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Comparative diagnostic accuracy of metagenomic next-generation sequencing and targeted next-generation sequencing for periprosthetic joint infection: A systematic review and meta-analysis 元基因组新一代测序和靶向新一代测序对假体周围关节感染的诊断准确性比较:系统回顾和荟萃分析。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106661
Lina Wang , Zhongyuan Zhao , Yuchi Zhao , Shengjie Dong , Shangxiang Feng , Li Cao , Kun Song

Objectives

The aim of this meta-analysis was to assess the diagnostic performance of metagenomic next-generation sequencing and targeted next-generation sequencing for periprosthetic joint infection (PJI).

Background

Next-generation sequencing (NGS) is increasingly used for diagnosing periprosthetic joint infection (PJI), but its clinical utility remains poorly defined. Discrepancies between metagenomic NGS (mNGS) and targeted NGS (tNGS) results pose a significant clinical challenge for PJI diagnosis. To address this, we conducted a systematic review and meta-analysis comparing the diagnostic accuracy of mNGS and tNGS for PJI.

Methods

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus from inception through June 1, 2025. Two reviewers independently extracted data and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and the area under the hierarchical summary receiver operating characteristic curve (AUC) were calculated.

Results

Following screening and eligibility assessment, 23 studies were included in the analysis. The pooled sensitivity and specificity for diagnosing PJI were 0.89 (95% CI: 0.84–0.93) and 0.92 (95% CI: 0.89–0.95) for mNGS, and 0.84 (95% CI: 0.74–0.91) and 0.97 (95% CI: 0.88–0.99) for tNGS. The DORs were 58.56 (95% CI: 38.41–89.26) for mNGS and 106.67 (95% CI: 40.93–278.00) for tNGS. The areas under the summary receiver-operating characteristic curves (AUCs) were 0.935 (95% CI: 0.90–0.95) for mNGS and 0.911 (95% CI: 0.85–0.95) for tNGS. Comparisons of DOR and AUC between mNGS and tNGS revealed no statistically significant differences (P > 0.05).

Conclusions

This meta-analysis indicates that mNGS demonstrates higher sensitivity and a numerically greater AUC than tNGS for diagnosing PJI, with acceptable specificity, although the difference in AUC was not statistically significant. Conversely, tNGS exhibits higher specificity and DOR, alongside acceptable sensitivity, making it valuable for confirming PJI. Overall, the diagnostic accuracy of both next-generation sequencing (NGS) methods is comparable, with each possessing distinct advantages and limitations.
目的:本荟萃分析的目的是评估宏基因组新一代测序和靶向新一代测序对假体周围关节感染(PJI)的诊断性能。背景:下一代测序(NGS)越来越多地用于诊断假体周围关节感染(PJI),但其临床用途仍不明确。宏基因组NGS (mNGS)和靶向NGS (tNGS)结果之间的差异对PJI的诊断提出了重大的临床挑战。为了解决这个问题,我们进行了一项系统综述和荟萃分析,比较了mNGS和tNGS对PJI的诊断准确性。方法:本研究遵循系统评价和荟萃分析的首选报告项目(PRISMA)指南。我们全面检索了PubMed, EMBASE, Cochrane Library, Web of Science和Scopus,从成立到2025年6月1日。两位审稿人独立提取数据并使用诊断准确性研究质量评估2 (QUADAS-2)工具评估研究质量。计算合并敏感性、特异性、诊断优势比(DOR)和分级汇总受试者工作特征曲线下面积(AUC)。结果:经过筛选和合格性评估,23项研究被纳入分析。mNGS诊断PJI的敏感性和特异性分别为0.89 (95% CI: 0.84-0.93)和0.92 (95% CI: 0.89-0.95), tNGS诊断PJI的敏感性和特异性分别为0.84 (95% CI: 0.74-0.91)和0.97 (95% CI: 0.88-0.99)。mNGS的DORs为58.56 (95% CI: 38.41 ~ 89.26), tNGS的DORs为106.67 (95% CI: 40.93 ~ 278.00)。mNGS和tNGS的总接受者-工作特征曲线下面积分别为0.935 (95% CI: 0.90-0.95)和0.911 (95% CI: 0.85-0.95)。mNGS与tNGS的DOR、AUC比较,差异无统计学意义(P < 0.05)。结论:本荟萃分析表明,mNGS在诊断PJI方面比tNGS具有更高的敏感性和更高的数值AUC,具有可接受的特异性,尽管AUC差异无统计学意义。相反,tNGS具有更高的特异性和DOR,以及可接受的灵敏度,使其对PJI的确认具有价值。总体而言,两种新一代测序(NGS)方法的诊断准确性具有可比性,每种方法都具有不同的优点和局限性。
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引用次数: 0
Cytomegalovirus reactivation and the host immune response in patients with sepsis 脓毒症患者巨细胞病毒再激活与宿主免疫反应。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106657
Justin de Brabander , David S.Y. Ong , Olaf L. Cremer , Lieuwe D.J. Bos , Hessel Peters-Sengers , Tom van der Poll

Objectives

We aimed to compare host response profiles between sepsis patients who develop cytomegalovirus (CMV) reactivation (reactivators) and those who do not (non-reactivators).

Methods

We performed a nested case-control study in CMV-seropositive sepsis patients from two Dutch ICUs. Reactivators (plasma CMV ≥100 IU/ml) were matched 1:1 to non-reactivators, based on length of stay until reactivation, disease severity, and other relevant criteria. We analysed 32 plasma biomarkers and whole-blood gene expression on the day of CMV reactivation (or matched time point for non-reactivators), three days prior, and at ICU admission.

Results

We compared 81 reactivators with 81 matched non-reactivators. In reactivators, six soluble immune checkpoint regulators increased longitudinally from three days before to the day of CMV viraemia onset. In contrast, biomarkers reflecting cytokine release, endothelial activation, coagulation, inflammation and organ damage remained stable. Structural equation modelling identified inhibitory checkpoint regulation as the only variable independently associated with CMV reactivation. Gene expression analysis three days before reactivation revealed upregulation of innate immunity, haemostasis, and CMV-related pathways, alongside downregulation of adaptive immunity and cytokine signalling pathways.

Conclusions

CMV reactivation in sepsis is preceded by broad immune dysregulation. These data provide insight into antiviral immune mechanisms that are impaired prior to reactivation and may inform preventive strategies.
目的:我们旨在比较发生巨细胞病毒(CMV)再激活(再激活者)和未发生巨细胞病毒(非再激活者)的败血症患者的宿主反应谱。方法:我们对来自荷兰两家icu的cmv血清阳性脓毒症患者进行了巢式病例对照研究。再激活者(血浆CMV≥100 IU/ml)与非再激活者1:1匹配,基于再激活前的停留时间、疾病严重程度和其他相关标准。我们分析了32种血浆生物标志物和全血基因在巨细胞病毒再激活当天(或非再激活者的匹配时间点)、三天前和ICU入院时的表达。结果:我们比较了81种再激活剂和81种匹配的非再激活剂。在再激活剂中,6种可溶性免疫检查点调节因子从巨细胞病毒血症发病前3天到发病当天呈纵向增加。相比之下,反映细胞因子释放、内皮活化、凝血、炎症和器官损伤的生物标志物保持稳定。结构方程模型确定抑制检查点调节是唯一与巨细胞病毒再激活独立相关的变量。再激活前三天的基因表达分析显示,先天免疫、止血和巨细胞病毒相关途径上调,适应性免疫和细胞因子信号通路下调。结论:败血症中巨细胞病毒的再激活先于广泛的免疫失调。这些数据为重新激活之前受损的抗病毒免疫机制提供了见解,并可能为预防策略提供信息。
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引用次数: 0
Monocyte iron load correlates with immune suppression and sepsis severity: A longitudinal analysis 单核细胞铁负荷与免疫抑制和败血症严重程度相关:一项纵向分析。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106660
Christina Mertens , Diana Reuter , Anand Ruban Agarvas , Judith Schenz , Bastian Winkelhausen , Anna Hafner , Christoph Kahlert , Maximilian Dietrich , Mascha O. Fiedler-Kalenka , Markus A. Weigand , Martina U. Muckenthaler , Dania Fischer

Background

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. In critically ill patients, iron biomarkers are closely linked to outcomes; yet the mechanistic role of iron metabolism in sepsis progression remains unclear.

Method

To address this knowledge gap, we conducted a longitudinal clinical study in 20 sepsis patients, tracking plasma iron biomarkers together with monocyte function and iron content over five consecutive days following sepsis onset. Some patients required red blood cell transfusions during the study period.

Results

We show that anemia of inflammation is an early and prominent feature of sepsis hallmarked by iron sequestration in blood monocytes, reduced plasma iron levels and anemia. Importantly, increased iron levels in monocytes are detected already at day one following the sepsis diagnosis and the degree of iron accumulation directly correlates with sepsis severity. High monocytic iron levels further correlate with decreased human leukocyte antigen DR (HLA-DR) expression on day one, suggestive of monocyte immunosuppression. Furthermore, in iron-loaded septic monocytes mRNA levels of the non-transferrin bound iron (NTBI) transporter ZRT/IRT-like Protein 8 were significantly increased, suggesting enhanced uptake of non-transferrin bound iron that may arise from hemolysis. Interestingly, we also show that the total iron binding capacity is an important predictor of sepsis mortality, while transfusions did not correlate with an altered iron and/or inflammatory status.

Conclusions

The study highlights that early iron accumulation in monocytes is a hallmark of sepsis and is closely linked to disease severity and progression. We expect that improved insights into iron metabolism in sepsis patients may pave the way to improving therapeutic options that balance iron levels and their effects on organ functions in the future.
背景:脓毒症是一种危及生命的疾病,是由对感染的免疫反应失调引起的。在危重患者中,铁生物标志物与预后密切相关;然而,铁代谢在脓毒症进展中的机制作用尚不清楚。方法:为了解决这一知识缺口,我们对20例脓毒症患者进行了纵向临床研究,在脓毒症发作后连续5天追踪血浆铁生物标志物、单核细胞功能和铁含量。在研究期间,一些患者需要输注红细胞。结果:我们发现炎症性贫血是脓毒症的早期和突出特征,其特征是血液单核细胞中的铁隔离,血浆铁水平降低和贫血。重要的是,在脓毒症诊断后的第一天就可以检测到单核细胞中铁水平的增加,铁积累的程度与脓毒症的严重程度直接相关。高单核细胞铁水平进一步与第一天人类白细胞抗原DR (HLA-DR)表达降低相关,提示单核细胞免疫抑制。此外,在铁负载的脓毒症单核细胞中,非转铁蛋白结合铁(NTBI)转运蛋白ZRT/ irt样蛋白8的mRNA水平显著升高,表明溶血可能导致非转铁蛋白结合铁的摄取增强。有趣的是,我们还表明,总铁结合能力是脓毒症死亡率的重要预测指标,而输血与铁和/或炎症状态的改变无关。结论:该研究强调单核细胞早期铁积累是败血症的标志,与疾病严重程度和进展密切相关。我们希望对败血症患者铁代谢的深入了解可能为改善平衡铁水平及其对器官功能的影响的治疗选择铺平道路。
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引用次数: 0
Reactogenicity and immunogenicity following heterologous and homologous third dose COVID-19 vaccination in UK adolescents (Com-COV3): A randomised controlled non-inferiority trial 英国青少年异源和同源第三剂COVID-19疫苗(Com-COV3)的反应原性和免疫原性:一项随机对照非劣效性试验
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106663
E. Kelly , M. Greenland , P. de Whalley , G.C. Macaulay , P.K. Aley , E. Plested , S. Koleva , J. Cotton , J. Kinch , T. Madupuri , R.C. Read , M. Ramsay , C. Cameron , D.P.J. Turner , P. Heath , P. Connor , K. Cathie , S.N. Faust , I. Banerjee , K. Man , X. Liu

Background

The emergence of SARS-CoV2 variants combined with waning vaccine-induced immunity and breakthrough infections has highlighted the need for booster doses to maintain protection against SARS-CoV2 infection and disease.

Methods

Com-COV3 was a phase II, multicentre, randomised controlled trial, recruiting across 11 UK sites from June 2022 to June 2023, with follow-up visits to February 2024. Healthy 12–15-year-olds who had received a two-30 μg dose BNT162b2 primary regimen at least 90 days previously were randomised 1:1:1:1:1 to receive either BNT162b2 30 μg, BNT162b2 10 μg (adult vaccine formulation), BNT162b2 10 μg (paediatric formulation), NVXCoV2373, or Meningococcal B vaccine (control). The primary objective was to determine if SARS-CoV-2 anti-spike antibody following a 10 μg dose of the adult formulation of BNT162b2 was non-inferior to the paediatric formulation at 28 days post-third vaccination. The last five participants were randomised using a 1:3:3:1:1 ratio to prioritise recruitment to the study groups required for the co-primary endpoint. Although recruitment ceased early, the sample size required to fulfil the primary objective was met.

Findings

281 participants were recruited (mean age 14 years old, 57% female). Adverse reactions were mostly mild-to-moderate. Local reactogenicity was mildest following NVXCoV2373. Frequency of adverse events was similar for both full dose and fractional dose BNT162b2 groups. Four serious adverse events occurred: three in the paediatric and one in the adult 10 μg BNT162b2 group. Immunogenicity of 10 μg BNT162b2 (adult) was both non-inferior and superior to that of 10 μg BNT162b2 (paediatric); adjusted geometric mean ratio (aGMR) anti-spike IgG 1.50 (one-sided 95% CI 1.25 to ∞). Compared with 30 μg BNT162b2, anti-spike IgG at day 28 post-third dose were similar in the 10 μg BNT162b2 (adult) group [aGMR 0.93 (95% CI 0.75–1.14)] and significantly lower in the 10 μg BNT162b2 (paediatric) [aGMR 0.64 (95% CI 0.52–0.78)] and NVXCoV2373 [aGMR 0.77 (95% CI 0.63–0.95)] groups. Compared with 30 μg BNT162b2, levels of neutralising antibodies against Omicron BA.5 and XBB.15 were similar across vaccine groups.

Interpretation

All booster regimens evaluated elicited a robust immune response. 10 μg fractional adult BNT162b2 vaccine demonstrated similar immunogenicity compared with 30 μg BNT162b2 and superior immunogenicity compared with 10 μg paediatric BNT162b2 vaccine. Fractional doses of the adult BNT162b2 vaccine are an alternative to the paediatric formulation for booster campaigns in adolescents.
背景:SARS-CoV2变异的出现,加上疫苗诱导的免疫力下降和突破性感染,突出了加强剂量以维持对SARS-CoV2感染和疾病的保护的必要性。方法:Com-COV3是一项II期、多中心、随机对照试验,于2022年6月至2023年6月在英国11个地点招募,随访至2024年2月。至少90天前接受过2- 30μg剂量BNT162b2初级方案的12-15岁健康儿童按1:1:1:1:1随机分组,分别接受BNT162b2 30μg、BNT162b2 10μg(成人疫苗制剂)、BNT162b2 10μg(儿科疫苗制剂)、NVXCoV2373或脑膜炎球菌B疫苗(对照)。主要目的是确定在第三次接种后28天,接种10μg剂量的成人剂型BNT162b2后的SARS-CoV-2抗刺突抗体是否优于儿科剂型。最后5名参与者使用1:3:3:1:1的比例随机分组,优先招募到共同主要终点所需的研究组。虽然征聘工作提前停止,但达到了实现主要目标所需的样本量。结果:281名参与者被招募(平均年龄14岁,57%为女性)。不良反应大多为轻至中度。NVXCoV2373的局部反应性最轻。BNT162b2全剂量组和部分剂量组的不良事件发生率相似。发生了4例严重不良事件:3例发生在儿科,1例发生在10μg BNT162b2成人组。10μg BNT162b2(成人)的免疫原性优于10μg BNT162b2(儿童);校正几何平均比(aGMR)抗峰值IgG 1.50(单侧95%CI 1.25至∞)。与30μg BNT162b2相比,第3次给药后第28天,10μg BNT162b2(成人)组的抗刺突IgG水平相似[aGMR 0.93 (95%CI 0.75 ~ 1.14)],而10μg BNT162b2(儿童)组[aGMR 0.64 (95%CI 0.52 ~ 0.78)]和NVXCoV2373 [aGMR 0.77 (95%CI 0.63 ~ 0.95)]的抗刺突IgG水平则显著低于10μg BNT162b2(儿童)组[aGMR 0.64 (95%CI 0.52 ~ 0.78)]。与30μg BNT162b2相比,不同疫苗组抗Omicron BA.5和XBB.15的中和抗体水平相似。解释:所有评估的强化方案都引起了强大的免疫反应。10μg分级成人BNT162b2疫苗与30μg BNT162b2疫苗具有相似的免疫原性,与10μg儿科BNT162b2疫苗具有更强的免疫原性。部分剂量的成人BNT162b2疫苗是用于青少年加强运动的儿科配方的替代方案。资助:国家卫生研究所、疫苗工作组和流行病防范创新联盟。
{"title":"Reactogenicity and immunogenicity following heterologous and homologous third dose COVID-19 vaccination in UK adolescents (Com-COV3): A randomised controlled non-inferiority trial","authors":"E. Kelly ,&nbsp;M. Greenland ,&nbsp;P. de Whalley ,&nbsp;G.C. Macaulay ,&nbsp;P.K. Aley ,&nbsp;E. Plested ,&nbsp;S. Koleva ,&nbsp;J. Cotton ,&nbsp;J. Kinch ,&nbsp;T. Madupuri ,&nbsp;R.C. Read ,&nbsp;M. Ramsay ,&nbsp;C. Cameron ,&nbsp;D.P.J. Turner ,&nbsp;P. Heath ,&nbsp;P. Connor ,&nbsp;K. Cathie ,&nbsp;S.N. Faust ,&nbsp;I. Banerjee ,&nbsp;K. Man ,&nbsp;X. Liu","doi":"10.1016/j.jinf.2025.106663","DOIUrl":"10.1016/j.jinf.2025.106663","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of SARS-CoV2 variants combined with waning vaccine-induced immunity and breakthrough infections has highlighted the need for booster doses to maintain protection against SARS-CoV2 infection and disease.</div></div><div><h3>Methods</h3><div>Com-COV3 was a phase II, multicentre, randomised controlled trial, recruiting across 11 UK sites from June 2022 to June 2023, with follow-up visits to February 2024. Healthy 12–15-year-olds who had received a two-30 μg dose BNT162b2 primary regimen at least 90 days previously were randomised 1:1:1:1:1 to receive either BNT162b2 30 μg, BNT162b2 10 μg (adult vaccine formulation), BNT162b2 10 μg (paediatric formulation), NVXCoV2373, or Meningococcal B vaccine (control). The primary objective was to determine if SARS-CoV-2 anti-spike antibody following a 10 μg dose of the adult formulation of BNT162b2 was non-inferior to the paediatric formulation at 28 days post-third vaccination. The last five participants were randomised using a 1:3:3:1:1 ratio to prioritise recruitment to the study groups required for the co-primary endpoint. Although recruitment ceased early, the sample size required to fulfil the primary objective was met.</div></div><div><h3>Findings</h3><div>281 participants were recruited (mean age 14 years old, 57% female). Adverse reactions were mostly mild-to-moderate. Local reactogenicity was mildest following NVXCoV2373. Frequency of adverse events was similar for both full dose and fractional dose BNT162b2 groups. Four serious adverse events occurred: three in the paediatric and one in the adult 10 μg BNT162b2 group. Immunogenicity of 10 μg BNT162b2 (adult) was both non-inferior and superior to that of 10 μg BNT162b2 (paediatric); adjusted geometric mean ratio (aGMR) anti-spike IgG 1.50 (one-sided 95% CI 1.25 to ∞). Compared with 30 μg BNT162b2, anti-spike IgG at day 28 post-third dose were similar in the 10 μg BNT162b2 (adult) group [aGMR 0.93 (95% CI 0.75–1.14)] and significantly lower in the 10 μg BNT162b2 (paediatric) [aGMR 0.64 (95% CI 0.52–0.78)] and NVXCoV2373 [aGMR 0.77 (95% CI 0.63–0.95)] groups. Compared with 30 μg BNT162b2, levels of neutralising antibodies against Omicron BA.5 and XBB.15 were similar across vaccine groups.</div></div><div><h3>Interpretation</h3><div>All booster regimens evaluated elicited a robust immune response. 10 μg fractional adult BNT162b2 vaccine demonstrated similar immunogenicity compared with 30 μg BNT162b2 and superior immunogenicity compared with 10 μg paediatric BNT162b2 vaccine. Fractional doses of the adult BNT162b2 vaccine are an alternative to the paediatric formulation for booster campaigns in adolescents.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"92 1","pages":"Article 106663"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670432","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
Interpretable machine learning based comorbidity specific mortality risk score for bloodstream infections 基于可解释机器学习的血液感染共病特定死亡风险评分。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106656
Chen Cui , Jinyi Zhao , Fei Mu , Dahua Wang , Yamei Li , Meng Tang , Kexin Sun , Rui Gong , Zhen Yan , Jingwen Wang

Objectives

Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase clinical data to predict 28-day mortality by integrating longitudinal trends and addressing comorbidity-driven heterogeneity.

Methods

The BSI Heterogeneity Score (BHScore) was developed using machine learning on longitudinal clinical data (first 7 days post-culture) from 2524 BSI patients at Xijing Hospital. The model uses interpretable methods to establish comorbidity-stratified thresholds (global, renal disease, liver disease, metastatic malignancy) to enhance prediction accuracy.

Results

The BHScore demonstrated superior discriminatory performance (area under the receiver operating characteristic curve: 0.81–0.91) and temporal stability compared to established scores including the Sequential Organ Failure Assessment (SOFA), representing an improvement of 10% to 25%. Our analysis revealed that coagulation biomarkers have greater prognostic significance in the malignancy subgroup, inflammatory thresholds are more sensitive in the liver disease subgroup, and urea levels exhibit U-shaped mortality curves in the renal disease subgroup. To support clinical application, a freely accessible web tool has been developed.

Conclusions

The BHScore enables the early identification of high-risk BSI patients with diverse comorbidities using straightforward clinical indicators, facilitating timely and targeted interventions to reduce mortality.
目的:血流感染(BSI)是脓毒症的主要原因,需要在有效管理的关键窗口期进行早期风险分层。我们的目标是建立一个模型,通过整合纵向趋势和解决合并症驱动的异质性,利用早期临床数据预测28天死亡率。方法:利用机器学习对西京医院2524例BSI患者的纵向临床数据(培养后7天)进行BSI异质性评分(BHScore)。该模型使用可解释的方法来建立合并症分层阈值(全局、肾脏疾病、肝脏疾病、转移性恶性肿瘤),以提高预测准确性。结果:与包括顺序器官衰竭评估(SOFA)在内的现有评分相比,BHScore表现出更好的区分性能(受试者工作特征曲线下面积:0.81-0.91)和时间稳定性,提高了10%至25%。我们的分析显示,凝血生物标志物在恶性肿瘤亚组中具有更大的预后意义,炎症阈值在肝脏疾病亚组中更敏感,尿素水平在肾脏疾病亚组中呈现u型死亡率曲线。为了支持临床应用,我们开发了一个免费访问的网络工具。结论:BHScore可以通过简单明了的临床指标,早期发现具有多种合并症的高危BSI患者,及时、有针对性地进行干预,降低死亡率。
{"title":"Interpretable machine learning based comorbidity specific mortality risk score for bloodstream infections","authors":"Chen Cui ,&nbsp;Jinyi Zhao ,&nbsp;Fei Mu ,&nbsp;Dahua Wang ,&nbsp;Yamei Li ,&nbsp;Meng Tang ,&nbsp;Kexin Sun ,&nbsp;Rui Gong ,&nbsp;Zhen Yan ,&nbsp;Jingwen Wang","doi":"10.1016/j.jinf.2025.106656","DOIUrl":"10.1016/j.jinf.2025.106656","url":null,"abstract":"<div><h3>Objectives</h3><div>Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase clinical data to predict 28-day mortality by integrating longitudinal trends and addressing comorbidity-driven heterogeneity.</div></div><div><h3>Methods</h3><div>The BSI Heterogeneity Score (BHScore) was developed using machine learning on longitudinal clinical data (first 7 days post-culture) from 2524 BSI patients at Xijing Hospital. The model uses interpretable methods to establish comorbidity-stratified thresholds (global, renal disease, liver disease, metastatic malignancy) to enhance prediction accuracy.</div></div><div><h3>Results</h3><div>The BHScore demonstrated superior discriminatory performance (area under the receiver operating characteristic curve: 0.81–0.91) and temporal stability compared to established scores including the Sequential Organ Failure Assessment (SOFA), representing an improvement of 10% to 25%. Our analysis revealed that coagulation biomarkers have greater prognostic significance in the malignancy subgroup, inflammatory thresholds are more sensitive in the liver disease subgroup, and urea levels exhibit U-shaped mortality curves in the renal disease subgroup. To support clinical application, a freely accessible web tool has been developed.</div></div><div><h3>Conclusions</h3><div>The BHScore enables the early identification of high-risk BSI patients with diverse comorbidities using straightforward clinical indicators, facilitating timely and targeted interventions to reduce mortality.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106656"},"PeriodicalIF":11.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145543714","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
The epidemic pattern of a chikungunya outbreak in China exhibits a three-stage migratory trend 基孔肯雅热疫情在中国的流行模式表现为三个阶段的迁移趋势。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-12-01 DOI: 10.1016/j.jinf.2025.106646
Jiajia Zhang , Juncheng Cai , Changhai Liu , Marco Túlio Dos Santos Costa , Tao Ren , Libin Chen
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引用次数: 0
Lipoarabinomannan (LAM) for the diagnosis of tuberculosis from sputum 脂阿拉伯甘露聚糖(LAM)对痰液结核的诊断价值。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-18 DOI: 10.1016/j.jinf.2025.106662
Steffen Pichlo, Patricia Sanchez Carballo, Maja Reimann, Nika Zielinski, Yassir Adam Shuaib, Niklas Köhler, Sönke Andres, Jan Heyckendorf , Barbara Kalsdorf, Ioana D. Olaru , Helmut J.F. Salzer , Christoph Lange
{"title":"Lipoarabinomannan (LAM) for the diagnosis of tuberculosis from sputum","authors":"Steffen Pichlo,&nbsp;Patricia Sanchez Carballo,&nbsp;Maja Reimann,&nbsp;Nika Zielinski,&nbsp;Yassir Adam Shuaib,&nbsp;Niklas Köhler,&nbsp;Sönke Andres,&nbsp;Jan Heyckendorf ,&nbsp;Barbara Kalsdorf,&nbsp;Ioana D. Olaru ,&nbsp;Helmut J.F. Salzer ,&nbsp;Christoph Lange","doi":"10.1016/j.jinf.2025.106662","DOIUrl":"10.1016/j.jinf.2025.106662","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106662"},"PeriodicalIF":11.9,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145566179","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
Evolving pneumococcal epidemiology and vaccine impact in the Netherlands, 2004–2024: Carriage and invasive disease 2004-2024年荷兰肺炎球菌流行病学和疫苗影响的演变:传播和侵袭性疾病。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-13 DOI: 10.1016/j.jinf.2025.106658
Maurits T. Wulffraat , Nelleke G. van de Weijer , Alienke J. Wijmenga-Monsuur , Paul Badoux , Anneke Steens , Debbie Smit , Rob Mariman , Krzysztof P. Trzciński , Nina M. van Sorge , Nynke Y. Rots , Marianne A. van Houten

