Clinical Strategies in Gene Screening Counseling for the Healthy General Population.

The burgeoning interest in precision medicine has propelled an increase in the use of genome tests for screening purposes within the healthy population. Gene screening tests aim to pre-emptively identify those individuals who may be genetically predisposed to certain diseases. However, as genetic screening becomes more commonplace, it is essential to acknowledge the unique challenges it poses. A prevalent issue in this regard is the occurrence of falsepositive results, which can lead to unnecessary additional tests or treatments, and psychological distress. Additionally, the interpretation of genomic variants is based on current research evidence, and can accordingly change as new research findings emerge, potentially altering the clinical significance of these variants. Conversely, a further prominent concern regards false assurances in genetic testing, as genetic tests can yield false-negative results, potentially posing a significant clinical risk. Moreover, the results obtained for the same disease can vary among different genetic testing services, due to differences in the types of variants assessed, the scope of tests, analytical methods, and the algorithms used for predicting diseases. Consequently, whereas genetic testing holds significant promise for the future of medicine, it poses unique challenges. If conducted without a full understanding of its implications, genetic testing may fail to achieve its purpose potentially hindering effective health management. Therefore, to ensure a comprehensive understanding of the implications of genetic testing within the general population, sufficient discussion and careful consideration should be given to counseling based on gene test results.

The association between platelet-related parameters and nonalcoholic fatty liver disease in a metabolically healthy nonobese population.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized by subclinical inflammation and is related to obesity and metabolic syndrome (MS), but it is also frequently observed in nonobese populations. We aimed to evaluate the relationship between the white blood cell count-to-mean platelet volume ratio (WBC/MPV), platelet-to-lymphocyte count ratio (PLR) and lymphocyte-monocyte ratio (LMR) in association with NAFLD, considering the presence of obesity and MS. Additionally, we aimed to investigate whether these parameters exhibited similar correlations in metabolic dysfunction-associated steatotic liver disease (MASLD) as observed in NAFLD. This cross-sectional study included subjects who underwent a comprehensive health evaluation, including blood tests and abdominal ultrasonography. Subgroup analyses were conducted based on obesity and MS. Out of a total 5929 subjects (3271 males, mean age 49.7 ± 10.6 years), 2253 (38.0%) had NAFLD. WBC/MPV was significantly higher, and PLR was significantly lower in subjects with NAFLD. In the analysis restricted to the nonobese (BMI < 25 kg/m2) population without MS, both WBC/MPV and PLR were independently associated with NAFLD: WBC/MPV (adjusted OR 3.366; 95% CI 2.238-5.066) and PLR (adjusted OR 0.997; 95% CI 0.996-0.999). When assessing the risk of NAFLD based on the WBC/MPV and PLR quartiles, the adjusted OR and 95% CI for the lowest quartile compared to the highest were 2.055 (95% CI 1.626-2.602) for WBC/MPV and 0.660 (95% CI 0.523-0.832) for PLR in the nonobese, metabolically healthy group. The levels of WBC/MPV and PLR were independently associated with NAFLD. Furthermore, in MASLD, an association with WBC/MPV, PLR and LMR was identified, similar to the results observed in NAFLD, even after adjusting for confounding variables. In conclusion, the present study demonstrated a significant association between NAFLD and platelet-related parameters, especially in nonobese, metabolically healthy subjects.

Density clustering-based automatic anatomical section recognition in colonoscopy video using deep learning.

Recognizing anatomical sections during colonoscopy is crucial for diagnosing colonic diseases and generating accurate reports. While recent studies have endeavored to identify anatomical regions of the colon using deep learning, the deformable anatomical characteristics of the colon pose challenges for establishing a reliable localization system. This study presents a system utilizing 100 colonoscopy videos, combining density clustering and deep learning. Cascaded CNN models are employed to estimate the appendix orifice (AO), flexures, and "outside of the body," sequentially. Subsequently, DBSCAN algorithm is applied to identify anatomical sections. Clustering-based analysis integrates clinical knowledge and context based on the anatomical section within the model. We address challenges posed by colonoscopy images through non-informative removal preprocessing. The image data is labeled by clinicians, and the system deduces section correspondence stochastically. The model categorizes the colon into three sections: right (cecum and ascending colon), middle (transverse colon), and left (descending colon, sigmoid colon, rectum). We estimated the appearance time of anatomical boundaries with an average error of 6.31 s for AO, 9.79 s for HF, 27.69 s for SF, and 3.26 s for outside of the body. The proposed method can facilitate future advancements towards AI-based automatic reporting, offering time-saving efficacy and standardization.

