Kahweol Inhibits Pro-Inflammatory Cytokines and Chemokines in Tumor Necrosis Factor-α/Interferon-γ-Stimulated Human Keratinocyte HaCaT Cells.

Atopic dermatitis (AD), marked by intense itching and eczema-like lesions, is a globally increasing chronic skin inflammation. Kahweol, a diterpene that naturally occurs in coffee beans, boasts anti-inflammatory, antioxidative, and anti-cancer properties. This research explores the anti-inflammatory action of kahweol on HaCaT human keratinocytes stimulated by tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), focusing on key signal transduction pathways. Our results demonstrate that kahweol markedly reduces the production of IL-1ß, IL-6, C-X-C motif chemokine ligand 8, and macrophage-derived chemokine in TNF-α/IFN-γ-activated HaCaT cells. Furthermore, it curtails the phosphorylation of key proteins in the mitogen-activated protein kinase (MAPK) pathways, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. Additionally, kahweol impedes the phosphorylation and nuclear translocation of the NF-κB p65 subunit and constrains its DNA-binding capability. It also hampers the phosphorylation, nuclear translocation, and DNA-binding activities of signal transducer and activator of transcription 1 (STAT1) and STAT3. Collectively, these findings suggest that kahweol hinders the generation of cytokines and chemokines in inflamed keratinocytes by inhibiting the MAPK, NF-κB, and STAT cascades. These insights position kahweol as a promising agent for dermatological interventions, especially in managing inflammatory skin conditions such as AD.

6-Shogaol Ameliorates Liver Inflammation and Fibrosis in Mice on a Methionine- and Choline-Deficient Diet by Inhibiting Oxidative Stress, Cell Death, and Endoplasmic Reticulum Stress.

Non-alcoholic steatohepatitis (NASH) is becoming an increasingly serious global health threat, distinguished by hepatic lipid accumulation, inflammation, and fibrosis. There is a lack of approved pharmaceutical interventions for this disease, highlighting the urgent need for effective treatment. This study explores the hepatoprotective potential of 6-shogaol, a natural compound derived from ginger, in a methionine- and choline-deficient (MCD) dietary mouse model of NASH. Male C57BL/6J mice were subjected to the MCD diet for 4 weeks to induce NASH, with concurrent intraperitoneal administration of 6-shogaol (20 mg/kg) three times a week. While 6-shogaol did not impact body weight, liver weight, or hepatic lipid accumulation, it effectively mitigated liver injury, inflammation, and fibrosis in MCD diet-fed mice. Mechanistically, 6-shogaol inhibited lipid and DNA oxidation, restored hepatic glutathione levels, and regulated the expression of pro-oxidant and antioxidant enzymes. Furthermore, 6-shogaol inhibited apoptosis and necroptosis, as indicated by a decrease in TUNEL-stained cells and downregulation of apoptosis- and necroptosis-associated proteins. Additionally, 6-shogaol alleviated endoplasmic reticulum (ER) stress, as demonstrated by decreased expression of molecules associated with unfolded protein response pathways. These findings underscore the potential of 6-shogaol as a therapeutic intervention for NASH by targeting pathways related to oxidative stress, cell death, and ER stress.

Eupatilin Ameliorates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Mice.

Acute kidney injury (AKI) is a common complication of sepsis. Eupatilin (EUP) is a natural flavone with multiple biological activities and has beneficial effects against various inflammatory disorders. However, whether EUP has a favorable effect on septic AKI remains unknown. Here, we examined the effect of EUP on lipopolysaccharide (LPS)-evoked AKI in mice. LPS-evoked renal dysfunction was attenuated by EUP, as reflected by reductions in serum creatinine and blood urea nitrogen levels. LPS injection also induced structural damage such as tubular cell detachment, tubular dilatation, brush border loss of proximal tubules, and upregulation of tubular injury markers. However, EUP significantly ameliorated this structural damage. EUP decreased serum and renal cytokine levels, prevented macrophage infiltration, and inhibited mitogen-activated protein kinase and NF-κB signaling cascades. Lipid peroxidation and DNA oxidation were increased after LPS treatment. However, EUP mitigated LPS-evoked oxidative stress through downregulation of NPDPH oxidase 4 and upregulation of antioxidant enzymes. EUP also inhibited p53-mediated apoptosis in LPS-treated mice. Therefore, these results suggest that EUP ameliorates LPS-evoked AKI through inhibiting inflammation, oxidative stress, and apoptosis.

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice.

Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.

