Elaeocarpus sylvestris var. ellipticus Extract and Its Major Component, Geraniin, Inhibit Herpes Simplex Virus-1 Replication.

Elaeocarpus sylvestris var. ellipticus (ES), which our research group had confirmed inhibits influenza A and SARS-CoV-2 viruses, was investigated to identify new potent and selective inhibitors of herpes simplex virus-1 (HSV-1) replication. To clarify the optimal condition for ES extract (ESE), ES was extracted at different concentrations of 0, 30, 50, 70, and 100%, to screen for its anti-HSV-1 effect. Among these ESE samples, ESE50 (50% concentration) exhibited the strongest inhibition of HSV-1 replication (EC50 23.2 µg/mL) while showing low cytotoxicity on host cells (IC50 342.8 µg/mL). The treatment of ESE50 clearly demonstrated a decrease in the expression of ICP0 in the lungs of HSV-1-infected BALB/c nude mice, compared to the MOCK group. Geraniin, which was isolated from ESE50 and analyzed using ESI-MS and 1D-(1H- and 13C-) and 2D-NMR, showed greater potency in inhibiting HSV-1 replication, as determined by the plaque reduction assay (EC50 8.3 µg/mL) and luciferase inhibition (EC50 36.9 µg/mL). The results demonstrate that ESE50 and geraniin show great potential as candidates for new drug discovery in the treatment of HSV-1 and related diseases.

Role of biomarkers in antimicrobial stewardship: physicians' perspectives.

Biomarkers are playing an increasingly important role in antimicrobial stewardship. Their applications have included use in algorithms that evaluate suspected bacterial infections or provide guidance on when to start or stop antibiotic therapy, or when therapy should be repeated over a short period (6-12 h). Diseases in which biomarkers are used as complementary tools to determine the initiation of antibiotics include sepsis, lower respiratory tract infection (LRTI), COVID-19, acute heart failure, infectious endocarditis, acute coronary syndrome, and acute pancreatitis. In addition, cut-off values of biomarkers have been used to inform the decision to discontinue antibiotics for diseases such as sepsis, LRTI, and febrile neutropenia. The biomarkers used in antimicrobial stewardship include procalcitonin (PCT), C-reactive protein (CRP), presepsin, and interleukin (IL)-1ß/IL-8. The cut-off values vary depending on the disease and study, with a range of 0.25-1.0 ng/mL for PCT and 8-50 mg/L for CRP. Biomarkers can complement clinical diagnosis, but further studies of microbiological biomarkers are needed to ensure appropriate antibiotic selection.

Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service.

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Comparison of Neutralizing Activity between Vaccinated and Unvaccinated Hospitalized COVID-19 Patients Infected with Delta, Omicron BA.1, or Omicron BA.2 Variant.

BACKGROUND: Understanding the immune response to evolving viral strains is crucial for evidence-informed public health strategies. The main objective of this study is to assess the influence of vaccination on the neutralizing activity of SARS-CoV-2 delta and omicron infection against various SARS-CoV-2 variants. METHODS: A total of 97 laboratory-confirmed COVID-19 cases were included. To assess the influence of vaccination on neutralizing activity, we measured the neutralizing activity of SARS-CoV-2 delta or omicron (BA.1 or BA.2) infection against wild-type (WT), delta, BA.1, and BA.2, with the results stratified based on vaccination status. RESULTS: The neutralizing activity against the WT, delta, and omicron variants (BA.1 and BA.2) was significantly higher in the vaccinated patients than those in the unvaccinated patients. In the unvaccinated individuals infected with the delta variant, the decrease in binding to BA.1 and BA.2 was statistically significant (3.9- and 2.7-fold, respectively) compared to the binding to delta. In contrast, vaccination followed by delta breakthrough infection improved the cross-neutralizing activity against omicron variants, with only 1.3- and 1.2-fold decreases in BA.1 and BA.2, respectively. Vaccination followed by infection improved cross-neutralizing activity against WT, delta, and BA.2 variants in patients infected with the BA.1 variant, compared to that in unvaccinated patients. CONCLUSIONS: Vaccination followed by delta or BA.1 infection is associated with improved cross-neutralizing activity against different SARS-CoV-2 variants. The enhanced protection provided by breakthrough infections could have practical implications for optimizing vaccination strategies.

