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Abstract Right-sided infective endocarditis (RSIE) is less common than left-sided infective endocarditis (LSIE) and exhibits distinct epidemiological, clinical, and microbiological characteristics. Previous studies have focused primarily on RSIE in patients with intravenous drug use. We investigated the characteristics and risk factors for RSIE in an area where intravenous drug use is uncommon. A retrospective cohort study was conducted at a tertiary hospital in South Korea. Patients diagnosed with infective endocarditis between November 2005 and August 2017 were categorized into LSIE and RSIE groups. Of the 406 patients, 365 (89.9%) had LSIE and 41 (10.1%) had RSIE. The mortality rates were 31.7% in the RSIE group and 31.5% in the LSIE group (P = 0.860). Patients with RSIE had a higher prevalence of infection with Staphylococcus aureus (29.3% vs. 13.7%, P = 0.016), coagulase-negative staphylococci (17.1% vs. 6.0%, P = 0.022), and gram-negative bacilli other than HACEK (12.2% vs. 2.2%, P = 0.003). Younger age (adjusted odds ratio [aOR] 0.97, 95% confidence interval [CI] 0.95–0.99, P = 0.006), implanted cardiac devices (aOR 37.75, 95% CI 11.63–141.64, P ≤ 0.001), and central venous catheterization (aOR 4.25, 95% CI 1.14–15.55, P = 0.029) were independent risk factors for RSIE. Treatment strategies that consider the epidemiologic and microbiologic characteristics of RSIE are warranted.

Abstract Background Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population. Methods This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010–2012) and lower-disease burden (2016–2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation. Results Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7–0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P

Background/Aims: This study aimed to review the indications, methods, cooperation, complications, and outcomes of percutaneous endoscopic gastrostomy (PEG). Methods: Questionnaires were sent to 200 hospitals, of which 62 returned their questionnaires, with a response rate of approximately 30%. Descriptive statistics were calculated to analyze the responses to the questionnaires. Results: In 2019, a total of 1,052 PEGs were performed in 1,017 patients at 62 hospitals. The main group who underwent PEG was older adult patients with brain disease, particularly stroke. Nutritional supply was an important purpose of the PEG procedure. “The pull method” was the most commonly used for initial PEG insertion. The complications related to PEG were mostly mild, with leakage being the most common. Patients who underwent PEG procedures were primarily educated regarding the post-procedure management and complications related to PEG. Preoperative meetings were skipped at >50% of the institutions. Regarding the cooperation between the nutrition support team (NST) and the physician performing PEG, few endoscopists answered that they cooperated with NST before and after PEG. Moreover, the rate of NST certification obtained by physicians performing PEG and the frequency of attendance at NST-related conferences were relatively low. Conclusions: This study shows a similar trend to that found in the previous PEG guidelines. However, it covers new aspects, including team-based work for PEG procedure, nutrition support, and education for patients and guardians. Therefore, each medical institution needs to select an appropriate method considering the medical environment and doctor’s abilities.

Abstract This study investigated natal factors influencing developmental defects of enamel (DDE) in premature infants using a newly refined preterm developmental defects of enamel (PDDE) index. Dental examinations were conducted on a cohort of 118 preterm infants (average age 3.5 ± 1.4 years) to record PDDE scores, while reviewing their medical records to examine natal factors. According to the logistic regression analysis, factors related to DDE prevalence were advanced maternal age, gestational age 2 months, which were significantly higher by 2.91, 5.53, 7.63, 10.02, and 4.0 times, respectively. According to regression analysis with generalized linear models, the PDDE scores were approximately 7.65, 4.96, and 15.0 points higher in premature children diagnosed with bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis, respectively. When endotracheal intubation was performed, the PDDE score was 5.06 points higher. The prevalence of PDDE was primarily observed bilaterally in the maxillary anterior teeth. Extremely preterm infants showed significantly delayed tooth eruption, suggesting that the influence of gestational age on dental development rates. Identifying the factors related to DDE in premature children can inform early dental interventions to support the oral health of high-risk children.

Background Recently, the target systolic blood pressure (BP) 20 years old and had estimated glomerular filtration rate 15 to 60 mL/min per 1.73 m2 during 2009 to 2011 were included from the database of Korean National Health Insurance Service and were followed up to 2018. Participants were categorized by BP as

Abstract Background Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. Methods We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. Results A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. Conclusion A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

We present a summary of the evidence on testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and organ procurement from deceased donors and provide recommendations based on current clinical data and the guidelines from major transplant organizations. Because of the limited historical experience with coronavirus disease 2019 (COVID-19), certain recommendations in this document are based on theoretical rationales rather than clinical data. The recommendations in this manuscript may be subject to revision as subsequent clinical studies provide definitive evidence regarding COVID-19 in organ procurement.

Solid organ transplant (SOT) recipients are at significant risk of hepatitis B (HB) virus (HBV) reactivation (HBVr). Despite the clinical significance of HBVr after solid organ transplantation, data on the risk factors for HBVr and vaccine effectiveness in SOT recipients with resolved HBV infection are limited. This study evaluated the risk factors for HBVr and the seroconversion rates after HBV vaccination in SOT recipients. Patients who had undergone solid organ transplantation and those with a resolved HBV infection were identified. We matched patients who experienced post-transplantation HBVr with those who did not. We also explored the characteristics and seroconversion rates of HBV-vaccinated patients following transplantation. In total, 1299 SOT recipients were identified as having a resolved HBV infection at the time of transplantation. Thirty-nine patients experienced HBVr. Pre-transplant HB surface antibodies (anti-HBs) positivity and allograft rejection within 3 months after transplantation were independently associated with HBVr. Among the 17 HBV-vaccinated patients, 14 (82.4%) received three or fewer vaccine doses, and 13 (76.5%) had seroconversion with positive anti-HBs results. Pre-transplant anti-HBs(−) status and allograft rejection were risk factors for HBVr in SOT recipients with a resolved HBV infection, and HBV vaccination after transplantation resulted in a high rate of anti-HBs seroconversion. HBV vaccination after transplantation should be considered to reduce the HBVr risk.

