Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM ( n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls ( n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children’s outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid–binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery.

中文翻译：

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炎症和上皮修复可预测复杂性严重急性营养不良的死亡率、再入院和生长恢复

严重急性营养不良 (SAM) 是营养不良中风险最高的形式，特别是当儿童因并发症需要住院治疗时。复杂性 SAM 是一种多系统疾病，住院患者和出院后死亡率较高，尤其是患有 HIV 等合并症的儿童；然而，复杂 SAM 的潜在发病机制尚不清楚。对因 SAM 住院的儿童进行靶向多重生物标志物分析（n= 264）对血浆样本进行了评估，并对津巴布韦和赞比亚三家医院招募时、出院时以及出院后 12 至 24 周和 48 周采集的粪便样本进行了炎症标志物评估。与营养充足的对照相比（n= 173），我们发现在基线时，复杂的 SAM 的特点是全身、内皮和肠道炎症，而 HIV 感染会加剧这种炎症。尽管营养已恢复，但这种情况持续了 48 周以上，并且与儿童的预后有关。血管内皮生长因子、胰高血糖素样肽-2 和肠脂肪酸结合蛋白的基线血浆浓度与接下来 48 周内较低的死亡率或再入院率独立相关。对基线生物标志物进行主成分分析后，代表生长因子的成分得分越高，与身高体重越大相关z48 周内评分恢复并降低死亡率或再入院率。相反，代表较高肠道和全身炎症的成分与较高的死亡率或再入院相关。这些发现强调了损伤组织的炎症与介导内皮和上皮再生的生长因子之间的相互作用，并支持进一步研究减少炎症和促进上皮修复的干预措施，作为降低死亡率和改善营养恢复的方法。