Screening Cohort Research Articles

Abstract 7489: Peripheral blood liquid biopsy for the screening of lung cancer

Abstract Lung cancer is the second most common type of cancer in both men and women and the leading cause of cancer-related mortality. Unfortunately, most patients have advanced stages (stage III or IV) at the time of diagnosis and the only U.S. Preventive Services Task Force-recommended screening test, Low Dose CT scan (LDCT), has a high false-positive rate. Therefore, there is an urgent need for the early detection of lung cancer with better discrimination between individuals with lung cancer and those without. In this study, we demonstrate the capability of a non-enrichment-based liquid biopsy workflow, the High Definition Single Cell Assay (HDSCA) to be used as a complementary tool to the current screening methodology. The HDSCA workflow can detect circulating cells of epithelial, mesenchymal, endothelial, and hematological origin, as well as acellular events such as oncosomes. This allows the investigation of the broad spectrum of circulating rare events for the potential identification of biomarkers associated with lung cancer. We investigated 52 peripheral blood samples collected from the second annual screening round of Manchester’s 'Lung Health Check' pilot of a community-based lung cancer screening cohort. Of these, 7 were subsequently diagnosed with non-small cell lung cancer, 2 with small cell lung cancer, and 43 were deemed at high risk of developing lung cancer. We additionally investigated 60 peripheral blood samples from individuals with no known pathology to use as controls. Within the screening cohort, a number of single rare analytes were found to have statistically significant differences between the lung cancer, high-risk cohort, and normal blood donor samples, which can potentially be biomarkers used to differentiate the cohorts. We also built a multi-analyte patient-level classification model utilizing the rare cellular and acellular events that stratified lung cancer patients from the normal donor individuals and high-risk cohort with high accuracy. Our results demonstrate the potential of liquid biopsy as a complementary screening approach for lung cancer. Citation Format: Jiyoun Seo, Stephanie N. Shishido, Jeremy Mason, Carmen Ruiz Velasco, Andrew Chen, Dominic Rothwell, Phil Crosbie, James Hicks, Caroline Dive, Peter Kuhn. Peripheral blood liquid biopsy for the screening of lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7489.

Development of hypertension models for lung cancer screening cohorts using clinical and thoracic aorta imaging factors

This study aims to develop and validate nomogram models utilizing clinical and thoracic aorta imaging factors to assess the risk of hypertension for lung cancer screening cohorts. We included 804 patients and collected baseline clinical data, biochemical indicators, coexisting conditions, and thoracic aorta factors. Patients were randomly divided into a training set (70%) and a validation set (30%). In the training set, variance, t-test/Mann–Whitney U-test and standard least absolute shrinkage and selection operator were used to select thoracic aorta imaging features for constructing the AIScore. Multivariate logistic backward stepwise regression was utilized to analyze the influencing factors of hypertension. Five prediction models (named AIMeasure model, BasicClinical model, TotalClinical model, AIBasicClinical model, AITotalClinical model) were constructed for practical clinical use, tailored to different data scenarios. Additionally, the performance of the models was evaluated using receiver operating characteristic (ROC) curves, calibration curves and decision curve analyses (DCA). The areas under the ROC curve for the five models were 0.73, 0.77, 0.83, 0.78, 0.84 in the training set, and 0.77, 0.78, 0.81, 0.78, 0.82 in the validation set, respectively. Furthermore, the calibration curves and DCAs of both sets performed well on accuracy and clinical practicality. The nomogram models for hypertension risk prediction demonstrate good predictive capability and clinical utility. These models can serve as effective tools for assessing hypertension risk, enabling timely non-pharmacological interventions to preempt or delay the future onset of hypertension.

