Einar Tollaksen Weme, Lin Thorstensen Brandal, Pål Arne Jenum, Astrid Louise Wester, Fredrik Müller
We aimed to estimate the prevalence of potentially diarrhoeagenic microbes (PDMs) in faecal samples from asymptomatic individuals in a high-income country, identify risk factors for carriage and to identify microbial factors that differ between PDMs in asymptomatic versus symptomatic individuals. Samples from 1000 asymptomatic participants were collected, together with a questionnaire, between 2015 and 2020 and examined by PCR for 11 PDMs. Isolates were characterised and potential risk factors were registered. Atypical enteropathogenic Escherichia coli (aEPEC), Yersinia enterocolitica, Shiga toxin-producing E. coli (STEC), enterotoxigenic E. coli (ETEC) and Campylobacter spp. were found in 163 (16%), 20 (2.0%), 17 (1.7%), 12 (1.2%) and 11 (1.1%) asymptomatic individuals, respectively. Other PDMs were rare. Only low virulent STEC, with stx1c, stx2b or stx2f, was detected. Travels outside Europe was a significant risk factor for detecting Campylobacter spp. (odds ratio (OR) 6.99; 95% CI 1.12–43.6) and ETEC (OR 11.4; 95% CI 1.26–102). Individuals ≥65 years of age had lower odds of carrying STEC (OR 0.11; 95% CI 0.02–0.57) or EPEC (OR 0.09; 95% CI 0.05–0.16) than individuals ≤5 years of age. The common finding of PDMs in asymptomatic individuals could have implications for the interpretation of positive findings in clinical samples and infection control measures.
我们的目的是估算高收入国家无症状人群粪便样本中潜在致泻微生物(PDMs)的流行率,确定携带的风险因素,并找出无症状人群与有症状人群中 PDMs 不同的微生物因素。研究人员在 2015 年至 2020 年期间收集了 1000 名无症状参与者的样本和调查问卷,并通过 PCR 检测了 11 种 PDM。对分离菌进行了定性,并登记了潜在的风险因素。在163名(16%)、20名(2.0%)、17名(1.7%)、12名(1.2%)和11名(1.1%)无症状者中分别发现了非典型肠致病性大肠杆菌(aEPEC)、小肠结肠耶尔森菌、产志贺毒素大肠杆菌(STEC)、肠毒性大肠杆菌(ETEC)和弯曲杆菌属。其他病原微生物很少见。只检出了stx1c、stx2b或stx2f型低毒性STEC。欧洲以外的旅行是检出弯曲杆菌属(几率比(OR)6.99;95% CI 1.12-43.6)和 ETEC(OR 11.4;95% CI 1.26-102)的重要风险因素。年龄≥65 岁者携带 STEC(OR 0.11;95% CI 0.02-0.57)或 EPEC(OR 0.09;95% CI 0.05-0.16)的几率低于年龄≤5 岁者。在无症状者中发现 PDMs 的情况很常见,这可能会对临床样本中阳性结果的解释和感染控制措施产生影响。
{"title":"Prevalence and characteristics of 11 potentially diarrhoeagenic microbes in asymptomatic individuals in Norway, 2015–2020","authors":"Einar Tollaksen Weme, Lin Thorstensen Brandal, Pål Arne Jenum, Astrid Louise Wester, Fredrik Müller","doi":"10.1111/apm.13478","DOIUrl":"10.1111/apm.13478","url":null,"abstract":"<p>We aimed to estimate the prevalence of potentially diarrhoeagenic microbes (PDMs) in faecal samples from asymptomatic individuals in a high-income country, identify risk factors for carriage and to identify microbial factors that differ between PDMs in asymptomatic versus symptomatic individuals. Samples from 1000 asymptomatic participants were collected, together with a questionnaire, between 2015 and 2020 and examined by PCR for 11 PDMs. Isolates were characterised and potential risk factors were registered. Atypical enteropathogenic <i>Escherichia coli</i> (aEPEC), <i>Yersinia enterocolitica</i>, Shiga toxin-producing <i>E. coli</i> (STEC), enterotoxigenic <i>E. coli</i> (ETEC) and <i>Campylobacter</i> spp. were found in 163 (16%), 20 (2.0%), 17 (1.7%), 12 (1.2%) and 11 (1.1%) asymptomatic individuals, respectively. Other PDMs were rare. Only low virulent STEC, with <i>stx1c</i>, <i>stx2b</i> or <i>stx2f</i>, was detected. Travels outside Europe was a significant risk factor for detecting <i>Campylobacter</i> spp. (odds ratio (OR) 6.99; 95% CI 1.12–43.6) and ETEC (OR 11.4; 95% CI 1.26–102). Individuals ≥65 years of age had lower odds of carrying STEC (OR 0.11; 95% CI 0.02–0.57) or EPEC (OR 0.09; 95% CI 0.05–0.16) than individuals ≤5 years of age. The common finding of PDMs in asymptomatic individuals could have implications for the interpretation of positive findings in clinical samples and infection control measures.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"797-806"},"PeriodicalIF":2.2,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandrine Moussa, Paul Alain Tagnouokam-Ngoupo, Fabienne Tombette, Alexandre Manirakiza, Yap Boum II, Guy Vernet, Richard Njouom, Laurent Belec, Jean-Christophe Plantier, Anfumbom Kfutwah
