Suppression of neointimal hyperplasia induced by arteriovenous anastomosis and balloon injury in rats by multimeric tumor necrosis factor-related apoptosis-inducing factor.

Excessive blood vessel wall thickening, known as intimal hyperplasia, can result from injury or inflammation and increase the risk of vascular diseases. Tumor necrosis factor-related apoptosis-inducing factor (TRAIL) plays key roles in tumor surveillance, autoimmune diseases, and apoptosis; however, its role in vascular stenosis remains controversial. Treatment with recombinant isoleucine zipper hexamerization domain soluble TRAIL (ILz(6):TRAIL) significantly inhibited the progression of neointimal hyperplasia (NH) induced by anastomosis of the carotid artery and jugular vein (AAV) dose dependently, and adenovirus expressing secretable ILz(6):TRAIL also inhibited NH induced by balloon injury in the femoral artery of rats. This study demonstrated the preventive and partial regressive effects of ILz(6):TRAIL on AAV- or balloon-induced NH.

Rational Design of Naphthol Groups Functionalized Bipolar Polymer Cathodes for High Performance Alkali-Ion Batteries.

Redox-active organic compounds gather significant attention for their potential application as electrodes in alkali ion batteries, owing to the structural versatility, environmental friendliness, and cost-effectiveness. However, their practical applications of such compounds are impeded by insufficient active sites with limited capacity, dissolution in electrolytes, and sluggish kinetics. To address these issues, a naphthol group-containing triarylamine polymer, namely poly[6,6'-(phenylazanediyl)bis(naphthol)] (poly(DNap-OH)) is rationally designed and synthesized, via oxidative coupling polymerization. It is capable of endowing favorable steric structures that facilitate fast ion diffusion, excellent chemical stability in organic electrolytes, and additional redox-active sites that enable a bipolar redox reaction. By exploiting these advantages, poly(DNap-OH) cathodes demonstrate remarkable cycling stability in both lithium-ion batteries (LIBs) and potassium-ion batteries (PIBs), showcasing enhanced specific capacity and redox reaction kinetics in comparison to the conventional poly(4-methyltriphenylamine) cathodes. Overall, this work offers insights into molecular design strategies for the development of high-performance organic cathodes in alkali-ion batteries.

Synthesis and Thermo-Responsive Behavior of Poly(N-isopropylacrylamide)-b-Poly(N-vinylisobutyramide) Diblock Copolymer.

Thermo-responsive diblock copolymer, poly(N-isopropylacrylamide)-block-poly(N-vinylisobutyramide) was synthesized via switchable reversible addition-fragmentation chain transfer (RAFT) polymerization and its thermal transition behavior was studied. Poly(N-vinylisobutyramide) (PNVIBA), a structural isomer of poly(N-isopropylacrylamide) (PNIPAM) shows a thermo-response character but with a higher lower critical solution temperature (LCST) than PNIPAM. The chain extension of the PNVIBA block from the PNIPAM block proceeded in a controlled manner with a switchable chain transfer reagent, methyl 2-[methyl(4-pyridinyl)carbamothioylthio]propionate. In an aqueous solution, the diblock copolymer shows a thermo-responsive behavior but with a single LCST close to the LCST of PNVIBA, indicating that the interaction between the PNIPAM segment and the PNVIBA segment leads to cooperative aggregation during the self-assembly induced phase separation of the diblock copolymer in solution. Above the LCST of the PNIPAM block, the polymer chains begin to collapse, forming small aggregates, but further aggregation stumbled due to the PNVIBA segment of the diblock copolymer. However, as the temperature approached the LCST of the PNVIBA block, larger aggregates composed of clusters of small aggregates formed, resulting in an opaque solution.

2023 Korean sexually transmitted infections guidelines by the Korean Association of Urogenital Tract Infection and Inflammation: Human papillomavirus vaccination.

