Comprehensive molecular characterization of TFE3-rearranged renal cell carcinoma.

TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.

Stem cell therapy for interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease with limited treatment options. Current multidisciplinary approach targeting bladder inflammation and urothelial dysfunction has limited durable effect that major surgery is ultimately required for both Hunner and non-Hunner type IC. Various investigational attempts are underway to avoid such operations and preserve the urinary bladder. Stem cell therapy is a fascinating option for treating chronic illnesses. Stem cells can self-renew, restore damaged tissue, and have paracrine effects. The therapeutic efficacy and safety of stem cell therapy have been demonstrated in numerous preclinical models, primarily chemically induced cystitis rat models. Only one clinical trial (phase 1 study) has investigated the safety of human embryonic stem cell-derived mesenchymal stem cells in three Hunner-type IC patients. Under general anesthesia, participants underwent cystoscopic submucosal stem cell injection (2.0 × 107 stem cells/5 mL). No safety issues were reported up to 12 months of follow-up and long-term follow-up (up to 3 years). Although there were variations in therapeutic response, all patients reported significant improvement in pain at 1 month postoperatively. One patient underwent fulguration of the Hunner lesion after the trial, but others reported an overall improvement in pain. The analysis on phase 1/2a trial which had several modifications in protocol is currently ongoing. Despite several limitations that need to be overcome, stem cell therapy could be a potential therapeutic option for treating IC/BPS. Clinical outcome on phase 1/2a trial is important and might provide more insight into the clinical application of stem cell therapy for IC/BPS.

Development of occupation-based exposure matrix of lead for Korean workers: challenges and opportunities.

OBJECTIVES: Industry- and occupation-based carcinogen exposure matrices play a pivotal role in preventing occupational cancer. While the Korean CARcinogen EXposure (K-CAREX) has been developed in recent years to assess exposure prevalence and intensity by industry, the feasibility of constructing an occupation-based exposure matrix remains unexplored. Hence, the objective of this study is to explore the potential of combining the nationwide work environment measurement database (WEMD) and the special health examination database (SHED) to develop a comprehensive occupation-based exposure matrix. METHODS: The WEMD provides information on airborne lead measurements, including industry codes, but it does not include data related to occupations. In contrast, the SHED contains information on both occupation and blood lead levels. By integrating these 2 databases, we attempted to assess airborne lead exposure levels by occupation. Additionally, we performed a rank correlation analysis to compare the airborne exposure levels with corresponding blood lead levels according to occupation. RESULTS: A total of 35 425 workers who both wore air samplers for lead and underwent special health examinations for lead were extracted between 2019 and 2021. An occupation-based exposure matrix was developed to evaluate the intensity of lead exposure across a range of occupations, encompassing 51 minor occupations and 70-unit occupations. Rank correlation analyses showed strong positive correlations between airborne lead and blood lead measurements according to occupation. CONCLUSIONS: Our study findings suggest that combining 2 nationwide surveillance databases can be an effective approach for creating an occupation-based exposure matrix. However, our results also highlight several limitations that need to be addressed in future studies to improve the accuracy and reliability of such matrices.

Evaluation on the Sex-Specific Association Between Cigarette Smoke Exposure and Inflammation Markers-C-Reactive Protein and White Blood Cell Count.