The respiratory syncytial virus prefusion F protein vaccine attenuates the severity of respiratory syncytial virus-associated disease in breakthrough infections in adults ≥60 years of age.

Background: Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022). Methods: In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models. Results: In the RSVPreF3 OA group (N = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group (N = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: -9.86, 23.85; p = 0.4125) and 0.0786 (95% CI: -0.0340, 0.1913; p = 0.1695). Conclusions: The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility.

COVID-19 versus Other Disease Etiologies as the Cause of ARDS in Patients Necessitating Venovenous Extracorporeal Membrane Oxygenation-A Comparison of Patients' Data during the Three Years of the COVID-19 Pandemic.

Considering the characteristics of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS), we compared the clinical course and outcomes of patients with ARDS who received venovenous extracorporeal membrane oxygenation (VV ECMO) based on the etiology of ARDS. This retrospective single-center study included adult patients with severe ARDS necessitating VV ECMO during the COVID-19 pandemic. Among 45 patients who received VV ECMO, 21 presented with COVID-19. COVID-19 patients exhibited lower sequential organ failure assessment scores (9 [8-12.75] versus 8 [4-11.5], p = 0.033) but longer duration of VV ECMO support (10.5 days [3.25-29.25] versus 28 days [10.5-70.5] p = 0.018), which was accompanied by an weaning off rate from VV ECMO in 12/24 (50%) versus 12/21 (57.1%) and 28-day mortality in 9/24 [37.5%] versus 2/21 [9.5%] in non-COVID-19 and COVID-19 patients (p = 0.767, p = 0.040), respectively. Finally, in the adjusted Cox regression model for hospital mortality, the hazard ratio of COVID-19 was not significant (hazard ratio 0.350, 95% confidence interval 0.110-1.115, p = 0.076). Although the VV ECMO period was longer, COVID-19 did not significantly impact ECMO weaning off and mortality rates. Nonetheless, judicious patient selections based on risk factors should be followed.

Effects of Vitamin D Deficiency on Sepsis.

A prospective cohort study was conducted to evaluate the effect of vitamin D deficiency on sepsis. A total of 129 patients were enrolled. The median age was 74 years old, with a median SOFA score of 7; septic shock was observed in 60 patients. The median vitamin D level in the overall population was 13 ng/mL. A total of 96 patients had vitamin D deficiency, whereas 62 patients were described to have severe vitamin D deficiency. Severe vitamin D deficiency significantly increased the 14-day mortality (adjusted hazard ratio (aHR) 2.57; 95% confidence interval [CI]: 1.03-6.43; p = 0.043), 28-day mortality (aHR 2.28; 95% CI: 1.17-4.45; p = 0.016), and in-hospital mortality (aHR 2.11; 95% CI: 1.02-4.36; p = 0.044). In Kaplan-Meier analysis, the severe vitamin D deficiency group had significantly higher 14-day and 28-day mortality rates compared with the non-deficient group. Evaluating the vitamin D levels in sepsis patients may become necessary in an aging society. Severe vitamin D deficiency can independently affect poor prognosis related to sepsis. Further studies are needed to evaluate whether vitamin D supplementation in sepsis patients with vitamin D deficiency can help improve the prognosis of sepsis in addition to improving bone mineral metabolism.

Fusion Protein of RBP and Albumin Domain III Reduces Lung Fibrosis by Inactivating Lung Stellate Cells.

