2.Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates
Beomki LEE ; Won Young HEO ; Jee Ah KIM ; Hyun-Seung LEE ; Narae HWANG ; Hyung-Doo PARK ; Se In SUNG ; Yun Sil CHANG ; Won Soon PARK ; Soo-Youn LEE
Annals of Laboratory Medicine 2023;43(2):153-166
Background:
Despite the popularity of the NeoBase 2 Non-derivatized MSMS assay (PerkinElmer, Turku, Finland), there are no reports of its comprehensive evaluation, including the ability to distinguish transient tyrosinemia of the newborn (TTN) from tyrosinemia type 1 (TYR 1) using succinylacetone (SUAC). No newborn screening (NBS) cutoffs for preterm neonates in the Korean population have been suggested. We evaluated the NeoBase 2 assay and identified analytes requiring different cutoffs in preterm neonates.
Methods:
Residual NBS dried blood spot samples and proficiency testing (PT) materials of the Newborn Screening Quality Assurance Program and the Korean Association of External Quality Assessment Service were used. Precision, accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), linearity, recovery, carryover, and performance of SUAC were evaluated. Cutoffs were determined, and analytes requiring different cutoffs in preterm neonates were investigated.
Results:
Mean CVs for within-run and between-day precision were within 15%. Accuracy analysis indicated high agreement with in-house derivatized assay results and results of other PT participants. All analytes demonstrated acceptable LOD, LLOQ, and linearity. Recoveries were acceptable, except for SUAC. Carryover was negligible. Cutoffs were established for all analytes; Tyr, adenosine, and C20:0-lysophosphatidylcholine required different cutoffs in preterm neonates. Differential diagnosis of TYR 1 and TTN was successful with simultaneous Tyr and SUAC measurement.
Conclusions
The NeoBase 2 assay demonstrated satisfactory performance. The additional analytes provide a wider diagnostic coverage, and the simultaneous measurement of Tyr and SUAC is efficient in excluding TYR 1. The new cutoffs for preterm neonates may decrease false-positive rates, without compromising diagnostic sensitivity.
3.Associations of Serum Uric Acid Level With Liver Enzymes, Nonalcoholic Fatty Liver Disease, and Liver Fibrosis in Korean Men and Women: A CrossSectional Study Using Nationally Representative Data
Jun Myong LEE ; Hye Won KIM ; So Young HEO ; Kyung Yi DO ; Jun Deok LEE ; Seul Ki HAN ; Soon Koo BAIK ; Moon Young KIM ; Sei-Jin CHANG
Journal of Korean Medical Science 2023;38(34):e267-
Background:
This study aimed to determine whether serum uric acid (SUA) levels are associated with various indices of liver damage in the adult Korean population.
Methods:
We used the Seventh (VII) Korean National Health and Nutritional Examination Surveys. Our study population comprised 6,007 men and 8,488 women. Levels of SUA were divided into four groups (≤ 5.3, 5.3–6.0, 6.0–7.0, and > 7.0 mg/dL for men and ≤ 4.0, 4.0–4.8, 4.8–6.0, and > 6.0 mg/dL for women). Elevated liver enzyme levels were defined as > 35 (men) and > 31 (women) IU/L for aspartate aminotransferase (AST), > 45 (men) and > 34 (women) IU/L for alanine aminotransferase (ALT). Hepatic steatosis index and fibrosis (FIB)-4 index was used to determine nonalcoholic fatty liver disease (NAFLD) and liver FIB, respectively. Adjusted odds ratios (aORs) were calculated by logistic regression analysis for liver enzymes, NAFLD, and liver FIB, according to the SUA level.
Results:
Among women, the 4.8–6.0 and > 6.0 mg/dL SUA groups showed higher ORs of elevated AST (aOR, 1.78 and 2.03; 95% confidence interval [CI], 1.37–2.32 and 1.40–2.96, respectively; P < 0.001) and the 4.0–4.8, 4.8–6.0, and > 6.0 mg/dL SUA groups showed a higher ORs of ALT elevation (aOR, 1.35, 2.26, and 2.37; 95% CI, 1.02–1.79, 1.72–2.97, and 1.60–3.50, respectively; P < 0.001) compared to the lowest level SUA group. Among women with normal ALT, > 6.0 mg/dL SUA group showed higher OR of NAFLD status (aOR, 1.52; 95% CI, 1.06–2.19). Among men and women with NAFLD, hyperuricemia showed higher ORs of liver FIB (aOR, 2.25 and 1.89; 95% CI, 1.21–4.19 and 1.09–3.27, respectively) than the lowest level SUA group.