Neoplasia detection in FIT positive screening colonoscopies compared with an age-controlled symptomatic cohort: a retrospective review

Colonoscopy following a positive FIT test in an average risk population is effective in reducing CRC incidence and mortality. While lower gastrointestinal symptoms remain a common cause for referral for colonoscopy, symptoms are poor predictors of clinically significant disease. The study was performed to compare neoplasia detection FIT +ve individuals and age-matched symptomatic cohorts. A single centre retrospective observational study was performed including all index colonoscopies performed on patients aged 60-70 from January 2015 to September 2021. Diagnostic yield was reported as adenoma detection rate, SSL detection rate, detection of high risk finding or adenocarcinoma. 8,106 colonoscopies were performed on patients aged 60-70 years. 3,695 (45.6%) originated from screening (FIT +ve). With exclusion criteria applied, 2,640 (59.9%) for screening and 1,767 (40.1%) for symptomatic patients were included. Median age in screening was 65 years (IQR 62-67) and 64 years in the symptomatic group (IQR 62-68), with male predominance in both groups (n=1,536, 58.1%, n=944, 53.4%). There were significant differences in both the ADR (56% vs 26.3%, p<0.01) and the SSLDR (10.4% vs. 8.1%, p=0.05) in the screening cohort compared to the symptomatic group. High risk findings (21.3% vs. 7.5%, p<0.01) were significantly more prevalent in the screening group with a considerably higher colorectal cancer (4.7% vs. 0.9%, p=<0.001) detection rate. FIT based triage significantly outperforms symptom based investigation for individuals in the 60-70 age group. Patients should be preferentially referred to organised colorectal cancer screening. FIT can be performed on symptomatic patients, to identify low risk individuals.

Genetics Visit Uptake Among Individuals Receiving Clinically Actionable Genomic Screening Results

Screening unselected populations for clinically actionable genetic disease risk can improve ascertainment and facilitate risk management. Genetics visits may encourage at-risk individuals to perform recommended management, but little has been reported on genetics visit completion or factors associated with completion in genomic screening programs. To identify factors associated with postdisclosure genetics visits in a genomic screening cohort. This was a cohort study of biobank data in a health care system in central Pennsylvania. Participants' exome sequence data were reviewed for pathogenic or likely pathogenic (P/LP) results in all genes on the American College of Medical Genetics and Genomics Secondary Findings list. Clinically confirmed results were disclosed by phone and letter. Participants included adult MyCode biobank participants who received P/LP results between July 2015 and November 2019. Data were analyzed from May 2021 to March 2022. Clinically confirmed P/LP result disclosed by phone or letter. Completion of genetics visit in which the result was discussed and variables associated with completion were assessed by electronic health record (EHR) review. Among a total of 1160 participants (703 [60.6%] female; median [IQR] age, 57.0 [42.1-68.5] years), fewer than half of participants (551 of 1160 [47.5%]) completed a genetics visit. Younger age (odds ratio [OR] for age 18-40 years, 2.98; 95% CI, 1.40-6.53; OR for age 41-65 years, 2.36; 95% CI, 1.22-4.74; OR for age 66-80 years, 2.60; 95% CI, 1.41-4.98 vs age ≥81 years); female sex (OR, 1.49; 95% CI, 1.14-1.96); being married (OR, 1.74; 95% CI, 1.23-2.47) or divorced (OR, 1.80; 95% CI, 1.11-2.91); lower Charlson comorbidity index (OR for score of 0-2, 1.76; 95% CI, 1.16-2.68; OR for score of 3-4, 1.73; 95% CI, 1.18-2.54 vs score of ≥5); EHR patient portal use (OR, 1.42; 95% CI, 1.06-1.89); living closer to a genetics clinic (OR, 1.64; 95% CI, 1.14-2.36 for <8.9 miles vs >20.1 miles); successful results disclosure (OR for disclosure by genetic counselor, 16.32; 95% CI, 8.16-37.45; OR for disclosure by research assistant, 20.30; 95% CI, 10.25-46.31 vs unsuccessful phone disclosure); and having a hereditary cancer result (OR, 2.13; 95% CI, 1.28-3.58 vs other disease risk) were significantly associated with higher rates of genetics visit completion. Preference to follow up with primary care was the most common reported reason for declining a genetics visit (68 of 152 patients [44.7%]). This cohort study of a biobank-based population genomic screening program suggests that targeted patient engagement, improving multidisciplinary coordination, and reducing barriers to follow-up care may be necessary for enhancing genetics visit uptake.

Improved Oral Health Is Associated with a Lower Risk of Late Onset Ankylosing Spondylitis: A Nationwide Cohort Study.