INTRODUCTION: Cigarette smoke increases peripheral white blood cell (WBC) count. However, the dose-dependent association between smoking and C-reactive protein (CRP), an important inflammatory marker, has been reported as inconsistent. AIMS AND METHODS: Here, we evaluated the associations between smoking and CRP using both smoking questionnaires and urine cotinine as exposure markers. The Korea National Health and Nutrition Examination Survey data were used for analyzing the associations. Multiple regression analyses were performed to examine the associations between cigarette smoke exposure, as assessed by questionnaires and urine cotinine, and health effects, as measured by CRP and WBC count, controlling for potential confounders. The confounders, including age, sex, body mass index, blood pressure, cholesterol, glucose, alanine aminotransferase, and uric acid, were selected a priori based on the literature. RESULTS: A total of 11 435 participants were included for analysis. For the exposure-response relationship, the results indicated a significant increase in CRP levels in male smokers compared to male nonsmokers (p = .002), whereas no significant increase was found in female smokers compared to female nonsmokers (p = .680). For the dose-response relationship, a significant positive association was observed between urine cotinine and CRP in male smokers (p = .018), whereas no significant association was found in female smokers (p = .508). WBC count consistently showed significant exposure-response and dose-response relationships in both sexes. CONCLUSIONS: WBC count was found to be a consistent effect marker of cigarette smoke exposure, while the association between CRP level and smoking was inconsistent and varied by sex. The sex-specific response to cigarette smoke exposure warrants further exploration in future studies. IMPLICATIONS: Cigarette smoke exposure is known to increase inflammation and has been thought to increase CRP, a significant inflammation marker. However, recent studies have reported conflicting results regarding the dose-dependent association between cigarette smoke exposure and CRP. This study found that the association between smoking and CRP is inconsistent and varies by sex, showing significant exposure response in men but not in women. Furthermore, the study suggests that WBC count is a more consistent marker for cigarette smoke exposure.

Evaluation of Temporal Trends of Lead Exposure in Korean Workers Using Workplace Monitoring Data.

BACKGROUND: Lead, which is widely used in various industrial settings, is a major health hazard for manufacturing workers. Therefore, control of lead exposure has been implemented in an effort to prevent lead-related health problems. In this study, our aim was to evaluate temporal trends in occupational lead exposure in Korean lead workers using data from monitoring of workplace exposure. METHODS: A nationwide work environment monitoring database, data from a work environment monitoring institution, and data extracted from a review paper were utilized. Different versions of standard industrial classification codes were aligned with the 10th Korean Standard Industrial Classification, which is generally consistent with the 4th revision of the International Standard Industrial Classification. The multiple data sources were combined and temporal trends over the period from 1994-2021 were estimated. In addition, separate estimation of temporal trends in the storage battery manufacturing industry over the period from 1987-2021 was also performed. RESULTS: A total of 444,296 personal airborne lead measurements were used for the estimation process. The temporal trends in occupational exposure to lead declined by -6% annually over the study period. In particular, levels of lead exposure in the storage battery manufacturing industry showed a steeper decline of -12% annually. CONCLUSIONS: Findings of our study showed that occupational exposure to lead declined over the period from 1994 to 2021 in Korea. However, adverse effects of exposure to lead on health should be regarded with caution. The results will be useful in conduct of epidemiological studies examining lead-related effects on health.

Enhanced osteogenesis of human urine-derived stem cells by direct delivery of 30Kc19α-Lin28A protein.

Urine-derived stem cells (USCs) are a promising source for regenerative medicine because of their advantages such as easy and non-invasive collection from the human body, stable expansion, and the potential to differentiate into multiple lineages, including osteoblasts. In this study, we propose a strategy to enhance the osteogenic potential of human USCs using Lin28A, a transcription factor that inhibits let-7 miRNA processing. To address concerns regarding the safety of foreign gene integration and potential risk of tumorigenicity, we intracellularly delivered Lin28A as a recombinant protein fused with a cell-penetrating and protein-stabilizing protein, 30Kc19α. 30Kc19α-Lin28A fusion protein exhibited improved thermal stability and was delivered into USCs without significant cytotoxicity. 30Kc19α-Lin28A treatment elevated calcium deposition and upregulated several osteoblast-specific gene expressions in USCs derived from multiple donors. Our results indicate that intracellularly delivered 30Kc19α-Lin28A enhances the osteoblastic differentiation of human USCs by affecting the transcriptional regulatory network involved in metabolic reprogramming and stem cell potency. Therefore, 30Kc19α-Lin28A may provide a technical advancement toward developing clinically feasible strategies for bone regeneration.

Therapeutic Applications of Plant-Derived Extracellular Vesicles as Antioxidants for Oxidative Stress-Related Diseases.

