Pub Date : 2024-06-01DOI: 10.1016/j.jmii.2023.10.015
Chin-Shiang Tsai , Jiun-Ling Wang , Ying-Shu Liao , Mizuho Fukushige , Chien-Shun Chiou , Wen-Chien Ko
While the incidence of shigellosis has decreased in developed nations due to improved living conditions and healthcare systems, it remains prevalent in economically developing regions. In recent years, a resurgence of shigellosis has been observed in the United States, Europe, and Taiwan, primarily among men having sex with men and people living with human immunodeficiency virus, along with a rise in antimicrobial resistance. This study aims to review the historical epidemiological trends and drug resistance in shigellosis, with a focus on Taiwan. A comprehensive search was conducted using various databases and sources, including non-English literature in Japanese and Chinese. In developed countries, Shigella sonnei and Shigella flexneri are the most common species, while Shigella dysenteriae infections are sporadic. In Taiwan, the classification and prevalence of Shigella species have evolved over time, with S. flexneri and S. sonnei being the predominant strains. Fluoroquinolone resistance and azithromycin non-susceptibility are the ongoing threat. In conclusion, shigellosis remains a significant global health concern, with recent increases in certain populations and antimicrobial resistance. Further research is necessary to understand the clinical significance and risk factors associated with asymptomatic carriers and to assess the impact of behavioral modifications and interventions in high-risk populations.
{"title":"Shigellosis in Taiwan: An old enteric pathogen with changing epidemiology and increasing antimicrobial resistance","authors":"Chin-Shiang Tsai , Jiun-Ling Wang , Ying-Shu Liao , Mizuho Fukushige , Chien-Shun Chiou , Wen-Chien Ko","doi":"10.1016/j.jmii.2023.10.015","DOIUrl":"10.1016/j.jmii.2023.10.015","url":null,"abstract":"<div><p>While the incidence of shigellosis has decreased in developed nations due to improved living conditions and healthcare systems, it remains prevalent in economically developing regions. In recent years, a resurgence of shigellosis has been observed in the United States, Europe, and Taiwan, primarily among men having sex with men and people living with human immunodeficiency virus, along with a rise in antimicrobial resistance. This study aims to review the historical epidemiological trends and drug resistance in shigellosis, with a focus on Taiwan. A comprehensive search was conducted using various databases and sources, including non-English literature in Japanese and Chinese. In developed countries, <em>Shigella sonnei</em> and <em>Shigella flexneri</em> are the most common species, while <em>Shigella dysenteriae</em> infections are sporadic. In Taiwan, the classification and prevalence of <em>Shigella</em> species have evolved over time, with <em>S. flexneri</em> and <em>S. sonnei</em> being the predominant strains. Fluoroquinolone resistance and azithromycin non-susceptibility are the ongoing threat. In conclusion, shigellosis remains a significant global health concern, with recent increases in certain populations and antimicrobial resistance. Further research is necessary to understand the clinical significance and risk factors associated with asymptomatic carriers and to assess the impact of behavioral modifications and interventions in high-risk populations.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 3","pages":"Pages 346-353"},"PeriodicalIF":7.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118223002062/pdfft?md5=3dc4141de1cd05db5f082c5bd2dfa2d8&pid=1-s2.0-S1684118223002062-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.jmii.2024.04.004
Yu-Lin Lee , Chun-Eng Liu , Hung-Jen Tang , Yu-Tsung Huang , Yao-Shen Chen , Po-Ren Hsueh
Background
The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales.
Methods
This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018–2019) and during the COVID-19 pandemic (2020–2021).
Results
A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC β-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel β-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam.
Conclusions
The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.