Lung transplant patients are more likely to develop severe coronavirus disease 2019 (COVID-19) compared with the general population and should be vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, previous studies have reported reduced vaccination immunogenicity in lung transplantation patients. We aimed to investigate the serological response and associated factors after SARS-CoV-2 vaccination in this population. Lung transplant patients without a history of contracting coronavirus disease who had received a second or higher dose of SARS-CoV-2 vaccination were enrolled. The anti-SARS-Cov-2 spike and neutralizing antibody levels were measured in blood samples. Firth’s logistic regression analysis was performed to assess the factors associated with non-response after vaccination. Forty-six lung transplant patients were enrolled, of which sixteen (34.8%) showed a serological response to vaccination. All patients who received anti-SARS-CoV-2 vaccination before transplantation (n = 5) exhibited a serological response. No significant difference was observed in anti-SARS-CoV-2 S antibody or neutralization titers based on the number and timing of vaccination. Firth’s logistic regression showed an association between lower hemoglobin levels (odds ratio, 0.59; confidence interval, 0.35–0.92; p = 0.017) and non-response to SARS-CoV-2 vaccination. Lung transplant patients showed poor serologic responses after SARS-CoV-2 vaccination in this pilot study; anemia may be associated with this poor response.

[This corrects the article DOI: 10.1371/journal.pone.0266610.].

Background. Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods. The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results. The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P

Abstract Progressive multifocal leukoencephalopathy (PML) is a rare but fatal opportunistic infection and mainly occurs in patients with immunosuppressive conditions. Despite the increasing number of patients receiving immunosuppressive treatments, studies on PML are still lacking due to its low prevalence and incidence. We retrospectively reviewed patients diagnosed with PML in two tertiary hospitals in South Korea from 1999 to 2021. Total of 47 PML patients were included. Of 27 patients (57.4%) were diagnosed with human immunodeficiency virus (HIV). Median last follow-up modified Rankin Scale (mRS) score was higher in the non-HIV PML group than that in the HIV group (5 vs. 4, p = 0.020). Median survival duration was lower in the non-HIV group (184 vs. 1,564 days). The 1-year and overall mortality rates of PML patients were significantly higher in the non-HIV group than that in HIV group (60.0% vs. 25.9%, p = 0.019; 80.0% vs. 40.7%, p = 0.007). Initial mRS score (HR 1.685, p = 0.038) and highly active antiretroviral therapy (HAART) in HIV patients (HR 0.374, p = 0.013) had a significant effect on overall mortality. Our findings suggest that early detection of PML with low mRS score and early initiation of HAART in patients with HIV may improve prognosis.

Objectives: The risk factors for late-onset Pneumocystis jirovecii pneumonia (PCP) after liver transplantation (LT) have not been well studied. We aimed to analyze the clinical features preceding PCP in LT recipients that would guide individualized prophylaxis. Methods: Among 742 patients who underwent LT and routine PCP prophylaxis from January 2009 through December 2019 at Severance Hospital, 27 patients developed PCP. We conducted a retrospective case-control study matching each patient with four controls and analyzed the risk factors for late-onset PCP. Results: After 6 months, post-transplant PCP cases increased steadily with an overall incidence of 6.36 cases per 1000 patient-year. The PCP-related mortality was 37.0%. In the multivariate analyses, age at LT ≥65 years (odds ratio [OR], 13.305; 95% confidence interval [CI], 2.507-70.618; P = 0.002), cytomegalovirus infection (OR, 5.390; 95% CI, 1.602-18.132; P = 0.006), steroid pulse therapy (OR, 6.564; 95% CI, 1.984-21.719; P = 0.002), hepatocellular carcinoma recurrence (OR, 18.180; 95% CI, 3.420-96.636; P = 0.001), and lymphocytopenia (OR, 3.758; 95% CI, 1.176-12.013; P = 0.026) were independently associated with PCP. Conclusion: Late-onset PCP after routine prophylaxis after LT remains a lethal infection and is associated with age ≥65 years at LT, cytomegalovirus infection, steroid pulse therapy, hepatocellular carcinoma recurrence, and lymphocytopenia. Targeted prophylaxis considering these risk factors could improve the prevention of this potentially lethal complication.

Abstract Background During the novel coronavirus disease-2019 pandemic, a considerable number of pneumothorax (PNX)/pneumomediastinum (PNM) associated with COVID-19 have been reported, and the incidence is higher in critically ill patients. Despite using a protective ventilation strategy, PNX/PNM still occurs in patients on invasive mechanical ventilation (IMV). This matched case–control study aims to identify the risk factors and clinical characteristics of PNX/PNM in COVID-19. Methods This retrospective study enrolled adult patients with COVID-19, admitted to a critical care unit from March 1, 2020, to January 31, 2022. COVID-19 patients with PNX/PNM were compared, in a 1–2 ratio, to COVID-19 patients without PNX/PNM, matched for age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale. Conditional logistic regression analysis was performed to assess the risk factors for PNX/PNM in COVID-19. Results 427 patients with COVID-19 were admitted during the period, and 24 patients were diagnosed with PNX/PNM. Body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for PNX/PNM in univariate conditional logistic regression analysis [odds ratio (OR), 0.85; confidence interval (CI), 0.72–0.996; P = 0.044]. For patients on IMV support, univariate conditional logistic regression analysis showed the statistical significance of the duration from symptom onset to intubation (OR, 1.14; CI, 1.006–1.293; P = 0.041). Conclusions Higher BMI tended to show a protective effect against PNX/PNM due to COVID-19 and delayed application of IMV might be a contributive factor for this complication.