Conclusion
High SUA levels may be associated with elevated liver enzymes and NAFLD, mainly in women. Even in women with normal ALT levels, SUA levels may predict the NAFLD status. Hyperuricemia may predict advanced liver FIB in both men and women with NAFLD. Further studies investigating the causal effects of SUA on liver damage are required.
4.Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study
Ji Hyun KIM ; Baek Gyu JUN ; Minjong LEE ; Hye Ah LEE ; Tae Suk KIM ; Jeong Won HEO ; Da Hye MOON ; Seong Hee KANG ; Ki Tae SUK ; Moon Young KIM ; Young Don KIM ; Gab Jin CHEON ; Soon Koo BAIK ; Dong Joon KIM ; Dae Hee CHOI
Clinical and Molecular Hepatology 2022;28(3):540-552
Background/Aims:
Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections.
Methods:
A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated.
Results:
The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, P<0.001) and qSOFA (AUROC, 0.67; 95% CI, 0.64–0.70; P<0.001) score. The CLIF-SOFA, CLIF-C-AD scores, Sepsis-3 criteria, septic shock, and qSOFA positivity were significantly associated with in-hospital mortality (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.19–1.28; aHR, 1.13; 95% CI, 1.09–1.17; aHR, 1.19; 95% CI, 1.15–1.24; aHR, 1.88; 95% CI, 1.42–2.48; aHR, 2.06; 95% CI, 1.55–2.72; respectively; all P<0.001). For CLIF-SOFA scores ≥6, in-hospital mortality was >10%; this is the cutoff point for the definition of sepsis.
Conclusions
Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.
5.Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study
Hakjun HYUN ; Min Joo CHOI ; Jung Yeon HEO ; Yu Bin SEO ; Eliel NHAM ; Jin Gu YOON ; Hye SEONG ; Ji Yun NOH ; Hee Jin CHEONG ; Woo Joo KIM ; Ju-Yeon CHOI ; Young Jae LEE ; Hye Won LEE ; Sung Soon KIM ; Byoungguk KIM ; Joon Young SONG
Journal of Korean Medical Science 2022;37(27):e210-
Background:
As the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated.Method: This prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs.
Results:
Fifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3–4 weeks, 55.7 ± 2.4 U/mL at 5–8 weeks, and 81.3 ± 2.5 U/mL at 10–12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5–8 weeks, and 124.4 ± 2.6 at 10–12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10 6 peripheral blood mononuclear cell was 25.0 (5.0–29.2) at baseline, 60.0 (23.3–178.3) at 5-8 weeks, and 35.0 (13.3–71.7) at 10–12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1–2, and resolved within two days.
Conclusion
Single-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5–8 weeks and rather decrease at 10–12 weeks after vaccination.Cross-reactive neutralizing activity against the Omicron variant was negligible.
6.Survey on the Status of Breastfeeding in Korean Medical Institution Workers
Tae Hyeong KIM ; Sung-Hoon CHUNG ; Jun Hwan KIM ; Youngmin AHN ; Son Moon SHIN ; Woo Ryoung LEE ; Eui Kyung CHOI ; Juyoung LEE ; Hye-Jung SHIN ; Euiseok JUNG ; Ju Sun HEO ; Jin A LEE ; Soon Min LEE ; Seong Phil BAE ; Jeonglyn SONG ; Chae-Young KIM ; Dae Yong YI
Journal of Korean Medical Science 2022;37(15):e120-
Background:
Human breast milk is essential and provides irreplaceable nutrients for early humans. However, breastfeeding is not easy for various reasons in medical institution environments. Therefore, in order to improve the breastfeeding environment, we investigated the difficult reality of breastfeeding through questionnaire responses from medical institution workers.
Methods:
A survey was conducted among 179 medical institution workers with experience in childbirth within the last five years. The survey results of 175 people were analyzed, with incoherent answers excluded.
