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This article, titled "An Unexpected Encounter During a Screening Colonoscopy in a Medical Tourist: A Diagnosis of Hymenolepis nana Infection," describes a case of Hymenolepis nana infection in a 55-year-old man from Kazakhstan who visited a health screening clinic in Korea. The man did not present any gastrointestinal symptoms but was found to have multiple whitish worms in his colon during a colonoscopy. The worms were identified as H. nana through morphological and molecular analysis. The article highlights the rarity of H. nana infections in Korea and emphasizes the importance of considering this parasite in the diagnosis of colonoscopy findings, particularly in the context of increasing foreign workers and medical tourists. [Extracted from the article]

Background: We evaluated the diagnostic performance of the FilmArray Blood Culture Identification Panel (BCID; bioMerieux) for the detection of bloodstream pathogens. Methods: From May to August 2022, up to 67 samples from positive blood cultures previously processed with BACTEC FX (BD) were collected and submitted to the BCID panel. BCID panel results were compared with traditional culture results. Results: We tested 67 positive blood culture samples; 13 samples were from pediatric bottles of BACTEC Peds Plus/F media (BD). The overall sensitivity of the BCID panel was 89.9% (62/69; 95% CI, 80.2 - 95.3%). For bloodstream pathogens targeted by the BCID panel, sensitivity was 98.4% (62/63; 95% CI, 90.7 - > 99.9%). Interestingly, Proteus species were additionally detected in 6 samples from pediatric blood culture bottles. Conclusions: BCID demonstrated high clinical sensitivity for target pathogens, but positive findings for unexpected multiple targets or Proteus species require cautious interpretation to avoid false positives. [ABSTRACT FROM AUTHOR]

Background: Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Methods: Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. Results: PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion: This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi. [ABSTRACT FROM AUTHOR]

Acquired fluconazole resistance (FR) in bloodstream infection (BSI) isolates of Candida albicans is rare. We investigated the FR mechanisms and clinical features of 14 fluconazole non-susceptible (FNS; FR and fluconazole-susceptible dose-dependent) BSI isolates of C. albicans recovered from Korean multicenter surveillance studies during 2006- 2021. Mutations causing amino acid substitutions (AASs) in the drug-target gene ERG11 and the FR-associated transcription factor genes TAC1, MRR1, and UPC2 of the 14 FNS isolates were compared with those of 12 fluconazole-susceptible isolates. Of the 14 FNS isolates, eight and seven had Erg11p (K143R, F145L, or G464S) and Tac1p (T225A, R673L, A736T, or A736V) AASs, respectively, which were previously described in FR isolates. Novel Erg11p, Tac1p, and Mrr1p AASs were observed in two, four, and one FNS isolates, respectively. Combined Erg11p and Tac1p AASs were observed in seven FNS isolates. None of the FR-associated Upc2p AASs were detected. Of the 14 patients, only one had previous azole exposure, and the 30-day mortality rate was 57.1% (8/14). Our data show that Erg11p and Tac1p AASs are likely to contribute to FR in C. albicans BSI isolates in Korea and that most FNS C. albicans BSIs develop without azole exposure. [ABSTRACT FROM AUTHOR]

