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Conflicting results have been reported regarding which of entecavir (ETV) or tenofovir disoproxil fumarate (TDF) is associated with better outcomes. Chronic hepatitis B patients who started ETV or TDF between 2010 and 2015 were analysed. The primary outcomes were hepatocellular carcinoma and death and transplantation. The impact of the treatment on the primary outcomes was analysed using Cox proportional hazards models in the entire and propensity score-matched cohorts. A total of 404 patients (180 and 224 in the ETV and TDF groups, respectively) were analysed. The median duration of follow-up was significantly longer in the ETV group (64.0 vs. 49.1 months; P P = 0.018) and sustained virological suppression (59.7% vs. 45.2%; P = 0.005) were significantly higher in the TDF group. TDF was associated with lower hepatocellular carcinoma [hazard ratio (HR) 0.31, 95% confidence interval (95% CI), 0.12‒0.79; P = 0.014]; however, statistical significance was not reached after adjusting sustained virological suppression using propensity score matching (HR 0.36, 95% CI 0.12‒1.14; P = 0.08). Death and transplantation was comparable. In conclusion, the impact of TDF on the lower hepatocellular carcinoma was blunted after adjusting sustained virological suppression. Further comparison in a larger number of patients who show sustained virological suppression over a longer period of time is needed.

Data regarding extraintestinal Clostridioides difficile infections (ECDIs) remain scarce and anecdotal. We conducted a retrospective cohort study to investigate characteristics and prognostic factors in patients with ECDI. From January 1997 through December 2018, 60 patients were enrolled and divided into three groups as follows: group A (gastrointestinal [GI] disruption caused by malignancy, n = 13); group B (GI disruption from causes other than malignancy, n = 25); group C (no GI disruption, n = 22). GI disruption was defined as compromised integrity of the GI tract caused by abdominal surgery, perforation, malignancy, enterocolitis, or bleeding. The incidence of ECDI was 2.53 per 100,000 admissions. The most common specimens yielded C. difficile were blood (36.7%), peritoneal fluid (20.0%), and abscesses (16.7%). Six patients (10.0%) had confirmed C. difficile enterocolitis, and 36 patients (60.0%) had a polymicrobial infection. C. difficile bacteremia was significantly more common in group A patients than those in groups B or C (53.8% vs. 48.0% vs. 13.6%, p = 0.02), as was the 30-day mortality rate (69.2% vs. 12.0% vs. 18.2%, respectively; p 0.001). In multivariate analysis, group A (adjusted odds ratio [aOR], 17.32; 95% confidence interval [CI], 2.96-101.21; p = 0.002) and an age of 65 years (aOR, 7.09; 95% CI, 1.31-38.45; p = 0.02) were independent risk factors for 30-day mortality. ECDI was uncommonly associated with C. difficile enterocolitis. Two factors, GI disruption caused by malignancy, and old age, were associated with significantly poorer short-term outcomes.

This study investigated resistance mechanisms and epidemiology of emerging linezolid-nonsusceptible Enterococcus faecalis (LNSEF) in a tertiary care hospital. LNSEF isolated from clinical samples were collected from November 2017 to June 2019. The isolates were investigated for linezolid resistance and the associated molecular mechanisms, including mutations of 23S rRNA domain V and acquisition of the cfr or optrA resistance gene. We used pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing for the molecular typing of the isolates. Among 4,318 E. faecalis isolates, 10 (0.23%) were linezolid-nonsusceptible. All LNSEF isolates were optrA-positive and cfr-negative. Of these isolates, five were sequence type (ST) 476, two ST585, one ST16, one ST16-like, and one ST480. Six LNSEF isolates obtained in the first year clustered to three types in the PFGE analysis: two ST476 isolates of type A, two ST585 isolates of type B, and two ST16 or ST16-like isolates of type C. Seven cases were of community-onset and three were hospital acquired, but total of eight were healthcare-associated including five community-onset. None of the patients had a history of linezolid treatment, and in one patient, we detected linezolid-susceptible E. faecalis one month before LNSEF detection. In conclusion, heterogenous clones of optrA-positive LNSEF emerged in the hospital mainly via community-onset.

We performed layer-specific strain analysis with speckle-tracking echocardiography to investigate the transmural difference of myocardial damage as the predicting factor for the viability of damaged myocardium in patients with ST segment elevation myocardial infarction (STEMI). We analysed patients with acute STEMI who had undergone primary percutaneous coronary intervention and echocardiography within 24 h from the intervention and 2 months after the event. Segmental strains of the left ventricular (LV) endocardium, myocardium, epicardium, and strain gradient (SG) between the endocardium and epicardium were evaluated. In 34 patients, 112 akinetic/dyskinetic and 94 hypokinetic segments were observed among 612 segments of the LV at baseline, and 65 akinetic/dyskinetic segments had viability. In our study, layer-specific strains were gradually deteriorated by their wall motion. SG was augmented in the hypokinetic segments where inhomogeneous wall motion impairment was progressed. SG in the akinetic/dyskinetic segments was different between the viable and non-viable myocardium and was maintained in viable segments. We therefore believe that significantly reduced SG is indicative of irreversible transmural damage in the acute stage of STEMI and can be suitably used as a parameter for predicting myocardial viability.