The Central African Republic (CAR) is characterized by widespread HIV epidemic with notable prevalence and genetic diversity. We herein analysed the genetic diversity of atypical non-M HIV-1 strains. In-house serotyping assays for variants of HIV-1 (M, N, O, P) and HIV-2 were used to test a biological collection of 6092 HIV-seropositive blood samples collected between 2003 and 2014 at the Institut Pasteur de Bangui. Samples indicative of recombinant M/O groups, HIV-2, or those that yield doubtful/negative results underwent further PCR tests and sequencing. We found six atypical HIV strains: specifically, three (0.05%) HIV-1 group O strains (subtype H) detected in samples from 2005, 2008 and 2009, alongside three (0.05%) HIV-2 strains (two group A and one group B) identified in samples from 2007 and 2009. HIV-1/O strains showed a genetic link to Cameroon and Gabon strains. This study highlights the dominance of HIV-1/M in the CAR's HIV epidemic over time and underscores the infrequent occurrence of HIV-1 group O and HIV-2 strains. These findings validate the efficacy of WHO-recommended HIV testing protocols and emphasize the need for adaptive surveillance and management strategies to confront the complexities introduced by the genetic diversity of HIV strains.
中非共和国(CAR)艾滋病疫情广泛,流行率和遗传多样性显著。我们在此分析了非典型非 M 型 HIV-1 株系的遗传多样性。我们使用内部 HIV-1(M、N、O、P)和 HIV-2 变体血清分型检测法,对班吉巴斯德研究所 2003 年至 2014 年间收集的 6092 份 HIV 血清阳性血样进行了生物检测。对表明存在重组 M/O 组、HIV-2 的样本或结果可疑/阴性的样本进行了进一步的 PCR 检测和测序。我们发现了六种非典型艾滋病毒菌株:特别是在 2005 年、2008 年和 2009 年的样本中发现了三种(0.05%)O 型艾滋病毒-1 株(H 亚型),以及在 2007 年和 2009 年的样本中发现的三种(0.05%)艾滋病毒-2 株(两种 A 型和一种 B 型)。HIV-1/O 株系与喀麦隆和加蓬株系存在遗传联系。这项研究突出表明,随着时间的推移,HIV-1/M 在中非共和国的艾滋病毒流行中占主导地位,并强调了 HIV-1 O 组和 HIV-2 株系的不常出现。这些研究结果验证了世界卫生组织推荐的艾滋病毒检测方案的有效性,并强调有必要制定适应性监测和管理策略,以应对艾滋病毒菌株基因多样性带来的复杂问题。
{"title":"Detection and characterization of HIV-1 group O and HIV-2 in the Central African Republic","authors":"Sandrine Moussa, Paul Alain Tagnouokam-Ngoupo, Fabienne Tombette, Alexandre Manirakiza, Yap Boum II, Guy Vernet, Richard Njouom, Laurent Belec, Jean-Christophe Plantier, Anfumbom Kfutwah","doi":"10.1111/apm.13474","DOIUrl":"10.1111/apm.13474","url":null,"abstract":"<p>The Central African Republic (CAR) is characterized by widespread HIV epidemic with notable prevalence and genetic diversity. We herein analysed the genetic diversity of atypical non-M HIV-1 strains. In-house serotyping assays for variants of HIV-1 (M, N, O, P) and HIV-2 were used to test a biological collection of 6092 HIV-seropositive blood samples collected between 2003 and 2014 at the Institut Pasteur de Bangui. Samples indicative of recombinant M/O groups, HIV-2, or those that yield doubtful/negative results underwent further PCR tests and sequencing. We found six atypical HIV strains: specifically, three (0.05%) HIV-1 group O strains (subtype H) detected in samples from 2005, 2008 and 2009, alongside three (0.05%) HIV-2 strains (two group A and one group B) identified in samples from 2007 and 2009. HIV-1/O strains showed a genetic link to Cameroon and Gabon strains. This study highlights the dominance of HIV-1/M in the CAR's HIV epidemic over time and underscores the infrequent occurrence of HIV-1 group O and HIV-2 strains. These findings validate the efficacy of WHO-recommended HIV testing protocols and emphasize the need for adaptive surveillance and management strategies to confront the complexities introduced by the genetic diversity of HIV strains.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"824-831"},"PeriodicalIF":2.2,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mads H. Christensen, Tim H. Jakobsen, Mads Lichtenberg, Frederik B. Hertz, Benny Dahl, Thomas Bjarnsholt
The rise in osteomyelitis and periprosthetic joint infections, in combination with increasing life expectancy and the prevalence of diabetes, underscores the urgent need for rapid and accurate diagnostic tools. Conventional culture-based methods are often time-consuming and prone to false-negatives, leading to prolonged and inappropriate antibiotic treatments. This study aims to improve osteomyelitis diagnostics by decreasing the time to detection and the time to an antibiotic susceptibility result to enable a targeted treatment using isothermal microcalorimetry (IMC). IMC measures heat flow in real-time, providing insights into bacterial metabolism without the need for labeling. Using clinical isolates from bone infections, assessing