Activated stellate cells play a role in fibrosis development in the liver, pancreas, and kidneys. The fusion protein R-III, which consists of retinol-binding protein and albumin domain III, has been demonstrated to attenuate liver and renal fibrosis by suppressing stellate cell activation. In this study, we investigated the efficacy of R-III against bleomycin-induced lung fibrosis in mice. R-III reduced lung fibrosis and primarily localized in autofluorescent cells in the lung tissue. Furthermore, we isolated lung stellate cells (LSCs) from rat lungs using the isolation protocol employed for hepatic stellate cells (HSCs). LSCs shared many characteristics with HSCs, including the presence of vitamin A-containing lipid droplets and the expression of alpha-smooth muscle actin and collagen type I, markers for activated HSCs/myofibroblasts. LSCs spontaneously transdifferentiated into myofibroblasts in in vitro culture, which was inhibited by R-III. These findings suggest that R-III may reduce lung fibrosis by inactivating LSCs and could be a promising treatment for extrahepatic fibrosis.

Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies.

Long-standing scarcity of efficacious treatments and tumor heterogeneity have contributed to triple-negative breast cancer (TNBC), a subtype with a poor prognosis and aggressive behavior that accounts for 10-15% of all new cases of breast cancer. TNBC is characterized by the absence of progesterone and estrogen receptor expression and lacks gene amplification or overexpression of HER2. Genomic sequencing has detected that the unique mutational profile of both the somatic and germline modifications in TNBC is staggeringly dissimilar from other breast tumor subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. Nevertheless, reports regarding the penetrance and risk of other susceptibility genes are relatively scarce. Recurring mutations (e.g., TP53 and PI3KCA mutations) occur together with rare mutations in TNBC, and the shared effects of genomic modifications drive its progression. Given the heterogeneity and complexity of this disease, a clinical understanding of the genomic modifications in TNBC can pave an innovative way toward its therapy. In this review, we summarized the most recent discoveries associated with the underlying biology of developmental signaling pathways in TNBC. We also summarize the recent advancements in genetics and epidemiology and discuss state-of-the-art vaccine-based therapeutic strategies for TNBC that will enable tailored therapeutics.

Association of scrub typhus with incidence of dementia: a nationwide population-based cohort study in Korea.

BACKGROUND: Scrub typhus is a mite-borne infectious rickettsial disease that can occur in rural and urban areas, with an especially high prevalence in older populations. This disease causes systemic vasculitis that can invade the central nervous system. Considering these characteristics, here we examined whether scrub typhus was associated with the occurrence of dementia, using large population-based cohort data. METHOD: This population-based cohort study enrolled patients aged 60-89 years using data from the Health Insurance Review and Assessment database of South Korea between 2009 and 2018. We defined scrub typhus and dementia using International Classification of Diseases, Tenth Edition diagnostic codes. The control group was stratified according to age and sex at a ratio of 1:5 to the case group in the study population. The index date was set after 90 days beyond the date of the scrub typhus diagnosis, while the observation period was from the time of the index appointment to December 31, 2020. The primary outcome was newly diagnosed dementia. The secondary outcome was dementia classification, such as Alzheimer's disease, vascular dementia, and other. All analyses were conducted by matching age, gender, and comorbidity. RESULTS: During the observation period, 10,460 of 71,047 (14.7%) people who had a history of scrub typhus versus 42,965 of 355,235 (12.1%) people in the control group, that is, with no history of scrub typhus, were diagnosed with dementia (adjusted hazard ratio, 1.12; 95% confidence interval, 1.10-1.15, p < 0.001). The Kaplan-Meier curves for time to cumulative incidence of dementia showed that the dementia incidence in both groups increased over time, while individuals with a past history of scrub typhus had a higher incidence of dementia than the control group. Second, the risk of Alzheimer's disease was significantly higher among patients with a history of scrub typhus (adjusted hazard ratio, 1.15; 95% confidence interval 1.13-1.18, p < 0.001). CONCLUSION: In conclusion, a history of scrub typhus infection in old age is significantly associated with an increase in dementia, especially Alzheimer's disease. Our results suggest that prevention and appropriate treatment of scrub typhus should be emphasized as a dementia prevention measure.

