Skip to main content
PLOS One logoLink to PLOS One
. 2025 Aug 21;20(8):e0319724. doi: 10.1371/journal.pone.0319724

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 1,#, Mohamad Shariff A Hamid 2,*, Badrul Akmal Hisham Md Yusoff 1,3,#, Norlelawati Mohamad 1,#, Ashril Yusof 4,#
Editor: Yaodong Gu5
PMCID: PMC12370102  PMID: 40839658

Abstract

Anterior cruciate ligament (ACL) injuries impact approximately 68.6 per 100,000 individuals annually, with ACL reconstruction (ACLR) being a common intervention for restoring knee stability in physically active individuals. Despite advancements in surgical techniques and rehabilitation protocols, patients often experience prolonged recovery, hamstring weakness, and neuromuscular deficits, increasing the risk of re-injury and osteoarthritis. Early-phase ACLR rehabilitation primarily focuses on managing pain, swelling, and quadriceps strength, frequently neglecting the critical role of hamstrings in knee stabilization. This leaves a gap in addressing imbalances that hinder functional recovery and return-to-sport timelines. Upper limb isometric training (ULIT) presents an innovative approach to enhance hamstring activation during the early rehabilitation phase. By leveraging the posterior myofascial kinetic chain (PMKC), ULIT indirectly stimulates hamstrings through bilateral static upper limb exercises, such as wall push up, shoulder extension and scapular retraction, promoting neuromuscular coordination and kinetic chain synergy. These exercises mitigate challenges associated with direct hamstring loading, such as arthrogenic muscle inhibition and graft protection needs. Preliminary research suggests upper limb resistance exercise at submaximal voluntary contraction facilitates inter-limb strength gains, improves core abdominals and hamstring activation, and reduces knee imbalances, supporting accelerated recovery and reduced re-injury risk. The ULIT demonstrates potential as an alternative warm-up exercise to promote hamstring activation and enhance overall readiness for physical activity. Emerging findings highlight ULIT as a safe and potentially effective supplementary intervention, but further research is essential to establish its role in ACLR rehabilitation and develop evidence-based protocols. This study aims to evaluate the effects of integrating ULIT into standard care rehabilitation on hamstring strength and physical function in early-phase postoperative ACLR patients with hamstring autograft. The findings could introduce a novel and effective strategy to optimize recovery, enhance functional outcomes, and support a safer return to sport.

Trial registration number: ACTRN12624001445561 and available at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388441&isReview=true.

Introduction

Anterior cruciate ligament (ACL) injuries affect 68.6 per 100,000 individuals annually [1], with ACL reconstruction (ACLR) recommended for physically active individuals experiencing knee instability [2]. Globally, ACLRs have surpassed 100,000 per year, growing annually by 2% [3]. Despite advancements, ACLR patients face prolonged recovery, with physical function limitations and an inability to return to sports for at least six months [4]. Factors such as graft type (e.g., hamstring autografts) and rehabilitation protocols contribute to chronic hamstring weakness and neuromuscular deficits, increasing the risk of re-injury, altered biomechanics, and osteoarthritis [57].

Current ACLR rehabilitation programs focus on managing pain and swelling, restoring quadriceps strength, and achieving full knee extension during the early postoperative phase, which spans the first 12 weeks [8,9]. Although these objectives are essential, they often overshadow the importance of hamstring rehabilitation. Rehabilitation protocols frequently emphasize quadriceps-dominant strategies, leaving a critical gap in addressing the hamstrings’ role in knee stabilization, hip and torso positioning, and injury prevention. Furthermore, early rehabilitation is hindered by challenges such as arthrogenic muscle inhibition (AMI), which disrupts neural pathways and impairs quadriceps and hamstring activation [10,11]. The necessity to protect the graft from excessive tensile forces further limits direct hamstring loading and stretching during this period [12].

Consequently, hamstring recovery within current protocols is often delayed, leading to imbalances in knee musculature that hinder overall functional recovery [13]. Structured neuromuscular rehabilitation has demonstrated improvements in muscle strength, but few clinical practice guidelines (CPGs) specifically address early hamstring strengthening, despite its vital role in reducing ACL shear forces and stabilizing the knee joint during dynamic activities [14,15]. High imbalances in knee muscle strength during early rehabilitation phases also slow recovery in the final stages [16,17].

