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Background During the COVID-19 pandemic, nurses might experience added emotional stress. This study examined the relationship between gratitude and psychological stress to explore effective psychological support among nurses. Methods A cross-sectional survey assessed the level of psychological distress in 646 nurses in Gwangju, South Korea, using the Perceived Stress Scale-10 (PSS-10), Gratitude Questionnaire-6 (K-GQ-6), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Maslach Burnout Inventory-General Survey (MBI-GS). Sociodemographic factors and COVID-19-related experiences were also examined. A linear regression model was used to determine the factors influencing perceived stress. Results The mean PSS-10 score was 19.0 ± 4.4. Linear regression analyses revealed that the MBI-GS-Exhaustion, PHQ-9, and GAD-7 scores were positively associated with perceived stress, while the MBI-GS-Professional efficacy score was inversely associated with perceived stress. Gratitude disposition using the K-GQ-6 score negatively predicted PSS-10 (β = 0.829, p Conclusions Psychological interventions that help cultivate gratitude and professional efficacy among nurses can help promote stress resilience throughout the course of the COVID-19 pandemic.

Summary Background There is growing evidence that super-spreading events (SSEs) and multiple-spreading events (MSEs) are a characteristic feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, data regarding the possibility of SSEs or MSEs in healthcare settings are limited. Methods This study was performed at a tertiary-care hospital in Korea. We analysed the nosocomial COVID-19 cases that occurred in healthcare workers and inpatients and their caregivers between January and 20th December 2020. Cases with two to four secondary cases were defined as MSEs and those with five or more secondary cases as SSEs. Findings We identified 21 nosocomial events (single-case events, N = 12 (57%); MSE + SSE, N = 9 (43%)) involving 65 individuals with COVID-19. Of these 65 individuals, 21 (32%) were infectors. The infectors tended to have a longer duration between symptom onset and diagnostic confirmation than did the non-infectors (median two days vs zero days, P=0.08). Importantly, 12 (18%) individuals were responsible for MSEs and one (2%) for an SSE, which collectively generated 35 (54%) secondary cases. Conclusion In a hospital with thorough infection-control measures, approximately 70% of the nosocomial cases of COVID-19 did not generate secondary cases, and one-fifth of the infectors were responsible for SSEs and MSEs, which accounted for approximately half of the total cases. Early case identification, isolation, and extensive contact tracing are important for the prevention of transmission and SSEs.

The purpose of this study is to examine the relationships among social support, parenting stress, and depression in single mothers with young children in South Korea. This study also explores whether parenting stress plays a mediating role in the relationship between social support and depression. Self-report questionnaires were administered to 202 South Korean mothers who were raising young children on their own because of divorce, separation, death, or having never married, and three research variables were measured: social support, parenting stress, and depression. Data were analyzed using PROCESS macro version 3.4 to examine whether parenting stress mediated the relationship between social support and depression in these single mothers. The results of this study showed close correlations among social support, parenting stress, and depression in single mothers, and that parental distress and parent-child dysfunctional interaction among the subfactors of parenting stress played a mediating role in the relationship between social support and depression. Because the results of this study indicate that providing social support for single mothers can reduce their depression, significant attention must be paid to implementing policies to reduce single mothers’ parenting stress for their psychological well-being and their children’s development.

Background: Metabolic syndrome (MetS) is closely associated with the aging process. However, changes in metabolic conditions and cardiac function that occur in middle aged population remain unclear. We evaluated longitudinal changes in metabolic parameters and cardiac function during a 3-year period in subjects with suspected MetS.Methods: We studied 191 participants with suspected MetS at baseline and after 3 years. Anthropometric parameters, including waist circumference (WC), and metabolic parameters, including fasting blood glucose and lipid profile were measured. Conventional echocardiography with two-dimensional speckle tracking was performed.Results: Mean age was 56.2±4.4 years, and there were 97 women (50.8%). Men had increased WC and triglycerides (TG) (WC 91.2±6.8 cm vs. 84.0±8.0 cm, P

BACKGROUND AND AIM Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long-term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. METHODS Treatment-naive chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were used to determine fibrotic burden. RESULTS In the entire population (n = 3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P

