Development of Cell Culture Platforms for Study of Trabecular Meshwork Cells and Glaucoma Development

BACKGROUND@#Various cell culture platforms that could display native environmental cue-mimicking stimuli were developed, and effects of environmental cues on cell behaviors were studied with the cell culture platforms. Likewise, various cell culture platforms mimicking native trabecular meshwork (TM) composed of juxtacanalicular, corneoscleral and uveal meshwork located in internal scleral sulcus were used to study effects of environmental cues and/or drug treatments on TM cells and glaucoma development. Glaucoma is a disease that could cause blindness, and cause of glaucoma is not clearly identified yet. It appears that aqueous humor (AH) outflow resistance increased by damages on pathway of AH outflow can elevate intraocular pressure (IOP). These overall possibly contribute to development of glaucoma. @*METHODS@#For the study of glaucoma, static and dynamic cell culture platforms were developed. Particularly, the dynamic platforms exploiting AH outflow-mimicking perfusion or increased IOP-mimicking increased pressure were used to study how perfusion or increased pressure could affect TM cells. Overall, potential mechanisms of glaucoma development, TM structures and compositions, TM cell culture platform types and researches on TM cells and glaucoma development with the platforms were described in this review. @*RESULTS@#AND CONCLUSION: This will be useful to improve researches on TM cells and develop enhanced therapies targeting glaucoma.

Genetic Diversity of the Pear Scab Fungus Venturia nashicola in Korea.

Scab disease caused by Venturia nashicola is of agroeconomic importance in cultivation of Asian pear. However, little is known about the degree of genetic diversity in the populations of this pathogen. In this study, we collected 55 isolates from pear scab lesions in 13 major cultivation areas in Korea and examined the diversity using sequences of internal transcribed spacer (ITS) region, ß-tubulin (TUB2), and translation elongation factor-1α (TEF-1α) genes as molecular markers. Despite a low level of overall sequence variation, we found three distinctive subgroups from phylogenetic analysis of combined ITS, TUB2, and TEF-1α sequences. Among the three subgroups, subgroup 1 (60% of isolates collected) was predominant compared to subgroup 2 (23.6%) or subgroup 3 (16.4%) and was distributed throughout Korea. To understand the genetic diversity among the subgroups, RAPD analysis was performed. The isolates yielded highly diverse amplicon patterns and none of the defined subgroups within the dendrogram were supported by bootstrap values greater than 30%. Moreover, there is no significant correlation between the geographical distribution and the subgroups defined by molecular phylogeny. Our data suggest a low level of genetic diversification among the populations of V. nashicola in Korea.

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Embryonic Stem Cells Lacking DNA Methyltransferases Differentiate into Neural Stem Cells that Are Defective in Self-Renewal

Background and Objectives@#DNA methyltransferases (Dnmts) play an important role in regulating DNA methylation during early developmental processes and cellular differentiation. In this study, we aimed to investigate the role of Dnmts in neural differentiation of embryonic stem cells (ESCs) and in maintenance of the resulting neural stem cells (NSCs). @*Methods@#and Results: We used three types of Dnmt knockout (KO) ESCs, including Dnmt1 KO, Dnmt3a/3b double KO (Dnmt3 DKO), and Dnmt1/3a/3b triple KO (Dnmt TKO), to investigate the role of Dnmts in neural differentiation of ESCs. All three types of Dnmt KO ESCs could form neural rosette and differentiate into NSCs in vitro. Interestingly, however, after passage three, Dnmt KO ESC-derived NSCs could not maintain their self-renewal and differentiated into neurons and glial cells. @*Conclusions@#Taken together, the data suggested that, although deficiency of Dnmts had no effect on the differentiation of ESCs into NSCs, the latter had defective maintenance, thereby indicating that Dnmts are crucial for self-renewal of NSCs.

