Myostatin gene invalidation does not prevent skeletal muscle mass loss during experimental sepsis in mice.

Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long-term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13-week-old C57BL/6J wild-type and myostatin knock-out male mice. Survival rates were similar in wild-type and myostatin knock-out mice seven days after CLP. Loss in muscle mass was also similar in wild-type and myostatin knock-out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3-ubiquitin ligases and autophagy-lysosome markers. This transcriptional response was blunted in myostatin knock-out mice. No change was observed in the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway. Muscle strength was similarly decreased in wild-type and myostatin knock-out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation-contraction coupling, suggesting that a long-term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation-contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis. KEY POINTS: Survival rates are similar in wild-type and myostatin knock-out mice seven days after the induction of sepsis. Loss in muscle mass and muscle strength are similar in wild-type and myostatin knock-out mice 4 and 7 days after the induction of an experimental sepsis. Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway remained unchanged. RT-qPCR analysis of autophagy-lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild-type and myostatin knock-out mice. Experimental sepsis induces greater variations in the mRNA levels of wild-type mice than those of myostatin knock-out mice, without providing any significant catabolic resistance or functional benefits.

MFI-11 Predicts Post-Operative Serious Complications in Patients Undergoing Surgery for Odontoid Fractures.

STUDY DESIGN: Retrospective Cohort. OBJECTIVES: The objective of this study was to analyze postoperative complications in different mFI-11 groups after surgery for odontoid fractures in a geriatric population. METHODS: A single center retrospective review of odontoid fractures surgery (between 2013 and 2022) in patients aged 65 years and older was conducted. The primary outcome was the occurrence of a major complication (Calvien-Dindo ≥4) within 30 days post-surgery. The secondary outcome was the occurrence of a major complication within 3 months after surgery, and death within 1-month post-surgery. Survival curve, multi-variate analysis was performed and adjusted receiver operating characteristic curves were generated. RESULTS: There were 92 patients included in this study, with a mean age of 80.5 years. Serious complication occurred for 16 patients (17%) during hospitalization. Multivariate analysis demonstrated an mFI 11 >.27 was strongly and independently associated with serious complications within 1-month post-surgery (OR = 16.7, 95% CI = 4.50-83), as well as serious complications within 3 months post-surgery (OR = 11.8, 95% CI = 3.48-49.1) and death within 1 month post-surgery (OR = 11.7; 95% CI = 3.02-60.4). The Receiver Operator Characteristics (ROC) curves for the three models all have an Area Under the Curve (AUC) value greater than 0.7. CONCLUSIONS: The mFI-11 is a straightforward and validated tool that can be used during the preoperative period to identify the patient's level of frailty and assess their risk of postoperative complications. Patients with mFI-11 ≥.27 are at greater risk of serious complications within 1 and 3 months' post-surgery and death within 1 month post-surgery.