1.Association Between Individual Air Pollution (PM 10 , PM2.5) Exposure and Adverse Pregnancy Outcomes in Korea: A Multicenter Prospective Cohort, Air Pollution on Pregnancy Outcome (APPO) Study
Tae Gyu AHN ; Young Ju KIM ; Gain LEE ; Young-Ah YOU ; Soo Min KIM ; Rin CHAE ; Young Min HUR ; Mi Hye PARK ; Jin-Gon BAE ; Soo-Jeong LEE ; Young-Han KIM ; Sunghun NA
Journal of Korean Medical Science 2024;39(13):e131-
Background:
Prenatal exposure to ambient air pollution is linked to a higher risk of unfavorable pregnancy outcomes. However, the association between pregnancy complications and exposure to indoor air pollution remains unclear. The Air Pollution on Pregnancy Outcomes research is a hospital-based prospective cohort research created to look into the effects of aerodynamically exposed particulate matter (PM) 10 and PM 2.5 on pregnancy outcomes.
Methods:
This prospective multicenter observational cohort study was conducted from January 2021 to June 2023. A total of 662 women with singleton pregnancies enrolled in this study. An AirguardK ® air sensor was installed inside the homes of the participants to measure the individual PM 10 and PM 2.5 levels in the living environment. The time–activity patterns and PM 100 and PM 2.5 , determined as concentrations from the time-weighted average model, were applied to determine the anticipated exposure levels to air pollution of each pregnant woman. The relationship between air pollution exposure and pregnancy outcomes was assessed using logistic and linear regression analyses.
Results:
Exposure to elevated levels of PM 10 throughout the first, second, and third trimesters as well as throughout pregnancy was strongly correlated with the risk of pregnancy problems according to multiple logistic regression models adjusted for variables. Except for in the third trimester of pregnancy, women exposed to high levels of PM 2.5 had a high risk of pregnancy complications. During the second trimester and entire pregnancy, the risk of preterm birth (PTB) increased by 24% and 27%, respectively, for each 10 μg/m 3 increase in PM 10. Exposure to high PM 10 levels during the second trimester increased the risk of gestational diabetes mellitus (GDM) by 30%. The risk of GDM increased by 15% for each 5 μg/m 3 increase in PM2.5 during the second trimester and overall pregnancy, respectively. Exposure to high PM 10 and PM 2.5 during the first trimester of pregnancy increased the risk of delivering small for gestational age (SGA) infants by 96% and 26%, respectively.
Conclusion
Exposure to high concentrations of PM 10 and PM 2.5 is strongly correlated with the risk of adverse pregnancy outcomes. Exposure to high levels of PM10 and PM2.5 during the second trimester and entire pregnancy, respectively, significantly increased the risk of PTB and GDM. Exposure to high levels of PM 10 and PM2.5 during the first trimester of pregnancy considerably increased the risk of having SGA infants. Our findings highlight the need to measure individual particulate levels during pregnancy and the importance of managing air quality in residential environment.
2.The introduction to air pollution on pregnancy outcome (APPO) study: a multicenter cohort study
Young Min HUR ; Sunwha PARK ; Eunjin KWON ; Young-Ah YOU ; AbuZar ANSARI ; Soo Min KIM ; Gain LEE ; Mi Hye PARK ; Kyung A LEE ; Soo Jung KIM ; Young-Han KIM ; Yeon-sung JUNG ; Geum Joon CHO ; Min-Jeong OH ; Sung Hun NA ; Se jin LEE ; Tae Gyu AN ; Jin-Gon BAE ; Yu-Hwan KIM ; Soo-Jeong LEE ; Na Kyung KIM ; Eun-Hee HA ; Young Ju KIM
Obstetrics & Gynecology Science 2023;66(3):169-180
Objective:
The air pollution on pregnancy outcome (APPO) study is a prospective hospital-based cohort study designed to investigate the maternal and fetal effects of a particulate matter with an aerodynamic below 10 μm (PM10) and PM2.5 (below 2.5 μm) exposure. This study aims to analyze a relationship between particulate matter and adverse pregnancy outcomes and to find related biomarkers and develop management guidelines.
Methods:
About 1,200 pregnant women are recruited for 3 years (from January 2021 to December 2023) from seven university hospitals to investigate the effects of particulate matter on pregnancy complications and adverse pregnancy outcomes. We collect biological samples by 5 mL of maternal venous blood and 15 mL of urine in each trimester of pregnancy, and 5 mL of umbilical cord blood and 2×2×2 cm of placental tissue are collected after delivery. In addition, by applying PM10 and PM2.5 concentration values and time-activity patterns from the time weighted average model, the individual predicted exposure of air pollution for the pregnant women are obtained.
