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Liver disease is a growing burden among people living with HIV (PLHIV) in resource-limited settings. As an indicator of liver disease, risk factors of high alanine aminotransferase (ALT) and cirrhosis were assessed among PLHIV in the TREAT Asia HIV Observational Database (TAHOD). Patients on combination antiretroviral therapy (cART) with a pre-cART ALT measurement and at least one follow-up ALT measurement were included. Factors associated with high ALT (ALT levels 5 times its upper limit of normal) were analyzed using repeated measure logistic regression over a 10-year follow-up period. Liver cirrhosis was defined as having an AST to Platelet Ratio Index score 1.5, fibrosis-4 score 3.25, or a clinical diagnosis of cirrhosis. Cox regression analysis stratified by site was used to analyze factors associated with cirrhosis among those in follow-up after 2015. Of 5182 patients, 101 patients (1.9%) had high ALT levels with hepatitis C virus (HCV) antibody positive (odds ratio [OR]: 4.98, 95% confidence interval [CI]: 2.82-8.77, p 0.001) and ever high alcohol consumption (OR: 2.33, 95% CI: 1.00-5.46, p = 0.050) as likely factors. Among 6318 PLHIV in the liver cirrhosis analysis, 151 (2%) developed cirrhosis (incidence rate = 0.82 per 100 person-years). Those HCV-antibody positive (hazard ratio [HR]: 5.54, 95% CI: 3.75-8.18, p 0.001) and had high alcohol consumption (HR: 2.06, 95% CI: 1.23-3.45, p = 0.006) were associated with liver cirrhosis. HCV-antibody positive and high alcohol consumption are factors associated with high ALT. With raised ALT levels as a known factor associated with liver cirrhosis, greater efforts are required in managing ALT levels and reducing the risk of developing liver cirrhosis among those positive for HCV-antibody and those who consume alcohol.

Acute thrombotic thrombocytopenic purpura (TTP) is a life-threatening emergency and plasma exchange (PEX) is the initial treatment shown to reduce acute mortality.To compare current practice in the United Kingdom (UK) against the standards set out in the 2012 British Society of Haematology guideline, and to better understand the issues affecting prompt initiation of PEX.The trainee research network HaemSTAR conducted a retrospective nationwide review of adults presenting to UK hospitals with a first episode of acute TTP.Data on 148 patients treated at 80 UK hospitals between 2014 and 2019 demonstrated that 64.8% of patients received PEX within 24 h. Diagnostic uncertainty was the most commonly cited reason for delayed treatment. Conversely, a shorter time to PEX occurred in patients who had red cell fragments or severe thrombocytopenia identified on their first complete blood count. Availability of on-site PEX was associated with a greater proportion of patients receiving PEX within 8 h compared to patients transferred, but by 24 h there was no difference between the two groups and two-thirds of all patients had received their first PEX. The mortality rate for patients that received PEX was 9.2%, with 27.8% of deaths linked to delayed treatment initiation.This is the first multi-center evaluation of treatment delays in acute TTP and it will inform targeted pathways to improve prompt access to life-saving intervention.

Posttraumatic cerebral infarction (PTCI) is a serious complication of traumatic brain injury (TBI), and the prevalence and risk factors of PTCI in TBI patients are in dispute. We systematically searched the literature in the PubMed, Embase, and Cochrane library up to October 2021 to identify studies on the prevalence and risk factors of PTCI in patients with TBI. The quality of observational studies was assessed by the Newcastle-Ottawa scale tool. Random-effects model was conducted. The Higgins`

Sedation can resolve anxiety and fear in patients undergoing endoscopy. The use of sedatives has increased in Korea. Appropriate sedation is a state in which the patient feels subjectively comfortable while maintaining the airway reflex for stable spontaneous breathing. The patient should maintain a state of consciousness to the extent that he or she can cooperate with the needs of the medical staff. Despite its benefits, endoscopic sedation has been associated with cardiopulmonary complications. Cardiopulmonary complications are usually temporary. Most patients recover without sequelae. However, they may progress to serious complications, such as cardiovascular collapse. Therefore, it is essential to screen high-risk patients before sedation and reduce complications by meticulous monitoring. Additionally, physicians should be familiar with the management of emergencies. The first Korean clinical practice guideline for endoscopic sedation was developed based on previous worldwide guidelines for endoscopic sedation using an adaptation process. The guideline consists of nine recommendations based on a critical review of currently available data and expert consensus when the guideline was drafted. These guidelines should provide clinicians, nurses, medical school students, and policy makers with information on how to perform endoscopic sedation with minimal risk.

