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Background Microhepatocellular carcinoma with a gross bile duct tumor thrombus is extremely rare, making the correct preoperative diagnosis difficult. Case presentation A 78-year-old man was referred to our department for close examination of a liver tumor that was incidentally detected using ultrasonography. Blood tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a 2-cm-sized hyperechoic mass with indistinct borders and hypoechoic margins at the origin of the right hepatic duct. Dynamic computed tomography showed a tumor with arterial phase predominance, a heterogeneous contrast effect, and prolonged enhancement. Cystic structures were observed in the tumors. In addition, localized dilatation of the caudate lobe bile duct was observed near the tumor. Cholangiography showed that the common bile duct, right and left hepatic ducts, and secondary branches did not have dilatation or stenosis. Biopsies of the bile duct revealed no malignancy. Under suspicion of intrahepatic intraductal papillary neoplasm of the bile duct, right hemi-hepatectomy was performed. The extrahepatic bile duct was preserved, because no tumor was found at the margin of the right hepatic duct during intraoperative frozen diagnosis. Macroscopically, the lesion was an 18 × 15 mm tumor occupying a dilated intrahepatic bile duct near the right hepatic duct, with a soft, fine papillary tumor. Based on morphology and immunostaining, tumor matched with moderately differentiated hepatocellular carcinoma. In addition, a 2 mm-sized hepatocellular carcinoma was observed in the liver parenchyma near the bile duct, where the tumor was located. Conclusions Based on these findings, the patient was diagnosed with small hepatocellular carcinoma with a gross bile duct tumor thrombus. The cystic part seen on the preoperative images was considered as a gap between the bile duct and the tumor thrombus. The patient recovered well with no signs of recurrence 20 months after surgery.

Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea.The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated.The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699).This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

Burnout is a form of negative emotional and physical response to job stress. This study aimed to investigate the prevalence of burnout among healthcare workers responding to the coronavirus disease 2019 (COVID-19) outbreak in Korea and to explore correlates of burnout among healthcare workers. A nationwide questionnaire-based survey was conducted from December 1, 2020, to January 29, 2021 on 1425 healthcare workers who worked in one of the 16 healthcare facilities designated for COVID-19 care, in public health centers, or as paramedics in Korea. Burnout was assessed using 16 Korean-adapted items based on the Oldenburg Burnout Inventory (OLBI). Data were collected using a structured questionnaire and analyzed using the R version 4.1.1 software program. OLBI results indicate clinically exhaustion in 84.5% (1204/1425) and clinically disengagement in 91.1% (1298/1425), and 77.3% (1102/1425) met the score criteria for both the exhaustion and disengagement subscales for burnout. Burnout rate was significantly increased in the group with chronic fatigue symptoms (Fatigue Severity Scale ≥ 3.22) after the outbreak of COVID-19 (OR, 3.94; 95% CI 2.80–5.56), in the female group (OR, 2.05; 95% CI 1.46–2.86), in the group with physical symptoms (Patient Health Questionnaire-15 ≥ 10) after the outbreak of COVID-19 (OR, 2.03; 95% CI 1.14–3.60), in the group with a higher Global Assessment of Recent Stress scale (OR, 1.71; 95% CI 1.46–2.01), in the group with post-traumatic stress symptoms (Primary Care Post-Traumatic Stress Disorder-5 ≥ 2) (OR, 1.47; 95% CI 1.08–2.01), and in the younger age group(OR, 1.45; 95% CI 1.22–1.72). The chronic fatigue symptoms were correlated with cumulative days of care (OR, 1.18; 95% CI 1.02–1.37). The physical symptoms were correlated with average contact hours with COVID-19 patients per day (OR, 1.34; 95% CI 1.17–1.54), and cumulative days of care (OR, 1.21; 95% CI 1.06–1.38). Most Korean healthcare workers suffered from burnout related to excessive workload during the COVID-19 pandemic. During a widespread health crisis like COVID-19, it is necessary to regularly check the burnout status in healthcare workers and reduce their excessive workload by supplementing the workforce and providing appropriate working hours sufficient rest hours.

BackgroundGBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) up to 2 weeks after the second dose, and safety data up to a median of 2.5 months follow-up.MethodsRandomised, active-controlled, observer-blinded, multinational study: Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination, n=1956) randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety); Cohort 2 (regardless of baseline serostatus; n=2080) randomised 5:1 (safety). Primary objectives: demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 versus ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity.FindingsAt 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03 / ChAdOx1-S) was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1). The between-group SCR difference of 10.76% (95% CI 7.68–14.32) satisfied the non-inferiority criterion (95% CI lower limit > −5%).The proportion of subjects with adverse events (AEs) after any vaccination was higher with GBP510/AS03 versus ChAdOx1-S for solicited local AEs (56.69% vs 49.20%), but was similar for solicited systemic AEs (51.21% vs 53.51%) and unsolicited AEs (13.27% vs 14.56%). No safety concerns were identified during follow-up for a median 2.5-months after the second vaccination.InterpretationGBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile.FundingThis work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.RESEARCH IN CONTEXTEvidence before this studyImmunobridging has been proposed as an approach for assessing new COVID-19 vaccines by comparing the immunogenicity of candidate vaccines with an active comparator with demonstrated clinical efficacy. We searched PubMed up to 26 October 2022 for immunobridging clinical trials comparing a candidate vaccine with an approved vaccine, using the terms “immunobridging”, “SARS-CoV-2”, “COVID-19”, and “vaccine”. A phase 2/3 study showed that the ChAdOx1 vaccine, manufactured by the Serum Institute of India after technology transfer from Oxford University/AstraZeneca, had a non-inferior immune response compared to the original ChAdOx1 (AZD1222) vaccine. A post hoc analysis of phase 2 data found that MVC-COV1901 vaccine (a protein subunit vaccine developed by Medigen Vaccine Biologics Corporation, Taiwan) was non-inferior to ChAdOx1 (AZD1222) with respect to neutralising antibody titres. A phase 3 study found that VLA2001 (an adjuvanted, inactivated whole-virus vaccine developed by Valneva, Austria) was superior to ChAdOx1 with respect to neutralising antibody titres and non-inferior with respect to seroconversion rates.Added value of this studyThis is the first study comparing the immunogenicity of recombinant SARS-CoV-2 protein nanoparticle vaccine GBP510 adjuvanted with AS03 versus ChAdOx1-S. Interim analysis found that two-dose vaccination with GBP510/AS03 induced stronger neutralising antibody immune responses compared with ChAdOx1-S against the ancestral D614G strain at 2 weeks after the second dose. GBP510/AS03 had an acceptable safety profile during a median 2.5 months of follow-up.Implications of the available evidenceThis interim analysis suggests that GBP510/AS03 induces strong neutralising antibody responses against SARS-CoV-2 ancestral strain and has an acceptable safety profile.

Background Although many deaths due to carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia occur within a few days after the onset of bacteremia, risk factors for early mortality (EM) have not been deeply investigated. We aimed to determine the risk factors for EM and the difference between risk factors associated with EM and late mortality (LM) in CRAB bacteremia. Methods All patients with CRAB bacteremia in 10 hospitals during a 1-year study period were identified. We prospectively collected patients’ clinical data, including microbiological and demographic data, underlying comorbidities, origin of bacteremia, severity of illness, antibiotic therapy, and mortality. Among the cases with mortality within 30 days, EM and LM were defined as death within 3 and more than 5 calendar days from the first positive blood culture, respectively. Results A total of 212 CRAB bacteremia cases were included in the analysis. Of 122 (57.5%) patients with 30-day mortality, EM was observed in 75 (61.5%) patients and LM in 39 (32.0%) patients. The proportion of severe sepsis or septic shock, Pitt score, and Sequential Organ Failure Assessment (SOFA) score were significantly higher in 30-day deaths than 30-day survivors. These factors of clinical severity were also significantly higher in patients with EM than those with LM. While urinary tract infection as the factor of site of infection and the severity of illness were independent predictors of LM, only factors representing the severity of illness were independent risk factors for EM. Appropriate empirical antibiotic therapy was associated with reduced risk of EM. Conclusion The difference between risk factors for EM and LM was identified in this study. Our data suggest that a large proportion of CRAB bacteremia with high severity progress to a rapidly fatal course, regardless of the underlying diseases or source of infection. Further studies might be needed to investigate the microbiological factors associated with CRAB and pathogen-host interaction in patients with EM. Disclosures All Authors: No reported disclosures.

Background Antibiotic resistance threatens public health worldwide, and inappropriate use of antibiotics is one of the main causes. Antibiotic use for asymptomatic bacteriuria (ABU) has been defined as “antibiotics never events”, and urinary tract infection (UTI) is one of the most common infectious diseases for which antibiotics are prescribed in Korea. To establish an effective antimicrobial stewardship strategy, a qualitative assessment of antibiotic use in actual clinical syndrome is necessary. Methods Cases of positive urine cultures (≥105 CFU/ml), performed in inpatient, outpatient, and emergency departments in April 2021 were screened in 26 hospitals located throughout Korea. Cases were classified into ABU, lower UTI, and upper UTI. The appropriateness of antibiotic use was retrospectively evaluated by infectious disease specialists using quality indicators based on the domestic clinical guideline for ABU and UTI. Figure 1.Study flow diagram Results A total of 2697 cases of ABU or UTI were included. The appropriateness of antibiotic use was assessed in 1157 cases with asymptomatic bacteriuria, 677 and 863 cases with lower and upper UTI (Figure 1). Antibiotics were prescribed in 21.7% (251 of 1157) of ABU without appropriate indication. Of 66 ABU cases with appropriate indication in which prophylactic antibiotics were prescribed, the duration of antibiotics was adequate in only 34.8% (Table 1). For lower UTI, the appropriateness of empirical and definite antibiotics was 77.8% (527 of 677) and 68.0% (353 of 519). In terms of upper UTI, 86.3% (745 of 863) and 78.2% (583 of 746) was appropriate, respectively. The duration of antibiotics was adequate in 65.7% (421 of 641) of lower UTI and 77.9% (592 of 760) in upper UTI (Table 2, 3). Conclusion This nationwide qualitative assessment of antibiotic use in ABU and UTI revealed that a significant proportion of antibiotics were prescribed inappropriately and, furthermore the duration of antibiotics was prolonged unnecessarily. Interventions for appropriate antibiotic use in ABU and UTI at the national level are required. Disclosures All Authors: No reported disclosures.

