PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Propensity score matched analysis for the safety and effectiveness of remdesivir in COVID-19 patients with renal impairment.

BACKGROUNDS: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. METHODS: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. RESULTS: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. CONCLUSION: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity.

Pneumonia-targeted lopinavir/ritonavir-based treatment for patients with COVID-19: an early-period retrospective single center observational study.

BACKGROUND: Robust evidenced treatment strategy for Coronavirus disease 2019 (COVID-19) has not been established yet. Early, targeted, comprehensive management approach can be essential. METHODS: A lopinavir/ritonavir (LPV/r)-based antiviral treatment was administered to the patients with computed tomography (CT)-documented pneumonia. Medical records of patients with COVID-19, previously discharged or hospitalized for ≥ 21 days at the Seoul Medical Center from January 29 to April 15, 2020 were reviewed to analyze clinical and virological outcomes. Patients were divided into two groups (PCR-Negative conversion group vs. Non-negative conversion group and requiring oxygen group vs. Non-requiring oxygen group). RESULTS: In total, 136 patients with a mean age of 41.8 ± 18.2 years were included with median 3-day delay of hospitalization after illness. Thirteen (9.56%) were initially asymptomatic, and 5 (3.67%) were persistently asymptomatic. Eighty-five (62.5%) had CT-documented pneumonia, 94% of whom received LPV/r treatments. A total of 53 patients (38.97%) had negative polymerase chain reaction (PCR) results within 28 days. Eight (9.4%) out of 85 pneumonic patients received oxygen supplementation. Patients with initial lower respiratory symptoms showed significant delay in PCR negative conversion (> 28 days) (odds ratio [OR] 0.166; 95% confidence interval [CI] 0.067-0.477; P < 0.001). However, antiviral treatment for pneumonic patients was significantly related with early conversion within 28 days (OR 3.049; 95% CI 1.128-8.243; P = 0.028). Increasing age increased the likelihood of oxygen supplementation requirement in the pneumonic patient group (OR 1.108; 95% CI 1.021-1.202; P = 0.014). CONCLUSIONS: Early, pneumonia targeted LPV/r-based antiviral therapy resulted in a significantly higher probability of negative conversion of PCR within 28 days compared to symptomatic treatment.

Clinical Course and Outcomes of Patients with Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Preliminary Report of the First 28 Patients from the Korean Cohort Study on COVID-19.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected pneumonia emerged in Wuhan, China in December 2019. In this retrospective multicenter study, we investigated the clinical course and outcomes of novel coronavirus disease 2019 (COVID-19) from early cases in Republic of Korea. METHODS: All of the cases confirmed by real time polymerase chain reaction were enrolled from the 1st to the 28th patient nationwide. Clinical data were collected and analyzed for changes in clinical severity including laboratory, radiological, and virologic dynamics during the progression of illness. RESULTS: The median age was 40 years (range, 20-73 years) and 15 (53.6%) patients were male. The most common symptoms were cough (28.6%) and sore throat (28.6%), followed by fever (25.0%). Diarrhea was not common (10.7%). Two patients had no symptoms. Initial chest X-ray (CXR) showed infiltration in 46.4% of the patients, but computed tomography scan confirmed pneumonia in 88.9% (16/18) of the patients. Six patients (21.4%) required supplemental oxygen therapy, but no one needed mechanical ventilation. Lymphopenia was more common in severe cases. Higher level of C-reactive protein and worsening of chest radiographic score was observed during the 5-7 day period after symptom onset. Viral shedding was high from day 1 of illness, especially from the upper respiratory tract (URT). CONCLUSION: The prodromal symptoms of COVID-19 were mild and most patients did not have limitations of daily activity. Viral shedding from URT was high from the prodromal phase. Radiological pneumonia was common from the early days of illness, but it was frequently not evident in simple CXR. These findings could be plausible explanations for the easy and rapid spread of SARS-CoV-2 in the community.

Clinical Course and Outcomes of 3,060 Patients with Coronavirus Disease 2019 in Korea, January-May 2020.

BACKGROUND: The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea. METHODS: Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation. RESULTS: The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3-4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5-7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50-59, 60-69, 70-79, and ≥ 80 years of age, respectively. CONCLUSION: In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.

Comparison of the efficacy of nafcillin and glycopeptides as definitive therapy for patients with methicillin-susceptible Staphylococcus aureus bacteremia: a retrospective cohort study.

BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin-susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment with ß-lactam. However, there are only few studies comparing treatment with antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin, with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS: Patients with MSSA bacteremia recruited from a tertiary referral hospital were enrolled in this retrospective cohort study. Demographic characteristics, laboratory data, and clinical outcome of the treatment were compared between a group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total of 188 patients with MSSA bacteremia were included in this study. The glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001) and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001) compared to the nafcillin group. The ratio of skin and soft tissue infections (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p = 0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p = 0.022) were higher in the nafcillin group. All-cause 28-day mortality was significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013). CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was higher in a group treated with glycopeptides than in a group treated with nafcillin. Therefore, the use of nafcillin should be considered as a definitive therapy for MSSA bacteremia.

The impact of production of extended-spectrum ß-lactamases on the 28-day mortality rate of patients with Proteus mirabilis bacteremia in Korea.

BACKGROUND: The incidence of Proteus mirabilis antimicrobial resistance, especially that mediated by extended-spectrum ß-lactamases (ESBLs), has increased. We investigated the impact of ESBL production on the mortality of patients with P. mirabilis bacteremia in Korea. METHODS: Patients diagnosed with P. mirabilis bacteremia between November 2005 and December 2013 at a 2000-bed tertiary care center in South Korea were included in this study. Phenotypic and molecular analyses were performed to assess ESBL expression. Characteristics and treatment outcomes were investigated among ESBL-producing and non-ESBL-producing P. mirabilis bacteremia groups. A multivariate analysis of 28-day mortality rates was performed to evaluate the independent impact of ESBLs. RESULTS: Among 62 P. mirabilis isolates from 62 patients, 14 expressed ESBLs (CTX-M, 2; TEM, 5; both, 6; other, 1), and the 28-day mortality rate of the 62 patients was 17.74%. No clinical factor was significantly associated with ESBL production. The 28-day mortality rate in the ESBL-producing group was significantly higher than that in the non-ESBL-producing group (50% vs. 8.3%, p = 0.001). A multivariate analysis showed that ESBL production (odds ratio [OR], 11.53, 95% confidence interval [CI], 2.11-63.05, p = 0.005) was independently associated with the 28-day mortality rate in patients with P. mirabilis bacteremia. CONCLUSIONS: ESBL production is significantly associated with mortality in patients with bacteremia caused by P. mirabilis. Rapid detection of ESBL expression and prompt appropriate antimicrobial therapy are required to reduce mortality caused by P. mirabilis bacteremia.

Metabolic Complications among Korean Patients with HIV Infection: The Korea HIV/AIDS Cohort Study.

Currently, metabolic complications are the most common problem among human immunodeficiency virus (HIV)-infected patients, with a high incidence. However, there have been very few studies regarding metabolic abnormalities published in Asia, especially in Korea. This cross-sectional study was performed to investigate the prevalence of and risk factors for metabolic abnormalities in 1,096 HIV-infected patients of the Korea HIV/AIDS cohort study enrolled from 19 hospitals between 2006 and 2013. Data at entry to cohort were analyzed. As a result, the median age of the 1,096 enrolled subjects was 46 years, and most patients were men (92.8%). The metabolic profiles of the patients were as follows: median weight was 63.8 kg, median body mass index (BMI) was 22.2 kg/m², and 16.4% of the patients had a BMI over 25 kg/m². A total of 5.5% of the patients had abdominal obesity (waist/hip ratio ≥ 1 in men, ≥ 0.85 in women). Increased levels of fasting glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides were present in 10.4%, 6.0%, 5.5%, and 32.1% of the patients. Decreased high-density lipoprotein (HDL) cholesterol levels were observed in 44.2% of the patients. High systolic blood pressure was present in 14.3% of the patients. In multivariate analysis, high BMI and the use of protease inhibitors (PIs) were risk factors for dyslipidemia in HIV-infected patients. In conclusion, proper diagnosis and management should be offered for the prevalent metabolic complications of Korean HIV-infected patients. Further studies on risk factors for metabolic complications are needed.

Predictive factors for unfavorable outcomes of tuberculous pericarditis in human immunodeficiency virus-uninfected patients in an intermediate tuberculosis burden country.