their response to antibiotics through IMC, we demonstrated that IMC could detect bacteria within 4 h and determine antimicrobial susceptibility profiles within 2–22 h (median 4.85, range 1.28–21.78). This is significantly faster than traditional methods. A decision tree, based on antibiotic susceptibility, accurately categorized pathogens, achieving high accuracy (74–100%), sensitivity (100%), and specificity (65–100%). These findings suggest that IMC could redefine diagnostics of bone and joint infections and potentially infections in general, offering timely and precise treatment guidance, thereby improving patient outcomes and reducing health care burdens. Further optimization and clinical validation are needed to fully integrate IMC into routine diagnostics.
{"title":"Antimicrobial susceptibility testing of bone and joint pathogens using isothermal microcalorimetry","authors":"Mads H. Christensen, Tim H. Jakobsen, Mads Lichtenberg, Frederik B. Hertz, Benny Dahl, Thomas Bjarnsholt","doi":"10.1111/apm.13470","DOIUrl":"10.1111/apm.13470","url":null,"abstract":"<p>The rise in osteomyelitis and periprosthetic joint infections, in combination with increasing life expectancy and the prevalence of diabetes, underscores the urgent need for rapid and accurate diagnostic tools. Conventional culture-based methods are often time-consuming and prone to false-negatives, leading to prolonged and inappropriate antibiotic treatments. This study aims to improve osteomyelitis diagnostics by decreasing the time to detection and the time to an antibiotic susceptibility result to enable a targeted treatment using isothermal microcalorimetry (IMC). IMC measures heat flow in real-time, providing insights into bacterial metabolism without the need for labeling. Using clinical isolates from bone infections, assessing their response to antibiotics through IMC, we demonstrated that IMC could detect bacteria within 4 h and determine antimicrobial susceptibility profiles within 2–22 h (median 4.85, range 1.28–21.78). This is significantly faster than traditional methods. A decision tree, based on antibiotic susceptibility, accurately categorized pathogens, achieving high accuracy (74–100%), sensitivity (100%), and specificity (65–100%). These findings suggest that IMC could redefine diagnostics of bone and joint infections and potentially infections in general, offering timely and precise treatment guidance, thereby improving patient outcomes and reducing health care burdens. Further optimization and clinical validation are needed to fully integrate IMC into routine diagnostics.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"814-823"},"PeriodicalIF":2.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
António Melo-Ferraz, Paulo Miller, Maria Begoña Criado, Maria Céu Monteiro, Cristina Coelho
This study investigates the antimicrobial properties of leukocyte- and platelet-rich fibrin (L-PRF) against Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 90028). Infections can hinder wound healing posing challenges. L-PRF's potential for regeneration and antimicrobial action has been studied. Considering the increasing concern about antibiotic resistance, assessing the antimicrobial properties of L-PRF provides valuable insights into its potential as a therapeutic agent in postoperative infections. Twenty volunteers were enrolled in the study, following ethical guidelines, and obtaining informed consent. Blood samples were collected and L-PRF was prepared. Microbial suspensions were prepared, and susceptibility testing was performed using the Kirby-Bauer agar diffusion method. The study revealed significant heterogeneity in the susceptibility to L-PRF. All L-PRF membrane samples exhibited antimicrobial activity against P. aeruginosa, with inhibition zones of 13 mm ± 3.85 SD. Enterococcus faecalis displayed inhibition diameter of 7.25 mm ± 5.15 SD. Candida albicans susceptibility to L-PRF varied among samples, with both inhibitory and non-inhibitory results. Results showed varying degrees of antimicrobial activity, particularly against P. aeruginosa, and highlight the complexity of the L-PRF-microorganism interaction. Further investigations are needed to elucidate the clinical implications and optimize the use of L-PRF.