Background: Long-term antiviral therapy (AVT) for chronic hepatitis B (CHB) reduces the risk of hepatocellular carcinoma (HCC). We assessed the temporal trends in the incidence of HCC over time during long-term AVT among Asian patients with CHB. Methods: Patients with CHB receiving entecavir/tenofovir (ETV/TDF) as a first-line antiviral were recruited from four academic hospitals in the Republic of Korea. We compared the incidence of HCC during and after the first 5 years of ETV/TDF treatment. Results: Among 3,156 patients, the median age was 49.6 years and males predominated (62.4%). During the follow-up, 9.0% developed HCC. The annual incidence of HCC per 100 person-years during the first 5 years (n = 1,671) and after the first 5 years (n = 1,485) was statistically similar (1.93% vs. 2.27%, P = 0.347). When the study population was stratified according to HCC prediction model, that is, modified PAGE-B score, the annual incidence of HCC was 0.11% versus 0.39% in the low-risk group ( 0.05). A Poisson regression analysis indicated that the duration of AVT did not significantly affect the overall trend of the incidence of HCC (adjusted annual incidence rate ratio = 0.85; 95% confidence interval, 0.66–1.11; P = 0.232). Conclusions: Despite long-term AVT, the risk of HCC steadily persists over time among patients with CHB in the Republic of Korea, in whom HBV genotype C2 predominates. Impact: Careful HCC surveillance is still essential.

BACKGROUND AND AIMS It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. Thus, early identification of advanced liver fibrosis is very important. This study evaluated the prognostic value of FIB-4, the aspartate transaminase to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-toplatelet ratio (GPR) for predicting HCC development using histological fibrosis stage as a reference in Asian chronic hepatitis B (CHB) patients. METHODS A total of 444 CHB patients who underwent liver biopsy and serological tests for determining noninvasive serum fibrosis markers were enrolled. All patients were followed to monitor HCC development. RESULTS The histological fibrosis stage showed best performance in predicting HCC development at 5 (area under the receiver operating characteristic curve [AUROC] = 0.783) and 7 years (AUROC = 0.766), followed by FIB-4 (AUROC = 0.753 at 5 years, 0.698 at 7 years), APRI (AUROC = 0.658 at 5 years, 0.572 at 7 years), and GPR (AUROC = 0.638 at 5 years, 0.603 at 7 years). When we classified risk groups according to the histological fibrosis stage (F4 vs. F0-3) and FIB-4 (FIB-4 ≥ 3.25 vs. FIB-4 < 3.25), patients in the high-risk group were found to have a significantly higher probability of developing HCC than those in the low-risk group (P=0.005 and 0.022, respectively, log-rank test). CONCLUSION Our study demonstrated that FIB-4 is useful for the noninvasive prediction of HCC development, while APRI and GPR were less useful.

We investigated the antifungal susceptibilities and the cyp51 mutant strains among Aspergillus fumigatus clinical isolates obtained from 10 university hospitals in Korea. Of the 84 isolates examined, two itraconazole-resistant isolates were found with no amino acid substitution in the cyp51A/cyp51B genes. However, 19 (23.2%) azole-susceptible isolates harbored amino acid substitutions: Nine isolates harbored one to five mutations in cyp51A with high polymorphism, and 11 isolates exhibited the same Q42L mutation in cyp51B. Overall, a low azole resistance rate and high frequency of cyp51A/cyp51B amino acid substitutions were observed in the azole-susceptible A. fumigatus isolates in Korea.

Aims Chemotherapy-induced cardiotoxicity (CIC) is a significant complication, meanwhile myocardial damage might differ depending on chemotherapy agents and their timing. The aim of this study was to evaluate serial changes of layer-specific myocardial function in patients with breast cancer and their differences by the development time of CIC and chemotherapy agent. Methods and results A total of 105 consecutive patients with breast cancer (age: 52.3 ± 9.3 years) were enrolled. Chemotherapy-induced cardiotoxicity occurred in 20 (19%) patients during 6 months. Endocardial and midmyocardial functions decreased in patients with or without CIC, with patients with CIC showing greater decreases during follow-up. Global longitudinal strain (GLS) change at 3 months was the most sensitive parameter to detect CIC. When new development of CIC was analysed at 6 months, GLS was reduced earlier than the decrease of left ventricular ejection fraction. In patients with CIC who were treated with anthracycline-based regimen for 3 months, endocardial GLS markedly decreased at 3 months and continued to decrease until 6 months. Patients with CIC who received trastuzumab therapy after anthracycline therapy showed further reduction in endocardial GLS at the 6-month follow-up, which was not shown in patients with CIC who received taxane therapy subsequently. Conclusion Myocardial function assessed by strain decreased in all patients with breast cancer receiving chemotherapy. The endocardial layer was the most vulnerable to chemotherapy-induced myocardial damage. Functional impairment was more profound in patients with CIC who received sequential anthracycline-trastuzumab chemotherapy. Thus, early evaluation of left ventricular function might be necessary for all patients with breast cancer to detect CIC.

Several surrogate biomarkers possess prognostic significance for heart failure (HF), and a decline in their respective values may predict clinical improvement. However, data on the prognostic value of these biomarkers during short-term follow-up after discharge in acute decompensated HF are scarce. We aim to evaluate the prognostic value of short-term follow-up of surrogate biomarkers for predicting the prognosis of hospitalized patients with acute decompensated HF. This multi-center, prospective study will enroll consecutive hospitalized patients with acute decompensated HF. All patients will undergo sampling and comparison of biomarkers, including plasma N-terminal pro-brain natriuretic peptide, growth differentiation factor 15, troponin-T, high-sensitivity C-reactive protein, and urinary albumin/creatinine ratio obtained within 1 month and 6 months after discharge from the index admission. The primary endpoint is a composite of cardiovascular mortality or HF hospitalization during 1 year of follow-up. We will investigate the prognostic value of multiple biomarkers for the primary endpoint. This trial will provide robust evidence for novel multi-biomarker strategies for acute decompensated HF in real-world settings.ClinicalTrials.gov Identifier: NCT04437628.

