Efficacy assessment of miltefosine and curcumin against Clonorchis sinensis infection.

Praziquantel (PZQ) is currently the only approved drug for treating clonorchiasis, but its poor efficacy against Clonorchis sinensis larvae has highlighted the need to develop newer drugs. In this study, to address this challenge, we investigated the anti-parasitic efficacy of miltefosine (MLT), curcumin (CUR), and PZQ against C. sinensis metacercariae (CsMC), newly excysted juvenile worms (CsNEJs), and adults. Larvicidal effects of MLT and CUR surpassed those elicited by PZQ in vitro. These two drugs exerted their effect against both CsMC and CsNEJs in a dose- and time-dependent manner. To confirm the effect of these drugs in vivo, Syrian golden hamsters were orally infected with 100 CsMC and subsequently treated with MLT, CUR, or PZQ at 1 and 4 weeks post-infection (wpi). MLT and CUR reduced the worm recoveries at 1 and 4 wpi, indicating that these drugs were efficacious against both larvae and adult C. sinensis. PZQ was only efficacious against adult worms. Interestingly, both MLT and CUR showed lower levels of C. sinensis-specific IgG responses than the infection control group, implying that worm burden and bile IgG responses could be correlated. These results indicate that MLT and CUR are efficacious against both larval and adult stages of C. sinensis, thereby highlighting their potential for further development as alternative therapeutic options for clonorchiasis.

Changing trends in the incidence and spectrum of cancers between 1990 and 2021 among HIV-infected patients in Busan, Korea.

BACKGROUND: Long-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce. MATERIAL AND METHODS: This retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period. RESULTS: Of the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990-1997 to 124.8 per 100,000 PYs in 2014-2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998-2005 to 49% in 2014-2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs. CONCLUSION: The incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.

Seroprevalence of Helicobacter pylori in human immunodeficiency virus-infected patients in a tertiary care hospital in Busan, South Korea.

INTRODUCTION: Human immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated. METHODS: Three hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies. RESULTS: The overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40-49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30-19.17), age of 50-59 years (OR = 3.93; 95% CI 1.05-14.73), CD4 cell counts of 350-500/µL (OR = 4.23; 95% CI 1.53-11.65), CD4 cell counts ≥500/µL (OR = 2.78; 95% CI 1.15-6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05-2.99). CONCLUSIONS: The seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40-59 years.

Influence of Vitamin D Deficiency on the Development of Opportunistic Infection in People Living with HIV/AIDS (PWHAs).

BACKGROUND: It is known that vitamin D is associated with immune cell growth, and an association between vitamin D deficiency and development of chronic infections such as tuberculosis has been reported. However, there have been few studies concerning the association between vitamin D deficiency and opportunistic infection (OI) in people living with HIV/AIDS (PWHA). METHOD: PWHAs who had vitamin D (25-OH vitamin D, 25OHD) test results from 2012 to 2017 were enrolled. All enrolled PWHAs were divided into a vitamin D-deficient group and non-deficient group according to the 25OHD cutoff set by ROC curve analysis. The rates of OIs were compared between the two groups. RESULTS: Among 440 enrolled PWHAs, 394 (89.5%) were male, 32 were ≥ 65 years (13.4%), 237 (53.9%) were ART-naïve, and 107 (24.3%) had CD4 + T cell < 200/L. Seventy-three cases of OIs occurred in 63 PWHAs (14.3%); the most common OI was tuberculosis (27, 6.1%) followed by pneumocystis pneumonia (PCP) (25, 5.7%), and Cytomegalovirus (CMV) diseases (10, 2.3%). In the ROC curve analysis, the AUC was 0.71 (95% CI 0.64- 0.79, P < 0.001) and the optimal cutoffs of 25OHD to predict OIs was 14 ng/mL.Overall OI development was significantly more prevalent in the vitamin D-deficiency group (aOR 3.05, 95% CI 1.43-6.48); tuberculosis (aOR 3.51, 95% CI 1.22-10.05) and CMV disease (aOR 10.13, 95% CI 1.11-92.03) were significantly associated with vitamin D deficiency, whereas PCP was not (aOR 1.32, 95% CI 0.44-3.98). CONCLUSION: Stringent cutoffs of vitamin D deficiency (< 14 ng/mL) were well correlated with development of OIs in PWHAs. Vitamin D deficiency was associated with development of OIs, particularly tuberculosis and CMV infections.