{"title":"Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018–2021","authors":"Yu-Lin Lee , Chun-Eng Liu , Hung-Jen Tang , Yu-Tsung Huang , Yao-Shen Chen , Po-Ren Hsueh","doi":"10.1016/j.jmii.2024.04.004","DOIUrl":"10.1016/j.jmii.2024.04.004","url":null,"abstract":"<div><h3>Background</h3><p>The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales.</p></div><div><h3>Methods</h3><p>This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and β-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018–2019) and during the COVID-19 pandemic (2020–2021).</p></div><div><h3>Results</h3><p>A total of 1231 Enterobacterales isolates were collected, predominantly <em>Escherichia coli</em> (55.6%) and <em>Klebsiella pneumoniae</em> (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, <em>p</em> < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC β-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel β-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower <em>in vitro</em> activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam.</p></div><div><h3>Conclusions</h3><p>The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 3","pages":"Pages 446-456"},"PeriodicalIF":7.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000720/pdfft?md5=d39e1d2737669808e4c7098ccb1a3658&pid=1-s2.0-S1684118224000720-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140584348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim of the study was the molecular characterization of 21 ceftazidime/avibactam resistant (CZA-R) Klebsiella pneumoniae strains, collected in the period October 2021–March 2022 from an Intensive Care COVID Unit in a Northern Italian Hospital.
Methods
After growth on selective/chromogenic culture media and susceptibility tests assessment, resistance genes content was ascertained for all the isolates by the HybriSpot 12 multiplexing, PCR and Whole-Genome Sequencing (WGS). Clonality was assessed by PFGE and MLST according to the Pasteur scheme. A SNPs-based phylogenetic tree was obtained comparing representative isolates and global genomes. The blaKPC gene horizontal transmission was evaluated by conjugation experiments. blaKPC-166 was cloned in a pCR2.1 vector and transformed in chemically competent TOP10 cells.
Results
Sixteen inpatients resulted positive for colonization and/or infection by KPC-producing K. pneumoniae (KPC-Kp) strains. The 21 CZA-R KPC-Kp isolates obtained showed MDR phenotype; susceptibility to meropenem was always retained. All the CZA-R KPC-Kp presented a novel blaKPC variant, named blaKPC-166, showing a single nucleotide substitution (T811C) compared to the blaKPC-94; but related to blaKPC-2.
Two different pulsotypes were detected
A in 18/21 and B in 1/21 cases, two strains from the same patient being untypable by PFGE. Interestingly, the outbreak was sustained by the high-risk clone ST307, although the ST22, ST6342, ST6418 and ST6811 have also been identified and associated to KPC-166. Worryingly, blaKPC-166 could be transferred horizontally and, after cloning, it conferred resistance to CZA.
Discussion
This novel variant confers CZA–resistance and carbapenems susceptibility restoration. As KPC-166 was found expressed by multiple Kp clones, greater efforts should be made to prevent the further dissemination of such strains in Italian clinical settings.
{"title":"A novel KPC-166 in ceftazidime/avibactam resistant ST307 Klebsiella pneumoniae causing an outbreak in intensive care COVID Unit, Italy","authors":"Aurora Piazza , Vittoria Mattioni Marchetti , Alessandra Bielli , Gherard Batisti Biffignandi , Francesca Piscopiello , Riccardo Giudici , Livia Tartaglione , Marco Merli , Chiara Vismara , Roberta Migliavacca","doi":"10.1016/j.jmii.2024.03.004","DOIUrl":"10.1016/j.jmii.2024.03.004","url":null,"abstract":"<div><h3>Introduction</h3><p>Aim of the study was the molecular characterization of 21 ceftazidime/avibactam resistant (CZA-R) <em>Klebsiella pneumoniae</em> strains, collected in the period October 2021–March 2022 from an Intensive Care COVID Unit in a Northern Italian Hospital.</p></div><div><h3>Methods</h3><p>After growth on selective/chromogenic culture media and susceptibility tests assessment, resistance genes content was ascertained for all the isolates by the HybriSpot 12 multiplexing, PCR and Whole-Genome Sequencing (WGS). Clonality was assessed by PFGE and MLST according to the Pasteur scheme. A SNPs-based phylogenetic tree was obtained comparing representative isolates and global genomes. The <em>bla</em>KPC gene horizontal transmission was evaluated by conjugation experiments. <em>bla</em>KPC-166 was cloned in a pCR2.1 vector and transformed in chemically competent TOP10 cells.