A case of coronavirus disease 2019-infected liver transplant donor.

Coronavirus disease 2019 (COVID-19) is a novel infectious disease that continues to spread on a global scale. There has been growing concern about donor-derived transmissions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present the case of a patient who underwent ABO-incompatible living donor liver transplantation without knowing that the liver donor was infected with COVID-19 during the donation procedure. In this case, the donor-derived transmission to the recipient was not identified, and the liver donor was found to be recovering from a COVID-19 infection. The donor-derived transmission was not identified.

Diagnostic performance of immunochromatography assay for rapid detection of IgM and IgG in coronavirus disease 2019.

Serologic assays have been developed to detect infection with coronavirus disease 2019 (COVID-19). This study was conducted to evaluate the diagnostic performance of an immunochromatography-based assay of human serum for COVID-19. The present study enrolled 149 subjects who had been tested by real-time reverse transcription-polymerase chain reaction (RT-PCR) for COVID-19 and were classified into two groups: 70 who were positive for COVID-19 and 79 who were negative for COVID-19 based on RT-PCR. An immunochromatography-based COVID-19 immunoglobulin G (IgG)/immunoglobulin M (IgM) rapid test on the sera of the study population was applied to measure the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve compared to RT-PCR, with a 95% confidence interval (CI). IgM or IgG antibodies were detected in 65 subjects (92.9%) classified as positive for COVID-19 and in three subjects (3.8%) classified as negative for COVID-19. The sensitivity and specificity percentages for IgM or IgG antibodies were 92.9% (95% CI: 84.1-97.6) and 96.2% (95% CI: 89.3-99.2), respectively, with 95.6% PPV and 93.8% NPV. The PPV rapidly improved with increasing disease prevalence from 19.8% to 96.1% in the presence of either IgM or IgG, while the NPV remained high with a change from 99.9% to 93.1%. The area under the ROC curve was 0.945 (95% CI: 0.903-0.988) for subjects with either IgM or IgG positivity. In conclusion, the immunochromatography-based COVID-19 IgG/IgM rapid test is a useful and practical diagnostic assay for detection of COVID-19, especially in the presence of IgM or IgG antibodies.

Pharmacological inhibition of p300 ameliorates steatosis, inflammation, and fibrosis in mice with non-alcoholic steatohepatitis.

The histone acetyltransferase p300 plays a pivotal role in regulating gene expression and cellular phenotype through epigenetic mechanisms. It significantly influences lipid metabolism, which is a key factor in the pathogenesis of non-alcoholic steatohepatitis (NASH), by modulating the transcription of genes involved in lipid synthesis and accumulation. This study aimed to investigate the protective potential of inhibiting p300 in NASH. Male C57BL/6J mice were subjected to a methionine- and choline-deficient (MCD) diet for 4 weeks to induce NASH, and during this period, the p300 inhibitor C646 (10 mg/kg) was administered three times a week. C646 treatment reduced the elevation of p300 expression and histone H3 acetylation, leading to a decrease in liver injury markers in the serum and an improvement in the histological abnormalities observed in MCD diet-fed mice. C646 also reduced lipid accumulation by modulating de novo lipogenesis and suppressed inflammation, including cytokine overproduction and macrophage infiltration. Furthermore, C646 mitigated liver fibrosis and myofibroblast accumulation. This protective effect was achieved through the inhibition of apoptosis by reducing p53 and Bax expression and the suppression of ferroptosis by decreasing lipid peroxidation while enhancing antioxidant defenses. Additionally, C646 alleviated endoplasmic reticulum stress, as evidenced by the downregulation of unfolded protein response signaling molecules. These results highlight the potential of p300 as a therapeutic target for NASH.

Vaccine effectiveness and the epidemiological characteristics of a COVID-19 outbreak in a tertiary hospital in Republic of Korea.