Background: The aim of this study was to evaluate the association of oral health status and habits with the occurrence of ankylosing spondylitis (AS) in a nationwide population-based cohort in a longitudinal setting. Methods: A total of 2,415,963 individuals aged 40-79 years who underwent oral health examinations were included from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort of Korea between 2003 and 2004. The occurrence of AS was analyzed according to the oral health status and oral hygiene habits. Results: Among 2,271,221 of the participants, AS occurred in 6366 (0.3%) participants over 16.7 years. The likelihood of AS was higher in participants who had periodontitis (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.20-1.46, p < 0.0001) and more missing teeth (HR: 1.68, 95% CI: 1.42-1.99, p < 0.0001). However, better oral hygiene habits such as frequent tooth brushing (HR: 0.77, 95% CI: 0.71-0.83, p < 0.0001) and a history of dental scaling within the last year (HR 0.88, 95% CI 0.82-0.95, p = 0.001) were associated with a lower occurrence of AS. Conclusions: Periodontitis and an increased number of missing teeth could be related to the occurrence of late-onset AS. Improved oral hygiene care may attenuate the likelihood of late-onset AS.

Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection.

Latent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals. Participants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples. A total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance. The MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection.

Abstract IA007: The WID-qEC test for simple and accurate endometrial cancer detection

Abstract Endometrial cancer incidence has been rising over the past ten years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We developed the WID-qEC test, a PCR-based test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12, using 726 cervico-vaginal samples from women with and without endometrial cancer. So far, the WID-qEC test has been validated in an additional 1388 women in various settings, including a case/control study utilizing self-samples and a nested case/control set from a screening cohort including samples taken up to 3 years prior to endometrial cancer diagnosis. In a recent prospective observational study (the EPI-SURE study), the primary aim was to compare the performance of conventional index imaging tests (i.e., sonography) with the WID-qEC test for endometrial cancer detection. We invited all women aged ≥ 45 years with abnormal uterine bleeding attending a tertiary gynecological diagnostic referral center in the UK between June and November 2022 to participate. A cervicovaginal sample for the WID-qEC test was obtained prior to the current diagnostic pathway, and the test was performed blinded to the clinical outcome. Patients were followed until diagnostic resolution or until June 12, 2023. Four hundred of the eligible 474 women consented to study participation; one patient withdrew. Based on 603 index imaging tests (i.e., sonography), 186 (46.6%) women were recommended for a reference histology test (i.e., biopsy+/-hysteroscopy). Twelve cancers were diagnosed. 198 reference histology test procedures detected nine cancers and missed two; one further cancer was directly diagnosed at hysterectomy without a prior reference test. Endometrial thickness assessment from an ultrasound scan was possible in 379 (95.0%) of the 399 women and a pre-specified cut-off of ≥ 4.5mm had sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of 90.9% (95% CI: 62.3-98.4), 79.1% (95% CI: 74.5-82.9), 11.8% (95% CI: 6.5-20.3) and 99.6% (95% CI: 98.0-99.9), respectively. Using a cut-off of &amp;gt; 3mm, the specificity was 45.8% (95% CI: 40.7–51.0) without a change in sensitivity. The WID-qEC test was possible in 390 (97.7%) of the 399 patients with 90.9% sensitivity (95% CI: 62.3-98.4), 92.1% specificity (95% CI: 88.9-94.4), a PPV of 25.6% (95% CI:14.6-41.1) and a NPV of 99.7% (95% CI: 98.3-99.9) when the pre-specified threshold (WID-qEC sumPMR ≥ 0.03) was applied. When a higher threshold was applied (WID-qEC sumPMR ≥ 0.3) the specificity increased to 97.3% (95% CI: 95.1-98.5) without a change in sensitivity. The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and, specifically, reduce the false positive rate by up to 95% (from 52.6% based on the endometrial thickness of &amp;gt; 3mm to 2.6% based on a WID-qEC sumPMR ≥ 0.3). Citation Format: Martin Widschwendter, Iona Evans, Daniel Reisel, Allison Jones, Alba Bajrami, Simrit Nijjar, Sarah A Solangon, Rupali Arora, Elisa Redl, Lena Schreiberhuber, Isma Ishaq-Parveen, Julia Rothärmel, Chiara Herzog, Davor Jurkovic. The WID-qEC test for simple and accurate endometrial cancer detection [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA007.

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: A nationwide birth cohort study in South Korea.