</p></div><div><h3>Results</h3><p>Sixteen inpatients resulted positive for colonization and/or infection by KPC-producing <em>K. pneumoniae</em> (KPC-Kp) strains. The 21 CZA-R KPC-Kp isolates obtained showed MDR phenotype; susceptibility to meropenem was always retained. All the CZA-R KPC-Kp presented a novel <em>bla</em>KPC variant, named <em>bla</em>KPC-166, showing a single nucleotide substitution (T811C) compared to the <em>bla</em>KPC-94; but related to <em>bla</em>KPC-2.</p></div><div><h3>Two different pulsotypes were detected</h3><p>A in 18/21 and B in 1/21 cases, two strains from the same patient being untypable by PFGE. Interestingly, the outbreak was sustained by the high-risk clone ST307, although the ST22, ST6342, ST6418 and ST6811 have also been identified and associated to KPC-166. Worryingly, <em>bla</em>KPC-166 could be transferred horizontally and, after cloning, it conferred resistance to CZA.</p></div><div><h3>Discussion</h3><p>This novel variant confers CZA–resistance and carbapenems susceptibility restoration. As KPC-166 was found expressed by multiple Kp clones, greater efforts should be made to prevent the further dissemination of such strains in Italian clinical settings.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 3","pages":"Pages 457-469"},"PeriodicalIF":7.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000677/pdfft?md5=2e736469fac2a72172d5b86673192c7d&pid=1-s2.0-S1684118224000677-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140399068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.jmii.2024.02.010
Chieh-Lung Chen , How-Yang Tseng , Wei-Cheng Chen , Shinn-Jye Liang , Chih-Yen Tu , Yu-Chao Lin , Po-Ren Hsueh
Background
The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship.
Methods
This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP.
Results
Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results.
Conclusions
This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.
{"title":"Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units","authors":"Chieh-Lung Chen , How-Yang Tseng , Wei-Cheng Chen , Shinn-Jye Liang , Chih-Yen Tu , Yu-Chao Lin , Po-Ren Hsueh","doi":"10.1016/j.jmii.2024.02.010","DOIUrl":"10.1016/j.jmii.2024.02.010","url":null,"abstract":"<div><h3>Background</h3><p>The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship.</p></div><div><h3>Methods</h3><p>This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP.</p></div><div><h3>Results</h3><p>Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results.</p></div><div><h3>Conclusions</h3><p>This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 3","pages":"Pages 480-489"},"PeriodicalIF":7.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000379/pdfft?md5=597e444adcd3ddb5a6d9c454423cb8cd&pid=1-s2.0-S1684118224000379-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1016/j.jmii.2024.05.007
Background
Granulomatous lymphadenitis, a histopathological diagnosis, often indicates infections, such as those caused by mycobacterial and fungal agents.
Methods
We conducted an analysis of 1098 granulomatous lymphadenitis cases, examining age distribution, lymph node locations, and laterality. Molecular detection of Bacillus Calmette-Guérin (BCG) was performed on archived formalin-fixed paraffin-embedded tissue specimens.
Results
Our analysis revealed a bimodal age distribution, notably with a minor peak in infants. These infantile cases predominantly featured axillary involvement, frequently occurring on the left side. Positive rates of BCG identification decreased with age: <1 year, 71%; 1–2 year, 33%; 2–3 year, 13%; 3–4 year, 0%. Remarkably, only one of the 14 cases with molecularly confirmed BCG lymphadenitis had comments regarding BCG in the pathological report. Compared with patients born after 2016 (BCG at 5–8 months), those born before 2016 (BCG at birth) developed BCG lymphadenitis at a wider age range with right skewness (before 2016, 13 ± 11 months [range, 3–33 months] vs. after 2016, 10 ± 2 months [range, 8–13 months]). Four of the 14 BCG-positive cases had congenital heart disease. Seven patients received anti-tuberculosis drugs following surgical excision. No surgical complications were reported.
Conclusions
BCG lymphadenitis constitutes a distinctive minor peak within the spectrum of granulomatous lymphadenitis in Taiwan. Pathologists should consider the possibility of BCG infection, especially in cases of infantile axillary, supraclavicular, neck lymphadenopathies on the left side. Moreover, BCG administration at 5–8 months may reduce delayed-onset BCG lymphadenitis.