Extracellular vesicles (EVs) composed of a lipid bilayer are released from various cell types, including animals, plants, and microorganisms, and serve as important mediators of cell-to-cell communication. EVs can perform a variety of biological functions through the delivery of bioactive molecules, such as nucleic acids, lipids, and proteins, and can also be utilized as carriers for drug delivery. However, the low productivity and high cost of mammalian-derived EVs (MDEVs) are major barriers to their practical clinical application where large-scale production is essential. Recently, there has been growing interest in plant-derived EVs (PDEVs) that can produce large amounts of electricity at a low cost. In particular, PDEVs contain plant-derived bioactive molecules such as antioxidants, which are used as therapeutic agents to treat various diseases. In this review, we discuss the composition and characteristics of PDEVs and the appropriate methods for their isolation. We also discuss the potential use of PDEVs containing various plant-derived antioxidants as replacements for conventional antioxidants.

Highly selective and quantitative in situ monitoring of cell surface proteins by SERS immunoassay system.

Due to their pivotal roles in many biological functions, cell surface proteins (CSPs) are often used for cancer prognosis, as evidenced by a number of studies that have reported significant changes in the expression levels of specific surface proteins depending on the stage of tumorigenesis and selection/variety of reprogrammed cells during cell fate conversion. Current CSP detection strategies suffer from poor selectivity and lack the ability for in situ analysis but maintain the spatial information between cells. Here, we have fabricated nanoprobes for surface-enhanced Raman scattering (SERS) immunoassays by conjugating a specific antibody onto silica-coated gold nanoparticles incorporating an individual Raman reporter (Au-tag@SiO2-Ab NPs) for highly sensitive and selective in situ detection in different types of cells. When multiple HEK293 cell lines stably expressing different levels of the CSP, ACE2, were investigated by the SERS immunoassay, we demonstrated that the level of ACE2 expression in each cell line could be statistically distinguished from that in the other cell lines, indicating the quantitative feature of this biosensing system. When detecting living cells without cell lysis or fixation, as well as fixed cells, the levels of the epithelial CSPs, EpCAM (epithelial cell adhesion molecule) and E-cadherin, were successfully determined using our Au-tag@SiO2-Ab NPs and SERS immunoassay system in a highly selective and quantitative manner without significant cytotoxicity. Hence, our work provides technical insight into the development of a biosensing platform for a variety of biomedical applications, such as cancer metastasis prognosis and the in situ monitoring of stem cell reprogramming and differentiation.

Pretreatment C-reactive protein-to-albumin ratio predicts clinical outcomes in patients with peripheral T-cell lymphoma.

PURPOSE: Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. MATERIALS AND METHODS: This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. A CAR cutoff value of 0.794 was determined, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (> 0.794) and low (≤ 0.794) CAR groups. RESULTS: After induction therapy, complete response was achieved in 8 (32.0%) and 39 patients (76.5%) in the high and low CAR groups, respectively. During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS and 5-year OS rates. Even with adjustment for the International Prognostic Index (≥ 3), Prognostic Index for PTCL-unspecified (≥ 3), and T cell score (≥ 2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04-7.86, p < 0.001) and OS (HR: 2.97, 95% CI: 1.33-6.64, p = 0.008). CONCLUSION: CAR may play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.

Development of Korean CARcinogen EXposure: Assessment of the Exposure Intensity of Carcinogens by Industry.

Background: Occupational cancer is a global health issue. The Korean CARcinogen EXposure (K-CAREX), a database of CARcinogen EXposure, was developed for the Korean labor force to estimate the number of workers exposed to carcinogens by industry. The present study aimed to estimate the intensity of exposure to carcinogens by industry, in order to supply complementary information about CARcinogen EXposure intensity to the K-CAREX. Methods: We used nationwide workplace monitoring data from 2014 to 2016 and selected target carcinogens based on the K-CAREX list. We computed the 95th percentile levels of measurements for each industry by carcinogens. Based on the 95th percentile level relative to the occupational exposure limit, we classified the CARcinogen EXposure intensity into five exposure ratings (1-5) for each industry. Results: The exposure ratings were estimated for 21 carcinogenic agents in each of the 228 minor industry groups. For example, 3,058 samples were measured for benzene in the manufacturing industry of basic chemicals. This industry was assigned a benzene exposure rating of 3. Conclusions: We evaluated the CARcinogen EXposure ratings across industries in Korean workers. The results will provide information on the exposure intensity to carcinogens for integration into the K-CAREX. Furthermore, it will aid in prioritizing control efforts and identifying industries of concern.