Concern about resistance to chlorhexidine has increased due to the wide use of the latter. The impact of the qacA/B and smr chlorhexidine tolerance genes on the outcome of methicillin-resistant Staphylococcus aureus (MRSA) infections is unclear. We evaluated the prevalence and clinical impact of, and microbiological risk factors for, qacA/B tolerance in MRSA bacteremia. MRSA bacteremia that occurred more than two days after intensive care unit admission between January 2009 and December 2018 was identified from a prospective cohort of S. aureus bacteremia in a tertiary-care hospital from South Korea. A total of 183 MRSA blood isolates was identified, and the major genotype found was ST5-MRSA-II (87.4%). The prevalences of qacA/B and smr were 67.2% and 3.8%, respectively. qacA/B-positive isolates were predominantly ST5-MRSA-II (96.7% [119/123]), the dominant hospital clone. In a homogenous ST5-MRSA-II background, qacA/B positivity was independently associated with septic shock (aOR, 4.85), gentamicin resistance (aOR, 74.43), and non-t002 spa type (aOR, 74.12). qacA/B positivity was found to have decreased significantly in ST5-MRSA-II in association with a decline in qacA/B-positive t2460, despite the increasing use of chlorhexidine since 2010 (P qac genes, and molecular characterization of their plasmids, are needed to understand their role in MRSA epidemiology.

Background We aimed to compare the clinical outcomes of patients with positive Xpert Carba-R assay results for carbapenemase-producing Enterobacterales (CPE) according to CPE culture positivity. Methods We retrospectively collected data for patients with positive CPE (positive Xpert Carba-R or culture) who underwent both tests from August 2018 to March 2021 in a 2700-bed tertiary referral hospital in Seoul, South Korea. We compared the clinical outcomes of patients positive for Xpert Carba-R according to whether they were positive (XPCP) or negative (XPCN) for CPE culture. Results Of 322 patients with CPE who underwent both Xpert Carba-R and culture, 313 (97%) were positive for Xpert Carba-R for CPE. Of these, 87 (28%) were XPCN, and 226 (72%) were XPCP. XPCN patients were less likely to have a history of previous antibiotic use (75.9% vs 90.3%; P = .001) and to have Klebsiella pneumoniae carbapenemase (21.8% vs 48.9%; P Conclusions Our study suggests that XPCN patients had lower rates of both infection and transmission than XPCP patients. The Xpert Carba-R assay is clinically useful not only for rapid identification of CPE but also for predicting risks of infection and transmission when performed along with culture.

Objectives: Laboratory-acquired infection (LAI) of SARS-CoV is well known, but MERS-CoV or SARS-CoV-2 LAI has not yet been reported. Beginning last November, COVID-19 cases increased among laboratory staff at our 2,700-bed tertiary-care hospital. A 7-day home-quarantine policy for healthcare workers when household members were confirmed with SARS-COV-2 was lifted February 28. We investigated LAI and its risk factors. Methods: From March 21 to 25, all confirmed cases of COVID-19 among 176 laboratory staff were surveyed with questionnaire to collect the following data: symptom onset and period, SARS-CoV-2 PCR–positive sample date, age, sex, infection in household members, close contact with COVID-19 confirmed staff, work type, work unit, possibility of LAI and LAI risk factors. Results: In total, 54 laboratory staff (30.1%) were confirmed with SARS-CoV-2 infection; first 1 person on November 28 and 1 person on November 30, 2021, then 13 in February 2022 and 39 later in 2022. Overall, 22 cases had previously infected household members, and 9 cases suspected that they had had hospital contact with an infected patients through phlebotomy or bedside tests. In total, 25 cases of possible LAI mainly occurred in clusters of 3, 6, or 7 people through person-to-person transmission of a coworker who had an infected family member. The remaining 9 cases, including 1 sample receptionist, 2 urine analysis technicians, and 6 SARS-CoV-2 PCR test staff, may have been infected through an infected sample. However, person-to-person transmission was still possible because most shared a changing room and lounge in the same work unit. Conclusions: The most important cause of LAI is person-to-person transmission between coworkers; therefore, home quarantine is an effective measure to prevent LAI when a household member is infected wish SARS-CoV-2. Handling of infected specimens may be the second most common cause of LAI.

Background: We evaluated the frequency of a positive result in follow-up blood cultures (FUBCs) and clinical outcome when FUBCs were not performed, in patients with a single Staphylococcus ...

The chemokine receptor CXCR7 has been suggested to play important roles in the progression of several types of cancers. However, few studies have investigated the biological roles of CXCR7 in head and neck squamous cell carcinoma (HNSCC). CXCR7 expression and its clinical implications were examined in 103 HNSCC tissues using immunohistochemistry (IHC). The biological roles and mechanisms of CXCR7-mediated signaling pathways were investigated in HNSCC cells through CXCR7 overexpression in vitro and in vivo. High expression of CXCR7 was significantly associated with tumor size (P = 0.007), lymph node metastasis (P = 0.004), and stage (P = 0.020) in HNSCC. Overexpression of CXCR7 in HNSCC cells enhanced cell migration and invasion in vitro and promoted lymph node metastasis in vivo. CXCR7 also induced epithelial–mesenchymal transition through PI3K/AKT. CXCR7 increased secretion of transforming growth factor-β1 (TGF-β1) and promoted EMT through phosphorylated Smad2/3. Taken together, our results provide functional and mechanistic roles of CXCR7 as a master regulator of oncogenic TGF-β1/Smad2/3 signaling in HNSCC, suggesting that CXCR7 might be a therapeutic target for the treatment of HNSCC.