Impact of 3-second rule for high confidence assignment on the performance of endoscopists for the real-time optical diagnosis of colorectal polyps.

BACKGROUND: Confusion between high and low confidence decisions in optical diagnosis hinders the implementation of real-time optical diagnosis in clinical practice. We evaluated the effect of a 3-second rule (decision time limited to 3 seconds for a high confidence assignment) in expert and nonexpert endoscopists. METHODS: This single-center prospective study included eight board-certified gastroenterologists. A 2-month baseline phase used standard real-time optical diagnosis for colorectal polyps < 10 mm and was followed by a 6-month intervention phase using optical diagnosis with the 3-second rule. Performance, including high confidence accuracy, and Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds, was measured. RESULTS: Real-time optical diagnosis was performed on 1793 patients with 3694 polyps. There was significant improvement in high confidence accuracy between baseline and intervention phases in the nonexpert group (79.2 % vs. 86.3 %; P = 0.01) but not in the expert group (85.3 % vs. 87.5 %; P = 0.53). Using the 3-second rule improved the overall performance of PIVI and SODA in both groups. CONCLUSIONS: The 3-second rule was effective in improving real-time optical diagnosis performance, especially in nonexperts.

A genome-wide association study implicates the pleiotropic effect of NMUR2 on asthma and COPD.

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct diseases that are associated with chronic inflammation. They share common features in terms of their advanced stages and genetic factors. This study aimed to identify novel genes underlying both asthma and COPD using genome-wide association study (GWAS) to differentiate between the two diseases. We performed a GWAS of asthma and COPD in 7828 Koreans from three hospitals. In addition, we investigated genetic correlations. The UK Biobank dataset was used for the replication studies. We found that rs2961757, located near neuromedin U receptor 2 (NMUR2) on chromosome 5, was genome-wide significant ([Formula: see text] = 0.44, P-valueAsthma-COPD = 3.41 × 10-8), and significant results were replicated with the UK Biobank data ([Formula: see text] = 0.04, P-valueAsthma-COPD = 0.0431). A positive genetic correlation was observed between asthma and COPD (39.8% in the Korean dataset and 49.8% in the UK Biobank dataset). In this study, 40-45% of the genetic effects were common to asthma and COPD. Moreover, NMUR2 increases the risk of asthma development and suppresses COPD development. This indicates that NMUR2 allows for better differentiation of both diseases, which can facilitate tailored medical therapy.

Colonoscopic image synthesis with generative adversarial network for enhanced detection of sessile serrated lesions using convolutional neural network.

Computer-aided detection (CADe) systems have been actively researched for polyp detection in colonoscopy. To be an effective system, it is important to detect additional polyps that may be easily missed by endoscopists. Sessile serrated lesions (SSLs) are a precursor to colorectal cancer with a relatively higher miss rate, owing to their flat and subtle morphology. Colonoscopy CADe systems could help endoscopists; however, the current systems exhibit a very low performance for detecting SSLs. We propose a polyp detection system that reflects the morphological characteristics of SSLs to detect unrecognized or easily missed polyps. To develop a well-trained system with imbalanced polyp data, a generative adversarial network (GAN) was used to synthesize high-resolution whole endoscopic images, including SSL. Quantitative and qualitative evaluations on GAN-synthesized images ensure that synthetic images are realistic and include SSL endoscopic features. Moreover, traditional augmentation methods were used to compare the efficacy of the GAN augmentation method. The CADe system augmented with GAN synthesized images showed a 17.5% improvement in sensitivity on SSLs. Consequently, we verified the potential of the GAN to synthesize high-resolution images with endoscopic features and the proposed system was found to be effective in detecting easily missed polyps during a colonoscopy.

Impact of comprehensive optical diagnosis training using Workgroup serrAted polypS and Polyposis classification on detection of adenoma and sessile serrated lesion.