Application of the postnatal urinary tract dilation classification system to predict the need for surgical intervention among neonates and young infants

Purpose@#The aim of this study was to validate the postnatal urinary tract dilation (UTD) classification system by correlating it with the need for surgical intervention. @*Methods@#Young infants who underwent ultrasound (US) examinations for prenatal hydronephrosis were retrospectively identified. The kidney units (KUs; right, left, or bilateral) were graded from UTD P0 (very low risk) to P3 (high risk) based on seven US criteria from the UTD system. Surgery-free survival curves were constructed using the Kaplan-Meier method. Univariable and multivariable Cox proportional-hazards regression analysis clustered by patients was performed. Interobserver agreement was analyzed using the weighted kappa coefficient. @*Results@#In total, 504 KUs from 336 patients (mean age, 18.3±15.9 days; range, 1 to 94 days; males, n=276) were included, with a median follow-up of 24.2 months. Fifty-eight KUs underwent surgical intervention. Significant differences were observed among the Kaplan-Meier curves stratified into UTD groups (P<0.001). The presence of anterior-posterior renal pelvic diameter ≥15 mm (hazard ratio [HR], 8.602; 95% confidence interval [CI], 1.558 to 43.065), peripheral calyceal dilation (HR, 8.190; 95% CI, 1.558 to 43.065), ureteral dilation (HR, 2.619; 95% CI, 1.274 to 5.380), parenchymal thickness abnormality (HR, 3.371; 95% CI, 1.574 to 7.223), bladder abnormality (HR, 12.209; 95% CI, 3.616 to 41.225) were significantly associated with the occurrence of surgery. The interobserver agreement was moderate to almost perfect agreement for US features (κ=0.564-0.898) and substantial for final UTD grades (κ=0.716). @*Conclusion@#The UTD classification system is reliable and appropriately stratifies the risk of surgical intervention.

Comparison of the International Normalized Ratio Between a Point-of-Care Test and a Conventional Laboratory Test: the Latter Performs Better in Assessing Warfarin-induced Changes in Coagulation Factors

Background@#Point-of-care testing (POCT) coagulometers are increasingly used for monitoring warfarin therapy. However, in high international normalized ratio (INR) ranges, significant discrepancy in the INR between POCT and conventional laboratory tests occurs. We compared the INR of POCT (CoaguChek XS Plus; Roche Diagnostics, Mannheim, Germany) with that of a conventional laboratory test (ACL TOP 750; Instrumentation Laboratory SpA, Milan, Italy) and explored possible reasons for discrepancy. @*Methods@#Paired POCT and conventional laboratory test INRs were analyzed in 400 samples from 126 patients undergoing warfarin therapy after cardiac surgery. Coagulation factor and thrombin generation tests were compared using the Mann–Whitney U test. Correlations between coagulation factors and INRs were determined using Pearson correlation coefficients. @*Results@#The mean difference in the INR between the tests increased at high INR ranges. Endogenous thrombin potential levels were decreased at INR <2.0 for CoaguChek XS Plus and 2.0< INR <3.0 for ACL TOP 750 compared with those at INR <2.0 for both tests, indicating a better performance of ACL TOP 750 in assessing thrombin changes. The correlation coefficients of coagulation factors were stronger for ACL TOP 750 INR than for CoaguChek XS Plus INR. Vitamin K-dependent coagulation factors were found to contribute to the INR discrepancy. @*Conclusions@#Decreases in vitamin K-dependent coagulation and anticoagulation factors can explain the significant discrepancy between the two tests in high INR ranges. Since conventional laboratory test INR values are more reliable than POCT INR values, a confirmatory conventional laboratory test is required for high INR ranges.

Comparison of Thyroid-Stimulating Hormone Results from Eight Different Reagents and Assay-Specific Korean Reference Interval for Subclinical Hypothyroidism Treatment

