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Alternating magnetic fields (AMF) and linezolid reduce Staphylococcus aureus biofilm in a large animal implant model
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-13 DOI: 10.1016/j.jinf.2024.106271

Objectives

We aimed to evaluate the effectiveness of alternating magnetic fields (AMF) combined with antibiotics in reducing Staphylococcus aureus biofilm on metal implants in a large animal model, compared to antibiotics alone.

Methods

Metal plates were inoculated with a clinical MRSA strain and then implanted into thirty-three ewes divided into three groups: positive control, linezolid only, and a combination of linezolid and AMF. Animals had either titanium or cobalt-chrome plates and were sacrificed at 5 or 21 days post-implantation. Blood and tissue samples were collected at various time points post-AMF treatment.

Results

In vivo efficacy studies demonstrated significant biofilm reduction on titanium and cobalt-chrome implants with AMF-linezolid combination treatment compared to controls. Significant bacterial reductions were also observed in surrounding tissues and bones. Cytokine analysis showed improved inflammatory responses with combination therapy, and histopathology confirmed reduced inflammation, necrosis, and bacterial presence, especially at 5 days post-implantation.

Conclusions

This study demonstrates that combining AMF with antibiotics significantly reduces biofilm-associated infections on metal implants in a large animal model. Numerical simulations confirmed targeted heating, and in vivo results showed substantial bacterial load reduction and reduced inflammatory response. These findings support the potential of AMF as a non-invasive treatment for prosthetic joint infections.

方法在金属板上接种临床 MRSA 菌株,然后将其植入 33 只母羊体内,分为三组:阳性对照组、仅利奈唑胺组以及利奈唑胺和 AMF 组合组。植入钛板或钴铬板的动物在植入后 5 天或 21 天时被处死。结果体内疗效研究表明,与对照组相比,AMF-利奈唑胺联合治疗可显著减少钛和钴铬植入物上的生物膜。周围组织和骨骼中的细菌也明显减少。细胞因子分析表明,联合疗法改善了炎症反应,组织病理学证实炎症、坏死和细菌存在减少,尤其是在植入后 5 天。数值模拟证实了有针对性的加热,体内结果显示细菌负荷大幅减少,炎症反应也有所减轻。这些发现支持了 AMF 作为一种非侵入性治疗方法治疗假体关节感染的潜力。
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引用次数: 0
The recent rapid rise in pertussis in Chaoyang District, Beijing: Improved recognition and diagnostic capabilities
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-13 DOI: 10.1016/j.jinf.2024.106272
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引用次数: 0
Corrigendum to “The relative vaccine effectiveness of high-dose vs standard-dose influenza vaccines in preventing hospitalization and mortality: A meta-analysis of evidence from randomized trials” [J Infect 89 (2024) 106187] 高剂量与标准剂量流感疫苗在预防住院和死亡方面的相对疫苗效力:来自随机试验证据的荟萃分析" [J Infect 89 (2024) 106187] 的更正
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-12 DOI: 10.1016/j.jinf.2024.106270
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引用次数: 0
Chatbots are just as good as professors in both factual recall and clinical scenario analysis: Emergence of a new tool in clinical microbiology and infectious disease
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-12 DOI: 10.1016/j.jinf.2024.106274
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引用次数: 0
Microbiology and outcomes of tubo-ovarian abscesses: A 5-year cohort of 105 cases 输卵管卵巢脓肿的微生物学和治疗效果:105 个病例的 5 年队列
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-10 DOI: 10.1016/j.jinf.2024.106253
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引用次数: 0
Machine learning to attribute the source of Campylobacter infections in the United States: A retrospective analysis of national surveillance data 通过机器学习确定美国弯曲杆菌感染来源:对国家监测数据的回顾性分析。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-07 DOI: 10.1016/j.jinf.2024.106265

Objectives

Integrating pathogen genomic surveillance with bioinformatics can enhance public health responses by identifying risk and guiding interventions. This study focusses on the two predominant Campylobacter species, which are commonly found in the gut of birds and mammals and often infect humans via contaminated food. Rising incidence and antimicrobial resistance (AMR) are a global concern, and there is an urgent need to quantify the main routes to human infection.