Epidemiologic outlook of therapy-related myeloid neoplasms and selection of high-risk patients: A Korean nationwide study.

BACKGROUND: Although a considerable proportion of patients with cancer receive chemotherapy (CT) or radiotherapy (RT), only a very few patients eventually develop therapy-related myeloid neoplasms (t-MNs). METHODS: To identify subsets of cancer patients who have substantially elevated risk of developing t-MNs. Incidences and risks of t-MNs after contemporary CT or RT in patients newly diagnosed major cancers during 2009-2013 were analyzed. By merging two Korean nationwide health care big data sets, patients were selected and observed on follow-up to until t-MN development or December 2019. RESULTS: Among 250,155 patients, 555 (0.22%) were diagnosed with t-MNs with a standard incidence ratio (SIR) of 3.40 (95% CI, 3.13-3.70). Patients had bone/joint cancers (SIR, 94.25; 95% CI, 50.71-137.80) and a remarkably high SIR for t-MN development. Patients receiving both CT and RT had the highest SIR (4.64; 95% CI, 4.08-5.20), followed by those receiving CT only (SIR, 3.30; 95% CI, 2.89-3.70). Contrarily, RT alone did not increase t-MN risk (SIR, 1.16; 95% CI, 0.76-1.56). More exposure to leukemogenic agents resulted in the higher t-MNs development. CONCLUSIONS: The increased risk of developing acute myeloid leukemia or myelodysplastic syndrome after CT and/or RT was confirmed and subsets with substantially elevated risk for developing t-MNs were found. Such patients would be suitable for a prospective cohort for investigating t-MN pathogenesis by time series analyses.

Assessment of sunlight exposure across industries and occupations using blood vitamin D as a biomarker.

OBJECTIVE: Exposure to ultraviolet (UV) radiation from sunlight induces the production of essential vitamin D, whereas overexposure to sunlight leads to skin cancer. Sunlight exposure has been measured using questionnaires, dosimeters, and vitamin D levels. Several studies have measured vitamin D in the working population; however, these studies were limited to certain occupations such as farmers and construction workers. In the present study, we evaluated sunlight exposure using blood vitamin D as an exposure surrogate across industries and occupations. METHODS: The Korea National Health and Nutrition Examination Survey (KNHANES) is a nationwide study representing the Korean population. We analyzed data from KNHANES between 2008 and 2009. We examined the association between vitamin D levels and pertinent personal, seasonal, residential, and occupational factors. Furthermore, we developed a multiple regression model with factors other than occupational factors (industry and occupation) and obtained residual values. We computed the third quartile (Q3) of the residuals and then calculated the fractions exceeding the Q3 level for each combination of industry and occupation. RESULTS: Age, sex, body mass index, year, season, latitude, living area, living in an apartment, industry, and occupation were significantly associated with vitamin D levels. Based on the exceeding fraction, the armed forces showed the highest exceeding fraction level of 0.71. CONCLUSIONS: Our results present the high exposure groups to sunlight across industries and occupations. Our results may provide a source for prioritizing occupational groups with a high risk of adverse health effects from sunlight exposure.

Discordance in Bone Mineral Density between the Lumbar Spine and Femoral Neck Is Associated with Renal Dysfunction.

PURPOSE: Bone mineral density (BMD) determined by dual-energy X-ray absorptiometry is considered a gold standard for diagnosing osteoporosis. Some people show discordance in BMD values measured at the femur and that at the lumbar spine (LS). The aim of the present study was to investigate whether differences in BMD T-scores between the LS and femur neck (FN) are associated with renal dysfunction in the general population of Korea. MATERIALS AND METHODS: We analyzed national data for 17306 adults from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. BMD T-score differences between LS and FN (termed BMD offset) were calculated by subtracting FN T-scores from LS T-scores. Diminished renal function was defined as estimated glomerular filtration rates (eGFR) less than 60 mL/min/1.73 m². RESULTS: Among those aged ≥50 years, BMD offset was negatively associated with eGFR levels. Additionally, eGFR levels decreased linearly across increasing BMD offset quartiles. Men and women with an offset of >1.5 showed a 4.79-times and 2.51-times higher risk of renal dysfunction, respectively, compared to individuals with an offset of ≤0, after adjusting for age, body mass index, educational level, current smoking, and physical activity. In contrast, there was little evidence of an association between renal dysfunction and BMD offset in subjects aged <50 years. CONCLUSION: Discordance between LS and FN BMDs was significantly associated with renal dysfunction in subjects aged ≥50 years. When assessing bone health in older chronic kidney disease patients, physicians should consider the possibility of BMD discordance between LS and FN.