The sensitivity of the (1-3)-β-D-glucan (BDG) diagnostic test for candidemia varies in different clinical settings, and its usefulness in early diagnosis of candidemia is suboptimal. We evaluated the sensitivity of the test for early candidemia prediction. All adult patients with culture-proven candidemia who underwent a serum Goldstream Fungus (1-3)-β-D-Glucan Test within seven days prior to candidemia onset at a tertiary referral hospital between January 2017 and May 2021 were included. Any-positive BDG results within seven days prior to candidemia onset were obtained in 38 out of 93 (40.9%) patients. The positive rate increased when the test was performed near the day of candidemia onset (P=0.04) but reached only 52% on the day of candidemia onset. We observed no significant differences between BDG-positive and -negative groups in terms of underlying disease, risk factors for candidemia, clinical presentation, origin of candidemia, and 30-day mortality. Candida albicans was significantly associated with positive BDG results than with all-negative BDG results (P=0.04). The Goldstream BDG test is unreliable for candidemia prediction because of its low sensitivity. Negative BDG results in patients with a high risk of invasive candidiasis should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: We reported two Fusobacterium nucleatum cases each of brain abscesses and pleural empyema, using 16S rRNA sequencing technology. Methods: We reviewed clinical records and microbiological findings in four patients with F. nucleatum infection. Results: All conventional culture results from peripheral blood, cerebrospinal fluid, and pleural fluid samples were found to be negative for this pathogen. Three patients were treated with antimicrobial agents for more than a week before specimen sampling. All patients recovered from their fusobacterial infections and were discharged. Conclusions: Molecular identification methods such as 16S rRNA sequencing should accompany conventional culture to detect obligate anaerobic bacteria in deep-seated sites and organs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess clinical performance of a rapid antigen test (RAT) for screening asymptomatic patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron outbreak. Methods: RAT with the routine real-time reverse transcription--polymerase chain reaction (rRT-PCR) using the same nasopharyngeal swab in universal transport medium was performed for rapid screening of asymptomatic caregivers of emergent patients from March to April 2022 in a tertiary-care hospital in Korea. Clinical performance of RAT compared to that analyzed by rRT-PCR was evaluated. Results: A total of 900 caregivers were enrolled in this study, of which 14 (1.6%) were RAT-positive and 44 (5.0%) were positive for rRT-PCR. Overall sensitivity and specificity of RAT were 31.8% and 100.0%, respectively. Conclusions: Caution must be taken when using RAT as a screening test for asymptomatic caregivers as this may lead to outbreaks among high-risk patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by fibroproliferative matrix molecule accumulation, collagen deposition, and apoptosis. Activated leukocyte cell-adhesion molecule (ALCAM; CD166) is a celladhesion molecule that has been implicated in adhesive and migratory attribution, including leukocyte homing and trafficking and cancer metastasis. We investigated the role of ALCAM on pulmonary fibrosis development in murine models. Thus, a bleomycin-induced pulmonary fibrosis model was established with wild-type and ALCAM2/2 mice. Pulmonary fibrosis was also induced in transforming growth factor-b1 (TGF-b1)- transgenic mice that conditionally overexpress TGF-b1 upon doxycycline administration. In both models, observed reduced ALCAM levels in lung tissue and BAL fluid in pulmonary fibrosis-induced wild-type mice compared with control mice. We also observed reduced ALCAM expression in the lung tissue of patients with pulmonary fibrosis compared with normal lung tissue. ALCAM2/2 mice showed an exacerbated lung fibrosis response compared with wild-type mice, and this was accompanied by increased cell death. Further investigation for identification of the signaling pathway revealed that PI3K and ERK signaling pathways are involved in bleomycin-induced fibrosis. Collectively, these results highlight that ALCAM plays a protective role in the pathogenesis of pulmonary fibrosis that inhibits epithelial cell apoptosis through the PI3K-Akt signaling pathway. Our findings demonstrate the potential of ALCAM as a therapeutic target for IPF and may aid the development of new strategies for the management and treatment of patients with IPF. [ABSTRACT FROM AUTHOR]

배경: Despite the known clinical benefit of remdesivir in SARS-CoV-2 infection, its usage has been limited in patients with impaired renal function due to concern about the liver and renal toxicities by the accumulation of sulfobutylether-β-cyclodextrin. We compared adverse events between remdesivir-treated and non-remdesivir-treated groups in COVID-19 patients with renal impairment. 방법: Adult COVID-19 patients with a glomerular filtration rate of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022 were retrospectively enrolled. Data on serum creatinine and liver chemistry tests at day 3 or 5, 10, 15, and 30 from admission or the start of remdesivir therapy were collected. 결과: A total of 101 patients with impaired renal function were enrolled including 34 patients receiving renal replacement therapy. Of 101 patients, 64 received remdesivir, while 37 did not. The median duration of remdesivir therapy was 4 (interquartile range, 3-5). Among patients who did not need dialysis initially, 18% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at day 3-5, while 43% (16/29) of non-remdesivir-treated patients did. The proportion of patients with AKI decreased over time in remdesivir-treated patients (Figure 1). At day 3-5, 20% (13/64) of remdesivir-treated patients developed liver injury (mostly mild injury), while 30% (11/37) of non-remdesivir-treated patients did. There was no significant increase in alanine aminotransferase level over time in remdesivir-treated patients (Figure 1). No serious renal and hepatic adverse events related to remdesivir were observed. 결론: No significant increases in liver and kidney injury associated with remdesivir therapy were observed. These findings suggest that remdesivir therapy should not be easily withheld due to safety concerns of sulfobutylether-β-cyclodextrin in COVID-19 patients with renal impairment. [ABSTRACT FROM AUTHOR]

