Effect of upper limb isometric training (ULIT) on hamstring strength in early postoperative anterior cruciate ligament reconstruction patients: Study protocol for a randomized controlled trial

Efri Noor Muhamad Hendri; Mohamad Shariff A. Hamid; Badrul Akmal Hisham Md. Yusoff; Norlelawati Mohamad; Ashril Yusof

doi:10.1371/journal.pone.0319724

Peer Review History

Original SubmissionFebruary 7, 2025
5 Mar 2025 Decision Letter - Yaodong Gu, Editor PONE-D-25-05294Effect of upper limb isometric training (ULIT) on hamstring strength in early postoperative anterior cruciate ligament reconstruction patients: study protocol for a randomized controlled trialPLOS ONE Dear Dr. A Hamid, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Apr 19 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The article titled " Effect of upper limb isometric training (ULIT) on hamstring strength in early postoperative anterior cruciate ligament reconstruction patients: study protocol for a randomized controlled trial " investigated the effect of upper limb isometric training (ULIT) on hamstring strength in the early rehabilitation stage after anterior cruciate ligament reconstruction (ACLR) surgery. By utilizing the posterior fascial kinetic chain (PMKC), ULIT can indirectly stimulate the hamstrings, promote neuromuscular coordination and kinetic chain synergy, thereby avoiding atherogenic muscle inhibition and graft protection problems caused by direct loading of the hamstrings. The study used a randomized controlled trial design to compare the effects of ULIT combined with a standard rehabilitation program with a simple standard rehabilitation program, and to evaluate changes in indicators such as hamstring strength, knee function, and flexibility in patients within 12 weeks after surgery, aiming to provide new and effective strategies for ACLR postoperative rehabilitation. Specific comments are shown below: 1. This study proposes that upper limb isometric training (ULIT) indirectly activates the hamstrings through the posterior myofascial kinetic chain (PMKC). Please elaborate on the biomechanical model or experimental evidence supporting this mechanism and provide quantitative data (e.g., electromyography or mechanical transmission efficiency) to verify the direct relationship between upper limb training and hamstring activation. 2. The ULIT study used an intensity of 50% of maximum voluntary contraction (MVC), but the basis for its selection was not clear. Based on the principles of sports biomechanics, please explain how this intensity setting optimizes the neuromuscular adaptation of the hamstrings and discuss the differences that different intensities (such as 30% vs. 70% MVC) may have on training effects. The study: New insights optimize landing strategies to reduce lower limb injury risk (https://doi.org/10.34133/cbsystems.0126) provides new insights into optimizing landing strategies to reduce the risk of lower limb injuries. This study can refer to the above references。 3. The article mentioned that upper limb training is transmitted to the lower limbs through the fascial chain. Please provide specific biomechanical data (such as surface electromyography, dynamic analysis or fascial tension measurement) to quantify the mechanical stimulation path and efficiency of upper limb movements (such as shoulder extension and wall push) on the hamstring muscles. 4. The study only evaluated the effects 12 weeks after surgery. Please discuss whether long-term use of ULIT may lead to increased compensatory loads on the upper limbs or imbalances in core stability and propose biomechanical indicators that should be monitored in subsequent studies (such as spinal mechanics, gait symmetry). Reviewer #2: The authors plan to evaluate the effects of upper limb isometric training on hamstring strength and physical function in postoperative anterior cruciate ligament reconstruction patients with hamstring autograft. 1. The ULIT consists of three isometric exercises. However, no detail information was provided. For example, how long, how often or how many wall push-up and so on. 2. Sample characteristics at baseline should be presented and compared for two arms. 3. Multiple imputation methods will be used to handle any missing data without further discussion on the mechanism of missingness. Also, shat if missing rate is high? ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0319724.r001
Revision 1
6 Apr 2025 Author Response Comments Reviewer 1 1. This study proposes that upper limb isometric training (ULIT) indirectly activates the hamstrings through the posterior myofascial kinetic chain (PMKC). Please elaborate on the biomechanical model or experimental evidence supporting this mechanism and provide quantitative data (e.g., electromyography or mechanical transmission efficiency) to verify the direct relationship between upper limb training and hamstring activation. Response to reviewer: We appreciate the reviewer's insightful comments regarding the proposed mechanism of upper limb isometric training (ULIT) indirectly activating the hamstrings through the posterior myofascial kinetic chain (PMKC). We acknowledge the need for a more detailed elaboration of the biomechanical model and experimental evidence supporting this mechanism. In the revised manuscript, particularly within the introduction section, we have significantly expanded our discussion to address this point. We have: 1. Elaborated on the Biomechanical Model: We have provided a more detailed description of the PMKC, emphasizing the interconnectedness of muscles and fascia from the upper limbs to the lower limbs. Specifically, the concept of the superficial back line illustrates how force transmission occurs via fascial connections linking the latissimus dorsi, thoracolumbar fascia, gluteus maximus, and hamstrings (Carvalhais et al., 2013; Marpalli et al., 2022b; Vleeming et al., 1995; Wilke et al., 2016). We've included relevant anatomical descriptions and biomechanical principles to support this model. 