Effects of Rehabilitation Exercise with Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction

Round 1

Reviewer 1 Report

Dear Authors,

In my opinion, the topic is interesting; however, I have some doubts regarding the methodological implant of this study, and some critical issues should be addressed.

 

Major revisions:

METHODS: The study design should be better clarified.

METHODS: The Authors should specify if the rehabilitation exercise program was supervised or not.

METHODS: The authors should better clarify who performed the analysis and who supervised the rehabilitation exercise program (qualification, degree).

RESULTS: This section should be improved, reporting the numbers of patients assessed for eligibility, and patients excluded, clarifying at least the main cause of exclusions. A study flowchart might improve the legibility of the study results.

DISCUSSION: Given that the authors in the "Introduction" section specify how sports activity can increase the risk of incurring knee injuries and how prevention is a key point in managing this problem, it could be useful to insert information about possible prevention strategies. For example, a theme that has been gaining ground in recent years is preventing injuries by studying better the biomechanics of the movements required by individual sports. Another important topic is the specific demands of the sport, which can be evaluated through match analysis. So, the analysis of movement and match analysis could play a fundamental role.

-       Zhou H, Xu D, Chen C, Ugbolue UC, Baker JS, Gu Y. Analysis of Different Stop-Jumping Strategies on the Biomechanical Changes in the Lower Limbs. Applied Sciences. 2021; 11(10):4633. doi: 10.3390/app11104633.

-       Demeco A, de Sire A, Marotta N, Spanò R, Lippi L, Palumbo A, Iona T, Gramigna V, Palermi S, Leigheb M, Invernizzi M, Ammendolia A. Match Analysis, Physical Training, Risk of Injury and Rehabilitation in Padel: Overview of the Literature. Int J Environ Res Public Health. 2022;19(7):4153. doi:10.3390/ijerph19074153.

-       Kunzmann E, Ford KR, Sugimoto D, Baca A, Hank M, Bujnovsky D, Mala L, Zahalka F, Maly T. Differences in External and Internal Load in Elite Youth Soccer Players within Different Match Timing Zones. Applied Sciences. 2022; 12(14):7230. doi: 10.3390/app12147230.

 

Minor revisions:

ABSTRACT: Some words have typing errors. For example, in the Abstract section, there are “rehabil-itation” and “param-eters”, while in the Results section there is the word “interven-tion”. Please correct any typing errors.

Author Response

We thank the reviewer for their guidance for further improving our revised manuscript (applsci-2048476) entitled “Effects of Rehabilitation Exercise with Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction”. As described below, we have responded to all the comments brought up by the reviewers and incorporated all the changes suggested by the reviewer.

 

Reviewer1:

Dear Authors,

In my opinion, the topic is interesting; however, I have some doubts regarding the methodological implant of this study, and some critical issues should be addressed.

 

Major revisions:

 

METHODS: The study design should be better clarified.

- Thank you for your valuable opinion. In order to clarify the Study design in this study, we added the CONSORT flow chart and added the contents of the study design.

‘The present study design is illustrated in Figure 2. All participants conducted a pre-test, 12-week of rehabilitation exercise program applied to each group, and a post-test. Pre-tests were performed after being diagnosed with an ACL rupture by an orthopedic surgeon. The pre-test was completed 1-day be-fore the ACL reconstruction, and post-test was conducted 2-days after the last rehabilitation exercise program. On the test day, all participants visited the Sports Medical Center at M hospital, and were tested after stabilization. All patients visited the rehabilitation center of M Hospital three times a week for 12 weeks and conducted it for 1 hour under supervision. The GRE group conducted a general rehabilitation movement, and the BFR group conducted a BFR movement along with the general rehabilitation movement. Before and after the 12-week rehabilitation exercise session, all participants underwent anthropometry (e.g., height and weight), the Lysolum score and the IKDC subjective score, muscle activity (e.g., quadriceps femoris), isokinetic muscular function (e.g., strength and endurance), and balance (e.g., Y-balance anterior, Y-balance posterior medial, and Y-balance posterior lateral).’