There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. During the follow-up period (median 6.92 years [IQR, 4.72-9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04-1.09] and postnatal [HR, 1.05; 95% CI, 1.01-1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.

A detection model of testis-derived circular RNAs in serum for predicting testicular sperm retrieval rate in non-obstructive azoospermia patients.

Microdissection testicular sperm extraction is an effective method to retrieve sperm from non-obstructive azoospermia patients. However, its successful rate is less than 50%. To identify the predictive value of circular RNAs in serum for sperm retrieval rate in non-obstructive azoospermia patients. 180 non-obstructive azoospermia patients were recruited in this study, including 84 individuals with successful sperm retrieval and 96 individuals with failed sperm retrieval. Our study contained two phases. First, 20 patients, selected from the 180 patients, were included in screening cohort. In this cohort, the top 20 circular RNAs from our previous testicular circRNA profiles were verified between successful and failed sperm retrieval groups using real-time polymerase chain reaction. Six circular RNAs with the most significantly different expressions were selected for further verification. Second, the 180 patients were included as discovery cohort to verify the six circular RNAs. Circular RNAs were extracted from serum in each participant. Logistic regression analysis was further performed to identify the predictive value and the area under the curve analysis was used to evaluate diagnostic efficiency, sensitivity, and specificity. Six circular RNAs including hsa_circ_0058058, hsa_circ_0008045, hsa_circ_0084789, hsa_circ_0000550, hsa_circ_0007422, and hsa_circ_0004099 showed aberrant expressions between the successful and failed sperm retrieval group. In addition, both single-circular RNA panels and multi-circular RNA panels were finally verified to be significant in predicting sperm retrieval rate. Notably, multi-circular RNAs panels demonstrated better predictive abilities compared with single-circRNA panels, and the combined panel of six-circular RNAs (risk score=1.094×hsa_circ_0058058+0.697×hsa_circ_0008045+0.718×hsa_circ_0084789-0.591×hsa_circ_0000550-0.435×hsa_circ_0007422-1.017×hsa_circ_0004099-1.561) exhibited the best predictive ability in the present study with an AUC of 0.977, a sensitivity of 91.7% and a specificity of 86.5%. A higher risk score indicated a higher risk of failure in sperm retrieval. Our study was the first to report that testis-derived circular RNAs in serum have the ability to predict sperm retrieval rate in non-obstructive azoospermia patients, whether it is a single-circular RNA or a combination of multi-circular RNAs.

Association between Chronic Kidney Disease and Chronic Rhinosinusitis: A Longitudinal Follow-Up Study Using a National Health Screening Cohort.

Chronic kidney disease (CKD) is a leading cause of global mortality. While recent reports suggest potential connections between CKD and chronic rhinosinusitis (CRS), further research is needed to elucidate the direct association between CKD and CRS. This study investigated the association between CKD and CRS using data from the Korean National Health Insurance Service Health Screening Cohort. Participants were recruited according to medical claim codes, and individuals with CKD were matched in a 1:4 ratio with the control group. Covariates, such as demographics, health-related data, and medical history were used. The incidence rates and hazard ratio of CRS were analyzed. A further analysis was performed based on the presence of nasal polyps. Among the 514,866 participants, 16,644 patients with CKD and 66,576 matched controls were included in the analysis. The CKD group demonstrated a higher incidence of CRS than the controls: 18.30 versus 13.10 per 10,000 person-years. The CKD group demonstrated a higher risk of CRS than the control group (1.28 adjusted hazard ratio). In additional analyses, the CKD group did not exhibit a statistically significant correlation for the development of CRS with nasal polyps. This study suggests that CKD is associated with an increased risk for CRS.

Small RNA-seq and clinical evaluation of tRNA-derived fragments in multiple myeloma: Loss of mitochondrial i-tRFHisGTG results in patients' poor treatment outcome.

Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA-derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM-related tRFs in ameliorating MM prognosis and risk stratification. Small RNA-seq was performed to profile tRFs in bone marrow CD138+ plasma cells, revealing the significant deregulation of the mitochondrial internal tRFHisGTG (mt-i-tRFHisGTG) in MM versus sMM/MGUS. The screening cohort of the study consisted of 147 MM patients, and mt-i-tRFHisGTG levels were quantified by RT-qPCR. Disease progression was assessed as clinical end-point for survival analysis, while internal validation was performed by bootstrap and decision curve analyses. Screening cohort analysis highlighted the potent association of reduced mt-i-tRFHisGTG levels with patients' bone disease (p = 0.010), osteolysis (p = 0.023) and with significantly higher risk for short-term disease progression following first-line chemotherapy, independently of patients' clinical data (HR = 1.954; p = 0.036). Additionally, mt-i-tRFHisGTG-fitted multivariate models led to superior risk stratification of MM patients' treatment outcome and prognosis compared to disease-established markers. Notably, our study highlighted mt-i-tRFHisGTG loss as a powerful independent indicator of post-treatment progression of MM patients, leading to superior risk stratification of patients' treatment outcome.

Cancer risk according to fasting blood glucose trajectories: a population-based cohort study

IntroductionDiabetes mellitus is known to increase the risk of cancer. Fasting blood glucose (FBG) levels can be changed over time. However, the association between FBG trajectory and cancer risk has...

Social factors and age play a significant role in cervical cancer and advanced-stage disease among Danish women

BackgroundFor cervical cancer (CC), the implementation of preventive strategies has the potential to make cervical cancer occurrence and death largely avoidable. To better understand the factors possibly responsible for cervical cancer, we aimed to examine possible differences in age and social parameters as well as screening status between women with low- or high-stage cervical cancer and matched controls.MethodsThrough the Danish Cancer Registry (DCR), women diagnosed with cervical cancer in Denmark between 1987 and 2016 were included. These were age- and residence-matched in a 1:5 ratio with controls from the general female population. The study population was sub grouped into a low-stage subpopulation with women with early-stage cervical cancer and matched controls and a high-stage subpopulation with women with late-stage cervical cancer and matched controls. Age and social parameters were compared within the subpopulations as well as between low- and high-stage cases. For part of the study population, screening attendance was examined to compare differences in adherence.ResultsOverall, we found that the risk of cervical cancer is significantly increased in socially disadvantaged women and not least non-attenders in screening. Interestingly, the high-stage subpopulation was significantly older than the low-stage subpopulation (p < 0.001), and when examining the impact of age further, we found that for cervical cancer cases, the risk of having low-stage disease decreases significantly with increasing age, whereas the risk of having high-stage disease increases significantly with increasing age. In the screening cohort, significantly less cases than controls were attenders in screening with the most pronounced differences seen in the old subpopulation (women aged 50–64 years) and in the high-stage subpopulation (p-values all < 0.001). Interestingly, when examining the risk of CC for attenders and non-attenders, we demonstrated that many social parameters continue to influence the risk of cervical cancer, even in women attending screening.ConclusionsOlder women, socially disadvantaged women, and non-attenders in screening are particularly vulnerable in terms of developing cervical cancer, especially high-stage disease. Therefore, improvements in the participating rate in screening as well as a revision of the current screening guidelines are needed.

Effect of Statins for Primary Prevention of Cardiovascular Disease According to the Fatty Liver Index

IntroductionNonalcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD). We investigated the primary preventive effect of statins on CVD according to the level of fatty liver index (FLI), which is a marker of NAFLD.MethodsWe conducted a nested case–control study on the basis of a nationwide health screening cohort in Korea. The participants were divided into tertiles (T1, T2, and T3) according to their FLI score. Cases were defined as individuals who developed CVD (composite of myocardial infarction and stroke). Three controls were matched to each case and multivariable conditional logistic regression analysis was performed.ResultsWithin a cohort of 206,263 participants without prior CVD, 7044 individuals suffered the primary outcome. For the nested case–control study, we selected these 7044 cases along with their corresponding 20,641 matched controls. Individuals in the T3 tertiles of FLI had a higher risk of CVD than those in the T1 tertile [adjusted odds ratio (OR) 1.30; 95% confidence interval (CI) 1.20–1.40, P < 0.001]. In sub-analyses based on FLI tertiles, statin therapy was associated with a lower risk of CVD (adjusted OR 0.72; 95% CI 0.61–0.85, P < 0.001) in the T3 tertile but not in the T1 and T2 tertiles.ConclusionsStatin therapy was associated with a reduced risk of CVD in individuals with high FLI but not in those with low FLI. Further research is needed to determine the pathophysiologic mechanism between statin and NAFLD.