{"title":"Exploring the antimicrobial potential of Leukocyte- and Platelet-Rich Fibrin – an in vitro study","authors":"António Melo-Ferraz, Paulo Miller, Maria Begoña Criado, Maria Céu Monteiro, Cristina Coelho","doi":"10.1111/apm.13468","DOIUrl":"10.1111/apm.13468","url":null,"abstract":"<p>This study investigates the antimicrobial properties of leukocyte- and platelet-rich fibrin (L-PRF) against <i>Enterococcus faecalis</i> (ATCC 29212), <i>Pseudomonas aeruginosa</i> (ATCC 27853), and <i>Candida albicans</i> (ATCC 90028). Infections can hinder wound healing posing challenges. L-PRF's potential for regeneration and antimicrobial action has been studied. Considering the increasing concern about antibiotic resistance, assessing the antimicrobial properties of L-PRF provides valuable insights into its potential as a therapeutic agent in postoperative infections. Twenty volunteers were enrolled in the study, following ethical guidelines, and obtaining informed consent. Blood samples were collected and L-PRF was prepared. Microbial suspensions were prepared, and susceptibility testing was performed using the Kirby-Bauer agar diffusion method. The study revealed significant heterogeneity in the susceptibility to L-PRF. All L-PRF membrane samples exhibited antimicrobial activity against <i>P. aeruginosa</i>, with inhibition zones of 13 mm ± 3.85 SD. <i>Enterococcus faecalis</i> displayed inhibition diameter of 7.25 mm ± 5.15 SD. <i>Candida albicans</i> susceptibility to L-PRF varied among samples, with both inhibitory and non-inhibitory results. Results showed varying degrees of antimicrobial activity, particularly against <i>P. aeruginosa,</i> and highlight the complexity of the L-PRF-microorganism interaction. Further investigations are needed to elucidate the clinical implications and optimize the use of L-PRF.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"859-868"},"PeriodicalIF":2.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristian Stærk, Christoffer Vogsen Heidtmann, Janni Søvsø Hjelmager, Jesper Dupont Ewald, Carsten Uhd Nielsen, Poul Nielsen, Thomas Emil Andersen
The purpose of this study was to establish a porcine model of urinary tract infection (UTI) with gram-positive uropathogens. Ten female domestic pigs were experimentally inoculated with human UTI isolates of Enterococcus faecalis (n = 3), Staphylococcus saprophyticus (n = 3), or Staphylococcus aureus (n = 4) and followed with regular urine samples. Bladders and kidneys were aseptically removed at termination (5–7 days post infection) and assessed by gross pathology and bacterial enumeration. Enterococcus faecalis (n = 3 of 3) and S. aureus (n = 2 of 4) successfully colonized the pig bladders. Inoculation with S. saprophyticus never resulted in detectable bacteriuria. All infected pigs had cleared the infection spontaneously before termination. Surprisingly, three (of four) pigs inoculated with S. aureus led to spontaneous infection with opportunistic pathogens. Also, one pig colonized with E. faecalis resulted in spontaneous infection with E. coli. In conlusion, the pig supports experimental UTI with E. faecalis for up to 24 h but not prolonged infection. S. aureus and S. saprophyticus fails to cause UTI in pigs and other animals should be considered for studying these pathogens.