OBJECTIVES: Many interventions have been attempted to improve adenoma detection rate (ADR) and sessile serrated lesion detection rate (SDR), and one of these interventions is educational training to recognize polyp characteristics. This study aimed to investigate the change in polyp detection rates of endoscopists before and after comprehensive training through the Gangnam-Real Time Optical Diagnosis (Gangnam-READI) program. METHODS: Fifteen gastroenterologists participated in a 1-year comprehensive training program that consisted of ex vivo and in vivo training that encompasses knowledge and skills in endoscopic characterization of colonic polyps using the Workgroup serrAted polypS and Polyposis (WASP) classification. We evaluated the impact of the training program by comparing the overall and individual ADR and SDR 6 months before and after the training. RESULTS: Overall, 18,280 polyps (9337 adenomas and 855 sessile serrated lesion) were collected. The optical diagnosis training had no significant impact on the difference in ADR after training compared to before training (47.7% vs. 46.5%, P = 0.608). A tendency for a decrease in ADR variance was noted among the endoscopists after training (74.9 vs. 32.7, P = 0.121). The overall pre-training period SDR was 4.5% and showed a statistically significant increase to 5.6%, 8.0%, and 7.1% in the first and second half of the training period, and post-training period, respectively (P = 0.003). The optical diagnosis training did not decrease variance in SDR (8.9 vs. 8.8, P = 0.985). CONCLUSION: Comprehensive optical diagnosis training with WASP classification has a significant impact on increasing the overall SDR of expert endoscopists.

Genome-Wide Association Study of Korean Asthmatics: A Comparison With UK Asthmatics.

PURPOSE: Although genome-wide association studies (GWASs) represent the most powerful approach for identifying genes that influence asthma, to date, no studies have established genetic susceptibility to asthma in the Korean population. This study aimed to identify genetic variants associated with adult Korean asthmatics and compare them with the significant single nucleotide polymorphisms (SNPs) of UK asthmatics from the UK Biobank. METHODS: Patients were defined as having asthma if they were diagnosed by a doctor or taking medications for asthma. Controls were defined as individuals without asthma or chronic obstructive pulmonary disease. We performed quality control, genotype imputation, GWAS, and PrediXcan analyses. In the GWAS, a P value of < 5 × 10-8 was considered significant. We compared significant SNPs between Korean and UK patients with asthma. RESULTS: A total of 1,386 asthmatic patients and 5,205 controls were analyzed. The SNP rs1770, located near the human leukocyte antigen (HLA)-DQB1, was the most significant SNP (P = 4.5 × 10-10). In comparison with 24 SNPs in a GWAS of UK asthmatics, six SNPs were significant with the same odds ratio (OR) direction, including signals related to type 2 inflammation (e.g., IL1RL1, TSLP, and GATA3) and mucus plugging (e.g., MUC5AC). HLA-DQA1 showed an opposite OR direction. The HLA-DQB1 gene demonstrated significantly imputed mRNA expression in the lung tissue and whole blood. CONCLUSIONS: The SNP rs1770 of HLA-DQB1 was the most significant in Korean asthmatics. Similarities and discrepancies were found in the genetic variants between Korean and UK asthmatics. GWAS of Korean asthmatics should be replicated and compared with those of GWAS of other ethnicities.

Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study.

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD); however, more than 25% of COPD patients are non-smokers, and gene-by-smoking interactions are expected to affect COPD onset. We aimed to identify the common genetic variants interacting with pack-years of smoking on FEV1/FVC ratios in individuals with normal lung function. A genome-wide interaction study (GWIS) on FEV1/FVC was performed for individuals with FEV1/FVC ratio ≥ 70 in the Korea Associated Resource cohort data, and significant SNPs were validated using data from two other Korean cohorts. The GWIS revealed that rs10947231 and rs8192575 met genome-wide significant levels; For [Formula: see text] the likelihood ratio (LR) test was conducted, and its P values, PLR, for rs10947231 and rs8192575 were 2.23 × 10-12 and 1.18 × 10-8, respectively. Interaction between rs8192575 and smoking is significantly replicated with two additional data (PINT = 0.0454, 0.0131). Expression quantitative trait loci, topologically associated domains, and PrediXcan analyses revealed that rs8192575 is significantly associated with AGER expression. SNPs on the 6p21 region are associated with FEV1/FVC, and the effect of smoking on FEV1/FVC differs among the associated genotypes.

Improved Accuracy in Optical Diagnosis of Colorectal Polyps Using Convolutional Neural Networks with Visual Explanations.