{"title":"Granulomatous lymphadenitis in Taiwan: Unraveling infantile peak and Bacillus Calmette-Guérin lymphadenitis","authors":"","doi":"10.1016/j.jmii.2024.05.007","DOIUrl":"10.1016/j.jmii.2024.05.007","url":null,"abstract":"<div><h3>Background</h3><p>Granulomatous lymphadenitis, a histopathological diagnosis, often indicates infections, such as those caused by mycobacterial and fungal agents.</p></div><div><h3>Methods</h3><p>We conducted an analysis of 1098 granulomatous lymphadenitis cases, examining age distribution, lymph node locations, and laterality. Molecular detection of Bacillus Calmette-Guérin (BCG) was performed on archived formalin-fixed paraffin-embedded tissue specimens.</p></div><div><h3>Results</h3><p>Our analysis revealed a bimodal age distribution, notably with a minor peak in infants. These infantile cases predominantly featured axillary involvement, frequently occurring on the left side. Positive rates of BCG identification decreased with age: <1 year, 71%; 1–2 year, 33%; 2–3 year, 13%; 3–4 year, 0%. Remarkably, only one of the 14 cases with molecularly confirmed BCG lymphadenitis had comments regarding BCG in the pathological report. Compared with patients born after 2016 (BCG at 5–8 months), those born before 2016 (BCG at birth) developed BCG lymphadenitis at a wider age range with right skewness (before 2016, 13 ± 11 months [range, 3–33 months] vs. after 2016, 10 ± 2 months [range, 8–13 months]). Four of the 14 BCG-positive cases had congenital heart disease. Seven patients received anti-tuberculosis drugs following surgical excision. No surgical complications were reported.</p></div><div><h3>Conclusions</h3><p>BCG lymphadenitis constitutes a distinctive minor peak within the spectrum of granulomatous lymphadenitis in Taiwan. Pathologists should consider the possibility of BCG infection, especially in cases of infantile axillary, supraclavicular, neck lymphadenopathies on the left side. Moreover, BCG administration at 5–8 months may reduce delayed-onset BCG lymphadenitis.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 5","pages":"Pages 749-759"},"PeriodicalIF":4.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000847/pdfft?md5=6db24abc319f843be5f6e51f34ffe7fe&pid=1-s2.0-S1684118224000847-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-24DOI: 10.1016/j.jmii.2024.05.006
Background
Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations.
Methods
We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected.
Results
A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m2 increase), but was not associated with HIV serostatus.
Conclusion
We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.
背景男性性腺功能减退症在艾滋病病毒感染者(PWH)中并不少见,估计发病率为 9% 至 16%。我们在 2021 年 2 月至 2022 年 11 月间招募了 HIV 阳性的男男性行为者(MSM),他们一直在接受稳定的抗逆转录病毒治疗,同时也招募了未感染 HIV 的 MSM。测量了血清游离睾酮水平、性激素结合球蛋白和其他相关激素。为了评估血清游离睾酮水平与所收集的临床变量之间的关系,我们进行了多元线性回归分析。与未感染 HIV 的 MSM 相比,感染 HIV 的 MSM 的年龄更高(中位数为 41 岁对 29.5 岁),症状性性腺功能减退症的发病率更高(8.3% 对 1.6%)。在年龄为 35 岁的男男性行为者中,两组之间的血清游离睾酮水平和性腺功能减退症患病率没有显著差异。在多元线性回归分析中,血清游离睾酮水平随着年龄的增长(每增加1岁减少1.14 pg/mL)和体重指数(BMI)的增加(每增加1kg/m2减少1.07 pg/mL)而显著下降,但与HIV血清状态无关。血清游离睾酮水平与年龄和体重指数呈负相关,但与 HIV 血清状态无显著相关性。
{"title":"Hypogonadism among HIV-positive men who have sex with men in Taiwan: Prevalence and associated factors","authors":"","doi":"10.1016/j.jmii.2024.05.006","DOIUrl":"10.1016/j.jmii.2024.05.006","url":null,"abstract":"<div><h3>Background</h3><p>Male hypogonadism is not uncommon in people with HIV (PWH), with estimated prevalence ranging from 9% to 16%. Existing data are limited on the serum testosterone levels in PWH in Asian populations.