Rapid and accurate diagnosis of influenza is crucial to contain influenza virus outbreaks. In clinical settings, lateral flow immunoassays (LFIAs) are widely used for rapid influenza antigen detection. The choice of label plays an important role in determining the sensitivity of the LFIA. Quantum dots are one of the most promising fluorescent reporters. Here, we evaluated a novel quantum dot-based assay, QuantumPACK Easy Influenza A + B (QuantumPACK Easy; BioSquare Inc., Korea). A total of 394 nasopharyngeal swab samples, including 94 influenza A virus-positive, 98 influenza B virus-positive, 175 influenza A and B virus-negative, and 27 other respiratory pathogen-positive samples, were collected. Samples were tested with QuantumPACK Easy, Allplex RP real-time RT-PCR assay (Allplex RP; Seegene, Korea), and Sofia Influenza A + B FIA (Sofia; Quidel, CA, USA). The sensitivity and specificity of QuantumPACK Easy was analyzed using the Allplex RP assay. The agreement between QuantumPACK Easy and Sofia assays was also analyzed. The sensitivity of QuantumPACK Easy for influenza A and B was 80.9% and 83.7%, respectively. The specificity of QuantumPACK Easy was 100%. Cross-reactivity with other respiratory pathogens was not observed. Total agreement between QuantumPACK Easy and Sofia was 89.6% (kappa 0.783). The sensitivity of the Sofia assay was 66.0% for influenza A virus and 61.2% for influenza B virus. QuantumPACK Easy had acceptable performance, with better sensitivity than a commercially available antigen detection assay, possibly due to the characteristics of the quantum dot.

The purpose of this study was to identify the mediating effects of perceived health status (PHS) and perceived organizational support (POS) in the association between emotional labor and burnout in public health nurses (PHNs). The participants were 207 PHNs convenience sampled from 30 public health centers and offices in Jeju, Korea. Data regarding emotional labor, PHS, POS, and burnout were collected between February and March 2021 using a structured questionnaire. Collected data were analyzed by Pearson’s correlation coefficient and multiple regression analysis. Burnout of PHNs was positively correlated with emotional labor (r = 0.64, p < 0.001) and negatively correlated with PHS (r = −0.51, p < 0.001) and POS (r = −0.51, p < 0.001). In the association between emotional labor and burnout, PHS (B = −1.36, p < 0.001) and POS (B = −0.42, p = 0.001) had a partial mediating effect. Reduction of burnout among PHNs requires not only effective management of emotional labor but also personal and organizational efforts to improve PHS and POS.

Objectives: Predicting hepatocellular carcinoma (HCC) in patients with chronic hepatitis B who received long-term therapy with potent nucleos(t)ide analogs is of utmost importance to refine the strategy for HCC surveillance. Methods: We conducted a multicenter retrospective cohort study to validate the CAGE-B and SAGE-B scores, HCC prediction models developed for Caucasian patients receiving entecavir (ETV) or tenofovir (TFV) for &gt, 5 years. Consecutive patients who started ETV or TFV at two hospitals in Korea from January 2009 to December 2015 were identified. The prediction scores were calculated, and model performance was assessed using receiver operating characteristics (ROC) curves. Results: Among 1557 patients included, 57 (3.7%) patients had HCC during a median follow-up of 93 (95% confidence interval, 73–119) months. In the entire cohort, CAGE-B predicted HCC with an area under the ROC curve of 0.78 (95% CI, 0.72–0.84). Models that have “liver cirrhosis” in the calculation, such as AASL (0.79 (0.72–0.85)), CU-HCC (0.77 (0.72–0.82)), and GAG-HCC (0.79 (0.74–0.85)), showed accuracy similar to that of CAGE-B (p &gt, 0.05), however, models without “liver cirrhosis”, including SAGE-B (0.71 (0.65–0.78)), showed a lower predictive ability than CAGE-B. CAGE-B performed well in subgroups of patients treated without treatment modification (0.81 (0.73–0.88)) and of male sex (0.79 (0.71–0.86)). Conclusions: This study validated the clinical usefulness of the CAGE-B score in a large number of Asian patients treated with long-term ETV or TFV. The results could provide the basis for the reappraisal of HCC surveillance strategies and encourage future prospective validation studies with liver stiffness measurements.

β-lactam–avibactam combinations have been proposed as carbapenem-sparing therapies, but little data exist on their in vitro activities in infections with high bacterial inocula. We investigated the in vitro efficacies and the inoculum effects of ceftazidime–avibactam and aztreonam–avibactam against extended-spectrum β-lactam-resistant Enterobacterales blood isolates. A total of 228 non-repetitive extended-spectrum β-lactam-resistant Escherichia coli and Klebsiella pneumoniae blood isolates were prospectively collected in a tertiary center. In vitro susceptibilities to ceftazidime, aztreonam, meropenem, ceftazidime–avibactam, and aztreonam–avibactam were evaluated by broth microdilution method using standard and high inocula. An inoculum effect was defined as an eightfold or greater increase in MIC when tested with the high inoculum. Of the 228 isolates, 99% were susceptible to ceftazidime–avibactam and 99% had low aztreonam–avibactam MICs (≤8 mg/L). Ceftazidime–avibactam and aztreonam–avibactam exhibited good in vitro activities; MIC50/MIC90 values were 0.5/2 mg/L, 0.125/0.5 mg/L, and ≤0.03/0.25 mg/L, respectively, and aztreonam–avibactam was more active than ceftazidime–avibactam. The frequencies of the inoculum effect with ceftazidime–avibactam and aztreonam–avibactam were lower than with meropenem (14% vs. 38%, p < 0.001 and 30% vs. 38%, p = 0.03, respectively). The β-lactam-avibactam combinations could be useful as carbapenem-sparing strategies, and aztreonam–avibactam has the better in vitro activity but is more subject to the inoculum effect than ceftazidime–avibactam.