Antimicrobial Susceptibility Trends and Risk Factors for Antimicrobial Resistance in Pseudomonas aeruginosa Bacteremia: 12-Year Experience in a Tertiary Hospital in Korea.

BACKGROUND: Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) have been on the rise worldwide, and delayed active antimicrobial therapy is associated with high mortality. However, few studies have evaluated increases in P. aeruginosa infections with antimicrobial resistance and risk factors for such antimicrobial resistance in Korea. Here, we analyzed changes in antimicrobial susceptibility associated with P. aeruginosa bacteremia and identified risk factors of antimicrobial resistance. METHODS: The medical records of patients with P. aeruginosa bacteremia who were admitted to a tertiary hospital between January 2009 and October 2020 were retrospectively reviewed. Antibiotic resistance rates were compared among the time periods of 2009-2012, 2013-2016, and 2017-2020 and between the intensive care unit (ICU) and non-ICU setting. Empirical antimicrobial therapy was considered concordant, if the organism was susceptible to antibiotics in vitro, and discordant, if resistant. RESULTS: During the study period, 295 patients with P. aeruginosa bacteremia were identified. The hepatobiliary tract (26.8%) was the most common primary site of infection. The rates of carbapenem-resistant P. aeruginosa (CRPA), MDRPA, and extensively drug-resistant P. aeruginosa (XDRPA) were 24.7%, 35.9%, and 15.9%, respectively. XDRPA showed an increasing trend, and CRPA, MDRPA, and XDRPA were also gradually increasing in non-ICU setting. Previous exposure to fluoroquinolones and glycopeptides and urinary tract infection were independent risk factors associated with CRPA, MDRPA, and XDRPA. Previous exposure to carbapenems was an independent risk factor of CRPA. CRPA, MDRPA, and XDRPA were associated with discordant empirical antimicrobial therapy. CONCLUSION: The identification of risk factors for antimicrobial resistance and analysis of antimicrobial susceptibility might be important for concordant empirical antimicrobial therapy in patients with P. aeruginosa bacteremia.

Prevalence and Risk Factors of Carbapenem-resistant Enterobacteriaceae Acquisition in an Emergency Intensive Care Unit in a Tertiary Hospital in Korea: a Case-Control Study.

BACKGROUND: Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are associated with high mortality rates and their treatment is difficult because treatment is limited to certain antibiotics, such as colistin and tigecycline. We aimed to perform active surveillance culture of CRE (ASC-CRE) to monitor the prevalence of CRE acquisition during intensive care unit (ICU) care and to examine the potential risk factors associated with CRE acquisition. METHODS: We conducted ASC-CRE on patients who were admitted to the ICU in the emergency room at a tertiary hospital. Rectal swabs were analyzed using methods established by the Centers for Disease Control and Prevention. To detect carbapenemase-producing CRE, a polymerase chain reaction assay to detect five carbapenemase genes (blaNDM, blaKPC, blaVIM, blaIMP-1, and blaOXA-48) was performed. RESULTS: There were 22 CRE acquisition in 21 patients (2.6%, 21/810) and the incidence of CRE acquisition was 4.3/1,000 person-days, respectively. The most common species detected was Klebsiella pneumoniae (72.7%, 16/22), and 9 carbapenemase-producing CREs (7 blaKPC and 2 blaNDM) were detected. Independent risk factors associated with CRE acquisition were men gender (adjusted odds ratio [aOR], 5.3; 95% confidence interval [CI], 1.3-21.3), history of admission within one year (aOR, 3.9; 95% CI, 1.2-12.1), co-colonization with multidrug-resistant Acinetobacter baumannii (aOR, 15.6; 95% CI, 3.6-67.8) and extended-spectrum ß-lactamases-producing bacteria (aOR, 4.7; 95% CI, 1.5-14.6), and exposure to glycopeptide antibiotics (aOR, 3.6; 95% CI, 1.3-9.9). CONCLUSION: The identification of patients with risk factors for CRE acquisition and early detection of CRE acquisition using ASC-CRE may be useful for CRE control.