Background and Objectives@#Recent guidelines from the Korean Thyroid Association have proposed a threshold of 6.8 mIU/L for diagnosing subclinical hypothyroidism based on local research findings. However, due to the lack of standardization/harmonization, thyroid-stimulating hormone (TSH) testing yields varying results across different reagent manufacturers. Hence, the use of uniform reference intervals is challenging. We aimed to establish assay-specific Korean reference interval for TSH. @*Materials and Methods@#We performed duplicate measurements on 100 serum samples with varying TSH concentrations (0-23 mIU/L) using eight different TSH reagents including Alinity I TSH (Abbott), Access TSH (Beckman Coulter), Elecsys TSH (Roche), TSH3UL (Siemens),TSH IRMA (Beckman Coulter), TSH1 RIA (Brahms), TSH IRMA TUBE II (Riakey), Turbo TSH IRMA (Izotop).Correlation and simple linear regression analyses were conducted among 8 reagents with Roche as the reference. @*Results@#The correlation coefficient for each reagent was notably high at 0.99. Through regression analysis, TSH values equivalent to the 6.8 mIU/L (Roche) were determined for each reagent as follows: Abbott 5.2 mIU/L, Beckman 6.5 mIU/L, Siemens 6.9 mIU/L, Beckman-Radioimmunoassay 7.4 mIU/L, Brahms 5.7 mIU/L, Riakey 5.3 mIU/L, Izotop 6.0 mIU/L. Conclusion: Given the observed differences in TSH values associated with different reagents, it is imperative to consider these differences when interpreting results within various clinical contexts and adapting them to clinical practice.

Comparison of upper and lower body forced air blanket to prevent perioperative hypothermia in patients who underwent spinal surgery in prone position: a randomized controlled trial / 대한마취과학회지

Background@#We compared upper- and lower-body forced-air blankets in terms of their ability to prevent perioperative hypothermia, defined as a reduction in body temperature to < 36.0°C, during the perioperative period in patients undergoing spine surgery in the prone position. @*Methods@#In total, 120 patients scheduled for elective spine surgery under general anesthesia were divided into an upper-warming group (n = 60) and a lower-warming group (n = 60). After inducing anesthesia and preparing the patient for surgery, including prone positioning, the upper and lower bodies of the patients in the upper- and lower-warming groups, respectively, were warmed using a forced-air warmer with specified upper and lower blankets. Body temperature was measured using a tympanic membrane thermometer during the pre- and post-operative periods and using a nasopharyngeal temperature probe during the intraoperative period. Patients were evaluated in terms of shivering, thermal comfort, and satisfaction in the post-anesthesia care unit (PACU). @*Results@#The incidence of intraoperative and postoperative hypothermia was lower in the upper-warming group than in the lower-warming group ([55.2% vs. 75.9%, P = 0.019] and [21.4% vs. 49.1%, P = 0.002]). Perioperative body temperature was higher in the upper-warming group (P < 0.001). However, intraoperative blood loss, postoperative thermal comfort scale and shivering scores, patient satisfaction, and PACU duration were similar in the two groups. @*Conclusions@#The upper-body blanket was more effective than the lower-body blanket for preventing perioperative hypothermia in patients who underwent spine surgery in the prone position.

A Prospective Comparative Study of Mobile Acoustic Uroflowmetry and Conventional Uroflowmetry / 대한배뇨장애요실금학회지

Purpose@#The aim of this study was to assess the performance of a mobile acoustic Uroflowmetry (UFM) application compared with standard UFM in the pediatric population. @*Methods@#A mobile acoustic UFM application represents a noninvasive method to estimate the urine flow rate by recording voiding sounds with a smartphone. Male pediatric patients who were undergoing UFM testing were prospectively recruited, and the voiding sounds were recorded and analyzed. The intraclass correlation coefficient (ICC) was used to compare the maximum flow rate (Qmax), average flow rate (Qavg), voiding time (VT), and voiding volume (VV) as estimated by acoustic UFM with those calculated by standard UFM. Differences in Qmax, Qavg, VT, and VV between the 2 UFM tests were determined using 95% Bland-Altman limits of agreement. @*Results@#A total of 16 male patients were evaluated. Their median age was 9 years. With standard UFM, the median Qmax, Qavg, VT, and VV were 18.7 mL/sec, 11.1 mL/sec, 15.2 seconds, and 157.8 mL, respectively. Strong correlations were observed between the 2 methods for Qmax (ICC=0.755, P=0.005), VT (ICC=0.974, P<0.001), and VV (ICC=0.930, P<0.001), but not for Qavg (ICC=0.442, P=0.135). The Bland-Altman plot showed good agreement between the 2 UFM tests. Flow patterns recorded by acoustic UFM and conventional UFM showed good visual correlations. @*Conclusions@#Acoustic UFM was comparable to standard UFM for male pediatric patients. Further validation of its performance in different toilet settings is necessary for broader use.

