001), and history of CAD in the family (P = 0.036). Although the association between smokers and calcium was statistically insignificant, it had clinical significance (P= 0.294). Out of 108 patients, MACE was observed in 16 (14.81%) patients with positive CACS at the 1-year follow-up. Conclusion:CACS measurement is often regarded as the primary non-invasive approach for risk stratification, MACE estimation, and promptly identifying high-risk asymptomatic individuals. Keywords: Coronary Artery Calcium Score; Cardiovascular Events; Coronary Calcification; Risk Stratificationa

Carotid artery screening in high risk asymptomatic individuals: outcomes of 3000 carotid screening

Carotid artery screening in high risk asymptomatic individuals: outcomes of 3000 carotid screening

Trend of the polyp and adenoma detection rate by sex and age in asymptomatic average-risk and high-risk individuals undergoing screening colonoscopy, 2012–2019

Adenoma detection rate (ADR) is an imperative quality measure for colorectal cancer (CRC) screening. This retrospective observational study aimed to determine the trend of polyp detection rate (PDR) and ADR in asymptomatic average- and high-risk participants in different age groups who underwent screening colonoscopy over the seven years from April 2012 to March 2019 in a tertiary gastroenterologyreferral center of Iran. Of 1676 participants, 51.8 % were men (mean age 52.3 years). The overall PDR and ADR were 22.7 %, and 13.5 %, respectively. Both Polyps and adenomas were more common in age groups 51–59 and ≥60 years in high-risk patients than in the corresponding groups of average-risk patients (p < 0.05). Also, both PDR and ADR were more frequent in men than in women among all studied age groups, but it was statistically significant only for the youngest age group (16.8 % versus 10.5 %, p < 0.05) for PDR and the oldest age group (19.7 % versus 13 %, p < 0.05) for ADR, respectively. The trend of total ADR was upward over 7 years in both average-risk (6.7 % to 13.3 %) and high-risk (9.8 % to 27 %) groups and across all age groups in both sexes. Multivariable logistic regression revealed that high-risk individuals had an elevated risk of adenoma compared with average-risk patients (OR: 1.6, p = 0.006). Substantial variation in thresholds of polyp and adenoma detection by age, sex, and risk categories emphasizes the need for a risk-adapted approach to CRC screening and prevention programs.

1916. Evaluation of nasal swab collection methods on a university campus during the SARS-CoV-2 pandemic

Abstract Background Characterizing SARS-CoV-2 outbreaks on university campuses is critical for informed public health measures and understanding transmission dynamics. Figure 1.Dropbox and Kiosk Samples Collected September 10, 2021 to April 23, 2022. Methods Faculty, staff, and students at a major public university in Seattle, WA, USA were enrolled in a COVID-19 testing study. Individuals could test using observed self-swabs at on-campus kiosks or unobserved self-swabs using a kit and returning it to a dropbox on campus. Sample collection volume for observed self-swabs was limited by staffing and space. All samples were returned to the laboratory and tested for SARS-CoV-2 by qRT-PCR. Results From September 10, 2021 to April 23, 2022, 38,400 individuals were enrolled in the study. Of these individuals, 5,089 used dropboxes only, 14,421 used kiosks only, and 5,820 used both. A total of 21,653 dropbox swabs and 75,493 observed self-swabs were collected. Median age was similar between individuals using dropboxes and observed self-swabs (20 vs. 22 years). A greater proportion of dropbox users were students compared to faculty and staff (students made up 83% of dropbox only population, 75% of kiosk only, and 86% of both, χ² p-value&amp;lt; 0.0001). Symptom data was reported for 65,349 swabs. Dropbox users were less likely to have symptoms compared to observed self-swab users (24% of swabs vs. 54%, χ² p-value&amp;lt; 0.0001). SARS-CoV-2 positivity was slightly lower for dropboxes compared to kiosks (4% vs. 5%; p=0.001). Dropboxes were highly utilized during periods of increased testing demand, including after academic breaks and variant emergence (Figure 1). Of the total tests distributed for use, a greater proportion of dropbox kits were unable to be resulted (6%) compared to observed self-swab kits (0.02%). Conclusion Dropboxes provided a flexible, high-volume collection method at times of increased testing demand. Individuals who used dropboxes were less likely to report symptoms and slightly less likely to test positive, suggesting a role for dropbox utilization in high-risk asymptomatic individuals during periods of high community transmission on a university campus. Disclosures Geoffrey S. Gottlieb, MD, PhD, Abbott Molecular Diagnostics: Grant/Research Support|Alere Technologies: Grant/Research Support|BMGF: Grant/Research Support|BMS: Grant/Research Support|Cerus Corp.: Grant/Research Support|Gilead Sciences: Grant/Research Support|Janssen Pharmaceutica: Grant/Research Support|Merck &amp; Co: Grant/Research Support|Roche Molecular Systems: Grant/Research Support|THERA Technologies/TaiMed Biologics: Grant/Research Support|ViiV Healthcare: Grant/Research Support Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Concordance of EUS and MRI/MRCP findings among high-risk individuals undergoing pancreatic cancer screening

