Scholarlink

Aim <p>Our objective was to increase our understanding of the effects of the time course of metabolic alterations on the risk of hospital-acquired pneumonia (HAP) and response to treatment in critically ill patients.</p> Methods <p>We first studied the blood metabolome at day 1, day 3-4 and day 6-7 of patients from a prospective, observational cohort of brain-injured patients in two French centres. We classified the metabolic response by unsupervised longitudinal consensus clustering. To evaluate the robustness of metabolic patterns, a Fast-and-Frugal Tree trained on the discovery cohort was applied to a replication dataset from the PREV-HAP randomised clinical trial testing interferon gamma-1b for the prevention of HAP in critically ill patients. The primary outcome was the association of metabolic response patterns with HAP.</p> Findings <p>Of the 128 patients analysed (330 samples), 57 (45%) had developed HAP and 21 (16%) acute respiratory distress syndrome (ARDS). Based on metabolites involved in fatty acid metabolism, we identified three metabolic response patterns associated with the risks of HAP (24%, 60% and 78% of HAP, respectively) and ARDS (6%, 16% and 43%, respectively). In a replication dataset (315 samples from 105 patients), we found similarities regarding blood metabolite temporal courses and associations with HAP (18%, 28% and 40% of HAP, respectively). Moreover, the probability of being discharged alive from the ICU with interferon gamma-1b was decreased in patients with low-risk metabolic response patterns and increased in patients with high-risk metabolic response patterns.</p> Conclusions <p>Longitudinal clustering classified metabolic response patterns into low-, moderate-, and high-risk groups for HAP and can help identify responders and non-responders to interferon gamma-1b after a single treatment injection.</p> Trial registration <p>Number clinicaltrial.gov NCT02003196 and NCT04793568 </p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Identification of a robust metabolic signature associated with hospital-acquired pneumonia and response to interferon-gamma treatment in critically ill patients

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月12日

查看全文
  • Melanie Petrier,
  • Debajyoti Sinha,
  • Florian P. Martin,
  • Cecile Poulain,
  • Delphine Flattres Duchaussoy,
  • Athanasios Ziogas,
  • Boris Novakovic,
  • Laura Hurtado-Navarro,
  • Anaísa V Ferreira,
  • Joost H. A. Martens,
  • Despoina Koulenti,
  • Laia Fernández-Barat,
  • Antoni Torres,
  • Emmanuel Montassier,
  • Mihai G. Netea,
  • Jeremie Poschmann,
  • Antoine Roquilly

摘要

Aim

Our objective was to increase our understanding of the effects of the time course of metabolic alterations on the risk of hospital-acquired pneumonia (HAP) and response to treatment in critically ill patients.

Methods

We first studied the blood metabolome at day 1, day 3-4 and day 6-7 of patients from a prospective, observational cohort of brain-injured patients in two French centres. We classified the metabolic response by unsupervised longitudinal consensus clustering. To evaluate the robustness of metabolic patterns, a Fast-and-Frugal Tree trained on the discovery cohort was applied to a replication dataset from the PREV-HAP randomised clinical trial testing interferon gamma-1b for the prevention of HAP in critically ill patients. The primary outcome was the association of metabolic response patterns with HAP.

Findings

Of the 128 patients analysed (330 samples), 57 (45%) had developed HAP and 21 (16%) acute respiratory distress syndrome (ARDS). Based on metabolites involved in fatty acid metabolism, we identified three metabolic response patterns associated with the risks of HAP (24%, 60% and 78% of HAP, respectively) and ARDS (6%, 16% and 43%, respectively). In a replication dataset (315 samples from 105 patients), we found similarities regarding blood metabolite temporal courses and associations with HAP (18%, 28% and 40% of HAP, respectively). Moreover, the probability of being discharged alive from the ICU with interferon gamma-1b was decreased in patients with low-risk metabolic response patterns and increased in patients with high-risk metabolic response patterns.

Conclusions

Longitudinal clustering classified metabolic response patterns into low-, moderate-, and high-risk groups for HAP and can help identify responders and non-responders to interferon gamma-1b after a single treatment injection.

Trial registration

Number clinicaltrial.gov NCT02003196 and NCT04793568