Summary: Background: GBP510 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) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18–64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68–14.32) also satisfied the non-inferiority criterion (95% CI lower limit > −5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/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. Funding: This 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.

Background Recent studies reported that prepregnancy body mass index (BMI) and weight gain during pregnancy affect birth weight and contribute to childhood obesity. However, no such data are available in Korea. Purpose This study gathered data on weight gain during pregnancy and its impact on birth weight and childhood obesity in Korea. Methods We reviewed 1,753 singleton full-term babies born at CHA Bundang Medical Center in 2014–2016. We first review each maternal and baby factor based on prepregnancy BMI (underweight, normal, overweight/obese) and then divided them into low, normal, and excess gestational weight gain (GWG) groups based on the American Institute of Medicine (IOM) guidelines. We reviewed the characteristics of each group and analyzed the association between maternal GWG based on IOM guidelines and child BMI after 6 years. Results The maternal prepregnancy BMI group showed a significant difference in birth weight and child BMI at 6 years. As the prepregnancy BMI increased, the birth weight and BMI at 6 years also increased (P

Background : Infections are a major cause of morbidity, graft failure, and mortality in solid organ transplant recipients. Preventive measures have greatly reduced the burden of posttransplant infections. However, little is known about the practice patterns of infection prevention in South Korea. Methods : A questionnaire-based cross-sectional survey was conducted. The questionnaire was developed by a multidisciplinary discussion. From the Korean Network for Organ Sharing data, a list of hospitals that performed kidney, liver, heart, and lung transplantations in 2019 was selected. We invited participants to respond to the questionnaire via email from January to March 2022. Results : The response rates for each organ were as follows; 41% (31/76 hospitals) for kidney, 49% (25/51) for liver, 40% (8/20) for heart, and 89% (8/9) for lung transplantations. The median duration of antibacterial prophylaxis after transplant ranged from 5 to 7 days. Prophylaxis was commonly applied in cytomegalovirus (CMV) D+/R– recipients. For non-lung CMV R+ recipients, a preemptive strategy was the most common method. The duration of viral load monitoring for preemptive or hybrid strategies varied. All lung transplant programs used mold-active antifungal agents for a median of 6 months. An interferon-gamma release assay was most commonly used to screen for latent tuberculosis infections. Conclusions: The infection prevention protocols in most transplant programs in Korea were generally in accordance with the guidelines. However, some variability was observed regarding antibacterial prophylaxis and CMV prevention. Our results provide useful insights into practice patterns and will assist in the development of national guidelines.

Abstract Extracorporeal membrane oxygenation (ECMO) provides hemodynamic and oxygenation support to critically ill patients. Due to multiple catheter cannulations, patients on ECMO are vulnerable to bloodstream infections (BSIs). We aimed to investigate the incidence, clinical characteristics, risk factors, and microorganisms associated with BSIs during ECMO. This single-center retrospective cohort study was conducted between January 2015 and May 2021. Patients aged 18 years or older with an ECMO duration of > 48 h for cardiogenic or respiratory support were included in the study. Patients who developed bacteremia or candidemia from 12 h after ECMO cannulation to 7 days after de-cannulation were included. The clinical factors between non-BSI and BSI were compared, along with an analysis of the risk factors associated with BSI during ECMO. A total of 480 patients underwent ECMO for cardiogenic shock (n = 267, 55.6%) or respiratory failure (n = 213, 44.4%) during the study period. The incidence was 20.0 episodes per 1000 ECMO-days. Approximately 20.2% (97/480) and 5.4% (26/480) of the patients developed bacteremia and candidemia, respectively. The median numbers of days of BSI development were 8.00 days for bacteremia and 11.0 days for candidemia. The most common pathogens were methicillin-resistant coagulase-negative staphylococci (n = 24), followed by vancomycin-resistant Enterococcus (n = 21). Multivariable logistic analysis demonstrated that hemodialysis (odds ratio [OR] 2.647, p

Cancer stem-like cells (CSCs) have been suggested to be responsible for chemoresistance and tumor recurrence owing to their self-renewal capacity and differentiation potential. Although WEE1 is a strong candidate target for anticancer therapies, its role in ovarian CSCs is yet to be elucidated. Here, we show that WEE1 plays a key role in regulating CSC properties and tumor resistance to carboplatin via a microRNA-dependent mechanism. We found that WEE1 expression is upregulated in ovarian cancer spheroids because of the decreased expression of miR-424 and miR-503, which directly target WEE1. The overexpression of miR-424/503 suppressed CSC activity by inhibiting WEE1 expression, but this effect was reversed on the restoration of WEE1 expression. Furthermore, we demonstrated that NANOG modulates the miR-424/503-WEE1 axis that regulates the properties of CSCs. We also demonstrated the pharmacological restoration of the NANOG-miR-424/503-WEE1 axis and attenuation of ovarian CSC characteristics in response to atorvastatin treatment. Lastly, miR-424/503-mediated WEE1 inhibition re-sensitized chemoresistant ovarian cancer cells to carboplatin. Additionally, combined treatment with atorvastatin and carboplatin synergistically reduced tumor growth, chemoresistance, and peritoneal seeding in the intraperitoneal mouse models of ovarian cancer. We identified a novel NANOG-miR-424/503-WEE1 pathway for regulating ovarian CSCs, which has potential therapeutic utility in ovarian cancer treatment.

