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Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are pivotal in combating coronavirus disease 2019 (COVID-19); however, the declining antibody titers postvaccination pose challenges for sustained protection and herd immunity. Although gut microbiome is reported to affect the early antibody response after vaccination, its impact on the longevity of vaccine-induced antibodies remains unexplored. Methods A prospective cohort study was conducted involving 44 healthy adults who received two doses of either the BNT162b2 or ChAdOx1 vaccine, followed by a BNT162b2 booster at six months. The gut microbiome was serially analyzed using 16S rRNA and shotgun sequencing, while humoral immune response was assessed using a SARS-CoV-2 spike protein immunoassay. Results Faecalibacterium prausnitzii was associated with robust and persistent antibody responses post-BNT162b2 vaccination. In comparison, Escherichia coli was associated with a slower antibody decay following ChAdOx1 vaccination. The booster immune response was correlated with metabolic pathways involving cellular functions and aromatic amino acid synthesis. Conclusions The findings of this study underscored the potential interaction between the gut microbiome and the longevity/boosting effect of antibodies following vaccination against SARS-CoV-2. The identification of specific microbial associations suggests the prospect of microbiome-based strategies for enhancing vaccine efficacy.

Background: We identified the uptake of people living with HIV (PLWH) using health-screening services and compared the screening rate with the general population, to identify factors associated with the use of screening services by PLWH. Methods: This population-based study used data from the Korean National Health Insurance, a single mandatory health insurance system covering all residents. The uptake rates for screening for general health, gastric cancer, and colorectal cancer, which were provided by a national health screening program with free of charge or minimal cost in Korea from 2010–2020. Factors associated with general health, gastric cancer, and colorectal cancer screening were also explored. Results: Screening uptake rates for general health, gastric cancer, and colorectal cancer in PLWH increased from 2010–2019 but decreased in 2020. The standardized screening ratio showed lower screening rates for general health, gastric cancer, and colorectal cancer in PLWH with 0.80 (95 % confidence interval (CI) = 0.77–0.83), 0.64 (95 % CI = 0.61–0.67), and 0.67 (95 % CI = 0.64–0.71) in 2019. Increased age, Charlson Comorbidity Index, and years since HIV diagnosis were associated with increased screening uptake in PLWH. Otherwise, PLWH recipients of medical aid programs received less for each screening compared to PLWH who paid insurance premiums higher than 50 %. An increased medication possession ratio of highly active antiretroviral therapy was associated with decreased general health and gastric cancer screening uptake but increased colorectal cancer screening uptake. Conclusions: Significant disparities in health-screening uptake were observed in PLWH compared to the general population in a nationwide organized screening setting without cost barriers.

Erythema nodosum (EN) is a skin manifestation of panniculitis characterized by symmetric, painful, tender nodules, and most cases are self-limiting. Few cases of EN following Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination have been reported, and they are generally self-limiting. We reported the challenging case of a 63-year-old Asian woman with EN that persisted for more than three months after a coronavirus disease-19 (COVID-19). There was no improvement despite topical steroid and NSAIDs treatment, and the patient was successfully treated with combination of high-dose steroid and NSAIDs. There were long-lasting symptoms involving various organ symptoms persisting over three months after COVID-19, which is known as Long COVID. As part of Long COVID, there are limited cases of skin manifestations. Given that immune dysregulation due to persistent coronaviruses may contribute to refractory EN, Erythema nodosum related to COVID-19 is rare, but can occur; clinicians should be aware of the occurrence of EN following COVID-19 infection.

BackgroundPlasmodium vivax malaria has been one of the most troublesome diseases in the Democratic People’s Republic of Korea (DPRK). Given that a majority of malaria cases are concentrated near the demilitarized zone, concerted elimination efforts from both the Republic of Korea (ROK) and DPRK are essential for a malaria-free Korean Peninsula. This study assessed the impact of rapid diagnostic tests (RDTs) and tafenoquine on malaria incidence in DPRK.MethodsWe patterned the current model structure from the previously developed Plasmodium vivax malaria dynamic transmission model for ROK. Model parameters were adjusted using demographic and climate data from malaria-risk areas in DPRK, and the model was calibrated to annual malaria incidences from 2014 to 2018 in DPRK, as reported by the World Health Organization. Subsequently, we estimated the preventable malaria cases over a decade after introducing RDTs and tafenoquine compared to using microscopy alone and primaquine, respectively. Sensitivity analysis was performed to account for uncertainty in model parameters.ResultsWhen comparing RDTs to microscopy, a one-day reduction in diagnostic time due to the introduction of RDTs led to a reduction in malaria incidence by 26,235 cases (65.6%) over the next decade. With a two-day reduction, incidences decreased by 33,635 (84.1%). When comparing a single dose of tafenoquine with a 14-day primaquine regimen, the former prevented 1,222 (77.5%) relapse cases and 4,530 (11.3%) total cases over the years.ConclusionThe continuous and simultaneous implementation of RDTs and tafenoquine emerges as a potent strategy to considerably reduce malaria in DPRK.

