## 4 Discussion  
Our study assessed a wide range of factors that influence a patient's quality of life including less reported factors such as emotional health, fatigue, anxiety/depression, and social functioning. AMI amputees demonstrated significant improvements across all surveys and sub-scores 12 months post-amputation within both physical and mental health domains. These results support the notion that the modified AMI amputation at both the transtibial and transfemoral level can meaningfully improve patients' quality of life compared to their pre-operative state.  
Compared to patients' pre-operative baseline, all eight health domains and component scores of the SF-36 significantly improved at 12 months post-amputation, suggesting that the AMI amputation leads to a multidimensional improvement in patients' quality of life beyond the commonly reported outcome measures of pain and physical functioning [9; 28; 29; 30]. The Physical Component Score had a greater mean increase than the Mental Component Score, which could indicate that the AMI procedure has a more substantial positive impact on patients' post-operative physical health versus their mental health.  
While results at timepoints other than baseline and 12 months post-operation were not explicitly discussed, it is pertinent to note that a significant improvement was demonstrated at 3 months, 6 months, and 9 months post-operation compared to baseline amongst all surveys and their sub-scores (Appendix A Tables A1-A5). Furthermore, significant improvements appear to persist in patients' annual survey responses at 24 months, 36 months, and 48 months post-operation (Figures 1-6). It is relevant to note that results beyond the 24 month mark appear to demonstrate some variability in some surveys; however, only a minority of our patient cohort has reached these annual timepoints to date and this variability may be more of a reflection of small sample size than a significant change in long-term outcomes. Therefore, definitive conclusions should not be drawn from the annual outcomes at this time.  
Further investigation is necessary to determine what factors correlate with the demonstrated outcomes. While this paper is currently in press, our team has also demonstrated significantly improved functionality based on physical therapy functional outcome measures. Based on the results of this investigation, we postulate a positive correlation between functional outcomes and PROMs scores. Furthermore, the presence of residual limb pain and phantom limb pain is considered an important post-operative outcome in the setting  
Figure 7: Mean SIP dysfunction scores at 0 to 48 months post-operation for patients undergoing a modified AMI amputation including standard error bars.  
of amputation [31; 32]. Multivariate analysis would be required to determine the impact of residual and phantom limb pain on our results.  
Limitations of this study include the possibility of bias due to patient self-reporting as well as patients' high expectations based on media coverage and publicly accessible literature regarding the novelty and promise of the AMI amputation procedure. It is also important to note that all patients in our cohort underwent elective amputations due to chronic pain from past trauma, congenital disorders, or vascular disorders, and often sought out our clinical trial as a last resort following other limb salvage attempts. An additional source of bias could arise because the senior author ([PERSON]) played a significant role in the development of the modified AMI amputation. Last, our results prompt us to ask the question of how our cohort's outcomes compare to those from other amputation techniques (e.g., standard amputation, amputation with TMR, and amputation with RPNI) and limb salvage procedures (e.g., fusion, joint replacement, and tissue/nerve reconstruction). A comparison of PROMs data between these procedures is key to determining whether the AMI amputation provides patients with a superior option with regard to optimizing their quality of life.