 

METHODS: The Authors should specify if the rehabilitation exercise program was supervised or not.

- Thank you for your valuable opinion. All rehabilitation exercise programs in this study were conducted under supervision.

 

METHODS: The authors should better clarify who performed the analysis and who supervised the rehabilitation exercise program (qualification, degree).

- Thank you for your valuable opinion. In order to clarify the Study design in this study, we added the CONSORT flow chart and added the contents of the study design. In addition, the analysis was conducted by the author with the first-class social analyst license, and the qualifications of the person who supervised the rehabilitation exercise program were added to the text as follows.

‘Our study included 30 patients undergoing acute reconstruction or planning due to ACL injury. Four subjects included in patients who underwent suture surgery after accompanying cartilage damage, patients whose initial muscle strength did not de-crease due to chronic damage, and elite athletes were excluded. Among a total of 26 patients, the general rehabilitation exercise group (GRE, n = 13) and blood flow re-striction group (BFR, n = 13) were assigned the same according to age, gender, height, and weight. All patients had ACL reconstruction performed by an authoritative knee orthopedic surgeon at M Hospital using own transplant method, and was performed by a rehabilitation team at the same hospital with a doctorate in physical therapy cer-tificate and rehabilitation. All evaluations were performed the same before and 12 weeks after ACL reconstruction. After the 12-week rehabilitation exercise program, post-evaluation was conducted on those who regularly visited the center three a week. One patient per each group who did not fall under this category were excluded from the participants, and a total of 24 participants (age: 29.3 ± 8.0 years; men 18 and women 6) were used for the analysis. The physical characteristics of the participants and CONSORT flow chart are shown in Table 1 and Figure 1.’

 

RESULTS: This section should be improved, reporting the numbers of patients assessed for eligibility, and patients excluded, clarifying at least the main cause of exclusions. A study flowchart might improve the legibility of the study results.

- Thank you for your valuable opinion. Sample size items have been added to clarify the eligibility of the minimum number of people in this study. The contents are as follows: In addition, the order of the research results is described in the study design measurement items.

‘2.9. Sample size

In this study, the G*power® Version 3.1.9.2 Software was used to calculate the minimum sample size. The maximum power threshold reported in Tenent et al. (2017) was used to calculate the priori sample size required for repeated measurement vari-ance analysis. A total of 24 participants were required to obtain a statistical power of 95% at an effect size of d = 0.6 and α = 0.05 including two conditions and two measurement points.’

 

DISCUSSION: Given that the authors in the "Introduction" section specify how sports activity can increase the risk of incurring knee injuries and how prevention is a key point in managing this problem, it could be useful to insert information about possible prevention strategies. For example, a theme that has been gaining ground in recent years is preventing injuries by studying better the biomechanics of the movements required by individual sports. Another important topic is the specific demands of the sport, which can be evaluated through match analysis. So, the analysis of movement and match analysis could play a fundamental role.

- Thank you for your valuable opinion. As the Reviewer said, efforts to prevent injuries are important. Therefore, I added the following references to the beginning of the discussion.

 

- Zhou H, Xu D, Chen C, Ugbolue UC, Baker JS, Gu Y. Analysis of Different Stop-Jumping Strategies on the Biomechanical Changes in the Lower Limbs. Applied Sciences. 2021; 11(10):4633. doi: 10.3390/app11104633.

- Demeco A, de Sire A, Marotta N, Spanò R, Lippi L, Palumbo A, Iona T, Gramigna V, Palermi S, Leigheb M, Invernizzi M, Ammendolia A. Match Analysis, Physical Training, Risk of Injury and Rehabilitation in Padel: Overview of the Literature. Int J Environ Res Public Health. 2022;19(7):4153. doi:10.3390/ijerph19074153.