</p></div><div><h3>Methods</h3><p>We enrolled HIV-positive men who have sex with men (MSM) and had been on stable antiretroviral therapy and MSM without HIV between February 2021 and November 2022. Serum free testosterone levels, sex hormone-binding globulins and other associated hormones were measured. Multiple linear regression analysis was performed to assess the association between serum free testosterone levels and clinical variables collected.</p></div><div><h3>Results</h3><p>A total of 447 MSM with HIV and 124 MSM without HIV were enrolled. Compared with MSM without HIV, MSM with HIV had a higher age (median, 41 versus 29.5 years) and prevalence of symptomatic hypogonadism (8.3% versus 1.6%). Among MSM who were aged <35 years, there were no significant differences in the serum free testosterone levels and prevalences of hypogonadism between the two groups. In multiple linear regression analysis, serum free testosterone level significantly decreased with advanced age (a decrease of 1.14 pg/mL per 1-year increase) and a higher body-mass index (BMI) (a decrease of 1.07 pg/mL per 1-kg/m<sup>2</sup> increase), but was not associated with HIV serostatus.</p></div><div><h3>Conclusion</h3><p>We found that MSM with HIV had a higher prevalence of symptomatic hypogonadism than MSM without HIV in Taiwan, which could be attributed to age difference. Serum free testosterone levels were negatively correlated with age and BMI, but did not show a significant correlation with HIV serostatus.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 5","pages":"Pages 739-748"},"PeriodicalIF":4.5,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000835/pdfft?md5=317a613a2f37f40dcfe496d846adff7c&pid=1-s2.0-S1684118224000835-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-16DOI: 10.1016/j.jmii.2024.02.003
Seow-Chin Ong , Hong-Wei Luo , Wei-Hung Cheng , Fu-Man Ku , Chih-Yu Tsai , Po-Jung Huang , Chi-Ching Lee , Yuan-Ming Yeh , Rose Lin , Cheng-Hsun Chiu , Petrus Tang
Background
Trichomonas vaginalis is parasitic protozoan that causes human urogenital infections. Accumulated reports indicated that exosomes released by this parasite play a crucial role in transmitting information and substances between cells during host-parasite interactions. Current knowledge on the protein contents in T. vaginalis exosome is mainly generated from three previous studies that used different T. vaginalis isolates as an experimental model. Whether T. vaginalis exosomes comprise a common set of proteins (core exosome proteome) is still unclear.
Methods
To explore the core exosome proteome in T. vaginalis, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the contents of sucrose ultracentrifugation-enriched exosome and supernatant fractions isolated from six isolates.
Results
Transmission electron microscopy (TEM) confirmed the presence of exosomes in the enriched fraction. Proteomic analysis identified a total of 1870 proteins from exosomal extracts. There were 1207 exosomal-specific proteins after excluding 436 ‘non-core exosomal proteins’. Among these, 72 common exosomal-specific proteins were expressed in all six isolates. Compared with three published T. vaginalis exosome proteome datasets, we identified 16 core exosomal-specific proteins. These core exosomal-specific proteins included tetraspanin (TvTSP1), the classical exosome marker, and proteins mainly involved in catalytic activity and binding such as ribosomal proteins, ras-associated binding (Rab) proteins, and heterotrimeric G proteins.
Conclusions
Our study highlighted the importance of using supernatant fraction from exosomal extract as a control to eliminate ‘non-core exosomal proteins’. We compiled a reference core exosome proteome of T. vaginalis, which is essential for developing a fundamental understanding of exosome-mediated cell communication and host-parasite interaction.