Surveillance of Coronavirus Disease 2019 (COVID-19) Testing in Clinical Laboratories in Korea

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, an online laboratory surveillance system was established to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-PCR (rRT-PCR) testing capacities and results. SARS-CoV-2 rRT-PCR testing data were collected from 97 clinical laboratories, including 84 medical institutions and 13 independent clinical laboratories in Korea. We assessed the testing capacities to utilize SARS-CoV-2 rRT-PCR based on surveillance data obtained from February 7th to June 4th, 2020 and evaluated positive result characteristics according to the reagents used and sample types. A total of 1,890,319 SARS-CoV-2 rRT-PCR testing were performed, 2.3% of which were positive. Strong correlations were observed between the envelope (E ) gene and RNA-dependent RNA polymerase (RdRp )ucleocapsid (N ) genes threshold cycle (Ct) values for each reagent. No statistically significant differences in gene Ct values were observed between the paired upper and lower respiratory tract samples, except in the N gene for nasopharyngeal swab and sputum samples. Our study showed that clinical laboratories in Korea have rapidly expanded their testing capacities in response to the COVID-19 outbreak, with a peak daily capacity of 34,193 tests. Rapid expansion in testing capacity is a critical component of the national response to the ongoing pandemic.

Establishment of Pediatric Reference Intervals for Routine Laboratory Tests in Korean Population: A Retrospective Multicenter Analysis

Background@#Reference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis. @*Methods@#Preoperative laboratory test results from 1,031 pediatric patients aged 0 month–18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. @*Results@#The pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups. @*Conclusions@#We determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.

Immunosuppressive Drug Measurement by Liquid Chromatography Coupled to Tandem Mass Spectrometry: Interlaboratory Comparison in the Korean Clinical Laboratories

Background@#Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) is increasingly used for immunosuppressive drug tests. However, most LC-MS/MS tests are laboratory-developed and their agreement is unknown in different Korean laboratories.This interlaboratory comparison study evaluated test reproducibility and identified potential error sources. @*Methods@#Test samples containing three concentrations of tacrolimus, sirolimus, everolimus, cyclosporine, and mycophenolic acid were prepared by pooling surplus samples from patients undergoing routine therapeutic drug monitoring and tested in duplicate in the participating 10 clinical laboratories. Reconstitution and storage experiments were conducted for the commonly used commercial calibrator set. The robust estimators of reproducibility parameters were calculated. Spearman’s rank correlation coefficient (rho, ρ) was used to evaluate the correlation between drugs. Multiple linear regression was used to determine whether the experimental conditions alter the calibration curves. @*Results@#The reproducibility coefficient of variation exceeded 10% only for sirolimus concentrations 1 and 2 (10.8% and 12.5%, respectively) and everolimus concentrations 1 and 2 (12.3% and 11.4%, respectively). The percent difference values showed weak correlations between sirolimus and everolimus (ρ = 0.334, P = 0.175). The everolimus calibration curve slope was significantly altered after reconstitution following prolonged 5°C storage (P = 0.015 for 14 days; P = 0.025 for 28 days); the expected differences at 6 ng/mL were 0.598% for 14 days and 0.384% for 28 days. @*Conclusions@#LC-MS/MS test reproducibility for immunosuppressive drugs seems to be good in the Korean clinical laboratories. Continuous efforts are required to achieve test standardization and harmonization, especially for sirolimus and everolimus.

Estimating the time of onset of testicular torsion using ultrasonography in an experimental rat model