The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII) and the Korea Disease Control and Prevention Agency updated the guidelines for human papillomavirus (HPV) vaccine against sexually transmitted HPV infections in Korea to respond to changing epidemiologic trends, evolving scientific evidence, and advances in laboratory diagnostics and research. Main purpose and recommendation of vaccination against HPV are as follows: (1) the purpose of HPV vaccine is to reduce the risk of genital warts and HPV-related cancers including cervical and vulvar cancer, head and neck cancer, anal cancer, and penile cancer; (2) in Korea, bivalent (16, 18) vaccines, quadrivalent vaccines (6, 11, 16, 18), and 9-valent vaccines (6, 11, 16, 18, 31, 33, 45, 52, 58) are used depending on the type of HPV; (3) bivalent and quadrivalent vaccines are national immunizations targeting girls aged 11-12 years and low-income young females aged 18-26 years (age and range of inoculation: routinely administered at 11 or 12 years of age, 2 doses at 0 and 6 months for 12-14 years of age; for females aged 15-26 years, 3 doses depending on the type of vaccine; vaccination can be given to those aged up to 45 years through consultation with a clinician); (4) in the case of administering 2 doses, at least 5 months apart; in the case of administering 3 doses, it is recommended to keep 4 weeks between the 1st and 2nd doses, 12 weeks between the 2nd and 3rd doses, and 5 months between the 1st and 3rd doses; (5) immunocompromised patients such as those with HIV, malignant neoplasms, and autoimmune diseases, and those undergoing transplantation or immunosuppressive therapy should receive 3 doses. HPV vaccine is not recommended during pregnancy.

Prevalence estimation of Tropheryma whipplei in duodenal biopsy tissues of Koreans.

Whipple's disease caused by Tropheryma whipplei is difficult to diagnose because of a broad spectrum of manifestations and non-specific clinical signs. In the current global era, the incidence of duodenal infection/inflammation caused by T. whipplei in Korea may has been underestimated. Here we estimated the prevalence of T. whipplei in duodenal biopsy tissues of Koreans using real-time PCRs (RT-PCRs). A total of 252 duodenal biopsy tissues were collected from Korean patients who underwent esophagogastroduodenoscopy and duodenal biopsy. DNA extracted from the duodenal biopsy tissues was analyzed using three RT-PCRs targeting T. whipplei-specific regions of the 16S-23S rRNA intergenic spacer, hsp65, and Dig15 in parallel. In the samples positive in RT-PCRs, direct sequencing was performed for each RT-PCR target. The prevalence of T. whipplei was estimated based on the RT-PCR and sequencing results. Among the analyzed samples, T. whipplei was not detected. The prevalence of T. whipplei in duodenal biopsy tissues of Koreans was estimated to be less than 0.4%. This is the first study to attempt to detect T. whipplei in duodenal biopsy tissues of Koreans and estimate its prevalence. Our findings infer that while T. whipplei carriers exist in Korea, the incidence of duodenal infection/inflammation caused by T. whipplei is extremely rare.

Changes in patient perceptions regarding ChatGPT-written explanations on lifestyle modifications for preventing urolithiasis recurrence.

Purpose: Artificial Intelligence (AI) imitating human-like language, such as ChatGPT, has impacted lives throughout various multidisciplinary fields. However, despite these innovations, it is unclear how well its implementation will assist patients in clinical situations. We evaluated changes in patient perceptions regarding AI before and after reading a ChatGPT-written explanation. Materials and methods: In total, 24 South Korean patients receiving urolithiasis treatment were surveyed through questionnaires. The ChatGPT explanatory note was provided between the first and second questionnaires, detailing lifestyle modifications for preventing urolithiasis recurrence. The study questionnaire was the Korean version of the General Attitudes toward Artificial Intelligence Scale, including positive and negative attitude items. Wilcoxon signed-rank tests were accomplished to compare questionnaire scores before and after receiving the explanatory note. A linear regression analysis with stepwise elimination was used to assess variable (demographic data) accuracy in predicting outcomes. Results: There were significant differences between total negative questionnaire scores pre- and post-surveys of ChatGPT, but not in the positive scores. Among variables, only education level significantly influenced mean score differences in the negative questionnaires. Conclusions: The negative perception change among urolithiasis patients after receiving the explanatory note provided by the AI chatbot program was observed, evidencing that patients with lower education levels expressed a more negative response. The explanatory note provided by the AI chatbot program could provoke an adverse change in AI perception. Negative human responses must be considered to improve and adapt new technology in health care. Only through changing patient perspectives will upgraded AI technology integrate into medical healthcare.