We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein.Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19-49 years for the GX-19 trial and healthy adults aged 19-54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1·5 mg or 3·0 mg), and the GX-19N trial participants received two 3·0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 (NCT044445389) and GX-19N (NCT04715997) trials are registered with ClinicalTrials.gov.Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 [50%] in the 1·5 mg group and 20 [50%] in the 3·0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1·5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0·0002 in the 1·5 mg GX-19 group; p0·0001 in the 3·0 mg GX-19; and p=0·0004 for the spike protein and p=0·0001 for the RBD in the 3·0 mg GX-19N group).GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2-specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity.The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare.

Although the prevalence and mortality of hepatitis is high in the Asia-Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART).Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD-LITE) cohort, on ART, and with follow-up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co-infection if they ever tested positive for HCV antibody (anti-HCV) or HBV surface antigen (HBsAg), respectively.In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti-HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti-HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response.Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment.

The passive transport of glucose and related hexoses in human cells is facilitated by members of the glucose transporter family (GLUT, SLC2 gene family). GLUT3 is a high-affinity glucose transporter primarily responsible for glucose entry in neurons. Changes in its expression have been implicated in neurodegenerative diseases and cancer. GLUT3 inhibitors can provide new ways to probe the pathophysiological role of GLUT3 and tackle GLUT3-dependent cancers. Through in silico screening of an ~ 8 million compounds library against the inward- and outward-facing models of GLUT3, we selected ~ 200 ligand candidates. These were tested for in vivo inhibition of GLUT3 expressed in hexose transporter-deficient yeast cells, resulting in six new GLUT3 inhibitors. Examining their specificity for GLUT1-5 revealed that the most potent GLUT3 inhibitor (G3iA, IC50 ~ 7 µM) was most selective for GLUT3, inhibiting less strongly only GLUT2 (IC50 ~ 29 µM). None of the GLUT3 inhibitors affected GLUT5, three inhibited GLUT1 with equal or twofold lower potency, and four showed comparable or two- to fivefold better inhibition of GLUT4. G3iD was a pan-Class 1 GLUT inhibitor with the highest preference for GLUT4 (IC50 ~ 3.9 µM). Given the prevalence of GLUT1 and GLUT3 overexpression in many cancers and multiple myeloma’s reliance on GLUT4, these GLUT3 inhibitors may discriminately hinder glucose entry into various cancer cells, promising novel therapeutic avenues in oncology.

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p Clinical trials registration: ClinicalTrials.gov (NCT02865369).

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, blaKPC, blaNDM, and blaOXA 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, blaNDM, 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.