Purpose@#We aimed to document the time of onset of ultrasonographic and histologic changes in the testes of a rat model following testicular torsion. @*Methods@#Twenty-five Sprague-Dawley rats were divided into four groups. All animals underwent preoperative Doppler ultrasonography. Groups 1, 2, and 3 underwent unilateral surgical torsion of the testis lasting for 72, 24, and 6 hours, respectively. Group 4 underwent a sham operation. The animals were followed with Doppler ultrasonography at 6, 24, 48, and 72 hours postoperatively. Histologic examinations were performed at the designated final time point for each group. @*Results@#After torsion, enlargement of the epididymal head and thickening of the spermatic cord over time were noted. Based on the ultrasonographic dimensions, the ratio of the epididymal volume increased with time following torsion (p=0.002). The torsed testes had an average weight gain of 0.27 g at 6 hours compared to the control testes, but an average weight loss of 0.22 g at 72 hours (P=0.006). Changes in testicular echotexture were noted as soon as 6 hours after torsion, but there was no consistent pattern of echotexture change thereafter. Histologically, viable tubules were seen 6 hours after torsion, while extensive hemorrhagic necrosis was found at 72 hours. @*Conclusion@#In evaluating testicular torsion, the enlargement ratio of the epididymis and thickening of the spermatic cord on Doppler ultrasonography may be useful for determining the urgency of immediate surgery. Changes in testicular echotexture may not be a reliable indicator of the time of onset.

Copeptin with high-sensitivity troponin at presentation is not inferior to serial troponin measurements for ruling out acute myocardial infarction

Objective@#We aimed to compare the multi-marker strategy (copeptin and high-sensitivity cardiac troponin I [hs-cTnI]) with serial hs-cTnI measurements to rule out acute myocardial infarction (AMI) in patients with chest pain. @*Methods@#This prospective observational study was performed in a single emergency department. To test the non-inferiority margin of 4% in terms of negative predictive value (NPV) between the multi-marker strategy (0 hour) and serial hs-cTnI measurements (0 and 2 hours), 262 participants were required. Samples for copeptin and hs-cTnI assays were collected at presentation (0 hour) and after 2 hours. The measured biomarkers were considered abnormal when hs-cTnI was >26.2 ng/L and when copeptin was >10 pmol/L. @*Results@#AMI was diagnosed in 28 patients (10.7%). The NPV of the multi-marker strategy was 100% (160/160; 95% confidence interval [CI], 97.7% to 100%), which was not inferior to that of serial hs-cTnI measurements (201/201; 100%; 95% CI, 98.2% to 100%). The sensitivity, specificity, and positive predictive value of the multi-marker strategy were 100% (95% CI, 87.7% to 100%), 68.1% (95% CI, 61.7% to 74.0%), and 27.2% (95% CI, 18.9% to 36.8%), respectively. The sensitivity, specificity, and positive predictive value of serial hs-cTnI measurements were 100% (95% CI, 87.7% to 100%), 85.5% (95% CI, 80.4% to 89.8%), and 45.2% (95% CI, 32.5% to 58.3%), respectively. @*Conclusion@#The multi-marker strategy (copeptin and hs-cTnI measurement) was not inferior to serial hs-cTnI measurements in terms of NPV for AMI diagnosis, with a sensitivity and NPV of 100%. Copeptin may help in the early rule-out of AMI in patients with chest pain.

Recommendations for the Use of Liquid Chromatography-Mass Spectrometry in the Clinical Laboratory: Part I. Implementation and Management

Clinical impact of healthcare-associated acquisition in cirrhotic patients with community-onset spontaneous bacterial peritonitis

Background/Aims@#Healthcare-associated (HCA) infection is a recently suggested new category of community-onset infections. The implications of HCA infections in terms of diagnosis, treatment, and outcomes of spontaneous bacterial peritonitis (SBP) are not well understood. We sought to delineate the differences between community-acquired (CA) SBP and HCA SBP with specific interest in the antimicrobial resistance of causative microorganisms and outcomes. @*Methods@#We conducted a retrospective cohort study of all SBP episodes with positive ascitic culture and/or blood culture from June 2000 to August 2011. Community-onset SBP episodes were included when they occurred within 48 hours after admission and were classified as CA SBP and HCA SBP based on the predefined criteria. @*Results@#A total of 188 episodes of community-onset SBP were analyzed (65.4% HCA SBP and 34.6% CA SBP). HCA SBP had a higher resistance rate to third-generation cephalosporin (6.8% vs. 1.6%, p = 0.168). The overall 30-day mortality was similar between both groups (37.4% vs. 41.5%, p = 0.638). The independent risk factors for 30-day all-cause mortality in community-onset SBP included high Child-Pugh score, acute kidney injury, and resistance to third-generation cephalosporins; HCA infection was not associated. @*Conclusions@#Hepatic functional status, renal dysfunction, and third-generation cephalosporin resistant pathogens more adversely affected the outcome of cirrhotic patients with community-onset SBP rather than HCA infection. The higher rate of third-generation cephalosporin resistance was notable in HCA SBP, which will require a novel approach to empirical antibiotic treatment selection in this population.