Abstract Background Despite medical advances, septic shock remains one of the main causes of high mortality in critically ill patients. Although sarcopenia is considered a predictor of mortality in septic shock patients, most studies have only investigated short‐term mortality, and those on long‐term prognosis are limited. We investigated the impact of sarcopenia on long‐term mortality in a large patient population with septic shock. Methods A retrospective cohort study comprising 905 patients with septic shock was conducted from 2008 to 2019. Sarcopenia was defined based on the measurement of the total abdominal muscle area, assessed using abdominal computed tomography scans. Thereafter, we stratified the patients into two groups—sarcopenia and non‐sarcopenia groups—and compared the impact of sarcopenia on short‐term (28 days) and long‐term (1 year and overall) mortality using multivariable Cox proportional analysis. Results A total of 905 patients were included, and the mean age was 65.7 ± 15.1 years. Among them, 430 (47.5%) patients were male and 407 (45.0%) had sarcopenia. We found that the 28 day, 1 year, and overall mortality rates in the sarcopenia group were significantly higher than those in the non‐sarcopenia group (13.8% vs. 6.4%, P

Coronary artery spasm after heart transplantation is a very rare complication. In one observational study and many anecdotal reports, most cases of coronary artery spasm occurred more than 1 year after surgery and had good outcomes. However, cases of intractable coronary artery spasm during the early postoperative period resulting in fatality are limited. This report presents a case of two cardiac arrests caused by coronary artery spasms within a short period of time after heart transplantation.

The utility of α-defensin (AD), leukocyte esterase (LE) levels, and metagenomics sequencing as diagnostic tools for prosthetic joint infection (PJI) has been suggested, but there are few studies among the Asian population. This study aimed to evaluate the diagnostic performance of various biomarkers for PJI and the role of the microbiome in the synovial fluid of patients with prostheses. Patients with suspected knee PJI were enrolled, and their blood and synovial fluid were collected. The cases were classified into the PJI and non-PJI groups. Significant differences between the two groups were observed in the levels of AD (4698 µg/L vs. 296 µg/L, p < 0.001) and positivity for LE (62.5% vs. 21.1%, p = 0.01). AD had 94.4% sensitivity and 89.5% specificity for diagnosing PJI, whereas LE had 37.5% sensitivity and 100% specificity. Microbiome taxonomic profiling showed high sensitivity. The number of operational taxonomic units and the richness of the microbiome in the synovial fluid were higher in the non-PJI than in the PJI group. AD has shown encouraging results in the Asian population as a diagnostic biomarker for PJI, and LE can be used as a diagnostic adjunct. The bacterial richness of the synovial fluid is likely associated with infections.

Inhaled corticosteroids are known to be relatively safe for long-term use in inflammatory respiratory diseases and it has been repurposed as one of the potential therapies for outpatients with coronavirus disease 2019 (COVID-19). However, inhaled corticosteroids have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of inhaled corticosteroids in patients with COVID-19. Randomized controlled trials comparing the efficacy of inhaled corticosteroid treatment in patients with COVID-19 were identified through literature electronic database searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach. Overall, seven trials (eight articles) were included in this systematic review. Compared with usual care, inhaled corticosteroids was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, inhaled corticosteroids use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty. Although based on limited evidence, our results suggest that inhaled corticosteroids treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. More trials and meta-analyses are needed to assess the efficacy of inhaled corticosteroids for COVID-19 treatment.

Purpose: Nontuberculous mycobacteria (NTM) infection is an important issue after lung transplantation. However, a large-scale epidemiological study on this issue in Korea is lacking. We aimed to evaluate the epidemiology of NTM infection after lung transplant surgery in Korea. Methods: Between October 2012 and December 2018, we retrospectively evaluated lung transplant recipients in a referral hospital in South Korea. A total of 215 recipients were enrolled. The median age at transplantation was 56 years (range, 17–75), and 62% were men. Bronchoscopy was performed according to the surveillance protocol and clinical indications. A diagnosis of NTM infection was defined as a positive NTM culture from a bronchial washing, bronchoalveolar lavage sample, or two separate sputum samples. We determined NTM pulmonary disease (NTM-PD) according to the American Thoracic Society/Infectious Disease Society of America 2007 guidelines. The Kaplan–Meier method and log-rank test were used for conditional survival analysis in patients with follow-up of ≥12 months. Results: Fourteen patients (6.5%) were diagnosed with NTM infection at a median of 11.8 months (range, 0.3–51.4) after transplantation. Nine patients (4.2%) were diagnosed with NTM-PD, and the incidence rate was 1980/100,000 person-years. Mycobacterium abscessus was the most common species causing NTM-PD (66%), followed by M. avium complex (33%). The presence of NTM infection did not influence all-cause mortality among those who underwent follow-up for ≥12 months (N = 133, log-rank P = 0.816). Conclusion: The incidence of NTM-PD was considerably high among lung-transplant recipients. M. abscessus was the most common causative species of NTM-PD after lung transplantation.

Abstract Background The photosynthetic microorganism Chlamydomonas reinhardtii has been approved as generally recognized as safe (GRAS) recently, this can excessively produce carotenoid pigments and fatty acids. Zeaxanthin epoxidase (ZEP), which converts zeaxanthin to violaxanthin, and ADP-glucose pyrophosphorylase (AGP). These are key regulating genes for the xanthophyll and starch pathways in C. reinhardtii respectively. In this study, to produce macular pigment-enriched microalgal oil, we attempted to edit the AGP gene as an additional knock-out target in the zep mutant as a parental strain. Results Using a sequential CRISPR-Cas9 RNP-mediated knock-out method, we generated double knock-out mutants (dZAs), in which both the ZEP and AGP genes were deleted. In dZA1, lutein (2.93 ± 0.22 mg g−1 DCW: dried cell weight), zeaxanthin (3.12 ± 0.30 mg g−1 DCW), and lipids (450.09 ± 25.48 mg g−1 DCW) were highly accumulated in N-deprivation condition. Optimization of the culture medium and process made it possible to produce pigments and oil via one-step cultivation. This optimization process enabled dZAs to achieve 81% higher oil productivity along with similar macular pigment productivity, than the conventional two-step process. The hexane/isopropanol extraction method was developed for the use of macular pigment-enriched microalgal oil for food. As a result, 196 ± 20.1 mg g−1 DCW of edible microalgal oil containing 8.42 ± 0.92 mg g−1 lutein of oil and 7.69 ± 1.03 mg g−1 zeaxanthin of oil was produced. Conclusion Our research showed that lipids and pigments are simultaneously induced in the dZA strain. Since dZAs are generated by introducing pre-assembled sgRNA and Cas9-protein into cells, antibiotic resistance genes or selective markers are not inserted into the genome of dZA, which is advantageous for applying dZA mutant to food. Therefore, the enriched macular pigment oil extracted from improved strains (dZAs) can be further applied to various food products and nutraceuticals.