Long-term monitoring and risk assessment of N-nitrosamines in the finished water of drinking water treatment plants in South Korea.

Approximately 99.1% of South Koreans have access to drinkable tap water from river basins. Due to such a high access rate, the South Korean government has been running, since 2013, a long-term program for monitoring the quality of tap water for drinking. Under this program, the maximum allowed concentrations of N-nitroso-di-n-methylamine (NDMA) and N-nitrosomethylethylamine (NMEA) are defined and applied. In this study, the data from this monitoring program were used to investigate the changes in six N-nitrosamine substances in the finished water of 33 drinking water treatment plants (DWTPs) in South Korea from 2013 to 2020, based on time and location. The effect of the applied water treatment steps on the appearance of N-nitrosamines was analyzed. The excess cancer risk (ECR) due to the oral intake of these substances was assessed. The results before the maximum allowed concentrations of NDMA and NMEA were defined showed that the oral intake ECR of these substances exceeded the carcinogenesis risk of one per one million people per year. After the maximum allowed concentrations of the substances were applied, the concentrations of the substances in the finished water of the DWTPs significantly dropped. The drinking water treated through sand filtration, and then with granular activated carbon, showed the highest efficiency in preventing the appearance of NDMA. Considering the potency of N-nitrosamines in tap water for drinking, the levels of these substances in the finished water of DWTPs in South Korea should be continuously monitored.

Estimation of Lead Exposure Intensity by Industry Using Nationwide Exposure Databases in Korea.

BACKGROUND: In a previous study, we estimated exposure prevalence and the number of workers exposed to carcinogens by industry in Korea. The present study aimed to evaluate the optimal exposure intensity indicators of airborne lead exposure by comparing to blood lead measurements for the future development of the carcinogen exposure intensity database. METHODS: Data concerning airborne lead measurements and blood lead levels were collected from nationwide occupational exposure databases, compiled between 2015 and 2016. Summary statistics, including the arithmetic mean (AM), geometric mean (GM), and 95th percentile level (X95) were calculated by industry both for airborne lead and blood lead measurements. Since many measurements were below the limits of detection (LODs), the simple replacement with half of the LOD and maximum likelihood estimation (MLE) methods were used for statistical analysis. For examining the optimal exposure indicator of airborne lead exposure, blood lead levels were used as reference data for subsequent rank correlation analyses. RESULTS: A total of 19,637 airborne lead measurements and 32,848 blood lead measurements were used. In general, simple replacement showed a higher correlation than MLE. The results showed that AM and X95 using simple replacement could be used as optimal exposure intensity indicators, while X95 showed better correlations than AM in industries with 20 or more measurements. CONCLUSION: Our results showed that AM or X95 could be potential candidates for exposure intensity indicators in the Korean carcinogen exposure database. Especially, X95 is an optimal indicator where there are enough measurements to compute X95 values.

Characteristics of the Molecular Weight of Polyhexamethylene Guanidine (PHMG) Used as a Household Humidifier Disinfectant.

