Contribution of laboratory medicine and emerging technologies to cardiovascular risk reduction via exposome analysis: an opinion of the IFCC Division on Emerging Technologies.

This opinion article highlights the critical role of laboratory medicine and emerging technologies in cardiovascular risk reduction through exposome analysis. The exposome encompasses all external and internal exposures an individual faces throughout their life, influencing the onset and progression of cardiovascular diseases (CVD). Integrating exposome data with genetic information allows for a comprehensive understanding of the multifactorial causes of CVD, facilitating targeted preventive interventions. Laboratory medicine, enhanced by advanced technologies such as metabolomics and artificial intelligence (AI), plays a pivotal role in identifying and mitigating these exposures. Metabolomics provides detailed insights into metabolic changes triggered by environmental factors, while AI efficiently processes complex datasets to uncover patterns and associations. This integration fosters a proactive approach in public health and personalized medicine, enabling earlier detection and intervention. The article calls for global implementation of exposome technologies to improve population health, emphasizing the need for robust technological platforms and policy-driven initiatives to seamlessly integrate environmental data with clinical diagnostics. By harnessing these innovative technologies, laboratory medicine can significantly contribute to reducing the global burden of cardiovascular diseases through precise and personalized risk mitigation strategies.

Automated calculation and reporting of vancomycin area under the concentration-time curve: a simplified single-trough concentration-based equation approach.

Vancomycin, a crucial antibiotic for Gram-positive bacterial infections, requires therapeutic drug monitoring (TDM). Contemporary guidelines advocate for AUC-based monitoring; however, using Bayesian programs for AUC estimation poses challenges. We aimed to develop and evaluate a simplified AUC estimation equation using a steady-state trough concentration (Ctrough) value. Utilizing 1,034 TDM records from 580 general hospitalized patients at a university-affiliated hospital in Ulsan, we created an equation named SSTA that calculates the AUC by applying Ctrough, body weight, and single dose as input variables. External validation included 326 records from 163 patients at a university-affiliated hospital in Seoul (EWUSH) and literature data from 20 patients at a university-affiliated hospital in Bangkok (MUSI). It was compared with other AUC estimation models based on the Ctrough, including a linear regression model (LR), a sophisticated model based on the first-order equation (VancoPK), and a Bayesian model (BSCt). Evaluation metrics, such as median absolute percentage error (MdAPE) and the percentage of observations within ±20% error (P20), were calculated. External validation using the EWUSH data set showed that SSTA, LR, VancoPK, and BSCt had MdAPE values of 6.4, 10.1, 6.6, and 7.5% and P20 values of 87.1, 82.5, 87.7, and 83.4%, respectively. External validation using the MUSI data set showed that SSTA, LR, and VancoPK had MdAPEs of 5.2, 9.4, and 7.2%, and P20 of 95, 90, and 95%, respectively. Owing to its decent AUC prediction performance, simplicity, and convenience for automated calculation and reporting, SSTA could be used as an adjunctive tool for the AUC-based TDM.

Machine Learning-Based Sample Misidentification Error Detection in Clinical Laboratory Tests: A Retrospective Multicenter Study.

BACKGROUND: In clinical laboratories, the precision and sensitivity of autoverification technologies are crucial for ensuring reliable diagnostics. Conventional methods have limited sensitivity and applicability, making error detection challenging and reducing laboratory efficiency. This study introduces a machine learning (ML)-based autoverification technology to enhance tumor marker test error detection. METHODS: The effectiveness of various ML models was evaluated by analyzing a large data set of 397 751 for model training and internal validation and 215 339 for external validation. Sample misidentification was simulated by random shuffling error-free test results with a 1% error rate to achieve a real-world approximation. The ML models were developed with Bayesian optimization for tuning. Model validation was performed internally at the primary institution and externally at other institutions, comparing the ML models' performance with conventional delta check methods. RESULTS: Deep neural networks and extreme gradient boosting achieved an area under the receiver operating characteristic curve of 0.834 to 0.903, outperforming that of conventional methods (0.705 to 0.816). External validation by 3 independent laboratories showed that the balanced accuracy of the ML model ranged from 0.760 to 0.836, outperforming the balanced accuracy of 0.670 to 0.773 of the conventional models. CONCLUSIONS: This study addresses limitations regarding the sensitivity of current delta check methods for detection of sample misidentification errors and provides versatile models that mitigate the operational challenges faced by smaller laboratories. Our findings offer a pathway toward more efficient and reliable clinical laboratory testing.

Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study.

BACKGROUND: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%-20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL. METHODS: In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114). RESULTS: In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738-0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567-0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65-111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival. CONCLUSION: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL.

Outcomes of systemic treatment according to germline mutational status in patients with metastatic pheochromocytoma and paraganglioma.

INTRODUCTION: Metastatic disease affects approximately 15% to 17% of patients with pheochromocytomas and paragangliomas (PPGLs). Unfortunately, treatment options for metastatic PPGLs are limited and rely on small, nonrandomized clinical trials. The impact of germline mutation status on systemic treatment outcomes remains unclear. To address these gaps, we retrospectively evaluated treatment outcomes in patients with PPGL. PATIENTS AND METHODS: Between December 2004 and December 2021, 33 patients were diagnosed with metastatic PPGLs and received systemic treatment at the Department of Oncology, Asan Medical Center, Seoul, South Korea. RESULTS: The median age of the patients was 49. Germline mutations were revealed in nine patients (39.1%) out of 23 who underwent germline testing, with SDHB mutation being the most frequent in 5 patients. Cyclophosphamide, vincristine, and dacarbazine (CVD) chemotherapy was administered to 18 patients, with an objective response rate (ORR) of 22% and a disease control rate (DCR) of 67%. The median progression-free survival (PFS) was 7.9 and the median overall survival (OS) was 36.2 months. Sunitinib was given to 6 patients, which had an ORR of 33%, a DCR of 83%, and a median PFS of 14.6 months. Notably, patients with SDHB/SDHD mutation (4 patients and one patient, respectively) who received CVD treatment had a significantly better OS than those without (median OS 94.0 months vs. 13.7 months, P = .01). CONCLUSION: Our study reveals that CVD and sunitinib are effective treatments for metastatic PPGLs. The results are consistent with previous studies and patients with SDHB and SDHD mutations may benefit most from CVD treatment.

Clinical Practice Guideline for Blood-based Circulating Tumor DNA Assays.

Circulating tumor DNA (ctDNA) has emerged as a promising tool for various clinical applications, including early diagnosis, therapeutic target identification, treatment response monitoring, prognosis evaluation, and minimal residual disease detection. Consequently, ctDNA assays have been incorporated into clinical practice. In this review, we offer an in-depth exploration of the clinical implementation of ctDNA assays. Notably, we examined existing evidence related to pre-analytical procedures, analytical components in current technologies, and result interpretation and reporting processes. The primary objective of this guidelines is to provide recommendations for the clinical utilization of ctDNA assays.

Impact of Academia-Government Collaboration on Laboratory Medicine Standardization in South Korea: analysis of eight years creatinine proficiency testing experience.

OBJECTIVES: To evaluate the performance of the Academia-Government Collaboration for Laboratory Medicine Standardization in Korea (KR-STDZN) based on data from KR-STDZN proficiency testing (KR-STDZN-PT) for creatinine over eight years (2015-2022). METHODS: We used KR-STDZN-PT data of creatinine tests from 2015 to 2022. Acceptance of the participating institutions' test results was assessed by calculating the acceptance performance as absolute bias (absBias%), total coefficient of variance (tCV%), and total error (TE%) for each sample using six measurements from each institution and true values of each reference material. The test result was considered acceptable when absBias%, tCV%, and TE% were <5.10, <3.20, and <11.40 %, respectively. The proportion of acceptable institutions among all participating institutions in each round was defined as the acceptance rate. Improvements in absBias%, tCV%, and TE% were analyzed using creatinine concentration ranges in samples. RESULTS: The number of participating institutions increased from 2015 to 2017 but remained consistent since 2018. The acceptance rates for absBias% and TE% increased from 52.2 and 77.6 %, in 2015 and to 90.7 and 96.3 %, in 2022, respectively. The acceptance rate for tCV% remained in the 90 % range for eight years. When creatinine <3 mg/dL, mean absBias%, and mean TE% improved significantly in 2021-2022 compared to 2015-2016 (p<0.05). When creatinine >3 mg/dL, acceptance performance did not improve. Mean tCV% remained consistent annually regardless of creatinine concentration. No significant variations in test methods were observed. CONCLUSIONS: The collaboration between academia and the government improved creatinine testing quality. Nevertheless, KR-STDZN must be expanded and refined.