BACKGROUND & AIMS: Narrow-band imaging (NBI) can be used to determine whether colorectal polyps are adenomatous or hyperplastic. We investigated whether an artificial intelligence (AI) system can increase the accuracy of characterizations of polyps by endoscopists of different skill levels. METHODS: We developed convolutional neural networks (CNNs) for evaluation of diminutive colorectal polyps, based on efficient neural architecture searches via parameter sharing with augmentation using NBIs of diminutive (≤5 mm) polyps, collected from October 2015 through October 2017 at the Seoul National University Hospital, Healthcare System Gangnam Center (training set). We trained the CNN using images from 1100 adenomatous polyps and 1050 hyperplastic polyps from 1379 patients. We then tested the system using 300 images of 180 adenomatous polyps and 120 hyperplastic polyps, obtained from January 2018 to May 2019. We compared the accuracy of 22 endoscopists of different skill levels (7 novices, 4 experts, and 11 NBI-trained experts) vs the CNN in evaluation of images (adenomatous vs hyperplastic) from 180 adenomatous and 120 hyperplastic polyps. The endoscopists then evaluated the polyp images with knowledge of the CNN-processed results. We conducted mixed-effect logistic and linear regression analyses to determine the effects of AI assistance on the accuracy of analysis of diminutive colorectal polyps by endoscopists (primary outcome). RESULTS: The CNN distinguished adenomatous vs hyperplastic diminutive polyps with 86.7% accuracy, based on histologic analysis as the reference standard. Endoscopists distinguished adenomatous vs hyperplastic diminutive polyps with 82.5% overall accuracy (novices, 73.8% accuracy; experts, 83.8% accuracy; and NBI-trained experts, 87.6% accuracy). With knowledge of the CNN-processed results, the overall accuracy of the endoscopists increased to 88.5% (P < .05). With knowledge of the CNN-processed results, the accuracy of novice endoscopists increased to 85.6% (P < .05). The CNN-processed results significantly reduced endoscopist time of diagnosis (from 3.92 to 3.37 seconds per polyp, P = .042). CONCLUSIONS: We developed a CNN that significantly increases the accuracy of evaluation of diminutive colorectal polyps (as adenomatous vs hyperplastic) and reduces the time of diagnosis by endoscopists. This AI assistance system significantly increased the accuracy of analysis by novice endoscopists, who achieved near-expert levels of accuracy without extra training. The CNN assistance system can reduce the skill-level dependence of endoscopists and costs.

Multidirectional Colonoscopy Quality Improvement Increases Adenoma Detection Rate: Results of the Seoul National University Hospital Healthcare System Gangnam Center Colonoscopy Quality Upgrade Project (Gangnam-CUP).

BACKGROUND: To prevent colorectal cancer, high-quality colonoscopy is advocated, undertaken by endoscopists with high adenoma detection rates (ADRs). Despite reports that various factors may impact ADRs, the significance of such factors is still unclear. AIMS: The analysis was aimed at quality-oriented interventions for boosting ADRs. METHODS: Study enrollees were adults subjected to screening colonoscopy between September 2013 and August 2016 at the Gangnam Center of Seoul National University Hospital Healthcare System. The investigation entailed six periods (P1-6) of 6 months each, during which serial multidirectional quality improvement efforts were instituted. In particular, we sought to further educate endoscopists, provide feedback on individual ADRs, and introduce a split-dose regimen, gauging results via the Boston Bowel Preparation Score. Changes in polyp detection rates (PDRs) and ADRs were then analyzed. RESULTS: A total of 13,430 colonoscopies were undertaken by 15 experienced endoscopists. Overall, the ADR increased from 45.6% (P1) to 48.2% (P6, p < 0.001). The PDR, ADR, and advanced adenoma detection rate (AdvADR) showed the greatest increases between P3 and P4 [PDR 67.8% → 71.2% (p < 0.001); ADR 44.1% → 47.7% (p = 0.001); AdvADR 2.3% → 3.3% (p = 0.028)] in keeping with the introduction of a split-dose regimen. The sessile serrated adenoma detection rate (SSADR) increased substantially from 2.1% (P1) to 7.9% (P6, p < 0.001), with the largest gain between P1 and P2, just after education (p = 0.023). CONCLUSIONS: Successful quality improvement in colonoscopy was achieved through comprehensive multidirectional efforts in education, feedback, and enhanced bowel preparation. Achieving high-level bowel preparation was paramount in ADR improvement. The SSADR was improved through education.

The exploration of feature extraction and machine learning for predicting bone density from simple spine X-ray images in a Korean population.