Glucose transporters and sodium glucose co-transporters cooperatively import glucose into energy-demanding organs in carcinogenic liver fluke Clonorchis sinensis.

BACKGROUND: The liver fluke Clonorchis sinensis imports large amounts of glucose to generate energy and metabolic intermediates through glycolysis. We hypothesized that C. sinensis absorbs glucose through glucose transporters and identified four subtypes of glucose transporter (CsGTP) and one sodium glucose co-transporter (CsSGLT) in C. sinensis. METHODOLOGY/PRINCIPAL FINDINGS: Expressed sequence tags encoding CsGTPs were retrieved from the C. sinensis transcriptome database, and their full-length cDNA sequences were obtained by rapid amplification of cDNA ends (RACE). The tissue distribution of glucose transporters in C. sinensis adults was determined using immunohistochemical staining. Developmental expression was measured using RT-qPCR. The transport and distribution of glucose into living C. sinensis were monitored using confocal microscopy. Membrane topology and key functional residues of CsGTPs were homologous to their counterparts in animals and humans. CsGTP1, 2, and 4 were transcribed 2.4-5.5 times higher in the adults than metacercariae, while CsGTP3 was transcribed 2.1 times higher in the metacercariae than adults. CsSGLT transcription was 163.6 times higher in adults than in metacercariae. In adults, CsSGLT was most abundant in the tegument; CsGTP3 and CsSGLT were localized in the vitelline gland, uterine wall, eggs, mesenchymal tissue, and testes; CsGTP4 was found in sperm and mesenchymal tissue; and CsGTP1 was mainly in the sperm and testes. In C. sinensis adults, exogenous glucose is imported in a short time and is present mainly in the middle and posterior body, in which the somatic and reproductive organs are located. Of the exogenous glucose, 53.6% was imported through CsSGLT and 46.4% through CsGTPs. Exogenous glucose import was effectively inhibited by cytochalasin B and phlorizin. CONCLUSIONS/SIGNIFICANCE: We propose that CsSGLT cooperates with CsGTPs to import exogenous glucose from the environmental bile, transport glucose across mesenchymal tissue cells, and finally supply energy-demanding organs in C. sinensis adults. Studies on glucose transporters may pave the way for the development of new anthelmintic drugs.

Temporal Trends in Syphilis Incidence among Men with HIV in Busan, Korea, 2005-2022: A Retrospective Cohort Study.

We aimed to assess the temporal trends of incident syphilis and its associated risk factors among men with HIV (Human Immunodeficiency Virus) in Korea during the COVID-19 pandemic. We conducted a retrospective cohort study of men with HIV attending an HIV clinic in Korea between 2005 and 2022. Of 767 men with HIV, 499 were included and contributed 3220 person-years (PY) of the observation period. Eighty-two patients were diagnosed with incident syphilis, with an overall incidence of 2.55/100 PY (95% confidence interval [CI] 20.56-31.53). The incidence of syphilis per 100 PY gradually decreased from 2.43 (0.79-7.42) in 2005-2007 to 1.85 (1.08-3.17) in 2014-2016; however, it increased to 3.0 (1.99-4.53) in 2017-2019, and further to 3.33 (2.26-4.89) in 2020-2022. A multivariate analysis identified young age (≤30 years versus >50, adjusted HR 6.27, 95% CI 2.38-16.56, p < 0.001), treponemal test positive at baseline (2.33, 1.48-3.67, p < 0.001), men who have sex with men (2.36, 1.34-4.16, p = 0.003), and history of incarceration (2.62, 1.21-5.67, p = 0.015) as risk factors for incident syphilis. Recently, syphilis incidence in men with HIV has increased in Korea, especially in young patients and at-risk groups, highlighting the need for enhanced regular screening and targeted behavioral interventions among these populations.

Clonorchis sinensis aggravated liver fibrosis by activating PARP-1 signaling to induce parthanatos via DNA damage.