Background Renal safety is a critical issue in chronic hepatitis B (CHB) patients receiving long-term entecavir (ETV) or tenofovir disofuroxil fumarate (TDF) therapy. We investigated their effects on estimated glomerular filtration rate (eGFR). Methods Treatment-naïve CHB patients receiving ETV or TDF for ≥1 year were recruited. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. We calculated average annual percent change (AAPC) in eGFR using Joinpoint regression. Results At beginning of observation, ETV group had unfavorable conditions than TDF group: lower eGFR and higher FIB-4 and APRI than TDF group (all P2 at sixth year; AAPC -0.09%; P=0.322), whereas that in TDF group (n=1,240) significantly decreased annually (101.9 at first year to 96.9 mL/min/1.73 m2 at sixth year; AAPC -0.88%; PP=0.001) or hypertension (AAPC -0.87%; P=0.001) experienced significant decrease in eGFR. Expectably, accompanying diabetes (AAPC -1.59%; p=0.011) or hypertension (AAPC -1.00%; p=0.002) tended to accelerate eGFR decrease. TDF treatment (odds ratio 1.66, P<0.001), along with eGFR2, serum albumin

The value of follow-up blood culture (FUBC) in Gram-negative bacteremia (GNB) management is controversial. We evaluated bedside risk predictors and their probabilities of yielding positive FUBCs in GNB.All adult patients with GNB in a 2700-bed tertiary center were retrospectively enrolled between January 2019 and December 2019. Only one initial GNB episode was included per patient. Positive FUBC was defined as isolation of the same organism in blood culture 48-72 h after the initial blood culture.A total of 2216 patients with GNB were identified, of whom 34.4% underwent FUBC. Of the 645 patients with FUBCs analyzed in the study, 89 (13.8%) had positive FUBCs. In multivariate analysis, hemodialysis [adjusted odds ratio (aOR), 2.6], fever on the day of FUBCs (aOR 3.6), intravascular device (aOR 2.4), no use of in vitro active antibiotic within 24 h (aOR 2.5), non-fermenting bacteria (aOR 4.7), and multidrug resistance (aOR 5.4) were independent risk factors for positive FUBCs. If microbiological results were excluded in multivariate analysis, hemodialysis, immunosuppressive treatment, fever on the day of FUBCs, and intravascular device were independent bedside risk predictors for positive FUBCs. The yield of FUBCs increased from 3.0% (95% CI 1.0-7.0) to 63.6% (95% CI 25.6-100) as the number of bedside risk predictors increased from 0 to 4. In addition, positive FUBCs were significantly associated with 30 day mortality.FUBCs may not need to be routinely used for patients with GNB bacteremia, and bedside risk predictors could be helpful in identifying patients for whom FUBC is likely to be useful.

Background The upper‐airway microbiota may be associated with the pathogenesis of asthma and useful for predicting acute exacerbation. However, the relationship between the lower‐airway microbiota and acute exacerbation in children with asthma is not well understood. We evaluated the characteristics of the airway microbiome using induced sputum from children with asthma exacerbation and compared the microbiota‐related differences of inflammatory cytokines with those in children with asthma. Methods We analysed the microbiome using induced sputum during acute exacerbation of asthma in children. We identified microbial candidates that were prominent in children with asthma exacerbation and compared them with those in children with stable asthma using various analytical methods. The microbial candidates were analysed to determine their association with inflammatory cytokines. We also developed a predictive functional profile using PICRUSt. Results A total of 95 children with allergic sensitisation including 22 with asthma exacerbation, 67 with stable asthma, and 6 controls were evaluated. We selected 26 microbial candidates whose abundances were significantly increased, decreased, or correlated during acute exacerbation in children with asthma. Among the microbial candidates, Campylobacter, Capnocytophaga, Haemophilus, and Porphyromonas were associated with inflammatory cytokines including macrophage inflammatory protein (MIP)‐1β, programmed death‐ligand 1, and granzyme B. Both Campylobacter and MIP‐1β levels were correlated with sputum eosinophils. Increased lipopolysaccharide biosynthesis and decreased glycan degradation were observed in children with asthma exacerbation. Conclusion Gram‐negative microbes in the lower airway were related to acute exacerbation in children with asthma. These microbes and associated cytokines may play a role in exacerbating asthma in children.