Rate of and Risk Factors for Loss to Follow Up in HIV-Infected Patients in Korea: The Korea HIV/AIDS Cohort Study.

BACKGROUND: Owing to antiretroviral therapy (ART), acquired immune deficiency syndrome (AIDS)-related mortality has significantly decreased. Retaining in care is an essential step for human immunodeficiency virus (HIV) care cascade. This study investigated the incidence of and risk factors for loss to follow-up (LTFU) in Korean people living with HIV (PLWH). MATERIALS AND METHODS: Data from the Korea HIV/AIDS cohort study (including prospective interval cohort and retrospective clinical cohort) were analyzed. LTFU was defined as not visiting the clinic for more than 1 year. Risk factors for LTFU were identified using the Cox regression hazard model. RESULTS: The study enrolled 3,172 adult HIV patients (median age, 36 years; male 92.97%). The median CD4 T cell count at enrollment was 234 cells/mm3 (interquartile range [IQR]: 85 - 373) and the median viral load at enrollment was 56,100 copies/mL (IQR: 15,000 - 203,992). The total follow-up duration was 16,487 person-years, and the overall incidence rate of LTFU was 85/1,000 person-years. In the multivariable Cox regression model, subjects on ART were less likely to have LTFU than subjects not on ART (hazard ratio [HR] = 0.253, 95% confidence interval [CI]: 0.220 - 0.291, P <0.0001). Among PLWH on ART, female sex (HR = 0.752, 95% CI: 0.582 - 0.971, P = 0.0291) and older age (>50: HR = 0.732, 95% CI: 0.602 - 0.890; 41 - 50: HR = 0.634, 95% CI: 0.530 - 0.750; 31 - 40: HR = 0.724, 95% CI: 0.618 - 0.847; ≤30: reference, P <0.0001) were associated with high rate of retention in care. The viral load at ART initiation ≥1,000,001 (HR = 1.545, 95% CI: 1.126 - 2.121, ≤10,000: reference) was associated with a higher rate of LTFU. CONCLUSION: Young and male PLWH may have a higher rate of LTFU, and an increased rate of LTFU may induce virologic failure.

Remnant Preservation of the Primary Vertical Graft in Revision Anterior Cruciate Ligament Reconstruction.

Background: The remnant preservation of a primary vertical graft in revision anterior cruciate ligament reconstruction (ACLR) can benefit anteroposterior stability. However, studies that address this concept are rare. Purpose: To evaluate clinical outcomes of remnant preservation of primary vertical graft in revision ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 74 patients with revision ACLR were included in this retrospective study. Remnant preservation revision ACLR was performed only in patients with primary vertical grafts. The patients were divided into 2 groups according to whether the primary remnant vertical graft was preserved (remnant group; n = 48) or absent or sacrificed (no-remnant group; n = 26). The remnant group was further divided according to the degree of remnant tissue: sufficiently preserved subgroup (graft coverage, ≥50%; n = 25) and insufficiently preserved subgroup (graft coverage, <50%; n = 23). Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) subjective form, Lysholm score, Tegner activity scale, manual laxity tests, and side-to-side difference in anterior tibial translation on Telos stress radiographs. Results: The mean time to final follow-up was 40.7 ± 16.8 months. The remnant group showed more improved results in the postoperative Lachman test and Telos side-to-side difference than did the no-remnant group (P = .017 and .016, respectively). The post hoc test revealed that the side-to-side difference in laxity in the sufficiently preserved subgroup significantly outperformed that in the no-remnant group (P = .001), although no significant difference existed between the insufficiently preserved and no-remnant subgroups (P = .850). The postoperative IKDC subjective form, Lysholm score, and Tegner activity scale did not show significant differences between the 2 groups (P = .480, .277, and .883, respectively). Conclusion: The remnant preservation of the primary vertical graft in revision ACLR may result in better anteroposterior stability. However, subjective outcomes in the remnant group did not exceed that of the no-remnant group. The subgroup analysis revealed that only sufficiently preserved remnants demonstrated better anteroposterior stability.