As coronavirus disease-2019 (COVID-19) becomes an endemic disease, the virus continues to evolve and become immunologically distinct from previous strains. Immune imprinting has raised concerns about bivalent mRNA vaccines containing both ancestral virus and Omicron variant. To increase efficacy against the predominant strains as of the second half of 2023, the updated vaccine formulation contained only the mRNA of XBB.1.5 sublineage. We conducted a multicenter, test-negative, case-control study to estimate XBB.1.5 monovalent vaccine effectiveness (VE) and present the results of an interim analysis with data collected in November 2023. Patients who underwent COVID-19 testing at eight university hospitals were included and matched based on age (19-49, 50-64, and ≥65 years) and sex in a 1:1 ratio. VE was calculated using the adjusted odds ratio derived from multivariable logistic regression. Of the 992 patients included, 49 (5.3%) received the XBB.1.5 monovalent vaccine at least 7 days before COVID-19 testing. Patients with COVID-19 (cases) were less likely to have received the XBB.1.5 monovalent vaccine (case 3.5% vs. control 7.2%, p=0.019) and to have a history of COVID-19 within 6 months (2.2% vs. 4.6%, p=0.068). In contrast, patients with COVID-19 were more likely to be healthcare workers (8.2% vs. 3.0%, p=0.001) and to have chronic neurological diseases (16.7% vs. 11.9%, p=0.048). The adjusted VE of the XBB.1.5 monovalent mRNA vaccine was 56.8% (95% confidence interval: 18.7-77.9%). XBB.1.5 monovalent mRNA vaccine provided significant protection against COVID-19 in the first one to two months after vaccination.

BackgroundThe assessment of long-term humoral and cellular immunity post-vaccination is crucial for establishing an optimal vaccination strategy.MethodsThis prospective cohort study evaluated adults (≥18 years) who received a BA.4/5 bivalent vaccine. We measured the anti-receptor binding domain immunoglobulin G antibody and neutralizing antibodies (NAb) against wild-type and Omicron subvariants (BA.5, BQ.1.1, BN.1, XBB.1 and EG.5) up to 9 months post-vaccination. T-cell immune responses were measured before and 4 weeks after vaccination.ResultsA total of 108 (28 SARS-CoV-2-naïve and 80 previously infected) participants were enrolled. Anti-receptor binding domain immunoglobulin G (U/mL) levels were higher at 9 months post-vaccination than baseline in SAR-CoV-2-naïve individuals (8,339 vs. 1,834, p

Recently, respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We aimed to develop an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM showed high coefficients of determination (r > 0.90), respectively. Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r = 0.90) and SC-TM (r = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM, but not with the attachment (G) protein.

ABSTRACTThe highdose quadrivalent influenza vaccine (QIVHD) has shown improved protection against influenza and its complications in older adults. We aimed to evaluate the costeffectiveness of QIVHD compared with QIVSD among Korean adults aged ≥ 65 years in reducing influenzarelated disease burden. We evaluated the 2016/2017 and 2017/2018 seasons and their average values using a static decision tree model. The difference in efficacy between standard-dose (SD) and high-dose (HD) was calculated based on the results of a clinical trial comparing Fluzone® High-Dose Vaccine and Fluzone® Vaccine in older adults. Incremental cost-effectiveness ratios (ICERs) were assessed from the healthcare system perspective. A discount rate of 4.5% was applied to life-year-gained (LYG) values and utilities. We performed deterministic and probabilistic sensitivity analyses to account for both epidemiological and economic sources of uncertainty. In the analysis of the 2017/2018 season, the QIV-HD strategy generated an excess of 0.00182 life-years (Lys)/person and 0.003953 quality-adjusted life-years (QALYs)/person compared with QIV-SD. The ICER was 6,467.56 United States Dollars (USD)/QALY. In the analysis from the 2016/2017 season, QIV-HD caused a surplus of 0.00117 Lys/person and 0.003272 QALYs/person compared with QIV-SD. ICER was 7,902.46 USD /QALY. From the average data of the 2016/2017 and 2017/2018 seasons, an excess of 0.00147 Lys/person and 0.003561 QALYs/person were generated using QIV-HD compared with QIV-SD, while the ICER was 7,190.44 USD /QALY. From the healthcare system perspective, QIV-HD was a more cost-effective vaccination option in reducing influenza-related disease burden and healthcare costs in Koreans aged ≥ 65 years compared with QIV-SD.

