http://localhost:8080/xmlui/handle/123456789/12117 157 - 280 2026-04-15T15:10:39Z http://localhost:8080/xmlui/handle/123456789/12179 Title: Increased SARS-CoV-2-related hospitalization and mortality in rheumatoid arthritis patients receiving rituximab therapy-a monocentric retrospective study Authors: Wang, Chrong-Reen; Hsu, Chih-Hui; Lin, Wei-Chieh Abstract: From 2022 April to 2024 August, retrospective analyses by multivariable logistic regression were conducted in 341 rheumatoid arthritis patients receiving rituximab (RTX), tofacitinib (TOF) or disease-modifying-antirheumatic drug (DMARD) alone therapy. Compared to DMARD alone or TOF treatment, RTX therapy had increased adjusted odds ratios of SARS-CoV-2-related hospitalization, pneumonia and mortality 2025-01-01T00:00:00Z http://localhost:8080/xmlui/handle/123456789/12164 Title: Comparison of a Sepsityper® kit and in-house membrane filtration methods for rapidly diagnosing positive blood cultures via MALDI‒TOF MS Authors: Tai-Fen, Lee; Tsai-Wen, Wan; Wei-Yu, Hsu; Xiang-Jun, Chen; Yu-Tsung, Huang Abstract: Background: Rapidly identifying pathogens and determining their antimicrobial susceptibilities using samples directly from flagged blood culture bottles pose significant challenges for clinical laboratories. Thus, a costeffective and efficient sample-processing method is urgently needed to address this issue. To fulfill this need, we developed a novel protocol to rapidly identify pathogens and determine their antimicrobial susceptibilities using samples directly from blood culture bottles. Methods: Samples were either processed by the Sepsityper kit or our in-house methods. In our approach, we processed the samples using either a nonionic surfactant (Triton X-100) or a NaOH-sodium dodecyl sulfate (SDS) solution, followed by membrane filtration (MF) and centrifugation. Subsequently, the samples were analyzed using MALDI-TOF mass spectrometry (MS) for identification and the Vitek® 2 for antimicrobial susceptibility determination. Results: In this study, 122 clinical blood culture samples were analyzed, and our MF protocol displayed enhanced accuracy in identifying gram-positive organisms (n = 58) and gram-negative bacilli (n = 64) compared to the Sepsityper method. In particular, the Triton-MF and SDS-MF techniques outperformed Sepsityper in identifying gram-negative bacilli, with accuracy rates of 92.2 %, 85.9 %, and 78.1 %, respectively. Notably, both the TritonMF and SDS-MF methods exhibited high categorical agreement (CA) for antimicrobial susceptibility testing (AST) for carbapenem against Enterobacterales, with CAs of 100 % and 98.7 %, respectively. Additionally, both methods exhibited a perfect CA and essential agreement of 100 % for Enterococcus faecium AST for vancomycin. Conclusion: These findings strongly indicate that our MF methods have the potential to streamline the identification and AST of bacteria in positive blood cultures. 2024-11-01T00:00:00Z http://localhost:8080/xmlui/handle/123456789/12163 Title: A novel Diguanylate cyclase VdcR has multifaceted regulatory functions in the pathogenicity of Vibrio vulnificus Authors: Chen, Yi-Wen; Tseng, Tien-Sheng; Chen, Kai-Ting; Lai, Shu-Jung Abstract: Background: Vibrio vulnificus is a Gram-negative pathogen that infects humans through foodborne or wound infections. Victims of V. vulnificus infections face significant health risks, including cellulitis and septicemia, which have rapid disease progression and high mortality rates. Diguanylate cyclase is responsible for producing the secondary messenger cyclic di-GMP. It plays a crucial role in regulating various bacterial physiological processes, such as motility, toxicity, and pathogenicity, through transcriptional regulation and affecting cyclic diGMP levels. However, the DGC-mediated pathogenicity regulation in V. vulnificus is still unclear. Methods: The vdcR gene in V. vulnificus was studied using a deletion strain (ΔVdcR) and an overexpression strain (oeVdcR) to understand its role in regulating the bacterium’s pathogenicity. The electrophoretic mobility shift assay and RT-qPCR confirmed VdcR’s impact on phosphodiesterase gene expression. To investigate how VdcR affects pathogenicity, V. vulnificus variant strains were assays for hemolysis, metalloprotease activity, cytotoxicity, resistance to phagocytosis, and lethality assays of the nematode Caenorhabditis elegans after infection. Results: This study discovered a virulence-associated diguanylate cyclase, VdcR, which serves as a transcriptional regulator to induce phosphodiesterases and reduce the accumulation of cyclic di-GMP. VdcR expression resulted in low hemolysis, metalloprotease, and cytotoxicity activity. It also improved the cell adhesion ability and antiphagocytosis activity to infect the host cell and escape the macrophage phagocytosis. The constitutively expressed VdcR in V. vulnificus caused low mortality rates in Caenorhabditis elegans survival assays. Conclusion: The above evidence demonstrated that VdcR suppresses the pathogenicity in V. vulnificus YJ016. 2024-11-01T00:00:00Z http://localhost:8080/xmlui/handle/123456789/12161 Title: Clinical characteristics and genomic changes of recurrent MethicillinResistant Staphylococcus aureus bacteremia Authors: Chang, Tu-Hsuan; Tang, Hung-Jen; Chen, Chi-Chung Abstract: Background: Recurrent or persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia presents significant clinical challenges. Comprehensive genomic-scale studies on the genetic changes in MRSA that correspond to refractory bacteremia are lacking. Method: From 2011 to 2019, MRSA blood isolates were collected from patients with persistent or recurrent bacteremia at a teaching hospital in southern Taiwan. Whole-genome sequencing (WGS) captured the genomic changes in strains responsible for refractory bacteremia, and the altered susceptibilities to specific antimicrobial agents were assessed through measurements of minimal inhibitory concentrations (MICs). Result: A total of 35 MRSA blood isolates from 15 patients with recurrent or persistent bacteremia were analyzed. Reduced susceptibilities to at least one anti-MRSA agent developed in strains from seven (46.7 %) patients. Of them, a non-synonymous mutation on a global regulator mgrA was associated with reduced daptomycin susceptibility, while an increase in vancomycin MIC was linked to mutations in genes encoding LCP family protein. A 16-fold increase in MIC to fusidic acid was connected to a mutation in the elongation factor G. These recurrent strains commonly exhibited a loss or acquisition of adhesion genes that were involved in biofilm formation, including fnbA, fnbB, and sdrD, and easG series genes of type VII secretion system. Conclusion: Changes in the susceptibility of successive strains to common anti-MRSA agents were frequently observed in recurrent MRSA bacteremia. These changes were linked to modifications in genes of regulatory cascade, peptidoglycan binding, adhesion, and type VII secretion system. 2024-11-01T00:00:00Z