Methods

During routine US national surveillance (2009–2019), 8856 Campylobacter genomes from human infections and 16,703 from possible sources were sequenced. Using machine learning and probabilistic models, we target genetic variation associated with host adaptation to attribute the source of human infections and estimate the importance of different disease reservoirs.

Results

Poultry was identified as the primary source of human infections, responsible for an estimated 68% of cases, followed by cattle (28%), and only a small contribution from wild birds (3%) and pork sources (1%). There was also evidence of an increase in multidrug resistance, particularly among isolates attributed to chickens.

Conclusions

National surveillance and source attribution can guide policy, and our study suggests that interventions targeting poultry will yield the greatest reductions in campylobacteriosis and spread of AMR in the US.

Data availability

All sequence reads were uploaded and shared on NCBI’s Sequence Read Archive (SRA) associated with BioProjects; PRJNA239251 (CDC / PulseNet surveillance), PRJNA287430 (FSIS surveillance), PRJNA292668 & PRJNA292664 (NARMS) and PRJNA258022 (FDA surveillance). Publicly available genomes, including reference genomes and isolates sampled worldwide from wild birds are associated with BioProject accessions: PRJNA176480, PRJNA177352, PRJNA342755, PRJNA345429, PRJNA312235, PRJNA415188, PRJNA524300, PRJNA528879, PRJNA529798, PRJNA575343, PRJNA524315 and PRJNA689604. Contiguous assemblies of all genome sequences compared are available at Mendeley data (assembled C. coli genomes doi: 10.17632/gxswjvxyh3.1; assembled C. jejuni genomes doi: 10.17632/6ngsz3dtbd.1) and individual project and accession numbers can be found in Supplementary tables S1 and S2, which also includes pubMLST identifiers for assembled genomes. Figshare (10.6084/m9.figshare.20279928). Interactive phylogenies are hosted on microreact separately for C. jejuni (https://microreact.org/project/pascoe-us-cjejuni) and C. coli (https://microreact.org/project/pascoe-us-ccoli).

目的:将病原体基因组监测与生物信息学相结合,可以通过识别风险和指导干预措施来加强公共卫生应对措施。本研究的重点是两种主要的弯曲杆菌,它们通常存在于鸟类和哺乳动物的肠道中,并经常通过受污染的食物感染人类。发病率上升和抗菌药耐药性(AMR)是全球关注的问题,因此迫切需要量化人类感染的主要途径:方法:在美国国家例行监测期间(2009-2019 年),对来自人类感染的 8856 个弯曲杆菌基因组和来自可能来源的 16703 个弯曲杆菌基因组进行了测序。利用机器学习和概率模型,我们锁定了与宿主适应性相关的基因变异,以确定人类感染的来源,并估计不同疾病储库的重要性:结果:家禽被确定为人类感染的主要来源,估计占病例的 68%,其次是牛(28%),野鸟(3%)和猪肉来源(1%)只占很小比例。还有证据表明,耐多药的情况有所增加,尤其是在鸡的分离物中:我们的研究表明,针对家禽的干预措施将在最大程度上减少美国的弯曲杆菌病和 AMR 传播:所有序列读数都已上传并共享到与 BioProjects 相关的 NCBI 序列读数档案 (SRA);PRJNA239251(CDC / PulseNet 监测)、PRJNA287430(FSIS 监测)、PRJNA292668 和 PRJNA292664(NARMS)以及 PRJNA258022(FDA 监测)。公开的基因组,包括参考基因组和从全球野生鸟类中采样的分离物,都与 BioProject 项目的登录相关联:PRJNA176480、PRJNA177352、PRJNA342755、PRJNA345429、PRJNA312235、PRJNA415188、PRJNA524300、PRJNA528879、PRJNA529798、PRJNA575343、PRJNA524315 和 PRJNA689604。比较的所有基因组序列的连续组装结果可在 Mendeley data(组装的大肠杆菌基因组 doi:10.17632/gxswjvxyh3.1;组装的空肠杆菌基因组 doi:10.17632/6ngsz3dtbd.1)中找到,单个项目和登录号可在补充表 S1 和 S2 中找到,其中还包括组装基因组的 pubMLST 标识符。Figshare (10.6084/m9.figshare.20279928).空肠大肠杆菌 (https://microreact.org/project/pascoe-us-cjejuni) 和大肠杆菌 (https://microreact.org/project/pascoe-us-ccoli) 的交互式系统发生分别托管在 microreact 上。
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引用次数: 0
Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: insights from prospectively collected data in the BRACE trial. COVID-19 和其他呼吸道疾病的前驱症状和持续症状:从 BRACE 试验的前瞻性数据中获得的启示。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-06 DOI: 10.1016/j.jinf.2024.106267
Ellie McDonald, Laure F Pittet, Simone E Barry, Marc Bonten, John Campbell, Julio Croda, Mariana G Croda, Margareth Pretti Dalcolmo, Andrew Davidson, Fernando F de Almeida E Val, Ms Glauce Dos Santos, Ms Kaya Gardiner, Ms Grace Gell, Amanda Gwee, Ms Ann Krastev, Marcus Vinícius Guimaraes Lacerda, Michaela Lucas, David J Lynn, Laurens Manning, Mr Nick McPhate, Kirsten P Perrett, Jeffrey J Post, Cristina Prat-Aymerich, Ms Lynne E Quinn, Peter C Richmond, Nicholas J Wood, Nicole L Messina, Nigel Curtis