The Gangwon-do Province in Korea features abundant limestone areas and numerous limestone caves; however, few studies have conducted systematic research on the limestone caves in this area. In this study, we observed and explored the biota of three undisclosed caves located in Pyeongchang-gun, Gangwon-do Province (Jangamgul Cave, Baramgul Cave, and Ssanggul Cave) to further understand their ecology. As a result, a total of four phyla, 12 classes, 30 orders, 77 families, and 125 species of cave organisms were discovered, including three phyla, 11 classes, 23 orders, 51 families, and 77 species in Jangamgul Cave; four phyla, 10 classes, 23 orders, 43 families, and 52 species in Baramgul Cave; and three phyla, nine classes, 20 orders, 41 families, and 54 species in Ssanggul Cave. Several threatened species such as Plecotus auritus (Linnaeus, 1758), designated as Class 2 endangered wildlife in Korea, Onychodactylus fischeri (Boulenger, 1886), designated as a least concern (LC) species by the IUCN, and Galloisiana sp., described as an extant species of the relict insect were found in this study. Our results are significant in providing information on the distribution of cave organisms living by adapting to the cave environment.

Although neoadjuvant chemotherapy (NAC)-gemcitabine plus S-1 (GS) has been reported to have a survival benefit in patients with resectable pancreatic ductal adenocarcinoma (PDAC), optimal candidates for NAC-GS have not been clearly identified.A total of 81 patients with PDAC who underwent pancreatectomy after NAC-GS between 2013 and 2019 were divided into 2 groups based on Evans classification: grade I (10% tumor cell destruction, n = 19) and grades II and III (10% tumor cell destruction, n = 62). Univariate and multivariate analyses using clinical characteristics available before initiation of NAC were performed to predict Evans classification grade I (Evans I).The overall survival in patients with Evans I was significantly lower than that in patients with Evans II and III (P0.001). Multivariate analysis revealed a carcinoembryonic antigen level of3.6 ng/mL (P = 0.001) and C-reactive protein to albumin ratio of0.062 (P = 0.017) as independent predictors for Evans I disease. Seven of 11 patients who met both criteria had Evans I disease.Serum carcinoembryonic antigen and C-reactive protein to albumin ratio are associated with Evans I disease in patients with PDAC who receive NAC-GS. Patients who meet both predictors may not be optimal candidates for NAC-GS.

Recently, the number of patients with pancreatic ductal adenocarcinoma (PDAC) who have received both neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) has been increasing. However, whether adverse events (AEs) during AC influence the prognosis of patients with resected PDAC who do or do not receive NAC remains uncertain. Patients with PDAC who underwent a pancreatectomy between 2011 and 2019 were divided into two groups: an upfront surgery (UFS) group (n = 72), and an NAC group (n = 77). Patients who received AC were then divided into two groups: an AE grade 0/1/2 group (AE-G-0/1/2) and an AE grade 3/4 group (AE-G-3/4). The relationship between AEs and patient outcome and predictors of AE-G-3/4 were investigated. AC was used in 54 and 65 patients in the UFS and NAC groups, respectively. In the NAC group, the relative dose intensity (RDI) and AC completion rate as well as the overall survival rate of patients with AE-G-3/4 (n = 15) during AC were significantly worse than those of patients with AE-G-0/1/2 (n = 50). However, similar differences were not observed in the UFS group. A multivariate analysis revealed that AE-G-3/4 during NAC, AC agent (gemcitabine), an albumin level

Two new species, Heteraphorura koreana sp. nov. and Psyllaphorura jirisana sp. nov., of the tribe Hymenaphorurini are described and illustrated based on materials from South Korea. Heteraphorura koreana sp. nov. belongs to the oriental species-group of the genus Heteraphorura, because of compound vesicles in the postantennal organ. This new species shares the same number of PAO with Heteraphorura pseudoseolagensis ( Martynova, 1981 ) from Russia, but differs in pso dorsal formula and lateral teeth of claw. Psyllaphorura jirisana sp. nov. is similar to Psyllaphorura sensillifera. (Martynova, 1981) from the Russian Far East, but can be distinguished by shape of vesicles in PAO, dorsal s-chaetae on head and ratio AS/unguis. www.zoobank.org/urn:lsid:zoobank.org:pub:F854CBFD-06D0-4396-B8D9-62468B427111 .