Item does not contain fulltext BACKGROUND: Rezafungin is a next-generation, once-a-week echinocandin in development for the treatment of candidaemia and invasive candidiasis and for the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis spp after blood and marrow transplantation. We aimed to compare the efficacy and safety of intravenous rezafungin versus intravenous caspofungin in patients with candidaemia and invasive candidiasis. METHODS: ReSTORE was a multicentre, double-blind, double-dummy, randomised phase 3 trial done at 66 tertiary care centres in 15 countries. Adults (≥18 years) with systemic signs and mycological confirmation of candidaemia or invasive candidiasis were eligible for inclusion and randomly assigned (1:1) to receive intravenous rezafungin once a week (400 mg in week 1, followed by 200 mg weekly, for a total of two to four doses) or intravenous caspofungin (70 mg loading dose on day 1, followed by 50 mg daily) for no more than 4 weeks. The primary endpoints were global cure (consisting of clinical cure, radiological cure, and mycological eradication) at day 14 for the European Medical Agency (EMA) and 30-day all-cause mortality for the US Food and Drug Administration (FDA), both with a target non-inferiority margin of 20%, assessed in the modified intention-to-treat population (all patients who received one or more doses of study drug and had documented Candida infection based on a culture from blood or another normally sterile site obtained within 96 h before randomisation). Safety was evaluated by the incidence and type of adverse events and deaths in the safety population, defined as all patients who received any amount of study drug. The trial is registered with ClinicalTrials.gov, NCT03667690, and is complete. FINDINGS: Between Oct 12, 2018, and Aug 29, 2021, 222 patients were screened for inclusion, and 199 patients (118 [59%] men; 81 [41%] women; mean age 61 years [SD 15·2]) were randomly assigned (100 [50%] patients to the rezafungin group and 99 [50%] patients to the caspofungin group). 55 (59%) of 93 patients in the rezafungin group and 57 (61%) of 94 patients in the caspofungin group had a global cure at day 14 (weighted treatment difference -1·1% [95% CI -14·9 to 12·7]; EMA primary endpoint). 22 (24%) of 93 patients in the rezafungin group and 20 (21%) of 94 patients in the caspofungin group died or had an unknown survival status at day 30 (treatment difference 2·4% [95% CI -9·7 to 14·4]; FDA primary endpoint). In the safety analysis, 89 (91%) of 98 patients in the rezafungin group and 83 (85%) of 98 patients in the caspofungin group had at least one treatment-emergent adverse event. The most common treatment-emergent adverse events that occurred in at least 5% of patients in either group were pyrexia, hypokalaemia, pneumonia, septic shock, and anaemia. 55 (56%) patients in the rezafungin group and 52 (53%) patients in the caspofungin group had serious adverse events. INTERPRETATION: Our data show that rezafungin was non-inferior to caspofungin for the primary endpoints of day-14 global cure (EMA) and 30-day all-cause mortality (FDA). Efficacy in the initial days of treatment warrants evaluation. There were no concerning trends in treatment-emergent or serious adverse events. These phase 3 results show the efficacy and safety of rezafungin and support its ongoing development. FUNDING: Cidara Therapeutics and Mundipharma.

An optimal sequential anti-hepatocellular carcinoma (HCC) agent that can be used after failed lenvatinib treatment has not been established. Here, we compared the outcomes of sorafenib and nivolumab as second-line agents after failed lenvatinib treatment in patients with advanced HCC.Patients with advanced HCC who had received sorafenib or nivolumab as second-line agents after failed lenvatinib treatment were recruited from two Korean tertiary institutions between November 2018 and June 2020.The median age of the 60 participants (52 treated with sorafenib and eight treated with nivolumab) at baseline was 56.8 years. The demographic, laboratory and tumor variables, as well as lenvatinib treatment duration, were similar between the two groups. The median durations of sorafenib and nivolumab treatment were 1.2 and 2.6 months, respectively ( P = 0.164). Twenty-four (40.0%) patients died during the follow-up period (median, 15.8 months). The median overall survival (OS) of the study population was 5.8 months. The median OS of patients treated with sorafenib was significantly longer than the median OS of patients treated with nivolumab (8.7 vs. 3.0 months; P = 0.046). Sorafenib treatment (vs. nivolumab) was independently associated with a lower risk of mortality (hazard ratio = 0.194; 95% confidence interval, 0.053-0.708; P = 0.013). Worse Eastern Cooperative Oncology Group performance status, larger maximal tumor size, lymph node metastases and higher total bilirubin levels were independently associated with increased mortality risk (all P 0.05).Lenvatinib-sorafenib sequential treatment resulted in significantly better survival did than lenvatinib-nivolumab sequential treatment in patients with advanced HCC. Larger studies are needed to validate our results.

Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown effects from serum impurities, and relatively low bioactivities against dose. In this study, we proposed a cell modulation method with melatonin for human umbilical cord MSCs (hUCMSCs) cultured in serum-free chemically defined media (CDM) to eliminate the effects of serum-derived impurities and promote regeneration-related activities. miRNAs highly associated with regeneration were selected and the expression levels of them were comparatively analyzed among various types of EVs depending on culture conditions. The EVs derived from melatonin-stimulated hUCMSCs in CDM (CDM mEVs) showed the highest expression levels of regeneration-related miRNAs, and 7 times more hsa-let-7b-5p, 5.6 times more hsa-miR-23a-3p, and 5.7 times more hsa-miR-100-5p than others, respectively. In addition, the upregulation of various functionalities, such as wound healing, angiogenesis, anti-inflammation, ROS scavenging, and anti-apoptosis, were proven using in vitro assays by simulating the characteristics of EVs with bioinformatics analysis. The present results suggest that the highly regenerative properties of hUCMSC-derived EVs were accomplished with melatonin stimulation in CDM and provided the potential for clinical uses of EVs.

Objectives We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV. Methods Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality. Results Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m2 , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236). Conclusions Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.

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.

BACKGROUND AND AIM Antiviral therapy (AVT) induces fibrosis regression in patients with chronic hepatitis B. We investigated long-term effects of entecavir (ETV) versus tenofovir (TDF) on fibrotic burden. METHODS Treatment-naive chronic hepatitis B patients who had begun ETV or TDF were recruited from four tertiary hospitals. The aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) were used to determine fibrotic burden. RESULTS In the entire population (n = 3277), although patients treated with ETV had higher baseline APRI (1.71 vs 1.07, P

INTRODUCTION The necessity of antiviral therapy (AVT) for hepatitis B virus (HBV)-infected compensated cirrhosis with low-level viremia (LLV) is controversial. Herein, we evaluated its natural history. METHODS From 3 tertiary hospitals, we enrolled untreated patients with compensated cirrhosis with persistent serum HBV-DNA levels

As the life expectancy of people living with HIV (PLWH) approaches that of the general population, the burden of comorbidities such as cardiovascular disease (CVD) is increasing. Regardless of HIV status, about 50% of CVD deaths worldwide occur in Asia, and Asian PLWH have a high prevalence of conventional CVD risk factors, such as smoking, dyslipidaemia, hypertension and insulin resistance or diabetes. As well as conventional CVD risk factors, PLWH have HIV-specific risk factors such as chronic inflammation, immune activation and endothelial damage, as well as risk factors related to antiretroviral therapy. This review describes the current knowledge on the epidemiology and risk factors of CVD in Asian PLWH and provides an Asian perspective on the recommendations for managing CVD risk in PLWH.

The association between chronic hepatitis B (CHB) and cardiovascular disease (CVD) remains unclear. We investigated the prevalence and risk factors of CVD in patients with CHB.Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analyzed. Significant liver fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile, highest Forns index quintile, or fibrosis-4 ≥ 2.67. The CVD risk was calculated using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score from the 2013 ACC/AHA Guidelines.Among the 506 subjects with CHB, 15 (3.0%) and 150 (29.6%) patients had a CVD history and significant liver fibrosis, respectively. Patients with CVD history were significantly older; showed a significantly higher prevalence of hypertension, metabolic syndrome, and significant liver fibrosis; and had a significantly higher platelet count, lower aspartate and alanine aminotransferase levels, higher triglyceride level, lower high-density lipoprotein level, and higher ASCVD risk than those without (all p 0.05). In multivariate analysis, higher ASCVD risk (odds ratio [OR] = 1.090) and significant liver fibrosis (OR = 4.341) independently predicted the risk of CVD history (p 0.05). The prevalence of CVD risk (6.7% vs. 1.4%; OR = 5.014) and high ASCVD risk ( 15%) (34.0% vs. 7.3%; OR = 6.538) was significantly higher in patients with significant liver fibrosis than in those without (all p 0.05).Significant liver fibrosis was independently associated with the risk of CVD history in patients with CHB. Prospective studies are needed to validate the longitudinal association between fibrotic burden and CVD development in patients with CHB.

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.