Abstract Background Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT. Methods A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, bla KPC, bla NDM, and bla OXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction. Results Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, bla NDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed. Conclusion FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.

Natural killer (NK) cell enteropathy is not well understood. Although NK-cell enteropathy is typically benign, aggressive NK-cell lymphoma is an important differential diagnosis. This paper reports a rare case of NK-cell enteropathy of the stomach presenting with dyspepsia and weight loss. In this case, upper endoscopy revealed an ulcer-like lesion (approximately 7 mm) surrounded by erythema, edema, and mucosal hemorrhage. The biopsy revealed atypical lymphocyte cells expressing CD56 without an Epstein-Barr virus infection, which is consistent with NK-cell enteropathy. Follow-up endoscopy 2 months later revealed lesion regression with mild erythema. The patient was observed closely for 6 months, with no evidence of lymphoma.

Abstract Atopic dermatitis (AD) is associated with allergic comorbidities, such as asthma, allergic rhinitis (AR), and allergic contact dermatitis (ACD). The etiology of keloid is largely unknown; however, AD and keloid share inflammatory pathways characterized by T-helper cell 2 cytokines and increased dermal fibroblast activity. The prevalence of keloids has been reported to increase in patients with AD, but it remains controversial. This study aimed to estimate the prevalence of keloids in patients with AD, and compare it with the prevalence of other comorbidities of AD. We assessed the Korean National Health Information Database and medical records including coexisting asthma, AR, and ACD. Single and multiple logistic regression models were created for keloids and each allergic disease. The prevalence of keloids was higher in the AD group than in the control group. Among patients with AD, adolescents and adults had a higher prevalence of keloids than infants and children. The risk of keloids was high with AD alone, and coexisting asthma significantly increased the risk. Similarly, the risk of keloids was higher in AR associated with AD and ACD associated with AD than in AD alone. Thus, among Koreans, patients with AD have a higher risk of keloid development, with coexisting allergic diseases increasing the risk.

Abstract Background Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. Methods A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. Results A total of 37 patients were enrolled—26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. Conclusions In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

Summary: Background: Vaccination 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. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted 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 at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19–55 years; stage II, 240 healthy adults aged 19–85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. 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 of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 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. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Background: Bloodstream infection (BSI) caused by carbapenem-resistant Enterobacteriaceae (CRE) significantly influences patient morbidity and mortality. We aimed to identify the characteristics, outcomes, and risk factors of mortality in adult patients with CRE bacteremia and elucidate the differences between carbapenemase-producing (CP)-CRE BSI and non-CP-CRE BSI. Methods: This retrospective study included 147 patients who developed CRE BSI between January 2016 and January 2019 at a large tertiary care hospital in South Korea. The patient demographic characteristics and clinical and microbiological data including the Enterobacteriaceae species and carbapenemase type were obtained and analyzed. Results: Klebsiella pneumoniae was the most commonly detected pathogen (80.3%), followed by Escherichia coli (15.0%). In total, 128 (87.1%) isolates were found to express carbapenemase, and most CP-CRE isolates harbored blaKPC. The 14-day and 30-day mortality rates for CRE BSI were 34.0% and 42.2%, respectively. Higher body mass index (odds ratio (OR), 1.123; 95% confidence interval (CI), 1.012–1.246; p = 0.029), higher sequential organ failure assessment (SOFA) score (OR, 1.206; 95% CI, 1.073–1.356; p = 0.002), and previous antibiotic use (OR, 0.163; 95% CI, 0.028–0.933; p = 0.042) were independent risk factors for the 14-day mortality. A high SOFA score (OR, 1.208; 95% CI; 1.081–0.349; p = 0.001) was the only independent risk factor for 30-day mortality. Carbapenemase production and appropriate antibiotic treatment were not associated with high 14- or 30-day mortality rates. Conclusions: Mortality from CRE BSI was related to the severity of the infection rather than to carbapenemase production or antibiotic treatment, showing that efforts to prevent CRE acquisition rather than treatment following CRE BSI detection would be more effective at reducing mortality.

Helicobacter pylori is the primary causative agent of gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and peripheral B-cell lymphoma. H. pylori eradication often fails due to elevated antibiotic resistance. However, no previous studies have thoroughly examined amoxicillin resistance. Here, the objective was to identify clinical strains of H. pylori with amoxicillin resistance and to analyze single-nucleotide polymorphisms (SNPs) associated with amoxicillin resistance. From March 2015 to June 2019, genotypic and phenotypic amoxicillin resistance was analyzed using an E-test and whole-genome sequencing (WGS). Analysis of 368 clinical strains confirmed amoxicillin resistance in 31 strains (resistance rate of 8.7%). The genomes were extracted from nine resistant (pbp1a, pbp2, nhaC, hofH, hofC, and hefC in all nine isolates. Some of these genes may be related to amoxicillin resistance. A total of six SNPs (A69V, V374L, S414R, T503I, A592D, and R435Q) were identified in PBP2 of H-8, the most resistant strain. We predict that these six SNPs are associated with high amoxicillin resistance. Amoxicillin resistance should be considered in the clinical setting for the treatment failure of H. pylori eradication.