Background: Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospective data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illnesses, identify factors associated with the risk of PACS, and explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses.

Methods: Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed. Symptom data were prospectively collected over 12 months, allowing detailed characterisation of symptom patterns. Participants with COVID-19 and non-COVID-19 respiratory illness episodes were compared, focussing on symptom severity, duration (including PACS using NICE and WHO definitions), and pre-existing symptoms.

Findings: Participants with COVID-19 had significantly more severe illness compared to those with non-COVID-19 respiratory illnesses (OR 7·4, 95%CI 5·6-9·7). Symptom duration meeting PACS definitions occurred in a higher proportion of COVID-19 cases than non-COVID-19 respiratory controls using both the NICE definition (2·5% vs 0·5%, OR 6·6, 95%CI 2·4-18·3) and the WHO definition (8·8% vs 3·7%, OR 2·5, 95%CI 1·4-4·3). When considering only participants with COVID-19, age (aOR 2·8, 95%CI 1·3-6·2), chronic respiratory disease (aOR 5·5, 95%CI 1·3-23·1), and pre-existing symptoms (aOR 3·0, 95%CI 1·4-6·3) were associated with an increased risk of developing PACS. Symptoms associated with PACS were also reported by participants in the months preceding their COVID-19 or non-COVID-19 respiratory illnesses (32% fatigue and muscle ache, 11% intermittent cough and shortness of breath).

Interpretation: Healthcare workers with COVID-19 experienced more severe and longer-lasting symptoms than those with non-COVID-19 respiratory illnesses, with a higher proportion meeting the WHO or NICE definitions of PACS. Age, chronic respiratory disease, and pre-existing symptoms increased the risk of developing PACS following COVID-19.

Funding: Bill & Melinda Gates Foundation [INV-017302] and others (see Acknowledgements).