Objective: To explore the effect of problematic mobile phone use on college students’ physical activity and their relationships. Methods: A cross-sectional study was conducted among 3980 college students from three universities in Jiangsu province by random cluster sampling. The International Physical Activity Questionnaire Short (IPAQ-SF) measured college students’ physical activity. The Mobile Phone Addiction Tendency Scale for College Students (MPATS) measured problematic mobile phone use tendencies. College students’ physical activity was measured by the International Physical Activity Questionnaire Short (IPAQ-SF), and the Mobile Phone Addiction Tendency Scale measured their mobile phone addiction tendency for College Students (MPATS). Results: (1) The proportions of the low-, medium-, and high-intensity physical activity were 83.5%, 10.7%, and 5.8%, respectively, with gender differences; The score of problematic mobile phone use tendency was 38.725 ± 15.139. (2) There were significant differences in problematic mobile phone use tendency among college students with different physical activity intensity (F = 11.839, p < 0.001, η2 = 0.007). (3) The level of physical activity was significantly correlated with the tendency of problematic mobile phone use (r = −0.173, p < 0.001). (4) Physical activity of college students could significantly predict the tendency of problematic mobile phone use (F (3,3605) = 11.296, p < 0.001). Conclusions: The physical activity of college students was mainly moderate to low intensity, while the tendency of problematic mobile phone use was high. College students’ physical activity level was one of the important constraints of problematic mobile phone use tendency.

IntroductionDespite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy.MethodsWe performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND50) against wild type (WT) SARS-CoV-2 and that of the Delta variant.ResultsWe conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2–99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7–100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0–87.1%; P <0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT).ConclusionDecreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.

Objective: Negative moods in college students have caused frequent extreme behaviors. This study analyzed the current status and correlation between physical activity and negative moods in college students. Methods: A cross-sectional study design was used in the present research. Data on college students’ physical activity and negative moods were collected using the Sports Questionnaire Star software. The questionnaires were administered to college students in five colleges and universities in Henan and Jiangsu Provinces, China, and a total of 3711 correctly completed questionnaires were returned. Data on sociological and demographic information, the International Physical Activity Questionnaire Short Form (IPAQ-SF), and the Depression Anxiety and Stress Scale (DASS) were collected. The research was conducted in December 2021. Results: The low-intensity physical activity rate among college students was 55.56%, while depression, anxiety, and stress symptoms were detected in 35.14%, 65.29%, and 10.99%of the college students, respectively. Depression (K = 35.58, p < 0.001) and anxiety (K = 15.56, p < 0.001) rates were significantly different among the different physical activity intensity groups. The proportion of students who perform high-intensity physical activities was lower than those who perform low- and moderate-intensity physical activities. Conclusion: Low physical activity and high anxiety are evident among college students, and prolonged moderate-to-low-intensity physical activity (including static behavior) induces depression and anxiety. In the future, further studies can be conducted on improving the physical activity intensity of college students, improving the mental health monitoring and intervention systems of college students, and exploring the dose–effect relationship between physical activity and negative moods.

Background 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. MethodsThis 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 hours 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. Results 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 1,000 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 ConclusionBSI is a common complication of patients receiving ECMO support and is associated with poor clinical outcomes. Determining the type of frequently isolated organisms and the median onset time of BSI would help in the selection of appropriate prophylactic antibiotics or antifungal agents.

Cirrhosis has prognostic value. We investigated whether the combined use of ultrasonography (US) and transient elastography (TE) to diagnose cirrhosis is beneficial for the risk assessment of hepatocellular carcinoma (HCC) and liver-related events in patients with chronic hepatitis B (CHB). A total of 9300 patients with CHB who underwent US and TE in two institutions between 2006 and 2018 were enrolled. TE value ≥13 kPa was set to indicate cirrhosis. Patients were divided into four groups: US(+)TE(+) (cirrhosis by US and TE), US(+)TE(-) (cirrhosis by US, but not by TE), US(-)TE(+) (cirrhosis by TE, but not by US) and US(-)TE(-) (non-cirrhosis by US and TE).The patients were predominantly male (n = 5474, 58.9%) with a mean age of 47.5 years. The proportions of patients with cirrhosis diagnosed by US and TE were 17.2% (n = 1595) and 13.2% (n = 1225), respectively. The proportion of patients with discordant results in diagnosing cirrhosis by US and TE was 18.7% (n = 1740). During follow-up (median: 60.0 months), HCC and liver-related events developed in 481 (5.2%) and 759 (8.2%) patients, respectively. The cumulative incidence rates of HCC and liver-related events were highest in the US(+)TE(+) group, intermediate-high in the US(-)TE(+) group, intermediate-low in the US(+)TE(-) group and lowest in the US(-)TE(-) group (overall p

