Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study

Kim Si-Ho,Hong Jin Yeong,Bae Seongman,Lee Hojin,Wi Yu Mi,Ko Jae-Hoon,Kim Bomi,Joo Eun-Jeong,Seok Hyeri,Shi Hye Jin,Yoo Jeong Rae,Hyun Miri,Kim Hyun ah,Jang Sukbin,Mun Seok Jun,Kim Jungok,Kim Min-Chul 대한의학회 2022 Journal of Korean medical science Vol.37 No.18

Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19- associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90- day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). Conclusion: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Tissue reactions to Implanted Intracanal Medicaments in Rats

Kim, Miri,Kim, Byunghyun,Kim, Wonkyung 大韓齒科保存學會 2004 Restorative Dentistry & Endodontics Vol.29 No.1

최근 근관나 치료 영역에서는 적절한 기계적 근관 성형과 근관 세척으로만 효과적으로 근관 내 미생물의 숫자를 감소시킬 수 있어 다른 약제의 사용은 권장되고 있지 않다. 그럼에도 불구하고 수 종의 근관내 약제는 감염된 근관에서 미생물의 숫자를 줄이고 근관 내용물의 불활성화와 삼출액을 줄이기 위해 사용되고 있다. 그 중 포름 알데하이드를 함유하고 있는 Depulpin®과 근관 치료학에서 오랫동안 널리 사용되어온 수산화 칼슘을 포함하고 있는 Tempcanal®과 Vitapex®등에 대한 세포 독성은 충분한 연구가 이루어지지 모한 상태이다. 이에 본 연구에서는 이들 약제가 백서에서의 세포 독성에 미치는 영향에 관하여 고찰하고자 하였다. Sprague-Dawley계 백서 숫놈 20마리를 사용하여, 각 각의 쥐는 케타민과 럼푼을 근육내 주사하여 마취하였고, 복부의 피하 부위를 절개한 뒤 3개씩의 Teflon-coating된 매식체를 삽입하였다. 매식체 안에는 각각 Tempcanal®, Vitapex®, Depulpin®을 넣고, 백서 20마리를 6개군으로 나누어 매식체 삽입 후 1주 뒤, 4주 뒤에 희생시켜 매식체 주위 조직을 잘라내고 10% 포르말린에 고정 후 파라핀에 포매 하였다. 미세 절단기로 4㎛로 연속 절단 후, hematoxy-line-eosin 염색 후 3명의 관찰자가 광학 현미경으로 관찰하여 염증의 정도를 4단계로 평가한 뒤 Kruskall-Wallis test(P<0.05)로 통계처리하였다. 그 결과 제 1군(Tempcanal® 7일후 군), 제 2군(Vitapex® 7일후 군), 제 3군 (Depulpin® 7일후 군)모두 중등도의 염증도를 보였으나, 세 군간에 통계학적 유의성은 없었다. 그러나 제 4군(Tempcanal®30일후 군), 제 5군(Vitapex® 30일후 군)의 경우에서는 약한 염증도를 보여주었으나, 제 6군 (Depulpin® 30일후 군)은 가장 심한 염증 반응과 함께 조직 괴사의 양상을 보여주었으며, 4,5군과 6군간에 통계학적 유의성을 보였다. 본 실험 결과, Depulpin®은 Tempcanal®와 Vitapex® 에 비해 높은 세포 독성을 보여주고 있으나, 좀 더 많은 임상적 검증이 필요할 것으로 사료된다.

The Effect of Estrogen Deficiency on Rat Pulpodentinal Complex

Kim, Miri,Yang, Won-Kyung,Baek, jin,Kim, Jong-Jin,Kim, Won-Kyung,Lee, Young-Kyoo 大韓齒科保存學會 2005 Restorative Dentistry & Endodontics Vol.30 No.5