Clinical performance of SARS-CoV-2 antigen-detection rapid diagnostic test using SERS-based lateral flow immunoassay.

Background: 'ACROSIS COVID-19 Ag (NPS)' kit (SG Medical, Seoul, Korea) is a newly developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-detection rapid diagnostic test (Ag-RDT) using surface-enhanced Raman scattering (SERS)-based lateral flow immunoassay (LFIA). We evaluated its clinical performance compared with STANDARD Q COVID-19 Ag (SD Biosensor, Suwon, Korea), a previously approved Ag-RDT. Methods: A total of 286 nasopharyngeal swab specimens were collected: 104 positive and 182 negative specimens in SARS-CoV-2 real-time reverse-transcription polymerase-chain-reaction (rRT-PCR). SARS-CoV-2-positive specimens were divided according to the cycle threshold (Ct) value in rRT-PCR. The clinical performance of ACROSIS was compared with that of STANDARD Q. Results: ACROSIS showed significantly higher sensitivity than STANDARD Q (92.3% vs. 85.6%, P = 0.02), especially in specimens with 25 ≤ Ct < 30 (78.6% vs. 42.9%). The Ct values of RdRp/S genes for 95% detection rates by ACROSIS and STANDARD Q were 25.8 and 23.0, respectively. Conclusions: This is the first study that evaluated the performance of ACROSIS compared with STANDARD Q. The overall clinical performance of ACROSIS was superior to that of STANDARD Q, especially in specimens with 25 ≤ Ct < 30. ACROSIS could be useful for SARS-CoV-2 Ag detection even in relatively low viral load specimens.

GPR119 activation by DA-1241 alleviates hepatic and systemic inflammation in MASH mice through inhibition of NFκB signaling.

BACKGROUND AND PURPOSE: GPR119 activation has been suggested to improve hyperglycemia, dyslipidemia and hepatic steatosis. But its therapeutic potential for metabolic dysfunction-associated steatohepatitis (MASH) are underexplored. Here, we investigated the effects of DA-1241, a novel GPR119 agonist, on MASH and explored its underlying mechanism of anti-inflammatory effects. EXPERIMENTAL APPROACH: The in vivo anti-MASH effect was assessed by examining the preventive effect in MS-MASH and Ob-MASH mice and the therapeutic effect in MASH with severe hyperglycemia and diet-induced obese (DIO)-MASH mice. Histological and biochemical changes in liver tissue were assessed. Both plasma and hepatic biomarkers related to inflammation and fibrosis were comprehensively analyzed. To understand its mode of action, changes in NFκB signaling were determined in HepG2 and THP-1 cells. KEY RESULTS: DA-1241 attenuated MASH progression and alleviated the MASH phenotypes in MASH mouse models with different etiologies, regardless of glucose-lowering activity. In DIO-MASH mice, DA-1241 significantly reduced biochemical parameters related to steatosis, inflammation and fibrosis in the liver with reduced plasma liver enzymes. When used in combination with a dipeptidyl peptidase 4 (DPP4) inhibitor, DA-1241 further improved the MASH phenotype by increasing endogenous glucagon-like peptide-1 effect. Notably, DA-1241 alone and in combination reduced liver inflammation and restored inflammation-related hepatic gene expression, leading to remission of systemic inflammation as assessed by plasma inflammatory cytokines and chemokines. We demonstrated that DA-1241 reduces macrophage differentiation through downregulation of NFκB signaling by activating GPR119. CONCLUSION: Our data suggest the therapeutic potential of DA-1241, alone and in combination with a DPP4 inhibitor, for MASH.

Oral chemotherapeutic agents in metastatic hormone-sensitive prostate cancer: A network meta-analysis of randomized controlled trials.