- Kunzmann E, Ford KR, Sugimoto D, Baca A, Hank M, Bujnovsky D, Mala L, Zahalka F, Maly T. Differences in External and Internal Load in Elite Youth Soccer Players within Different Match Timing Zones. Applied Sciences. 2022; 12(14):7230. doi: 10.3390/app12147230.

 

Minor revisions:

ABSTRACT: Some words have typing errors. For example, in the Abstract section, there are “rehabil-itation” and “param-eters”, while in the Results section there is the word “interven-tion”. Please correct any typing errors.

- Thank you for your valuable opinion. We have reviewed all the contents and corrected the typing error.

Reviewer 2 Report

This research work is very interesting. Some minor comments are:

1. English grammar needs a significant change.

2. Typos also.

3. Figure 1 is very blurry. Please replace it with a high-resolution figure.

4. Introduction section should be filled with more latest articles.

Author Response

We thank the reviewer for their guidance for further improving our revised manuscript (applsci-2048476) entitled “Effects of Rehabilitation Exercise with Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction”. As described below, we have responded to all the comments brought up by the reviewers and incorporated all the changes suggested by the reviewer.

 

Reviewer2:

This research work is very interesting. Some minor comments are:

 

1. English grammar needs a significant change.

- Thank you for your valuable opinion. Grammar has been modified throughout the manuscript.

 

2. Typos also.

- Thank you for your valuable opinion. I corrected all typo errors in the content.

 

3. Figure 1 is very blurry. Please replace it with a high-resolution figure.

- Thank you for your valuable opinion. Figure 1 has been replaced with high-resolution.

 

4. Introduction section should be filled with more latest articles.

- Thank you for your valuable opinion. You have added the latest article to the introduction section.

Emery, C.A.; Pasanen, K. Current trends in sport injury prevention. Best Pract Res Clin Rheumatol 2019, 33, 3-15, doi:10.1016/j.berh.2019.02.009.

Parsons, J.L.; Coen, S.E.; Bekker, S. Anterior cruciate ligament injury: towards a gendered environmental approach. Br J Sports Med 2021, 55, 984-990, doi:10.1136/bjsports-2020-103173.

Reviewer 3 Report

Dear Authors,

The manuscript at this stage requires improvements. Below suggestions with line indication:

4 – Please consider the journal template and instructions for authors in all  manuscript. Suggestion for space between names and affiliation´s numbers.

20-21 – Please abbreviate ACL in the fist appearance in the abstract.

22-24 – Text incorrections, please correct.

24-25 – Words incorrectly written, please correct.

32-34 – Clearer message suggested, preferably with practical applications.

70 – Please describe in full “KAATSU”.

73 - Please describe in full “BFR” (first appearance in text).

76/78/81 “BFR” suggested. Please confirm in all manuscript the abbreviated words.

85 – “using the test results who participated” – Please improve the English in this line and throughout the manuscript.

86 – ACL.

92 – Please describe inclusion criteria.

100-102 – 2x “Declaration of Helsinki” – Please review.

119 – Please improve figure quality and correct the text in the legend considering the journal template and instructions for authors

174-191 – Please consider splitting the paragraph (too much text in V1).

169-200 - A figure is suggested to resume the text and provide readers with more clear and fast interpretation information.

Please describe, in detail, the procedures during the evaluation and program. Where were the evaluations performed? Warm-up description? Familiarization? Conditions (temperature, humidity?) Order of testing? Time of day (circadian effect). Previous nutrition? Previous training experience of subjects? Who collected the data and monitored the program, training, and experience? Instruments and respective manufacturers? Clothes of subjects? What about details of the program, namely time of training and rest between repetitions and sets? All details should be considered and detailed.

202-209 – Please describe statistical power.

207 – Please provide reference and values associated to intervals.

218 – Please format table 2 and legend considering the journal template and instructions for authors.

223 – “VMO, VLO, and RF” – Please describe in full.

230 – Please remove the space.

232 – Table 3 is missing.

