Toxoplasma gondii is an obligate intracellular parasite that stimulates production of high levels of proinflammatory cytokines, which are important for innate immunity. NLRs, i.e., nucleotide-binding oligomerization domain (NOD)-like receptors, play a crucial role as innate immune sensors and form multiprotein complexes called inflammasomes, which mediate caspase-1-dependent processing of pro-IL-1β. To elucidate the role of inflammasome components in T. gondii-infected THP-1 macrophages, we examined inflammasome-related gene expression and mechanisms of inflammasome-regulated cytokine IL-1β secretion. The results revealed a significant upregulation of IL-1β after T. gondii infection. T. gondii infection also upregulated the expression of inflammasome sensors, including NLRP1, NLRP3, NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and NAIP, in a time-dependent manner. The infection also upregulated inflammasome adaptor protein ASC and caspase-1 mRNA levels. From this study, we newly found that T. gondii infection regulates NLRC4, NLRP6, NLRP8, NLRP13, AIM2, and neuronal apoptosis inhibitor protein (NAIP) gene expressions in THP-1 macrophages and that the role of the inflammasome-related genes may be critical for mediating the innate immune responses to T. gondii infection.
Apoptosis ; Cytokines ; Gene Expression ; Immunity, Innate ; Inflammasomes* ; Macrophages* ; Multiprotein Complexes ; Negotiating ; Neurons ; Parasites ; RNA, Messenger ; Toxoplasma* ; Up-Regulation

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Background/Aims: Chronic obstructive pulmonary disease (COPD) management guidelines have increasingly emphasised the importance of exacerbation prevention, and the role of blood eosinophil count (BEC) as a biomarker for inhaled corticosteroids (ICS) response. This study aimed to describe the distribution and stability of BEC and understand real-world treatment patterns among COPD patients in South Korea. Methods: This was a retrospective database analysis using data obtained from the KOrea COPD Subgroup Study (KOCOSS) registry between January 2012 and August 2018. KOCOSS is an ongoing, longitudinal, prospective, multi-centre, non-interventional study investigating early COPD amongst South Korean patients. BEC stability was assessed by calculating the intra-class correlation (ICC) coefficient. “Exacerbators” were patients who had a record of ≥ 1 exacerbation in the 12 months prior to the visit. Results: The study included 2,661 patients with a mean age of 68.6 years. Most patients were male (92.0%). Mean BEC was significantly higher in exacerbators compared to non-exacerbators. Patients with ≥ 2 exacerbations at baseline had a less stable BEC over time (ICC = 0.44) compared to non-exacerbators (ICC = 0.57). Patients with BEC ≥ 300 cells/μL at baseline predominantly received triple therapy (43.8%). Conclusions This study may further develop current understanding on BEC profiles amongst COPD patients in South Korea. BEC measurements are stable and reproducible among COPD patients, which supports its use as a potential biomarker.

Background: The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Background: The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Purpose: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. Materials and Methods: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. Results: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. Conclusions Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.