OBJECTIVE: Osteoporosis is hard to detect before it manifests symptoms and complications. In this study, we evaluated machine learning models for identifying individuals with abnormal bone mineral density (BMD) through an analysis of spine X-ray features extracted by deep learning to alert high-risk osteoporosis populations. MATERIALS AND METHODS: We retrospectively used data obtained from health check-ups including spine X-ray and dual-energy X-ray absorptiometry (DXA). Consecutively, we selected people with normal and abnormal bone mineral density. From the regions of interest of X-ray images, deep convolutional networks were used to generate image features. We designed prediction models for abnormal BMD using the image features trained by machine learning classification algorithms. The performances of each model were evaluated. RESULTS: From 334 participants, 170 images of abnormal (T scores < - 1.0 standard deviations (SD)) and 164 of normal BMD (T scores > = - 1.0 SD) were used for analysis. We found that a combination of feature extraction by VGGnet and classification by random forest based on the maximum balanced classification rate (BCR) yielded the best performance in terms of the area under the curve (AUC) (0.74), accuracy (0.71), sensitivity (0.81), specificity (0.60), BCR (0.70), and F1-score (0.73). CONCLUSION: In this study, we explored various machine learning algorithms for the prediction of BMD using simple spine X-ray image features extracted by three deep learning algorithms. We identified the combination for the best performance in predicting high-risk populations with abnormal BMD.

Association between CT-Measured Abdominal Skeletal Muscle Mass and Pulmonary Function.

A relationship between lung function and sarcopenia has been suggested. This study aimed to evaluate the association between lung function and abdominal skeletal muscle mass, as measured by computed tomography (CT). The clinical records of 1907 subjects (1406 males, mean age 53.1 ± 9.2 years), who underwent routine health check-ups, including spirometry and abdominal CT, were retrospectively reviewed. The CT-measured skeletal muscle index (SMICT, cm2/(kg/m2) was defined as the skeletal muscle area of the third lumbar vertebrae (L3) level that is normalized by the body mass index. The mean values of forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) gradually increased as the SMICT quartiles increased (all p for trend < 0.05). The proportions of subjects with less than 80% of the predicted FVC (%) and predicted FEV1 (%) significantly decreased as the SMICT quartiles increased (all p for trend < 0.05). The ß regression coefficients for FVC and FEV1 significantly increased as the SMICT quartiles increased after adjusting for other confounding variables (p for trend < 0.05). This study showed that abdominal muscle mass, which was precisely measured by CT, independently affected lung function proportionally after adjusting for confounding factors in relatively healthy adults.

Improved Real-Time Optical Diagnosis of Colorectal Polyps Following a Comprehensive Training Program.

BACKGROUND & AIMS: The optimal training method for endoscopic characterization of colorectal polyps using narrow-band imaging is uncertain, and sessile serrated lesions (SSLs) optical diagnosis data are lacking. We aimed to evaluate a comprehensive training program for real-time optical diagnosis of colorectal polyps, including SSLs. METHODS: We performed a single-institution prospective study of 15 endoscopists trained with the Workgroup Serrated Polyps and Polyposis classification system. After the first phase of in vivo optical diagnosis, their performances were evaluated. After re-education for insufficient competency, they began the second phase. The learning curves and performance on 2 preservation and incorporation of valuable endoscopic innovations benchmarks were assessed. RESULTS: A total of 7294 polyps, including 486 SSLs, were diagnosed in real-time. The overall accuracy improved from 73.5% in the first phase to 77.1% in the second. The accuracy with high confidence was 79.4% and 85.1% in the first and second phases, respectively. In the first and second phases, the negative predictive values for diminutive neoplastic polyps were 82.1% and 92.5%, respectively, and concordances of the surveillance intervals were 80.7% and 89.7%, respectively. Eight endoscopists achieved the preservation and incorporation of valuable endoscopic innovations benchmarks after the second phase compared with none after the first. In contrast, the high confidence rate decreased from 74.6% to 70.2% as training progressed. CONCLUSION: A comprehensive training program for real-time optical diagnosis significantly improved performance and reduced individual variability in less-experienced endoscopists. ClinicalTrials.gov no: NCT02516748.

The Association between Nonalcoholic Fatty Liver Disease and CT-Measured Skeletal Muscle Mass.