{"title":"The core exosome proteome of Trichomonas vaginalis","authors":"Seow-Chin Ong , Hong-Wei Luo , Wei-Hung Cheng , Fu-Man Ku , Chih-Yu Tsai , Po-Jung Huang , Chi-Ching Lee , Yuan-Ming Yeh , Rose Lin , Cheng-Hsun Chiu , Petrus Tang","doi":"10.1016/j.jmii.2024.02.003","DOIUrl":"10.1016/j.jmii.2024.02.003","url":null,"abstract":"<div><h3>Background</h3><p><em>Trichomonas vaginalis</em> is parasitic protozoan that causes human urogenital infections. Accumulated reports indicated that exosomes released by this parasite play a crucial role in transmitting information and substances between cells during host-parasite interactions. Current knowledge on the protein contents in <em>T. vaginalis</em> exosome is mainly generated from three previous studies that used different <em>T. vaginalis</em> isolates as an experimental model. Whether <em>T. vaginalis</em> exosomes comprise a common set of proteins (core exosome proteome) is still unclear.</p></div><div><h3>Methods</h3><p>To explore the core exosome proteome in <em>T. vaginalis</em>, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the contents of sucrose ultracentrifugation-enriched exosome and supernatant fractions isolated from six isolates.</p></div><div><h3>Results</h3><p>Transmission electron microscopy (TEM) confirmed the presence of exosomes in the enriched fraction. Proteomic analysis identified a total of 1870 proteins from exosomal extracts. There were 1207 exosomal-specific proteins after excluding 436 ‘non-core exosomal proteins’. Among these, 72 common exosomal-specific proteins were expressed in all six isolates. Compared with three published <em>T. vaginalis</em> exosome proteome datasets, we identified 16 core exosomal-specific proteins. These core exosomal-specific proteins included tetraspanin (TvTSP1), the classical exosome marker, and proteins mainly involved in catalytic activity and binding such as ribosomal proteins, ras-associated binding (Rab) proteins, and heterotrimeric G proteins.</p></div><div><h3>Conclusions</h3><p>Our study highlighted the importance of using supernatant fraction from exosomal extract as a control to eliminate ‘non-core exosomal proteins’. We compiled a reference core exosome proteome of <em>T. vaginalis</em>, which is essential for developing a fundamental understanding of exosome-mediated cell communication and host-parasite interaction.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 2","pages":"Pages 246-256"},"PeriodicalIF":7.4,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000409/pdfft?md5=21361a39dd637e30c232671d521e30d2&pid=1-s2.0-S1684118224000409-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139919362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-08DOI: 10.1016/j.jmii.2024.01.008
Pek Kee Chen , Yi-Tzu Lee , Chia-Ying Liu , Tran Thi Dieu Thuy , Kieu Anh , Jiunn-Jong Wu , Chun-Hsing Liao , Yu-Tsung Huang , Yu-Chen Chen , Cheng-Yen Kao
Background
This study aimed to characterize carbapenem-nonsusceptible Acinetobacter (CNSA) isolated from patients with bacteremia from 1997 to 2015.
Methods
A total of 173 CNSA (12.3%) was recovered from 1403 Acinetobacter isolates. The presence of selected β-lactamase genes in CNSA was determined by PCR amplification. The conjugation test was used to determine the transferability of metallo-β-lactamase (MBL)-carrying plasmids. Whole genome sequencing in combination with phenotypic assays was carried out to characterize MBL-plasmids.
Results
In general, a trend of increasing numbers of CNSA was observed. Among the 173 CNSA, A. baumannii (54.9%) was the most common species, followed by A. nosocomialis (23.1%) and A. soli (12.1%). A total of 49 (28.3%) CNSA were extensively drug-resistant, and all were A. baumannii. The most common class D carbapenemase gene in 173 CNSA was blaOXA-24-like (32.4%), followed by ISAba1-blaOXA-51-like (20.8%), ISAba1-blaOXA-23 (20.2%), and IS1006/IS1008-blaOXA-58 (11.6%). MBL genes, blaVIM-11,blaIMP-1, and blaIMP-19 were detected in 9 (5.2%), 20 (11.6%), and 1 (0.6%) CNSA isolates, respectively. Transfer of MBL genes to AB218 and AN254 recipient cells was successful for 7 and 6 of the 30 MBL-plasmids, respectively. The seven AB218-derived transconjugants carrying MBL-plasmids produced less biofilm but showed higher virulence to larvae than recipient AB218.
Conclusions
Our 19-year longitudinal study revealed a stable increase in CNSA during 2005–2015. blaOXA-24-like, ISAba1-blaOXA-51-like, and ISAba1-blaOXA-23 were the major determinants of Acinetobacter carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to A. baumannii virulence.