{"title":"The infectious capacity of Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus saprophyticus in a porcine model of urinary tract infection","authors":"Kristian Stærk, Christoffer Vogsen Heidtmann, Janni Søvsø Hjelmager, Jesper Dupont Ewald, Carsten Uhd Nielsen, Poul Nielsen, Thomas Emil Andersen","doi":"10.1111/apm.13469","DOIUrl":"10.1111/apm.13469","url":null,"abstract":"<p>The purpose of this study was to establish a porcine model of urinary tract infection (UTI) with gram-positive uropathogens. Ten female domestic pigs were experimentally inoculated with human UTI isolates of <i>Enterococcus faecalis</i> (n = 3), <i>Staphylococcus saprophyticus</i> (n = 3), or S<i>taphylococcus aureus</i> (n = 4) and followed with regular urine samples. Bladders and kidneys were aseptically removed at termination (5–7 days post infection) and assessed by gross pathology and bacterial enumeration. <i>Enterococcus faecalis</i> (n = 3 of 3) and <i>S</i>. <i>aureus</i> (n = 2 of 4) successfully colonized the pig bladders. Inoculation with <i>S</i>. <i>saprophyticus</i> never resulted in detectable bacteriuria. All infected pigs had cleared the infection spontaneously before termination. Surprisingly, three (of four) pigs inoculated with <i>S</i>. <i>aureus</i> led to spontaneous infection with opportunistic pathogens. Also, one pig colonized with <i>E</i>. <i>faecalis</i> resulted in spontaneous infection with <i>E</i>. <i>coli</i>. In conlusion, the pig supports experimental UTI with <i>E</i>. <i>faecalis</i> for up to 24 h but not prolonged infection. <i>S</i>. <i>aureus</i> and <i>S</i>. <i>saprophyticus</i> fails to cause UTI in pigs and other animals should be considered for studying these pathogens.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"807-813"},"PeriodicalIF":2.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Several microbiome studies have recently demonstrated microbial dysbiosis in various chronic inflammatory skin diseases, and it is considered an important role in the pathogenesis. Although the role of skin dysbiosis in inflammatory skin diseases is debatable, the local microenvironment is considered essential concerning compositional changes and functional alterations of the skin microbiota. Indeed, various local nutrients (e.g., lipids), pH values, water, oxygen, and antimicrobial peptides may affect the level of skin dysbiosis in these skin diseases. In particular, in atopic dermatitis and hidradenitis suppurativa, significant changes in skin dysbiosis have been associated with local aberrant host immune changes. In this review, the potential pathogenic crosstalk between the host and the microbiota is reviewed in relation to the physical, chemical, and biological microenvironments of various chronic inflammatory skin diseases.
{"title":"Microenvironmental host–microbe interactions in chronic inflammatory skin diseases","authors":"Lene Bay, Gregor Borut Jemec, Hans Christian Ring","doi":"10.1111/apm.13464","DOIUrl":"10.1111/apm.13464","url":null,"abstract":"<p>Several microbiome studies have recently demonstrated microbial dysbiosis in various chronic inflammatory skin diseases, and it is considered an important role in the pathogenesis. Although the role of skin dysbiosis in inflammatory skin diseases is debatable, the local microenvironment is considered essential concerning compositional changes and functional alterations of the skin microbiota. Indeed, various local nutrients (e.g., lipids), pH values, water, oxygen, and antimicrobial peptides may affect the level of skin dysbiosis in these skin diseases. In particular, in atopic dermatitis and hidradenitis suppurativa, significant changes in skin dysbiosis have been associated with local aberrant host immune changes. In this review, the potential pathogenic crosstalk between the host and the microbiota is reviewed in relation to the physical, chemical, and biological microenvironments of various chronic inflammatory skin diseases.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"974-984"},"PeriodicalIF":2.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erkki-Ville Wirta, Hanna Elomaa, Maarit Ahtiainen, Marja Hyöty, Toni T. Seppälä, Teijo Kuopio, Jan Böhm, Jukka-Pekka Mecklin, Juha P. Väyrynen
To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell–T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.