Clonorchis sinensis is an important food-borne zoonotic parasite that is highly associated with liver fibrosis and cholangiocarcinoma. Further understanding of the pathogenesis of C. sinensis, especially liver fibrosis, could help us develop novel strategies for controlling clonorchiasis. Poly (ADP-ribose) polymerase-1 (PARP-1) can induce cellular parthanatos which is reported to be involved in liver fibrosis. Currently, whether C. sinensis could activate PARP-1 signaling to induce parthanatos or whether parthanatos play a role in C. sinensis-induced liver fibrosis is not clear. In the present study, the expression of PARP-1 and parthanatos indicators were detected in C. sinensis-infected mouse liver and in human intrahepatic biliary epithelial cells (HiBEpiCs) incubated with excretory/secretory products (ESPs) of C. sinensis. To explore the role of PARP-1 in C. sinensis infection, PARP-1 inhibitor NMS-P118 was used to block PARP-1 expression in vivo and vitro. The mortality rate, body weight, worm load, liver and bile duct lesions as well as PARP-1 and parthanatos indicators in C57BL/6 mice infected with C. sinensis, or in HiBEpiCs incubated with C. sinensis ESPs and NMS-P118 were analyzed and compared to the group without NMS-P118. The results showed that C. sinensis infection induced the activation of PARP-1 signaling as well as the translocation of AIF and MIF into the nucleus in mouse liver. ESPs of C. sinensis could induce PARP-1 up-regulation, ATP depletion and DNA damage in HiBEpiCs, indicating that C. sinensis could induce parthanatos. Inhibiting PARP-1 with NMS-P118 significantly reduced liver fibrosis and the number of larvae, increased the survival rate and body weight gain of the mice infected with C. sinensis. In addition, NMS-P118 decreased the expression of PARP-1 and alleviated ATP depletion as well as DNA damage in HiBEpiCs incubated with ESPs of C. sinensis. Our data indicated that C. sinensis and its ESPs could activate PARP-1 signaling to induce cellular parthanatos. NMS-P118 treatment alleviated liver fibrosis and promoted survival of the mice by inhibiting PARP-1, which suggested that PARP-1 could be used as a potential therapeutic target against clonorchiasis.

Kudoa septempunctata Spores Cause Acute Gastroenteric Symptoms in Mouse and Musk Shrew Models as Evidenced In Vitro in Human Colon Cells.

Kudoa septempunctata is a myxosporean parasite that infects the trunk muscles of olive flounder (Paralichthys olivaceus) and has been reported to cause foodborne illnesses in humans. However, the molecular mechanisms underlying K. septempunctata spore toxicity remain largely unknown. In this study, the gastroenteropathy of K. septempunctata was examined in human colon adenocarcinoma cells as well as experimental mice inoculated with spores. We found that K. septempunctata decreased transepithelial resistance and disrupted epithelial tight junctions by deleting ZO-1 in Caco-2 monolayers. Additionally, serotonin (5-HT), an emetic neurotransmitter, was increased in K. septempunctata-inoculated cells. In vivo, K. septempunctata spores induced diarrhea in suckling mice (80% in ddY and 70% in ICR mice), with a minimum provocative dose of 2 × 105 K. septempunctata spores. In house musk shrews, K. septempunctata induced emesis within 1 h and induced serotonin secretion in the intestinal epithelium. In conclusion, K. septempunctata may induce diarrhea and emesis by increasing intestinal permeability and serotonin secretion.

Ten-Year Trends of Hepatitis A Seroprevalence in People Living with HIV in Korea.

Epidemiological information on hepatitis A among people living with HIV (PLHIV) in Korea is scarce. This retrospective study was performed at a tertiary care hospital and included 756 PLHIV with anti- hepatitis A virus (HAV) IgG tests. Between 2012 and 2021, the age at anti-HAV IgG seroconversion is gradually delayed, and the proportion of individuals susceptible to HAV infection increased among adult PLHIV in Korea. The independent risk factors for HAV seropositivity were female sex and HBs antigen (Ag) positivity. Therefore, HAV vaccination is highly recommended for young PLHIV, especially for women or HBsAg-positive individuals.

Nationwide population-based incidence of cancer among patients with HIV/AIDS in South Korea.