BACKGROUND/AIM An association between the pathological response to neoadjuvant chemotherapy (NAC) and the efficacy of adjuvant chemotherapy (AC) in patients with pancreatic ductal adenocarcinoma (PDAC) remains unknown. PATIENTS AND METHODS A total of 121 patients with PDAC who underwent a pancreatectomy between January 2013 and March 2020 were divided into two groups: an upfront surgery (UFS) group (n=42), and an NAC (gemcitabine plus S-1) group (n=79). In the NAC group, the pathological response was evaluated using the Evans classification. RESULTS The overall survival was significantly higher in patients with an AC relative dose intensity (RDI) ≥80% than in patients with an AC RDI

This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19.This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021.A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2.At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis.

The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed.We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model.During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss.A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

This study explored the relationship between integrase strand transfer inhibitor (INSTI)-based anti-retroviral agents and weight gain over time, and the risk factors for weight gain in Korean people living with human immunodeficiency virus (PLWH).The study was conducted retrospectively in PLWHs 18 years of age or older who took one of three INSTI-based single-tablet regimens (STRs) (tenofovir disoproxil fumarate/emtricitabine/elvitegravir/cobicistat [TDF/F/EVG/c], tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat [TAF/F/EVG/c], and abacavir/lamivudine/dolutegravir [ABC/3TC/DTG]) for more than 2 years at three university-affiliated hospitals in South Korea from May 2014 to December 2020. Analysis was performed in the treatment-naïve and treatment-experienced groups, respectively.Individual INSTI-based STRs were associated with weight gain at the 24-month follow up in both treatment-naïve (n = 179) and treatment-experienced (n = 290) groups. Body mass index (BMI) categories changed over time for TAF/F/EVG/c and ABC/3TC/DTG, with significant increases in the rates of overweight and obesity in treatment-naïve patients, whereas there was no change for TDF/F/EVG/c. TAF/F/EVG/c significantly increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) compared to other regimens over 24 months. In the treatment-naïve group, a baseline CD4INSTI-based STR continued to increase body weight at the 24-month follow up in treated and untreated Korean PLWH. Exercise, together with demographic-, HIV-, and anti-retroviral therapy-related factors, influenced weight gain. Therefore, when prescribing an INSTI-based STR, weight gain and metabolic changes should be closely monitored in PLWH with these risk factors.

SUMMARYBackgroundVaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles displaying the receptor-binding domain (RBD) in a highly immunogenic array.MethodsWe conducted a randomized, placebo-controlled, observer-blinded, phase 1/2 trial to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19–85 years. The main outcomes included solicited and unsolicited adverse events; anti-SARS-CoV-2 RBD IgG antibody and neutralizing antibody responses; T-cell immune responses.FindingsOf 328 participants who underwent randomization, 327 participants received at least 1 dose of vaccine. Each received either 10 μg GBP510 adjuvanted with AS03 (n = 101), 10 μg unadjuvanted GBP510 (n = 10), 25 μg GBP510 adjuvanted with AS03 (n = 104), 25 μg unadjuvanted GBP510 (n = 51), or placebo (n = 61). Most solicited adverse events were mild-to-moderate in severity and transient. Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic adverse events. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163.6/2599.2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 μg/25 μg) by 14 days after the second dose. Two-dose vaccination with 10 μg or 25 μg GBP510 adjuvanted with AS03 induced high titers of neutralizing antibody via pseudovirus (1369.0/1431.5 IU/mL) and wild-type virus (949.8/861.0 IU/mL) assays.InterpretationGBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3.FundingCoalition for Epidemic Preparedness InnovationsRESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for research articles published by December 31, 2021, using the terms “COVID-19” or “SARS-CoV-2,” “vaccine,” and “clinical trial.” In previously reported randomized clinical trials, we found that mRNA vaccines were more immunogenic than adenovirus-vectored vaccines. Solicited adverse events were more frequent and more severe in intensity after the first dose compared to the second dose for adenovirus-vectored vaccines, whereas they increased after the second dose of mRNA or recombinant spike-protein nanoparticle vaccines.Added value of this studyThis is the first human study evaluating the immunogenicity and safety of recombinant SARS-CoV-2 protein nanoparticle with and without adjuvant AS03, designed to elicit functional cross-protective responses via receptor-binding domain (RBD). Both 10 and 25 μg of GBP510 with AS03 formulations were well tolerated with an acceptable safety profile. Potent humoral immune responses against the SARS-CoV-2 RBD were induced and peaked by day 42 (14 days after the second dose). In addition, GBP510 adjuvanted with AS03 elicited a noticeable Th1 response, with production of IFN-γ, TNF-α, and IL-2. IL-4 was inconsistent and IL-5 nearly inexistent response across all groups.Implications of the available evidenceThe results from this phase 1/2 trial indicate that GBP510 adjuvanted with AS03 has an acceptable safety profile with no vaccine-related serious adverse events. Two-dose immunization with GBP510 adjuvanted with AS03 induced potent humoral and cellular immune responses against SARS-CoV-2.

