Clinical Practice Guidelines for Pre-Analytical Procedures of Plasma Epidermal Growth Factor Receptor Variant Testing.

Standardization of cell-free DNA (cfDNA) testing processes is necessary to obtain clinically reliable results. The pre-analytical phase of cfDNA testing greatly influences the results because of the low proportion and stability of circulating tumor DNA (ctDNA). In this review, we provide evidence-based clinical practice guidelines for pre-analytical phase procedures of plasma epidermal growth factor receptor gene () variant testing.

Alteration of transthyretin and thyroxine-binding globulin in major depressive disorder: multiple reaction monitoring-based proteomic analysis.

Background: Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.

Methods: A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation.

A nationwide utilization survey of therapeutic drug monitoring for five antibiotics in South Korea.

Purpose: The current status of therapeutic drug monitoring (TDM) assay utilization by clinical laboratories in South Korea remains little known. We investigated the TDM status of five antibiotics known for nephrotoxicity (vancomycin, amikacin, gentamicin, tobramycin, and teicoplanin) for the improvement of TDM in South Korea among patients with infectious diseases using a cross-sectional nationwide survey.

Patients And Methods: We developed an online questionnaire and collected responses using a user-friendly web-based platform.

Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Isolates in Korea between 2014 and 2016.

Background: Several factors contribute to differences in serotype distribution. We investigated the serotype distribution and antimicrobial resistance of isolated between 2014 and 2016 in Korea.

Methods: We collected a total of 1,855 isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR.

Experience with therapeutic drug monitoring of three antifungal agents using an LC-MS/MS method in routine clinical practice.

Therapeutic drug monitoring (TDM) of voriconazole, itraconazole, and posaconazole is a useful tool for treatment of fungal infections. We validated a simple and reliable LC-MS/MS method using simple protein precipitation for simultaneous determination of voriconazole, itraconazole, and posaconazole. The linearity, accuracy, precision, carryover, and matrix effects were validated.

Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia.

Aims: We aimed to investigate the impact of various genetic polymorphisms affecting thiopurine metabolism pathways and toxicity in paediatric acute lymphoblastic leukaemia patients for the first time in Korea.

Methods: From May 2006 to September 2016, 139 paediatric acute lymphoblastic leukaemia patients treated with combination chemotherapy including 6-mercaptopurine were included in the study. One hundred and twenty-three variants in 43 genes, including TMPT and NUDT15, were screened using targeted genotyping, such as a MassARRAY system, direct sequencing and polymerase chain reaction-restriction fragment length polymorphism methods.

Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome.

Background: The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.

Therapeutic drug monitoring of teicoplanin using an LC-MS/MS method: Analysis of 421 measurements in a naturalistic clinical setting.

Teicoplanin is a glycopeptide antibiotic used for treatment of severe Gram-positive bacterial infection. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for therapeutic drug monitoring (TDM) of teicoplanin and to review our clinical experience. We established an LC-MS/MS method to analyze serum concentration of teicoplanin using simple protein precipitation with a 5 min run time for each sample.

Differentially expressed genes related to major depressive disorder and antidepressant response: genome-wide gene expression analysis.

Treatment response to antidepressants is limited and varies among patients with major depressive disorder (MDD). To discover genes and mechanisms related to the pathophysiology of MDD and antidepressant treatment response, we performed gene expression analyses using peripheral blood specimens from 38 MDD patients and 14 healthy individuals at baseline and at 6 weeks after the initiation of either selective serotonin reuptake inhibitor (SSRI) or mirtazapine treatment. The results were compared with results from public microarray data.

Evaluation of Stability of Thiopurine Metabolites Using a Validated LC-MS/MS Method.

Measurement of thiopurine metabolites is helpful to monitor adverse effects and assess compliance in patients on thiopurine treatment. The purpose of this study was to develop and validate an analytical method for measurement of thiopurine metabolites, thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN), in RBCs. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 6-TGN and 6-MMPN and evaluated the stability of the thiopurine metabolites in RBC and whole blood states without any preprocessing at various storage conditions.

Variations in plasma concentrations of tamoxifen metabolites and the effects of genetic polymorphisms on tamoxifen metabolism in Korean patients with breast cancer.

Inter-individual variation in tamoxifen metabolism in breast cancer patients is caused by various genetic and clinical factors. We measured the plasma concentrations of tamoxifen and its metabolites and investigated genetic polymorphisms influencing those concentrations. We measured the concentrations of tamoxifen, endoxifen, N-desmethyltamoxifen (NDM), and 4-hydroxytamoxifen (4-OH tamoxifen) in 550 plasma specimens from 281 breast cancer patients treated with tamoxifen.

Measurements of 6-thioguanine nucleotide levels with TPMT and NUDT15 genotyping in patients with Crohn's disease.

The association between the 6-thioguanine nucleotide (6-TGN) level and clinical remission in Crohn's disease (CD) remains controversial. Thiopurine-induced leukopenia is a life-threatening complication of CD in Asians that was recently shown to strongly correlate with NUDT15 genetic variants. This study aimed to determine the relationship between thiopurine metabolite levels and therapeutic response, and to investigate the association of NUDT15, TPMT, and thiopurine metabolites with leukopenia in patients with CD.