BACKGROUND: In areas where Mycobacterium tuberculosis is endemic, tuberculosis is known to be the most common cause of pericarditis. However, the difficulty in diagnosis may lead to late complications such as constrictive pericarditis and increased mortality. Therefore, identification of patients at a high risk for poor prognosis, and prompt initiation of treatment are important in the outcome of TB pericarditis. The aim of this study is to identify the predictive factors for unfavorable outcomes of TB pericarditis in HIV-uninfected persons in an intermediate tuberculosis burden country. METHODS: A retrospective review of 87 cases of TB pericarditis diagnosed at a tertiary referral hospital in South Korea was performed. Clinical characteristics, treatment outcomes, complications during treatment, duration of treatment, and medication history were reviewed. Unfavorable outcome was defined as constrictive pericarditis identified on echocardiography performed 3 to 6 months after initial diagnosis of TB pericarditis, cardiac tamponade requiring emergency pericardiocentesis, or death. Predictive factors for unfavorable outcomes were identified. RESULTS: Of the 87 patients, 44 (50.6%) had unfavorable outcomes; cardiac tamponade (n = 36), constrictive pericarditis (n = 18), and mortality (n = 4). 14 patients experienced both cardiac tamponade and constrictive pericarditis. During a 1 year out-patient clinic follow up, 4 patients required repeat pericardiocentesis and pericardiectomy was performed in 0 patients. In the multivariate analysis, patients with large amounts of pericardial effusion (P = .003), those with hypoalbuminemia (P = .011), and those without cardiovascular disease (P = .011) were found to have a higher risk of unfavorable outcomes. CONCLUSION: HIV-uninfected patients with TB pericarditis are at a higher risk for unfavorable outcomes when presenting with low serum albumin, with large pericardial effusions, and without cardiovascular disease.

Treatment Outcomes of Patients Treated for Pulmonary Tuberculosis after Undergoing Gastrectomy.

Gastrectomy is a proxy of malnutrition, which may lead to increased risk for developing pulmonary tuberculosis (TB). Malabsorption in gastrectomy patients could lead to low serum levels of rifampicin, which may be related to higher treatment failure. However, there is limited information on treatment outcomes of TB in patients who have undergone gastrectomy. This study aims to determine treatment outcomes and adverse effects in patients treated for TB after undergoing gastrectomy for gastric cancer. During the study period, 112 patients were treated for active TB that developed after gastrectomy for gastric cancer. Among them, we selected 15 patients who were culture positive at initial diagnosis and had evidence of active TB on imaging studies; namely, the remaining 97 patients without initial culture or imaging studies were excluded. We thus performed a case-control study of gastric cancer patients treated for TB after undergoing gastrectomy (n = 15). The control group was defined as age- and sex-matched TB patients who had not received gastrectomy (n = 45). Treatment failure in clinical, microbiological aspects, and adverse events were analyzed. Patients who had undergone gastrectomy exhibited higher 4-month clinical failure rates, compared to non-gastrectomy patient: 4 (26.7%) vs. 1 (2.2%), P = 0.012. Gastrointestinal adverse effects were more frequent in patients with gastrectomy, compared to non-gastrectomy patients: 9 (60%) vs. 5 (11.1%), P < 0.001. In conclusion, patients treated for TB after undergoing gastrectomy are associated with higher rates of gastrointestinal adverse events and treatment failure.

Productivity changes in OECD healthcare systems: bias-corrected Malmquist productivity approach.

This study evaluates productivity changes in the healthcare systems of 30 Organization for Economic Co-operation and Development (OECD) countries over the 2002-2012 periods. The bootstrapped Malmquist approach is used to estimate bias-corrected indices of healthcare performance in productivity, efficiency and technology by modifying the original distance functions. Two inputs (health expenditure and school life expectancy) and two outputs (life expectancy at birth and infant mortality rate) are used to calculate productivity growth. There are no perceptible trends in productivity changes over the 2002-2012 periods, but positive productivity improvement has been noticed for most OECD countries. The result also informs considerable variations in annual productivity scores across the countries. Average annual productivity growth is evenly yielded by efficiency and technical changes, but both changes run somewhat differently across the years. The results of this study assert that policy reforms in OECD countries have improved productivity growth in healthcare systems over the past decade. Countries that lag behind in productivity growth should benchmark peer countries' practices to increase performance by prioritizing an achievable trajectory based on socioeconomic conditions. For example, relatively inefficient countries in this study indicate higher income inequality, corresponding to inequality and health outcomes studies. Although income inequality and globalization are not direct measures to estimate healthcare productivity in this study, these issues could be latent factors to explain cross-country healthcare productivity for future research. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy of hybrid therapy as first-line regimen for Helicobacter pylori infection compared with sequential therapy.