Background The aim of this study was to verify the safety and feasibility of our selection criteria for middle hepatic vein (MHV) reconstruction in living donor liver transplantation (LDLT) using right lobe grafts. Methods A total of 153 LDLTs were performed using right lobe grafts in a tertiary hospital from 2006 to 2016. Among them, 52 cases without MHV reconstruction were compared with 101 recipients who underwent LDLT using right lobe graft with MHV reconstruction. Both groups were compared regarding indications for reconstruction, short-term and long-term complications, operative details, and outcomes. Results The two groups differed only in cold ischemic time (108.19 ± 49.81 minutes vs 146.37 ± 58.74 minutes) preoperatively. Short-term posttransplant outcomes, long-term overall survival, and long-term disease-free survival showed no significant differences between the 2 groups. After propensity score matching for both groups with and without MHV reconstruction to eliminate selection bias, the 2 groups were comparable. Conclusions We found that our selection criteria for performing MHV reconstruction in LDLT using right lobe graft were feasible and safe. A routine MHV reconstruction is not necessary if the right lobe graft graft-to-recipient weight ratio is ≥1.0, right hepatic vein draining territory volume is ≥0.8, and recipient Model for End-Stage Liver Disease score is

Background: Fecal microbiota transplantation against gut colonization using a multidrugresistant organism is a technique used to treat infections through normalizing the gut microbiota via fecal microbiota transplantation in patients with confirmed colonization by carbapenem-resistant Enterobacteriaceae (CRE) or vancomycin-resistant enterococci (VRE) based on a fecal culture test within the past one week. In this study, we aimed to determine the safety and effectiveness of this technique. Methods: The safety and effectiveness were assessed via a systematic review. A literature search was conducted using five Korean databases, such as KoreaMed, and international databases, including Ovid-MEDLINE, Ovid-EMBASE, and Cochrane Library. Results: Main results are described here. From the studies retrieved using the aforementioned search strategy, the remaining 581 studies were screened using the inclusion and exclusion criteria, resulting in the selection of nine studies for further consideration. In terms of safety, many studies reported deaths and adverse reactions associated with different causes. Fewer studies reported the rate of colonization; however, the effect of colony rate was inconsistent when compared to no treatment group. Additionally, none of the studies assessed the recurrence rate, a decrease in the prevalence of diseases related to infection by multidrugresistant bacteria, and the quality of life. Conclusion: Fecal bacterial colonization for the decolonization of intestinal multidrugresistant bacteria was evaluated using a technique that requires further research as there is insufficient literature evidence to validate its safety and efficacy in treating infections through normalizing the intestinal flora of patients with confirmed colonization by CRE or VRE.

Genetic and nutritional factors contribute to the development of non-alcoholic fatty liver disease (NAFLD); however, gene-diet interactions in NAFLD development are poorly understood. In this case-control study, a large dataset from the Korean Genome and Epidemiology Study cohort (

Background The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum β-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia. Methods Data from pediatric patients aged ≤ 18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia at Asan Medical Center Children’s Hospital, Seoul, Korea between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by the sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables. Results A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n = 29) and K. pneumoniae (n = 24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure on day 2 and 30-day all-cause mortality [adjusted odds ratio (OR) 1.0; 95% confidence interval (CI) 0.22–4.88, and adjusted OR 0.1; 95% CI 0.01–1.56]. Conclusions The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible.

We investigated whether baseline and on-treatment alanine aminotransferase (ALT) levels during entecavir (ETV) therapy are associated with achieving subcirrhotic liver stiffness (LS) and hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV)-related cirrhosis.We analyzed data from 347 treatment-naïve patients with HBV-related cirrhosis, who started ETV between 2006 and 2011 and were followed up for5 years without developing HCC. The study outcomes were achieving subcirrhotic LS at 5 years of ETV, and risk of HCC development beyond 5 years of ETV. Subcirrhotic LS was defined as12 kPa by transient elastography.After 5 years of ETV, 227 (65.4%) patients achieved subcirrhotic LS. During a median follow-up of 9.2 years, 49 (14.1%) patients developed HCC beyond 5 years of ETV. ALT levels at baseline, at 1 year of ETV therapy, and 5 years of ETV therapy were not associated with the probability of achieving subcirrhotic LS at 5 years of ETV therapy or risk of HCC development beyond 5 years of ETV therapy (all P.05). Patients achieving subcirrhotic LS at 5 years of ETV therapy had significantly lower risk of HCC development than those who did not (adjusted hazard ratio, 0.33; 95% confidence interval, 0.17-0.64; P = .001).Baseline and on-treatment ALT levels were not associated with achieving subcirrhotic LS at 5 years of ETV therapy or with risk of HCC development beyond 5 years of ETV therapy in patients with HBV-related cirrhosis. Achieving subcirrhotic LS at 5 years of ETV therapy was independently associated with lower risk of HCC development beyond 5 years of ETV therapy.