{"title":"A 19-year longitudinal study to characterize carbapenem-nonsusceptible Acinetobacter isolated from patients with bloodstream infections and the contribution of conjugative plasmids to carbapenem resistance and virulence","authors":"Pek Kee Chen , Yi-Tzu Lee , Chia-Ying Liu , Tran Thi Dieu Thuy , Kieu Anh , Jiunn-Jong Wu , Chun-Hsing Liao , Yu-Tsung Huang , Yu-Chen Chen , Cheng-Yen Kao","doi":"10.1016/j.jmii.2024.01.008","DOIUrl":"10.1016/j.jmii.2024.01.008","url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to characterize carbapenem-nonsusceptible <em>Acinetobacter</em> (CNSA) isolated from patients with bacteremia from 1997 to 2015.</p></div><div><h3>Methods</h3><p>A total of 173 CNSA (12.3%) was recovered from 1403 <em>Acinetobacter</em> isolates. The presence of selected β-lactamase genes in CNSA was determined by PCR amplification. The conjugation test was used to determine the transferability of metallo-β-lactamase (MBL)-carrying plasmids. Whole genome sequencing in combination with phenotypic assays was carried out to characterize MBL-plasmids.</p></div><div><h3>Results</h3><p>In general, a trend of increasing numbers of CNSA was observed. Among the 173 CNSA, <em>A. baumannii</em> (54.9%) was the most common species, followed by <em>A. nosocomialis</em> (23.1%) and <em>A. soli</em> (12.1%). A total of 49 (28.3%) CNSA were extensively drug-resistant, and all were <em>A. baumannii</em>. The most common class D carbapenemase gene in 173 CNSA was <em>bla</em><sub>OXA-24-like</sub> (32.4%), followed by IS<em>Aba1</em>-<em>bla</em><sub>OXA-51-like</sub> (20.8%), IS<em>Aba1</em>-<em>bla</em><sub>OXA-23</sub> (20.2%), and IS<em>1006</em>/IS<em>1008</em>-<em>bla</em><sub>OXA-58</sub> (11.6%). MBL genes, <em>bla</em><sub>VIM-11,</sub> <em>bla</em><sub>IMP-1</sub>, and <em>bla</em><sub>IMP-19</sub> were detected in 9 (5.2%), 20 (11.6%), and 1 (0.6%) CNSA isolates, respectively. Transfer of MBL genes to AB218 and AN254 recipient cells was successful for 7 and 6 of the 30 MBL-plasmids, respectively. The seven AB218-derived transconjugants carrying MBL-plasmids produced less biofilm but showed higher virulence to larvae than recipient AB218.</p></div><div><h3>Conclusions</h3><p>Our 19-year longitudinal study revealed a stable increase in CNSA during 2005–2015. <em>bla</em><sub>OXA-24-like</sub>, IS<em>Aba1</em>-<em>bla</em><sub>OXA-51-like</sub>, and IS<em>Aba1</em>-<em>bla</em><sub>OXA-23</sub> were the major determinants of <em>Acinetobacter</em> carbapenem resistance. MBL-carrying plasmids contribute not only to the carbapenem resistance but also to <em>A. baumannii</em> virulence.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 2","pages":"Pages 288-299"},"PeriodicalIF":7.4,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000355/pdfft?md5=2293ab1d6065e034dc8887b86a613198&pid=1-s2.0-S1684118224000355-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-06DOI: 10.1016/j.jmii.2024.01.009
Yuan Wang , Yingying Ma , Luying Xiong, Xueting Wang, Yanzi Zhou, Xiaohui Chi, Tao Chen, Hao Fu, Qixia Luo , Yonghong Xiao
Purposes
This study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant Acinetobacter baumannii (MDR-AB).
Methods
We used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays.
Results
Both POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL.
Conclusion
Nearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.