背景:有些人在感染 COVID-19 (急性 COVID-19 后综合征;PACS)和其他病毒感染后症状持续存在。本研究利用一项国际试验的前瞻性数据,比较 COVID-19 和非 COVID-19 呼吸道疾病后的症状,确定与 PACS 风险相关的因素,并探讨 COVID-19 和非 COVID-19 呼吸道疾病前后的症状模式:分析了来自四个国家医护人员参与的多中心随机对照试验(BRACE 试验)的数据。前瞻性地收集了12个月的症状数据,以便详细描述症状模式。研究人员对患有 COVID-19 和未患有 COVID-19 的呼吸道疾病的参与者进行了比较,重点关注症状的严重程度、持续时间(包括使用 NICE 和 WHO 定义的 PACS)以及之前存在的症状:研究结果:与非 COVID-19 呼吸系统疾病患者相比,COVID-19 患者的病情明显更严重(OR 7-4,95%CI 5-6-9-7)。根据NICE定义(2-5% vs 0-5%,OR 6-6,95%CI 2-4-18-3)和WHO定义(8-8% vs 3-7%,OR 2-5,95%CI 1-4-4-3),COVID-19病例中符合PACS定义的症状持续时间比例高于非COVID-19呼吸系统对照组。如果仅考虑 COVID-19 的参与者,年龄(aOR 2-8,95%CI 1-3-6-2)、慢性呼吸道疾病(aOR 5-5,95%CI 1-3-23-1)和原有症状(aOR 3-0,95%CI 1-4-6-3)与 PACS 患病风险的增加有关。参与者在患 COVID-19 或非 COVID-19 呼吸系统疾病前的几个月中也报告了与 PACS 相关的症状(32% 疲劳和肌肉酸痛,11% 间歇性咳嗽和呼吸急促):患 COVID-19 的医护人员比未患 COVID-19 呼吸系统疾病的医护人员症状更严重、持续时间更长,符合世界卫生组织或 NICE PACS 定义的比例更高。年龄、慢性呼吸道疾病和原有症状会增加感染 COVID-19 后出现 PACS 的风险:比尔及梅琳达-盖茨基金会 [INV-017302] 及其他(见致谢)。
{"title":"Antecedent and persistent symptoms in COVID-19 and other respiratory illnesses: insights from prospectively collected data in the BRACE trial.","authors":"Ellie McDonald, Laure F Pittet, Simone E Barry, Marc Bonten, John Campbell, Julio Croda, Mariana G Croda, Margareth Pretti Dalcolmo, Andrew Davidson, Fernando F de Almeida E Val, Ms Glauce Dos Santos, Ms Kaya Gardiner, Ms Grace Gell, Amanda Gwee, Ms Ann Krastev, Marcus Vinícius Guimaraes Lacerda, Michaela Lucas, David J Lynn, Laurens Manning, Mr Nick McPhate, Kirsten P Perrett, Jeffrey J Post, Cristina Prat-Aymerich, Ms Lynne E Quinn, Peter C Richmond, Nicholas J Wood, Nicole L Messina, Nigel Curtis","doi":"10.1016/j.jinf.2024.106267","DOIUrl":"https://doi.org/10.1016/j.jinf.2024.106267","url":null,"abstract":"<p><strong>Background: </strong>Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospective data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illnesses, identify factors associated with the risk of PACS, and explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses.</p><p><strong>Methods: </strong>Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed. Symptom data were prospectively collected over 12 months, allowing detailed characterisation of symptom patterns. Participants with COVID-19 and non-COVID-19 respiratory illness episodes were compared, focussing on symptom severity, duration (including PACS using NICE and WHO definitions), and pre-existing symptoms.</p><p><strong>Findings: </strong>Participants with COVID-19 had significantly more severe illness compared to those with non-COVID-19 respiratory illnesses (OR 7·4, 95%CI 5·6-9·7). Symptom duration meeting PACS definitions occurred in a higher proportion of COVID-19 cases than non-COVID-19 respiratory controls using both the NICE definition (2·5% vs 0·5%, OR 6·6, 95%CI 2·4-18·3) and the WHO definition (8·8% vs 3·7%, OR 2·5, 95%CI 1·4-4·3). When considering only participants with COVID-19, age (aOR 2·8, 95%CI 1·3-6·2), chronic respiratory disease (aOR 5·5, 95%CI 1·3-23·1), and pre-existing symptoms (aOR 3·0, 95%CI 1·4-6·3) were associated with an increased risk of developing PACS. Symptoms associated with PACS were also reported by participants in the months preceding their COVID-19 or non-COVID-19 respiratory illnesses (32% fatigue and muscle ache, 11% intermittent cough and shortness of breath).</p><p><strong>Interpretation: </strong>Healthcare workers with COVID-19 experienced more severe and longer-lasting symptoms than those with non-COVID-19 respiratory illnesses, with a higher proportion meeting the WHO or NICE definitions of PACS. Age, chronic respiratory disease, and pre-existing symptoms increased the risk of developing PACS following COVID-19.</p><p><strong>Funding: </strong>Bill & Melinda Gates Foundation [INV-017302] and others (see Acknowledgements).</p>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Real-world performance of a single-use, analyser-free, molecular point-of-care test for COVID-19 used in the emergency department: Results of a prospective trial (ED-POC) 急诊科使用的一次性、无分析仪、COVID-19分子床旁检验的实际性能:前瞻性试验(ED-POC)的结果。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-05 DOI: 10.1016/j.jinf.2024.106264

Background

A novel single-use, analyser-free, molecular point-of-care test for SARS-CoV-2 (Veros COVID-19 test, Sherlock Biosciences) could reduce time to results and improve patient care and flow in the emergency department (ED), but its performance in this setting is unknown.

