Chronic critical illness, how to manage it?

Garcı́a-de-Lorenzo, Abelardo; Añón, J.M.; Asensio, M.J.; Burgueño, P.

doi:10.1016/j.medine.2022.02.017

Cited by 2 publications

(2 citation statements)

References 9 publications

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“…Chronic critical illness patients experience prolonged hospitalization, impaired wound healing, severe disability, and long-term neurocognitive deficits (12,13). They also have higher mortality rates and lower chances of being discharged from hospitals compared with rapid-recovery ICU patients, with in-hospital mortality rates reaching up to 31% and long-term mortality rates up to 75% (14). Furthermore, CCI patients require complex critical care and consume significant healthcare resources (7).…”

Section: Introductionmentioning

confidence: 99%

Chronic Critical Illness-Induced Muscle Atrophy: Insights From a Trauma Mouse Model and Potential Mechanism Mediated via Serum Amyloid A

Lei,

Feng,

Zhang

et al. 2024

Shock

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Background Chronic critical illness (CCI), which was characterized by persistent inflammation, immunosuppression, and catabolism syndrome (PICS), often leads to muscle atrophy. Serum amyloid A (SAA), a protein upregulated in critical illness myopathy, may play a crucial role in these processes. However, the effects of SAA on muscle atrophy in PICS require further investigation. This study aims to develop a mouse model of PICS combined with bone trauma to investigate the mechanisms underlying muscle weakness, with a focus on SAA. Methods Mice were used to examine the effects of PICS following bone trauma on immune response, muscle atrophy, and bone healing. The mice were divided into two groups: a bone trauma group and a bone trauma with cecal ligation and puncture (CLP) group. Tibia fracture surgery was performed on all mice, and PICS was induced through CLP surgery in the PICS group. Various assessments were conducted, including weight change analysis, cytokine analysis, hematological analysis, grip strength analysis, histochemical staining, and immunofluorescence staining for SAA. In vitro experiments using C2C12 cells (Myoblasts) were also conducted to investigate the role of SAA in muscle atrophy. The effects of inhibiting receptor for advanced glycation endproducts (RAGE) or JAK2 on SAA-induced muscle atrophy were examined. Bioinformatic analysis was conducted using a dataset from the GEO database to identify differentially expressed genes and construct a co-expression network. Results Bioinformatic analysis confirmed that SAA was significantly upregulated in muscle tissue of patients with ICU-induced muscle atrophy. The PICS animal models exhibited significant weight loss, spleen enlargement, elevated levels of pro-inflammatory cytokines, and altered hematological profiles. Evaluation of muscle atrophy in the animal models demonstrated decreased muscle mass, grip strength loss, decreased diameter of muscle fibers, and significantly increased expression of SAA. In vitro experiment demonstrated that SAA decreased myotube formation, reduced myotube diameter, and increased the expression of muscle atrophy-related genes. Furthermore, SAA expression was associated with activation of the FOXO signaling pathway, and inhibition of RAGE or JAK2/STAT3-FOXO signaling partially reversed SAA-induced muscle atrophy. Conclusions This study successfully develops a mouse model that mimics PICS in CCI patients with bone trauma. SAA plays a crucial role in muscle atrophy through the JAK2/STAT3-FOXO signaling pathway, and targeting RAGE or JAK2 may hold therapeutic potential in mitigating SAA-induced muscle atrophy.

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Section: Introductionmentioning

confidence: 99%

Chronic Critical Illness-Induced Muscle Atrophy: Insights From a Trauma Mouse Model and Potential Mechanism Mediated via Serum Amyloid A

Lei,

Feng,

Zhang

et al. 2024

Shock

View full text Add to dashboard Cite

show abstract

“…Long-stay patients in the ICU have special needs [2]. It has been estimated that approximately 5% of ICU admissions have prolonged stays for 2 weeks or even longer [3].…”

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confidence: 99%