239 – Please review the text and consider deleting “And”.

243 – Please format table 4 and legend considering the journal template and instructions for authors.

254 – Please format table 5 and legend considering the journal template and instructions for authors.

272 – Please do not start paragraph with abbreviation.

278 – “BFR”.

314 – Please consider “and” instead of “&”.

320-325 – Please review, it is confusing.

331 – Please remove “(Erickson et al., 2019)”.

336 – “BFR”.

259-363 – Please consider being more objective in the discussion section and deeper analyse the results of the study.

373 – Please provide suggestion for future research.

375-383 – Please consider reformulating the conclusions section considering clear/direct and take-home messages, if possible, with practical application.

389 – All REFs format should be reviewed in detail, considering the journal´s template and instructions for authors. For example, journal´s should be abbreviated. REF 20 title in uppercase and in other REFs in lowercase.

Please carefully review the English throughout the manuscript.

Author Response

We thank the reviewer for their guidance for further improving our revised manuscript (applsci-2048476) entitled “Effects of Rehabilitation Exercise with Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction”. As described below, we have responded to all the comments brought up by the reviewers and incorporated all the changes suggested by the reviewer.

 

Reviewer3:

 

Dear Authors,

 

The manuscript at this stage requires improvements. Below suggestions with line indication:

 

4 – Please consider the journal template and instructions for authors in all manuscript. Suggestion for space between names and affiliation´s numbers.

- Thank you for your valuable opinion. I modified the space between the name and affiliation’s number by referring to the journal template.

20-21 – Please abbreviate ACL in the fist appearance in the abstract.

- Added ACL abbreviation to Line 21.

22-24 – Text incorrections, please correct.

- Thank you for your valuable opinion. I modified the text as below. ‘Among a total of 24 patients, the general rehabilitation exercise group (GRE, n = 12) and blood flow restriction group (BFR, n = 12) were assigned the same. The GRE group conducted a general rehabilitation exercise, and the BFR group conducted a BFR exercise along with the general re-habilitation exercise. All participants were performed the rehabilitation exercise program session for 60 minutes three a week for 12 weeks under supervision.’

24-25 – Words incorrectly written, please correct.

- Thank you for your valuable opinion. We have reviewed text incorrections and corrected the typing error.

32-34 – Clearer message suggested, preferably with practical applications.

- Thank you for your valuable opinion. We have clearly modified it as follows.

‘Our study confirmed that rehabilitation exercise program with the BFR after ACL reconstruction is a more effective rehabilitation modality for improving muscle activity during muscle contraction and muscle function compared with the GRE. Therefore, it is recommended used BFR as an effective rehabilitation program for rapid recovery after ACL reconstruction.’

70 – Please describe in full “KAATSU”.

- Thank you for your valuable opinion. KAATSU is a unique name for a company that deals with blood flow restriction equipment developed in Japan, not abbreviations. It is used in training to limit blood flow by the Kaatsu Master device developed by Dr. Yoshiaki Sato.

73 - Please describe in full “BFR” (first appearance in text).

- I revised it according to the reviewer's instructions.

76/78/81 “BFR” suggested. Please confirm in all manuscript the abbreviated words.

- We have reviewed and revised all manuscripts as instructed by the reviewer.

85 – “using the test results who participated” – Please improve the English in this line and throughout the manuscript.

- Thank you for your valuable opinion. We have reviewed and improved all the manuscripts as instructed by the reviewer. It is shown on the revised manuscript 88 line.

86 – ACL.

- I revised it according to the reviewer's instructions.

92 – Please describe inclusion criteria.

- Thank you for your valuable opinion. Added description to CONSORT flow chart.

100-102 – 2x “Declaration of Helsinki” – Please review.

- Thank you for your valuable opinion. Duplicate contents have been deleted.

119 – Please improve figure quality and correct the text in the legend considering the journal template and instructions for authors

- Thank you for your valuable opinion. I improved the quality of the figure. The legend has been modified in consideration of the journal template guidelines.