Methods

Adults aged ≥18 years presenting to Southampton General Hospital (UK) with suspected COVID-19 were tested with the Veros COVID-19 test in addition to standard of care near-patient PCR. Measures of diagnostic accuracy were calculated for the Veros COVID-19 test stratified by Ct value. Discrepant results underwent viral culture.

Findings

Between Jan 16 and May 2, 2023, 400 patients were enrolled with a median (IQR) age of 60 (34−77) and 141 (35·3%) were SARS-CoV-2 positive by PCR. The Veros test gave valid results on the first test in 384 (96·0%), and sensitivity and specificity were 127/141 (90·1%, 95%CI 83·9–94·5) and 258/259 (99·6%, 95%CI 97·9–100) overall. For those with high or moderate viral load (Ct ≤30), sensitivity was 125/129 (96·9%, 95%CI 92·3–99·2). One (7·1%) of 14 PCR positive/Veros test negative samples was culture positive. Median (IQR) time from sample collection to result was 19 (18−20) mins with the Veros test versus 73 (59−92) mins with PCR (p < 0·0001).

Interpretation

The Veros COVID-19 test generated results in near real-time, around 1 h sooner than rapid, near-patient, analyser-based PCR, and accuracy was excellent for samples with moderate and high viral loads. The Veros test represents a step-change in molecular diagnostics for infection and could significantly reduce time to results and improve patient management in EDs and other settings.

背景:一种新型的一次性、无需分析仪的SARS-CoV-2分子床旁检测试剂盒(Veros COVID-19检测试剂盒,Sherlock Biosciences公司)可以缩短检测结果产生的时间,改善急诊科(ED)的病人护理和流程,但其在这种情况下的性能尚不清楚:方法:在英国南安普顿综合医院就诊的≥18 岁疑似 COVID-19 的成人除了接受标准的就近病人 PCR 检测外,还接受了 Veros COVID-19 检测。根据 Ct 值分层计算了 Veros COVID-19 检验的诊断准确度。对结果不明确者进行病毒培养:2023年1月16日至5月2日期间,400名患者入组,中位(IQR)年龄为60(34-77)岁,141人(35-3%)PCR检测结果为SARS-CoV-2阳性。384 人(96-0%)在第一次检测时就得到了有效的 Veros 检测结果,总体敏感性和特异性分别为 127/141(90-1%,95%CI 83-9-94-5)和 258/259(99-6%,95%CI 97-9-100)。对于高或中度病毒载量(Ct ≤30)的患者,灵敏度为 125/129(96-9%,95%CI 92-3-99-2)。14 份 PCR 阳性/Veros 检测阴性样本中有 1 份(7-1%)培养阳性。从样本采集到检测结果的时间中位数(IQR)为:Veros 检测 19 (18-20) 分钟,PCR 检测 73 (59-92) 分钟(p解释:Veros COVID-19 检测从样本采集到检测结果的时间中位数(IQR)为 19 (18-20) 分钟,PCR 检测 73 (59-92) 分钟:Veros COVID-19 检验结果几乎是实时生成的,比基于分析仪的快速、接近病人的 PCR 早约 1 小时,而且对于中度和高度病毒载量样本的准确性非常高。Veros检验代表了感染分子诊断的一个进步,可以大大缩短检验结果的产生时间,改善急诊室和其他环境中的病人管理:数据共享:本研究中分析和展示的所有去身份化参与者数据可在发表后向相应作者索取。
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引用次数: 0
Plasma MERTK is causally associated with infection mortality 血浆 MERTK 与感染死亡率存在因果关系。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-04 DOI: 10.1016/j.jinf.2024.106262

Background

Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated.

Methods

We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants). Since many plasma proteins also predict non-infection mortality, we focussed on those associated with >1.5-fold risk of infection mortality in an analysis excluding survivors. Protein quantitative trait scores (pQTS) were then used to identify whether genetically predicted protein levels also associated with infection mortality. To conduct Two Sample MR, we performed a genome-wide association study (GWAS) of infection mortality using UK Biobank participants without plasma proteomic data (n = 363,953 including 984 infection deaths).