Cancers are the leading cause of death among people living with HIV/AIDS (PLWHA); however, nationwide studies on cancer incidence are limited. We aimed to determine the trends in the incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) among Korean PLWHA. Data from the National Health Insurance Sharing Service from 2004 to 2017 were collected. Age- and sex-adjusted standardized incidence ratios (SIRs) for various cancer types relative to the general population were calculated. Of the 11,737 PLWHA followed-up for 65,052 person-years (PYs), 445 (ADCs, 130 and NADCs, 298) developed cancer. The incidence rate of ADCs decreased, whereas that of NADCs remained unchanged. PLWHA were at an increased risk of ADCs (SIR: 12.6, 95% CI: 10.6-15.0), including Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, and some NADCs, including anal cancer, lung cancer, liver cancer, and oropharyngeal cancer. Of the 396 patients who received antiretroviral therapy (ART), 215 with optimal adherence had lower incidence rates for ADCs and NADCs than those with non-optimal adherence. The 5-year survival rate of PLWHA with NADCs was 57.8%. Close surveillance and routine screening of cancers and improvement in ART adherence are required to improve the clinical outcomes of PLWHA.

Regdanvimab in patients with mild-to-moderate SARS-CoV-2 infection: A propensity score-matched retrospective cohort study.

BACKGROUND: Regdanvimab (CT-P59) is a neutralizing antibody authorized in Republic of Korea for the treatment of adult patients with moderate or mild-COVID-19 who are not on supplemental oxygen and have high risk of progressing to severe disease (age ≥ 50 years or comorbidities). This study evaluated the clinical efficacy, safety and medical utilization/costs associated with real-world regdanvimab therapy. METHODS: This non-interventional, retrospective cohort study included adult patients with confirmed mild-to-moderate SARS-CoV-2 infection. Patients treated with regdanvimab were compared with controls who had received other therapies. The primary endpoint was the proportion of patients progressing to severe/critical COVID-19 or death due to SARS-CoV-2 infection up to Day 28. Propensity score matching was applied to efficacy analyses. RESULTS: Overall, 552 patients were included in the Safety and Efficacy Sets (regdanvimab, n = 156; control, n = 396) and 274 patients in the propensity score-matched (PSM) Efficacy Set (regdanvimab, n = 113; control, n = 161). In the PSM Set, the risk of severe/critical COVID-19 or death was significantly lower in the regdanvimab group (7.1% vs 16.1%, P = 0.0263); supplemental oxygen was required by 8.0% and 18.6% of patients in the regdanvimab and control groups, respectively (P = 0.0128). There were no unexpected safety findings in the regdanvimab group. Medical utilization analysis showed an overall cost reduction with regdanvimab compared with control treatments. CONCLUSIONS: Regdanvimab significantly reduced the proportion of patients progressing to severe/critical disease or dying of SARS-CoV-2 infection. This study shows the potential benefits of regdanvimab in reducing disease severity and improving medical utility in patients with COVID-19.

Prevalence and patterns of illicit drug use in people with human immunodeficiency virus infection in Korea.

BACKGROUND: Data on illicit drug use by Korean people infected with HIV are lacking. Here, we examined the prevalence and patterns of illicit drug use among people infected with HIV in Korea. MATERIAL AND METHODS: In this cross-sectional study, we included all patients infected with HIV who visited a tertiary care hospital in Korea from January 1990 to May 2020. Sociodemographic data of patients, including drug use, were collected at the first visit and during follow-up. RESULTS: Among 1,267 patients, 5.13% reported the use of an illicit drug in their lifetime, and 2.61% were users of injection drugs. The most commonly used drugs were cannabis/marijuana and methamphetamine, followed by nitrite inhalants, cocaine, dextromethorphan, carisoprodol, and 3,4-methylenedioxymethamphetamine. The illicit drug users tended to be younger than non-users, homosexuals/bisexuals, and infected with hepatitis C virus (HCV); they had a higher CD4+ cell count than non-users. Among 65 users of illicit drugs, only 24.6% revealed their drug use at the first visit interview, and 24.6% reported using two or more drugs in their lifetime. Individuals who used injection drugs were more likely to be arrested for drug-related charges than the users of non-injection drugs. Moreover, they tended to be heavy users of illicit drugs, to report using two or more drugs in their lifetime, and to be HCV seropositive. In contrast, the users of non-injection drugs were more likely to be experimental users and to start using drugs overseas for the first time, but less likely to report their drug use at the first interview. CONCLUSIONS: The prevalence of illicit drug use in people with HIV infection in Korea may have been underestimated. Further research based on more accurate measurements are warranted.