Usefulness and performance evaluation of serum KL-6 and SP-A assays in healthy individuals and patients with interstitial lung disease.

BACKGROUND: Interstitial lung abnormalities (ILAs) are associated with the risk of progression to interstitial lung diseases (ILDs). Krebs von den Lungen 6 (KL-6) and surfactant protein (SP)-A have been used as biomarkers of ILDs. In this study, we evaluated the levels of these biomarkers and identified their clinical correlations in healthy individuals to assess their usefulness in the diagnosis of ILAs. METHODS: The patient samples were categorized into three groups: healthy, disease, and ILD groups. We used the automated immunoassay HISCL KL-6 and SP-A assay kits. The analytical performance evaluation involved precision, linearity, comparison, establishment of reference intervals, and determination of the cutoff points. We also analyzed the correlations between presence of abnormalities on chest radiography and computed tomography (CT) or pulmonary function test (PFT) and serum levels in the healthy group. RESULTS: KL-6 and SP-A assays showed good analytical performance. The KL-6 and SP-A cutoff values were 304 U/mL and 43.5 ng/mL between the ILD and healthy groups, respectively, which were lower than the values recommended by the manufacturer. In the clinical correlations with radiological findings, SP-A values in subjects with lung abnormalities on CT scans were significantly higher than those in normal scans. There was no significant difference in KL-6 and SP-A levels among PFT patterns; however, both serum levels in the mixed pattern showed higher values than those in the other patterns. CONCLUSIONS: The results revealed a positive association between increased serum levels of SP-A and KL-6 and clinical characteristics as incidental findings on chest imaging and reduced lung function.

Total PSA Test Performance Evaluation on Cobas Pure and Measurement System Comparison with Different Calibrators.

BACKGROUND: This study investigated the performance evaluation of total prostate specific antigen (tPSA) testing using Cobas Pure integrated solutions system (calibrated against WHO IS 96/670) and the comparison with established measurement systems with different traceability. METHODS: The evaluation was performed in terms of imprecision, linearity, detection limit, and correlation with Alinity i (calibrated against WHO IS 96/670) and Unicel DxI 800 (calibrated against the manufacturer's working calibrators). RESULTS: Within-laboratory reproducibility and repeatability were observed less than 1.2%. Linearity was achieved within the claimed analytical measurement range. The claimed LoB and LoD were experimentally verified. All the correlation coefficients among the assays indicated good correlation, but the significant mean bias with Unicel DxI 800 using a different calibrator were observed. CONCLUSIONS: Since the tPSA calibrators against different traceability is still commercially available, our research could convey the impact of calibration on tPSA results as well as the performance information of a new assay for tPSA.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Intuitive Modification of the Friedewald Formula for Calculation of LDL-Cholesterol.

Background: High LDL-cholesterol (LDL-C) is an established risk factor for cardiovascular disease and is considered an important therapeutic target. It can be measured directly or calculated from the results of other lipid tests. The Friedewald formula is the most widely used formula for calculating LDL-C. We modified the Friedewald formula for a more accurate and practical estimation of LDL-C. Methods: Datasets, including measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-C concentrations were collected and assigned to derivation and validation sets. The datasets were further divided into five groups based on triglyceride concentrations. In the modified formula, LDL-C was defined as total cholesterol - HDL-cholesterol - (triglyceride/adjustment factor). For each group, the adjustment factor that minimized the difference between measured LDL-C and calculated LDL-C using modified formula was obtained. For validation, measured LDL-C and LDL-C calculated using the modified formula (LDL-CM), Friedewald formula (LDL-CF), Martin-Hopkins formula (LDL-CMa), and Sampson formula (LDL-CS) were compared. Results: In the derivation set, the adjustment factors were 4.7, 5.9, 6.3, and 6.4 for the groups with triglyceride concentrations <100, 101-200, 201-300, and >300 mg/dL, respectively. In the validation set, the coefficient of determination (R2) between measured and calculated LDL-C was higher for LDL-CM than for LDL-CF (R2=0.9330 vs. 0.9206). The agreement according to the National Cholesterol Education Program Adult Treatment Panel III classification of LDL-C was 86.36%, 86.08%, 86.82%, and 86.15% for LDL-CM, LDL-CF, LDL-CMa, and LDL-CS, respectively. Conclusions: We proposed a practical, improved LDL-C calculation formula by applying different factors depending on the triglyceride concentration.