Findings

After adjusting for clinical risk factors, 1142 plasma proteins were associated with risk of infection mortality (false discovery rate <0.05). 259 proteins were associated with >1.5-fold increased risk of infection versus non-infection mortality. Of these, we identified genetically predicted increasing MERTK concentration was associated with increased risk of infection mortality. MR supported a causal association between increasing plasma MERTK protein and infection mortality (odds ratio 1.46 per unit; 95% CI 1.15- 1.85; p = 0.002).

Conclusion

Plasma MERTK is causally associated with infection mortality and warrants exploration as a potential therapeutic target.

背景:尽管已有公共卫生、抗微生物和疫苗干预措施,但传染病仍是导致死亡的主要原因。我们的目的是确定与感染死亡率相关的血浆蛋白质组,然后应用孟德尔随机化(MR)方法得出可能存在因果关系的生物标志物:我们利用英国生物库血浆蛋白质组数据,将2923种血浆蛋白质与2019年12月31日前的感染死亡率联系起来(52520名参与者中的240起事件)。由于许多血浆蛋白也能预测非感染死亡率,因此在排除幸存者的分析中,我们将重点放在与感染死亡风险>1.5倍相关的血浆蛋白上。然后使用蛋白质定量性状评分(pQTS)来确定基因预测的蛋白质水平是否也与感染死亡率相关。为了进行两个样本 MR,我们利用没有血浆蛋白质组数据的英国生物库参与者(n=363,953,包括 984 例感染死亡病例)对感染死亡率进行了全基因组关联研究(GWAS):在对临床风险因素进行调整后,1,142种血浆蛋白与感染死亡风险相关(感染与非感染死亡风险的误发现率增加1.5倍)。其中,我们发现基因预测的 MERTK 浓度增加与感染死亡风险增加有关。MR支持血浆MERTK蛋白增加与感染死亡率之间的因果关系(每单位的几率比1.46;95% CI 1.15- 1.85;P=0.002):结论:血浆 MERTK 与感染死亡率存在因果关系,值得将其作为潜在的治疗靶点进行研究。
{"title":"Plasma MERTK is causally associated with infection mortality","authors":"","doi":"10.1016/j.jinf.2024.106262","DOIUrl":"10.1016/j.jinf.2024.106262","url":null,"abstract":"<div><h3>Background</h3><p>Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated.</p></div><div><h3>Methods</h3><p>We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants). Since many plasma proteins also predict non-infection mortality, we focussed on those associated with &gt;1.5-fold risk of infection mortality in an analysis excluding survivors. Protein quantitative trait scores (pQTS) were then used to identify whether genetically predicted protein levels also associated with infection mortality. To conduct Two Sample MR, we performed a genome-wide association study (GWAS) of infection mortality using UK Biobank participants without plasma proteomic data (n = 363,953 including 984 infection deaths).</p></div><div><h3>Findings</h3><p>After adjusting for clinical risk factors, 1142 plasma proteins were associated with risk of infection mortality (false discovery rate &lt;0.05). 259 proteins were associated with &gt;1.5-fold increased risk of infection versus non-infection mortality. Of these, we identified genetically predicted increasing MERTK concentration was associated with increased risk of infection mortality. MR supported a causal association between increasing plasma MERTK protein and infection mortality (odds ratio 1.46 per unit; 95% CI 1.15- 1.85; p = 0.002).</p></div><div><h3>Conclusion</h3><p>Plasma MERTK is causally associated with infection mortality and warrants exploration as a potential therapeutic target.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001968/pdfft?md5=63cb4a714a6a9cfc30b449602c92d717&pid=1-s2.0-S0163445324001968-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
16S ribosomal RNA gene amplicons in diagnosis of infectious diseases 16S 核糖体 RNA 基因扩增片段在传染病诊断中的应用。
IF 14.3 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2024-09-03 DOI: 10.1016/j.jinf.2024.106263
{"title":"16S ribosomal RNA gene amplicons in diagnosis of infectious diseases","authors":"","doi":"10.1016/j.jinf.2024.106263","DOIUrl":"10.1016/j.jinf.2024.106263","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016344532400197X/pdfft?md5=f4fc53b5211769aea79fb16e12bb83ea&pid=1-s2.0-S016344532400197X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Infection
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