Results:
Of the 175 people surveyed, a total of 108 people (61.7%) worked during the day, and 33 people (18.9%) worked in three shifts. Among 133 mothers who stayed with their babies in the same nursing room, 111 (93.3%) kept breastfeeding for more than a month, but among those who stayed apart, only 10 (71.4%) continued breastfeeding for more than a month (P = 0.024). Ninety-five (88.0%) of daytime workers, 32 (94.1%) two-shift workers, and 33 (100%) three-shift workers continued breastfeeding for more than a month (P = 0.026). Workers in general hospitals tended to breastfeed for significantly longer than those that worked in tertiary hospitals (P = 0.003). A difference was also noted between occupation categories (P = 0.019), but a more significant difference was found in the comparison between nurses and doctors (P = 0.012). Longer breastfeeding periods were noted when mothers worked three shifts (P = 0.037). Depending on the period planned for breastfeeding prior to childbirth, the actual breastfeeding maintenance period after birth showed a significant difference (P = 0.002). Of 112 mothers who responded to the question regarding difficulties in breastfeeding after returning to work, 87 (77.7%) mentioned a lack of time caused by being busy at work, 82 (73.2%) mentioned the need for places and appropriate circumstances.
Conclusion
In medical institutions, it is recommended that environmental improvements in medical institutions, the implementation of supporting policies, and the provision of specialized education on breastfeeding are necessary to promote breastfeeding.
7.Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma
Jae Seung LEE ; Young Eun CHON ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Wonseok KANG ; Moon Seok CHOI ; Geum-Youn GWAK ; Yong-Han PAIK ; Joon Hyeok LEE ; Kwang Cheol KOH ; Seung Woon PAIK ; Hwi Young KIM ; Tae Hun KIM ; Kwon YOO ; Yeonjung HA ; Mi Na KIM ; Joo Ho LEE ; Seong Gyu HWANG ; Soon Sun KIM ; Hyo Jung CHO ; Jae Youn CHEONG ; Sung Won CHO ; Seung Ha PARK ; Nae-Yun HEO ; Young Mi HONG ; Ki Tae YOON ; Mong CHO ; Jung Gil PARK ; Min Kyu KANG ; Soo Young PARK ; Young Oh KWEON ; Won Young TAK ; Se Young JANG ; Dong Hyun SINN ; Seung Up KIM ;
Yonsei Medical Journal 2021;62(1):12-20
Purpose:
Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC.
Materials and Methods:
Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR.
Results:
Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001).
Conclusion
High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.
8.Factors Influencing Posttraumatic Growth in Patients with Lung Cancer
Young Suk KIM ; Jin Ha MOON ; Young Suk LEE ; Yeon Woo KIM ; Gyu Rim HEO ; Soon Keum OH
Journal of Korean Clinical Nursing Research 2021;27(1):98-108
Purpose:
This study was conducted to identify the factors influencing the posttraumatic growth (PTG) in patients with lung cancer and to provide basic data for nursing intervention development to improve PTG and adaptation.
Methods:
The study included 126 non-small cell lung cancer patients initially diagnosed at the Lung Cancer Center, C University Hospital in S city, Gyeonggi-do. Patients were asked to complete a questionnaire consisting of demographic characteristics, disease characteristics, posttraumatic growth, cancer coping, social support, and resilience. Data were analyzed using t-tests, ANOVA, and Pearson's correlation and multiple regression analysis.
Results:
The mean score for PTG in lung cancer patients was 56.39, cancer coping was 61.31, social support was 61.09, and resilience was 92.77. Significant positive correlations were found for PTG and cancer coping (r=.75, p<.001), social support (r=.52, p<.001) and resilience (r=.63, p<.001). Factors contributing to PTG of lung cancer patients were cancer coping (β=.53 p<.001), perceived health status(β=.20, p=.002), resilience (β=.21, p=.010) and importance of religion (β=.15, p=.013). This model explained about 64.0% of variances of PTG (F=29.58, p<.001).
Conclusion
It is necessary to develop new nursing intervention programs to improve PTG for patients with lung cancer based on strategies to enhance coping and resilience to recovery. Longitudinal studies examining temporal changes in PTG among patients with lung cancer are suggested for future studies in this regard.