Congenital uterine anomalies (CUA) may influence reproductive performance, resulting in adverse pregnancy associated complications. This study aimed to assess the association of CUA subtypes with reproductive, obstetric, and perinatal outcomes. We performed a systematic search of the MEDLINE, EMBASE, and Cochrane libraries for studies comparing pregnancy outcomes between women with CUA and those with a normal uterus. The random effects model was used to estimate the odds ratios (ORs) with a 95% confidence interval (CI). Women with CUA had a lower rate of live births (OR 0.47, 95% CI 0.33–0.69), and a higher rate of first trimester miscarriage (OR, 1.79, 95% CI, 1.34–2.4), second trimester miscarriage (OR 2.92, 95% CI 1.35–6.32), preterm birth (OR 2.98, 95% CI 2.43–3.65), malpresentation (OR 9.1, 95% CI 5.88–14.08), cesarean section (OR 2.87, 95% CI 1.56–5.26), and placental abruption (OR 3.12, 95% CI 1.58–6.18). Women with canalization defects appear to have the poorest reproductive performance during early pregnancy. However, unification defects were associated with obstetric and neonatal outcomes throughout the course of pregnancy. It may be beneficial for clinicians to advise on potential complications that may be increased depending on the type and severity of CUA.

Population-based data are lacking regarding whether fatty liver is a risk factor for hepatocellular carcinoma (HCC) and mortality in patients with chronic viral hepatitis.To investigate the association of fatty liver with HCC incidence and mortality in patients with chronic viral hepatitis using a nationwide cohort METHODS: We included 57,385 patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC) who underwent health examinations. The patients were divided into three groups: no fatty liver, fatty liver index (FLI)30, grade 1 (G1) fatty liver: 30≤ FLI60, and grade 2 (G2) fatty liver: FLI60.During a median 8.4-year follow-up, we documented 3496 HCC cases and 4146 deaths. Compared to patients with no fatty liver (n = 35,018), the risk of HCC was significantly higher in patients with G1 fatty liver (n = 14,544) (adjusted hazard ratio [aHR] = 1.50, 95% confidence interval [CI] = 1.38-1.64) and G2 fatty liver (n = 7,823) (aHR = 1.88, 95% CI = 1.67-2.12). The risk of mortality was significantly higher in patients with G1 fatty liver (aHR = 1.53, 95% CI = 1.41-1.66) and G2 fatty liver (aHR = 2.16, 95% CI = 1.94-2.42) compared to patients with no fatty liver.Concurrent fatty liver was associated with a higher risk of HCC and mortality in patients with chronic viral hepatitis. Our results suggest the importance of management of fatty liver to reduce the risks of HCC and mortality in patients with chronic viral hepatitis.

Background: Active surveillance tests for carbapenemase-producing Enterobacteriaceae (CPE) are recommended in patients showing risk factors for colonization by these bacteria. There are limited data however on whether surveillance tests for anatomic sites other than the stool would be useful to detect CPE colonization, and we investigated this in our present study.Methods: Retrospective analysis was performed on cases at our tertiary care hospital during a 5-year period. Patients with CPE colonization had been admitted to our surgical intensive care unit (SICU) or sub-ICU for liver transplantation in this period and undergone surveillance tests for both the stool and other sites. Patients were grouped as stool CPE negative (but which included CPE positive cases from initial sputum and other site tests) or positive. Results: Among the total study cohort of 158 patients, 138 (87.3%) were included in the stool CPE positive group and the remaining 20 (12.7%) in the stool CPE negative group. While the sensitivity of CPE surveillance testing of the stool was 87.3% (95% CI 81.1-92.1), the sensitivity when combining stool and sputum samples was 93.7% (88.7-96.9). The transmission rates were similar for patients showing CPE positivity in the stool, sputum and other sites, at 4.8% (27/557), 4.7% (3/64), and 6.7% (1/15), respectively (p = 0.95).Conclusions: The sensitivity of CPE detection in a stool sample is suboptimal for ruling out CPE colonization and the transmission rates are similar between stool-positive or -negative cases. Thus, combining surveillance of the stool with other sites may be needed for detecting CPE.

BACKGROUND Rapid and accurate diagnosis of influenza virus (Flu) and respiratory syncytial virus (RSV) is important for managing both the patient and laboratory. We compared the cobas Influenza A/B & RSV assay (cobas Liat) with the Simplexa Flu A/B & RSV assay (Simplexa) to evaluate which test method is more advantageous considering the resources of the laboratory and results of test performance. METHODS A total of 236 respiratory specimens from patients referred for respiratory virus testing were retrospectively evaluated; 53 specimens tested positive for each of Flu A, Flu B, and RSV, and 77 specimens tested negative based on the results of the reference method, i.e., the Seegene Allplex Respiratory Panel 1/2/3 (Seegene, Seoul, Korea). The turnaround time (TAT) was 20 minutes per specimen for cobas Liat and 78 minutes per eight speci-mens for Simplexa. The total hands-on time was around one minute per specimen for both tests. The specimen volume required for testing was 200 µL for cobas Liat and 50 µL for Simplexa. Seegene Allplex Respiratory Panel 1/2/3 was used as the reference method. RESULTS The number of invalid results was 1 (0.4%) for cobas Liat and 10 (4.2%) for Simplexa (p < 0.05). All results were consistent with those of the reference method in cobas Liat. The sensitivity and specificity for Flu A, Flu B, and RSVA were 100% with Simplexa. However, the sensitivity for RSVB was 80.0% with Simplexa, which was a statistically significant difference with the finding for cobas Liat (p < 0.05). Comparison of the cycle threshold (Ct) values of RSV for Simplexa with the reference method showed correlation as continuous variables (p < 0.001) with a higher propensity for obtaining Ct values with Simplexa, the exception being the six false negative results; their Ct values were more than 30 in the reference method. CONCLUSIONS Cobas Liat showed accurate performance with a rapid TAT and a good workflow efficiency. Cobas Liat is more efficient than Simplexa as a point-of-care test for the detection of RSV.