Hyperoxia is frequently used for treating acute respiratory failure, but it can cause acute lung injury. Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is localized in mitochondria and related to reactive oxygen species production, inflammation, and apoptosis, which are the features of hyperoxic acute lung injury (HALI). However, the contribution of NLRX1 in HALI has not been addressed, so we designed to demonstrate the role of NLRX1 in hyperoxia. A murine model of HALI was generated in wild-type mice (WT) and NLRX1−/− mice by exposing them to over 95% oxygen for 72 h. As a result, NLRX1 expression was elevated in mice exposed to hyperoxia. In acute lung injury, levels of inflammatory cells, protein leakage, cell cytotoxicity, and pro-inflammatory cytokines were diminished in NLRX1−/− mice compared to WT mice. In survival test, NLRX1−/− mice showed alleviated mortality under hyperoxic conditions, and apoptotic cell death and caspase expression and activity were reduced in NLRX1−/− mice. Furthermore, levels of MAPK signaling proteins ERK 1/2, JNK, and p38 were decreased in NLRX1-deficient mice than in WT mice exposed to hyperoxia. This study reveals that the genetic deficiency of NLRX1 dampens hyperoxia-induced apoptosis, suggesting NLRX1 acts as a pivotal regulator of HALI.

We retrospectively examined all initial positive SARS-CoV-2 test results using three real-time PCR tests from patients without a history of COVID-19 collected from September to October 2021 at a university-affiliated hospital.We defined a possible false-positive (PFP) case as a positive case that showed negative results upon per-forming a confirmatory test on the same specimen. Positivity% and PFP% were defined as the number of first positive and the number of PFP cases divided by the total test numbers, respectively.The positivity%/PFP% values were 0.76%/0.10%, 0.29%/0.02%, and 0.21%/0.03% for the Xpert, Allplex, and cobas tests, respectively. Six (75%) cobas PFP cases were RdRp-only positive. All PFP cases analyzed by Xpert except one had cycle threshold values ≥ 40. Contamination during extraction was suspected in five of the 10 PFP cases analyzed by Allplex, which requires a separate extraction step.Care must be taken when analyzing first-positive cases as these may be false-positive signals.

Background Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. Methods This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. Discussion This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. Trial registration The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.

Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the progression of diabetic kidney disease. However, the mechanisms underlying this renoprotective benefit are not completely understood. We evaluated whether SGLT2 inhibition reduces cellular senescence in the kidney and investigated the molecular pathways involved in the renoprotective effect. Materials and methods Dapagliflozin (1 mg/kg), glimepiride (2.5 mg/kg), or vehicle was administered daily via oral gavage for 8 weeks in db/db mice. Expression levels of ageing marker genes (p21, p16, and p53) and oxidative stress were measured in the kidney using real-time RT-PCR, immunohistochemistry, and western blot analysis. For in vitro analysis, HK-2 cells, a human renal tubular epithelial cell line, were pretreated with H2 O2 to induce cellular senescence, and the levels of ageing markers were measured after treatment with β-hydroxybutyrate (β-HB) or NRF2-specific siRNA. Results Expression levels of ageing marker genes (p21, p16, and p53) and senescence-associated secretory phenotypes of the kidney were increased in the vehicle-treated db/db (db/db+vehicle) group compared with the db/+ group, and this increase was markedly reversed in the dapagliflozin-treated db/db (db/db+SGLT2i) group, but not in the glimepiride-treated db/db (db/db+SU) group. In the kidneys of mice in the db/db+SGLT2i group, oxidative stress and DNA damage were also reduced compared with those in the db/db+vehicle and db/db+SU groups. Dapagliflozin increased plasma β-HB, which reduced H2 O2 -induced DNA damage and senescence in HK-2 cells. β-HB-induced NRF2 nuclear translocation mediated anti-senescent effects by inducing antioxidant pathways. Conclusions Dapagliflozin prevented the progression of diabetic kidney disease by inhibiting cellular senescence and oxidative stress via ketone-induced NRF2 activation. This article is protected by copyright. All rights reserved.