BACKGROUND AND AIM: Recent prospective studies have shown that the sequential therapy has not achieved the target Helicobacter pylori eradication rate of > 80% in Korea. The aim of this study was to therefore assess the efficacy of the hybrid therapy as a first-line treatment for H. pylori eradication in a prospective trial. METHODS: From December 2012 to August 2013, 184 patients with confirmed H. pylori infections received either the 14-day hybrid therapy or the 14-day sequential therapy. Eradication outcomes were evaluated using a 13C-urea breath test at least 4 weeks after treatment cessation. RESULTS: A total of 184 patients (90 receiving hybrid treatment and 94 receiving sequential treatment) completed the study. The eradication rates of the hybrid and sequential therapy groups were 81.1% (73/90; 95% confidence interval [CI] = 73.0-89.2%) and 79.8% (75/94; 95%CI = 71.7-87.9%), respectively, by intention-to-treat analysis (P = 0.821). By per protocol analysis, eradication rates were 85.9% (73/85; 95%CI = 78.5-93.3%) and 82.0% (73/89; 95%CI = 74.0-89.9%; P = 0.489), respectively. There were no significant intergroup differences in treatment compliance or discontinuation induced by severe side effects. CONCLUSIONS: The hybrid therapy achieved acceptable eradication rate (85.9%), but not statistically significantly higher rates than the sequential therapy (82.0%). Further studies are therefore needed to identify first-line treatments with even better eradication rates in the Korean population.

Pooled nucleic acid testing to identify antiretroviral treatment failure during HIV infection in Seoul, South Korea.

BACKGROUND: There have been various efforts to identify less costly but still accurate methods for monitoring the response to HIV treatment. We evaluated a pooling method to determine if this could improve screening efficiency and reduce costs while maintaining accuracy in Seoul, South Korea. METHODS: We conducted the first prospective study of pooled nucleic acid testing (NAT) using a 5 minipool + algorithm strategy versus individual viral load testing for patients receiving antiretroviral therapy (ART) between November 2011 and August 2012 at an urban hospital in Seoul, South Korea. The viral load assay used has a lower level of detection of 20 HIV RNA copies/ml, and the cost per assay is US$ 136. The 5 minipool +algorithm strategy was applied and 43 pooled samples were evaluated. The relative efficiency and accuracy of the pooled NAT were compared with those of individual testing. RESULTS: Using the individual viral load assay, 15 of 215 (7%) plasma samples had more than 200 HIV RNA copies/ml. The pooled NAT using the 5 minipool + algorithm strategy was applied to 43 pooled samples; 111 tests were needed to test all samples when virologic failure was defined at HIV RNA ≥ 200 copies/ml. Therefore, 104 tests were saved over individual testing, with a relative efficiency of 0.48. When evaluating costs, a total of US$ 14,144 was saved for 215 individual samples during 10 months. The negative predictive value was 99.5% for all samples with HIV RNA ≥ 200 copies/ml. CONCLUSIONS: The pooled NAT with 5 minipool + algorithm strategy seems to be a very promising approach to effectively monitor patients receiving ART and to save resources.

Case Report: Cryptococcal Meningitis in a Previously Immunocompetent Patient with Coronavirus Disease 2019.

Cryptococcus neoformans infections occur most frequently in immunocompromised patients. Here, we report a case of cryptococcal meningitis in a previously immunocompetent 78-year-old female patient after treatment of COVID-19. Underlying diseases included hypertension, hyperlipidemia, and diabetes. The patient was critically ill and was treated with remdesivir, baricitinib, and dexamethasone. During hospitalization, her mental state changed, and C. neoformans was detected in the cerebrospinal fluid. She died despite receiving antifungal treatment. Treatment of COVID-19 may be a predisposing factor for C. neoformans infection. There is a need for concern and countermeasures for opportunistic fungal infections that may accompany COVID-19.

Meta-analysis: is sequential therapy superior to standard triple therapy for Helicobacter pylori infection in Asian adults?