배경: Bacteremia caused by carbapenemase-producing Enterobacterales (CPE) is a growing concern due to its high mortality and limited treatment option. We evaluated the characteristics of subsequent CPE bacteremia in CPE stool carriers and analyzed risk factors for CPE bacteremia compared with non-CPE Enterobacter bacteremia. 방법: We retrospectively analyzed adult patients confirmed to have CPE colonization in stool surveillance culture in a tertiary hospital between January 2018 and February 2022. All episodes of Enterobacterales bacteremia within 6 months after CPE colonization were identified. 결과: During the study periods, a total of 1,174 patients were identified as CPE stool carriers. Of these patients, 58 (4.9%) experienced 70 episodes of subsequent CPE bacteremia after CPE colonization, whereas 102 (8.7%) had 123 episodes of subsequent non-CPE Enterobacterales bacteremia. Colonization with KPC producer, K. pneumoniae, and E. coli was significantly associated with CPE bacteremia (Table 1). Subsequent Enterobacterales bacteremia in CPE carriers was more frequently caused by non-CPE than by CPE (8.7% vs. 4.9%, p <0.001). When comparing the first episode of Enterobacterales bacteremia according to carbapenemase production, colonization with KPC producer and K. pneumoniae, multiple sites colonization, high Pitt’s score, ICU care, recent abdominal surgery, and prior carbapenem use were significantly associated with CPE bacteremia (Table 2). Multivariable analysis revealed that ICU care (adjusted odds ratio [aOR]: 4.09, 95% confidence interval 1.52 to 11.01, p <0.01), KPC colonizer (aOR: 4.22, p <0.01) and abdominal surgery within a week (aOR: 13.15, p =0.03) were independent risk factors for CPE bacteremia. 결론: In CPE carriers, non-CPE Enterobacterales were 1.8 times more likely to cause bacteremia than CPE. In a CPE carrier in ICU, colonized with KPC, and recent history of intraabdominal surgery, empirical therapy for CPE should be considered when sepsis is suspected. [ABSTRACT FROM AUTHOR]

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<0.001; TG 184.4±116.3 mg/dL vs. 128.2±53.6 mg/dL, P<0.001), and reduced global longitudinal strain (GLS) (-15.4%±2.1% vs. -17.1%±2.0%, P<0.001) compared to women. After 3.4 years, values of WC and TG did not change in men but increased in women (all P<0.05). The absolute value of left ventricular (LV) GLS did not change in men but was reduced in women (P=0.011). Change in TG was independently associated with worsening of LV GLS only in women (standardized ß, -0.309; 95% confidence interval, -0.130 to -0.009; P=0.025). Conclusion: In middle aged population, a vulnerable period for metabolic disturbance, cardiac remodeling tended to progress, which was prominent in women. Progression of adiposity and dyslipidemia after menopause may accelerate subclinical cardiac remodeling in middle-aged women. Lifestyle modification and medical interventions may help prevent further cardiac dysfunction in these subjects. [ABSTRACT FROM AUTHOR]

Background: Bloodstream infection (BSI) is an important complication of extracorporeal membranous oxygenation (ECMO) and a major cause of mortality. This study evaluated the epidemiological and clinical characteristics of BSI that occur during ECMO application according to microbial etiology. Methods: Adult patients who underwent ECMO from January 2009 to December 2016 were retrospectively analyzed for BSI episodes at a 2,700-bed, tertiary center. Epidemiological and clinical characteristics and outcomes of BSI were evaluated and were compared for etiologic groups (gram-positive cocci, gram-negative rods, and fungi groups). Risk factors for 14-day mortality were analyzed. Results: A total of 1,100 patients underwent ECMO during the study period, and 65 BSI episodes occurred in 61 patients. The BSI incidence was 8.3 episodes/1,000 ECMO days, which significantly decreased over time (P = 0.03), primarily in gram-positive cocci BSI. Gram-positive cocci, gram-negative rods, and fungi accounted for 38%, 40%, and 22% of the 73 blood isolates, respectively. Baseline characteristics were comparable between groups. Catheter-related infection (CRI) and pneumonia were the most common sources of BSI; 52% of gram-positive cocci BSIs and 79% of fungi BSIs were caused by CRI, and 75% of gram-negative BSIs by pneumonia. Patients with gram-negative rods BSI died more frequently and earlier than those with other BSIs. Independent risk factors for 14-day mortality were older age and gramnegative rods BSI. Conclusions: The decreased BSI incidence during ECMO was mainly because of the decrease of gram-positive cocci BSI. The high early mortality of gram-negative rods BSI makes prevention and adequate treatment necessary. [ABSTRACT FROM AUTHOR]

