5-Year Follow-Up of Advanced Therapy Use in High-Risk Diabetic Foot Ulcers
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe study addresses an important clinical issue: the long-term outcomes of advanced biologic wound treatments in high-risk diabetic foot ulcer patients. The five-year follow-up adds value to the original research, offering insights into long-term mortality, re-ulceration, and amputation risk.
The study lacks a direct comparison to a control group receiving standard care. Without this, it is difficult to determine whether DAMA treatment provides a significant advantage. The study suggests that DAMA use does not increase the risk of mortality or amputation. However, without a control group, this statement should be softened to indicate association rather than causation.
Define “minor” and “major” amputations clearly.
More comparison with studies that had control groups would be beneficial.
in the discussion section, for completeness, it would be useful to cite some references regarding 3 important areas:
1- anticoagulant therapy (there are worldwide multicenter surveys of vascular surgeons regarding the use of rivaroxaban)
2- if the patients have performed complex recanalizations (there are studies that describe the recanalization of chronic femoropopliteal total occlusions also with the use of an intravascular ultrasound–guided re-entry catheter or the bidirectional approach, and typical patients are diabetics)
3- Sex-Related Differences (it may be a factor associated with mortality in patients with chronic limb ischemia, typical of diabetic patients)
Author Response
Comment 1: The study lacks a direct comparison to a control group receiving standard care. Without this, it is difficult to determine whether DAMA treatment provides a significant advantage. The study suggests that DAMA use does not increase the risk of mortality or amputation. However, without a control group, this statement should be softened to indicate association rather than causation.
RESPONSE 1: Thank you for highlighting this concern. We have adjusted our verbiage in both the abstract (page 1) and discussion (page 12) accordingly and appreciate the insight. One of the reasons we initiated the original study was because of the lack of studies with DAMA use in patients who are at high risk for amputation. Most studies focus on neuropathic ulcers with no associated complications (osteo, PAD, charcot). Thus, we were not able to find similar studies (intervention with DAMA for moderate to high risk patients) that had control groups. Thurs, we have focused on patients with DFUs and PAD to compare mortality and morbidity knowing that there is a lack of an intervention arm.(references 4, 5, 11, 12) In addition, we incorporated information on a 'real world' study that included DFUs (page 3 line 117-125 reference 14) which did not report a control group but the study population does more closely resemble ours.
Comment 2: Define “minor” and “major” amputations clearly.
RESPONSE 2: This was clearly an oversight on our part and we have added that clarification into the introduction section of the paper. Thank you! (Page 2 lines 60-64)
Comment 3: More comparison with studies that had control groups would be beneficial.
in the discussion section, for completeness, it would be useful to cite some references regarding 3 important areas:
1- anticoagulant therapy (there are worldwide multicenter surveys of vascular surgeons regarding the use of rivaroxaban)
2- if the patients have performed complex recanalizations (there are studies that describe the recanalization of chronic femoropopliteal total occlusions also with the use of an intravascular ultrasound–guided re-entry catheter or the bidirectional approach, and typical patients are diabetics)
3- Sex-Related Differences (it may be a factor associated with mortality in patients with chronic limb ischemia, typical of diabetic patients)
Comment 3: We are in full agreement that comparison with controlled studies (and systematic reviews) would enhance this report. Upon further review of the literature, it became apparent that there were several areas that would relate directly to our report. We have now incorporated information from systematic reviews and controlled studies addressing healing rates, amputation rates, rates of recurrence and related mortality of those with CLI (page 2, references 4,5,. We are hopeful you will support the areas that we focused on for the comparisons as they seemed to correlate well with our objectives and our data. Thank you
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript “5-year Follow-up of Advanced Therapy Use in High-risk Diabetic Foot Ulcers “ by Doucette et al. reports the early treatment with dehydrated amniotic (DAMA) tissue in patients with diabetic foot ulcers of moderate to high amputation risk results in the same outcomes as noted in current research of patients with low risk for amputation. This work is well designed. Here are the comments and suggestions:
- Some more important results can be added to the Abstract.
- In Table 1, the 5-year follow-up seem more mean age than that of the Initial study. Could the mean age also affect the outcome of this study?
- Some results can be presented in figures or plots.
Author Response
COMMENT 1 Some more important results can be added to the Abstract.
RESPONSE 1 We added information about hospitalizations - we would be happy to revisit this if you had something specific you thought would enhance the abstract
COMMENT 2 In Table 1, the 5-year follow-up seem more mean age than that of the Initial study. Could the mean age also affect the outcome of this study?
RESPONSE 2: That is an interesting consideration as the average age of this cohort (minus the 2 younger initial subjects) could create a bias though with the small numbers (and the scope of this work) we do not have a clear answer.
COMMENT 3 Some results can be presented in figures or plots.
RESPONSE 3: We totally agree and were fortunate to have a new biostatistician join our department who helped analyzed and develop visual representation of some of our data. Figures 1 Death by year and cause page 6, Figure 2 Ulcer recurrence Page 6, Figure 3; Number of Veteran by Amputation Type and LImb Page 6 Figure 4; Hospital admission cause page 10, Figure 5 Admissions due to DFU/complications vs all cause page 11.