A relationship between nonalcoholic fatty liver disease (NAFLD) and sarcopenia has been suggested. The aim of this study was to evaluate the association between NAFLD and skeletal muscle mass measured by computed tomography (CT). The clinical records of individuals visiting our center for a routine health check-up who underwent abdominal ultrasonography and abdominal CT scanning were retrospectively reviewed. Sarcopenia was diagnosed according to body mass index (BMI)-adjusted skeletal muscle mass, which was measured by CT (CT-measured skeletal muscle index (SMICT)). Of the 1828 subjects (1121 males; mean age 54.9 ± 9.5 years), 487 (26.6%) were obese (BMI ≥ 25 kg/m²), and 454 (24.8%) had low muscle mass. Sarcopenic subjects had a significantly higher prevalence of NAFLD than nonsarcopenic subjects, regardless of obesity (35.9% vs. 26.8%, p = 0.004 in the nonobese group; 76.6% vs. 63.0%, p = 0.003 in the obese group). Sarcopenia was significantly associated with the risk of NAFLD (adjusted odds ratio (OR) (95% confidence interval (CI)), 1.51 (1.15⁻1.99)), and the risk of NAFLD increased with increasing severity of sarcopenia (adjusted OR (95% CI), 1.45 (1.09⁻1.92) vs. 2.51 (1.16⁻5.56), mild vs. severe sarcopenia, respectively). When the risk of NAFLD was analyzed according to the SMICT quartiles, the adjusted OR and 95% CI for the lowest muscle mass quartile compared to the highest were 1.78 (1.17⁻2.72) in males and 2.39 (1.13⁻5.37) in females. Low skeletal muscle mass, which was precisely measured by CT, is independently associated with NAFLD, suggesting that sarcopenia is a risk factor for NAFLD.

Genetic Polymorphisms Associated with the Neutrophil⁻Lymphocyte Ratio and Their Clinical Implications for Metabolic Risk Factors.

BACKGROUND: The neutrophil⁻lymphocyte ratio (NLR) is a valuable prognostic or predictive biomarker in various diseases, but the genetic factors that underlie the NLR have not been studied. We attempted to investigate polymorphisms related to NLR phenotype and analyze their ability to predict metabolic risks. METHODS: A genome-wide association study was performed with log-transformed NLR using an Affymetrix Axiom™ KORV1.1-96 Array. Regression models for metabolic risk status were designed using the identified significant single-nucleotide polymorphisms (SNPs). RESULTS: We identified four SNPs near the TMEM116, NAA25, and PTPN11 genes that were associated with the NLR. The top SNP associated with the log-transformed NLR was rs76181728 in TMEM116. A case⁻control study was performed to analyze the metabolic risks associated with each SNP after adjusting for age, sex, and body mass index (BMI). Three SNPs displayed significant odds ratios (ORs) for increased blood pressure and increased waist circumference. In the regression model for metabolic syndrome, rs76181728 showed a significant association (OR = 1.465, 95% confidence interval (CI) = 1.091⁻1.969, P = 0.011) after adjustment for the NLR phenotype. CONCLUSIONS: We identified four novel SNPs that are associated with the NLR in healthy Koreans. SNPs in relevant genes might therefore serve as biomarkers for metabolic risks.

Genome-wide assessment of gene-by-smoking interactions in COPD.

Cigarette smoke exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) and its interactions with genetic variants could affect lung function. However, few gene-smoking interactions have been reported. In this report, we evaluated the effects of gene-smoking interactions on lung function using Korea Associated Resource (KARE) data with the spirometric variables-forced expiratory volume in 1 s (FEV1). We found that variations in FEV1 were different among smoking status. Thus, we considered a linear mixed model for association analysis under heteroscedasticity according to smoking status. We found a previously identified locus near SOX9 on chromosome 17 to be the most significant based on a joint test of the main and interaction effects of smoking. Smoking interactions were replicated with Gene-Environment of Interaction and phenotype (GENIE), Multi-Ethnic Study of Atherosclerosis-Lung (MESA-Lung), and COPDGene studies. We found that individuals with minor alleles, rs17765644, rs17178251, rs11870732, and rs4793541, tended to have lower FEV1 values, and lung function decreased much faster with age for smokers. There have been very few reports to replicate a common variant gene-smoking interaction, and our results revealed that statistical models for gene-smoking interaction analyses should be carefully selected.

Osteoporosis and fracture after gastrectomy for stomach cancer: A nationwide claims study.

