Journal of Cachexia Sarcopenia and Muscle最新文献

Skeletal muscle (SM) is an integral organ component in the pathophysiology of many acute and chronic diseases. But is there a ‘gold’ standard or accepted reference method for quantifying the amount and composition of human SM mass? Exploring that question led us to recognize the existence of a SM measurement paradigm that divides methods into two broad categories, in vitro and in vivo. In vitro methods quantify SM mass, weighing intact muscles as part of whole cadaver evaluations, only 51 of which are reported in medical literature with no recent additions. In vivo methods are used to evaluate SM in vivo, and two tiers were revealed in our analyses. An upper tier that included three methods considered ‘reference’ approaches for their accuracy and precision: computed tomography, magnetic resonance imaging and dual-energy X-ray absorptiometry. A lower in vivo method tier included bioimpedance analysis, three-dimensional imaging, several approaches involving creatine metabolism, ultrasound and anthropometry. A feature common to all of the lower tier methods is their need for calibration or validation against reference approaches in the upper in vivo method tier. A critical review of the three in vivo reference methods in the upper tier revealed widely variable SM volume/mass acquisition protocols, image analysis methods and applied terminology. Some reports espouse an upper tier reference method as the ‘gold’ standard while providing minimal details of exactly how and what was measured, thus making replication in follow-up studies difficult. Any technical issues related to an in vivo reference method are propagated to the in vivo methods in the lower tier that are calibrated or validated against them. Our review of in vivo reference methods of quantifying SM mass and composition led us to two broad recommendations. First, published reports including these reference methods should provide enough details related to acquisition and analysis protocols so that readers can replicate their findings. Second, an effort should be made to apply precise terminology in published reports in order to avoid confusion on exactly what was measured; suggestions are made on definitions of commonly used terms when referring to body composition compartments. Lastly, because there is no consensus on what constitutes a ‘gold’ standard for SM measurement, we suggest expert groups convene in the future to recommend optimum approaches and working guidelines for quantifying muscle mass and composition in vivo.

Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, presents a multifaceted challenge that affects both skeletal muscle function and cardiomyocyte homeostasis, causing progressive degeneration and life-threatening cardiac complications by adolescence. Current treatments fail to prevent poor prognoses, and while FDA-approved therapies show promise in targeting dystrophin restoration, including RNA-based approaches and microdystrophin gene therapy, clinical evidence supporting their efficacy remains limited. Substantial challenges persist, particularly in achieving effective cardiac targeting, ensuring long-term safety and developing scalable treatments. Alternative therapies addressing muscle and cardiac pathophysiology are being explored alongside dystrophin-based approaches. DMD treatment is increasingly focusing on heart targeting with optimized cardiac-specific delivery strategies. Human-induced pluripotent stem cells (hiPSCs) enable DMD modelling, bridging pathophysiology and clinical phenotypes. DMD patient–specific hiPSC-derived cardiomyocytes (hiPSC-CMs) serve as in vitro models for disease mechanisms and therapy, with 3D cardiac models, either self-organizing (spheroids) or moulded, expanding on hiPSC-CMs to reflect cell interactions and myocardial tissue architecture. Advanced methods like 2D cell sheets, patches and engineered 3D human cardiac models show potential for improving cell engraftment and functional recovery in injured hearts, but their direct therapeutic application in DMD remains speculative due to extensive muscle mass loss; the complexity of cardiac and skeletal muscle interactions; and unresolved challenges related to cell integration, maturation and long-term function. Considering the premature state of cell-based therapies in this complex disease, current DMD treatment efforts focus on genetic approaches. Progress will likely depend on combining dystrophin-restoring strategies with therapies targeting disease mechanisms and improving cardiac delivery.