Re-identification and Characterization of Multidrug-Resistant Corynebacterium haemomassiliense-Like Organisms from Humans.

Recently, non-diphtheriae Corynebacterium spp. have been increasingly reported in patients. In addition, several novel species of Corynebacterium isolated from humans. Here, we report two cases of human infections caused by Corynebacterium haemomassiliense-like organisms, which had not been identified at the species level by MALDI-TOF MS analysis. They were revealed to be closely related to C. haemomassiliense, a recently described species by three housekeeping genes (16S rRNA, rpoB, and gyrA) and phenotypic features. Both strains were multidrug-resistant but susceptible to vancomycin, meropenem, and linezolid. Our report suggests that human infections by the recently described Corynebacterium species may not be limited to a specific region, in addition to difficulty of classifying the genus Corynebacterium.

Indirect Decompression Using Oblique Lumbar Interbody Fusion Revision Surgery Following Previous Posterior Decompression: Comparison of Clinical and Radiologic Outcomes Between Direct and Indirect Decompression Revision Surgery.

OBJECTIVE: This study compared the radiological and clinical outcomes with transforaminal lumbar interbody fusion (TLIF) to evaluate the effect of indirect decompression through oblique lumbar interbody fusion (OLIF) as revision surgery. METHODS: We enrolled patients who underwent single-level fusion with revision surgery at the same level as the previous decompression level. We retrospectively reviewed 25 patients who underwent OLIF from 2017 to 2018 and 25 who received TLIF from 2014 to 2018. Radiologic and clinical outcomes were evaluated by cross-sectional area (CSA) of the spinal canal, thickness and area of ligamentum flavum (LF), subsidence, disc height, fusion rate, Oswestry Disability Index (ODI), and visual analogue scale (VAS). RESULTS: Compared with OLIF, the thickness and area of the LF after surgery were significantly less in TLIF, and the resulting CSA extension was also significantly higher. However, both groups showed improvement in ODI and VAS after surgery, and there was no difference between the groups. Complications related to the posterior approach in TLIF were 4 cases, and in OLIF, there were 2 cases that underwent additional posterior decompression surgery and 6 cases of transient paresthesia. CONCLUSION: Since complications associated with the posterior approach can be avoided, OLIF is a safer and useful minimally invasive surgery. Therefore, appropriate indications are applied, OLIF is a good alternative to TLIF when revision surgery is considered.

Mortality and Causes of Death among Individuals Diagnosed with Human Immunodeficiency Virus in Korea, 2004-2018: An Analysis of a Nationwide Population-Based Claims Database.

The mortality rate and causes of death among individuals diagnosed with human immunodeficiency virus (HIV) infection in Korea were described and compared to those of the general population of Korea using a nationwide population-based claims database. We included 13,919 individuals aged 20-79 years newly diagnosed with HIV between 2004 and 2018. The patients' vital status and cause of death were linked until 31 December 2019. Standardized mortality ratios (SMRs) for all-cause death and specific causes of death were calculated. By the end of 2019, 1669 (12.0%) of the 13,919 HIV-infected participants had died. The survival probabilities of HIV-infected individuals at 1, 5, 10, and 15 years after diagnosis in Korea were 96.2%, 91.6%, 85.9%, and 79.6%, respectively. The main causes of death during the study period were acquired immunodeficiency syndrome (AIDS; 59.0%), non-AIDS-defining cancer (8.2%), suicide (7.4%), cardiovascular disease (4.9%), and liver disease (2.7%). The mortality rate of men and women infected with HIV was 5.60-fold (95% CI = 5.32-5.89) and 6.18-fold (95% CI = 5.30-7.09) that of men and women in the general population, respectively. After excluding deaths due to HIV, the mortality remained significantly higher, with an SMR of 2.16 (95% CI = 1.99-3.24) in men and 3.77 (95% CI = 3.06-4.48) in women. HIV-infected individuals had a higher overall mortality than the general population, with AIDS the leading cause of mortality. Additionally, mortality due to non-AIDS-related causes was higher in HIV-infected individuals.