BACKGROUND: Healthcare facilities are high-risk sites for infection. This study analyzed the epidemiological characteristics of a coronavirus disease 2019 (COVID-19) outbreak in a tertiary hospital after COVID-19 vaccination had been introduced in Republic of Korea. Vaccine effectiveness (VE) and shared anti-infection strategies are also assessed. METHODS: The risk levels for 4,074 contacts were evaluated. The epidemiological characteristics of confirmed cases were evaluated using the chi-square test. The "1 minus relative risk" method was used to determine VE in preventing infection, progression to severe disease, and death. In the largest affected area (the 8th floor), a separate relative risk analysis was conducted. A multivariate logistic regression analysis (with 95% confidence interval [CIs]) was used to identify transmission risk factors with a significance level <10% via the backward elimination method. RESULTS: In total, 181 cases of COVID-19 were confirmed, with an attack rate of 4.4%. Of those cases, 12.7% progressed to severe disease, and 8.3% died. In the cohort isolation area on the 8th floor, where 79.0% of the confirmed cases occurred, the adjusted odds ratio was 6.55 (95% CI, 2.99-14.33) and 2.19 (95% CI, 1.24-3.88) for caregivers and the unvaccinated group, respectively. VE analysis revealed that 85.8% of the cases that progressed to severe disease and 78.6% of the deaths could be prevented by administering a second vaccine. CONCLUSION: Caregiver training for infection prevention and control is necessary to reduce infection risk. Vaccination is an important intervention to reduce the risk of progression to severe disease and death.

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

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

Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019.

BACKGROUND/AIMS: The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. METHODS: This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. RESULTS: Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. CONCLUSION: Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.

The Advantages of Indocyanine Green Fluorescence Imaging in Detecting and Treating Pediatric Hepatoblastoma: A Preliminary Experience.

Background: Currently, indocyanine green (ICG) fluorescence imaging enables radical surgical resection in hepatoblastoma (HB) and has beneficial uses; however, its usage in pediatric patients is still limited. Methods: From 2015 to 2019, 17 hepatoblastoma patients underwent 22 fluorescence-guided surgery using ICG. ICG (0.3 mg/kg) was intravenously injected 24-48 h before the operation. With ICG/NIR camera, intraoperative identification of biological structures and demarcation of mass were conducted. Results: ICG fluorescence-guided surgery was performed for hepatoblastoma in 22 cases: 16, 1, and 2 cases underwent anatomic resection, partial hepatectomy, and liver transplantation, respectively. Six patients accompanied lung metastasis at the time of surgery, and two patients underwent lung surgery using ICG. The median interval from ICG injection to surgery was 38.3 h (range, 20.5-50.3 h). The median tumor size was 36.5 mm (range, 2-132 mm). According to the pathologic finding, the median safety margin was secured for 6 mm (range, 0-11 mm) and there was no residual finding at the liver at the follow-up computed tomography (CT). Conclusions: ICG fluorescence imaging in children with HB was feasible and safe for tumor demarcation and enhancing the accuracy of radical tumor resection.

Prognostic Implication of Baseline Sarcopenia for Length of Hospital Stay and Survival in Patients With Coronavirus Disease 2019.

BACKGROUND: The impact of sarcopenia on clinical outcomes of coronavirus disease 2019 (COVID-19) is not clearly determined yet. We aimed to investigate the association between baseline sarcopenia and clinical outcomes in patients with COVID-19. METHODS: All hospitalized adult patients with COVID-19 who had baseline chest computed tomography (CT) scans at a Korean university hospital from February 2020 to May 2020 were included. The main outcome was time from hospital admission to discharge. Death was considered as a competing risk for discharge. Baseline skeletal muscle cross-sectional area at the level of the 12th thoracic vertebra was measured from chest CT scans. The lowest quartile of skeletal muscle index (skeletal muscle cross-sectional area divided by height-squared) was defined as sarcopenia. RESULTS: Of 121 patients (median age, 62 years; 44 men; 29 sarcopenic), 7 patients died and 86 patients were discharged during the 60-day follow-up. Patients with sarcopenia showed a longer time to discharge (median, 55 vs 28 days; p < .001) and a higher incidence of death (17.2% vs 2.2%; p = .004) than those without sarcopenia. Baseline sarcopenia was an independent predictor of delayed hospital discharge (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [95% CI], 0.23-0.96), but was not independently associated with mortality in patients with COVID-19 (aHR, 3.80; 95% CI, 0.48-30.26). The association between baseline sarcopenia and delayed hospital discharge was consistent in subgroups stratified by age, sex, comorbidities, and severity of COVID-19. CONCLUSIONS: Baseline sarcopenia was independently associated with a prolonged hospital stay in patients with COVID-19. Sarcopenia could be a prognostic marker in COVID-19.

Clinical significance of ¹8F-fluoro-dexoxyglucose positron emission tomography in patients with adult-onset Still's disease: report of two cases and review of literatures.