NDM-4-producing Klebsiella pneumoniae (NDM-4-KP) was detected from the patient who had previously been injured and hospitalized for 5 days in Vietnam in a neurosurgical intensive care unit (NSICU) of a Korean tertiary-care hospital in December 2016. He admitted with ventilator-associated pneumonia and NDM-4-KP was isolated, which was subsequently detected in two other NSICU patients. All NDM-4-KP isolates from patient and environmental surveillance cultures were sequence type 11. Colonization of three patients persisted for 5-12 months. Dedicated environmental cleaning was added to single room isolation of NDM-4-KP patients and universal chlorhexidine bathing, and no further transmission of NDM-4-KP occurred. This is the first report of NDM-4-KP in a Korean hospital where a patient with a history of hospitalization abroad was the index case initiating an outbreak involving three patients. The spread of newly introduced CPE was controlled using a bundle of infection control.

Background & Aims It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naive patients with CHB. Methods From 2012 to 2014, treatment-naive patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed. Results In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years [PY], respectively; adjusted hazard ratio [HR] 0.975 [p = 0.852] by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 [p = 0.884] and 0.998 [p = 0.988], respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR 1.202 [p = 0.451]). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 [p = 0.385] and 1.239 [p = 0.360], respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p >0.05). Conclusions The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results. Lay summary It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by defective skin barrier and Th2 immune responses. Chitinase 3-like 1 (CHI3L1), also known as breast regression protein 39 (BRP-39) in mice and human homologue YKL-40, plays important roles in Th2 inflammation and allergen sensitization. CHI3L1 has been implicated in a variety of diseases including asthma characterized by inflammation, apoptosis and tissue remodelling, but its role in AD remains elusive. Objective The aim of this study was to investigate the role of CHI3L1 in the development and progression of AD. Results We investigated YKL-40 levels in the serum and skin of AD patients by ELISA and immunofluorescence, respectively. Using a murine model of AD induced by ovalbumin (OVA), we investigated Th2 immune responses, M2 macrophage activation and skin barrier gene expression using wild-type (WT) and BRP-39 null mutant (BRP-39-/- ) mice. YKL-40 level was significantly increased in serum of AD patients. In addition, both mRNA and protein expression levels of BRP-39 were higher in OVA-sensitized WT mice than in control mice. OVA-sensitized BRP-39-/- mice showed decreased epidermal thickness, lower total serum IgE, Th2 cytokine levels and CD4+ effector T cell populations than OVA-sensitized WT mice. Induction of BRP-39 was dominant in dermal macrophages. BRP-39 deficiency was found to be involved in M2 macrophage activation. Consistently, the YKL-40 level in the skin of AD patients was higher than in normal subjects and it was expressed in dermal macrophages. BRP-39 deficiency attenuated dysregulation of skin barrier and tight junction genes. Conclusions and clinical relevance These findings demonstrate that CHI3L1 mediates the development of AD induced by OVA, affecting Th2 inflammation, M2 macrophage activation and skin barrier function.

This study investigated the association between obesity type and obstructive coronary artery disease (CAD) in postmenopausal women.Study data were obtained from a nation-wide registry, composed of 659 women older than 55 years with chest pain undergoing elective invasive coronary angiography in the suspicion of CAD. Obstructive CAD was defined as angiographic findings of ≥50% diameter stenosis with any major epicardial coronary artery. Overall obesity was defined as a body mass index of ≥25 kg/m, and central obesity was defined as a waist circumference of ≥85 cm.A total of 311 women (47.2%) had obstructive CAD. The incidence of overall obesity was not different between participants with and without obstructive CAD (P = 0.340), but the prevalence of obstructive CAD was significantly higher in participants with central obesity than those without (55.5% vs 41.0%, P 0.001). There was no significant difference in body mass index between participants with and without obstructive CAD (P = 0.373). Multivariable analysis showed that central obesity was associated with obstructive CAD even after controlling for potential confounders (odds ratio, 1.61; 95% confidence interval, 1.10-2.34; P = 0.013). However, overall obesity was not associated with obstructive CAD in the same multivariable analysis (P = 0.228).Central obesity but not overall obesity is associated with obstructive CAD in postmenopausal women with stable chest pain undergoing invasive coronary angiography. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A440.

The clinical characteristics and outcomes of Streptococcus dysgalactiae subspecies equisimilis (SDSE) bacteremia cases have not been adequately evaluated. We retrospectively enrolled consecutive adult patients with SDSE or S. agalactiae (group B streptococci, GBS) bacteremia at a tertiary care hospital (Republic of Korea) from August 2012 to December 2016. We compared the incidence, seasonality, clinical characteristics, and outcomes of 52 SDSE bacteremia cases with 151 GBS bacteremia cases. The incidence of SDSE and GBS bacteremia in these patients was 1.28/100,000 and 4.22/100,000 person-days, respectively. Most SDSE bacteremia cases were of community-onset infection (SDSE 94.2% vs GBS 83.4%; p = 0.052). Lancefield group G was the most common bacteria type among SDSE isolates (43/47; 91.5%). Patients with SDSE bacteremia were older (median, 68.0 years vs 61.0 years; p = 0.03). In both groups, solid tumor was the most common underlying disease, and more than half of the patients were immunocompromised (51.9% vs 54.3%; p = 0.77). Chronic kidney disease was more common in the SDSE group (19.2% vs 5.3%; p