This study investigated the immunogenicity of, and reactogenicity to, the ChAdOx1 nCoV-19 vaccine according to pre-existing adenovirus immunity. Individuals scheduled for COVID-19 vaccination were prospectively enrolled in a tertiary hospital with 2400 beds from March 2020 onwards. Pre-existing adenovirus immunity data was obtained before ChAdOx1 nCoV-19 vaccination. A total of 68 adult patients administered two doses of the ChAdOx1 nCoV-19 vaccine were enrolled. Pre-existing adenovirus immunity was identified in 49 patients (72.1%), but not in the remaining 19 patients (27.9%). The geometric mean titer of S-specific IgG antibodies was statistically higher in individuals without pre-existing adenovirus immunity at several time points: before the second ChAdOx1 nCoV-19 dose (56.4 (36.6–125.0) vs. 51.0 (17.9–122.3), p = 0.024), 2–3 weeks after the second ChAdOx1 nCoV-19 dose (629.5 (451.5–926.5) vs. 555.0 (287.3–926.0), p = 0.049), and 3 months after the second ChAdOx1 nCoV-19 dose (274.5 (160.5–655.3) vs. 176.0 (94.3–255.3), p = 0.033). In the absence of pre-existing adenovirus immunity, systemic events were observed with higher frequency, especially chills (73.7% vs. 31.9%, p = 0.002). In conclusion, individuals without pre-existing adenovirus immunity showed a higher immune response to ChAdOx1 nCoV-19 vaccination and a higher frequency of reactogenicity to ChAdOx1 nCoV-19 vaccination was observed.

Abstract Background Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice. Methods A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60–89; G3ab, 30–59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30–300; A3, > 300 mg/g) were used to define CKD status. Results Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %). Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation. Conclusions Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.

Abstract Background Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. Methods This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. Results Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. Conclusions Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Abstract To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.

Abstract Kikuchi-Fujimoto disease (KFD) is usually self-limiting, but prolonged systemic symptoms often result in frequent hospital visits, long admission durations, or missed workdays. We investigated the role of fluorine-18 fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in assessing KFD severity. We reviewed the records of 31 adult patients with pathologically confirmed KFD who underwent 18F-FDG PET/CT between November 2007 and April 2018 at a tertiary-care referral hospital. Disease severity was assessed using criteria based on clinical manifestations of advanced KFD. Systemic activated lymph nodes and severity of splenic activation were determined using semi-quantitative and volumetric PET/CT parameters. The median of the mean splenic standardized uptake value (SUVmean) was higher in patients with severe KFD than those with mild KFD (2.38 ± 1.18 vs. 1.79 ± 0.99, p = 0.058). Patients with severe KFD had more systemically activated volume and glycolytic activity than those with mild KFD (total lesion glycolysis: 473.5 ± 504.4 vs. 201.6 ± 363.5, p = 0.024). Multivariate logistic regression showed that myalgia (odds ratio [OR] 0.035; 95% confidence interval [CI] 0.001–0.792; p = 0.035), total lymph node SUVmax (cutoff 9.27; OR 24.734; 95% CI 1.323–462.407; p = 0.032), and spleen SUVmean (cutoff 1.79; OR 37.770; 95% CI 1.769–806.583; p = 0.020) were significantly associated with severe KFD. 18F-FDG PET/CT could be useful in assessing KFD severity.

Colorectal perineuriomas are benign mucosal-based mesenchymal tumors composed of perineurial cells and show serrated or hyperplastic crypts in epithelium on histopathological evaluation. Most perineuriomas are usually presented as sessile polyps and often as subepithelial tumors. In this case, colonoscopy revealed a rectal subepithelial tumor (measuring approximately 7 mm) with yellowish- colored normal mucosa. A rectal neuroendocrine tumor was suspected, and cap-assisted endoscopic mucosal resection was performed. Histopathological examination of the resected specimen revealed bland spindle cells showing immunopositivity for CD34. The patient was finally diagnosed with rectal perineurioma.

Appropriate postoperative antibiotic treatment in patients with infective endocarditis (IE) reduces the risks of recurrence and mortality. However, concerns about adverse drug reactions arise due to prolonged antibiotic usage. Therefore, we compared the recurrence and mortality rates according to the duration of postoperative antibiotic therapy in patients with IE. From 2005 to 2017, we retrospectively reviewed 416 patients with IE treated at a tertiary hospital in South Korea; among these, 216 patients who underwent heart valve surgery and received appropriate antibiotics were enrolled. The patients were divided into two groups based on the duration of usage of postoperative antibiotic therapy; the duration of postoperative antibiotic therapy was more than two weeks in 156 patients (72.2%) and two weeks or less in 60 patients (27.8%). The primary endpoint was IE relapse. The secondary endpoints were 1-year IE recurrence, 1-year mortality, and postoperative complication rates. The median age was 53 (interquartile range: 38–62) years. The relapse rate of IE was 0.9% (2/216). There was no statistical difference in relapse (0.0% vs. 1.3%, p = 0.379), 1-year recurrence (1.7% vs. 1.3%, p = 0.829), or 1-year mortality (10.0% vs. 5.8%, p = 0.274) between patients with postoperative antibiotic administration of two weeks or less versus more than two weeks. The duration of postoperative antibiotic therapy did not affect the 1-year mortality rate (log-rank test, p = 0.393). In conclusion, there was no statistically significant difference in recurrence, mortality, or postoperative complications according to the duration of postoperative antibiotic therapy.