2. Incorporated Supporting Experimental Evidence: To further support this, we have incorporated surface electromyography (sEMG) data from previous studies demonstrating a 15–25% increase in biceps femoris activation and a 10–18% increase in semitendinosus activation during upper limb isometric contractions at approximately 50% MVC. This highlights the role of neuromuscular coordination facilitated by kinetic chain dynamics (Jungseo et al., 2014; Krause et al., 2018; Manca et al., 2021; Sato & Maruyama, 2007). We believe these additions strengthen the rationale for our proposed mechanism and provide clearer evidence of the relationship between ULIT and hamstring activation. Kindly refer to the introduction section Page 4 – 5 (line 79 to 94) 2. The ULIT study used an intensity of 50% of maximum voluntary contraction (MVC), but the basis for its selection was not clear. Based on the principles of sports biomechanics, please explain how this intensity setting optimizes the neuromuscular adaptation of the hamstrings and discuss the differences that different intensities (such as 30% vs. 70% MVC) may have on training effects. The study: New insights optimize landing strategies to reduce lower limb injury risk (https://doi.org/10.34133/cbsystems.0126) provides new insights into optimizing landing strategies to reduce the risk of lower limb injuries. This study can refer to the above references. Response to reviewer: Thank you so much for raising the important question regarding the selection of 50% MVC for the ULIT protocol. We acknowledge that a clearer justification for this intensity is crucial for understanding the study's implications. In the revised manuscript, specifically within the intervention section of the methods, we have elaborated on the rationale behind choosing 50% MVC. This choice was made based on the principles of sports biomechanics and neuromuscular adaptation, aiming to optimize hamstring activation through the PMKC without inducing excessive fatigue or compromising form. Here's a breakdown of our justification, which is now included within the manuscript itself: 1. Neuromuscular Adaptation: Research indicates that intensities at or above 40% MVC effectively stimulate neuromuscular adaptation while preventing excessive fatigue (Manca et al., 2021). Specifically, 50% MVC optimally recruits Type IIA muscle fibers, enhancing force transmission and kinetic chain efficiency while minimizing early fatigue and excessive tension (Petajan, 1991; Valenčič et al., 2024). 2. Intensity Comparison: Lower intensities (e.g., 30% MVC) primarily activate slow-twitch fibers, leading to limited force production and reduced adaptation. In contrast, higher intensities (e.g., 70% MVC) may induce early fatigue and mechanical inefficiency, potentially compromising sustained engagement in rehabilitation exercises (Avrillon et al., 2024; Miller et al., 2019). Clinical Relevance: Additionally, findings from Xu et, al. suggest that optimizing muscle activation and movement strategies plays a crucial role in injury prevention and rehabilitation, further supporting our intensity selection. In the revised intervention section, we have incorporated a discussion of these points, emphasizing the balance between activation and fatigue, and the practical considerations that influenced our choice. We have provided references that support our selection of 50% MVC and how other intensities would be less ideal. By providing a more detailed explanation grounded in biomechanical principles and supported by relevant literature, we believe we have addressed the reviewer's concerns and provided a clearer justification for the chosen intensity. Kindly refer to the Methods: Intervention group section, page 13 – 15 (line 250 - 298) 3. The article mentioned that upper limb training is transmitted to the lower limbs through the fascial chain. Please provide specific biomechanical data (such as surface electromyography, dynamic analysis or fascial tension measurement) to quantify the mechanical stimulation path and efficiency of upper limb movements (such as shoulder extension and wall push) on the hamstring muscles. Response to reviewer: Thank you for your thoughtful comment and for highlighting the need for specific biomechanical data to quantify the mechanical stimulation path and efficiency of upper limb movements on the hamstring muscles. In response, we have expanded the introduction to provide additional explanation on this mechanism, supported by functional anatomy and biomechanical research. As noted in our earlier response, we have also included surface electromyography (sEMG) data from previous studies, which demonstrate a 15–25% increase in biceps femoris activation and a 10–18% increase in semitendinosus activation during upper limb isometric contractions at approximately 50% MVC. This evidence highlights the role of neuromuscular coordination facilitated by kinetic chain dynamics. We believe these additions address your concerns and provide clearer evidence of the biomechanical relationship between upper limb training and hamstring activation. Kindly refer to the introduction section, page 4 – 4 (line 79 - 94) 4. The study only evaluated the effects 12 weeks after surgery. Please discuss whether long-term use of ULIT may lead to increased compensatory loads on the upper limbs or imbalances in core stability and propose biomechanical indicators that should be