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 specimens 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. [ABSTRACT FROM AUTHOR]

We investigated the clinical outcomes and molecular mechanisms of fluconazole-resistant (FR) Candida glabrata bloodstream infections. Among 1,158 isolates collected during multicenter studies in South Korea during 2008-2018, 5.7% were FR. For 64 patients with FR bloodstream infection isolates, the 30-day mortality rate was 60.9% and the 90-day mortality rate 78.2%; these rates were significantly higher than in patients with fluconazole-susceptible dose-dependent isolates (30-day mortality rate 36.4%, 90-day mortality rate 43.8%; p<0.05). For patients with FR isolates, appropriate antifungal therapy was the only independent protective factor associated with 30-day (hazard ratio 0.304) and 90-day (hazard ratio 0.310) mortality. Sequencing of pleiotropic drug-resistance transcription factor revealed that 1-2 additional Pdr1p amino acid substitutions (except genotype-specific Pdr1p amino acid substitutions) occurred in 98.5% of FR isolates but in only 0.9% of fluconazole-susceptible dose-dependent isolates. These results highlight the high mortality rate of patients infected with FR C. glabrata BSI isolates harboring Pdr1p mutations. [ABSTRACT FROM AUTHOR]

Background: Mycobacterial burden is low in extrapulmonary specimens, making diagnosis and treatment difficult. Xpert MTB/RIF is a real-time PCR assay for the detection of Mycobacterium tuberculosis and rifampin resistance. This study evaluated the performance of the Xpert MTB/RIF assay in extrapulmonary specimens. Methods: Acid-Fast Bacilli (AFB) smear, culture, and Xpert MTB/RIF were performed on extrapulmonary specimens. Mycobacterial culture was performed on BACTEC MGIT liquid for 6 weeks and 2% Ogawa medium for 8 weeks. Overall sensitivity and specificity of Xpert MTB/RIF was estimated using culture as a gold standard. Xpert MTB/RIF sensitivity and cycle-threshold (Ct) values according to AFB smear grade were evaluated. The sensitivity, specificity, and concordance of rifampin resistance compared to the phenotypic drug sensitivity test were evaluated. Results: A total of 1,289 specimens were included in the study. The overall sensitivity and specificity of the Xpert MTB/RIF assay were 59.4% (41/69, 95% CI 46.9 - 70.9%) and 99.3% (1,212/1,220, 95% CI 98.7 - 99.7), respectively. Positive predictive value of Xpert MTB/RIF was 83.7% (41/49, 95% CI 69.8 - 92.2) and negative predictive value was 97.7% (1,212/1,240, 95% CI 96.7 - 98.5%). Xpert MTB/RIF assay sensitivity significantly increased with increases in AFB smear grade (p < 0.001). AFB smear grades and Xpert MTB/RIF Ct values were negatively correlated. Rifampin resistance results of Xpert MTB/RIF and culture showed a concordance rate of 97.2%. Conclusions: The Xpert MTB/RIF assay could be used to replace the AFB smear for the diagnosis of extrapulmonary tuberculosis, and has high specificity for the detection of rifampin resistance. [ABSTRACT FROM AUTHOR]