9.The Impact of Erosive Reflux Esophagitis on the Decline of Lung Function in the General Population
Hye-Rin KANG ; Ye Jin LEE ; Ha Youn LEE ; Tae Yun PARK ; Jung-Kyu LEE ; Eun Young HEO ; Hee Soon CHUNG ; Seung Ho CHOI ; Deog Kyeom KIM
Journal of Korean Medical Science 2021;36(5):e29-
Background:
The impact of reflux esophagitis on the decline of lung function has been rarely reported. This study was performed to evaluate the association between erosive reflux esophagitis and lung function changes.
Methods:
We included patients with normal lung function who underwent esophagogastroduodenoscopy for health screening from a health screening center. Patients with persistent erosive reflux esophagitis on two discrete endoscopic examinations were designated as the erosive reflux esophagitis group. We also selected patients without erosive reflux esophagitis and matched them 1:4 with patients from the erosive reflux esophagitis group. We estimated annual forced expiratory volume in 1 second (FEV1 ) and forced vital capacity (FVC) changes from baseline and compared these estimates by the linear mixed regression model. We also estimated the biannual incidence of chronic obstructive pulmonary disease (COPD).
Results:
In total, 1,050 patients (210 patients with erosive reflux esophagitis, and 840 matched controls) were included. The median follow-up duration for spirometry was six years. In patients with erosive reflux esophagitis, mild reflux esophagitis (A grade) was most common (165 patients, 78.6%). The adjusted annual FEV1 change in patients with erosive reflux esophagitis was −51.8 mL/yr, while it decreased by 46.8 mL/yr in controls (P = 0.270).The adjusted annual FVC decline was similar between the two groups (−55.8 vs. −50.5 mL/ yr, P = 0.215). The estimated COPD incidence during the follow-up period was not different between the erosive reflux esophagitis and control groups.
Conclusion
In patients with normal lung function, the presence of erosive reflux esophagitis did not affect the annual declines in FEV1 or FVC.
10.Mesenchymal Stem Cells Derived from Wharton’s Jelly Can Differentiate into Schwann Cell-Like Cells and Promote Peripheral Nerve Regeneration in Acellular Nerve Grafts
Soon Jin CHOI ; Suk Young PARK ; Young Ho SHIN ; Seung-Ho HEO ; Kang-Hyun KIM ; Hyo In LEE ; Jae Kwang KIM
Tissue Engineering and Regenerative Medicine 2021;18(3):467-478
BACKGROUND:
Schwann cells (SCs) secrete neurotrophic factors and provide structural support and guidance during axonal regeneration. However, nearby nerves may be damaged to obtain primary SCs, and there is a lack of nervous tissue donors. We investigated the potential of Wharton’s Jelly-derived mesenchymal stem cells (WJ-MSCs) in differentiating into Schwann cell-like cells (WJ-SCLCs) as an alternative to SCs. We also examined whether implantation of WJ-SCLCsladen acellular nerve grafts (ANGs) are effective in inducing functional recovery and nerve regeneration in an animal model of peripheral nerve injury.
METHODS:
The differentiation of WJ-MSCs into WJ-SCLCs was determined by analyzing SC-specific markers. The secretion of neurotrophic factors was assessed by the Neuro Discovery antibody array. Neurite outgrowth and myelination of axons were found in a co-culture system involving motor neuron cell lines. The effects of ANGs on repairing sciatic nerves were evaluated using video gait angle test, isometric tetanic force analysis, and toluidine blue staining.
RESULTS:
Compared with undifferentiated WJ-MSCs, WJ-SCLCs showed higher expression levels of SC-specific markers such as S100b, GFAP, KROX20, and NGFR. WJ-SCLCs also showed higher secreted amounts of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and granulocyte-colony stimulating factor than did WJ-MSCs.WJ-SCLCs effectively promoted the outgrowth and myelination of neurites in motor neuron cells, and WJ-SCLCs laden ANGs significantly facilitated peripheral nerve regeneration in an animal model of sciatic nerve injury.
CONCLUSION
WJ-MSCs were readily differentiated into WJ-SCLCs, which effectively promoted the regeneration of peripheral nerves. Transplantation of WJ-SCLCs with ANGs might be useful for assisting peripheral nerve regeneration.

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