Immunogenicity after outbreak response immunization activities among young healthcare workers with secondary vaccine failure during the measles epidemic in Korea, 2019.

BACKGROUND: Despite high vaccination coverage, measles outbreaks have been reported in measles elimination countries, especially among healthcare workers in their 20 and 30 s. This study was designed to identify measles-susceptible individuals and to evaluate whether primary or secondary vaccine failure occurred during measles outbreak response immunization (ORI) activities. METHODS: The study population was divided into three groups as follows: natural immunity group (Group 1), vaccine-induced immunity group (Group 2), and vaccine failure group (Group 3). We evaluated the immunogenicity of measles among healthcare workers using three methods-enzyme-linked immunoassays, plaque reduction neutralization tests, and avidity assays. The results were assessed at baseline, 4 weeks after, and 6 months after the completion of measles-mumps-rubella (MMR) vaccination. RESULTS: In total, 120 subjects were enrolled, with 40 subjects in each group. The median age of Group 3 was 29 years, which was significantly lower than that of the other groups. The baseline negative measles virus (MeV) IgG in Group 3 increased to a median value of 165 AU/mL at 4 weeks after ORI and was lower than that in Groups 1 and 2. The median neutralizing antibody titer was highest in Group 1, and this was significantly different from that in Group 2 or Group 3 at 4 weeks (944 vs. 405 vs. 482 mIU/mL, P = 0.001) and 6 months (826 vs. 401 vs. 470, P = 0.011) after ORI. The rates of high MeV avidity IgG were highest in Group 2, and these were significantly different from those in Groups 1 or 3 at 4 weeks (77.5 vs. 90% vs. 88.6%, P = 0.03) and 6 months (81 vs. 94.8 vs. 82.1%, P = 0.01) after ORI. CONCLUSIONS: Considering the MeV-neutralizing antibodies and IgG avidity after MMR vaccination in measles-susceptible group, vaccine failure is inferred as secondary vaccine failure, and further data regarding the maintenance of immunogenicity are needed based on long-term data. The MeV-neutralizing antibody levels were highest in the natural immunity group, and the primary vaccine-induced immunity group showed the highest rates of high MeV IgG avidity.

Developing a multiplex loop-mediated isothermal amplification assay (LAMP) to determine severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are endemic zoonotic diseases that pose significant public health threats in East Asia. As these two diseases share common clinical features, as well as overlapping disease regions, it is difficult to differentiate between SFTS and scrub typhus. A multiplex reverse-transcription loop­mediated isothermal amplification (RT-LAMP) assay was developed to detect large segments and GroES genes for SFTS virus (SFTSV) and Orientia tsutsugamushi (OT). The performance of the RT-LAMP assay was compared and evaluated with those of commercial PowerChek™ SFTSV real-time PCR and LiliF™ TSUTSU nested PCR for 23 SFTS and 12 scrub typhus clinical samples, respectively. The multiplex SFTSV/OT/Internal control (IC) RT-LAMP assay showed comparable sensitivity (91.3%) with that of commercial PowerChek™ SFTSV Real-time PCR (95.6%) and higher sensitivity (91.6%) than that of LiliF™ TSUTSU nested PCR (75%). In addition, the multiplex SFTSV/OT RT-LAMP assay showed 100% specificity and no cross-reactivity for blood from uninfected healthy patients and samples from patients infected with other fever viruses. Thus, the multiplex SFTSV/OT/IC RT-LAMP assay could serve as a useful point-of-care molecular diagnostic test for SFTS and scrub typhus.