Background/Objectives: Surveillance with endoscopic ultrasonography (EUS) and MRI/magnetic retrograde cholangiopancreatography (MRCP) is recommended for individuals at high risk for pancreatic cancer. We sought to characterize the findings of these surveillance exams and define the level of concordance between these two modalities. Methods173 asymptomatic high-risk individuals (HRIs) meeting criteria for pancreatic cancer surveillance underwent EUS, MRI/MRCP, or both between 2008 and 2021. Clinical records were reviewed in all cases. ResultsHRIs underwent an average of 3.6 ± 3.2 surveillance exams over a period of 3.3 ± 3.5 years. Abnormalities including intraductal papillary mucinous neoplasms (IPMNs), solid lesions, and parenchymal irregularities were identified in 50.9% (n = 88). Four of these abnormalities (2.3%) had worrisome features, defined by cyst size, thickened/enhancing cyst walls, rapid growth rate, or change in main pancreatic duct diameter. All four worrisome lesions were seen on both MRI/MRCP and EUS. No pancreatic cancers were detected. Baseline EUS and MRI/MRCP exams were compared in 106 patients for concordance, and most (n = 66, 62.3%) were concordant. High levels of concordance were specifically observed for a dilated main pancreatic duct (p < 0.01) and cystic lesions >5 mm (p = 0.01). Among discordant cases, most (30/40; 75%) involved abnormal tissue heterogeneity seen primarily on EUS. None of these discordant lesions ultimately developed worrisome features. ConclusionsWorrisome pancreatic lesions were uncommon in our high-risk pancreatic cancer population and were detected by both EUS and MRI/MRCP. There was mild discordance with respect to less worrisome findings, but these discrepancies were not associated with any adverse clinical outcomes.

Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients.

BackgroundAtrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations.MethodsTwo hundred seventy-four subjects aged 65–75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately.ResultsAtrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665–0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654–0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively.ConclusionBlood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

Is Biannual Surveillance for Pancreatic Cancer Sufficient in Individuals With Genetic Syndromes or Familial Pancreatic Cancer?

Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at increased risk of developing PC. These high-risk individuals (HRIs) may benefit from PC surveillance. A PC surveillance program was developed to evaluate the detection of premalignant lesions and early-stage PCs using biannual imaging and to determine whether locally advanced or metastatic PCs develop despite biannual surveillance. From January 2013 to April 2020, asymptomatic HRIs were enrolled and followed with alternating MRI and endoscopic ultrasound every 6 months. Of 75 HRIs, 43 (57.3%) had a germline mutation in a PC susceptibility gene and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 individuals (34.7%), but only 2 developed progressive lesions. One patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole-genome sequencing of this patient's PC and of a second patient with PJS-associated PC from the same kindred revealed biallelic inactivation of STK11 in a KRAS-independent manner. A review of 3,853 patients from 2 PC registries identified an additional patient with PJS-associated PC. All 3 patients with PJS developed advanced PC consistent with the malignant transformation of an underlying BD-IPMN in &lt;6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN that harbored polyclonal KRAS mutations. PC surveillance identifies a high prevalence of BD-IPMNs in HRIs. Patients with PJS with BD-IPMNs may be at risk for accelerated malignant transformation.

Carotid artery screening in high risk asymptomatic individuals: outcomes of 3000 carotid screening.