Risk-based lung cancer screening in heavy smokers: a benefit–harm and cost-effectiveness modeling study

BackgroundAnnual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit–harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals.MethodsWe conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained.ResultsCompared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened.ConclusionsRisk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit–harm trade-offs and improve the cost-effectiveness of lung cancer screenings.

Metabolic dysfunction-associated fatty liver disease increases the risk of type 2 diabetes mellitus in young Korean adults

AimsTo investigate the impact of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) on the risk of type 2 diabetes mellitus in young Korean adults. MethodsData were sourced from the Korean National Health Insurance Service-Health Screening Cohort, comprising adults aged 20–39 who underwent health examinations between 2009 and 2012. Participants were grouped based on the presence of MAFLD and nonalcoholic fatty liver disease (NAFLD), both individually and in combination. The categorizations included Neither-FLD, NAFLD-only, MAFLD-only, or Both-FLD. Incident diabetes was identified through claims data during the follow-up period. ResultsAmong 6,232,656 participants, 676,747 (10.8 %) had MAFLD. During a median follow-up of 9.5 years, 182,291 incident diabetes cases were identified. Multivariate analysis revealed a significantly higher diabetes risk in the MAFLD group compared to those in the Non-MAFLD group (HR = 6.148, 95 % CI, 6.084–6.212). Notably, diabetes incidence was highest in FLI ≥ 60 subgroup with BMI ≥ 23 and metabolic syndrome. ConclusionsMAFLD is associated with a 6.1-fold increased diabetes risk in young adults, underscoring the urgent need for early intervention to mitigate this risk.

Accuracy of digital chest x-ray analysis with artificial intelligence software as a triage and screening tool in hospitalized patients being evaluated for tuberculosis in Lima, Peru.

Tuberculosis (TB) transmission in healthcare facilities is common in high-incidence countries. Yet, the optimal approach for identifying inpatients who may have TB is unclear. We evaluated the diagnostic accuracy of qXR (Qure.ai, India) computer-aided detection (CAD) software versions 3.0 and 4.0 (v3 and v4) as a triage and screening tool within the FAST (Find cases Actively, Separate safely, and Treat effectively) transmission control strategy. We prospectively enrolled two cohorts of patients admitted to a tertiary hospital in Lima, Peru: one group had cough or TB risk factors (triage) and the other did not report cough or TB risk factors (screening). We evaluated the sensitivity and specificity of qXR for the diagnosis of pulmonary TB using culture and Xpert as primary and secondary reference standards, including stratified analyses based on risk factors. In the triage cohort (n = 387), qXR v4 sensitivity was 0.91 (59/65, 95% CI 0.81-0.97) and specificity was 0.32 (103/322, 95% CI 0.27-0.37) using culture as reference standard. There was no difference in the area under the receiver-operating-characteristic curve (AUC) between qXR v3 and qXR v4 with either a culture or Xpert reference standard. In the screening cohort (n = 191), only one patient had a positive Xpert result, but specificity in this cohort was high (>90%). A high prevalence of radiographic lung abnormalities, most notably opacities (81%), consolidation (62%), or nodules (58%), was detected by qXR on digital CXR images from the triage cohort. qXR had high sensitivity but low specificity as a triage in hospitalized patients with cough or TB risk factors. Screening patients without cough or risk factors in this setting had a low diagnostic yield. These findings further support the need for population and setting-specific thresholds for CAD programs.

Lipidomic profiles in serum and urine in children with steroid sensitive nephrotic syndrome