Epidemiological and phylogenetic analysis for non-B subtypes of human immunodeficiency virus type 1 in Busan, Korea.

Recent data on non-B subtypes' epidemiology among patients infected with human immunodeficiency virus-1 (HIV-1) in Korea are lacking. We aimed to assess the changing trends in the epidemiology of non-B subtypes of HIV-1 in Korea using phyloepidemiological analyses. We analyzed the demographic records and sequencing data obtained from genotypic drug resistance tests between 2005 and 2019 from 517 patients infected with HIV attending a tertiary care hospital in Busan, Korea. Subtyping and phylogenetic analyses with reference sequences were performed. Additionally, transmission clusters were identified via maximum-likelihood trees. Non-B subtypes accounted for 21.3% of the 517 sequences. CRF01_AE (52.7%) was the most common non-B subtype, followed by CRF02_AG (16.4%), A1 (11.8%), and C (5.5%). The prevalence of non-B subtypes decreased from 36.4 to 13.4% by 2009, while it increased to 27.4% between 2015 and 2019. Among patients with non-B subtypes, the proportion of overseas sailors decreased from 66.7 to 7.5%; contrarily, the proportion of men-who-have-sex-with-men (MSM) increased from 0 to 46.9% over the study period. We identified 8 transmission clusters involving non-B subtypes, with sizes ranging from 2 to 4 patients, including 3 clusters containing MSM. Our results highlight the changes in the epidemiological trends of non-B subtypes of HIV-1 in Korea.

Comparative outcomes of lopinavir/ritonavir and hydroxychloroquine for the treatment of COVID-19 with mild-to-moderate severity: A retrospective observational study.

BACKGROUND: Lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ) are both being used to treat coronavirus disease 2019 (COVID-19), but their relative effectiveness is unknown. The purpose of this study was to compare the clinical outcomes of patients treated for COVID-19 with LPV/r or HCQ. METHODS: A retrospective observational study was conducted at 2 hospitals in Busan, South Korea, where approximately 90% of COVID-19 patients were hospitalised during February/March 2020. All patients aged ≥15 years that were hospitalised with mild or moderately severe COVID-19 received LPV/r or HCQ as their initial treatment and were included in the analysis. RESULTS: Among the 72 patients with mild-to-moderate disease severity on admission, 45 received LPV/r and 27 received HCQ as their initial therapy. A higher proportion of the LPV/r group had pneumonia on admission (LPV/r, 49% vs HCQ, 15%), but there were no other significant differences in the demographic or clinical characteristics between groups. Switching therapy due to clinical failure was significantly more common in the HCQ group than in the LPV/r group (41% [11/27] and 2% [1/45], respectively, P = .001). Disease progression was also significantly more common in the HCQ group than in the LPV/r group (44% [12/27] and 18% [8/45], respectively, P = .030). CONCLUSION: Based on our study results, HCQ shows no apparent advantage compared to LPV/r for preventing progression to severe disease in patients with COVID-19.

(-)-Epigallocatechin-3-gallate increases cell proliferation and neuroblasts in the subgranular zone of the dentate gyrus in adult mice.

Neurogenesis is regulated by several factors such as age, stress and pharmacological agents. We observed the effects of (-)-epigallocatechin-3-gallate (EGCG), a major catechin of green tea, on neurogenesis in mice. The animals were orally administered EGCG for 4 weeks. Brain sections were stained using a marker for cell proliferation (Ki67 and BrdU) and neuroblasts (doublecortin, DCX). In all groups, Ki67, BrdU and DCX immunoreaction were observed in the subgranular zone of the dentate gyrus. Oral administration of EGCG significantly increased the number of Ki67-, BrdU- and DCX-immunoreactive cells as well as BrdU/DCX-colabled cells in the subgranular zone when compared to those in the vehicle-treated group. These results indicate that oral administration of EGCG can enhance cell proliferation and increase the number of neuroblasts in mice hippocampal dentate gyrus.

