I want to thank the opportunity to review the article "Association of Incident Diabetic Foot Ulcer with Lower-Extremity Amputation Risk: The Prospective Seattle Diabetic Foot Study".
The study was well conducted, the article was clearly written, and the topic was somewhat relevant. Although the link between a diabetes-related ulcer and lower extremity amputation was already addressed in previous studies, the authors added some novelty by studying the link between an incident ulcer and amputation in a sound cohort.
There are, however, several aspects that require further clarification and/or changes.
In the introduction, it should be stated that besides the evidence provided by retrospective studies, there is also a biological plausibility that may justify the absence of prospective studies. Therefore, further rationale should be provided for the novelty and relevance of this study.
In the research design and methods, I suggest providing previous references for studies that described the study population and data collection in further detail.
Line 191, please provide the full description of the abbreviations.
Line 198, please define lost-to-follow-up as they seem not to have existed in line 251.
In the statistical analysis, please justify why means and standard deviations were provided, although several variables will expectably have an asymmetrical distribution.
It would be interesting to provide data for a patient analysis as a sensitivity analysis.
Line 237, please clarify how variables were selected to be included in the models and if having only 72 LEA does not limit this selection.
Also, please clarify if collinearity between variables was accounted for or justify why it is not necessary.
I suggest providing a median number of clinic evaluations and follow-up duration. If not, please discuss that for a mean of 4.9 years of follow-up, patients attended an average of 1 appointment every 2 years (mean of 2.4).
In Table 1, please change "per cent with an amputation" to "amputation occurrence (%)" and provide % in the male's N feet column.
Also, please clarify how, on the dorsal foot TcPO2, a lower percentage of LEA gave origin to a 1.41 HR.
Please clarify why the number of participants in Table 2 is different from Table 1.
Line 412, please consider a potential survivor bias.
Line 440, please add that in this study, only 29 people presented with Charcot's foot, which may have impacted the precision of the estimates.
The discussion should address that the profile of people followed in diabetic foot clinics has changed over the years. Having a cohort that ended its recruitment in 2002 may not capture these changes and may provide outdated estimates.

Thank you very much for taking the time to reply to the reviewers' comments.
I only have minor suggestions that I believe can be easily attended to:
Reviewer #1
Comment #5 please report the number of people lost to follow-up
Comment #7 Thank you for the information. Please add it to the discussion and highlight the relevance of conducting both analysis
Comment #12 Please clarify with a note on the tables the reason for the differences, so that the reader can easily understand it.