The primary aims of the study to evaluate the efficacy of carotid screening tests to identify asymptomatic carotid artery stenosis among high-risk patients and early prevention of stroke. The estimated prevalence of asymptomatic severe carotid stenosis (≥70%) in the general adult population ranges up to 3.1%. However, the prevalence is higher in comorbid individuals. This makes it important to perform screening testing for early diagnosis and treatment in predetermined high-risk patients. In this prospective study, 3000 selected patients screened during March 2017 and September 2018 at the most populated family health center. Participants selected among registered individuals who have at least one of the risk factors such as hypertension, hyperlipidemia, diabetes mellitus, obesity, and smoking. All the participants were asymptomatic and above the age of 55. Bilateral carotid artery screening performed by Duplex Ultrasonography (DUSG) at the first call and one year later. Patients with severe carotid and/or coronary artery stenosis treated by surgical revascularization or stent implantation in the light of the latest guidelines. Carotid screening among high-risk asymptomatic individuals is of great importance to identify severe carotid artery as well as coronary artery stenosis. Patient education during screening may play a crucial role in preventing the disease.

AAUS guidelines 2021 revision sexually transmitted infection (STIs) diagnostic strategy for STI

AAUS guidelines 2021 revision sexually transmitted infection (STIs) diagnostic strategy for STI

Artificial Intelligence-Assisted Identification of Genetic Factors Predisposing High-Risk Individuals to Asymptomatic Heart Failure.

Heart failure (HF) is a global pandemic public health burden affecting one in five of the general population in their lifetime. For high-risk individuals, early detection and prediction of HF progression reduces hospitalizations, reduces mortality, improves the individual’s quality of life, and reduces associated medical costs. In using an artificial intelligence (AI)-assisted genome-wide association study of a single nucleotide polymorphism (SNP) database from 117 asymptomatic high-risk individuals, we identified a SNP signature composed of 13 SNPs. These were annotated and mapped into six protein-coding genes (GAD2, APP, RASGEF1C, MACROD2, DMD, and DOCK1), a pseudogene (PGAM1P5), and various non-coding RNA genes (LINC01968, LINC00687, LOC105372209, LOC101928047, LOC105372208, and LOC105371356). The SNP signature was found to have a good performance when predicting HF progression, namely with an accuracy rate of 0.857 and an area under the curve of 0.912. Intriguingly, analysis of the protein connectivity map revealed that DMD, RASGEF1C, MACROD2, DOCK1, and PGAM1P5 appear to form a protein interaction network in the heart. This suggests that, together, they may contribute to the pathogenesis of HF. Our findings demonstrate that a combination of AI-assisted identifications of SNP signatures and clinical parameters are able to effectively identify asymptomatic high-risk subjects that are predisposed to HF.

Genome-wide 5hmC profiles to enable cancer detection and tissue of origin classification in breast, colorectal, lung, ovarian, and pancreatic cancers.

3044 Background: Epigenomics assays have recently become popular tools for identification of molecular biomarkers, both in tissue and in plasma. In particular 5-hydroxymethyl-cytosine (5hmC) method, has been shown to enable the epigenomic regulation of gene expression and subsequent gene activity, with different patterns, across several tumor and normal tissues types. In this study we show that 5hmC profiles enable discrete classification of tumor and normal tissue for breast, colorectal, lung ovary and pancreas. Such classification was also recapitulated in cfDNA from patient with breast, colorectal, lung, ovarian and pancreatic cancers. Methods: DNA was isolated from 176 fresh frozen tissues from breast, colorectal, lung, ovary and pancreas (44 per tumor per tissue type and up to 11 tumor tissues for each stage (I-IV)) and up to 10 normal tissues per tissue type. cfDNA was isolated from plasma from 783 non-cancer individuals and 569 cancer patients. Plasma-isolated cfDNA and tumor genomic DNA, were enriched for the 5hmC fraction using chemical labelling, sequenced, and aligned to a reference genome to construct features sets of 5hmC patterns. Results: 5hmC multinomial logistic regression analysis was employed across tumor and normal tissues and identified a set of specific and discrete tumor and normal tissue gene-based features. This indicates that we can classify samples regardless of source, with a high degree of accuracy, based on tissue of origin and also distinguish between normal and tumor status.Next, we employed a stacked ensemble machine learning algorithm combining multiple logistic regression models across diverse feature sets to the cfDNA dataset composed of 783 non cancers and 569 cancers comprising 67 breast, 118 colorectal, 210 Lung, 71 ovarian and 100 pancreatic cancers. We identified a genomic signature that enable the classification of non-cancer versus cancers with an outer fold cross validation sensitivity of 49% (CI 45%-53%) at 99% specificity. Further, individual cancer outer fold cross validation sensitivity at 99% specificity, was measured as follows: breast 30% (CI 119% -42%); colorectal 41% (CI 32%-50%); lung 49% (CI 42%-56%); ovarian 72% (CI 60-82%); pancreatic 56% (CI 46%-66%). Conclusions: This study demonstrates that 5hmC profiles can distinguish cancer and normal tissues based on their origin. Further, 5hmC changes in cfDNA enables detection of the several cancer types: breast, colorectal, lung, ovarian and pancreatic cancers. Our technology provides a non-invasive tool for cancer detection with low risk sample collection enabling improved compliance than current screening methods. Among other utilities, we believe our technology could be applied to asymptomatic high-risk individuals thus enabling enrichment for those subjects that most need a diagnostic imaging follow up.