Innovative approaches that integrate indirect hamstring activation techniques, such as Upper Limb Isometric Training (ULIT), offer promising solutions. ULIT leverages the posterior myofascial kinetic chain (PMKC) to indirectly enhance core abdominal muscles and hamstring activation through upper limb isometric exercises [18,19]. Biomechanical models suggest that force transmission through the PMKC occurs via fascial connections between the latissimus dorsi, thoracolumbar fascia, gluteus maximus, and hamstrings, facilitating neuromuscular coordination and interconnected muscle synergies [2023]. Experimental evidence, particularly electromyography (EMG) studies, supports this mechanism, demonstrating significant enhancements in core abdominal and hamstring activation during upper limb isometric contractions [2427]. EMG analysis reveals that shoulder abduction and extension at 50% MVC elicit a 15–25% increase in biceps femoris activation compared to resting conditions, while scapular retraction exercises augment semitendinosus activity by approximately 10–18% [24,28]. This indirect activation is attributed to kinetic chain dynamics, which optimize neuromuscular recruitment, improve joint stability, and enhance movement efficiency. By addressing knee imbalances and addressing challenges such as pain, swelling, and graft protection requirements in the early stages of anterior cruciate ligament reconstruction (ACLR) rehabilitation, ULIT offers a safe and effective strategy for improving hamstring strength and stability. Incorporating ULIT into early ACLR rehabilitation programs may accelerate recovery and mitigate the risk of reinjury.

Research indicates that isometric training at 50% of maximum voluntary contraction can promote inter-limb strength gains, making ULIT a promising early rehabilitation tool [2931]. It prepares patients for dynamic movements, reduces knee imbalances, and supports functional recovery. Incorporating ULIT into early ACLR rehabilitation programs could optimize hamstring strength and stability, accelerate recovery and reduce the risk of re-injury.

While the theoretical framework and preliminary research provide insights into the potential mechanisms, physiological adaptations, and clinical implications of upper limb isometric training (ULIT) for hamstring strength during early-phase ACLR rehabilitation, robust clinical evidence remains limited. Current evidence offers limited guidance on the optimal intensity, volume, and frequency of ULIT, leaving its impact on hamstring strength and functional outcomes in the ACLR population less established [3235].

This study aims to investigate the effects of incorporating specific bilateral ULIT into standard rehabilitation care on hamstring strength and physical function in early-phase postoperative ACLR patients with hamstring autograft.

We hypothesize that participants receiving ULIT in addition to standard care will demonstrate better hamstring strength at 12 weeks post-operatively compared to those receiving standard care rehabilitation alone. Emerging findings suggest ULIT as a safe and potentially effective supplementary therapy for enhancing hamstring activation. However, further research is needed to clarify its clinical role and develop evidence-based protocols to improve patient outcomes.

The primary objective of this study is to investigate the effects of ULIT combined with standard care rehabilitation on hamstring strength in early phase postoperative ACLR patients. The secondary objectives are to compare the effects of ULIT and standard care on improving physical function, enhancing hamstring flexibility, and assessing patient adherence post-ACLR.

Materials and methods

Study design

This study is a longitudinal, parallel-group, concealed allocation, assessor-blinded, randomised (1:1) controlled trial conducted at a tertiary hospital. Participants who meet the eligibility criteria, provide informed consent, and complete baseline measurement testing will be randomly assigned to the study. Participants will be informed that they will be randomly allocated to one of two study groups: 1) the intervention group (ULIT combined with the standard care ACLR rehabilitation protocol) or 2) the control group (standard care rehabilitation protocol).

Ethics

The trial will be conducted at the Orthopaedic Clinic and Physiotherapy Unit of Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur. Ethics approval for the trial protocol (version 1, 24 September 2024) was obtained from the Institutional Review Board (IRB) of the Universiti Kebangsaan Malaysia Research Ethics Committee (RECUKM)(Ethics Ref. no: JEP-2024–860) (S1 Appendix). The protocol has been registered with the Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au) (Registration no: ACTRN12624001445561 and available at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388441&isReview=true.), ensuring compliance with the ethical principles outlined in the Declaration of Helsinki (2000).

Sample size

Sample size calculations were conducted using IBM SPSS Statistics (Version 29) for the primary outcome: differences between the means of hamstring maximum voluntary isometric contraction peak force. Based on the population standard deviation of 0.71 for the primary outcome measure, as reported in the previous study [11], and setting the Type I error at 0.05, the Type II error at 0.2, and the power at 80%, the minimum required sample size is 14 patients per group. To account for an expected attrition rate of 10%, 16 participants are planned for inclusion in each study group.