The Korean fir (Abies koreana Wilson) is native to the higher mountains of South Korea, including the upper part of the Mt. Hallasan National Park, which is designated as the Biosphere Reserve of the United Nations Educational, Scientific, and Cultural Organization. This species is considered as endangered and climate-sensitive bioindicator. We collected a species of Anurophorus (Collembola) from withered and rolled leaves of Korean fir, which is distributing at >1,300 m in altitude on Mt. Hallasan. There are 6 species of this genus in the Korean Peninsula, except the collected species (designated as Anurophorus sp.) with clear differences among them. Anurophorus sp. is most similar to A. laricis Nicolet in the general pattern of body chaetotaxy but was characterized by the number of knobbed hairs on tibiotarsi of all legs. Partial DNA sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene were used as DNA barcodes to distinguish the species and to verify its usefulness. It shows clear difference in genetic distance between studied other Anurophorus spp. The result indicates that the COI barcodes is a useful tool for species discrimination of Anurophorus, and Anurophorus sp. studied here is likely to be new to science.

Background/purpose No effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched-chain amino acids (BCAA) on the recurrence-free survival (RFS) after hepatic resection in HCC patients. Methods In this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery-alone group. The BCAA group received BCAA (Livact® ) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS. Results Between January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery-alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P = .579) or OS (P = .268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of Conclusions Oral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance.

Background After pandemic, A(H1N1)pdm09 is generally known to be associated with younger adults' infection and greater severity than seasonal A(H3N2) but some inconsistences between recent studies exist. Objectives We aimed to compare the epidemiology and clinical outcomes of A(H1N1)pdm09 and A(H3N2) to verify and consolidate about the knowledge of known differences of subtypes. Methods Data were retrospectively collected from the hospital‐based influenza morbidity and mortality surveillance in South Korea in nine tertiary care hospitals, from August 31, 2014, to August 25, 2018. Patients with H1N1pdm09 or H3N2 infection admitted in the emergency room or ward were recruited. Results A total of 1747 patients had influenza A and were divided into two groups those with A(H1N1)pdm09 (n = 240) and those with A(H3N2) (n = 1507). A(H1N1)pdm09 group had younger age (mean age ± standard deviation 50.0 ± 18.8 in H1N1 vs 53.4 ± 21.1 in H3N2, P = .030), lower influenza vaccination (27.9% vs 43.9%, P

Objectives: This study evaluated the incidence, risk factors, and clinical characteristics of complications of candidaemia in adults, with a focus on endophthalmitis, endocarditis, and osteoarticular infections. Methods: All patients ≥18 years old with candidaemia in two Korean tertiary hospitals from 2007 to 2016 were investigated. Complications of candidaemia were defined as the presence of endophthalmitis, endocarditis, or osteoarticular infections documented in patients with candidaemia. The clinical characteristics and risk factors for candidaemia with complications were analysed in the patients who underwent ophthalmological examinations. Results: Of 765 adult patients with candidaemia, 34 (4.4%) met the definition of complications, including endophthalmitis in 29 (3.8%), endocarditis in 4 (0.5%), and osteoarticular infections in 3 (0.4%). Of the 225 patients who underwent ophthalmological examinations, 29 (12.9%) had endophthalmitis. Candida albicans was an independent risk factor for complicated candidaemia (OR, 5.12; 95% CI, 2.17–12.09; P < 0.001). Although the mortality rate was no higher in complicated candidaemia, the duration of antifungal therapy was longer (23.1 ± 17.6 vs. 16.4 ± 10.8 days, P = 0.042), and 13 patients (39.3%) underwent additional procedures or surgery. Conclusions: Complications of candidaemia occurred in 4.4% of adult patients. C. albicans was an independent risk factor for complicated candidaemia in adults. Complications of candidaemia might need prolonged treatment and additional procedures or surgery. Therefore, careful evaluation and active treatment of candidaemia with complications should be encouraged. Keywords: Candidaemia, Complication, Candida albicans