BACKGROUND AND AIM: Although several meta-analyses suggested that sequential therapy (SQT) is superior to standard triple therapy (STT) for the eradication of Helicobacter pylori, these results were mainly based on the studies from Italy. The aim of this study was to assess the efficacy of 10-day SQT for H. pylori infection compared with STT in Asian adults. METHODS: We performed an electronic search of the Cochrane Library, Medline, and Embase up to April 21, 2013, with no language restrictions. Randomized controlled trials comparing 10-day SQT with STT for H. pylori eradication in Asian adults were included in this analysis. The primary outcome measures were the risk ratios (RRs) for successful eradication of H. pylori based on intention to treat comparing SQT with STT. The secondary outcome measures were the RRs for side effects. RESULTS: Seventeen randomized controlled trials with a total of 3419 participants (1591 for SQT and 1828 for STT) met the inclusion criteria. The eradication rate was 81.8% (95% CI: 78.9-84.6) for SQT and 74.3% (95% CI: 69.6-78.8) for SST, respectively. The pooled RR was 1.10 (95% CI: 1.04-1.16, P = 0.0005), which demonstrated significant superiority of SQT over STT, and the number needed to treat was 14 (95% CI: 9-29). There were no significant differences between SQT and STT in the risk of side effects (the pooled RR: 0.98, 95% CI: 0.87-1.10, P = 0.73). CONCLUSION: Ten-day SQT appears to be superior to STT for H. pylori eradication in Asian adults. However, the pooled efficacy is lower than results from earlier European studies.

A comparison of the predicted risk for cardiovascular disease between HIV-infected and uninfected persons in Korea.

BACKGROUND: The introduction of highly active antiretroviral therapy (HAART) has extended the life expectancy of persons infected with the human immunodeficiency virus type 1 (HIV-1). However, cardiovascular disease (CVD) is currently an increasing concern for HIV-infected persons. METHODS: We conducted a cross-sectional case-control study to evaluate and compare the 10-y cardiovascular risk of HIV-infected Koreans who had been receiving HAART for over 6 months and age- and sex-matched uninfected persons who visited a health promotion center, by calculating Framingham risk scores (FRS). RESULTS: The average 10-y risk for cardiovascular events (FRS) was 7.07% (2-45) in the HIV group and 6.87% (1-37) in the control group (p = 0.77), corresponding to the very low risk group. Among HIV patients, the FRS was above 10% (low to moderate cardiovascular risk) in 19.9% of the patients, and above 20% (high risk) in 1.7% of the patients. In the healthy control group, the FRS was above 10% in 16.8% and above 20% in 2.7% (p = 0.57). The FRS was not significantly different for HIV-infected patients treated with protease inhibitor (PI)-based HAART and those treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART (7.26 ± 6.3 and 6.81 ± 4.4, respectively, p = 0.69). CONCLUSIONS: The predicted cardiovascular risk of HIV-infected Koreans on HAART by FRS equation was low and similar to that of age- and sex-matched healthy control persons. However, the possibility remains that actual cardiovascular events could be underestimated. The next step for predicting the cardiovascular risk is to calculate the Data Collection of Adverse Events of Anti-HIV Drugs (D:A:D) equation risks.

Increased incidence of teicoplanin-non-susceptible Staphylococcus epidermidis strains: a 6-year retrospective study.

Glycopeptide antibiotics (vancomycin and teicoplanin) are usually used for the treatment of Staphylococcus epidermidis infections owing to their increased oxacillin resistance. However, S. epidermidis strains with decreased susceptibility to teicoplanin have become increasingly incident in recent years. We aimed to identify the characteristics of teicoplanin-non-susceptible (Teico-NS) S. epidermidis isolated at our hospital and analyze its relationship with teicoplanin usage. We retrospectively evaluated 328 S. epidermidis strains isolated from clinical isolates between January 2016 and December 2021. All strains were susceptible to vancomycin (minimal inhibitory concentration (MIC) ≤ 4 mg/L). The annual incidence for S. epidermidis strains with an elevated teicoplanin MIC of 8 mg/L ranged from 22.2 to 28.9%. In addition, in 2021, the number of S. epidermidis strains with teicoplanin MIC ≥ 16 mg/L rapidly increased (n = 13, 32.5%). Furthermore, teicoplanin use increased annually until 2019; however, in 2020, it decreased abruptly due to the COVID 19 pandemic. Thus, we could not confirm the existence of a clear correlation between teicoplanin usage and increased incidence of S. epidermidis with reduced teicoplanin-susceptibility. We showed the increased incidence of Teico-NS S. epidermidis in recent years. Further studies are needed to identify the mechanisms and risk factors for teicoplanin-resistance in S. epidermidis.