Inhibition of Cross-Reactive Carbohydrate Determinant–Specific IgEs Reduce False Positive Reponses to Multiple Allergen Simultaneous Test–Immunoblot Assay: A Case Study

Cross-reactive carbohydrate determinants (CCDs) are simple carbohydrates linked to amino acid chains; they are found in pollens, vegetable foods, insect, and Hymenoptera venoms and are broadly cross-reactive with CCD-specific IgE antibodies. A man in his fifties was evaluated using a multiple allergen simultaneous test–immunoblot assay. On the PROTIA Allergy-Q 64 inhalant panel (ProteomeTech, Korea), reactions to 37 of 59 antigens were observed except mammalian antigens, and cross-reactivity owing to anti-CCD antibodies was suspected. After ProGlycAn CCD-blocker (ProGlycAn, Austria) treatment, the patient exhibited no response to CCD allergens, and the number of allergens showing positive reactions was reduced to 15. We further tested a total of 7 samples from patients who were suspected to have CCD-related cross-reactivity. For these 8 patients, the average number of positive reactions to allergens was reduced from 33 (range 24-36) to 8 (range 0-19) after CCD-blocker treatment. We concluded that CCD-blocker treatment in sample with anti-CCD antibodies can reduce the false positive reponse and provide more specific information about allergens.

Recommendations for Liquid Chromatography-Mass Spectrometry in the Clinical Laboratory: Part III. Quality Assurance

The use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in clinical laboratories is increasing and is likely to expand into even more clinical venues in the future. Mass spectrometry is the standard method for analyte identification in the clinical chemistry field; however, differences in mass spectrometry protocols and handling affect the accuracy and reliability of these tests and prevent direct comparisons of results between laboratories. For example, the results of laboratories using LC-MS/MS methods are less likely to be reproducible than those of laboratories using conventional, automated methods. This is due to inadequate handling of the equipment and/or poor quality control after the implementation of the method, which may result in unnecessary medical expenditures or even adverse outcomes for the patients. Unfortunately, guidelines to monitor the accuracy of LC-MS/MS-based clinical tests are still lacking. In general, the quality control methods used in conventional clinical tests could also be applied to LC-MS/MS. However, additional quality control methods specific to LC-MS/MS techniques must be continuously employed to maintain the same quality level achieved during method development and verification. This report is intended to help clinical laboratories that operate LC-MS/MS improve the accuracy and reliability of their testing by providing guidance for quality assurance and improvement, based on a collection of existing guidelines and expert opinions from the literature.

Recommendations for Liquid Chromatography-Mass Spectrometry in the Clinical Laboratory: Part II. Method Validation

The demand for obtaining test results using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for accurate diagnosis in the field of laboratory medicine is expected to increase, but it is still not easy to introduce diagnostic methods using LC-MS/MS into clinical laboratories for many reasons. There are many different methods used to evaluate the performance of LC-MS/MS in clinical laboratories, which have not been standardized to date. Thus, various data have been analyzed and described based on the type of validation method used and the criteria needed to introduce a new test using LC-MS/MS in a clinical laboratory. Relevant data from home and abroad were reviewed to include the minimum number of validation items required and methods of implementation. In general, the items required for a full validation of the quantitative test and various guidelines were used to summarize the following validation items: accuracy, precision, calibration, specificity, ion suppression or improvement, limit of detection, limit of quantification, stability, reference interval, carryover, and dilution integrity. Among these, the first five items mentioned beforehand are essential parameters for LC-MS/MS validation and are presented in numerous guidelines. The other parameters are required for further verification depending on the characteristics of the analysis and the analytes. This recommendation is intended to outline and present the validation methods that should be carried out when introducing new tests in clinical laboratories using LC-MS/MS with reference to the existing guidelines and literature containing expert opinions.

A Case of Breakthrough COVID-19 during Hydroxychloroquine Maintenance

There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 μg/L and 4,890 μg/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.