Background: Multiple oral chemotherapeutic agents for metastatic hormone-sensitive prostate cancer (mHSPC) have been developed for conjugated use with conventional androgen deprivation therapy (ADT). Several randomized controlled trials (RCTs) report significant benefits in mHSPC patients. Therefore, we compared overall survival (OS) and progression-free survival (PFS) benefits among considerable mHSPC oral chemotherapeutic agents. Materials and methods: We investigated mHSPC treatment efficacy through a systematic RCT-trial literature review (PubMed, Embase, Web of Science, the Cochrane Library, and Scopus). Two reviewers independently screened, extracted data, and assessed bias risk in duplicate. Results: We identified 18 RCTs (n = 13,509). Concerning OS, ADT + abiraterone, ADT + abiraterone + docetaxel, ADT + apalutamide, ADT + bicalutamide, ADT + darolutamide + docetaxel, ADT + enzalutamide, ADT + orteronel, and ADT + rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT + bicalutamide, nilutamide, flutamide, ADT + bicalutamide + palbociclib, and ADT + nilutamide. ADT + docetaxel with androgen receptor targeted agent (ARTA) triplet therapy was not among the top three treatments determined through ranking analysis. Conclusions: Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT + docetaxel SOC. Even so, ADT + docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.

Cortical representation of musical pitch in event-related potentials.

Neural coding of auditory stimulus frequency is well-documented; however, the cortical signals and perceptual correlates of pitch have not yet been comprehensively investigated. This study examined the temporal patterns of event-related potentials (ERP) in response to single tones of pitch chroma, with an assumption that these patterns would be more prominent in musically-trained individuals than in non-musically-trained individuals. Participants with and without musical training (N = 20) were presented with seven notes on the C major scale (C4, D4, E4, F4, G4, A4, and B4), and whole-brain activities were recorded. A linear regression analysis between the ERP amplitude and the seven notes showed that the ERP amplitude increased or decreased as the frequency of the pitch increased. Remarkably, these linear correlations were anti-symmetric between the hemispheres. Specifically, we found that ERP amplitudes of the left and right frontotemporal areas decreased and increased, respectively, as the pitch frequency increased. Although linear slopes were significant in both groups, the musically-trained group exhibited marginally steeper slope, and their ERP amplitudes were most discriminant for frequency of tone of pitch at earlier latency than in the non-musically-trained group (~ 460 ms vs ~ 630 ms after stimulus onset). Thus, the ERP amplitudes in frontotemporal areas varied according to the pitch frequency, with the musically-trained participants demonstrating a wider range of amplitudes and inter-hemispheric anti-symmetric patterns. Our findings may provide new insights on cortical processing of musical pitch, revealing anti-symmetric processing of musical pitch between hemispheres, which appears to be more pronounced in musically-trained people. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-023-00274-y.

Effectiveness of fosfomycin-based antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy: A Korean multicenter study.

PURPOSE: Recent studies have highlighted increasing infectious complications due to fluoroquinolone (FQ)-resistant organisms in men undergoing transrectal ultrasound-guided prostate biopsy (TRUSPB). This study investigated whether fosfomycin (FM)-based antibiotic prophylaxis reduces infections after TRUSPB and identified risk factors for infective complications. MATERIALS AND METHODS: A multicenter study was conducted in the Republic of Korea from January 2018 to December 2021. Patients undergoing prostate biopsy with FQ or FM-based prophylaxis were included. The primary outcome was the post-biopsy infectious complication rate after FQ (group 1) or FM-based antibiotic prophylaxis with FM alone (group 2) or FQ and FM (group 3). Risk factors for infectious complications after TRUSPB were secondary outcomes. RESULTS: Patients (n=2,595) undergoing prostate biopsy were divided into three groups according to the type of prophylactic antibiotics. Group 1 (n=417) received FQ before TRUSPB. Group 2 (n=795) received FM only and group 3 (n=1,383) received FM and FQ before TRUSPB. The overall post-biopsy infectious complication rate was 1.27%. The infectious complication rates were 2.4%, 1.9%, and 0.5% in groups 1, 2, and 3, respectively (p=0.002). In multivariable analysis, predictors of post-biopsy infectious complications included an association with health care utilization (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.74-12.4; p=0.002) and combination antibiotic prophylaxis (FQ and FM) (adjusted OR, 0.26; 95% CI, 0.09-0.69; p=0.007). CONCLUSIONS: In comparison with monotherapy with FM or FQ, combination antibiotic prophylaxis (FQ and FM) showed a lower rate of infectious complications after TRUSPB. Utilization of health care was an independent risk factor for infectious complications after TRUSPB.

Urinary tract infection after radiation therapy or radical prostatectomy on the prognosis of patients with prostate cancer: a population-based study.