ABSTRACTAntiangiogenic therapy is a recognized method for countering the immunosuppressive tumor microenvironment (TME) and improving anti-tumor immunity. PB101 is a glycosylated decoy receptor that binds to VEGF-A and PlGF with high affinity, based on the VEGFR1 backbone. Here, we elucidated PB101-induced remodeling of tumor angiogenesis and immunity, which enhances anti-PD-L1 immune checkpoint blockade. PB101 inhibited tumor growth by suppressing angiogenesis and enhancing CD8+ T cell infiltration into the tumors. PB101 induced robust reprogramming of antitumor immunity and activates intratumoral CD8+ T cells. Anti-tumor efficacy of PB101 is mostly dependent on CD8+ T cells and IFN-γ. PB101 reprograms tumor immunity in a manner distinct from that of the conventional VEGF decoy receptor, VEGF-trap. With its potent immune-modulating capability, PB101 synergizes with an anti-PD-L1, triggering strengthened antitumor immunity. Combining PB101 and anti-PD-L1 could establish durable protective immunity against tumor recurrence and metastasis. The findings of this study offer scientific rationales for further clinical development of PB101, particularly when used in combination with immune checkpoint inhibitors, as a potential treatment for advanced cancers.

ZnO nanosheets with nanograin distributions, high mesoporosity, and ultrathin thickness have garnered considerable attention owing to their intriguing properties, such as high surface-to-volume ratio and chemical reactivity. Although various methods for fabricating two-dimensional structures have been reported, the surfactant-assisted method is advantageous as it produces nanosheet structures at the water–air interface without affecting the crystal structure of the material. This study developed an innovative surfactant-assisted synthesis method to fabricate flower-like Zinc Oxide (f-ZnO) nanostructures. The synthesis, performed at a mild temperature of 70 °C, yields f-ZnO with high surface area-to-volume ratios and porous morphology. The f-ZnO demonstrates photoelectrochemical (PEC) performance due to increased interfacial contact with electrolytes and the formation of a wurtzite ZnO crystal structure. Additionally, f-ZnO exhibits sensitivity and selectivity as a hydrogen sulfide (H2S) gas sensor. This facile synthesis method opens new avenues for developing functional oxide nanostructures for sensors, catalysts, and energy storage systems.

Objectives: The CoV2-001 phase I randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up. Design: A total of 45 vaccine-naïve participants were recruited between December 31, 2020, and March 30, 2021. GLS-5310, encoding for the SARS-CoV-2 spike and open reading frame 3a (ORF3a) proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations. Results: GLS-5310 was well tolerated with no serious adverse events reported. Antibody and T cell responses were dose-independent. Anti-spike antibodies were induced in 95.5% of participants with an average geometric mean titer of ∼480 four weeks after vaccination and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination geometric mean titer of 28.4. T cell responses were induced in 97.8% of participants, averaging 716 site forming units/106 cells four weeks after vaccination, increasing to 1248 at week 24, and remaining greater than 1000 through 48 weeks. Conclusion: GLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

IgE is a critical component of the allergic response and therapeutic targeting can alleviate symptomology. Here the authors propose the combined use of Bifidobacterium longum and a FcεRIα extracellular domain linked to a IgD/IgG4 hybrid Fc domain fusion protein called IgETRAP and show reduction of mast cell and IgE levels in models of food allergy.

ObjectivesSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects gut luminal cells through the angiotensin-converting enzyme-2 receptor and disrupts the gut microbiome. We investigated whether the gut microbiome in the early stage of SARS-CoV-2 infection was associated with the prognosis of coronavirus disease (COVID-19).MethodsThirty COVID-19 patients and 16 healthy controls were prospectively enrolled. Blood and stool samples and clinical details were collected on days 0 (enrollment), 7, 14, and 28. Participants were categorized into four groups by their clinical course.ResultsGut microbiota composition varied during the clinical course of COVID-19 and was closely associated with cytokine levels (p=0.003). A high abundance of the genus Dialister (linear discriminant analysis [LDA] effect size: 3.97856, p=0.004), species Peptoniphilus lacrimalis (LDA effect size: 4.00551, p=0.020), and Anaerococcus prevotii (LDA effect size: 4.00885, p=0.007) was associated with a good prognosis. Starch, sucrose, and galactose metabolism was highly activated in the gut microbiota of the poor prognosis group. Glucose-lowering diets, including whole grains, were positively correlated with a good prognosis.ConclusionGut microbiota may mediate the prognosis of COVID-19 by regulating cytokine responses and controlling glucose metabolism, which is implicated in the host immune response to SARS-CoV-2.

BackgroundWhether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised.MethodsA prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3–4 weeks, 3 months, and 6 months after booster vaccination.ResultsA total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections.ConclusionBooster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required.

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.

Bivalent COVID-19 vaccines that contain BA.1 or BA.4/BA.5 have been introduced worldwide in response to pandemic waves of Omicron subvariants. This prospective cohort study was aimed to compare neutralizing antibodies (Nabs) against Omicron subvariants (BA.1, BA.5, BQ.1.1, BN.1, and XBB.1) before and 3–4 weeks after bivalent booster by the types of SARS-CoV-2 variants in prior infections and bivalent vaccine formulations. A total of 21 participants were included. Prior BA.1/BA.2-infected, and BA.5-infected participants showed significantly higher geometric mean titers of Nab compared to SARS-CoV-2-non-infected participants after bivalent booster (BA.1, 8156 vs. 4861 vs. 1636; BA.5, 6515 vs. 4861 vs. 915; BQ.1.1, 697 vs. 628 vs. 115; BN.1, 1402 vs. 1289 vs. 490; XBB.1, 434 vs. 355 vs. 144). When compared by bivalent vaccine formulations, Nab titers against studied subvariants after bivalent booster did not differ between BA.1 and BA.4/BA.5 bivalent vaccine (BA.1, 4886 vs. 5285; BA.5, 3320 vs. 4118; BQ.1.1, 311 vs. 572; BN.1, 1028 vs. 1095; XBB.1, 262 vs. 362). Both BA.1 and BA.4/BA.5 bivalent vaccines are immunogenic and provide enhanced neutralizing activities against Omicron subvariants. However, even after the bivalent booster, neutralizing activities against the later Omicron strains (BQ.1.1, BN.1, and XBB.1) would be insufficient to provide protection.

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.

Abstract Peritoneal recurrence (PR) is a major relapse pattern of colorectal cancer (CRC). We investigated whether peritoneal immune cytokines can predict PR. Cytokine concentrations of peritoneal fluid from CRC patients were measured. Patients were grouped according to peritoneal cancer burden (PCB): no tumor cells (≤ pT3), microscopic tumor cells (pT4), or gross tumors (M1c). Cytokine concentrations were compared among the three groups and the associations of those in pT4 patients with and without postoperative PR were assessed. Of the ten cytokines assayed, IL6, IL10, and TGFB1 increased with progression of PCB. Among these, IL10 was a marker of PR in pT4 (N = 61) patients based on ROC curve (p = 0.004). The IL10 cut-off value (14 pg/mL) divided patients into groups with a low (7%, 2 of 29 patients) or high (45%, 16 of 32 patients) 5-year PR (p

Objectives: To compare epidemiologic features of the second and third waves of the coronavirus disease 2019 (COVID-19) pandemic in South Korea. Methods: Nationwide COVID-19 data were collected between 6 May and 30 December 2020. The degree of social activity was estimated using an Internet search trend analysis program for leisure-related keywords, including ‘eating-out’, ‘trip’ and ‘get directions’ (transportation). Demographics, transmission chains, case fatality rates, social activity levels and public health responses were compared between the second (13 August–18 September 2020) and third (4 November 2020–present) waves. Results: In comparison with the second wave, the third wave was characterized by delayed strengthening of social distancing policies (3 vs. 15 days), longer duration (36 vs. >56 days) and a higher case fatality rate (0.91% vs. 1.26%). There were significant differences in transmission chains between the second and third waves (P < 0.01). In comparison with the second wave, the proportion of local clusters (24.8% vs. 45.7%) was lower in the third wave, and personal contact transmission (38.5% vs. 25.9%) and unknown routes of transmission (23.5% vs. 20.8%) were higher in the third wave. Conclusion: Early and timely interventions with strengthened social distancing policies should be implemented to suppress and control the COVID-19 pandemic effectively.