A biannual pancreatic cancer surveillance program identifies a high prevalence of intraductal papillary mucinous neoplasms: accelerated malignant transformation in Peutz-Jeghers syndrome

Presenter: Yifan Wang MD | McGill University Background: Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at higher risk of developing PC. Surveillance of high-risk individuals (HRIs) may allow earlier detection of PC and its precursor lesions. Since advanced-stage PCs have been reported despite annual surveillance, shorter interval surveillance may be justified. Methods: From 2013 to 2020, asymptomatic HRIs were enrolled in a PC surveillance program alternating between magnetic resonance imaging and endoscopic ultrasound every 6 months. Results: Of 75 HRIs enrolled, 43 (57.3%) had a germline mutation in a PC susceptibility gene (GS), and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 (34.7%) individuals, but only 2 developed progressive lesions. Despite biannual surveillance, one patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole genome sequencing of this patient’s PC and of a second PJS-associated PC from the kindred revealed that both tumours were driven by biallelic inactivation of STK11 in a KRAS-independent manner. From a review of 3,853 patients across two PC registries, we identified one additional PJS patient with PC. Importantly, all 3 PJS patients developed advanced PC consistent with malignant transformation of an underlying BD-IPMN in < 6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN which harboured polyclonal KRAS mutations. Furthermore, we found that colloid-type PCs, which develop from IPMNs, display COSMIC signature 17. Conclusion: Biannual PC surveillance identifies a high rate of BD-IPMNs in HRIs, but only a minority of these progress to PC. Our findings suggest that BD-IPMNs in patients with PJS are at risk of rapid malignant transformation. In PJS individuals, a lower threshold for resection of BD-IPMNs may be more effective than shortening surveillance intervals.

Clinical and serological profile of asymptomatic and non-severe symptomatic COVID-19 cases: Lessons from a longitudinal study in primary care in Latin America.

BackgroundChile has one of the highest incidences of COVID-19 infection in the world. Primary care can play a key role in early detection and containment of the disease. There is a lack of information on the clinical profile of patients with suspected COVID-19 in primary care, and controversy on the effectiveness of rapid serologic tests in the diagnosis and surveillance of the disease.AimTo assess the effectiveness of rapid serologic testing in detection and surveillance of COVID-19 cases in primary care.Design & settingA longitudinal study was undertaken, which was based on a non-random sample of 522 participants, including 304 symptomatic patients and 218 high-risk asymptomatic individuals. They were receiving care at four primary health clinics in an underserved area in Santiago, Chile.MethodThe participants were systematically assessed and tested for COVID-19 with reverse transcriptase-polymerase chain reaction (RT-PCR) and serology at baseline, and were followed clinically and serologically for 3 weeks.ResultsThe prevalence rate of RT-PCR confirmed COVID-19 cases were 3.5 times higher in symptomatic patients (27.5%; 95% confidence interval [CI] = 22.1 to 32.8) compared with asymptomatic participants (7.9%; 95% CI = 4.3 to 11.6). Similarly, the immune response was significantly different between both groups. Sensitivity of serologic testing was 57.8% (95% CI = 44.8 to 70.1) during the third week of follow-up and specificity was 98.4% (95% CI = 95.5 to 99.7).ConclusionRapid serologic testing is ineffective for detecting asymptomatic or non-severe cases of COVID-19 at early stages of the disease, but can be of value for surveillance of immunity response in primary care. The clinical profile and immune response of patients with COVID-19 in primary care differs from those in hospital-based populations.

Coronary artery calcium in primary prevention.

Identifying high-risk asymptomatic individuals remains the cornerstone ofcardiovascular disease prevention. Coronary artery calcium is a highly specific marker of atherosclerosis that can be quantified using non-contrast computed tomography. The resulting calcium score has the capacity to improve current methods of risk stratification. The aim of this article is to provide an overview of calcium scoring, including its method of acquisition, indications, interpretation and role in prognostication. Calcium score has been shown to convincingly predict future cardiovascular risk in the asymptomatic population across a wide range of ethnicities, ages and sexes. Individuals at intermediate Framingham risk benefit the most from calcium scoring, which can be used to inform the need for preventive pharmacotherapy. Calcium scoring can be repeated after five years to reassess cardiovascular risk, especially when there is a decision to defer statin therapy on the basis of absence of coronary calcium.