Prospective data are limited regarding dynamic adulthood weight changes and hepatocellular carcinoma (HCC) risk. We included 77,238 women (1980–2012) and 48,026 men (1986–2012), who recalled young-adult weight [age 18 years (women); 21 years (men)], and provided biennially updated information regarding weight, body mass index (BMI), and comorbidities. Overall adulthood weight change was defined as the difference in weight (kilograms) between young-adulthood and present. Using Cox proportional hazards models, we calculated multivariable adjusted HRs (aHR) and 95% confidence intervals (CI). Over 3,676,549 person-years, we documented 158 incident HCC cases. Elevated HCC risk was observed with higher BMI in both young-adulthood and later-adulthood [continuous aHRs per each 1 unit = 1.05; 95% CI = 1.02–1.09 (Ptrend = 0.019), and 1.08; 95% CI = 1.06–1.10 (Ptrend = 0.004), respectively]. Moreover, overall adulthood weight gain was also significantly associated with increased HCC risk (aHR per each 1-kg increase = 1.03; 95% CI = 1.01–1.08; Ptrend = 0.010), including after further adjusting for young-adult BMI (Ptrend = 0.010) and later-adult BMI (Ptrend = 0.008). Compared with adults with stable weight (±5 kg), the multivariable-aHRs with weight gain of 5– Prevention Relevance: Our data suggest that maintaining a stable weight during adulthood, specifically by preventing weight gain, could represent an important public health strategy for the prevention of hepatocellular carcinoma.

Heart failure with preserved ejection fraction (HFpEF) is a significantly symptomatic disease and has a poor prognosis similar to that of heart failure with reduced ejection fraction (HFrEF). Contrary to HFrEF, HFpEF is difficult to diagnose, and the recommended diagnostic algorithm of HFpEF is complicated. Several therapies for HFpEF have failed to reduce mortality or morbidity. HFpEF is thought to be a complex and heterogeneous systemic disorder that has various phenotypes and multiple comorbidities. Therefore, therapeutic strategies of HFpEF need to change depending on the phenotype of the patient. This review highlights the pharmacologic and nonpharmacologic treatment of HFpEF.

Abnormal bowel movements have been related to a variety of hepatocellular carcinoma (HCC) risk factors such as dyslipidemia, diabetes and altered metabolism of bile acids and gut microbiota. However, little is known about whether bowel movement frequency affects the risk of developing HCC. We followed 88 123 women in the Nurses' Health Study (NHS) and 28 824 men in the Health Professionals Follow-up Study (HPFS) for up to 24 years. The Cox proportional hazards regression model was used to calculate multivariable hazard ratios (HRs) and confidence intervals (95%CI). We documented 101 incident HCC cases. Compared to those with daily bowel movements, participants with bowel movement more than once per day had a multivariable HR of 1.93 (95%CI: 1.18 to 3.16) in the pooled cohorts. For the same comparison, the positive association appeared stronger for men (2.72, 95% CI: 1.14 to 6.44) than for women (1.63, 95% CI: 0.87 to 3.06) but there was no statistically significant heterogeneity by sex (P-value = .31). We found null associations between bowel movement every 2 days or less and the risk of HCC (HR = 1.05, 95%CI: 0.62 to 1.79). The HR (95%CI) for participants who used laxatives regularly relative to those who never used laxatives was 1.00 (0.64 to 1.55). Our results suggest participants with bowel movement more than once daily is associated with a higher risk of developing HCC compared to those with daily bowel movements. These findings need to be confirmed and potential mechanisms underlying this association need to be elucidated.

The clinical significance of Clostridium tertium bacteremia is still uncertain. We evaluated the incidence, clinical characteristics, and outcomes of C. tertium bacteremia and identified differences between neutropenia and non-neutropenia. All adult patients with C. tertium bacteremia in a 2700-bed tertiary center between January 2004 and November 2021 were retrospectively enrolled. The first episode of C. tertium bacteremia in each patient was included in the analysis. Among 601 patients with Clostridium species bacteremia, 62 (10%) had C. tertium bacteremia, and of these 62 patients, 39 (63%) had had recent chemotherapy, and 31 (50%) had neutropenia or hematologic malignancy. C. tertium bacteremia originated frequently from a gastrointestinal tract infection such as enterocolitis (34%), primary bacteremia (29%), and secondary peritonitis (18%), and 34% of patients had polymicrobial bacteremia. Hematologic malignancy, prior antibiotic treatment, neutropenic enterocolitis, and primary bacteremia were significantly associated with C. tertium bacteremia in neutropenic patients, whereas solid tumor, hepatobiliary disease, secondary peritonitis, polymicrobial bacteremia, and a higher frequency of eradicable infection foci were significantly associated with C. tertium bacteremia in non-neutropenic patients. There was 15% 30-day mortality. APACHE II score (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-2.1) and secondary peritonitis (aOR, 25.9; 95% CI, 3.0-224.7) were independent risk factors for 30-day mortality. The prevalence of C. tertium bacteremia is low, and the characteristics of C. tertium bacteremia are significantly different between neutropenic and non-neutropenic patients. Appropriate investigation for gastrointestinal mucosal injury should be performed to improve treatment outcomes in this form of bacteremia.

Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced using a Nextera DNA Flex Kit (Illumina) and the MiseqDx (Illumina) instrument. All isolates harbored the same Msh2p substitution, V239L, associated with multilocus sequence type 7 and a Pdr1p substitution, L825P, that caused azole resistance. Of six isolates with increased AMB MICs (≥2 mg/L), three harboring the Erg6p A158fs mutation had AMB MICs ≥ 8 mg/L, and three harboring the Erg6p R314K, Erg3p G236D, or Erg3p F226fs mutation had AMB MICs of 2–3 mg/L. Four isolates harboring the Erg6p A158fs or R314K mutation had fluconazole MICs of 4–8 mg/L while the remaining six had fluconazole MICs ≥ 256 mg/L. Two isolates with micafungin MICs > 8 mg/L harbored Fks2p (I661_L662insF) and Fks1p (C499fs) mutations, while six isolates with micafungin MICs of 0.25–2 mg/L harbored an Fks2p K1357E substitution. Using WGS, we detected novel mechanisms of AMB and echinocandin resistance; we explored mechanisms that may explain the complex relationship between AMB and azole resistance.

배경: SARS-CoV-2 실시간 역전사 중합효소연쇄반응(rRT-PCR) 검사에서 미결정 결과는 하나 이상의 표적 유전자가 양성이나 전부 양성은 아닌 경우로, 임상 검사실에서 결과를 판독할 때 문제가 된다. 이에 미결정 결과의 원인과 임상적 의의를 분석하였다.방법: rRT-PCR은 E, RdRp, N 등 3가지 표적유전자를 갖춘 Allplex 2019-nCoV assay(Seegene Inc., Korea)로 실시하였다. 2020년 3월부터 6월까지 발생한 모든 미결정 결과에 대해서 lot 번호별 발생빈도, 검체종류, 증폭 곡선의 Ct 및 peak 값, 양성 표적 유전자, 추적 검사와 재검 결과를 분석하였다.결과: 총 43,268건의 검사가 시행되었고, 93건의 미결정 결과를 얻었다. 그 중 49건이 11명의 코로나 19 확진자에서 나왔고, 44건이 비확진자에서 나왔다. 확진자는 미결정결과가 진단 후 11.9 ± 4.7일 뒤 나타났고, 그로부터 8.8 ± 5.5일 뒤에 음성으로 전환되었다. 비확진자에서는 재검 결과 모두 음성이었고, 81.8%가 총 8개 lot 중 2개에서 발생했다. 미결정 결과에서 가장 많이 검출된 표적 유전자는 확진자에서는 N (55.4%), 비확진자에서는 RdRp (61.2%)였다. 증폭 곡선의 Ct값과 peak은 COVID-19 확진자와 비확진자 사이에 차이는 없었다.결론: 미결정 결과는 양성이나 음성으로 보고해서는 안되며, COVID-19 확진자의 경우 재검 없이 바로 미결정 결과로 보고하고, 비확진자 또는 신환의 경우 재검을 해서 확인하여 보고한다.

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 naive 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.

Background: The efficacy of non-carbapenems as an empirical antibiotic for extended-spectrum β-lactamases (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia in children remains controversial. We compared clinical and microbial outcomes according to the types of empirical antibiotics for treating pediatric patients with ESBL-producing E. coli and K. pneumoniae bacteremia.Methods: Data from pediatric patients aged ≤18 years who were hospitalized with monomicrobial ESBL-producing E. coli or K. pneumoniae bacteremia between January 2014 and May 2019 were analyzed retrospectively. The impact of empirical therapy was assessed as 30-day all-cause mortality and 2-day microbiological outcomes evaluated by sterility of blood cultures collected on day 2 after empirical antibiotic administration. Logistic regression analysis was used to control for the effects of confounding variables.Results: A total of 53 patients with bacteremia caused by ESBL-producing E. coli (n=29) and K. pneumoniae (n=24) were included in this study; the median age was 3.6 years, and all had underlying comorbidities. As empirical antibiotics, 27 patients were treated with meropenem, and non-carbapenem agents were administered to 26 patients; 84.6% (22/26) were converted to carbapenem antibiotics as the definitive antibiotic by day 2 after empirical antibiotic administration. Overall, the 30-day all-cause mortality of ESBL-producing E. coli and K. pneumoniae bacteremia was 17.0% (9/53). After adjustment, there was no statistically significant association of use of a non-carbapenem agent as an empirical antibiotic with microbiological failure at day 2 and 30-day all-cause mortality [adjusted odds ratio (OR), 1.0; 95% confidence interval (CI), 0.22–4.88, and adjusted OR, 0.1; 95% Cl, 0.01–1.56].Conclusions: The empirical use of non-carbapenems might not be a risk factor for mortality and early microbiological outcomes in pediatric patients with ESBL-producing E. coli and K. pneumoniae BSI if early transition to appropriate antimicrobial therapy was possible.