Association between measured or calculated small dense low-density lipoprotein cholesterol and oxidized low-density lipoprotein in subjects with or without type 2 diabetes mellitus.

BACKGROUND: Small dense low-density lipoprotein (sdLDL) possesses atherogenic potential and is predicted to be susceptible to atherogenic modifications, which further increases its atherogenicity. However, studies on the association between measured or estimated sdLDL cholesterol (sdLDL-C) levels and atherogenic modification in diverse population groups are lacking. METHODS: Surplus serum samples were collected from male subjects with type 2 diabetes mellitus (DM) under treatment (n = 300) and without DM (non-DM; n = 150). sdLDL and oxidized LDL (oxLDL) levels were measured using the Lipoprint LDL subfractions kit (Quantimetrix Corporation) and the Mercodia oxidized LDL competitive enzyme-linked immunosorbent assay kit (Mercodia), respectively. The estimated sdLDL-Cs were calculated from two relevant equations. The effects of sdLDL-C on oxLDL were assessed using multiple linear regression (MLR) models. RESULTS: The mean (±SD) of measured sdLDL-C and oxLDL concentrations were 11.8 ± 10.0 mg/dl and 53.4 ± 14.2 U/L in the non-DM group and 0.20 ± 0.81 mg/dl and 46.0 ± 15.3 U/L in the DM group, respectively. The effects of measured sdLDL-Cs were significant (p = 0.031), whereas those of estimated sdLDL-Cs were not (p = 0.060, p = 0.116) in the non-DM group in the MLR models. The effects of sdLDL-Cs in the DM group were not significant. CONCLUSION: In the general population, high level of sdLDL-C appeared to be associated with high level of oxLDL. The equation for estimating sdLDL-C developed from a general population should be applied with caution to a special population, such as patients with DM on treatment.

Accuracy of the New Creatinine-based Equations for Estimating Glomerular Filtration Rate in Koreans.

Background: New creatinine-based estimated glomerular filtration rate (eGFR) equations, including the 2021 Chronic Kidney Disease Epidemiology Collaboration (2021 CKD-EPI) and European Kidney Function Consortium (EKFC) equations, have been introduced recently. We assessed the performance of the 2021 CKD-EPI and EKFC equations in the Korean population. Methods: We analyzed 1,654 Korean patients aged ≥18 years who underwent chromium-51-ethylenediamine tetraacetic acid GFR measurements (mGFR). Bias (eGFR-mGFR), root mean square error (RMSE), and proportion of eGFR within 30% of mGFR (P30) of the 2009 CKD-EPI, 2021 CKD-EPI, and EFKC equations were compared. The concordance rate between eGFR and mGFR categories was evaluated. Both eGFR and mGFR categories were classified into six groups: ≥90, 89-60, 59-45, 44-30, 29-15, and <15 mL/min/1.73 m2. Results: The median bias (mL/min/1.73 m2) was 1.8 for the 2009 CKD-EPI equation, 4.8 for the 2021 CKD-EPI equation, and -0.3 for the EKFC equation. The P30 and RMSE were 78.2% and 17.0 for the 2009 CKD-EPI equation, 75.6% and 17.4 for the 2021 CKD-EPI equation, and 80.0% and 16.7 for the EKFC equation, respectively. The overall GFR category concordance rate between eGFR and mGFR was 63.4% for the 2009 CKD-EPI equation, 60.5% for the 2021 CKD-EPI equation, and 61.0% for the EKFC equation. Conclusions: Among the three eGFR equations, the EKFC equation had the smallest bias and highest P30 in Koreans. The 2009 CKD-EPI equation had a lower bias than the 2021 CKD-EPI equation.

Observation of a new type of self-generated current in magnetized plasmas.

A tokamak, a torus-shaped nuclear fusion device, needs an electric current in the plasma to produce magnetic field in the poloidal direction for confining fusion plasmas. Plasma current is conventionally generated by electromagnetic induction. However, for a steady-state fusion reactor, minimizing the inductive current is essential to extend the tokamak operating duration. Several non-inductive current drive schemes have been developed for steady-state operations such as radio-frequency waves and neutral beams. However, commercial reactors require minimal use of these external sources to maximize the fusion gain, Q, the ratio of the fusion power to the external power. Apart from these external current drives, a self-generated current, so-called bootstrap current, was predicted theoretically and demonstrated experimentally. Here, we reveal another self-generated current that can exist in a tokamak and this has not yet been discussed by present theories. We report conclusive experimental evidence of this self-generated current observed in the KSTAR tokamak.

Strategies to shorten turnaround time in outpatient laboratory.

BACKGROUND: Turnaround time (TAT) is one of the most important indicators of laboratory quality. For the outpatient routine chemistry tests whose results are checked by clinicians on the same day, we set a quality goal that >90% of these samples should be reported within 60 min. As more than 20% of the samples failed to achieve this goal in 2020, we introduced an additional autoanalyzer and a real-time monitoring system to improve this rate. METHODS: As the TAT of the pre-analytical phase is the greatest contributor to TAT, we divided it into sampling, sample transport, and sample preparation times. An additional autoanalyzer was introduced, and its effect on TAT improvement was evaluated with the TAT data of June and July 2020. A real-time monitoring system was introduced to sort delayed samples, and its effect was assessed with the TAT data of June and July 2021. TAT data from December 2019 to January 2020 were set as baseline controls. RESULTS: The preparation time comprised the largest proportion of TAT. Although there was a slight decrease in overall TAT after the introduction of the above two strategies, the target TAT achievement rate increased significantly from 78.5% to 88.7% (p < 0.001). CONCLUSIONS: We checked the cause of TAT prolongation and introduced new strategies to improve it. The addition of an autoanalyzer per se was not so effective but was better when combined with the real-time monitoring system. Such strategies would increase the quality of the laboratory services.

Practical Considerations for Clinical Laboratories in Top-down Approach for Assessing the Measurement Uncertainty of Clinical Chemistry Analytes.

Background: The top-down (TD) approach using internal quality control (IQC) data is regarded a practical method for estimating measurement uncertainty (MU) in clinical laboratories. We estimated the MU of 14 clinical chemistry analytes using the TD approach and evaluated the effect of lot changes on the MU. Methods: MU values were estimated using subgrouping by reagent lot changes or using the data as a whole, and both methods were compared. Reagent lot change was simulated using randomly generated data, and the mean values and MU for two IQC datasets (different QC material lots) were compared using statistical methods. Results: All MU values calculated using subgrouping were lower than the total values; however, the average differences were minimal. The simulation showed that the greater the increase in the extent of the average shift, the larger the difference in MU. In IQC data comparison, the mean values and MU exhibited statistically significant differences for most analytes. The MU calculation methods gave rise to minimal differences, suggesting that IQC data in clinical laboratories show no significant shift. However, the simulation results demonstrated that notable differences in the MU can arise from significant variations in IQC results before and after a reagent lot change. Additionally, IQC material lots should be treated separately when IQC data are collected for MU estimation. Conclusions: Lot changes in IQC data are a key factor affecting MU estimation and should not be overlooked during MU estimation.

Age Group-specific Reference Intervals for the Elecsys Anti-Müllerian Hormone Assay in Healthy Korean Women: a Nationwide Population-based Study.

Background: Anti-Müllerian hormone (AMH) is one of the most reliable markers of ovarian reserve. Automated AMH assays are widely used in clinical laboratories, but reference intervals for the Elecsys AMH assay for Asian populations have not yet been determined. We aimed to determine reference intervals in healthy Korean women. Methods: The study included 1,450 women aged 19 to 54 years who participated in the Korea National Health and Nutrition Examination Survey between 2013 and 2016. The study participants were divided into seven 5-year age groups. AMH and progesterone concentrations were measured using Roche Elecsys assays, and bone morphogenetic protein-15 (BMP15) was genotyped for the detection of major variants. Age group-specific reference intervals for AMH were established as recommended by the CLSI EP28-A3c guidelines. Results: The mean age was 37.4 years. AMH concentrations decreased with increasing age, especially after 40 years, with the median AMH decreasing from 30.9 pmol/L in participants of 19-24 years to 0.071 pmol/L in participants of 50-54 years. The mid-95 percentile AMH reference intervals decreased from 7.93-81.21 pmol/L in participants of 19-24 years to 0.07-3.86 pmol/L in participants of 50-54 years. Disease-associated BMP15 variants were not detected. Conclusions: We determined Elecsys AMH assay reference intervals in healthy Korean women. The results may provide basic information for the interpretation of AMH concentrations and assessment of ovarian reserve in Korean women.

Prevalence and endoscopic treatment outcomes of upper gastrointestinal neoplasms in familial adenomatous polyposis.

BACKGROUND: Although upper gastrointestinal (GI) neoplasms are not rare in patients with familial adenomatous polyposis (FAP), few studies have focused on them and the long-term outcomes of their treatment by endoscopy. Therefore, we aimed to investigate the prevalence and endoscopic treatment outcomes of upper GI neoplasms in patients with FAP. METHODS: Among 215 patients diagnosed with FAP between January 1991 and December 2019, 208 who underwent esophagogastroduodenoscopy were eligible. The clinical features and endoscopic treatment outcomes of upper GI neoplasms were retrospectively investigated and analyzed. RESULTS: Among the enrolled patients, 113 (54.3%) had one or more upper GI neoplasms: gastric adenoma (n = 34), gastric cancer (n = 7), nonampullary duodenal adenoma (n = 86), and ampullary adenoma (n = 53). Among patients with gastric neoplasms (n = 37), 24 (64.9%) underwent treatment (endoscopic treatment: 22, surgery: 2). No tumor-related mortality occurred during median follow-up of 106 months (interquartile range [IQR] 63-174). Endoscopic treatment was performed in 47 (54.7%) of 86 patients with nonampullary duodenal adenoma and in 32 (60.4%) of 53 patients with ampullary adenoma. No patient underwent surgery for duodenal neoplasms, and no tumor-related mortality occurred during median follow-up of 88 months (IQR 42-145). The proportion of patients with increased Spigelman stage at 2 years after the initial diagnosis or treatment was significantly higher in untreated group than in the group treated for duodenal neoplasms (27.3% vs. 0.0%, p = 0.001). CONCLUSION: Endoscopic surveillance in FAP patients is important for the detection and treatment of upper GI neoplasms in early stage. In particular, endoscopic therapy for duodenal neoplasms can reduce the severity of duodenal polyposis.

Effect of Outlier Elimination on the 99th Percentile Upper Reference Limits of High-Sensitivity Cardiac Troponin I Assays Based on a Strictly Selected Healthy Reference Population.

BACKGROUND: We established high-sensitivity cardiac troponin I (hsTnI) 99th percentile upper reference limits (URLs) for the Centaur XPT High-Sensitivity Troponin I assay (Centaur hsTnI; Siemens, Erlangen, Germany) and Atellica IM High-Sensitivity Troponin I assay (Atellica hsTnI; Siemens) and assessed the effect of outlier elimination. METHODS: The reference population comprised 380 men and 387 women, satisfying the strict systematic reference population criteria. After reference population verification by the N-terminal pro-B-type natriuretic peptide (NT-proBNP) assay, 99th percentile URLs for Centaur hsTnI and Atellica hsTnI were calculated before and after outlier elimination. RESULTS: The 99th percentile URL for Centaur hsTnI was 60.4 (men, 74.7; women, 57.5) ng/L and that for Atellica hsTnI was 59.6 (men, 75.2; women, 55.1) ng/L. After the elimination of 61 (8.0%) outlier samples in Centaur hsTnI and 58 (7.6%) in Atellica hsTnI, the 99th percentile URLs were 13.5 ng/L (men, 15.3 ng/L; women, 11.9 ng/L) and 13.4 ng/L (men, 15.5 ng/L; women, 12.9 ng/L), respectively, significantly lower than those before outlier elimination. The CVs at the 99th percentile URLs were 5.2% and 3.5%, respectively. The measurable fractions among the reference population were 91.5% and 93.4%, respectively. Performance evaluation of Atellica B-type natriuretic peptide (BNP), Atellica NT-proBNP, Centaur hsTnI, and Atellica hsTnI showed outstanding results. CONCLUSIONS: The Korean hsTnI 99th percentile URLs calculated in this study were significantly lower after outlier elimination than before. Centaur hsTnI and Atellica hsTnI meet the "Guideline acceptable" and "Level 3 (second generation, high sensitivity)" requirements, satisfying international standards.