Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
Department of Agricultural, Food & Nutritional Science, Human Nutrition Research Unit, University of Alberta, Edmonton, AB, Canada.
Appl Physiol Nutr Metab. 2023 Oct 1;48(10):751-756. doi: 10.1139/apnm-2023-0176. Epub 2023 Jul 20.
Sarcopenia, sarcopenic obesity, malnutrition, and cachexia clinical guidelines were created by expert consensus over the past decade. These pathological states all share in common deficits in skeletal muscle mass, and in some cases muscle function, which adversely impact patient outcomes. Early identification is key as some detrimental outcomes are potentially preventable with available treatments. The four guidelines share common design features: patients suspected of having the condition are first screened with a focused clinical history; if positive, the next step is evaluation with either a measure of body "form" (e.g., mass, shape, and composition) or function (e.g., mechanical, endurance, and metabolic); combined form and functional criteria are also recognized. The form and functional "gateway" nodes establish whether or not to proceed with further evaluations and treatments. Intensive discussions among experts focus on selection of these gateway nodes and the final choice is made when consensus is reached. Form and functional measures are often treated as equivalent alternatives when framed in the context of "outcomes" for which they are intended to predict. Here we adapt a classic biological concept stating that "function follows form" to show that pathophysiological links are present between these two different muscle qualities and clinical outcomes. We argue that a hierarchy exists such that outcomes closely follow functions that, in turn, follow form…the OFF rule. The OFF rule explains why functional measures often show stronger associations with outcomes than those quantifying form, helps to frame debates on how to structure the gateway nodes used to identify patients for further evaluation and treatment, and sets out a pathophysiological structure for developing future outcome prediction models.
肌肉减少症、肌少症合并肥胖症、营养不良和恶病质的临床指南是过去十年间通过专家共识制定的。这些病理状态都存在骨骼肌质量下降，某些情况下还伴有肌肉功能下降，这会对患者的预后产生不利影响。早期识别是关键，因为一些不良结局可能可以通过现有治疗来预防。这四条指南具有共同的设计特征：首先，对疑似患有该疾病的患者进行有针对性的临床病史筛查；如果阳性，下一步是使用身体“形态”（如质量、形状和组成）或功能（如机械、耐力和代谢）的测量方法进行评估；也认可形态和功能联合标准。形态和功能“门户”节点确定是否进行进一步评估和治疗。专家之间进行了深入讨论，重点是选择这些门户节点，最终选择是在达成共识时做出的。在为预期的“结果”构建框架时，形态和功能测量通常被视为等效的替代方法。在这里，我们改编了一个经典的生物学概念，即“功能决定形态”，以表明这两种不同的肌肉质量与临床结果之间存在病理生理联系。我们认为存在一种层次结构，结果密切跟随功能，功能又跟随形态……即“OFF 规则”。OFF 规则解释了为什么功能测量通常比定量形态的测量与结果具有更强的关联，有助于围绕如何构建用于识别患者以进行进一步评估和治疗的门户节点展开辩论，并为开发未来的结果预测模型提供了病理生理学结构。