Purpose Postoperative delirium (POD) is a common complication in elderly patients after major abdominal surgery for cancer. Although POD is related with a poor outcome, there have not been many reports about POD after abdominal surgery in Korea. The aims of study were to analyze the characteristics and surgical outcomes of elderly patients with POD and to identify the risk factors of POD. Methods From November 2016 to January 2019, we prospectively enrolled 63 patients who were aged ≥75 years and underwent major abdominal surgery for cancer. POD was daily assessed for up to 10 days postoperatively with the Confusion Assessment Method and a validated chart review. Results POD occurred in eight patients (12.7%). Univariate analysis showed that the occurrence of POD was related to sodium

Abstract Background The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. “Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs),” and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of “tumoral PD-L1/immune cell PD-L1/CD8+ TILs” may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.

AIM: To investigate and compare the visual and refractive outcomes of small incision lenticule extraction (SMILE), laser assisted sub-epithelial keratomileusis (LASEK), and LASEK combined with corneal collagen cross-linking (LASEK-CXL) surgery in patients with less than 500 μm of central corneal thickness (CCT). METHODS: The retrospective medical records review was conducted on the patients with CCT less than 500 μm treated with SMILE, LASEK, and LASEK-CXL. There was a total of 172 eyes, 76 eyes were in the SMILE group, 53 eyes in the LASEK group, and 43 eyes in the LASEK-CXL group. Uncorrected distance visual acuity (UDVA), spherical equivalent refraction (SE), and corneal haze were followed up in the three groups for 12mo. RESULTS: At 12mo postoperatively, there were no statistically significant differences in UDVA and in the absolute value of SE between the three groups. The predictability within ±0.50 D in the SMILE group (85.5%) was significantly higher than in both the LASEK group (64.2%, P

BackgroundHealthcare-associated pneumonia (HCAP) lies in the intersection of community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP). Although HCAP is excluded from the revised HAP guideline, reassessment for HCAP is needed considering its heterogeneous characteristics.MethodsThe microbiological distribution, antibiotic resistance, and clinical outcomes in CAP, HCAP, and HAP were studied retrospectively. The susceptibility to standard CAP regimens (β-lactams plus macrolide or fluoroquinolone monotherapy) and rates of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa) infections were evaluated in the CAP group and HCAP subgroups.ResultsIn total, 933 cases were included (CAP, n = 557; HCAP, n = 264; HAP, n = 112). In the CAP and HCAP cases, Streptococcus pneumoniae (7.4% vs. 5.7%) and P. aeruginosa (9.2% vs. 18.6%) were the most common gram-positive and gram-negative pathogens. Staphylococcus aureus (methicillin-resistant, 2.7%; methicillin-susceptible, 2.4%) and carbapenem-resistant Acinetobacter baumannii (20.5%) were the most common Gram-positive and Gram-negative pathogens in the HAP group, respectively. Higher susceptibility to levofloxacin was observed in CAP and HCAP isolates than that to β-lactam agents. However, levofloxacin non-susceptibility was significantly higher in long-term care facility (LTCF)-onset HCAP compared to community-onset HCAP (43.6% vs. 22.7%, P = 0.014).ConclusionHCAP showed higher rates of P. aeruginosa and MRSA infections than CAP. Empirical antipseudomonal therapy should be considered in the treatment of HCAP. Prior isolation of P. aeruginosa was the most important risk factor for P. aeruginosa infection.

Face masks are used to protect the wearer from harmful external air and to prevent transmission of viruses from air exhaled by potentially infected wearers to the surrounding people. In this study, we examined the potential utility of masks for collecting viruses contained in exhaled breath and detected the collected viruses via various molecular tests. Using KF94 masks, the inner electrostatic filter was selected for virus collection, and an RNA extraction protocol was developed for the face mask. Virus detection in worn mask samples was performed using PCR and rolling circle amplification (RCA) tests and four different target genes (N, E, RdRp, and ORF1ab genes). The present study confirmed that the mask sample tests showed positive SARS-CoV-2 results, similar to the PCR tests using nasopharyngeal swab samples. In addition, the quantity of nucleic acid collected in the masks linearly increased with wearing time. These results suggest that samples for SARS-CoV-2 tests can be collected in a noninvasive, quick, and easy method by simply submitting worn masks from subjects, which can significantly reduce the hassle of waiting at airports or public places and concerns about cross-infection. In addition, it is expected that miniaturization technology will integrate PCR assays on face masks in the near future, and mask-based self-diagnosis would play a significant role in resolving the pandemic situation.