Objective: Previous studies that evaluated cardiovascular risk factors considered age as a potential confounder. We aimed to investigate the impact of cardiovascular disease (CVD) and its risk factors on fatal outcomes according to age in patients with COVID-19.Methods: A systematic literature review and meta-analysis was performed on data collected from PubMed and Embase databases up to 11 June 2020. All observational studies (case series or cohort studies) that assessed in-hospital patients were included, except those involving the paediatric population. Prevalence rates of comorbid diseases and clinical outcomes were stratified by mean patient age in each study (ranges: <50 years, 50-60 years and ≥60 years). The primary outcome measure was a composite fatal outcome of severe COVID-19 or death.Results: We included 51 studies with a total of 48 317 patients with confirmed COVID-19 infection. Overall, the relative risk of developing severe COVID-19 or death was significantly higher in patients with risk factors for CVD (hypertension: OR 2.50, 95% CI 2.15 to 2.90; diabetes: 2.25, 95% CI 1.89 to 2.69) and CVD (3.11, 95% 2.55 to 3.79). Younger patients had a lower prevalence of hypertension, diabetes and CVD compared with older patients; however, the relative risk of fatal outcomes was higher among the former.Conclusions: The results of the meta-analysis suggest that CVD and its risk factors (hypertension and diabetes) were closely related to fatal outcomes in COVID-19 for patients across all ages. Although young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.Prospero Registration Number: CRD42020198152. [ABSTRACT FROM AUTHOR]

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". [ABSTRACT FROM AUTHOR]

External quality assessment (EQA) is essential for ensuring reliable test results, especially when laboratories are using assays authorized for emergency use for newly emerging pathogens. We developed an EQA panel to assess the quality of real-time reverse transcription PCR assays being used in South Korea to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the participation of 23 public health organization laboratories and 95 nongovernmental laboratories involved in SARS-CoV-2 testing, we conducted qualitative and semiquantitative performance assessments by using pooled respiratory samples containing different viral loads of SARS-CoV-2 or human coronavirus OC43. A total of 110 (93.2%) laboratories reported correct results for all qualitative tests; 29 (24.6%) laboratories had >1 outliers according to cycle threshold values. Our EQA panel identified the potential weaknesses of currently available commercial reagent kits. The methodology we used can provide practical experience for those planning to conduct evaluations for testing of SARS-CoV-2 and other emerging pathogens in the future. [ABSTRACT FROM AUTHOR]

This study investigated resistance mechanisms and epidemiology of emerging linezolidnonsusceptible 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 communityonset. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase-producing Enterobacteriaceae (CPE) are highly drug-resistant pathogens. Screening the contacts of newly-identified CPE patients is crucial for nosocomial transmission control. We evaluated the acquisition rate of CPE in close contacts as a function of CPE genotype. Materials and Methods: This study was conducted in Asan Medical Center, a 2,700-bed, tertiary teaching hospital in Seoul, Korea, between November 2010 and October 2017. Index cases were defined as patients with positive tests for CPE from any infected or colonized site during hospitalization who had no direct epidemiologic linkage with existing CPE patients; close contact patients were defined as those whose hospital stay overlapped with the stay of an index case for at least one day and who occupied the same room or intensive care unit (ICU). Secondary patients were defined as those who produced positive CPE culture isolates from surveillance cultures that had the same CPE enzyme as that of the index case patients. Results: A total of 211 index case patients and 2,689 corresponding contact patients were identified. Of the contact patients, 1,369 (50.9%) including 649 New-Delhi metallo-betalactamase- 1 (NDM-1) and 448 Klebsiella pneumoniae carbapenemase (KPC)-producing CPE exposures were screened, and 44 secondary patients (3.2%; 95% confidence interval 2.3 - 4.3%) were positive for NDM-1-producing CPE (16 patients) and KPC-producing (24 patients) CPE. The CPE acquisition rate (5.4%) for KPC-producing CPE exposures was significantly higher than that for NDM-1 exposures (2.7%) (P = 0.01). Conclusion: The CPE acquisition rate was 3.2% among close contacts sharing a multi-patient room, with about a two-fold higher risk of KPC-producing CPE than NDM-1-producing CPE. [ABSTRACT FROM AUTHOR]

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<0.05). Cirrhosis significantly predicted the risk of HCC development in subgroups with and without ongoing AVT at enrollment, regardless of adjustment. Conclusions: Our study showed that cirrhosis, not AVT and HBV-related variables, was associated with HCC development in a cohort of patients with heterogeneous HBV status. Our results may help clinicians apply individualized surveillance strategies according to fibrotic status in patients with CHB. [ABSTRACT FROM AUTHOR]