Adult-onset Still's disease (AOSD) is a multi-systemic inflammatory disease that usually presents with high fever and variable systemic features. The pathogenesis and etiology of AOSD have not yet been clearly determined. In addition, there is no diagnostic test for AOSD. Even though some useful diagnostic criteria or laboratory findings, such as serum ferritin levels, have been proposed, useful imaging studies for the diagnosis or follow-up of AOSD have not been developed. We performed (18)F-fluoro-dexoxyglucose positron emission tomography ((18)F-FDG PET) on two AOSD patients who presented with a fever of unknown origin. In these patients, we initially identified abnormally increased FDG uptake in multiple lymph nodes, the spleen, or bone marrow. We then identified significantly decreased uptake during a follow-up study. On the basis of these cases, we suggest that (18)F-FDG PET may have the potential in the diagnosis of AOSD, as well as monitor clinical changes in the disease. More further investigation of (18)F-FDG PET in AOSD is needed in larger population.

The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic that had affected more than eight million people worldwide by June 2020. Given the importance of the presence of diabetes mellitus (DM) for host immunity, we retrospectively evaluated the clinical characteristics and outcomes of moderate-to-severe COVID-19 in patients with diabetes. METHODS: We conducted a multi-center observational study of 1,082 adult inpatients (aged ≥18 years) who were admitted to one of five university hospitals in Daegu because of the severity of their COVID-19-related disease. The demographic, laboratory, and radiologic findings, and the mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM. In addition, 1:1 propensity score (PS)-matching was conducted with the DM group. RESULTS: Compared with the non-DM group (n=847), patients with DM (n=235) were older, exhibited higher mortality, and required more intensive care. Even after PS-matching, patients with DM exhibited more severe disease, and DM remained a prognostic factor for higher mortality (hazard ratio, 2.40; 95% confidence interval, 1.38 to 4.15). Subgroup analysis revealed that the presence of DM was associated with higher mortality, especially in older people (≥70 years old). Prior use of a dipeptidyl peptidase-4 inhibitor or a renin-angiotensin system inhibitor did not affect mortality or the clinical severity of the disease. CONCLUSION: DM is a significant risk factor for COVID-19 severity and mortality. Our findings imply that COVID-19 patients with DM, especially if elderly, require special attention and prompt intensive care.

Suggested Indications for Enucleation of Solid Pseudopapillary Neoplasms in Pediatric Patients.

Background: Solid pseudopapillary neoplasms (SPNs) are rare, low-grade, malignant neoplasms that can occur in pediatric patients. Although complete resection of the tumor is the principle treatment, SPN enucleation (EN) has been reported to be effective in children. This study aimed to examine the feasibility and safety of EN by comparing it with conventional pancreatectomy (CP), and to present the indications for its use in pediatric patients. Methods: We retrospectively reviewed the medical records of 66 patients who underwent surgery for SPN at our institution from October 1992 to April 2018. Surgical methods, postoperative complications, hospital stay, and recurrence were compared. Results: Of the 66 patients, 15 (22.7%) were treated with EN and 51 (77.3%) were treated with CP. The mean duration of EN operation was 262 min (±145 min) and of CP was 345 min (±195 min). There was no statistically significant difference between the two methods (P = 0.13). To objectively compare the mass size between patients, we introduced a tumor size/intraperitoneal width ratio, which also revealed no significant difference between the 2 surgery groups (P = 0.21). The EN group had one case of recurrence at the resection site. The complications observed were fluid collection, splenic infarctions, hematomas, pancreatic fistulas, portal vein thromboses, and chylous drainage, among which pancreatic fistulas were the most frequent followed by moderate-severe fistulas in the EN group (P < 0.001). The mean postoperative fasting time (EN 17.0 ± 8.7 days vs. CP 5.1 ± 3.3 days, P < 0.001) and mean hospital stay (EN 23.4 ± 10.0 days vs. CP 13.2 ± 6.5 days, P = 0.002) showed statistically significant differences. Conclusion: Compared with CP treatment, EN of SPNs in children has the disadvantages of prolonged fasting times and hospital stays to recover from moderate pancreatic fistulas. However, if appropriate indications are applied, EN can be considered a safe and effective surgical procedure for children.

Preliminary Report of Seroprevalence of Anti-Measles Immunoglobulin G among Healthcare Workers of 6 Teaching Hospitals of Daegu, Korea in 2019.

The measles outbreak in Daegu of January 2019 made 6 teaching hospitals' organization test the measles immunity of their healthcare workers (HCWs). We found that 6,935 (75.9%) of 9,132 HCWs tested seropositive for anti-measles immunoglobulin G (IgG), and seropositivity rate was very different between 6 hospitals (range, 59.9-93.1%). The seroprevelence was lowest in the age of twenties, but the rate was different between 6 hospitals (range 47.0-85.5%). Therefore, to prevent measles from spreading to HCWs, each hospital should make their own data periodically about anti-measles IgG seropositivity of their HCWs.

Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study.

BACKGROUND: While herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population. METHODS: For a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100. RESULTS: We enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) -5.8%-51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65-74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4-77.5)] and against NBPP [effectiveness 35.0% (2.3-56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6-98.8) for PPV23-unique serotypes and 81.3% (38.6-94.3) for PPV23 serotypes excluding serotype 3. CONCLUSIONS: This study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.

Clinical significance of spontaneous Aeromonas bacterial peritonitis in cirrhotic patients: a matched case-control study.

BACKGROUND: Although Aeromonas species are known to cause bacteremia in patients with cirrhosis, less is known about spontaneous bacterial peritonitis (SBP) caused by Aeromonas species in these patients. METHODS: We performed a retrospective, matched case-control study (1:2 ratio) consisting of patients presenting with SBP due to Aeromonas species from January 1997 through December 2006. Control subjects were patients with SBP caused by other organisms and were matched to the patients by age (+/- 1 year) and sex. RESULTS: We identified 43 patients with SBP due to Aeromonas species, 40 (93%) of whom had Aeromonas hydrophila infection and 3 (7%) of whom had Aeromonas sorbia infection. There were 81 control subjects, of whom 38 (47%) were infected with Escherichia coli, 25 (31%) were infected with Klebsiella species, 12 (15%) were infected with Streptococcus species, and 6 (7%) were infected with other bacteria. Baseline Child-Pugh class and model for end-stage liver disease score did not differ between groups. A significant increase in the incidence of infection during the warm season (July-September) was observed in the group with SBP due to Aeromonas species, compared with the group with SBP due to other bacteria (63% vs. 25%; P < .001). Diarrheal episodes were significantly more frequent in the group with SBP due to Aeromonas species (26% vs. 6%; P = .002). There were no statistically significant differences between groups with regard to appropriateness of initial antibiotic therapy,3-day mortality, and 30-day cumulative survival. In the group with Aeromonas infection, the in-hospital mortality rate was 23%; septic shock was the only independent prognostic factor of in-hospital mortality (odds ratio, 34.5;95% confidence interval, 1.9-640.6; P = .02). CONCLUSION: Aeromonas species should be considered to be a causative organism of SBP in cirrhotic patients presenting with diarrheal episodes during the warm season. Compared with SBP caused by other organisms, SBP due to Aeromonas species was not associated with more-advanced cirrhosis.

Effects of a plasmid-encoded qnrA1 determinant in Escherichia coli strains carrying chromosomal mutations in the acrAB efflux pump genes.

The qnrA1 gene was cloned into a plasmid vector and transformed into Escherichia coli strains carrying chromosomal mutations in the acrAB drug efflux system. In acrAB-deleted strains, and in strains overexpressing acrAB, viable qnrA conferred higher MIC levels (at least a 32-fold increase) for fluoroquinolones than were observed in the parent strains.

Adult invasive pneumococcal disease in the Republic of Korea: Risk medical conditions and mortality stratified by age group.

OBJECTIVES: This study aimed to characterize the risk factors for mortality in adult patients with invasive pneumococcal disease (IPD) stratified by age groups, after implementation of the national immunization program of 23-valent polysaccharide vaccine (PPSV23) for those aged ≥65 years in the Republic of Korea (ROK). METHODS: Clinical data and pneumococcal isolates from adult patients with IPD (≥18 years of age) were collected prospectively from 20 hospitals through the nationwide surveillance program from March 2013 to October 2015. RESULTS: A total of 319 patients with IPD were enrolled. Median age was 69 years. Overall in-hospital mortality was 34.2%: 17.1% in those aged 18-49 years, 23.7% in those aged 50-64 years, 33.0% in those aged 65-74 years, and 51.0% in those aged ≥75 years (p<0.001). In particular, early death within 7days of hospitalization accounted for 60.6% (66/109). While old age (≥65 years), higher Pitt bacteremia score (≥4), and bacteremic pneumonia were independently associated with IPD mortality in all age groups, an additional mortality risk factor of immunocompromised status was identified for patients aged 50-64 years. PPSV23 serotypes accounted for 64.4% (122/189) of the pneumococcal isolates serotyped. CONCLUSIONS: This study suggests that vaccine-type IPD continues to place a substantial burden on older adults in the ROK, necessitating an effective vaccination strategy for those at higher risk.