monitored in subsequent studies (such as spinal mechanics, gait symmetry). Response to reviewer: Thank you for your insightful comment. We acknowledge the need to assess potential compensatory loads and imbalances from prolonged ULIT use beyond 12 weeks. While our study focuses on early rehabilitation, future research should monitor long-term neuromuscular adaptations using surface electromyography (sEMG) to analyze muscle activation patterns and firing rates, along with video kinematic analysis to assess movement quality. These considerations have been incorporated into the discussion to guide future studies in refining ULIT protocols and ensuring long-term safety in ACLR rehabilitation. Kindly refer to the Discussion sections, page 20 (line 386 - 389) and page 21 (line 393 – 407) Reviewer 2 1. The ULIT consists of three isometric exercises. However, no detail information was provided. For example, how long, how often or how many wall push-up and so on. Response to reviewer: We sincerely appreciate your request for additional details regarding the ULIT protocol. In response, we have revised the manuscript to include specific information on the duration, frequency, and repetitions of the exercises. These details have been sourced from the ANZCTR clinical registry (ACTRN12624001445561) (Appendix 5). We believe this addition enhances the clarity and completeness of the methodology. Thank you for your valuable feedback, which has helped us improve the manuscript. Kindly refer to the Methods: Intervention group section, page 13 – 15 (line 250 – 270, and 288 - 298) as well as Appendix 5. 2. Sample characteristics at baseline should be presented and compared for two arms. Response to reviewer: We sincerely appreciate the your suggestion to present and compare baseline sample characteristics between the two study arms. In the revised manuscript, key baseline characteristics, including age, sex, body mass index (BMI), relevant clinical history, baseline functional scores, and other pertinent demographic between groups will be recorded. To ensure a thorough comparison, we will conduct appropriate statistical tests (e.g., independent t-tests, chi-square tests, or Mann-Whitney U tests as applicable) to assess differences between the groups. Any notable variations will be highlighted and discussed in relation to their potential impact on study outcomes. We believe this addition will enhance the clarity and robustness of our findings. Thank you for your valuable feedback, which has helped us strengthen our manuscript. Kindly refer to the Statistical analysis section, page 18 (line 339 to 346) 3. Multiple imputation methods will be used to handle any missing data without further discussion on the mechanism of missingness. Also, shat if missing rate is high? Response to reviewer: We appreciate your insightful comment regarding the handling of missing data. We acknowledge that the mechanism of missingness plays a crucial role in determining the most appropriate method for handling incomplete data. In the revised manuscript, we will assess the missing data mechanism (missing completely at random (MCAR), missing at random (MAR), or missing not at random (MNAR) using diagnostic tests like Little’s MCAR test to determine the suitability of multiple imputation (MI). If the data conform to MAR or MCAR, multiple imputation (MI) will be employed; for MNAR patterns, we will investigate sensitivity analyses or pattern-mixture models. For high missing rates, additional strategies will include increasing imputations, incorporating auxiliary variables to improve MI, and performing complete-case analysis for comparison. These considerations will be detailed in the methodology section to ensure transparency. Kindly refer to the statistical analysis section, page 18 – 19 (line 347 to 357) Attachments Attachment Submitted filename: Response to Reviewers 5 April 2025.docx https://doi.org/10.1371/journal.pone.0319724.r002
21 Apr 2025 Decision Letter - Yaodong Gu, Editor Effect of upper limb isometric training (ULIT) on hamstring strength in early postoperative anterior cruciate ligament reconstruction patients: study protocol for a randomized controlled trial PONE-D-25-05294R1 Dear Dr. A Hamid, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This manuscript presents a well-designed randomized controlled trial (RCT) protocol investigating the effect of upper limb isometric training (ULIT) on hamstring strength in patients during the early postoperative phase following anterior cruciate ligament reconstruction (ACLR). The topic is both novel and clinically meaningful, addressing an understudied area that may offer valuable insights into neurophysiological cross-education and postoperative rehabilitation strategies. The methodology is clearly described, with appropriate inclusion/exclusion criteria, intervention design, outcome measures, and ethical considerations. The proposed use of both objective strength testing and patient-reported outcome measures strengthens the study's clinical relevance and translational potential. Furthermore, the sample size calculation and randomization procedure are adequate for ensuring statistical rigor. Reviewer #2: Thank you for addressing the raised comments and concerns. I have no further comments on the current version of manuscript. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #1: No Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0319724.r003
Formally Accepted
Acceptance Letter - Yaodong Gu, Editor PONE-D-25-05294R1 PLOS ONE Dear Dr. A Hamid, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Yaodong Gu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0319724.r004

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