난소 절제술을 시행한 백서에서 에스트로겐 호르몬의 결핍으로 인한 상아-치수 복합체의 변화를 관찰하였다. 30마리의 암놈 Sprague-Dawley rats을 두 군으로 나누어 1 군은 Sham-surgery를 시행하였고, 2 군은 양측 난소 절제술을 시행하였다. 백서는 12주 뒤에 모두 희생시켜, 하악 치아와 인접한 치주조직을 포함하여 절제하였고, 10% 중성 포르말린 용액에 고정하였다. 두 군의 차이점을 비교하기 위하여 방사전 사진을 촬영하고, osteonectin을 이용한 면역 화학 염색법을 시행하였다. 조직 형태학적 차이점을 측정하기 위하여 영상 분석 프로그램을 사용하였고, 분석 방법으로는 Paired t-test를 사용하였다 (p < 0.05). Osteonectin을 이용한 면역 화학 염색 결과, 두 군간에는 유의성 있는 차이점이 존재하였다. 난소 절제술을 시행한 백서군에서는 전상아질층의 두께가 현저히 증가하였고, Sham-surgery 군에서는 전상아질 층과 치수 조직에서 osteonectin이 좀 더 특이적으로 염색되어 나타났다. 이러한 결과로 결론지어보면, 백서에서 인위적으로 난소 절제술을 시행하였을 때 광화되지 않은 전상아질층의 두께가 증가하고 치수 조직과 전상아질층내의 osteonectin 함량이 감소되며, 결국 에스트로겐 결핍은 조상아 세포의 기전을 변화시킨다고 할 수 있다. The purpose of this study was to investigate the effects of estrogen deficiency on pulpodentinal complex of tooth in ovariectomized rats. Thirty female Sprague- Dawley rats, 10 weeks old, were used. Rats were grouped into two groups. One group (n = 15) was subjected to sham surgery (SHAM) and the other group (n = 15) was ovariectomized bilaterally (OVX). Animals were sacrificed 12 weeks later, and their mandibular molars and associated periodontal supporting tissues were dissected out, and fixed in 10% buffered formalin. For comparison of groups, immunostained for osteonectin. Histomorphometrical measurement of change of teeth was performed using an image analysis system and paired t- test was used and the level of significance for overall differences was set at p < 0.05. In immunostaining of osteonectin, they were significantly different from each other. The predentin thickness in OVX rats was wider than in SHAM rats. And in SHAM rats, osteonectin was more specifically stained in predentin areas than in OVX rats. These results indicate that estrogen deficiency increased the unmineralized predentin areas and decreased osteonectin content in pulpal tissues in rats. If our result is applicable to human studies, odotoblast is affected by estrogen deficiency.

GO-31 : Steroid Receptor Activator induces tumor proliferation and invasion through the Notch pathway in the human ovarian cancer

( Hee Jung Kim ),( Seon Mi Baek ),( Hee Jin Nam ),( Miri Hyun ),( Ga Won Yim ),( Eun Ji Nam ),( Sunghoon Kim ),( Sang Wun Kim ),( Young Tae Kim ) 대한산부인과학회 2014 대한산부인과학회 학술대회 Vol.100 No.-

목적: Long non-coding RNAs (LncRNAs) have been recently found to be critical regulators of the epigenome. Steroid receptor RNA activator (SRA) ncRNA enhances nuclear receptor and myogenic differentiation 1 (MyoD)-mediated transcription but also participates in specific corepressor complexes. SRA RNA levels might affect some biological functions, such as proliferation, apoptosis, steroidogenesis, and myogenesis, has been reported. However, the exact function and mechanism of SRA in human ovarian cancer remains unclear. Here, we investigated that Notch signaling is hyperactivated in metastatic ovarian cancer cells that express SRA. 방법: SRA1 expression was determined by real-time RT-PCR. SRA1 was down-regulated by transfection with siRNA. The effects of SRA1 depletion as well as Notch pathway and their impact on ovarian cancer cell proliferation, migration and invasion were examined by qRT-PCR, wound healing, matrigel invasion chamber, western blotting and CCK-8 assays. 결과: The expression of SRA1 in ovarian cancer tissues was significantly higher than that in normal tissues. Real-time RT-PCR results showed high expression levels of SRA in SKOV3, TOV112D and OVCA429 human ovarian cancer cell lines. Knockdown of SRA decreased cell proliferation, migration, and invasion in OVCA429 cells. Additionally, SRA knockdown decreased the expression of vascular endothelial growth factor, matrix metalloproteinase-9 and epithelial-mesenchymal transition (EMT), which are important for cell motility and metastasis. Mechanistic investigation revealed that Notch1, Hes1 and p300 proteins could be inhibited by SRA depletion. 결론: These results suggest that SRA1 promotes tumor aggressiveness through the Notch pathway. It indicated that that SRA1 may serve as potential gene therapy in ovarian cancer.