Adherence k principům kardiovaskulární prevence u osob s vysokým rizikem

Asymptomatic high-risk individuals represent one of the highest priorities of cardiovascular prevention, in clinical practice frequently overlooked. We analyzed the real adherence to recommended principles of cardiovascular prevention in primary care subjects.Our analysis is based on random general population sample, examined in the frame of post-MONICA survey in 2016/17. Each subject was categorized with regard to its individual cardiovascular risk (based on Sixth Joint European Guidelines) and the real adherence to recommended targets was ascertained.In total 898 subjects aged 25-75 years (47% males) were analyzed. Of them, 16.7% were classified into &#8220;very high risk&#8220; and 36.8% into &#8220;high risk&#8220; subgroup; remaining 46.5% were only at moderate or low risk. Regarding adherence to recommended principles, in &#8220;very high risk&#8220; category only 58.7% abstain from any form of tobacco, 38% reported appropriate physical activity (150 minutes of at least moderate activity weekly), 16.7% had recommended body constitution (BMI 20-25 kg/m2 ), 39.3% appropriate blood pressure (.

Coronary artery calcium testing: A call for universal coverage.

Heart attacks kill more Americans than all cancers combined. Fatal heart attack victims have no symptoms until minutes before they die, hence early detection of high-risk asymptomatic individuals is needed. Even though heart attacks kill and cost more than cancers, as a nation we spend over 20 times more on screening for asymptomatic cancer than for asymptomatic atherosclerotic cardiovascular disease (ASCVD), the underlying cause of heart attacks. Currently, payers only cover screening for risk factors of ASCVD such as blood pressure and blood cholesterol. This approach tends to miss high-risk and over-treat low-risk individuals. Although treadmill stress testing with ECG is not indicated for ASCVD detection in asymptomatic individuals, it is done often, and frequently leads to misleading conclusions or unnecessary downstream diagnostic procedures. For example, former President Clinton had passed his treadmill stress tests for several years during his presidential annual checkup but had a heart attack shortly after his presidency. This common practice is a waste of our limited resources. Instead, a more accurate risk assessment using coronary artery calcium (CAC) testing is available; and has just been adopted by ACC/AHA guidelines, however payers do not cover it. CAC is measured non-invasively with a 5-minute CT-scan of the heart, and costs less than $200, whereas cancer screening with colonoscopy and mammography costs over $3000. There is an opportunity to save lives and dollars if CAC testing is covered for appropriately selected individuals. Texas has already passed HB1290 to mandate CAC coverage. Other states must step up and take actions.

The clinical impact of MRI screening for BRCA mutation carriers: the first report in Japan

BackgroundThere is no consensus on the appropriate surveillance for high-risk women with breast cancer in Japan. We investigated their imaging features and pathological characteristics to build a proper surveillance system for asymptomatic high-risk individuals in the future.MethodsWe retrospectively reviewed 93 female (median age 43 years) BRCA1 and BRCA2 mutation carriers from our institutional clinical database from 2011 to 2017. The study population was composed of 112 breast cancers. Mammography and MRI were reviewed by examiners blinded to patients’ clinical history. Final surgical or biopsy histopathology served as the reference standard in all the patients.ResultsFifty-nine breast cancers met selection criteria; of these, 30 were BRCA1-associated tumors, and 29 were BRCA2-associated tumors. Invasive ductal carcinoma was the most prevalent type in both BRCA1 and BRCA2. There were statistically significant differences in phenotype, nuclear grade, and Ki-67 labeling index between BRCA1 and BRCA2 mutation carriers. Additionally, imaging findings on mammography and MRI were statistically different. Tumors in BRCA2 carriers demonstrated mammographic calcifications more frequently, while those in BRCA1 carriers demonstrated a mass or architectural distortion (P < 0.001). Enhancement pattern on MRI also significantly differed between the two subgroups (P = 0.006). The size of MRI-detected lesions was statistically smaller than the size of those detected by other modalities (P = 0.004).ConclusionsThe imaging and histological characteristics of BRCA1/2 mutation carriers were consistent with other countries’ studies. MRI-detected lesions were significantly smaller than lesions detected by non-MRI modality. All lesions in BRCA1 mutation carriers could be detected by MRI.