BACKGROUND: We aimed to assess the trends in urinary tract infections (UTIs) and prognosis of patients with prostate cancer after radical prostatectomy (RP) and radiation therapy (RT) as definitive treatment options. METHODS: The data of patients diagnosed with prostate cancer between 2007 and 2016 were collected from the National Health Insurance Service database. The incidence of UTIs was evaluated in patients treated with RT, open/laparoscopic RP, and robot-assisted RP. The proportional hazard assumption test was performed using the scaled Schoenfeld residuals based on a multivariable Cox proportional hazard model. Kaplan-Meier analysis were performed to assess survival. RESULTS: A total of 28,887 patients were treated with definitive treatment. In the acute phase (< 3 months), UTIs were more frequent in RP than in RT; in the chronic phase (> 12 months), UTIs were more frequent in RT than in RP. In the early follow-up period, the risk of UTIs was higher in the open/laparoscopic RP group (aHR, 1.63; 95% CI, 1.44-1.83; p < 0.001) and the robot-assisted RP group (aHR, 1.26; 95% CI, 1.11-1.43; p < 0.001), compared to the RT group. The robot-assisted RP group had a lower risk of UTIs than the open/laparoscopic RP group in the early (aHR, 0.77; 95% CI, 0.77-0.78; p < 0.001) and late (aHR, 0.90; 95% CI, 0.89-0.91; p < 0.001) follow-up periods. In patients with UTI, Charlson Comorbidity Index score, primary treatment, age at UTI diagnosis, type of UTI, hospitalization, and sepsis from UTI were risk factors for overall survival. CONCLUSIONS: In patients treated with RP or RT, the incidence of UTIs was higher than that in the general population. RP posed a higher risk of UTIs than RT did in early follow-up period. Robot-assisted RP had a lower risk of UTIs than open/laparoscopic RP group in total period. UTI characteristics might be related to poor prognosis.

Exploring the vaccine-induced immunity against severe acute respiratory syndrome coronavirus 2 in healthcare workers.

We aimed to analyze the kinetics of T-cell-mediated and B-cell-mediated humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before and after booster vaccination, as well as the impacts of the in vitro test results the type of vaccination on the prediction of SARS-CoV-2 infection. A total of 240 healthcare workers vaccinated twice were serially tested using an interferon gamma release assay (IGRA) and a neutralizing antibody (nAb). At the end of the study, we investigated the history of SARS-CoV-2 infection of all the enrolled participants to analyze the effects of the test results and the type of vaccination on SARS-CoV-2 infection. Overall, the positive rates were 52.3% and 80.0% for IGRA and 84.6% and 100% for the nAb test before and after booster vaccination, respectively. However, the positive rates were 52.8% for IGRA and 100% for nAb 3 months after booster vaccination. The in vitro test results and the type of vaccination were not associated with SARS-CoV-2 infection. The antibody response caused by the SARS-CoV-2 vaccination lasted more than 6 months, although the response of the T-cells disappeared rapidly after 3 months. However, these in vitro results and the type of vaccination cannot be used for predicting the risk of SARS-CoV-2 infection.

Gemcitabine-cisplatin versus MVAC chemotherapy for urothelial carcinoma: a nationwide cohort study.

This study assessed the trends in methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine-cisplatin (GC) regimens in Korean patients with metastatic urothelial carcinoma (UC) and compared the side effects and overall survival (OS) rates of the two regimens using nationwide population-based data. The data of patients diagnosed with UC between 2004 and 2016 were collected using the National Health Insurance Service database. The overall treatment trends were assessed according to the chemotherapy regimens. The MVAC and GC groups were matched by propensity scores. Cox proportional hazard analysis and Kaplan-Meier analysis were performed to assess survival. Of 3108 patients with UC, 2,880 patients were treated with GC and 228 (7.3%) were treated with MVAC. The transfusion rate and volume were similar in both the groups, but the granulocyte colony-stimulating factor (G-CSF) usage rate and number were higher in the MVAC group than in the GC group. Both groups had similar OS. Multivariate analysis revealed that the chemotherapy regimen was not a significant factor for OS. Subgroup analysis revealed that a period of ≥ 3 months from diagnosis to systemic therapy enhanced the prognostic effects of the GC regimen. The GC regimen was widely used as the first-line chemotherapy in more than 90% of our study population with metastatic UC. The MVAC regimen showed similar OS to the GC regimen but needed greater use of G-CSF. The GC regimen could be a suitable treatment option for metastatic UC after ≥ 3 months from diagnosis.