174-191 – Please consider splitting the paragraph (too much text in V1).

- Thank you for your valuable opinion. The contents of the exercise program were splitting the paragraph and modified as much as possible.

169-200 - A figure is suggested to resume the text and provide readers with more clear and fast interpretation information.

- Thank you for your valuable opinion. As the reviewer pointed out, I added the contents of the exercise program as figure.

Please describe, in detail, the procedures during the evaluation and program. Where were the evaluations performed? Warm-up description? Familiarization? Conditions (temperature, humidity?) Order of testing? Time of day (circadian effect). Previous nutrition? Previous training experience of subjects? Who collected the data and monitored the program, training, and experience? Instruments and respective manufacturers? Clothes of subjects? What about details of the program, namely time of training and rest between repetitions and sets? All details should be considered and detailed.

- Thank you for your valuable opinion. We tried to describe the evaluation and program progress as specifically as possible. I've added what the reviewer pointed out throughout the text.

Line 93 ‘All patients had ACL reconstruction performed by an authoritative knee orthopedic surgeon at M Hospital using own transplant method, and was performed by a rehabilitation team at the same hospital with a doctorate in physical therapy certificate and rehabilitation.

Line 132 ‘All measurements were conducted at the rehabilitation center of M Hospital, and the environment was maintained at 23±2 degrees Celsius and 50±5% humidity. All patients visited the hospital at the time of the AM9:00-10:00 to perform measurements. As for the measurement clothes, short-sleeved shirts and shorts provided by the rehabilitation center of M Hospital were worn.’

202-209 – Please describe statistical power.

- Thank you for your valuable opinion. Sample size items have been added to clarify describe statistical power in this study. The contents are as follows:

‘2.9. Sample size

In this study, the G*power® Version 3.1.9.2 Software was used to calculate the minimum sample size. The maximum power threshold reported in Tenent et al. (2017) was used to calculate the priori sample size required for repeated measurement variance analysis. A total of 24 participants were required to obtain a statistical power of 95% at an effect size of d = 0.6 and α = 0.05 including two conditions and two measurement points.’

207 – Please provide reference and values associated to intervals.

- Thank you for your valuable opinion. As the reviewer pointed out, I added values associated to interval.

218 – Please format table 2 and legend considering the journal template and instructions for authors.

- Thank you for your valuable opinion. I sympathized with what the reviewer pointed out and revised Table 2.

223 – “VMO, VLO, and RF” – Please describe in full.

- Thank you for your valuable opinion. It is shown in line 164.

Line 164 'vastus medialis oblique (VMO), rectus femoris (RF), and vastus lateralis oblique (VLO)'

230 – Please remove the space.

- Spaces removed successfully.

232 – Table 3 is missing

- Table 3 overlaps with Table 2, so it seems that we couldn't check it. The table has been modified to prevent movement.

239 – Please review the text and consider deleting “And”.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

243 – Please format table 4 and legend considering the journal template and instructions for authors.

- Thank you for your valuable opinion. I sympathized with what the reviewer pointed out and revised Table 4.

254 – Please format table 5 and legend considering the journal template and instructions for authors.

- Thank you for your valuable opinion. I sympathized with what the reviewer pointed out and revised Table 5.

272 – Please do not start paragraph with abbreviation.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

278 – “BFR”.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

314 – Please consider “and” instead of “&”.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

320-325 – Please review, it is confusing.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

‘In order to bring about improvement in muscle function, metabolic stress induced through proper muscle mechanical tension and exercise, and damage to the integrity of individual muscle fibers by destroying the skeletal muscle structure, and induction of cellular responses through stimulation of the mTOR pathway are proposed [34]. In this way, given that the improvement of muscle function occurs by appropriate stimulation, we carefully predict that the stimulation of BFR exercise implemented in this study was an appropriate program that could show positive changes in muscle function and muscle activity improvement.’