Background Annually, about 80% of the Korean elderly aged ≥65 years receive influenza vaccination. Repeated annual vaccination has been suggested as an important factor of poor influenza vaccine effectiveness (VE), though reported conflicting results. Methods During the consecutive A/H3N2-dominant influenza seasons between 2012 and 2015, we comparatively evaluated the VE (repeated vs. current season only) against laboratory-confirmed influenza, pneumonia and hospitalization in the elderly aged ≥65 years with influenza-like illness (ILI). Clinical and demographic data were collected prospectively, and vaccination status of prior and current seasons was verified using the immunization registry data of Korean Centers for Disease Control and Prevention. Results During the first A/H3N2-dominant season in 2012–2013, influenza vaccine showed statistically significant effectiveness against influenza A infection only and when vaccinated in the current season only (VE 53%, 95% CI 15–77). In the latter two seasons (2013–2015 years), the adjusted VE for influenza A was indistinguishable between repeated vaccination and vaccination in the current season only. Conclusion During consecutive influenza A/H3N2 epidemics, poor influenza vaccine effectiveness may be more pronounced among the elderly population with a high annual vaccine uptake rate.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA).We prospectively searched for MRAB and MRPA pneumonia cases and matched them with controls with susceptible-organism pneumonia and non-infected cases from ten hospitals over a 6-month period. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalization, age (years ± 10), sex, and admission date within 60 days. The total additional direct medical cost was estimated by the multistate model. A total of 108 cases of MRAB pneumonia [MRAB-P] and 28 cases of MRPA pneumonia [MRPA-P] were identified. The 90-day mortality rate was 37.0% and 39.3% for MRAB-P and MRPA-P, respectively. The additional medical costs were $42,203 and $35,556 for MRAB-P and MRPA-P, respectively. The estimated number of MRAB-P and MRPA-P cases were 1,309–2,483 and 339–644, respectively with estimated deaths being 485–920 and 133–253 in a year, respectively. The annual socioeconomic burden was $12,053,593–$22,898,271 and $15,241,883–$28,994,008, respectively. We estimated that MRAB-P and MRPA-P occurred in 1,648–3,172 patients, with 618–1,173 deaths, and caused $27,295,476–$51,892,279 in socioeconomic burden nationwide. It is time to investigate and invest in prevention of multidrug-resistant bacterial pneumonia.

We aimed to estimate the socioeconomic burden of pneumonia due to multidrug-resistant Acinetobacter baumannii (MRAB) and Pseudomonas aeruginosa (MRPA). We prospectively searched for MRAB and MRPA pneumonia cases and matched them with susceptible-organism pneumonia and non-infected patients from 10 hospitals. The matching criteria were: same principal diagnosis, same surgery or intervention during hospitalisation, age, sex, and admission date within 60 days. We calculated the economic burden by using the difference in hospital costs, the difference in caregiver costs, and the sum of productivity loss from an unexpected death. We identified 108 MRAB pneumonia [MRAB-P] and 28 MRPA pneumonia [MRPA-P] cases. The estimated number of annual MRAB-P and MRPA-P cases in South Korea were 1309-2483 and 339-644, with 485-920 and 133-253 deaths, respectively. The annual socioeconomic burden of MRAB-P and MRPA-P in South Korea was $64,549,723-122,533,585 and $15,241,883-28,994,008, respectively. The results revealed that MRAB-P and MRPA-P occurred in 1648-3127 patients, resulted in 618-1173 deaths, and caused a nationwide socioeconomic burden of $79,791,606-151,527,593. Multidrug-resistant organisms (MDRO) impose a great clinical and economic burden at a national level. Therefore, controlling the spread of MDRO will be an effective measure to reduce this burden.

As the coronavirus disease 2019 (COVID-19) pandemic is ongoing, heavy workload of healthcare workers (HCWs) is a concern. This study investigated the workload of HCWs responding to the COVID-19 outbreak in South Korea.A nationwide cross-sectional survey was conducted from September 16 to October 15, 2020, involving 16 healthcare facilities (4 public medical centers, 12 tertiary-care hospitals) that provide treatment for COVID-19 patients.Public medical centers provided the majority (69.4%) of total hospital beds for COVID-19 patients (n = 611), on the other hand, tertiary care hospitals provided the majority (78.9%) of critical care beds (n = 57). The number of beds per doctor (median [IQR]) in public medical centers was higher than in tertiary care hospitals (20.2 [13.0, 29.4] versus 3.0 [1.3, 6.6],As the severity of COVID-19 patients increases, the number of HCWs required increases. Because the workload of HCWs responding to the COVID-19 outbreak is much greater than other situations, a workforce management plan regarding this perspective is required to prevent burnout of HCWs.