This study was planned to evaluate the incidence and risk factors of osteoporosis and fracture after gastrectomy for stomach cancer using a nationwide claims database in South Korea.Data from 41,512 patients (50-79 years) who underwent gastrectomy for stomach cancer from 2008 to 2010 with at least 5 years of follow-up were obtained from the Health Insurance Review and Assessment Service database. Patients diagnosed with osteoporosis and prescribed bisphosphonate or raloxifene or who experienced osteoporotic fractures after gastrectomy were operationally defined as osteoporosis. Osteoporotic fracture was defined as a fracture at common osteoporotic fracture sites (spine, pelvis, hip, forearm, or rib).In total, 37,076 patients were included in the final analysis. The incidences of postgastrectomy osteoporosis and osteoporotic fractures were 41.9 and 27.6 cases per 1000 person-years, respectively. Multivariate analysis showed that older age (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.79-1.96), female gender (HR 2.46; 2.35-2.58), total gastrectomy (HR 1.10; 1.04-1.16), and diabetes (HR 1.16; 1.11-1.22) were significantly associated with osteoporosis and that older age (HR 1.90; 95% CI 1.80-2.01), female gender (HR 1.50; 1.41-1.58), total gastrectomy (HR 1.17; 1.10-1.25), chemotherapy (HR 1.06; 1.00-1.12), and diabetes (HR 1.26; 1.19-1.33) were significantly associated with fractures. Osteoporotic fractures occurred a median 3.1 years after gastrectomy. Among the 5175 fracture patients, 780 (15.1%) experienced multisite fractures, mostly in the elderly and chemotherapy groups.The osteoporosis and osteoporotic fracture incidences are high in patients within a relatively short timeframe after gastrectomy for stomach cancer. Systematic management of osteoporosis is necessary after this surgery.

The longitudinal association between changes in lung function and changes in abdominal visceral obesity in Korean non-smokers.

Obesity, particularly abdominal obesity, might be related to decreased lung function. We aimed to investigate whether obesity indices are associated with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in asymptomatic non-smokers through a longitudinal cohort study. The clinical records of 1,145 subjects (428 males, mean age 52.3 years) who underwent a comprehensive health evaluation, including spirometry and abdominal fat computed tomography, at least twice between 2007 and 2014 were retrospectively reviewed and analysed. The mean follow-up period was 1,105 days (over 3.0 years). The baseline total adipose tissue (TAT) and visceral adipose tissue (VAT) were inversely associated with both FEV1 and FVC (P < 0.05). The longitudinal study found that increasing TAT and VAT were significantly related to decreasing FEV1 and FVC, whereas decreasing TAT and VAT were related to increasing FEV1 and FVC in both males and females (P < 0.05). The strength and consistency of these associations were clearer in males than in females. However, no significant relationship was found between changes in subcutaneous adipose tissue and changes in lung function. In Korean non-smokers, longitudinal changes in abdominal visceral fat were found to be inversely related to changes in lung function over a mean period of three years. These results suggest that decreasing abdominal visceral obesity could increase lung function despite ageing.

Identifying Helminth Infections via Routine Fecal Parasitological Examinations in Korea.

We conducted this study to explore the extent of occult helminth infection identified by fecal parasitological examinations or organ-specific examinations such as colonoscopy and abdominal ultrasonography (US) during health checkups. We analyzed 197,422 fecal samples from 99,451 subjects who received health checkups at a single center over 10 years. We found that 3,472 (1.8%) samples from 3,342 (3.4%) subjects tested positive for parasitic ova, including clonorchiasis, metagonimiasis, trichuriasis, ascariasis, trichostrongylosis, taeniasis, and enterobiasis. The detection rate for clonorchiasis was higher in those who were taking their first examination than in those who had been examined previously. The detection rate for clonorchiasis decreased gradually over the 10 years. Only 2.5% of the patients with clonorchiasis showed US or computed tomography (CT) images that were compatible with the disease. Clonorchiasis patients who had abdominal US or CT images that suggested clonorchiasis were older and had lower body mass indices and higher eosinophil counts than did those whose US or CT images did not suggest the disease. We observed worms in 9% of the patients with trichuriasis who had received a colonoscopy. Colonoscopy also uncovered adult worms in 0.03% of subjects who were not identified as having Trichuris trichiura ova in their fecal helminth examinations. In summary, our study shows that occult helminth infection is fairly frequently identified by a variety of methods during health checkups, which suggests that doctors need to make greater effort to identify and treat occult helminth infections in Korea.