It is unclear whether changes in lipid profile and liver biochemistry are associated with advanced fibrosis.Patients diagnosed with non-alcoholic fatty liver disease (NAFLD) between 2009 and 2017 were included. The changes in blood tests were calculated as follows: [(value at 6 months - value at baseline)/value at baseline] × 100. The endpoint was advanced fibrosis determined by the NAFLD fibrosis score, calculated every year from diagnosis until 2019. Cox proportional hazards models were used to identify factors predicting advanced fibrosis.After a median follow-up of 31.7 (19.4-50.8) months, advanced fibrosis occurred in 64 (6.3%) of 1021 patients. Gamma-glutamyl transpeptidase (GGT) levels (72.9 vs 51.1 IU/L; P = 0.23) and ΔGGT (+6.0% vs -6.9%; P = 0.06) were higher in the advanced fibrosis group. ΔGGT (hazard ratio [HR] 1.03; P 0.001) was significantly associated with advanced fibrosis after adjusting for age and platelet count. The positive ΔGGT group showed a higher incidence of advanced fibrosis and the 1-standard deviation increment in ΔGGT showed a significant association with advanced fibrosis both in statin users (HR, 1.35) and in non-users (HR, 1.31; Ps 0.05). The restricted cubic spline model identified a positive correlation between ΔGGT and the NAFLD fibrosis scores (P 0.001). ΔGGT showed sensitivity of 64.2%, specificity of 52.6%, and negative predictive value of 98.3% in predicting advanced fibrosis.ΔGGT calculated at 6 months following NAFLD diagnosis is associated with advanced fibrosis.

The prevalence of food allergy, triggered by T-helper type 2 (Th2) cell-mediated inflammation, is increasing worldwide. Interleukin (IL)-18 plays an important role in inflammatory diseases by binding with the IL-18 receptor. IL-18/IL-18 receptor α (IL-18Rα) is a cofactor for immunoglobulin E (IgE) production and Th2 cell development. Studies have not investigated the association between the IL-18/IL-18Rα signaling pathway and food allergy. Here, we investigated the role of IL-18Rα in food allergy induction and development.Wild-type (WT) and IL-18Rα-null mutant (IL-18RαIL-18Rα expression was increased in WT mouse intestines after OVA treatment. Food allergy-induced IL-18RαIL-18Rα regulates allergic reactions and immune responses by regulating T cell responses in food allergies. Moreover, IL-18Rα is involved in the STAT/SOCS signaling pathways. Targeting IL-18Rα signaling might be a novel therapeutic strategy for food allergy.

Background and Aims Robust evidence regarding the impact of disease activity on pregnancy outcomes in women with inflammatory bowel disease [IBD] is crucial for both clinicians and patients in preparing a birth plan. We sought to perform a systematic review and meta-analysis to assess the pooled influences of disease activity on pregnancy outcomes in women with IBD. Methods We searched MEDLINE, EMBASE and the COCHRANE library to identify articles comparing pregnancy outcomes between active and inactive IBD at the time of conception or during pregnancy. A meta-analysis was performed using a random-effects model to pool estimates and report odds ratios [ORs]. Results A total of 28 studies were identified as eligible for the meta-analysis. In women with active IBD, the pooled ORs for low birth weight [LBW], preterm birth, small for gestational age [SGA], spontaneous abortion and stillbirths were respectively 3.81 (95% confidence interval [CI] 1.81–8.02), 2.42 [95% CI 1.74–3.35], 1.48 [95% CI 1.19–1.85], 1.87 [95% CI 1.17–3.0] and 2.27 [95% CI 1.03–5.04] compared to women with inactive IBD. In the subgroup analysis based on disease type, women with active ulcerative colitis had an increased risk of LBW, preterm birth and spontaneous abortion. Women with active Crohn’s disease had a higher risk of preterm birth, SGA and spontaneous abortion. Conclusions Active IBD during the periconception period and pregnancy is associated with an increased risk of adverse pregnancy outcomes. Our data suggest that pregnancy should be planned when the disease is quiescent, and continuous disease control is important even during pregnancy.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early detection of COVID-19 and immediate isolation of infected patients from the naive population are important to prevent further pandemic spread of the infection. Real-time reverse transcription (RT)-PCR to detect SARS-CoV-2 RNA is currently the most reliable diagnostic method for confirming COVID-19 worldwide. Guidelines for clinical laboratories on the COVID-19 diagnosis have been recently published by Korean Society for Laboratory Medicine and the Korea Centers for Disease Control and Prevention. However, these formal guidelines do not address common practical laboratory issues related to COVID-19 real-time RT-PCR testing and their solutions. Therefore, this guideline is intended as a practical and technical supplement to the "Guidelines for Laboratory Diagnosis of COVID-19 in Korea".