BackgroundSteroid-sensitive nephrotic syndrome (SSNS) accounts for approximately 80% of cases of nephrotic syndrome. The involvement of aberrant lipid metabolism in early SSNS is poorly understood, warranting further investigation. This study aimed to explore alterations in lipid metabolism associated with SSNS pathogenesis. MethodsA screening cohort containing serum (50 SSNS, 37 controls) and urine samples (27 SSNS, 26 controls) was analyzed by untargeted lipidomic profiling using UHPLC-QTOF-MS. Then, a validation cohort (20 SSNS, 56 controls) underwent further analysis to check the potential clinical application by ROC curve analysis. ResultsLipidomic profiling of serum and urine samples revealed significant lipid alterations in SSNS patients, with the alterations in the serum samples being more significant. An elevated concentration of PE and PG and downregulated concentration of FA were observed in SSNS serum. A total of 38 dysregulated lipids and 5 lipid metabolic pathways were identified in the serum samples in SSNS patients. Validation in the second cohort confirmed differential regulation of nine kinds of lipids, including 5 up-regulated substances [SM d33:2 (m/z = 686.5361), SHexCer d34:1 (m/z = 779.521), PI 20:4_22:4 (m/z = 934.5558), Cer_NS d18:1_23:0 (m/z = 635.6216), and GM3 d36:1 (m/z = 1180.7431)], as well as 4 down-regulated substances: [CE 18:1 (m/z = 650.601), PE 38:6 (m/z = 763.5205), PC 17:0_20:4 (m/z = 795.5868) and EtherPC 16:2e_20:4 (m/z = 763.5498)]. ConclusionsUntargeted lipidomic analysis successfully identified specific lipid class changes in patients with SSNS, providing a deeper understanding of lipid alterations and underlying mechanisms associated with SSNS.

Prevalence, Performance and Predictors of Electrocardiographic Left Ventricular Hypertrophy in Male Black Athletes: A Retrospective Study

Introduction QRS voltages for electrocardiographic left ventricular hypertrophy (ECG-LVH) are more prominent in Black athletes than non-Black athletes. The underlying physiological relationships of ECG-LVH in BA remain enigmatic despite their greater predisposition to arterial hypertension. Objectives To determine the frequency of eight eponymous ECG-LVH criteria in male collegiate athletes in Nigeria; To determine the diagnostic performance of the most prevalent criteria; To determine the predictors of ECG-LVH. Methods 34 (thirty-four) athletes and 49 (forty-nine) non-athletic controls with normal electrocardiograms and echocardiograms were retrospectively recruited from an existing pre-participation screening cohort. They were all normotensive, non-obese and normoglycemic, and matched for age and body mass index (BMI). Results The four most frequent criteria were Sokolow-Lyon index (67.6% vs. 36.7%; χ2 = 7.7; p = .006), Romhilt’s criterion (52.9% vs. 8.2%; χ2 = 20.6; p &lt; .001), Peguero-Lo Presti criterion (38.2% vs. 22.4%; χ2 = 2.43; p &lt; .144), and Mazzoleni’s criterion (35.3% vs. 4.1%; χ2 = 13.95; p &lt; .001). The sensitivity, specificity and accuracy of these criteria ranged between 23.8%–57.1%, 38.5%–53.9%, and 32.4%–50.0%, respectively. Athletic activity (OR = 4.49; 95% confidence interval, CI = 1.63–12.36; p = .004) and lower BMI (OR = 0.78; 95% CI = 0.63–0.97; p = .026) were independent predictors of ECG-LVH by the Sokolow-Lyon criterion. Conclusions Voltage ECG-LVH criteria all poorly predict the presence of echocardiographic LVH in young male Black athletes. However, the Sokolow-Lyon criterion seems to be associated with a benign cardio-metabolic profile in such athletes and appears hypothetically superior to other voltage criteria for identifying physiological cardiac remodeling in them. This hypothesis should be tested in future studies.

Hospital-based screening outperforms primary care screening as a means of achieving hepatitis C virus micro-elimination

AimTo assess the respective performances of a HCV screening program in a hospital setting and a HCV screening model applied concomitantly in a primary care centre. MethodsAdult patients consecutively admitted to hospital for ambulatory surgery were screened for anti-HCV antibodies (hospital screening cohort, HPSC), as were patients receiving blood tests for medical reasons in a primary care centre (primary care screening cohort, PCSC). Serum anti-HCV and HCV RNA levels were tested by ELISA and real-time PCR, respectively. ResultsSeroprevalence of HCV infection was 2.2 % in the HPSC and 1.4 % in the PCSC (p = 0.044). All viraemic patients (0.2 % in HPSC and 0.1 % in PCSC) were treated with direct-acting antivirals and 85.7 % experienced a sustained virological response. ConclusionsHospital-based HCV screening outperformed primary care-centered screening, significantly increasing HCV case findings.