Results:
The average exposure of PM10 and PM2.5 of the participants in the entire period of pregnancy, was exceeded the World Health Organization air quality guidelines (an annual level, PM10 >15 μg/m3, PM2.5 >5 μg/m3). Moreover, it was revealed that the PM concentration was increasing toward the 3rd trimester of pregnancy.
Conclusion
The APPO study will be able to identify the degree of exposure to air pollution in pregnant women and use it as basic data for estimating individual exposure to particulate matter. And the results of the APPO study will facilitate in the development of health management for pregnant women against air pollution.
3.Antiviral Resistance in Human Cytomegalovirus Due to UL54 Mutations Without UL97 Mutations
Kuenyoul PARK ; Kyu-Hwa HUR ; Heungsup SUNG ; Sang-Ho CHOI ; Mi-Na KIM
Annals of Clinical Microbiology 2022;25(2):45-51
Background:
The concurrent detection of human cytomegalovirus (CMV) with UL97 and UL54 mutations is crucial for prescribing adequate antiviral treatment when drug-resistant CMV infection is suspected. We investigated the frequency of resistance-conferring mutations among patients with persistent or recurrent CMV infection and further reviewed the subgroup with UL54 mutations without UL97 mutations.
Methods:
Patients with persistent or recurrent CMV infection after 4 weeks of treatment with ganciclovir or foscarnet were consecutively enrolled between November 2012 and May 2019.The direct sequencing of UL97 and UL54 was performed to detect resistance mutations in CMV.
Results:
A total of 101 sequencing datasets were obtained from 65 enrolled patients.CMV UL97 and UL54 mutations were detected in 15.4% (10/65) and 9% (6/65) of patients, respectively. The CMV retrieved from two patients (3%) had mutations in both genes. Four patients with CMV UL54 mutations alone had a history of haploidentical peripheral blood stem cell transplantation, and foscarnet was administered for over 4 weeks to these patients; 21.5% of patients had suspected resistant CMV infection with either UL97 or UL54 mutations.
Conclusion
In this study, CMV UL54 mutations but not UL97 mutations were found in patients subjected to prolonged foscarnet administration for CMV disease.
4.The First Case of Bacteremia Caused by Bordetella hinzii in Korea
Joonsang YU ; Sihwan KIM ; Kyu-Hwa HUR ; Heungsup SUNG ; Mi-Na KIM
Annals of Clinical Microbiology 2022;25(3):103-109
Bordetella hinzii is a nonfermenting, gram-negative rod and a rare opportunistic pathogen that can cause respiratory infections, bacteremia, and cholangitis. Here, we report the first case of bacteremia caused by B. hinzii in Korea. A 59-year-old man was admitted for the biopsy of a mass lesion in the left lower lobe, which was detected during a health screening. The blood cultures collected from the patient with high fever (> 39℃), which developed 4 hours after the biopsy, yielded gram-negative rods. The gram-negative bacilli were identified as B. hinzii using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and PCR sequencing of the 16S rRNA gene. After 9 days of antimicrobial treatment with ampicillin/sulbactam, piperacillin/tazobactam, or meropenem, the patient improved and was discharged.
5.Epidemiologic Linkage of COVID-19Outbreaks at Two University-affiliated Hospitals in the Seoul Metropolitan Area in March 2020
Kuenyoul PARK ; Jaewoong LEE ; Kihyun LEE ; Jiwon JUNG ; Sung-Han KIM ; Jina LEE ; Mauricio CHALITA ; Seok-Hwan YOON ; Jongsik CHUN ; Kyu-Hwa HUR ; Heungsup SUNG ; Mi-Na KIM ; Hae Kyung LEE
Journal of Korean Medical Science 2021;36(4):e38-
Background:
Coronavirus disease 2019 (COVID-19) outbreaks emerged at two universityaffiliated hospitals in Seoul (hospital A) and Uijeongbu City (hospital S) in the metropolitan Seoul area in March 2020. The aim of this study was to investigate epidemiological links between the outbreaks using whole genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods:
Fifteen patients were enrolled in the study, including four non-outbreak (A1–A4) and three outbreak cases (A5–A7) in hospital A and eight cases (S1–S8) in hospital S. Patients' hospital stays, COVID-19 symptoms, and transfer history were reviewed. RNA samples were submitted for WGS and genome-wide single nucleotide variants and phylogenetic relationships were analyzed.
Results:
The index patient (A5) in hospital A was transferred from hospital S on 26 March.Patients A6 and A7 were the family caregiver and sister, respectively, of the patient who shared a room with A5 for 4 days. Prior to transfer, A5 was at the next bed to S8 in the emergency room on 25 March. Patient S6, a professional caregiver, took care of the patient in the room next to S8's room for 5 days until 22 March and then S5 for another 3 days.WGS revealed that SARS-CoV-2 in A2, A3, and A4 belong to clades V/B.2, S/A, and G/B.1, respectively, whereas that of A5–A7 and S1-S5 are of the V/B.2.1 clade and closely clustered. In particular, SARS-CoV-2 in patients A5 and S5 showed perfect identity.