{"title":"The impact of preoperative treatments on the immune environment of rectal cancer","authors":"Erkki-Ville Wirta, Hanna Elomaa, Maarit Ahtiainen, Marja Hyöty, Toni T. Seppälä, Teijo Kuopio, Jan Böhm, Jukka-Pekka Mecklin, Juha P. Väyrynen","doi":"10.1111/apm.13467","DOIUrl":"10.1111/apm.13467","url":null,"abstract":"<p>To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell–T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 12","pages":"1046-1060"},"PeriodicalIF":2.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.13467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vaijayanthi Saravanan, Vinoj Gopalakrishnan, Maria Infant Majula Shifani Mahendran, Rajan Vaithianathan, Sowmya Srinivasan, Vinoth Boopathy, SriKrishna Krishnamurthy
Bacterial biofilm plays a vital role in influencing several diseases, infections, metabolic pathways and communication channels. Biofilm influence over colorectal cancer (CRC) has been a booming area of research interest. The virulence factors of bacterial pathogen have a high tendency to induce metabolic pathway to accelerate CRC. The bacterial species biofilm may induce cancer through regulating the major signalling pathways responsible for cell proliferation, differentiation, survival and growth. Activation of cancer signals may get initiated from the chronic infections through bacterial biofilm species. Integrin mediates in the activation of major pathway promoting cancer. Integrin-mediated signals are expected to be greatly influenced by biofilm. Integrins are identified as an important dimer, whose dysfunction may alter the signalling cascade specially focusing on TGF-β, PI3K/Akt/mToR, MAPK and Wnt pathway. Along with biofilm shield, the tumour gains greater resistance from radiation, chemotherapy and also from other antibiotics. The biofilm barrier is known to cause challenges for CRC patients undergoing treatment.
{"title":"Biofilm mediated integrin activation and directing acceleration of colorectal cancer","authors":"Vaijayanthi Saravanan, Vinoj Gopalakrishnan, Maria Infant Majula Shifani Mahendran, Rajan Vaithianathan, Sowmya Srinivasan, Vinoth Boopathy, SriKrishna Krishnamurthy","doi":"10.1111/apm.13466","DOIUrl":"10.1111/apm.13466","url":null,"abstract":"<p>Bacterial biofilm plays a vital role in influencing several diseases, infections, metabolic pathways and communication channels. Biofilm influence over colorectal cancer (CRC) has been a booming area of research interest. The virulence factors of bacterial pathogen have a high tendency to induce metabolic pathway to accelerate CRC. The bacterial species biofilm may induce cancer through regulating the major signalling pathways responsible for cell proliferation, differentiation, survival and growth. Activation of cancer signals may get initiated from the chronic infections through bacterial biofilm species. Integrin mediates in the activation of major pathway promoting cancer. Integrin-mediated signals are expected to be greatly influenced by biofilm. Integrins are identified as an important dimer, whose dysfunction may alter the signalling cascade specially focusing on TGF-β, PI3K/Akt/mToR, MAPK and Wnt pathway. Along with biofilm shield, the tumour gains greater resistance from radiation, chemotherapy and also from other antibiotics. The biofilm barrier is known to cause challenges for CRC patients undergoing treatment.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 10","pages":"688-705"},"PeriodicalIF":2.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BamA, an Omp85 superfamily member, is universally conserved and essential for cell viability. Using anti-Oma87 antibodies, we focus on understanding the effect of Oma87 of Acinetobacter baumannii on pathogenicity. Oma87 was expressed, purified, and used to induce anti-Oma87 antibodies in BALB/c mice. Acute toxicity of the protein was evaluated in mice. HeLa cells were infected with both live and killed A. baumannii 19606 and a clinical isolate. The effects of anti-Oma87 sera on A. baumannii adherence, internalization, and proliferation in HeLa cells were studied. The roles of microfilaments and microtubules in A. baumannii invasion were demonstrated by Actin disruption. Reduced bacterial population and biofilm formation were noted. The ability of A. baumannii to provoke autophagy through Oma87 induction leads to incomplete autophagy and potentially facilitates bacterial replication. Actin-mediated uptake, attachment, and invasion demonstrated A. baumannii survival and multiplication within vacuoles in the host cell. The findings underscore the potential of Oma87 as a therapeutic intervention target in infections caused by A. baumannii. This comprehensive analysis contributes valuable information for understanding the virulence mechanisms of A. baumannii, potentially guiding future strategies to combat infections caused by this pathogen.