Several prediction scores for the early detection of hepatocellular carcinoma (HCC) are available. We validated the predictive accuracy of age, albumin, sex, liver cirrhosis (AASL), RESCUE-B, PAGE-B and modified PAGE-B (mPAGE-B) scores in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF). Between 2007 and 2014, 3171 patients were recruited (1645, ETV; 1517, TDF). The predictive accuracy of each prediction score was assessed. The mean age of the study population (1977 men; 1194 women) was 48.8 years. Liver cirrhosis was present in 1040 (32.8%) patients. During follow-up (median, 58.2 months), 280 (8.8%) patients developed HCC; these patients were significantly older; more likely to be male; had significantly higher proportions of liver cirrhosis, hypertension and diabetes; and had significantly higher values for the four risk scores than those who did not develop HCC (all P < .05). Older age (hazard ratio [HR] = 1.048), male sex (HR = 2.142), liver cirrhosis (HR = 3.144) and prolonged prothrombin time (HR = 2.589) were independently associated with an increased risk of HCC (all P < .05), whereas a higher platelet count (HR = 0.996) was independently associated with a decreased risk of HCC (P < .05). The predictive accuracy of AASL score was the highest for 3- and 5-year HCC predictions (areas under the curve [AUCs] = 0.818 and 0.816, respectively), followed by RESCUE-B, PAGE-B and mPAGE-B scores (AUC = 0.780-0.815 and 0.769-0.814, respectively). In conclusion, four HCC prediction scores were assessed in Korean CHB patients treated with ETV or TDF. The AASL score showed the highest predictive accuracy.

Chemotherapy has led to improved survival in patients with breast cancer; however, it is associated with an increased risk of cardiac dysfunction and heart failure. We investigated the protective effects of rosuvastatin and candesartan, alone and in combination, in a doxorubicin- and trastuzumab-induced rat model of cardiomyopathy.Forty-two rats were allocated into six groups (G1-G6): G1, control; G2, doxorubicin only; G3, doxorubicin + trastuzumab; G4, doxorubicin + trastuzumab + rosuvastatin; G5, doxorubicin + trastuzumab + candesartan; and G6, doxorubicin + trastuzumab + rosuvastatin + candesartan. Doxorubicin and trastuzumab were sequentially administered for 28 days. Left ventricular end-systolic dimension and longitudinal strain (LS) were assessed via echocardiography. Left ventricular (LV) performance was evaluated using a microcatheter in the LV apex on day 28. Blood for biomarker analysis was collected from the inferior vena cava before sacrifice.Doxorubicin in combination with trastuzumab increased the LV end-systolic dimension but worsened LS compared with the control group (all P .05). The level of C-reactive protein was lower in the rosuvastatin treatment group (P = .007) than in the controls but not in the candesartan treatment group. Both rosuvastatin and candesartan attenuated the increase in glutathione. Candesartan treatment improved +dP/dt (P = .011), whereas rosuvastatin did not. In the combination treatment group, the worsening of LS was significantly attenuated compared with that in either the rosuvastatin or candesartan group (all P .05).In a rat model of doxorubicin- and trastuzumab-induced cardiomyopathy, rosuvastatin alleviated systemic inflammation, while candesartan improved LV performance. Combination therapy with rosuvastatin and candesartan demonstrated additional preventive effects on myocardial strain. The protective mechanisms of rosuvastatin and candesartan appear to be different but complementary in chemotherapy-induced cardiomyopathy.

Biodegradable porous microspheres, which were initially used as supports for cell growth, are known to have the advantages of maintaining a differentiated cell phenotype and allowing for cell expansion owing to their large surface area. The use of porous microspheres ensures good retention of engrafted cells as platforms for cell delivery. In this study, injectable and porous poly(D, L-lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a microfluidic system. These microspheres had a relatively uniform size and a porous and interconnected internal structure. The prepared PLGA microspheres were used as stem cell carriers for therapy. Here, we demonstrated the feasibility of mesenchymal stem cell (MSC)-loaded microspheres as cell therapy agents for liver damage. The results obtained from a chemically induced liver damage model showed that MSC-loaded microspheres effectively promoted liver recovery. These findings clearly show the feasibility of using injectable microspheres for the therapy and regeneration of tissues.