GO-19 : Synergistic effect of COX-2 inhibitor on paclitaxel-induced apoptosis in the human ovarian cancer cell

( Hee Jung Kim ),( Ga Won Yim ),( Eun Ji Nam ),( Seon Mi Baek ),( Miri Hyun ),( Sunghoon Kim ),( Sang Wun Kim ),( Jae Wook Kim ),( Young Tae Kim ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

In vitro studies have revealed that treatment of various human cancer cell lines with specific cyclooxygenase inhibitor regulates apoptotic cell death. It is currently proposed that the combination of celecoxib (COX-2 inhibitor) with paclitaxel improves the efficacy of cancer treatment. Three ovarian cancer cell lines, OVCAR-3, SKOV3 and A2780, were exposed to paclitaxel and celecoxib. Cell viability was evaluated using a cell counting kit-8 assay. Apoptosis was evaluated using Annexin-V/7-AAD staining and cellular DNA fragmentation ELISA. Caspase-3 was examined by the Caspase-3 Colorimetric Assay kit. Caspase-9 and cleavage of poly ADP-ribose polymerase were determined by western blotting. Expression of nuclear factor-κB was assessed using Trans AM kits and immunofluorescence. Vascular endothelial growth factor and Akt activation were studied by RT-PCR and western blotting. A combination of celecoxib with paclitaxel augments anticancer effects more efficiently than paclitaxel alone as evidenced by decreased cell viability and enhanced apoptosis in OVCAR-3, SKOV3 and A2780 cells. Pretreatment with celecoxib also increased activation of caspase-9, -3 and cleaved PARP following paclitaxel-treatment. NF-κB activity assay revealed that activation of NF-κB induced by paclitaxel is downregulated by celecoxib. We also noted that celecoxib inhibited paclitaxel induced VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphory-lation of Akt. OVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib through downregulation of NF-κB and Akt activation, suggesting that celecoxib may work synergistically with paclitaxel to inhibit different targets and ultimately produce anticancer effects. Combining celecoxib with paclitaxel may represent a anti-ovarian cancer strategy.

Healthcare Workforce Response to The Coronavirus Disease Outbreak in Daegu, Korea: A Multi-Center, Cross-Sectional Survey

Kwon Hyun Hee,Kim Hye In,Kwon Ki Tae,Hwang Soyoon,Kim Shin-Woo,Kim Yoonjung,Kim Hyun ah,Hyun Miri,Hong Hyo-Lim,Kim Min Jung,Hur Jian,Hong Kyung Soo 대한감염학회 2022 Infection and Chemotherapy Vol.54 No.2

Background Securing an available healthcare workforce is critical to respond to coronavirus disease 2019 (COVID-19); however, research investigating Korea’s COVID-19 staffing response is rare. To present the fundamental data of healthcare staff in response to the surge in COVID-19 cases, we investigated the healthcare workforce response in Daegu, South Korea, which experienced the first largest outbreak of COVID-19 outside of China. Materials and Methods In response to the COVID-19 outbreak, this retrospective cross-sectional study analyzed data on the scale and characteristics of healthcare workers (HCWs). Additionally, it analyzed the clinical and epidemiological characteristics of HCWs infected with COVID-19 in six major teaching hospitals (five tertiary and one secondary) in Daegu from January 19 to April 30, 2020. Results During this study period, only 1.3% (n = 611) of the total hospitalized patients (n = 48,807) were COVID-19 inpatients, but they occupied 6.0% (n = 303) of the total hospital beds (n = 5,056), and 23.7% (n = 3,471) of all HCWs (n = 14,651) worked in response to COVID-19. HCWs participating in COVID-19-related works comprised 50.6% (n = 1,203) of doctors (n = 2,379), 26.3% (n = 1,571) of nurses (n = 5,982), and 11.4% (n = 697) of other HCWs (n = 6,108). Only 0.3% (n = 51) of HCWs (n = 14,651) developed COVID-19 infections from community-acquired (66.7%) or hospital-acquired (29.4%). Nurses were affected predominantly (33.3%), followed by doctors (9.8%), caregivers (7.8%), radiographers (5.9%), and others (45.1%), including nurse aides and administrative, facility maintenance, telephone appointment centers, and convenience store staff. All HCWs infected with COVID-19 recovered completely. The 32.7% (n = 333) of individuals (n = 1,018) exposed to HCWs who had COVID-19 were quarantined, and only one case of secondary transmission among them occurred. Conclusion The COVID-19 pandemic has necessitated significant staffing and facility usage, which is disproportionate to the relatively low number of COVID-19 inpatients, imposing a substantial burden on healthcare resources. Therefore, beyond the current reimbursement level of the Korean National Health Insurance, a new type of rewarding system is needed to prepare hospitals for the emerging outbreaks of infectious diseases. Keeping HCWs safe from COVID-19 is crucial for maintaining the healthcare workforce during a sudden massive outbreak. Further studies are needed to determine the standards of required HCWs through detailed research on the working hours and intensity of HCWs responding to COVID-19.