Determination of the release from isolation for coronavirus disease 2019 (COVID-19) in immunocompromised patients who need additional hospitalization for treatment of non-COVID-19 related disease is important to prevent nosocomial transmission. However, there is insufficient evidence for an extended isolation period.In September 2021, when the Delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in the nephrology ward of a tertiary hospital in Gwangju, Korea. We conducted epidemiological investigations and whole-genome sequencing (WGS) of this virus.A man who underwent kidney transplantation was admitted to our hospital for the treatment of acute kidney injury. He was diagnosed with asymptomatic COVID-19 infection during a pre-admission screening test on September 1, 2021 and underwent isolation. After 10 days of isolation in the COVID-19-designated ward, he was transferred to the general nephrology ward. He underwent steroid pulse therapy (September 17 to September 23,60 mg/day prednisolone) due to acute T-cell rejection. On September 28, 2021, the first patient with COVID-19 was identified in the nephrology ward, and a rapid-response team was activated to identify additional patients with COVID-19 and prevent the spread of COVID-19. Epidemiological investigations revealed that 12 patients, two caregivers, and three healthcare workers from the nephrology ward were diagnosed with COVID-19. The WGS of specimens from 14 nosocomial outbreak samples and released an index patient exhibited the same Delta variant originating from the B.1.617.2 lineage. This hospital-acquired COVID-19 outbreak in the nephrology ward resulted in two (11.7%) deaths in patients who underwent kidney transplantation.We demonstrated that an immunocompromised patient can cause a nosocomial outbreak due to the prolonged shedding of infectious viruses. Prolonged isolation in patients under active immunosuppressive therapy may be necessary to prevent transmission, especially in the hospital setting.

BackgroundMultidrug-resistant organisms (MDROs), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug resistant Acinetobacter baumannii (MRAB), multidrug resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) are particularly important public health threats, but their detailed clinical outcomes and socioeconomic burden are adequately addressed.MethodsWe prospectively searched for these MDROs bacteraemia cases with matched controls from 10 hospitals across Korea, in a 6-month period, in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had similar principal diagnosis at admission time, major surgery or intervention during hospitalization, age (± 10 years), sex, and within ± 60 days of admission date. We collected detailed clinical information and estimated the total additional direct medical cost of each MDRO bacteraemia case using the multistate model. ResultsOf 486 MDRO bacteraemia cases identified for MRSA, MRAB, MRPA, CRE, and VRE, at 260, 87, 18, 20, and 101, respectively, their 90-day mortality rates (overall, 40.3%) were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. Their additional medical costs (overall, $27,700) were $15,768, $35,682, $39,908, $72,051, and $33,662 (compared to the no-infection group), respectively. Overall, these five MDRO bacteraemia cases occurred in 7,979 patients, caused 3,280 deaths, and cost $294,505,002 (range, $170,627,020 to $416,094,679) socioeconomic loss. ConclusionsTremendous clinical and economic burden occurred with MDRO bacteraemia compared with those of antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed to urgently prevent the increase, spread and expansion of antibiotic-resistant bacteria.

Invasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era.Prospective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates.A total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180.PCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.

The coronavirus disease 2019 (COVID-19) pandemic has caused health problems and distress among healthcare workers (HCWs), so supportive measures to promote their health and relieve distress are needed.We conducted two rounds of Delphi surveys with 20 COVID-19-related frontline healthcare professionals and public officials. The surveys evaluated means of supporting HCWs' health by improving health care systems and working environments in terms of effectiveness and urgency. The validity of the measures was assessed by calculating the content validity ratio.The top-priority measures to support HCWs were "secure isolation units capable of treating severe cases" in the facility infrastructure category, "secure nursing staff dedicated for patients in the intensive care units" in the personnel infrastructure category, "improve communication between central office and frontline field" in the cooperation system category, "support personal protective equipment and infection control supplies" in the aid supplies category, and "realization of hazard pay" in the physical/mental health and compensation category.There was consensus among the experts on the validity and priorities of policies in the facility, personnel, cooperation, supplies, and compensation categories regarding measures to promote COVID-19 related HCWs' health.

Objectives: We conducted an in vitro investigation of the activity of rifamycins against planktonic and biofilm states of Staphylococcus aureus and Staphylococcus epidermidis isolates from patients with prosthetic joint infections (PJIs), characterised their rpoB gene mutations, and analysed the clinical outcomes of rifampicin-resistant isolates. Methods: A total of 110 staphylococcal isolates were collected from patients with PJI. Antimicrobials tested using the broth microdilution method included rifampicin, rifabutin, rifapentine and rifaximin. We evaluated rpoB gene mutations to identify rifampicin resistance mechanisms. Clinical outcomes were assessed in rifampicin-resistant isolates. Results: The 110 staphylococcal isolates included 85 S. aureus (55% methicillin-resistant) and 25 S. epidermidis (100% methicillin-resistant). Seven S. aureus isolates and two S. epidermidis isolates were resistant to rifampicin [minimum inhibitory concentration (MIC) ≥2 μg/mL] and these isolates exhibited rpoB gene mutations. Among the 78 rifampicin-susceptible S. aureus isolates and 23 S. epidermidis isolates, 76 S. aureus isolates (97.4%) and all S. epidermidis isolates (100%) were highly susceptible (MIC ≤ 0.06 μg/mL) to other rifamycins. The minimum biofilm bactericidal concentrations for ≥50% of isolates (MBBC50) to rifampicin, rifabutin, rifapentine and rifaximin were 4, 1, 2 and 4 μg/mL for S. aureus and 1, 0.125, 0.25 and 0.5 μg/mL for S. epidermidis, respectively, among rifampicin-susceptible isolates. Among nine patients bearing rifampicin-resistant isolates, only three (33%) had successful outcomes. Conclusion: Rifamycins other than rifampicin show promising antistaphylococcal activity, including antibiofilm activity. Rifamycin-resistant staphylococci exhibit rpoB gene mutations.