In this study, we investigated the hepatoprotective properties of 3,5-dicaffeoylquinic acid (DQA), a polyphenolic compound from green coffee beans, against dimethylnitrosamine (DMN)-induced hepatic fibrosis rat models. DQA, up to 10 μM concentration, did not exhibit any cytotoxic effect on Chang liver cells and Huh7 cells. DMN-treated rats showed typical biological symptoms of hepatic fibrosis, i.e., loss of body weight and pathological elevation of serum biomarkers for hepatic function. However, oral administration of DQA recovered body weight, and maintained serum biochemical markers such as albumin, bilirubin, ALP, ALT and AST in the normal range. Notably, histological and western assay proved DQA significantly alleviated collagen accumulation (α-smooth muscle actin, alpha 1 collagen type I) in liver tissue. The upregulated tissue expression of erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) suggested DQA upregulated the representative antioxidant enzymes and ameliorated the progression of hepatic fibrosis in DMN-treated rats.

Aim Abundant evidence indicates that estrogen (E2) plays a protective role against hypertension. Yet, the mechanism underlying the antihypertensive effect of E2 is poorly understood. In this study, we sought to determine the mechanism through which E2 inhibits salt-dependent hypertension. Methods and results To this end, we performed a series of in-vivo and in-vitro experiments employing a rat model of hypertension that is produced by deoxycorticosterone acetate (DOCA)-salt treatment after uninephrectomy. We found that E2 prevented DOCA-salt treatment from inducing hypertension, raising plasma arginine-vasopressin (AVP) level, enhancing the depressor effect of the V1a receptor antagonist (Phenylac1, D-Tyr(Et)2, Lys6, Arg8, des-Gly9)-vasopressin, and converting GABAergic inhibition to excitation in hypothalamic magnocellular AVP neurons. Moreover, we obtained results indicating that the E2 modulation of the activity and/or expression of NKCC1 (Cl- importer) and KCC2 (Cl- extruder) underpins the effect of E2 on the transition of GABAergic transmission in AVP neurons. Lastly, we discovered that, in DOCA-salt-treated hypertensive ovariectomized rats, CLP290 (prodrug of the KCC2 activator CLP257, intraperitoneal injections) lowered blood pressure and plasma AVP level and hyperpolarized GABA equilibrium potential to prevent GABAergic excitation from emerging in the AVP neurons of these animals. Conclusion Based on these results, we conclude that E2 inhibits salt-dependent hypertension by suppressing GABAergic excitation to decrease the hormonal output of AVP neurons. Translational perspective Numerous studies have shown that sex steroids can impact blood pressure (BP) and premenopausal women have a lower incidence of hypertension than age-matched men. Postmenopausal women no longer enjoy this beneficial difference. The causal mechanisms are not clear and hormone replacement therapy with estradiol (E2) does not consistently lower BP in postmenopausal women. In this study we showed that rats treated with CLP290 to control GABAergic excitation in AVP neurons have the same phenotype as E2-supplemented rats in BP and plasma AVP level. This result indicates that CLP290 leverages the same pathway of E2 protective effects against salt-dependent hypertension, and therefore, raises the possibility that classes of drugs like CLP290 may have some utility as alternative antihypertensives in persons resistant to or contraindicated for E2 therapy.

The risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment-naive patients with chronic hepatitis B (CHB) receiving entecavir 0.5 mg/d were stratified into three groups according to entecavir start time: early (2007-2010), middle (2011-2012) and late (2013-2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5 years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n = 672); 1.5%, 5.1% and 8.9% (middle cohort; n = 757); and 1.2%, 5.3% and 10.6% (late cohort; n = 1013; P > .05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child-Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis (P

Objective In the absence of standardized methods for Mycoplasma pneumoniae detection, we evaluated the diagnostic value of polymerase chain reaction (PCR) and IgM assays for detecting M. pneumoniae infection in children during a recent Korean outbreak. Methods The diagnostic performances of PCR and IgM assays for M. pneumoniae in 1,109 clinical specimens were evaluated by the Japanese Respiratory Society (JRS) scoring system as an interim reference standard. Results The level of agreement between both tests was fair. As analyzed by the JRS scoring system, the sensitivity of PCR was 45.2% in the group aged Conclusion The sensitivity of PCR is relatively low but is superior to that of IgM assays such that diagnostic performance can be improved by both test methods in patients aged