Diagnostic and prognostic value of presepsin and procalcitonin in non-infectious organ failure, sepsis, and septic shock: a prospective observational study according to the Sepsis-3 definitions.

BACKGROUND: We investigated the diagnostic and prognostic value of presepsin among patients with organ failure, including sepsis, in accordance with the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). METHODS: This prospective observational study included 420 patients divided into three groups: non-infectious organ failure (n = 142), sepsis (n = 141), and septic shock (n = 137). Optimal cut-off values of presepsin to discriminate between the three groups were evaluated using receiver operating characteristic curve analysis. We determined the optimal cut-off value of presepsin levels to predict mortality associated with sepsis and performed Kaplan-Meier survival curve analysis according to the cut-off value. Cox proportional hazards model was performed to determine the risk factors for 30-day mortality. RESULTS: Presepsin levels were significantly higher in sepsis than in non-infectious organ failure cases (p < 0.001) and significantly higher in patients with septic shock than in those with sepsis (p = 0.002). The optimal cut-off value of the presepsin level to discriminate between sepsis and non-infectious organ failure was 582 pg/mL (p < 0.001) and between sepsis and septic shock was 1285 pg/mL (p < 0.001). The optimal cut-off value of the presepsin level for predicting the 30-day mortality was 821 pg/mL (p = 0.005) for patients with sepsis. Patients with higher presepsin levels (≥ 821 pg/mL) had significantly higher mortality rates than those with lower presepsin levels (< 821 pg/mL) (log-rank test; p = 0.004). In the multivariate Cox proportional hazards model, presepsin could predict the 30-day mortality in sepsis cases (hazard ratio, 1.003; 95% confidence interval 1.001-1.005; p = 0.042). CONCLUSIONS: Presepsin levels could effectively differentiate sepsis from non-infectious organ failure and could help clinicians identify patients with sepsis with poor prognosis. Presepsin was an independent risk factor for 30-day mortality among patients with sepsis and septic shock.

Anti-varicella zoster virus and related anti-inflammation effects of ethanolic extract of Elaeocarpus sylvestris.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES. AIM OF THE STUDY: In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES. METHODS: and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells. RESULTS: To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1ß, IL-6, and TNF-α. CONCLUSION: E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.

Feasibility of ultraviolet light-emitting diode irradiation robot for terminal decontamination of coronavirus disease 2019 (COVID-19) patient rooms.

OBJECTIVE: To investigate the feasibility of using an ultraviolet light-emitting diode (UV LED) robot for the terminal decontamination of coronavirus disease 2019 (COVID-19) patient rooms. METHODS: We assessed the presence of viral RNA in samples from environmental surfaces before and after UV LED irradiation in COVID-19 patient rooms after patient discharge. RESULTS: We analyzed 216 environmental samples from 17 rooms: 2 from airborne infection isolation rooms (AIIRs) in the intensive care unit (ICU) and 15 from isolation rooms in the community treatment center (CTC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in 40 (18.5%) of 216 samples after patient discharge: 12 (33.3%) of 36 samples from AIIRs in the ICU, and 28 (15.6%) of 180 samples from isolation rooms in the CTC. In 1 AIIR, all samples were PCR negative after UV LED irradiation. In the CTC rooms, 14 (8.6%) of the 163 samples were PCR positive after UV LED irradiation. However, viable virus was not recovered from the culture of any of the PCR-positive samples. CONCLUSIONS: Although no viable virus was recovered, SARS-CoV-2 RNA was detected on various environmental surfaces. The use of a UV LED disinfection robot was effective in spacious areas such as an ICU, but its effects varied in small spaces like CTC rooms. These findings suggest that the UV LED robot may need enough space to disinfect rooms without recontamination by machine wheels or insufficient disinfection by shadowing.