Network Pharmacological Analysis of a New Herbal Combination Targeting Hyperlipidemia and Efficacy Validation In Vitro.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein-protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Electrochemical Cloud Point Temperature from Thermoamperometry: Real-Time Analysis for Phase Transition of Thermoresponsive Polymers.

Cloud point temperature (Tcp) is a thermal index used to define the phase transition of thermoresponsive polymers. In this study, we used electrochemical techniques to obtain an electrochemical cloud point temperature (Tecp) that exhibits the more accurate phase transition temperature and can replace Tcp. Thermoamperometry on an ultramicroelectrode was conducted with a poly(arylene ether sulfone) (PES10) as a model system to obtain a current-temperature (i-T) curve in real time; the Tecp of the PES10 was determined from the i-T curve. The i-T curve shows an unprecedented current decrease in the PES10 solution despite increasing temperature; on the other hand, the current increased linearly with increasing temperature in the solution without PES10. This phenomenon was analyzed by considering the characteristics of PES10 during phase transition, such as dynamic viscosity, temperature of the solution, and electrode impedance. It was confirmed that the current drops shown in the i-T curves were mainly due to the decrease of real electrode area. The comparison of Tecp and Tcp showed that both depended similarly on the concentrations of the thermoresponsive polymer and the supporting electrolyte. The results reveal that by adjusting the concentration of polymer and electrolyte in an organic solution, Tecp, as a new analytical method, can be used in electric circuit-based energy storage appliances such as Li-ion batteries and supercapacitors.

Shifting role of cytoreductive nephrectomy according to type of systemic therapy: A nationwide cohort study.

PURPOSE: The best protocol of cytoreductive nephrectomy (CN) and systemic therapy (ST) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear. We sought to evaluate overall survival (OS) in patients with mRCC treated with ST with or without CN. METHODS: We collected data from the National Health Insurance Service database. We excluded 2 years of washout period, 2 years of follow-up period, other cancer diagnoses within 2 years, and ≥4 months interval between ST and CN. The patients were divided into two groups according to whether CN was performed. Kaplan-Meier, propensity score matching, Cox regression model, and incremental survival analyses were conducted. Additionally, we performed subgroup analysis according to whether cytokine therapy or targeted therapy was used as first-line ST. RESULTS: Of 6478 patients, 1707 (26.4%) underwent CN. The CN group showed significantly better OS than the no CN group (p < 0.001). In the cytokine therapy subgroup, patients who underwent CN had significantly higher OS than those who did not (p < 0.001). In the targeted therapy subgroup, no significant difference was found (p = 0.867). In multivariate analysis, CN was associated with better OS in the total cohort (hazard ratio 0.819, p < 0.001). The incremental OS benefit of CN ranged from +0.98 in patients who survived for <24 months to +2.13 in those who survived during all periods. CONCLUSION: About a quarter patients with mRCC from a nationwide database were treated with CN and ST. CN was beneficial in specific patients with mRCC. Patient selection is crucial for obtaining the benefits of CN.

Evaluation of ichroma™ COVID-19 interferon gamma release assay for detection of vaccine-induced immunity in healthcare workers.