Introduction Chronic hepatitis B is an important public health concern. Introduction of oral nucleos(t)ide analogs (NAs), inhibitors of hepatitis B virus (HBV) polymerase, was a milestone that lowered the high viral loads associated with an increased risk of liver-related complications. Areas covered Although the currently available NAs are effective in suppressing viral replication, anti-HBV treatment in principle requires lifelong drug administration, and some patients have limitations such as the incidence of liver cancer and the likelihood of toxicities following long-term treatment despite viral suppression. Besifovir dipivoxil maleate (BSV), an oral nucleotide analog, is a prodrug that is metabolized to its active form. It has consistent and well-characterized pharmacokinetics in animals and human. In clinical studies, BSV exhibits significant and potent viral suppression of HBV replication with maintenance of antiviral efficacy for over 192 weeks without resistance, or renal and bone toxicities. Herein, the authors discuss the data of BSV and provide the reader with their expert opinion. Expert opinion BSV is a newly developed antiviral agent against HBV. This new agent has strong antiviral activity with low toxicity and a high barrier to resistance. Because there is concern that patients treated with a high dose of BSV require carnitine supplementation, BSV with carnitine supplementation is recommended during antiviral therapy.

The influence of hepatic steatosis on the natural history of chronic hepatitis B (CHB) virus is unclear. Therefore, we investigated whether concurrent steatosis in patients with CHB influences the probability of hepatitis B surface antigen (HBsAg) loss, fibrosis progression and hepatocellular carcinoma (HCC) development. This study enrolled treatment-naïve patients with virologically (HBV DNA2,000 IU/ml) and biochemically (alanine aminotransferase level40 IU/L) quiescent CHB who underwent transient elastography between January 2004 and December 2015 and completed 3 years of follow-up. RESULTS: The mean age of the study population (n = 720) was 52.0 years, and there were more men than women (n = 419, 58.2%). The mean HBV DNA level was 321.6 IU/ml. During the 3-year period, 74 (10.3%) patients achieved HBsAg seroclearance. Lower HBV DNA levels (hazard ratio = 0.995, p .05) were independently associated with HBsAg seroclearance, while hepatic steatosis was not (p .05). Fibrosis progressed in 89 (12.4%) patients. Male gender (odds ratio [OR] = 1.720) and higher body mass index (OR = 1.083) were independently associated with an increased probability of fibrosis progression (all p .05), while higher total cholesterol levels (OR = 0.991) and higher liver stiffness values (OR = 0.862) were independently associated with a decreased probability of fibrosis progression (all p .05). HCC developed in 46 (6.4%) patients. Male gender (OR = 3.917) and higher AST levels (OR = 1.036) were independently associated with an increased probability of HCC development (p .05). Hepatic steatosis was not associated with the probability of HBsAg seroclearance, fibrosis progression or HCC development in patients quiescent CHB in our study. Further studies with longer follow-up periods are required to validate our findings.

Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

Purpose Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. Materials and methods This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or life-threatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. Results Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002). No transfusion-related side effects were observed. Conclusion CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

Controlled attenuation parameter (CAP) can evaluate hepatic steatosis in patients with chronic hepatitis B (CHB). However, prognostic implications of CAP value remain unclear. We evaluated the association between CAP and the risk of hepatocellular carcinoma (HCC) in patients with CHB under antiviral therapy and maintained virologic response. A total of 1823 CHB patients who were taking nucleos(t)ide analogue and showing suppressed hepatitis B virus replication were analyzed. The primary outcome was incident HCC during follow-up. Patients were grouped into those with and without advanced chronic liver disease (ACLD) (liver stiffness measurement cutoff: 10 kPa), and those with and without hepatic steatosis (CAP cutoff: 222 dB/m). During 6.4 years of follow-up, 127 patients (7.0%) newly developed HCC. Among patients with ACLD (n = 382), the cumulative HCC incidence rate was lower for those with CAP ≥ 222 (11.0% at 5 years) than those with CAP