Large-scale clinical validation of biomarkers for pancreatic cancer using a mass spectrometry-based proteomics approach.

We performed an integrated analysis of proteomic and transcriptomic datasets to develop potential diagnostic markers for early pancreatic cancer. In the discovery phase, a multiple reaction monitoring assay of 90 proteins identified by either gene expression analysis or global serum proteome profiling was established and applied to 182 clinical specimens. Nine proteins (P < 0.

Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects.

Background: Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals.

Methods: Atorvastatin 80 mg was given to 50 healthy Korean male volunteers.

Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines.

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea.

Serum Cytokine Levels in Major Depressive Disorder and Its Role in Antidepressant Response.

Objective: Cytokines have been reported to have key roles in major depressive disorder (MDD). However, much less is known about cytokines in MDD and antidepressant treatment due to the diversity of cytokines and the heterogeneity of depression. We investigated the levels of cytokines in patients with MDD compared with healthy subjects and their associations with antidepressant response.

Severe Fever with Thrombocytopenia Syndrome in Patients Suspected of Having Scrub Typhus.

To determine prevalence of severe fever with thrombocytopenia syndrome in South Korea, we examined serum samples from patients with fever and insect bite history in scrub typhus-endemic areas. During the 2013 scrub typhus season, prevalence of this syndrome among patients suspected of having scrub typhus was high (23.0%), suggesting possible co-infection.

A simple and rapid analytical method based on solid-phase extraction and liquid chromatography-tandem mass spectrometry for the simultaneous determination of free catecholamines and metanephrines in urine and its application to routine clinical analysis.

Objectives: Urinary catecholamines and metanephrines are biochemical indicators of pheochromocytoma. We developed and validated a rapid and precise analytical method based on solid-phase extraction (SPE) and liquid chromatography separation coupled to tandem mass spectrometry (LC-MS/MS) for measuring urinary free catecholamines and metanephrines in a clinical setting.

Methods: Following SPE purification of catecholamines and metanephrines from urine specimens, chromatographic separation and quantitative detection were performed using LC-MS/MS.

A proposal for an individualized pharmacogenetic-guided isoniazid dosage regimen for patients with tuberculosis.

Background/aim: Isoniazid (INH) is an essential component of first-line anti-tuberculosis (TB) treatment. However, treatment with INH is complicated by polymorphisms in the expression of the enzyme system primarily responsible for its elimination, N-acetyltransferase 2 (NAT2), and its associated hepatotoxicity. The objective of this study was to develop an individualized INH dosing regimen using a pharmacogenetic-driven model and to apply this regimen in a pilot study.

The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy.

Objective: We compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring.

Exposure-outcome analysis in depressed patients treated with paroxetine using population pharmacokinetics.

Purpose: This study investigated population pharmacokinetics of paroxetine, and then performed an integrated analysis of exposure and clinical outcome using population pharmacokinetic parameter estimates in depressed patients treated with paroxetine.

Patients And Methods: A total of 271 therapeutic drug monitoring (TDM) data were retrospectively collected from 127 psychiatric outpatients. A population nonlinear mixed-effects modeling approach was used to describe serum concentrations of paroxetine.

Development and validation of liquid chromatography-tandem mass spectrometry method for quantification of plasma metanephrines for differential diagnosis of adrenal incidentaloma.

High-resolution imaging techniques have increased the detection rate of adrenal incidentaloma. We developed a method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detection of plasma free metanephrine (MN) and normetanephrine (NMN) and evaluated its analytical performance and clinical efficacy in differential diagnosis of adrenal incidentaloma. After solid-phase extraction, chromatographic isolation of the analytes and internal standard was achieved by column elution in the LC-MS/MS system.

Correlation of genetic polymorphisms with clinical outcomes in pemetrexed-treated advanced lung adenocarcinoma patients.

Aim: Pemetrexed is a commonly used chemotherapeutic agent for lung adenocarcinoma patients. We investigated the impact of the genetic polymorphisms on the therapeutic efficacy of pemetrexed in lung adenocarcinoma patients.

Materials & Methods: We performed genotying of 51 polymorphisms of 13 genes in 243 lung adenocarcinoma patients treated with pemetrexed as a single agent for second or more line of therapy.

Application of whole exome sequencing to a rare inherited metabolic disease with neurological and gastrointestinal manifestations: a congenital disorder of glycosylation mimicking glycogen storage disease.

Background: Rare inherited metabolic diseases with neurological and gastrointestinal manifestations can be misdiagnosed as other diseases or remain as disorders with indeterminate etiologies. This study aims to provide evidence to recommend the utility of whole exome sequencing in clinical diagnosis of a rare inherited metabolic disease.

Methods And Results: A 4-month-old female baby visited an outpatient clinic due to poor weight gain, repeated seizure-like episodes, developmental delay, and unexplained hepatomegaly with abnormal liver function test results.