Comparison of Clinical Outcomes for Glycopeptides and Beta-Lactams in Methicillin-Susceptible Staphylococcus Aureus Bloodstream Infections.

PURPOSE: This study aimed to provide compelling evidence of anti-staphylococcal beta-lactam use for methicillin-susceptible Staphylococcus aureus bloodstream infection (MSSA BSI). MATERIALS AND METHODS: We retrospectively collected data on patients with MSSA BSI who were admitted to two academic tertiary-care hospitals from 2010 to 2018. Only patients who received nafcillin, cefazolin, vancomycin, or teicoplanin as definitive therapy were included. The primary outcome was 28-day mortality. To perform unbiased comparisons between both treatments, we used inverse probability of treatment weighting (IPTW) analysis. RESULTS: A total of 359 patients were divided into two groups based on the definitive therapy used: beta-lactams (n=203), including nafcillin or cefazolin; and glycopeptides (n=156), including vancomycin or teicoplanin. In the IPTW analysis, glycopeptides were associated with significantly increased odds of 28-day mortality (adjusted odds ratio, 3.37; 95% confidence interval, 1.71-6.61; p<0.001). The rate of primary outcome in prespecified subgroups was largely consistent with the main analysis. CONCLUSION: Definitive therapy with beta-lactams in patients with MSSA BSI was associated with lower 28-day mortality compared to definitive therapy with glycopeptides.

Loss of thyroid gland circadian PER2 rhythmicity in aged mice and its potential association with thyroid cancer development.

Molecular clocks operate in peripheral tissues, including endocrine glands, and play important regulatory roles in this context. However, potential age-related changes in the expression rhythmicity of clock genes and the effects of these changes on the thyroid gland remain unknown. In the present study, we evaluated the expression rhythmicity of peripheral thyroid clock genes in aged mice using RNA-seq transcriptomic analysis in young (3.5-month) versus aged (20-month) mice. In addition, we determined the cellular effects of silencing of PER2, a major clock gene regulator, in human thyroid cell lines. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) in the thyroid glands of aged mice were involved in mitogen-activated protein kinase (MAPK) signaling, chemokine signaling, circadian entrainment, PI3K/AKT signaling, and Apelin signaling. The expression of circadian clock genes Arntl/Bmal1 was significantly downregulated in thyroid glands of aged mice, whereas the expression of genes involved in regulation of cell proliferation, migration, and tumorigenesis was upregulated. Peripheral thyroid clock genes, particularly Per mRNA and PER2 protein, were downregulated in the thyroid glands of aged mice, and circadian oscillation of these genes was declined. Knockdown of the circadian clock gene PER2 in human thyroid follicular cells induced AP-1 activity via JNK MAPK signaling activation, which increased cell proliferation. Furthermore, the aging-related loss of PER2 circadian oscillation activated the AP-1 transcription factor via the JNK MAPK pathway, which could contribute to thyroid hyperplasia, a common age-related condition.

Ruptured pseudoaneurysm of the internal maxillary artery in zygomaticomaxillary fracture: a case report.

Post-traumatic pseudoaneurysms of internal maxillary artery are rare, but may be life-threatening. When arterial damage leads to pseudoaneurysm formation, delayed intractable epistaxis can occur. We report our experience with the diagnosis and management of a ruptured internal maxillary arterial pseudoaneurysm that was discovered preoperatively in a patient with a zygomaticomaxillary complex (ZMC) fracture. He presented to the emergency room with epistaxis, which ceased shortly, and sinus hemorrhage was observed with a fracture of the posterior maxillary wall. The patient was scheduled for open reduction and internal fixation (ORIF) of the ZMC fracture. However, immediately before surgery, uncontrolled epistaxis of unknown origin was observed. Angiography indicated a pseudoaneurysm of the posterior superior alveolar artery. Selective endovascular embolization was performed, and hemostasis was achieved. After radiologic intervention, ORIF was successfully implemented without complications. Our case shows that in patients with a posterior maxillary wall fracture, there is a risk of uncontrolled bleeding in the perioperative period that could be caused by pseudoaneurysms, which should be considered even in the absence of typical symptoms.