研究目的本研究确定了多粘菌素B(POLB)和秋水仙素(COL)与其他16种试验抗菌药物在抑制耐多药鲍曼不动杆菌(MDR-AB)方面的协同作用:我们采用棋盘试验确定了药物之间对浙江省某三级医院2019年50例临床MDR-AB的协同作用,将组合分为拮抗、独立、相加或协同。结果表明,POLB和COL对MDR-AB的疗效均优于POLB和COL:结果:当 POLB 和 COL 与这 16 种测试药物联合使用时,两者显示出相似的杀菌效果。只有少数菌株(2%)与 POLB 和头孢哌酮/舒巴坦(CSL)联合使用时出现拮抗作用。利福布丁(RFB;90%/96%)、利福平(RIF;60%/78%)和利福喷汀(RFP;56%/76%)与 POLB 和 COL 的协同作用比例较高。时间致死试验也证实了 POLB 和利福霉素类复方制剂的协同效应。1/2毫微克的利福霉素暴露与1/2毫微克的POLB或COL结合使用时,可达到清除细菌的效果:结论:通过棋盘试验和时间致死试验,多粘菌素与其他药物联合使用时几乎没有拮抗作用,这表明多粘菌素在联合治疗中可能有效。POLB/COL与RFB、RIF和RFP的组合显示出明显的协同作用,其中RFB的效果最好。
{"title":"Comparison of in vitro synergy between polymyxin B or colistin in combination with 16 antimicrobial agents against multidrug-resistant Acinetobacter baumannii isolates","authors":"Yuan Wang , Yingying Ma , Luying Xiong, Xueting Wang, Yanzi Zhou, Xiaohui Chi, Tao Chen, Hao Fu, Qixia Luo , Yonghong Xiao","doi":"10.1016/j.jmii.2024.01.009","DOIUrl":"10.1016/j.jmii.2024.01.009","url":null,"abstract":"<div><h3>Purposes</h3><p>This study determined the synergy of polymyxin B (POLB) and colistin (COL) with 16 other tested antimicrobial agents in the inhibition of multidrug-resistant <em>Acinetobacter baumannii</em> (MDR-AB).</p></div><div><h3>Methods</h3><p>We used chequerboard assays to determine synergy between the drugs against 50 clinical MDR-AB from a tertiary hospital in the Zhejiang province in 2019, classifying combinations as either antagonistic, independent, additive, or synergistic. The efficacy of hit combinations which showed highest synergistic rate were confirmed using time-kill assays.</p></div><div><h3>Results</h3><p>Both POLB and COL displayed similar bactericidal effects when used in combination with these 16 tested drugs. Antagonism was only observed for a few strains (2%) exposed to a combination of POLB and cefoperazone/sulbactam (CSL). A higher percentage of synergistic combinations with POLB and COL were observed with rifabutin (RFB; 90%/96%), rifampicin (RIF; 60%/78%) and rifapentine (RFP; 56%/76%). Time-kill assays also confirmed the synergistic effect of POLB and rifamycin class combinations. 1/2 MIC rifamycin exposure can achieve bacterial clearance when combined with 1/2 MIC POLB or COL.</p></div><div><h3>Conclusion</h3><p>Nearly no antagonism was observed when combining polymyxins with other drugs by both chequerboard and time-kill assays, suggesting that polymyxins may be effective in combination therapy. The combinations of POLB/COL with RFB, RIF, and RFP displayed neat synergy, with RFB showing the greatest effect.</p></div>","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 2","pages":"Pages 300-308"},"PeriodicalIF":7.4,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118224000367/pdfft?md5=a07244cdece736d734c2de539bed8277&pid=1-s2.0-S1684118224000367-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01DOI: 10.1016/j.jmii.2023.10.002
Ching-Yen Tsai , Guan-Jhou Chen , Chin-Shiang Tsai , Bo-Huang Liou , Chia-Jui Yang , Hung-Chin Tsai , Chi-Ying Lin , Sung-Hsi Huang , Kuan-Yin Lin , Ning-Chi Wang , Tun-Chieh Chen , Chen-Hsiang Lee , Chien-Ching Hung , Taiwan HIV Study Group
{"title":"Corrigendum to Evolution of estimated glomerular filtration rate in HIV/HCV-coinfected patients who received direct-acting antivirals: A multicenter retrospective study [J Microbiol Immunol Infect 56 (2023) 718–728]","authors":"Ching-Yen Tsai , Guan-Jhou Chen , Chin-Shiang Tsai , Bo-Huang Liou , Chia-Jui Yang , Hung-Chin Tsai , Chi-Ying Lin , Sung-Hsi Huang , Kuan-Yin Lin , Ning-Chi Wang , Tun-Chieh Chen , Chen-Hsiang Lee , Chien-Ching Hung , Taiwan HIV Study Group","doi":"10.1016/j.jmii.2023.10.002","DOIUrl":"10.1016/j.jmii.2023.10.002","url":null,"abstract":"","PeriodicalId":56117,"journal":{"name":"Journal of Microbiology Immunology and Infection","volume":"57 1","pages":"Pages 209-210"},"PeriodicalIF":7.4,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1684118223001937/pdfft?md5=6a8b974297578f511cf15a28d898e49e&pid=1-s2.0-S1684118223001937-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41221177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}