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 <0.05). The major MRSA strains comprised 24 ST5-agr2- SCCmecII, 11 ST72-agr 1-SCCmecIV, and five ST8-agr1-SCCmecIV strains. Of 26 agr2- SCCmecII strains, including two MSSA strains, 25 were multidrug-resistant, 18 were tstpositive, and 13 were agr-defective, whereas only five of the 18 agr1-SCCmecIV strains were multidrug-resistant, and all were tst-negative and agr-intact. agr1-SCCmecIV and ST8- agr1-SCCmecIV strains were more likely than agr2-SCCmecII strains to be COHA. Conclusions: MRSA was highly prevalent in both COHA and HA bacteremia. The introduction of virulent CA-MRSA strains may be an important cause of increased HA-MRSA bacteremia in VHS hospitals. [ABSTRACT FROM AUTHOR]

Candida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. glabrata. To address this question in Korea, we investigated antifungal resistance and non-synonymous mutations of the mismatch repair gene (msh2 mutations) in C. glabrata BSI isolates, as well as associated clinical characteristics, and compared the results according to MLST genotype. We assessed a total of 209 C. glabrata BSI isolates from seven hospitals in Korea for 2 years (2009 and 2014). Clinical features of candidemia and their outcomes were analyzed for 185 available cases. According to MLST, ST7 (47.8%) was the most common type, followed by ST3 (22.5%); the remainder represented 28 types of minor STs (29.7%). Fluconazole-resistance (FR) rates for ST7, ST3, and other strains were 9.0% (9/100), 8.5% (4/47), and 4.8% (3/62), respectively, and all were susceptible to amphotericin B and micafungin. All ST7 isolates harbored the V239L mutation in msh2, known to confer hypermutability, while 91.5% of ST3 isolates did not harbor the msh2 mutation. Overall, isolates of the same ST had identical msh2 mutations, with the exception of nine isolates. The msh2 mutations were identified in 68.8% (11/16) of the FR isolates and 67.4% (130/193) of the fluconazole susceptible-dose dependent isolates. There was no significant difference in all clinical characteristics between ST3 and ST7. However, the 30-day mortality of C. glabrata candidemia due to the two major ST (ST3 or ST7) strains was significantly higher than that of candidemia due to other minor ST strains (45.1 vs. 25.0%, p < 0.05). Multivariate logistic regression analysis also showed that two major STs (ST3 and ST7) were independent predictors of 30-day mortality. This study showed for the first time that two STs (ST7 and ST3) were predominant among BSI isolates in Korea, and that C. glabrata BSI isolates belonging to two major MLST genotypes are characterized by higher mortality. In addition, most msh2 mutations align with MLST genotype, irrespective of FR. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC). Materials and Methods Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a threedimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatment weighting (IPTW) method was used to minimize confounding bias. Results Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m² for males and ≤ 43.0 cm/m² for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associated with prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival. Conclusion The presence of sarcopenia at HCC diagnosis is independently associated with survival. [ABSTRACT FROM AUTHOR]