감염; 쯔쯔가무시 환자에서의 심전도 변화 및 임상 양상에 대한 고찰

김정민 ( Jeong Min Kim ),현미리 ( Miri Hyun ),김현아 ( Hyun Ah Kim ),김미경 ( Mi Kyung Kim ),김진영 ( Jin Young Kim ),권기영 ( Ki Young Kwon ),류성열 ( Seong Yeol Ryu ) 대한내과학회 2014 대한내과학회지 Vol.86 No.3

Background/Aims: Most scrub typhus patients have normal electrocardiography (ECG) findings. Recently, however, several cases with ECG changes were reported. However, few studies have examined the ECG changes in scrub typhus. Methods: The ECG and demographic data of patients infected with Orientia tsutsugamushi seen at Dongsan Medical Center from January 2008 to June 2012 were reviewed retrospectively. Patients with pre-existing cardiac disease were excluded. The initial and follow-up ECG findings, demographic characteristics, and laboratory findings was examined. Results: The group in which the initial ECG showed an arrhythmia had a higher blood urea nitrogen (BUN) level than the normal and ischemic groups (median 26.0 vs. 15.0 vs. 15.5 mg/dL, p = 0.041). The group with a sustained abnormality in the follow-up ECG had higher BUN (median 17.0 vs. 15.0 mg/dL, p = 0.022) and creatinine (median 1.30 vs. 0.90 mg/dL, p = 0.026) levels than the normal ECG group. In addition, the group with a sustained abnormality in the follow-up ECG had a higher rate of intensive care unit (ICU) admission (30.8% vs. 5.3%, p = 0.015) and longer treatment period (average 9 vs. 6 days, p = 0.027) than the other groups. Conclusions: In our study, more than 30% of the patients with scrub typhus showed ECG abnormalities. Those with an arrhythmic ECG change on presentation had high BUN levels. The sustained ECG abnormality group had high BUN and creatinine levels, and an increased ICU admission rate and length of stay. We should pay attention to the ECG findings on presentation and during the treatment of scrub typhus.

랑데부/도킹 기술검증용 위성 개발

김해동(Hae-Dong Kim),최원섭(Won-Sup Choi),조동현(Dong-Hyun Cho),김민기(Min-Ki Kim),김진형(Jin-Hyung Kim),심은섭(Eun-Sup Sim),임성민(Seongmin Lim),김지석(Ji-Seok Kim),정미리(Miri Jeong) 한국항공우주학회 2019 한국항공우주학회 학술발표회 논문집 Vol.2019 No.4

Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea

Shi Hye Jin,Nham Eliel,Kim Bomi,Joo Eun-Jeong,Cheong Hae Suk,Hong Shin Hee,Hyun Miri,Kim Hyun ah,Jang Sukbin,Rhee Ji-Young,Kim Jungok,Kim Sungmin,Cho Hyun Kyu,Wi Yu Mi,Cheon Shinhye,Kim Yeon-Sook,Lim 대한의학회 2022 Journal of Korean medical science Vol.37 No.22

Background: Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea. Methods: We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics. Results: During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m2 . Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m2 ), and the one remaining patient died from a secondary infection. Conclusion: About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

Clinical Characteristics and Risk Factors for Mortality in Critical COVID-19 Patients Aged 50 Years or Younger During Omicron Wave in Korea: Comparison With Patients Older Than 50 Years of Age

Shi Hye Jin,Yang Jinyoung,Eom Joong Sik,Ko Jae-Hoon,Peck Kyong Ran,Kim Uh Jin,Jung Sook In,Kim Seulki,Seok Hyeri,Hyun Miri,Kim Hyun Ah,Kim Bomi,Joo Eun-Jeong,Cheong Hae Suk,Jun Cheon Hoo,Wi Yu Mi,Kim 대한의학회 2023 Journal of Korean medical science Vol.38 No.28

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. Methods: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. Results: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m2 or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043–1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584–14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042–8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691–98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294–10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. Conclusion: Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.