(1) Background: Household humidifier disinfectant (HD) brands containing polyhexamethylene guanidine (PHMG) have been found to cause the most HD-associated lung injuries (HDLIs) in the Republic of Korea. Nevertheless, no study has attempted to characterize the potential association of the health effects, including HDLI, with the physicochemical properties of PHMG dissolved in different HD brands. This study aimed to characterize the molecular weight (MW) distribution, the number-average molecular weight (Mn), the weight-average molecular weight (Mw), and the structural types of PHMG used in HD products. (2) Methods: Quantitative measurements were made using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The Mn, Mw, and MW distributions were compared among various HD products. (3) Results: The mean Mn and Mw were 542.4 g/mol (range: 403.0-692.2 g/mol) and 560.7 g/mol (range: 424.0-714.70 g/mol), respectively. The degree of PHMG oligomerization ranged from 3 to 7. The MW distribution of PHMG indicated oligomeric compounds regardless of the HD brands. (4) Conclusions: Based on the molecular weight distribution, the average molecular weight of PHMG, and the degree of polymerization, the PHMG collected from HDLI victims could be regarded as an oligomer. PHMG, as used in household humidifiers, should not be exempted from toxic chemical registration as a polymer. Further study is necessary to examine the association of PHMG oligomeric compounds and respiratory health effects, including HDLI.

AI-based improvement in lung cancer detection on chest radiographs: results of a multi-reader study in NLST dataset.

OBJECTIVE: Assess if deep learning-based artificial intelligence (AI) algorithm improves reader performance for lung cancer detection on chest X-rays (CXRs). METHODS: This reader study included 173 images from cancer-positive patients (n = 98) and 346 images from cancer-negative patients (n = 196) selected from National Lung Screening Trial (NLST). Eight readers, including three radiology residents, and five board-certified radiologists, participated in the observer performance test. AI algorithm provided image-level probability of pulmonary nodule or mass on CXRs and a heatmap of detected lesions. Reader performance was compared with AUC, sensitivity, specificity, false-positives per image (FPPI), and rates of chest CT recommendations. RESULTS: With AI, the average sensitivity of readers for the detection of visible lung cancer increased for residents, but was similar for radiologists compared to that without AI (0.61 [95% CI, 0.55-0.67] vs. 0.72 [95% CI, 0.66-0.77], p = 0.016 for residents, and 0.76 [95% CI, 0.72-0.81] vs. 0.76 [95% CI, 0.72-0.81, p = 1.00 for radiologists), while false-positive findings per image (FPPI) was similar for residents, but decreased for radiologists (0.15 [95% CI, 0.11-0.18] vs. 0.12 [95% CI, 0.09-0.16], p = 0.13 for residents, and 0.24 [95% CI, 0.20-0.29] vs. 0.17 [95% CI, 0.13-0.20], p < 0.001 for radiologists). With AI, the average rate of chest CT recommendation in patients positive for visible cancer increased for residents, but was similar for radiologists (54.7% [95% CI, 48.2-61.2%] vs. 70.2% [95% CI, 64.2-76.2%], p < 0.001 for residents and 72.5% [95% CI, 68.0-77.1%] vs. 73.9% [95% CI, 69.4-78.3%], p = 0.68 for radiologists), while that in cancer-negative patients was similar for residents, but decreased for radiologists (11.2% [95% CI, 9.6-13.1%] vs. 9.8% [95% CI, 8.0-11.6%], p = 0.32 for residents and 16.4% [95% CI, 14.7-18.2%] vs. 11.7% [95% CI, 10.2-13.3%], p < 0.001 for radiologists). CONCLUSIONS: AI algorithm can enhance the performance of readers for the detection of lung cancers on chest radiographs when used as second reader. KEY POINTS: • Reader study in the NLST dataset shows that AI algorithm had sensitivity benefit for residents and specificity benefit for radiologists for the detection of visible lung cancer. • With AI, radiology residents were able to recommend more chest CT examinations (54.7% vs 70.2%, p < 0.001) for patients with visible lung cancer. • With AI, radiologists recommended significantly less proportion of unnecessary chest CT examinations (16.4% vs. 11.7%, p < 0.001) in cancer-negative patients.

Prediction of clinical outcomes through assessment of sarcopenia and adipopenia using computed tomography in adult patients with acute myeloid leukemia.

