The goal of this clinical trial is to study whether physical therapy can reduce NLRP3 inflammasome activation and muscle atrophy in patients with critical illness myopathy (CIM). It will also explore the role of NLRP3 inflammasome in the pathophysiology of CIM. The main questions this study aims to answer are: Is NLRP3 inflammasome activation associated with muscle atrophy through the upregulation of atrogenes? Does physical therapy attenuate NLRP3 inflammasome activation in skeletal muscle, thereby contributing to the prevention or reduction of muscle atrophy in CIM? Researchers will compare enhanced physical therapy using servo-assisted bed cycling (Motomed Letto®) in critically ill patients at risk of developing CIM during the early phase of ICU stay to conventional physical therapy (standard physiotherapy), to assess whether physical therapy reduces NLRP3 inflammasome activation and muscle degradation. Participants will: Be randomized to receive either conventional physical therapy or enhanced physical therapy (Motomed Letto®) for 7 consecutive days. A control group of patients without CIM will also be included. Undergo assessments of NLRP3 activity, muscle atrophy markers, and transcriptomic profiles from serum and vastus lateralis muscle biopsies. Be clinically evaluated using the SOFA scale and muscle ultrasound for CIM diagnosis. Be followed up for changes in muscle strength and physical functionality. Provide sociodemographic and clinical information to be recorded throughout the study.
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Relative mRNA expression of NLRP3, IL-1β, and IL-18 in muscle tissue (RT-qPCR)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Protein expression of phospho-p65S536 and total p65 (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Ratio of cleaved/uncleaved caspase-1, IL-1β, and GSDMD-NT (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Plasma concentrations of IL-1β and IL-18 (ELISA)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Expression of oxidative stress markers and cathepsin B (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Expression of cathepsin B (RT-qPCR)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Ultrastructural mitochondrial damage and lysosomal vacuolization (TEM)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Muscle fiber diameter (immunofluorescence)
Timeframe: Baseline and Day 7 (on the final day of intervention)
mRNA expression of atrogenes: MuRF1, Atrogin-1, MUSA1, TRIM62, TRIM32
Timeframe: Baseline and Day 7 (on the final day of intervention)
Myosin/actin ratio (Western blot)
Timeframe: Baseline and Day 7 (on the final day of intervention)
Sarcomeric organization (TEM)
Timeframe: Baseline and Day 7 (on the final day of intervention)