{"title":"Modulation with anti-Oma87 antibodies of cytotoxicity, adherence, and internalization of Acinetobacter baumannii in human cervical carcinoma epithelial cells","authors":"Zahra Panji, Mohammadreza Jalali Nadoushan, Zahra Fekrirad, Iraj Rasooli","doi":"10.1111/apm.13465","DOIUrl":"10.1111/apm.13465","url":null,"abstract":"<p>BamA, an Omp85 superfamily member, is universally conserved and essential for cell viability. Using anti-Oma87 antibodies, we focus on understanding the effect of Oma87 of <i>Acinetobacter baumannii</i> on pathogenicity. Oma87 was expressed, purified, and used to induce anti-Oma87 antibodies in BALB/c mice. Acute toxicity of the protein was evaluated in mice. HeLa cells were infected with both live and killed <i>A. baumannii</i> 19606 and a clinical isolate. The effects of anti-Oma87 sera on <i>A. baumannii</i> adherence, internalization, and proliferation in HeLa cells were studied. The roles of microfilaments and microtubules in <i>A. baumannii</i> invasion were demonstrated by Actin disruption. Reduced bacterial population and biofilm formation were noted. The ability of <i>A. baumannii</i> to provoke autophagy through Oma87 induction leads to incomplete autophagy and potentially facilitates bacterial replication. Actin-mediated uptake, attachment, and invasion demonstrated <i>A. baumannii</i> survival and multiplication within vacuoles in the host cell. The findings underscore the potential of Oma87 as a therapeutic intervention target in infections caused by <i>A. baumannii</i>. This comprehensive analysis contributes valuable information for understanding the virulence mechanisms of <i>A. baumannii</i>, potentially guiding future strategies to combat infections caused by this pathogen.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"843-858"},"PeriodicalIF":2.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Several investigations have been carried out to explore the genetic association of TLR4 codon variants, specifically Asp299Gly and Thr399Ile, and susceptibility to sepsis, but the results have been contradictory. The present study aimed to conduct a meta-analysis to draw a definitive conclusion regarding the role of TLR4 genetic variants (Asp299Gly and Thr399Ile) in sepsis. A thorough literature search was conducted using the PubMed, Scopus, and Science Direct databases. The inclusion and exclusion criteria were established to ensure the accuracy of the data. The Comprehensive Meta-Analysis Software v4 was utilized to perform the meta-analysis and related analyses. A total of 13 studies were analyzed, including 2328 sepsis cases and 2495 healthy controls for the TLR4 Asp299Gly variant. Eight studies provided genotype data for the rs4986791 polymorphism. The Asp299Gly variant showed a marginal protective effect in the allele (p = 0.08, odds ratio = 0.71) and dominant (p = 0.09, odds ratio = 0.71) genetic models, although it was not statistically significant. The trial sequential analysis indicated that further case–control studies are necessary to draw definitive conclusions about the TLR4 polymorphisms in sepsis. The TLR4 Asp299Gly variant may have a protective effect against sepsis. However, additional research with larger sample sizes across diverse populations is required to validate this finding.
{"title":"Association of TLR4 polymorphisms (Asp299Gly and Thr399Ile) with sepsis: a meta-analysis and trial sequence analysis","authors":"Jingjing Mu, Yue Shen, Furong Zhu, Qixia Zhang","doi":"10.1111/apm.13463","DOIUrl":"10.1111/apm.13463","url":null,"abstract":"<p>Several investigations have been carried out to explore the genetic association of TLR4 codon variants, specifically Asp299Gly and Thr399Ile, and susceptibility to sepsis, but the results have been contradictory. The present study aimed to conduct a meta-analysis to draw a definitive conclusion regarding the role of TLR4 genetic variants (Asp299Gly and Thr399Ile) in sepsis. A thorough literature search was conducted using the PubMed, Scopus, and Science Direct databases. The inclusion and exclusion criteria were established to ensure the accuracy of the data. The Comprehensive Meta-Analysis Software v4 was utilized to perform the meta-analysis and related analyses. A total of 13 studies were analyzed, including 2328 sepsis cases and 2495 healthy controls for the TLR4 Asp299Gly variant. Eight studies provided genotype data for the rs4986791 polymorphism. The Asp299Gly variant showed a marginal protective effect in the allele (p = 0.08, odds ratio = 0.71) and dominant (p = 0.09, odds ratio = 0.71) genetic models, although it was not statistically significant. The trial sequential analysis indicated that further case–control studies are necessary to draw definitive conclusions about the TLR4 polymorphisms in sepsis. The TLR4 Asp299Gly variant may have a protective effect against sepsis. However, additional research with larger sample sizes across diverse populations is required to validate this finding.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"132 11","pages":"869-880"},"PeriodicalIF":2.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}