We investigated the prevalence of metabolic syndrome (MetS) in all or nonobese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and compared it with age- and gender-matched controls. Also, we assessed the effect of variables at diagnosis on the risk of cardiovascular disease (CVD) in all or nonobese AAV patients. In this study, 173 AAV patients and 344 controls were included and MetS was defined by the National Cholesterol Education Program Adults Treatment Panel III criteria. The obesity based on body mass index (BMI) was defined as BMI ≥ 25 kg/m2. The follow-up duration was defined as the period from diagnosis to the last visit or to each poor outcome occurrence. The median age of AAV patients was 58.7 years and 57 patients were men. The prevalence of MetS was 50.9% in all AAV patients and 46.5% in nonobese AAV patients, which were significantly higher than 37.8% in all controls and 28.2% in nonobese controls. In Kaplan–Meier survival analysis, Mets at diagnosis significantly reduced the cumulative CVD-free survival rate in both all and nonobese AAV patients. In the multivariable Cox hazards model analysis, CVD during follow-up was significantly associated with both Birmingham vasculitis activity score (BVAS) (HR 1.159) and MetS at diagnosis (HR 9.036) in nonobese AAV patients. The prevalence of MetS at diagnosis in all or nonobese AAV patients was significantly higher than those in all or nonobese controls. Furthermore, both BVAS and MetS at diagnosis increased the risk of CVD in nonobese AAV patients.

Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second-line regimen.Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median0.80 was classified into the non-routine VL sites. VF was defined as VL ≥1000 copies/ml during first-line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution.Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non-routine VL testing sites. The median follow-up was 9 years (IQR 5-13). The median age was 35 (30-42) years; 68% were male and 5729 (91%) started non-nucleoside reverse-transcriptase inhibitor-based regimen. The median pre-ART CD4 count in PLHIV from routine VL sites was lower compared to non-routine VL sites (144 vs. 156 cells/mmPLHIV from non-routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under-utilized VL testing.

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.

Background Attention deficit hyperactivity disorder (ADHD) patients often use complementary and alternative medicine to treat symptoms, and acupuncture is one option. This systematic review aims to assess whether acupuncture is an effective treatment for attention deficit hyperactivity disorder (ADHD). Methods We will search nine databases from their inception: PubMed, AMED, CINAHL, EMBASE, the Cochrane Central Register of Controlled Trials, RISS, KoreaMed, KISS, and the China National Knowledge Infrastructure database. Two investigators will independently review the selected studies, extract the data, and analyze them. The Cochrane Risk of Bias Assessment Tool will be used to assess the risk of bias. Discussion Because this is a systematic review, no ethical approval is needed. The systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to support health policy and practice. Trial registration number Reviewregistry1345.

Hypertrophic cardiomyopathy (HCM) is a common heritable cardiomyopath. Although considerable effort has been made to understand the pathogenesis of HCM, the mechanism of how long noncoding RNA (lncRNA)-associated competing endogenous RNA (ceRNA) network result in HCM remains unknown. In this study, we acquired a total of 520 different expression profiles of lncRNAs (DElncRNAs) and 371 messenger RNAs (mRNA, DEGs) by microarray and 33 microRNAs (DEmiRNAs) by sequencing in plasma of patients with HCM and healthy controls. Then lncRNA–miRNA pairs were predicted using miRcode and starBase and crossed with DEmiRNAs. MiRNA–mRNA pairs were retrieved from miRanda and TargetScan and crossed with DEGs. Combined with these pairs, the ceRNA network with eight lncRNAs, three miRNAs, and 22 mRNAs was constructed. lncRNA RP11-66N24.4 and LINC00310 were among the top 10% nodes. The hub nodes were analyzed to reconstruct a subnetwork. Furthermore, quantitative real-time polymerase chain reaction results showed that LINC00310 was significantly decreased in patients with HCM. For LINC00310, GO analysis revealed that biological processes were enriched in cardiovascular system development, sprouting angiogenesis, circulatory system development, and pathway analysis in the cGMP-PKG signaling pathway. These results indicate that the novel lncRNA-related ceRNA network in HCM and LINC00310 may play a role in the mechanism of HCM pathogenesis, which could provide insight into the pathogenesis of HCM.