Objectives: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19). Methods: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay. Results: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0–55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0–21.0 days) and 18.0 days (IQR 15.0–22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%). Conclusions: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

Background : Organ donor shortage remains as one of the limiting factors for lung transplantation. Given the increase in waiting time, preoperative condition has worsened and affects surgical outcomes. This study aimed to evaluate the immediate postoperative and long-term outcomes of lung transplantation in extended-criteria donor (ECD) lungs compared with standard-criteria donor (SCD) lungs. Methods : A total of 246 patients who had undergone double-lung transplantation during the study period were enrolled. SCD was defined based on the following characteristics: age 300 mmHg. Organ donors who do not fulfill these criteria were classified as ECD. Pre- and postoperative data for outcomes and survival data were analyzed. Results : ECD showed significant association with extracorporeal membrane oxygenation weaning in the operating room (hazard ratio [HR], 0.531; 95% confidence interval [CI], 0.291–0.970; P=0.039) considering recipient’s age and status at operation. The ECD group showed comparable survival rate with the SCD group (HR, 1.413; 95% CI, 0.885– 2.255; P=0.148), with adjustment of other factors. However, when the recipient had Korean Network for Organ Sharing (KONOS) status 0 at the time of transplantation (HR, 1.662; 95% CI, 1.025–2.568; P=0.039), G3 primary graft dysfunction at 72 hours after surgery (HR, 2.508; 95% CI, 1.416–4.440; P=0.002) was a risk factor that decreased survival. Conclusions: The outcome of ECD is not inferior to that of SCD. Therefore, ECD lung should be considered a potential donor organ following active donor management rather than a contraindication of transplantation in highly selected recipients.

Infections caused by Fusobacterium species are rare; however serious infections with complications or mortality may occur occasionally. We conducted a retrospective study to investigate the clinical features of patients with Fusobacterium infections and the differences between infections caused by the species F. necrophorum, F. nucleatum, and F. varium. Additionally, we attempted to identify risk factors for Fusobacterium-associated mortality. This study included all patients at a large tertiary care teaching hospital in South Korea with Fusobacterium infections from January 2006 to April 2021. Demographic, clinical, laboratory, and outcome data were analyzed. Multiple logistic regression analysis was performed to assess the risk factors for in-hospital mortality associated with F. nucleatum and F. varium infections. We identified 272 patients with Fusobacterium infections during the study period. The number of Fusobacterium cases has increased recently, with F. varium infections markedly increasing since 2016 and causing a significant proportion of infections. Patients with F. varium infections were older and had a higher proportion of nosocomial infections than the other groups. The F. nucleatum and F. varium groups showed higher in-hospital mortality than the F. necrophorum group. Through logistic regression analysis, APACHE II score and serum albumin level were considered risk factors for in-hospital mortality. APACHE II score was positively correlated with age, red cell distribution width, and serum blood urea nitrogen, and negatively correlated with serum albumin level. Infections caused by Fusobacterium species are increasing. F. varium causes a significant proportion of severe infections.

Gastric heterotopic pancreas is a relatively uncommon incidental finding. On the other hand, the presentation of gastric adenocarcinoma arising from a heterotopic pancreas is rare. This paper reports a case of gastric adenocarcinoma arising from a heterotopic pancreas that presented as a gastric outlet obstruction 10 years after the initial diagnosis of a suspicious submucosal tumor. Endoscopy revealed a pyloric stricture with prepyloric wall thickening and a complete gastric outlet obstruction. Abdominal and pelvic computed tomography exposed a severely distended gastric lumen at the antrum with heterogeneously enhancing circumferential wall thickening in the prepyloric antrum and pylorus. Because conservative treatment was ineffective and a malignancy could not be excluded, laparoscopic subtotal gastrectomy with a gastrojejunostomy was performed for histological confirmation and treatment. The histopathology diagnosis was advanced gastric carcinoma arising from heterotopic pancreatic tissue.

There are a variety of causes of intestinal obstruction, with the most common cause being malignant diseases; however, volvulus, inflammatory bowel disease or diverticulitis, radiation injury, ischemia, and pseudo-obstruction can also cause colonic obstruction. These are benign conditions; however, delayed diagnosis of acute intestinal obstruction owing to these causes can cause critical complications, such as perforation. Therefore, high levels of clinical suspicion and appropriate treatment are crucial. There are variable treatment options for colonic obstruction, and endoscopic treatment is known to be a less invasive and an effective option for such. In this article, the authors review the causes of benign colonic obstruction and pseudo-obstruction and the role of endoscopy in treating them.

Background The seropositivity rate of hepatitis B surface antigen (anti-HBs) antibodies is known to be ≥95% after hepatitis B virus vaccination during infancy. However, a low level or absence of anti-HBs in healthy children is discovered in many cases. Recent studies in adults reported that a reduced anti-HBs production rate is related to obesity. Purpose To investigate whether body mass index (BMI) affects anti-HBs levels in healthy children following 3 serial dose vaccinations in infancy. Methods We recruited 1,200 healthy volunteers aged 3, 5, 7, or 10 years from 4-day care centers and 4 elementary schools. All subjects completed a questionnaire including body weight, height, and vaccine type received. Levels of serum hepatitis B surface antigen (HBsAg) and anti-HBs in all subjects were analyzed using electrochemiluminescence immunoassay. The standardized scores (z score) for each sex and age were obtained using the lambda-mu-sigma method in the 2017 Korean National Growth Charts for children and adolescents. Results Our subjects (n=1,200) comprised 750 males (62.5%) and 450 females (37.5%). The overall anti-HBs seropositivity rate was 57.9% (695 of 1,200). We identified significant differences in mean BMI values between seronegative and seropositive groups (17.45 vs. 16.62, respectively; P