Background: Carbapenem-resistance (CR) causes poor clinical outcomes and has limited treatment options. We aim to evaluate the differences in clinical characteristics and impact of carbapenem-resistance on outcomes between Acinetobacter baumannii (ABA) and Pseudomonas aeruginosa (PAE) bacteraemia. Methods: We prospectively identified all patients with ABA and PAE bacteraemia in 10 hospitals over a 1-year period and collected their detailed clinical information. Treatment failure was defined as all-cause 30-day mortality, persistent bacteraemia, or recurrence within 30 days.Results: We included 304 ABA and 241 PAE bacteraemia cases. CR was detected in 216 ABA (71%) and 55 PAE (23%). Treatment failure was significantly higher in CR-ABA than in CR-PAE (60.6% vs. 34.5%, P = 0.001). Multivariate analyses were stratified by patient data according to CR and the appropriateness of empirical therapy. For ABA patients, severe sepsis or septic shock and high Pitt bacteraemia score were independent risk factors for treatment failure in the inappropriate empirical antibiotics group. Pneumonia was a significant risk factor in the appropriate group. For PAE patients, hospital-acquired infection and high Pitt bacteraemia score were independent risk factors for treatment failure in both groups. CR was an independent risk factor in ABA for treatment failure in both the inappropriate (adjusted odds ratio [aOR]: 6.17, 95% confidence interval [CI]: 1.13-33.75, P = 0.036) and appropriate empirical treatment groups (aOR: 4.15, 95% CI: 1.16-14.84, P = 0.029), but not for patients with PAE bacteraemia. Conclusions: We demonstrated significant differences in the clinical characteristics and impact of CR on the clinical outcomes between ABA and PAE bacteraemia. Our findings suggest that different approaches may be needed to treat ABA and PAE bacteraemia.

BackgroundDendritic cells (DCs) are specialized antigen-presenting cells known to bridge innate and adaptive immune reactions. However, the relationship between circulating DCs and Orientia tsutsugamushi infection is unclear. Therefore, this study aimed to examine the level and function of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), two subsets of circulating DCs, in scrub typhus patients.MethodsThe study included 35 scrub typhus patients and 35 healthy controls (HCs). pDC and cDC levels, CD86 and CD274 expression, and cytokine levels were measured using flow cytometry.ResultsCirculating pDC and cDC levels were found to be significantly reduced in scrub typhus patients, which were correlated with disease severity. The patients displayed increased percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs in the peripheral blood. The alterations in the levels and surface phenotypes of pDCs and cDCs were recovered in the remission state. In addition, the production of interferon (IFN)-α and tumor necrosis factor (TNF)-α by circulating pDCs, and interleukin (IL)-12 and TNF-α by circulating cDCs was reduced in scrub typhus patients. Interestingly, our in vitro experiments showed that the percentages of CD86+ pDCs, CD274+ pDCs, and CD274+ cDCs were increased in cultures treated with cytokines including IFN-γ, IL-12, and TNF-α.ConclusionsThis study demonstrates that circulating pDCs and cDCs are numerically deficient and functionally impaired in scrub typhus patients. In addition, alterations in the expression levels of surface phenotypes of pDCs and cDCs could be affected by pro-inflammatory cytokines.

The first surge of coronavirus disease 2019 (COVID-19) cases began on June 27, 2020 in Gwangju metropolitan city, located in the southwestern part of South Korea, with a population of 1,501,000. Local governments and the Korean Center for Disease Control and Prevention immediately started an epidemiologic investigation and traced the contacts of patients using a wide variety of data sources, including location data from mobile devices, credit card transaction, and closed-circuit television footage. Until July 16, 2020, 138 community transmission cases and 10 infection clusters were identified across the city. Through contact tracing, epidemiologic relatedness was found in 136 (98.6%) of 138 cases. Our investigation showed how the extensive and meticulous contact tracing suppressed COVID-19 outbreak in a populated city.

Highlights • There are virus carriers in the asymptomatic population • The duration of viral shedding may be short in asymptomatic carriers • Fourteen days of isolation after diagnosis may be sufficient in entirely asymptomatic cases, From 71 laboratory-confirmed cases, we found three presymptomatic patients and 10 entirely asymptomatic infections. In two of the three incubation period patients, the viral titer in the presymptomatic period was very high (Ct value 35 RT-PCR within 14 days after diagnosis. Patients who have COVID-19 may already be infectious before there are symptoms, and 14 days of isolation after diagnosis may be sufficient in entirely asymptomatic cases.