331 – Please remove “(Erickson et al., 2019)”.

- Thank you for your valuable opinion. I removed it as the reviewer pointed out.

336 – “BFR”.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

259-363 – Please consider being more objective in the discussion section and deeper analyse the results of the study.

-Thank you for your valuable opinion. In this study, increasing early exercise intensity to prevent frequent femoral parietal muscle atrophy after ACL reconstruction provides the most effective rehabilitation process and may help return to daily life. Therefore, we discuss that the BFR application conducted in this study was appropriate and effective. Thank you for the reviewer's comment. Please review it again.

373 – Please provide suggestion for future research.

- Thank you for your valuable opinion. In the text, we added the contents of the future research suggestion to line 413.

‘Suggesting future studies, it is judged that studies using ultrasound and MRI are needed to elucidate the mechanisms of muscle activity and hypertrophy in patients who underwent ACL reconstruction. In addition, research is needed to verify the effects of promoting energy metabolism and increasing thigh muscle strength when BFR is applied to improve health.’

375-383 – Please consider reformulating the conclusions section considering clear/direct and take-home messages, if possible, with practical application.

- Thank you for your valuable opinion. We have clearly modified it as follows.

‘Our study confirmed that rehabilitation exercise program with the BFR after ACL reconstruction is a more effective rehabilitation modality for improving muscle activity during muscle contraction and muscle function compared with the GRE. Therefore, it is recommended used BFR as an effective rehabilitation program for rapid recovery after ACL reconstruction.’

389 – All REFs format should be reviewed in detail, considering the journal´s template and instructions for authors. For example, journal´s should be abbreviated. REF 20 title in uppercase and in other REFs in lowercase.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

Please carefully review the English throughout the manuscript.

- Thank you for your valuable opinion. Grammar has been modified throughout the manuscript.

Round 2

Reviewer 1 Report

Dear Authors,

In my opinion, the topic is interesting and actual, and the manuscript is well written.

The results are intriguing and might significantly improve knowledge in this field.

You have significantly improved the manuscript following my suggestions, and for this reason, in my opinion, the article is suitable for the Journal.

Author Response

Reviewer1:

Dear Authors,

In my opinion, the topic is interesting and actual, and the manuscript is well written.

The results are intriguing and might significantly improve knowledge in this field.

You have significantly improved the manuscript following my suggestions, and for this reason, in my opinion, the article is suitable for the Journal.

- Thank you for your positive assessment. We thank the reviewer for their guidance for further improving our revised manuscript (applsci-2048476) entitled “Effects of Rehabilitation Exercise with Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction”.

Reviewer 3 Report

Dear authors,

Thank you for considering my suggestions and incorporating them into the manuscript. 

Below suggestions related to this last version (v2), with line indication.

The page number in the center and end of each page should be removed.

21 – “(ACL)” should appear in the text before “reconstruction”.

73-76 – Please revise the English.

93-103 – Please revise the text and the English.

115 – Please improve the quality of figure 1.

117 – Please format the figure footer and consider improving the text.

126 – “and conducted it for 1 hour under supervision” please improve the English.

134-135 – Please revise the English.

137 - Please improve the quality of figure 2.

209 – Please revise the text.

219 - Please improve the quality of figure 3.

306 – Please revise the text.

309 – Please revise “(1RM20~30%)”.

 

416 – Please describe MRI in full.

 

436 - All REFs format should be revised in detail, considering the journal´s template and instructions for authors. For example, REF 22 title in uppercase and in other REFs in lowercase. Also, for example the paragraph of the text in not according to the journal template and instructions for authors.

 

Please carefully read the next manuscript version after considering the above feedback and from the other reviewers. It is also very important to consider improving the English throughout the manuscript.

Author Response

Reviewe:

 

Dear authors,

Thank you for considering my suggestions and incorporating them into the manuscript.

Below suggestions related to this last version (v2), with line indication.

The page number in the center and end of each page should be removed.

- I removed it as the reviewer pointed out.