Sarcopenia and adipopenia have prognostic significance in cancer. Analysis of a single abdominal computed tomography (CT) section at the third lumbar vertebra has been widely adopted for this purpose. The approach using a single section at the first lumbar vertebra level (L1) may extend clinical viability. We evaluated the prognostic value of sarcopenia and adipopenia assessed using a CT section at L1 in acute myeloid leukemia (AML). Data from 96 patients with available imaging were retrospectively reviewed. Patients with sarcopenia (37.5%) had significantly worse overall survival (OS) (median 17.8 months vs. not reached, p = 0.038) and treatment-related mortality (TRM) (22.2% vs. 3.0%, p = 0.0019) than those without. Subcutaneous adipopenia (51.0%) was significantly associated with inferior OS (median 17.9 months vs. not reached, p = 0.0011), progression-free survival (PFS) (median 6.2 months vs. not reached, p = 0.004), and TRM (16.3% vs. 4%, p = 0.024). Visceral adipopenia (30.2%) was associated with poor OS (12.7 vs. 31.7 months, p = 0.0055) and PFS (3.7 vs. 31.7 months, p = 0.003). Multivariable analyses found sarcopenia, subcutaneous adipopenia and visceral adipopenia were significant negative prognostic factors for OS. Sarcopenia and adipopenia assessed using a single CT section at the L1 level are useful in predicting the prognosis of AML.

Development of Korean CARcinogen EXposure: An Initiative of the Occupational Carcinogen Surveillance System in Korea.

OBJECTIVE: To prevent occupational cancers, carcinogen exposure surveillance systems have been developed in many countries. This study aimed to develop a carcinogen exposure database specific to South Korea. METHODS: Twenty known human carcinogens were selected for this study. The International Standard Classification of Industry was used for a classification scheme of industries. Three nationwide occupational exposure databases, the Work Environment Measurement Database, the Special Health Examination Database, and the Work Environment Condition Survey, were used to calculate reference exposure prevalence estimates by carcinogen and industry. Then, 37 professional industrial hygienists with at least 19 years of field experience provided their own exposure prevalence estimates, after reviewing the abovementioned reference estimates derived from three data sources. The median value of the experts' estimates was used as the final exposure prevalence. Finally, the number of exposed workers was computed by multiplying the final exposure prevalence by the number of workers extracted from the 2010 national census data by carcinogen and industry. RESULTS: The exposure prevalence and the number of exposed workers were calculated according to 20 carcinogen and 228 minor industrial groups, assuming year 2010 circumstances. The largest population was exposed to welding fumes (326 822 workers), followed by ultraviolet radiation (238 937 workers), ionizing radiation (168 712 workers), and mineral oil mist (146 798 workers). CONCLUSIONS: Our results provide critical data on carcinogen exposure for the prevention of occupational cancers.

High level of pre-treatment C-reactive protein to albumin ratio predicts inferior prognosis in diffuse large B-cell lymphoma.

The C-reactive protein-to-albumin ratio (CAR) has not been assessed in diffuse large B cell lymphoma (DLBCL, the most common non-Hodgkin lymphoma). This retrospective study evaluated the prognostic value of CAR in 186 DLBCL patients. A CAR value of 0.158 was selected as the most discriminative cut-off for identifying patients with high CAR values (73/141 patients, 51.8%). During a median follow-up of 32.5 months, the high CAR group had significantly poorer complete response to induction therapy (64.4% vs. 92.6%; p < 0.001), 3-year overall survival (OS) (68.3% vs. 96.2%; p < 0.0001), and 3-year progression-free survival (PFS) (53.5% vs. 88.0%; p < 0.0001). After adjusting for the International Prognostic Index components, a high CAR value independently predicted poor OS (HR: 6.02, 95% CI 1.19-30.38; p = 0.030) and PFS (HR: 3.62, 95% CI 1.40-9.36; p = 0.008). In an independent validation cohort (n = 50), patients with CAR > 0.158 also showed worse 3-year OS (47.9% vs. 87.2%, p = 0.0035) and 3-year PFS (36.1% vs. 82.1%, p = 0.0011). A high CAR remained significantly associated with poor outcomes for > 60-year-old patients (OS: p = 0.0038, PFS: p = 0.0015) and younger patients (OS: p = 0.0041, PFS: p = 0.0044). Among older patients, a high CAR value also predicted non-relapse mortality (p = 0.035). Therefore, the CAR might complement the International Prognostic Index in DLBCL cases.