Osteonecrosis of the Femoral Head in Korean Patients with Human Immunodeficiency Virus Infection.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a disabling condition that often necessitates total hip arthroplasty (THA). Although ONFH occurs more frequently among patients with human immunodeficiency virus (HIV) than among the general population, there is little epidemiological information regarding ONFH in Korean patients with HIV. In the present study, we aimed to investigate the incidence and clinical features of ONFH among Korean patients with HIV. MATERIALS AND METHODS: In this retrospective study, we reviewed the medical records of 1,250 Korean patients with HIV treated from January 1990 to December 2019. A standardised data collection sheet was used to obtain clinical information. Imaging data were analysed by a radiologist in accordance with the 2019 revised version of the Association Research Circulation Osseous (ARCO) staging system for ONFH. RESULTS: Among the 1,250 included patients, 13 patients (1.04%; 3 women, 10 men) were diagnosed with ONFH. The overall incidence of ONFH was 1.29 per 1,000 person-years (PYs) (95% confidence interval [CI]: 0.7 - 2.4 per 1,000 PYs). Median age among the 13 patients with ONFH was 47 years (interquartile range [IQR]: 41 - 57 years). The median duration since HIV diagnosis was 4.8 years (IQR: 2.3 - 10.1 years). The median CD4 cell count at the time of ONFH diagnosis was 381 cells/ mm³ (IQR: 161 - 551 cells/mm³). At the initial diagnosis of ONFH, 83.3% of patients exhibited bilateral involvement. ARCO stage 3 or 4 osteonecrosis was observed in 83% of patients. Among 22 hips, stage 1 ONFH was noted in 2 (9.1%), stage 2 ONFH was noted in 7 (31.8%), stage 3 ONFH was noted in 9 (40.9%), and stage 4 ONFH was noted in 4 (18.2%). THA was eventually performed in 84.6% of patients. Five (38.5%) patients had a history of steroid use, 4 (30.8%) patients had a history of alcohol abuse and 10 (76.9%) were smokers. Eight (61.5%) patients had a history of acquired immune deficiency syndrome-defining illness, including 7 with tuberculosis and 1 with pneumocystis pneumonia. Nine patients (69.2%) had a nadir CD4 cell count <200/µL, and 3 (23.1%) had a history of bone fracture. Overall, 84% of patients were exposed to antiretroviral therapy, while 54% had taken protease inhibitors for more than 1 year. CONCLUSION: Considering that relatively high incidence of ONFH in patients with HIV, a high index of suspicion for those with risk factors and those with groin or hip pain for is required in HIV-infected patients.

Short Communication: Trends in Transmitted Drug Resistance in Treatment-Naive HIV Patients in Korea.

Transmitted drug resistance (TDR) in treatment-naive HIV patients can contribute to failure of initial antiretroviral therapy. In Korea, there has been a gradual increase in TDR, but the recent increase in the use of integrase strand transfer inhibitors (INSTIs) could affect TDR trends and INSTI resistance mutations. We evaluated the patterns of TDR in newly diagnosed HIV patients over time from 2011 to 2019. We analyzed the genotypic resistance of strains in 336 patients and sequenced the integrase gene in 71 among 336 subjects. The overall prevalence of TDR was 5.9% (20 of 336 patients), and it showed a tendency to increase over time (5.1% in 2011-2013, 6.1% in 2014-2016, and 7.2% in 2017-2019; p = .3018). Furthermore, non-nucleoside reverse transcriptase inhibitor resistance showed a marginally significant increase over time (1.45% in 2011-2013, 3.48% in 2014-2016, and 6.02% in 2017-2019; p = .0505). Regarding transmitted INSTI resistance mutation, there were no major INSTI resistance mutations but several accessory INSTI resistance mutations and predominant natural polymorphisms. This study shows several significant changes in TDR and suggests the importance of continuous surveillance of TDR and genetic variation in the integrase region.

Dysfunctional accessory gene regulator (agr) as a prognostic factor in invasive Staphylococcus aureus infection: a systematic review and meta-analysis.

The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05-1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20-1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03-1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27-0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17-5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia.