手术时的蛋白质组学特征与假体周围关节感染的疾病分期和手术结果相关。

IF 4.7 1区 生物学 Q1 MICROBIOLOGY
mBio Pub Date : 2025-10-08 Epub Date: 2025-08-28 DOI:10.1128/mbio.01700-25
Kathleen O'Connor, Christina Koscianski, Nicholas Larson, Kiran K Mangalaparthi, Cody Hoffmann, Nicholas A Bedard, Khaled Elmenawi, Merrick T Ducharme, Jessica D Hohenstein, Daniel O'Brien, Akhilesh Pandey, Robin Patel
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引用次数: 0

摘要

假体周围关节感染(PJI)是关节置换术失败最常见和最难治疗的形式。虽然基于发病率和成本,清创、抗生素和种植体保留(DAIR)治疗比一期或两期种植体置换更可取,但并不是所有采用这种治疗策略的病例都成功。根据症状持续时间,目前建议在感染被认为处于“急性”期时采用DAIR;尽管采用了这种选择策略,DAIR的失败率仍然很高。一种更客观的预测DAIR成功的方法可以通过限制DAIR失败来改善患者的预后。为了探索这种可能性,我们对95名PJI患者的声学流体样本进行了先进的蛋白质组学分析,使用接近延伸试验(PEA),另外77个样本使用液相色谱串联质谱(LC-MS/MS)进行了补充蛋白质组学分析。稀疏偏最小二乘微分分析(sPLS-DA)将已知结果的DAIR患者样本(n = 19)分为成功组和不成功组,预测DAIR手术结果(曲线下面积[AUC]: 1;平均“遗漏一人”AUC: 0.6)。“蛋白修复”基因本体(GO)通路中预测DAIR手术结果的蛋白显著富集(P-adj = 0.02)。此外,与PJI症状持续时间相关的蛋白质组学特征将样本分为短症状持续时间和长症状持续时间PJI。总之,一项基于症状持续时间的7261种独特的人类蛋白质的研究分离了pji相关样本,并确定了预测DAIR成功的蛋白质组学特征。慢性感染通常持续数月至数年,急性感染持续数天至数周。然而,人们对从急性感染到慢性感染的转变知之甚少。假体周围关节感染(PJI)被认为是“慢性”治疗比“急性”治疗更具挑战性。当症状持续时间较短时,推荐采用恢复时间和成本较低的手术,清创、抗生素和种植体保留(DAIR);然而,即使在这个精选的患者组中,DAIR也与高治疗失败率相关。需要一种方法来更好地识别那些在接受DAIR治疗后预计会取得成功的患者。在这里,从人类临床PJI样品中测量了7000多种蛋白质,并显示能够根据症状持续时间分离样品。重要的是,确定了预测DAIR成功的蛋白质组学谱。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Proteomic profile at the time of surgery correlates with disease stage and surgical outcome in periprosthetic joint infection.

Periprosthetic joint infection (PJI) is the most common and difficult to treat form of arthroplasty failure. While treatment with debridement, antibiotics, and implant retention (DAIR) is preferable to one- or two-stage implant exchange based on morbidity and cost, outcomes are not successful in all cases selected for this management strategy. DAIR is currently recommended when infection is perceived to be in an "acute" phase, based on symptom duration; despite this selection strategy, DAIR failure rates are high. A more objective means of predicting DAIR success could improve patient outcomes by limiting DAIR failures. To explore this possibility, advanced proteomic analysis of sonicate fluid samples from 95 subjects with PJI was performed using proximity extension assay (PEA), with 77 samples additionally undergoing complementary proteomics analysis with liquid chromatography with tandem mass spectrometry (LC-MS/MS). Sparse partial least squares differentiation analysis (sPLS-DA) separated samples from patients who underwent DAIR with known outcomes (n = 19) into successful or unsuccessful groups, predicting DAIR surgical outcome (area under the curve [AUC]: 1; mean "leave one out" AUC: 0.6). Proteins predictive of DAIR surgical outcome were significantly enriched for the "protein repair" Gene Ontology (GO) pathway (P-adj = 0.02). Additionally, proteomic signatures associated with symptom duration in PJI categorized samples into short and long symptom duration PJI. In summary, an investigation of 7,261 unique human proteins separated PJI-associated samples based on symptom duration and identified a proteomic profile predictive of DAIR success.IMPORTANCEChronic infections are generally understood to last months to years, with acute infections lasting days to weeks. The transition from acute to chronic infection is, however, poorly understood. Periprosthetic joint infection (PJI) has been considered more challenging to treat when "chronic" than when "acute." A surgery preferred for its recovery time and cost-debridement, antibiotics, and implant retention (DAIR)-is recommended for PJI management when symptom duration is short; yet, even in this select patient group, DAIR is associated with a high treatment failure rate. A means to better identify those predicted to have a successful outcome if they undergo DAIR is needed. Here, over 7,000 proteins from human clinical PJI samples were measured and shown to be able to separate samples based on symptom duration. Importantly, a proteomic profile predictive of DAIR success was identified.

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来源期刊
mBio
mBio MICROBIOLOGY-
CiteScore
10.50
自引率
3.10%
发文量
762
审稿时长
1 months
期刊介绍: mBio® is ASM''s first broad-scope, online-only, open access journal. mBio offers streamlined review and publication of the best research in microbiology and allied fields.
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