Objectives

Since pneumococcal conjugate vaccines (PCVs) were introduced into the Dutch childhood National Immunization Program in 2006, colonization and invasive disease of Streptococcus pneumoniae have declined, alongside shifts in serotype prevalence towards non-vaccine serotypes (NVTs). To monitor changes and estimate the added value of higher-valent PCVs, serotype-specific carriage, invasive pneumococcal disease (IPD) and invasive disease potential were analyzed.

Methods

During the winters of 2018/2019 and 2022/2023 pneumococcal carriage was determined among 24-month-old children and parents, and compared to carriage studies from 2005 to 2016. IPD data from Dutch surveillance (2004–2024) were included. Pneumococcal isolates were serotyped using agglutination and Quellung. Serotype-specific disease potential determined as odds ratios (OR) for IPD versus carriage.

Results

Pneumococcal carriage in children decreased from 66% in 2005 to 49% in 2018/2019 and 46% in 2022/2023. In 2022/2023, 29% of children carried NVTs, followed by PCV20- (11%), PCV13- (4%), PCV15- (2%) and PCV10- (0%) specific serotypes. Among parents, carriage declined from 17% in 2005 to 2% by 2022/2023. IPD incidence increased from 6·7 to 8·4 per 100,000 children under 5 years between 2018–2020 and 2022–2024, predominantly caused by an increase in serotype 19A. Serotypes 8 and 3 have the highest invasive disease potential.