Since it first emerged in December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly worldwide. During the pandemic of an emerging infectious disease, it is very important to prevent nosocomial outbreaks and operate hospitals safely to maintain their functions. In this article, we present the strategies for safe hospital operations based on the experiences of the Republic of Korea early in the COVID-19 pandemic. Each hospital should maintain multiple layers of defenses to prevent even small cracks in the hospital’s quarantine system.

Objectives: In 2014, South Korea expanded its national health insurance coverage to include newer antifungal agents, such as echinocandins. This study aimed to investigate the effects of policy change on the prescription patterns of antifungals, medical costs and clinical outcomes of candidemia. Methods: This retrospective cohort enrolled hospitalized patients with candidemia at three tertiary care hospitals in South Korea from January 2012 to December 2015. The utilization of antifungal agents, medical costs, length of hospital stay (LOS), and mortality before and after the health-care benefit expansion were compared, and the factors associated with all-cause 28-day mortality during the study period were analyzed. Results: A total of 769 candidemia cases were identified. The incidence of candidemia did not significantly vary during the study period (P = 0.253). The proportion of echinocandins, as the initial antifungal agent, and medical costs associated with candidemia significantly increased since the change in insurance coverage (P

University students, especially those living in dormitories, are known to have a high risk of invasive meningococcal disease. We performed a longitudinal study to investigate the change in Neisseria meningitidis carriage rates and identify the risk factors for carriage acquisition in university students in South Korea. We recruited university entrants who were admitted to a student dormitory. Pharyngeal swabs were taken from participants at baseline, 1 month, and 3 months, and the subjects completed a questionnaire. Culture and real-time polymerase chain reaction (PCR) for species-specific ctrA and sodC genes were performed. The cultured isolates or PCR-positive samples were further evaluated for epidemiologic characterization using serogrouping, PorA typing, FetA typing, and multilocus sequence typing (MLST). At the first visit, we enrolled 332 participants who were predominantly male (64.2%) with a median age of 19 years. Meningococcal carriage rates increased from 2.7% (95% confidence interval [CI] 0.9-4.4%) at baseline to 6.3% (95% CI 3.4-9.0%) at 1 month and 11.8% (95% CI 7.8-15.6%) at 3 months. Nongroupable isolates accounted for 50.0% of all isolates, with serogroup B being the next most prevalent (24.1%). In the study population, male sex (OR 2.613, 95% CI 1.145-5.961, p = 0.022) and frequent pub or club visits (OR 3.701, 95% CI 1.536-8.919, p = 0.004) were significantly associated with meningococcal carriage. Based on serotype and MLST analyses, six carriers transmitted meningococci to other study participants. N. meningitidis carriage rates among new university entrants who lived in a dormitory significantly increased within the first 3 months of dormitory stay, probably owing to the transmission of identical genotype among students. Based on the risk of meningococcal disease, meningococcal vaccination should be considered for students before dormitory admission.

Abstract Backgrounds Several studies have evaluated the impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined with antimicrobial stewardship in patients with positive blood cultures; clinical outcomes improved. However, in many hospitals, antimicrobial stewardship is not available because of restricted medical resources. Thus, we investigated the impact of evaluation by MALDI-TOF MS on the clinical outcomes of patients with bacteremia and fungemia treated in a clinical setting lacking an antimicrobial stewardship program (ASP). Methods We designed a pre–post quasi experimental study and retrospectively reviewed the medical records of patients aged > 18 years old with bacteremia and fungemia during two periods: October–December 2012 and October–December 2013. Conventional methods were used to detect microbial pathogens in 2012, and MALDI-TOF MS was employed in 2013. Clinical outcomes compared between periods were the time to pathogen identification, time to effective therapy, 30-day all-cause mortality, time to microbiological clearance, length of ICU stay, and rate of recurrence of the same bloodstream infection (BSI). Results A total of 556 patients were enrolled; 302 patients in 2012, and 254 in 2013. The use of MALDI-TOF MS without an ASP reduced the time to pathogen identification (86.4 vs. 63.5 h, P

Abstract Background Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with β-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. Methods Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. Results A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p