Abstract 17154: Machine Learning Outperforms ACC/AHA CVD Risk Calculator in MESA Offering new opportunities for Short-Term Risk Prediction and Early Detection of the Vulnerable Patient

Introduction: Machine learning (ML) is poised to revolutionize healthcare. Current national guidelines for prediction and prevention of atherosclerotic cardiovascular disease (ASCVD) use ACC/AHA Pooled Cohort Equation Risk Calculator which relies on traditional risk factors and linear statistical models. Unfortunately, this approach yields a low level of sensitivity and specificity. The low sensitivity results in missing high-risk individuals who need intensive therapy and the low specificity results in millions of people unnecessarily recommended drugs such as statin. We aimed to utilize Machine Learning (ML) to create a more accurate predictor of ASCVD events and whom to recommend statin. Methods: We developed and validated a ML Risk Calculator based on Support Vector Machines (SVMs) using the latest 13-year follow up dataset from MESA (Multi-Ethnic Study of Atherosclerosis) of 6,459 participants who were free of cardiovascular disease at baseline. We provided identical input to the ACC/AHA and ML risk calculators and compared their accuracy. We also validated the ML model in another longitudinal cohort: the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO). Results: According to the ACC/AHA Risk Calculator and a 7.5% 10-year risk threshold, 46.0% would be recommended statin. Despite this high proportion, 23.8% of the 480 “Hard CVD” events occurred in those not recommended statin, resulting in sensitivity (Sn) 0.76, specificity (Sp) 0.56, and AUC 0.71. In contrast, ML Risk Calculator recommended statin to 11.4%, and only 14.4% of “Hard CVD” events occurred in those not recommended statin, resulting in Sn 0.86, Sp 0.95, and AUC 0.92. Similar results were seen in prediction of “All CVD” events. Conclusions: The ML Risk Calculator outperformed the ACC/AHA Risk Calculator by recommending less drug therapy, yet missing fewer events. Additional studies are underway to validate the ML model in other cohorts and to explore its ability in predicting short-term (1-5 years) events with additional biomarkers including imaging. Machine learning is paving the way for early detection of asymptomatic high-risk individuals destined to a CVD event in the near future, the Vulnerable Patient.

Screening to Detect Precursor Lesions of Pancreatic Adenocarcinoma in High-risk Individuals: A Single-center Experience.

Objective of the workPancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Early diagnosis is the most important factor for improving prognosis. Evidence is beginning to accumulate that screening and surveillance may lead to the early detection of precursor lesions and/or pancreatic cancer in asymptomatic individuals. Proper screening methods and identification of such precursor lesions may enable effective pre-emptive interventions to prevent further fatalities. The primary objective of this project was to examine the feasibility of identifying precursor or early cancerous lesions in high-risk individuals by endoscopic ultrasound (EUS) screening to prevent the deaths from pancreatic cancer.Research aimPancreatic cancer screening guidelines, based on consensus opinions, have been applied in various tertiary centers around the world; however, evidence for effectiveness is lacking. At Rambam Health Care Campus, we have established a cohort of high-risk individuals, and we report our local 10-year experience results of screening for pancreatic cancer.MethodsBetween 2008 and 2018, a cohort of 123 asymptomatic high-risk individuals came for annual/biannual EUS screening for pancreatic cancer. Retrospective and prospectively collected data were obtained, analyzed, and compared on the basis of several variables. These variables include age at beginning of screening, gender, smoking, obesity, diabetes, and presence of tumor markers, as well as the patients’ personal and family history of cancers. Findings on each EUS are described.ResultsThree patients out of 123 underwent potentially life-saving surgery as a result of this screening program. All of these three had only one first-degree relative (FDR) with pancreatic cancer at the time of their first screenings, but two eventually had a second FDR with PC. Findings from 296 EUS exams regarding smoking, obesity, and other risk factors are presented. Minor, possibly trivial, EUS findings are found to be common. Detection of precursor pancreatic lesions is feasible with EUS screenings.ConclusionsAdherence was an important limiting factor in screening. Better stratification of patients according to specific risk factors, including thorough genetics and family history, may direct when and how to initiate screening. International collaborations, such as the International Cancer of Pancreas Screening (CAPS) Consortium, of which Rambam is a collaborating partner, are needed to collate evidence for impact of screening to prevent pancreatic cancer morbidity and mortality, and are essential to achieve proof of concept. Different countries with varying health-care systems and budgets can find variance of appropriateness of screening procedures.