Conclusions

This study shows stabilized pneumococcal carriage from 2018 to 2023 with low invasive disease potential for common serotypes, except for serotype 19A. However, rising IPD incidence from other non-vaccine serotypes highlights the need for higher-valency vaccines. The newly introduced PCV15 covers 58% of IPD cases, while PCV20 could cover 73%.
目的:自从2006年将肺炎球菌结合疫苗(PCVs)引入荷兰儿童国家免疫规划以来,肺炎链球菌的定植和侵袭性疾病有所下降,同时血清型患病率向非疫苗血清型(NVTs)转变。分析血清型特异性携带、侵袭性肺炎球菌病(IPD)和侵袭性疾病的可能性,以监测高价pcv的变化并估计其附加值。方法:在2018/2019年和2022/2023年冬季,对24月龄儿童和家长进行肺炎球菌携带测定,并与2005-2016年的携带研究进行比较。纳入了荷兰监测(2004-2024年)IPD数据。用凝集法和Quellung法对分离的肺炎球菌进行血清分型。血清型特异性疾病的可能性由IPD与携带的比值比(OR)决定。结果:儿童肺炎球菌携带率从2005年的66%下降到2018/2019年的49%和2022/2023年的46%。在2022/2023年,29%的儿童携带NVTs,其次是PCV20-(11%)、PCV13-(4%)、PCV15-(2%)和PCV10-(0%)特定血清型。在父母中,乘车比例从2005年的17%下降到2022/2023年的2%。2018-2020年和2022-2024年期间,IPD发病率从每10万名5岁以下儿童6.7例增加到8.4例,主要原因是血清型19A增加。血清型8和3具有最高的侵袭性疾病可能性。结论:本研究显示,2018-2023年肺炎球菌携带稳定,除19A血清型外,其他常见血清型的侵袭性疾病可能性较低。然而,其他非疫苗血清型引起的IPD发病率上升,突出表明需要更高效价的疫苗。新引入的PCV15可覆盖58%的IPD病例,而PCV20可覆盖73%。
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引用次数: 0
Plasmodium falciparum gene expression signatures and antibody profiling implicate the fikk, phist, and surf multigene families in severe malaria syndromes 恶性疟原虫基因表达特征和抗体谱分析暗示fikk、phist和surf多基因家族在严重疟疾综合征中的作用。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-12 DOI: 10.1016/j.jinf.2025.106655
Bryan E. Cummings , Emily M. Stucke , Drissa Coulibaly , Jonathan G. Lawton , Rafal S. Sobota , Abdoulaye Kassoum Kone , Bourama Kane , Bouréima Guindo , Bourama Tangara , Mody Sissoko , Fayçal Maiga , Karim Traore , Aichatou Diawara , Amidou Traore , Ali Thera , Antoine Dara , Amadou Niangaly , Modibo Daou , Issa Diarra , Youssouf Tolo , Mark A. Travassos
Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (fikk, phist, and surf) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.
恶性疟原虫是毒性最强的疟原虫,可导致危及生命的脑型疟疾和严重疟疾性贫血等严重疟疾综合征。在马里的一项病例对照研究中,我们通过比较来自严重疟疾病例的RNA-seq数据与匹配的有或没有脑疟疾病史的简单疟疾对照者的RNA-seq数据,确定了脑疟疾、严重疟疾贫血和具有这两种综合征的并发疾病中的寄生虫基因表达。虽然严重疟疾性贫血的比较产生了相对较低水平的差异表达,但脑疟疾和并发疾病的比较产生了涉及疾病严重程度升级过程的多基因家族(fikk, phist和surf)的显著差异表达,如细胞粘附性和红细胞重塑。我们用急性和恢复期血清检测了具有这些抗原的定制微阵列。患有严重疟疾的儿童在严重疟疾感染后对这些蛋白质的亚群产生抗体反应,这表明在疾病期间暴露于这些抗原以及它们作为发展针对严重疟疾的自然保护性免疫的靶标的潜力。我们的研究结果解决了严重疟疾贫血中寄生虫基因表达的知识空白。此外,这些结果扩大了与严重疟疾发病机制有关的多基因家族的范围,并强调了全转录组方法在全面了解严重疾病方面的效用,特别是在开发治疗方法或疫苗时。
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引用次数: 0
Long-term impact of nirsevimab on prevention of respiratory syncytial virus infection using a real-world global database 使用真实世界的全球数据库研究尼塞维单抗对预防呼吸道合胞病毒感染的长期影响。
IF 11.9 1区 医学 Q1 INFECTIOUS DISEASES Pub Date : 2025-11-07 DOI: 10.1016/j.jinf.2025.106652
Taito Kitano , Shinya Tsuzuki , Haruhisa Fukuda , Sayaka Yoshida

Objective

The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database.

Methods

This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching.

Results

A total of 4627, 861, and 532 children aged <24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p<0.001), 0.67 [0.48, 0.94] (p<0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively.

Conclusion

This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.
目的:尼塞维单抗(nirseimab)是一种长效单克隆抗体,对6个月以上呼吸道合胞病毒(RSV)感染的婴儿的预防作用尚未得到评价。本研究的目的是利用全球数据库评估尼罗维单抗在RSV感染后6个月以上的预防效果。方法:这是一项使用全球数据库(TriNetX)的多中心回顾性研究。参与者是在2023年7月至2025年6月期间需要进行RSV微生物检测(PCR或抗原检测)的24个月以下儿童。倾向评分匹配后,将6个月内、6 - 11个月和12个月以上接受最后一剂尼西莫单抗的儿童与未接受任何尼西莫单抗剂量的儿童按流行季节进行比较。结果:共有4,627,861和532名年龄的儿童。结论:本研究表明,尼塞维单抗对RSV感染的预防作用在给药后维持了长达12个月,而未观察到超过12个月的预防作用。由于一些重要的局限性,本研究的结果需要谨慎解释。
{"title":"Long-term impact of nirsevimab on prevention of respiratory syncytial virus infection using a real-world global database","authors":"Taito Kitano ,&nbsp;Shinya Tsuzuki ,&nbsp;Haruhisa Fukuda ,&nbsp;Sayaka Yoshida","doi":"10.1016/j.jinf.2025.106652","DOIUrl":"10.1016/j.jinf.2025.106652","url":null,"abstract":"<div><h3>Objective</h3><div>The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database.</div></div><div><h3>Methods</h3><div>This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching.</div></div><div><h3>Results</h3><div>A total of 4627, 861, and 532 children aged &lt;24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p&lt;0.001), 0.67 [0.48, 0.94] (p&lt;0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively.</div></div><div><h3>Conclusion</h3><div>This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"91 6","pages":"Article 106652"},"PeriodicalIF":11.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483615","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
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Journal of Infection
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