Comparison of Measurable Residual Disease in Pediatric B-Lymphoblastic Leukemia Using Multiparametric Flow Cytometry and Next-Generation Sequencing

Measurable residual disease (MRD) testing, a standard procedure in B-lymphoblastic leukemia (B-ALL) diagnostics, is assessed using multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) analysis of immunoglobulin gene rearrangements. We evaluated the concordance between eight-color, two-tube MFC-MRD the LymphoTrack NGS-MRD assays using 139 follow-up samples from 54 pediatric patients with B-ALL. We also assessed the effect of hemodilution in MFC-MRD assays. The MRD-concordance rate was 79.9% (N = 111), with 25 (18.0%) and 3 (2.2%) samples testing positive only by NGSMRD (MFC − NGS + MRD) and MFC-MRD (MFC + NGS − MRD), respectively. We found a significant correlation in MRD values from total nucleated cells between the two methods (r = 0.736 [0.647–0.806], P < 0.001). The median MRD value of MFC − NGS + MRD samples was estimated to be 0.0012% (0.0001%–0.0263%) using the NGS-MRD assays. Notably, 14.3% of MFC − NGS + MRD samples showed NGS-MRD values below the limit of detection in the MFC-MRD assays. The percentages of hematogones detected in MFC-MRD assays significantly differed between the discordant and concordant cases (P < 0.001). MFC and NGS-MRD assays showed relatively high concordance and correlation in MRD assessment, whereas the NGS-MRD assay detected MRD more frequently than the MFC-MRD assay in pediatric B-ALL. Evaluating the hematogone percentages can aid in assessing the impact of sample hemodilution.

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 indepth 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.

Acral Pigmentation in Peutz-Jeghers Syndrome: Dermoscopic Findings and Treatment with the Q-Switched Nd:YAG Laser

Peutz-Jeghers syndrome (PJS; MIM 175200) is an autosomal dominant multiple-organ cancer syndrome. It is characterized by brown macules distributed in the perioral skin, oral mucosa, hands and feet, and hamartomatous gastrointestinal polyps that can eventually lead to intestinal obstruction, abdominal pain, bleeding, and anemia. Patients with PJS are at a higher risk of ovarian, testicular, breast, lung, and pancreatic cancers. This predisposition is due to the pathogenic variant in serine/threonine kinase 11 (STK11) gene located on chromosome 19p13.3. Here, we present the dermoscopic findings, histopathologic features of acral pigmentation, and DNA sequencing results of the patient with PJS. We also report a successful removal of acral pigmentation using the Q-switched Nd:YAG laser (QSNYL) treatment. Our results suggest that QSNYL therapy could be a treatment option for acral pigmentation in patients with PJS.

Alterations in the Occipital Cortex of Drug-Naïve Adults With Major Depressive Disorder: A Surface-Based Analysis of Surface Area and Cortical Thickness

Objective@#Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD. @*Methods@#A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups. @*Results@#We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased. @*Conclusion@#Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.

Molecular basis and diagnosis of thalassemia

Thalassemia is characterized by the impaired synthesis of globin chains due to disease-causing variants in α- or β-globin genes. In this review, we provide an overview of the molecular basis underlying α- and β-thalassemia, and of the current technologies used to characterize these disease-causing variants for the diagnosis of thalassemia.Understanding these molecular basis and technologies will prove to be beneficial for the accurate diagnosis of thalassemia.

Molecular basis and diagnosis of thalassemia

Thalassemia is characterized by the impaired synthesis of globin chains due to disease-causing variants in α- or β-globin genes. In this review, we provide an overview of the molecular basis underlying α- and β-thalassemia, and of the current technologies used to characterize these disease-causing variants for the diagnosis of thalassemia.Understanding these molecular basis and technologies will prove to be beneficial for the accurate diagnosis of thalassemia.

Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

Effects of Pyridoxal-5'-Phosphate on Aminotransferase Activity Assay

BACKGROUND: Pyridoxal-5'-phosphate (P5P), a coenzyme of the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) reactions, is required to measure aminotransferase levels (IFCC method). However, a modified IFCC method that uses a reagent devoid of P5P is commonly used in laboratories in Korea. To determine the differences between the two methods, we compared aminotransferase levels measured by using the IFCC method and modified IFCC method. METHODS: Serum levels of AST and ALT, with and without P5P, were measured in 2,318 patients. Based on the allowable limits of performance set by the Royal College of Pathologists of Australasia (RCPA), differences between the two methods were analyzed under various conditions. RESULTS: Higher AST and ALT values were obtained by the IFCC method compared to modified IFCC method, showing significant differences between the two methods (AST, 5.8±14.2 IU/L; ALT, 2.8±6.9 IU/L) (P<0.001). Values exceeding RCPA criteria were more frequently observed in emergency orders (AST, 65.8%; ALT, 14.4%) than in routine orders (AST, 3.2%; ALT, 9.6%), as well as in inpatient wards (AST, 70.4%; ALT, 18.5%) compared to outpatient clinics (AST, 56.6%; ALT, 10.0%). However, the differences between the two methods were not significant among the disease groups, except for the acute myocardial infarction group. CONCLUSIONS: The method using reagents without P5P underestimated aminotransferase activity. The effect of P5P was more significant in patients with acute myocardial infarction, considered as P5P-deficient. In conclusion, the IFCC method with P5P should be applied for measuring AST and ALT serum levels.

First Korean Case of Cedecea lapagei Pneumonia in a Patient With Chronic Obstructive Pulmonary Disease

No abstract available.

Metabolic Syndrome and the Risk for Chronic Kidney Disease among Korean Women / 가정의학회지

BACKGROUND: Metabolic syndrome (MetS), characterized by abdominal obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, high blood pressure, and high fasting glucose level, is a common risk factor for cardiovascular diseases and associated complications. We examined the relationship between the metabolic syndrome and risk of chronic kidney disease (CKD) in Korean women. METHODS: We used data from 10,170 women, aged 30-89 years, who had visited a health examination center at a tertiary care hospital in 2006. The data were studied cross-sectionally. MetS was identified using the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). CKD was defined as an estimated GFR < 60 ml/min per 1.73 m2. The multivariable-adjusted (adjustment for age, education, body mass index (BMI), alcohol drinking, smoking, previous coronary heart disease, menopauses and physical inactivity) odds ratio of CKD (95% CI) associated with each component of the metabolic syndrome was calculated using the logistic regression models. RESULTS: A total of 1,039 participants have MetS. The multivariable-adjusted odds ratios (OR) of CKD in participants with MetS, hypertriglyceridemia and high blood pressure compared with participants without such factors were 2.68 (95% CI, 1.77-4.06), 1.96 (95% CI, 1.34-2.88), and 2.00 (95% CI, 1.38-2.89). Compared with the participants with no MetS traits, those with one, two, equal to or more than three traits of MetS had OR of CKD of 1.24 (95% CI, 0.75-2.06), 1.56 (95% CI, 0.89-2.75), and 2.18 (95% CI, 1.21-3.93), respectively. CONCLUSION: We found that Korean women with MetS had an increased risk for developing CKD. Finally, earlier identification and management of MetS might improve patient health and prevent progression of CKD.