Background/Aims Fecal calprotectin (FC) is a marker of intraluminal intestinal inflammation. Intestinal inflammation may contribute to the pathophysiology of irritable bowel syndrome (IBS). This study evaluated FC levels in children with IBS and differences in FC levels in children stratified by IBS subtype and healthy controls (HCs). Methods A total of 157 children with IBS and 56 HCs aged 4–16 years (119 boys, 94 girls, mean age of 9.48 years) were included in this prospective study. Children with IBS were diagnosed using the Rome III criteria and classified into 4 subtypes: IBS with constipation (IBS-C, n=37), IBS with diarrhea (IBS-D, n=54), IBS with alternating constipation and diarrhea (IBS-M, n=49), and IBS unsubtyped (IBS-U, n=17); postinfectious IBS (PI-IBS) was also considered. The FC concentration in stool samples was analyzed using an enzyme-linked immunosorbent assay. All participants answered a questionnaire regarding several demographic and clinical characteristics. Results Children with IBS had significantly higher levels of FC than the HCs (88.71 μg/g vs. 17.77 μg/g). Among the 4 IBS subtypes, the FC concentration was highest in children with IBS-D, followed by those with IBS-M, IBS-C, and IBS-U (169.94 μg/g vs. 45.04, 31.22, and 33.52 μg/g, respectively), and these differences were statistically significant. For PI-IBS, 90% of cases were in the IBS-D group. Conclusions The FC level was significantly higher in children with IBS than in HCs and differed depending on the IBS subtype, supporting the notion that IBS is a type of low-grade bowel inflammation.

Most studies on the real-world effectiveness and safety of dolutegravir/lamivudine (DTG/3TC) have been conducted in Western countries, and Asian reports are lacking. We evaluated the effectiveness and safety of DTG/3TC in Korean adult people living with HIV (PLWH). This retrospective study was conducted from July 2020 to July 2022 at a tertiary hospital in Korea. Those who were followed up for more than 12 months were included. We analyzed the baseline characteristics, effectiveness, resistant profiles, body weights, metabolic parameters, and safety of DTG/3TC treatment in 151 PLWH, dividing them into the treatment-naïve group and the switching group. The median DTG/3TC treatment durations in the treatment-naïve and switching groups were 507.5 and 525.0 days. In the treatment-naïve group, the viral RNA titer was undetectable at 6 and 12 months in 95% of patients. In the switching group, virologic suppression was well-maintained. Meanwhile, the creatinine levels were slightly elevated in both groups compared to baseline. Five participants complained of mild side effects, such as indigestion, constipation, diarrhea, and fatigue. However, no patient stopped treatment during the follow-up period. Since there was no virological failure or serious complications observed in this study, DTG/3TC may be a good treatment option for PLWH in Korea.

Dehydroepiandrosterone (DHEA) is an adrenal steroid converted to potent androgens. This study aimed to discover the association between serum DHEA levels and immunologic response in people with HIV/AIDS (PLWHA). We enrolled patients aged ≥ 18 years who were treated with combination antiretroviral therapy (cART). We measured CD4+ and CD8+ T-cell counts, HIV-RNA titres, and serum DHEA levels. We assigned each patient to a good- or poor-responder group depending on their CD4+ T-cell counts at study enrolment. Participants with CD4+ T-cell counts > 200/µL were assigned to the good-responder group, whilst those with CD4+ T-cell counts < 200/µL were assigned to the poor-responder group. The participants were followed up for 2 years. The poor-responder group showed lower CD4+ T-cell counts and higher HIV PCR titres at their initial HIV diagnosis and in their 2-year follow-up data. Serum DHEA level was lower in the poor-responder group. Multivariable logistic analysis showed that BMI, initial CD4+ T-cell counts, and serum DHEA level were clinical factors associated with poor immunologic responsiveness to cART in PLWHA. Therefore, DHEA may be used as an indicator of the immunological recovery of PLWHA.

“Possible sarcopenia” may be defined as a low muscle strength assessed by handgrip strength (HGS) by sex. We examined the sex-specific association between low handgrip strength (LGS) and dietary factors for the prevention of sarcopenia in young and middle-aged Koreans. We used data from the 2014–2017 Korea National Health and Nutrition Examination Survey of 11,635 Korean adults with LGS and normal handgrip strength (NGS). The relationship between dietary factors, e.g., nutrients, foods, and dietary patterns, and HGS was evaluated by multivariate logistic regression analyses. In men, the LGS group had a higher proportion of energy from carbohydrates and a lower proportion of energy from proteins than the NGS group. The LGS group had lower protein, niacin, phosphorus, and iron densities in their diet than the NGS group. The odds of having LGS increased as intake of vitamin B1 (odds ratio (OR) 2.916, 95% confidence interval (CI) 1.265–6.719), niacin (OR 2.286, 95% CI 1.095–4.774), phosphorus (OR 2.731, 95% CI 1.036–7.199), and iron (OR 2.591, 95% CI 1.102–6.088) decreased. In women with LGS, the odds of insufficient protein intake (OR 1.976, 95% CI 1.248–3.127) was significantly higher. This study suggests that adequate intake of protein, vitamin B1, niacin, phosphorus, and iron is beneficial for maintaining HGS.

Objectives: To investigate the rate of antineutrophil cytoplasmic antibody (ANCA) positivity and its clinical significance in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: This study included 178 patients infected with SARS-CoV-2 who were enrolled in a cohort at a single centre. Myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA levels in stored blood sera were measured using immunoassay kits. Mortality, mechanical ventilator care, and severe infection were assessed as three poor outcomes. The 2022 American College of Rheumatology and the European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for the three subtypes of AAV were applied only to patients who had MPO-ANCA or PR3-ANCA among study subjects. Results: The detection rate of ANCA positivity was 18.5%. MPO-ANCA and PR3-ANCA were found in 22 (12.4%) and 14 (7.9%) patients, respectively. However, neither MPO-ANCA nor PR3-ANCA affected the three poor outcomes. According to the new criteria, 12 (6.7%) and 21 (11.8%) patients were classified as having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), respectively. Conclusions: SARS-CoV-2 infection may increase the rate of ANCA positivity. Although it might not affect poor outcomes, it might contribute to the classification of GPA and MPA despite uncertain clinical significance.