Conclusion
WGS is a useful tool to understand epidemiology of SARS-CoV-2. It is the first study to elucidate the role of patient transfer and caregivers as links of nosocomial outbreaks of COVID-19 in multiple hospitals.
6.Vaginal health in women and the possibility of predicting preterm birth through microbiome analysis
Young Min HUR ; Mi Na KANG ; Young Ju KIM
Journal of the Korean Medical Association 2021;64(12):833-840
With the recent development of next-generation sequencing technology, the microbiome in the body is being revealed in detail. It is also possible to describe the normal vaginal microenvironment and, more specifically, any changes in pregnancy. Moreover, we present the hypothesis that the microbiome is a contributing factor to preterm birth (PTB).Current Concepts: High estrogen status stimulates the maturation and proliferation of vaginal epithelial cells and the accumulation of glycogen, which promotes lactic acid production and maintains the vaginal environment at an acidic pH. The vaginas of most premenopausal women are predominantly colonized by Lactobacillus which plays an important role in local defense. Recently, it has also been reported that there are several specific types of Lactobacillus species, while other anaerobes, including Gardnerella and Atopobium also coexist in the vagina. Vaginal dysbiosis is defined as various expressions of microorganisms, secretion of specific metabolites, and changes in pH. During pregnancy, a multitude of microbiome changes occur in the oral cavity, gut, vagina, and placenta. The risk of PTB increases if the microbiome changes to one of dysbiosis. It is possible to analyze the characteristic microbiome composition related to PTB and to develop biomarkers predicting PTB. It is necessary to educate patients based on these findings.Discussion and Conclusion: Microbiome analysis has contributed significantly to understanding the association between women’s vaginal health and PTB. Continued research will also contribute to public health by assisting in the prediction and prevention of PTB.
7.Evaluation of Two Commercial Kits for Rapid Detection and Typing of Carbapenemase in Carbapenem-Resistant Enterobacterales
Seunghoo LEE ; Kyu-Hwa HUR ; Yunsil CHUNG ; Heungsup SUNG ; Mi-Na KIM
Annals of Clinical Microbiology 2021;24(2):45-53
Background:
Rapid detection of carbapenemase-producing Enterobacterales (CPE) is desirable to guide antimicrobial therapy and infection control. The NG-Test Carba5 (Carba5;NG Biotech, France) rapid multiplex lateral flow immunoassay and BD MAX Check-Points CPO Assay (CPO; BD Diagnostic Systems, USA) fully automated real-time PCR assay were evaluated for the detection of KPC, NDM, VIM, IMP, and OXA-48-like group in a culture colony compared to genotyping using conventional PCR.
Methods:
Among the clinical isolates of carbapenem-resistant Enterobacterales (CRE) collected from 2013 to 2019, up to 20 isolates for each carbapenemase type, and approximately 60 carbapenemase-negative CRE were enrolled. Genotyping of carbapenemases were performed using single-target PCR for KPC, NDM, and OXA-48-like group and the multiplex PCR for VIM, IMP, GIM, SIM, and SPM. All isolates were tested with Carba5 and CPO. The discrepant results were resolved by single-target specific conventional PCR or GeneXpert Carba-R Assay (Carba-R; Cepheid, USA).
Results:
Of 147 CREs, 82 were CPE (55.8%) including 20 KPC, 22 NDM, 17 VIM, three IMP, and 13 OXA-48-like group, and seven double carbapenemase-positive (three KPC/VIM, two NDM/ VIM, one KPC/NDM, and one NDM/OXA-48-like group) isolates. Carba5 and CPO detected all CPE correctly along with two more IMP-producing CPE. The sensitivity and specificity of both kits were equally 100% and 97%. Two false IMP-positives were confirmed IMP-positive with Carba-R and IMP-specific single-target PCR.
Conclusion
Carba5 and CPO reliably detect and differentiate five common carbapenemases in cultured colonies. Carba5, faster and simpler, is preferred as a spot test.
8.Evaluation of Two Commercial Kits for Rapid Detection and Typing of Carbapenemase in Carbapenem-Resistant Enterobacterales
Seunghoo LEE ; Kyu-Hwa HUR ; Yunsil CHUNG ; Heungsup SUNG ; Mi-Na KIM
Annals of Clinical Microbiology 2021;24(2):45-53
Background:
Rapid detection of carbapenemase-producing Enterobacterales (CPE) is desirable to guide antimicrobial therapy and infection control. The NG-Test Carba5 (Carba5;NG Biotech, France) rapid multiplex lateral flow immunoassay and BD MAX Check-Points CPO Assay (CPO; BD Diagnostic Systems, USA) fully automated real-time PCR assay were evaluated for the detection of KPC, NDM, VIM, IMP, and OXA-48-like group in a culture colony compared to genotyping using conventional PCR.