Rationale: The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation.Objectives: In this study, we investigated the role of ALCAM in the development of inflammation in allergic asthma.Methods: An ovalbumin (OVA)-induced allergic asthma model was established in wild-type (WT) and ALCAM-deficient (ALCAM-/-) mice. T-cell proliferation was evaluated in cocultures with dendritic cells (DCs). Bone marrow-derived dendritic cells (BMDCs) from WT and ALCAM-/- mice were cultured and adoptively transferred to OT-II mice for either OVA sensitization or challenge. An anti-ALCAM antibody was administered to assess its therapeutic potential. ALCAM concentrations in the sputum and serum of children with asthma were quantified by ELISA.Measurements and Main Results: Inflammatory responses were lower in ALCAM-/- mice than in WT mice, and T cells cocultured with DCs from ALCAM-/- mice showed reduced proliferation relative to those cocultured with DCs from WT mice. A decreased inflammatory response was observed upon adoptive transfer of BMDCs from ALCAM-/- mice as compared with that observed after transfer of BMDCs from WT mice. In addition, anti-ALCAM antibody-treated mice showed a reduced inflammatory response, and sputum and serum ALCAM concentrations were higher in children with asthma than in control subjects.Conclusions: ALCAM contributes to OVA-induced allergic asthma by stimulating T-cell activation and proliferation, suggesting it as a potential therapeutic target for allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Cases of infective endocarditis (IE) require prompt etiological diagnosis for effective treatment. Molecular methods can aid in rapid and reliable diagnosis of culturenegative IE cases. We evaluated the utility of 16S rDNA PCR and sequencing in determining the causative agents of IE in valve tissues, especially when specimens were obtained after initiation of antimicrobial therapy. Methods: We performed 16S rDNA PCR and sequencing in heart valve specimens and medical records review of 80 patients who underwent protocol-based cardiac surgery from 2013 to 2015. One patient did not meet the criteria for IE. Sixty-five (81.3%) and 14 patients (17.5%) were diagnosed as having definite IE and possible IE, respectively. Blood and heart valve biopsy tissue were examined by using routine microbiological methods. Results: Blood cultures in our hospital were IE-positive for 33 patients (41.8%), whereas 49 patients (62.0%) showed positive blood cultures when initial blood cultures performed at the referring hospital were included. Eighteen (22.8%) and 40 patients (50.6%) were IE-positive in valve tissue cultures and 16S rDNA PCR, respectively. Bacteria in the Streptococcus mitis group (n=26) were the most common etiological agents of IE. Eight (10.1%) culture-negative specimens tested positive by 16S rDNA PCR. In five of eight PCR-positive and culture-negative cases, fastidious or anaerobic organisms were the cause of IE. Conclusions: Direct 16S rDNA PCR and sequencing can be used as a supplementary method to conventional blood and biopsy culture testing, especially in culture-negative IE cases that are negative for IE by culture. [ABSTRACT FROM AUTHOR]

We evaluated the impact of revised Clinical and Laboratory Standards Institute (CLSI) breakpoints for broad-spectrum cephalosporins (BSCs) on the susceptibilities of 1,742 isolates of Enterobacter species, Serratia marcescens, Citrobacter freundii, and Morganella morganii. The 2011 CLSI criteria for cefotaxime and ceftazidime reduced the rates of susceptibility by 2.9% and 5.9%, respectively. The 2014 CLSI criteria for cefepime reduced the rate of susceptibility by 13.9%, and categorized 11.8% isolates as susceptible-dose dependent (SDD) for cefepime. Among 183 isolates with extended-spectrum β-lactamase (ESBL) phenotype, implementation of the new criteria reduced the rates of susceptibility to cefotaxime, ceftazidime, and cefepime by 2.8%, 14.8%, and 53.6%, respectively. The proportion of ESBL phenotype among BSC-susceptible isolates was low (0.9% for cefotaxime, 3.0% for ceftazidime, and 3.3% for cefepime). In summary, implementation of new CLSI criteria led to little change in susceptibility to cefotaxime and ceftazidime but a substantial change in susceptibility to cefepime. The recognition of revised CLSI criteria for BSC and SDD will help clinicians to select the optimal antibiotic and dosing regimen. [ABSTRACT FROM AUTHOR]

Background: Enterobacter species are important nosocomial pathogens, and there is growing concern about their ability to develop resistance during antimicrobial therapy. However, few data are available on the clinical characteristics and outcomes of Enterobacter spontaneous bacterial peritonitis (SBP).Methods: We retrospectively identified all patients with SBP caused by Enterobacter species admitted to a tertiary care hospital between January 1997 and December 2013. Each case was age- and sex-matched with four patients with Escherichia coli SBP.Results: A total of 32 cases with Enterobacter SBP and 128 controls with E. coli SBP were included. Twenty-one (65.6 %) cases and 111 (86.7 %) controls had Child-Pugh class C (P = 0.006). Cases were significantly more likely to have hepatocellular carcinoma (65.6 % vs. 37.5 %, P = 0.004) and upper gastrointestinal bleeding (28.1 % vs. 9.4 %, P = 0.005). The initial response to empirical therapy (81.3 % vs. 81.2 %, P = 0.995) and the 30-day mortality (37.5 % vs. 28.9 %, P = 0.35) were not significantly different between the groups. Drug resistance emerged in one case and in no controls (4.3 % [1/23] vs. 0 % [0/98], P = 0.19).Conclusions: Compared with E. coli SBP, patients with Enterobacter SBP more frequently had hepatocellular carcinoma and upper gastrointestinal bleeding, yet clinical outcomes were comparable. Development of resistance during third-generation cephalosporin therapy was infrequent in patients with Enterobacter SBP. [ABSTRACT FROM AUTHOR]