21 – “(ACL)” should appear in the text before “reconstruction”.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

73-76 – Please revise the English.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

‘Recently, blood flow restriction (BFR) training developed by Dr. Yoshiaki Sato has been recommended, and BFR limits blood flow to muscles with the Kaatsu Master device, inducing a hypoxic environment in muscles and resulting in effective muscle hypertrophy and muscle strength improvement.’

93-103 – Please revise the text and the English.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out. The contents are as follows:

‘Our study included 30 patients undergoing acute reconstruction or planning due to an ACL injury. Among them, four participants were excluded: patients who under-went suture surgery after an accompanying cartilage injury; patients whose initial muscle strength did not decrease due to chronic damage; and elite athletes. A total of 26 patients were assigned equally to the general rehabilitation exercise group (GRE, n = 13) and the blood flow restriction group (BFR, n = 13) according to age, gender, height, and weight. All participants underwent ACL reconstruction by an authorized knee orthopedic surgeon at M Hospital using the autograft transplantation method, and rehabilitation training was performed by a rehabilitation team trainer with a physical therapy certificate and rehabilitation degree at the same hospital. All evaluations were performed the same way before ACL reconstruction and after the 12-week rehabilitation exercise program. All participants were required to visit the hospital rehabilitation center for 12 weeks, three times a week, but one participant from each group not in this category was excluded, with a total of 24 participants (age: 29.3 ± 8.0 years, male: n = 18, female: n = 6) being used for the analysis. The physical characteristics of the participants and the CONSORT flow chart are shown in Table 1 and Figure 1.’

115 – Please improve the quality of figure 1.

- Thank you for your valuable opinion. As you pointed out, the quality of Figure 1 has been improved.

117 – Please format the figure footer and consider improving the text.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out.

126 – “and conducted it for 1 hour under supervision” please improve the English.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out. The contents are as follows:

‘All participants visited the rehabilitation center at M Hospital three times a week for 12 weeks and performed GRE and BFR exercise under trainer supervision for a total of 60 minutes.’

134-135 – Please revise the English.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out. The contents are as follows:

- All measurements were conducted at the rehabilitation center of M Hospital, and the room temperature and humidity were maintained at 23±2°C and 50±5%.

137 - Please improve the quality of figure 2.

- Thank you for your valuable opinion. As you pointed out, the quality of Figure 2 has been improved.

209 – Please revise the text.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out

‘All GRE were performed in three sets of 15 repetitions. The rehabilitation exercise program conducted in this study is shown in Figure 3.’

219 - Please improve the quality of figure 3.

- Thank you for your valuable opinion. As you pointed out, the quality of Figure 3 has been improved.

306 – Please revise the text.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out

‘Blood flow restriction (BFR) was a method of inducing a hypoxic environment in tissues by restricting blood flow to the muscles by applying pressure to the arms and legs using a device during exercise.’

309 – Please revise “(1RM20~30%)”.

- Thank you for your valuable opinion. I revised it as the reviewer pointed out

‘(20-30% of 1-RM)’

416 – Please describe MRI in full.

-Thank you for your valuable opinion. As you pointed out, I added the full name of MRI.

‘magnetic resonance imaging (MRI)’

436 - All REFs format should be revised in detail, considering the journal´s template and instructions for authors. For example, REF 22 title in uppercase and in other REFs in lowercase. Also, for example the paragraph of the text in not according to the journal template and instructions for authors.

- Thank you for your valuable opinion. As you pointed out, we revised and supplemented the journal consistently in consideration of the template and the author's guidelines.

Please carefully read the next manuscript version after considering the above feedback and from the other reviewers. It is also very important to consider improving the English throughout the manuscript.

- Thank you for your valuable opinion. As you pointed out, I tried to improve my English throughout the manuscript. We thank the reviewer for their guidance in further improving our revised manuscript (applsci-2048476) entitled “Effects of Rehabilitation Exercise with Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction”.