Methods:
Among the clinical isolates of carbapenem-resistant Enterobacterales (CRE) collected from 2013 to 2019, up to 20 isolates for each carbapenemase type, and approximately 60 carbapenemase-negative CRE were enrolled. Genotyping of carbapenemases were performed using single-target PCR for KPC, NDM, and OXA-48-like group and the multiplex PCR for VIM, IMP, GIM, SIM, and SPM. All isolates were tested with Carba5 and CPO. The discrepant results were resolved by single-target specific conventional PCR or GeneXpert Carba-R Assay (Carba-R; Cepheid, USA).
Results:
Of 147 CREs, 82 were CPE (55.8%) including 20 KPC, 22 NDM, 17 VIM, three IMP, and 13 OXA-48-like group, and seven double carbapenemase-positive (three KPC/VIM, two NDM/ VIM, one KPC/NDM, and one NDM/OXA-48-like group) isolates. Carba5 and CPO detected all CPE correctly along with two more IMP-producing CPE. The sensitivity and specificity of both kits were equally 100% and 97%. Two false IMP-positives were confirmed IMP-positive with Carba-R and IMP-specific single-target PCR.
Conclusion
Carba5 and CPO reliably detect and differentiate five common carbapenemases in cultured colonies. Carba5, faster and simpler, is preferred as a spot test.
9.Causes and Clinical Relevance of Inconclusive SARS-CoV-2 Real-Time Reverse TranscriptionPCR Test Results
Aram KIM ; Heerah LEE ; Kyu Wha HUR ; Heungsup SUNG ; Mi-Na KIM
Annals of Clinical Microbiology 2020;23(4):251-259
Background:
Inconclusive SARS-CoV-2 real-time reverse transcription-PCR (rRT-PCR) test results, which are positive for one or more target genes but not all, are problematic in clinical laboratories. In this study, we aimed to investigate the cause and clinical relevance of such inconclusive results.
Methods:
rRT-PCR was performed using the Allplex 2019-nCoV assay kit (Seegene Inc., Korea) targeting the following three genes: E, RdRp, and N. For all inconclusive test results reported from March to June 2020, the frequency per kit, lot number, specimen type, cycle threshold (Ct) and peak values of the amplification curves, positive target genes, and results of repeated or consecutive tests were analyzed.
Results:
A total of 43,268 tests were conducted, of which 93 (0.21%) were inconclusive—49 from 11 coronavirus disease 2019 (COVID-19) patients and 44 from non-COVID-19 patients.In COVID-19 patients, the results were inconclusive 11.9 ± 4.7 days after diagnosis and were negative 8.8 ± 5.5 days after the inconclusive results were reported. However, in nonCOVID-19 patients, they were all negative upon retest and 81.8% of them were identified to have yielded in 2 out of 8 lots. The most frequently positive target genes were N (55.4%) in COVID-19 and RdRp (61.2%) in non-COVID-19 patients, respectively. No difference was observed in the Ct or peak values of the amplification curves for inconclusive samples between COVID-19 and non-COVID-19 cases.
Conclusion
Inconclusive test results should be reported neither positive nor negative. Such results can be reported as inconclusive without retesting in COVID-19 patients; however, they should certainly be confirmed by a retest in non-COVID-19 patients or newly diagnosed cases.
10.The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Mi Kyung KIM ; Jae-Han JEON ; Sung-Woo KIM ; Jun Sung MOON ; Nan Hee CHO ; Eugene HAN ; Ji Hong YOU ; Ji Yeon LEE ; Miri HYUN ; Jae Seok PARK ; Yong Shik KWON ; Yeon-Kyung CHOI ; Ki Tae KWON ; Shin Yup LEE ; Eon Ju JEON ; Jin-Woo KIM ; Hyo-Lim HONG ; Hyun Hee KWON ; Chi Young JUNG ; Yin Young LEE ; Eunyeoung HA ; Seung Min CHUNG ; Jian HUR ; June Hong AHN ; Na-young KIM ; Shin-Woo KIM ; Hyun Ha CHANG ; Yong Hoon LEE ; Jaehee LEE ; Keun-Gyu PARK ; Hyun Ah KIM ; Ji-Hyun LEE
Diabetes & Metabolism Journal 2020;44(4):602-613
Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. Compared with the non-DM group ( DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

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