## 2 Patients and Methods
### Patient-Reported Outcome Measures Instruments  
Subjects completed five surveys at nine timepoints throughout their enrollment: preoperatively, 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 24 months, 36 months, and 48 months post-operatively. The surveys were administered using REDCap 13.1.37 (Research Electronic Data Capture) electronic data capture tools hosted at the Brigham & Women's Hospital (BWH). REDCap is a secure, web-based software platform designed to support data capture for research studies, providing an intuitive interface for validated data capture. All surveys have been previously validated for assessment of patients with lower extremity injuries and/or amputations. Descriptions of the surveys utilized are as follows.  
The EQ-5D-3L consists of five dimensions: mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression. Each dimension has three levels: no problems (1), some problems (2), and extreme problems (3). The response to each dimension results in a five-number health state (e.g., 12312) that is transformed into an index value from 0 to 1. A higher index value indicates a better health state. Respondents also designate their overall health state according to a Visual Analogue Scale (VAS) on a 0- to 100-point scale where 0 indicates worst health state imaginable and 100 indicates best health state imaginable [18,19].  
The Lower Extremity Functional Scale (LEFS) consists of 20 questions and is scored on a scale of 0-80 points, with a higher score indicating higher functionality [20].  
The PROMIS-57 is a collection of short forms assessing seven PROMIS domains (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities) with 8 questions per domain. Each domain yields a T-score metric with the mean of the US general population equal to 50 \(\pm\) 10. In the domains of Pain Interference, Fatigue, Anxiety/Depression, Sleep Disturbance, and Depression/Sadness, a higher score indicates that the patient is more likely to have a negative outcome within that domain. In the domains of Physical Function and Ability to Participate in Social Roles and Activities, a higher score indicates that the patient is more likely to have a positive outcome within that domain [21,22].  
The Short-form 36 (SF-36) is a 36-item short form designed to assess eight health domains for the purpose of evaluating a patient's health-related quality of life. The health domains include physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional wellbeing, social functioning, pain, and general health. The eight health domain scores can be summarized by a physical and mental component score (PCS and MCS). The PCS and MCS are calculated as a weighted sum of all eight domain scores. However, the PCS heavily weighs Physical Functioning, Role Limitations Due to Physical Health, Pain, General Health, and Energy/Fatigue. Conversely, the MCS heavily weighs Social Functioning, Role Limitations Due to Emotional Problems, and Emotional Well-being [23,24,25].  
Figure 1: Illustration of AMI construction in the setting of (**A**) transtibial amputation and (**B**) trans-femoral amputation.  
The Sickness Impact Profile (SIP) is a 136-item questionnaire designed to assess a patient's general dysfunction amongst 12 categories including sleep and rest, eating, work, home management, recreation and pastimes, ambulation, mobility, body care and movement, social interaction, alertness behavior, emotional behavior, and communication. An overall dysfunction score is calculated where the score ranges from 0 to 100%. A lower score indicates less dysfunction [26].