Background We have reported that partial PERK attenuation using PERK inhibitors (PI) enhanced glucose-stimulated insulin secretion (GSIS) from pancreatic islets and mice through induction of ER chaperone BIP. Therefore, we investigated if PI would have the same effects in a diabetic condition as well. Methods GSK2606414 was treated to mouse islets under 20-mM glucose and 0.5-mM palmitate to examine GSIS. To generate a mouse model of type 2 diabetes mellitus (DM), male C57BL/6J mice were fed with high-fat diet and injected with streptozotocin. Several doses (6–16 mg/kg/day) of GSK2656157 and glimepiride were administrated to the mice for 8 weeks, and metabolic phenotypes were evaluated such as body weight, blood glucose levels, insulin secretion and sensitivity, and then changes in the pancreas were measured. Results High-glucose and palmitate treatment significantly increased PERK phosphorylation in the isolated islets. Suppression of GSIS and glucose-stimulated Ca2+ transit was also observed. PI at 40 nM which decreased PERK phosphorylation by 40% significantly recovered the GSIS and cytosolic calcium. In the mice where significant weight gain and prominent hyperglycemia were induced, PI at 10 mg/kg/day significantly enhanced GSIS and reduced blood glucose levels compared to the vehicle. The effects were similar to those by 10 mg/kg/day of glimepiride. Administration of PI did not induce changes in beta cell mass or pancreatic insulin contents, however, high dose PI decreased pancreatic weight. Conclusion PI at low dose significantly enhanced GSIS in vitro and in vivo under metabolic stress and improved hyperglycemia in the mice mimicking type 2 DM, suggesting a potential as a new therapeutic approach for type 2 DM.

Background and aims Metabolic syndrome (MetS) is a cluster of multiple risk factors including central obesity that may lead to cardiac damage and cardiovascular events. We investigated whether visceral obesity induces cardiac structural and functional remodeling independently from central obesity and other risk factors in subjects with suspected MetS. Methods and results We studied 229 participants with suspected MetS. Visceral fat area (VFA) was measured by bioelectrical impedance analysis. Left ventricular (LV) mass index, early diastolic velocity of mitral annulus (e′), and LV global longitudinal strain (GLS) were measured by echocardiography. Subjects were categorized into high and low VFA group (VFAh and VFAl). MetS was more prevalent in the VFAh than in the VFAl (p = 0.004). The VFAh had a higher waist circumference (WC) than the VFAl (p Conclusions Visceral obesity assessed by VFA was well correlated with parameters of MetS. Visceral obesity, but not central obesity measured by WC, was independently associated with structural and functional cardiac remodeling in subjects with suspected MetS. It suggests that visceral obesity should be considered as an important risk factor for cardiac damage in dysmetabolic subjects. Trial registration NCT02077530 (date of registration: November 1, 2013).

BACKGROUND No study has examined the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in Korean veterans' hospitals. We investigated the microbiological and clinical epidemiology of S. aureus bacteremia at the central Veterans Health Services (VHS) hospital in Korea. METHODS Patients with S. aureus bacteremia were consecutively enrolled from February to August 2015. Bacteremia was classified as hospital-acquired (HA), community-onset healthcare-associated (COHA), or community-acquired (CA). MRSA bacteremia risk factors were analyzed. Species identification, antimicrobial susceptibility, and presence of luk and tst were tested. Staphylococcal cassette chromosome mec (SCCmec) typing, spa sequence typing agr polymorphism typing, and multilocus sequence typing were performed. Biofilm production and δ-hemolysin activity were measured to determine agr function. RESULTS In total, 60 patients were enrolled (30 HA, 23 COHA, and seven CA bacteremia); 44 (73.3%) had MRSA bacteremia (26 HA, 16 COHA, and two CA). MRSA bacteremia occurred more frequently in non-CA patients and those who had received antibiotic treatment within the past month (P

Background/Aims: Antiviral therapy (AVT) reduces the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). This multicenter retrospective study investigated the effects of AVT and hepatitis B virus (HBV)-related factors on the risk of HCC development in a cohort with heterogeneous HBV status. Methods: A total of 1,843 patients with CHB from two institutions were included in this study. Ultrasound and laboratory tests, including the α-fetoprotein test, were conducted regularly to detect HCC development. Results: The mean age of our study population (1,063 men and 780 women) was 49.4 years. Cirrhosis was identified in 617 patients (33.5%). During follow-up (median, 42.5 months), 81 patients developed HCC (1.39% per person-year). A total of 645 patients (35.0%) received ongoing AVT at enrollment. Ongoing AVT was not significantly associated with the risk of HCC development (all p>0.05). HBV-related variables (HBV DNA level, hepatitis B e antigen status, and alanine aminotransferase level) were also not significantly associated with the risk of HCC development (all p>0.05). In contrast, cirrhosis was significantly associated with the risk of HCC development, regardless of adjustment (adjusted hazard ratio=4.098 to 7.020; all p

Candida auris was first identified in Japan from specimens obtained from the ear, but most reports since have reported invasive infections or non-ear based cases. We reviewed all the microbiology records from a single center in South Korea from February 2016 to July 2018. One hundred eleven isolates were positive for C. auris from 79 patients. All 79 patients positive for C. auris had positive ear discharge samples. All but one of the patients with C. auris had been to the otorhinolaryngology clinic. Symptom-driven ear culture was done for all but one patient, whose culture was performed for surveillance. Ear discharges were mostly purulent (60%) or serous (34%). We performed the environmental cultures at the otorhinolaryngology outpatient clinic to evaluate the environmental contamination of C. auris, but C. auris was not isolated from medical equipment and environmental surfaces.