OBJECTIVES: We compared the performance of a new interferon gamma release assay (IGRA) format assay, the ichroma™ COVID-19 IGRA (IGRA-SARS), with that of the widely used QuantiFERON SARS-CoV-2 ELISA kit (QFN-SARS) in vaccinated healthcare workers (HCWs). Additionally, we analyzed the long-term changes in IGRA results after the final vaccine dose. METHODS: A total of 383 specimens from 281 HCWs were enrolled in this study, and the results of SARS-IGRA and QFN-SARS assays were compared. In addition, we performed the receive operator curve analysis to estimate the optimal cut-off value for IGRA-SARS. RESULTS: For all specimens, IGRA-SARS and QFN-SARS showed 75.7% and 64.2% of the positive results, respectively. The absolute agreement between IGRA-SARS and QFN-SARS was 80.0%, and the Fleiss' κ value was 0.525, indicating moderate agreement. ROC curve analysis of the IGRA-SARS results showed a cut-off value of >0.254 IU/mL, which was consistent with the manufacturer's specifications. The positive rates of both IGRA assays decreased significantly after a postvaccination period of 6 months. CONCLUSIONS: IGRA-SARS showed acceptable performance in the detection of vaccine-induced immunity against COVID-19; however, harmonization of IGRA assays has not yet been achieved. Additionally, the significant decline of positive rates of IGRA after the last vaccination would support the necessity of booster vaccination after a postvaccination period of 6 months.

Prevalence and detection of Tropheryma whipplei in the stools of Korean patients with diarrhea using real-time PCRs.

BACKGROUND: The prevalence of Tropheryma whipplei varies depending on age, region, and underlying disease. We estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea using real-time PCR (RT-PCR) and compared three RT-PCR targets, rpoB, hsp65, and Dig15. METHODS: A total of 1404 nucleic acid samples extracted from the stools of Korean patients with diarrhea were tested using an initial RT-PCR targeting T. whipplei-specific regions of 16S-23S rRNA intergenic spacer. Subsequently, the samples positive for the initial RT-PCR were tested using the follow-up RT-PCRs targeting rpoB, hsp65, and Dig15 and analyzed by sequencing to confirm the presence of T. whipplei. We estimated the prevalence of T. whipplei and compared them according to gender and age. We also compared the performance of three targets in the follow-up RT-PCRs. RESULTS: T. whipplei was detected in 1.4% of all samples (20 of 1404), and there were no differences according to gender and age. In pediatric samples (≤ 19 years), T. whipplei was detected higher in children aged 6-19 than in those aged 1-5 (2.7% vs. 0.7%, P = 0.01). Sensitivities of the rpoB, hsp65, and Dig15 RT-PCR were 50.0%, 85.0%, and 95.0%, respectively; specificities were 100.0%, 100.0%, and 84.6%, respectively. CONCLUSIONS: This is the first study that estimated the prevalence of T. whipplei in the stools of Korean patients with diarrhea. This study demonstrated the presence of T. whipplei in stools of Koreans, even though the bacterium was detected low. The RT-PCRs targeting hsp65 and Dig15 showed reliable performance, and a multiplex PCR including these targets is expected to be useful for T. whipplei detection.

Neoadjuvant versus adjuvant chemotherapy in upper tract urothelial carcinoma: A nationwide cohort study.

PURPOSE: This study aimed to evaluate the trend of adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC) in patients who underwent radical nephroureterectomy with bladder cuff excision (NUx) for upper tract urothelial carcinoma (UTUC) to compare the perioperative outcomes and overall survival (OS) between AC and NAC using nationwide population-based data. MATERIALS AND METHODS: We collected data on patients diagnosed with UTUC and treated with NUx between 2004 and 2016 using the National Health Insurance Service database, and evaluated the overall treatment trends. The AC and NAC groups were propensity score-matched. Cox proportional hazard and Kaplan-Meier analyses were used to assess survival. RESULTS: Of the 8,705 enrolled patients, 6,627 underwent NUx only, 94 underwent NAC, and 1,984 underwent AC. The rate of NUx without perioperative chemotherapy increased from 70.8 to 78.2% (R2 = 0.632; p < 0.001). The rates of dialysis (p = 0.398), TUR-BT (p = 1.000), and radiotherapy (p = 0.497) after NUx were similar. In the Kaplan-Meier curve, the NAC and AC groups showed no significant difference (p = 0.480). In multivariate analysis, treatment with AC or NAC was not associated with OS (hazard ratio 0.83, 95% confidence interval 0.49-1.40, p = 0.477). CONCLUSION: The use of NUx without perioperative chemotherapy has tended to increase in South Korea. Dialysis, TUR-BT, and radiotherapy rates after NUx were similar between the NAC and AC groups. There was no significant difference in OS between the NAC and AC groups. Proper perioperative chemotherapy according to patient and tumor conditions should be determined by obtaining more evidence of UTUC.