Participants recruitment

Eligible participants for this study are patients diagnosed with an ACL tear, with or without a concomitant meniscal injury, who are scheduled for ACL reconstruction surgery. Prospective participants will receive an invitation to join the study at least two weeks prior to their surgery. They will be identified from the elective surgery list at the Orthopaedic Clinic of HCTM. Eligibility of participants will be determined through the patient’s medical records, a physical examination conducted by the surgeon, and direct communication with the patient. The principal investigator will explain the details of the trial to potential participants and provide them with written information for reference (S2 Appendix). Participants are required to provide written consent (S3 Appendix) to confirm their participation. Patients who choose not to participate will maintain standard rehabilitative care.

Inclusion and exclusion criteria

Participants eligible for inclusion must be aged between 18 and 45 years and scheduled for ACLR using an ipsilateral hamstring tendon autograft, with or without a meniscal injury. They must also be proficient in English and capable of providing informed consent. Participants will be excluded if they are undergoing revision ACL surgery, have multi-ligament injuries such as instability in the collateral, posterolateral, medial, or posterior cruciate ligaments, are using allografts, or have sustained upper limb or contralateral lower limb injuries after ACL surgery.

Randomization

Following baseline assessments, participants will be randomly allocated to either the intervention or control group through a computer-generated sequence with a 1:1 allocation ratio. Group assignments will be hidden within sealed, numbered envelopes, which will be securely stored in a locked cabinet. Non-research personnel from the Orthopaedic Department will unseal the next envelope and notify the attending physiotherapist of the group allocation.

Blinding

Outcome assessors and data managers will remain blinded to treatment allocation. Participants will be instructed not to disclose their treatment received to the physician or medical officer performing assessments. Treatment allocation will only be revealed in exceptional cases, such as potential harm or critical care needs. Upon the conclusion of the trial, physiotherapists and patients were requested to speculate on the treatment administered to each participant. The success of blinding will be assessed using the ‘blinding index’ as described by James et al. [36]. Fig 1 depicts the SPIRIT schedule and an overview of the study design.

Fig 1. SPIRIT schedule of enrollment, interventions, and assessments.

Fig 1

Study outcomes

Patients’ sociodemographic information, including gender, date of birth, ethnic background, sport and level of participation, will be recorded. Additionally, information on education level, physical activity level, and previous medical history will be collected.

Primary outcome: quadriceps and hamstring maximum voluntary isometric strength (MVIC).

The primary outcome of this study is the peak force of quadriceps and hamstring muscles strength assessed using the maximum voluntary isometric contraction (MVIC) tests. The MVIC test will be performed at enrolment (pre-operative), 4-, 8- and 12-weeks follow-up sessions. The maximal voluntary isometric contraction (MVIC) will be measured using a built-in handheld dynamometer and inclinometer (Active Force 2™), following the methodology described by a previous study [14]. Patients will be positioned in high sitting with hips flexed at 90° and knees bent at 60°. The dynamometer will be securely placed 5 cm above the lateral malleolus to ensure consistent force measurement. Participants will be instructed to exert maximal effort during the contraction while maintaining proper positioning and stabilization. This standardized approach, as outlined by previous studies, ensures reliable and reproducible measurements of MVIC in assessing hamstring strength. Patients will perform three MVICs of knee extension, each lasting five seconds, to evaluate quadriceps strength, followed by knee flexion testing for the hamstrings [37]. A one-minute rest period will be provided between quadriceps and hamstring tests to reduce muscle fatigue [38]. This standardized approach ensures reliable and reproducible measurements of MVIC for both muscle groups.

The assessor will provide consistent instructions and verbal encouragement during tests. Participants will be instructed to exert maximum force by pushing with their quadriceps or pulling with their hamstrings against the dynamometer. Both the average and best peak force scores will be recorded [39].

Secondary outcomes: International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) questionnaire.

Patients will complete the IKDC-SKF questionnaire (S4 Appendix) to evaluate their perception of daily knee function and associated symptoms [7,40]. The questionnaire is straightforward, allowing patients to understand and complete it independently. It has been specifically designed and validated for patients undergoing ACL reconstruction, and it covers all the domains in the International Classification of Functioning, Disability, and Health (ICF) [41]. The IKDC has good validity and responsiveness, with excellent test-retest reliability 84% confirmation of preset hypotheses for construct validity and 86% for responsiveness [40,42].

Secondary outcomes: Active knee extension test (AKET).

Active knee extension test (AKET) for hamstring range of movement assessment. The AKE test is an active test that is safe as the participant dictates the endpoint and has been recommended and often used to measure hamstring tightness [43]. The AKET will be performed using an inclinometer to measure the knee extension angle (KEA). The participant lies supine, with their hip in a 90° flexion position and a flat position for the contralateral leg. Patients will be asked to extend their knee until they feel maximum tightness in the posterior thigh without pain, maintaining a relaxed ankle position to reduce the impact of the gastrocnemius muscle. One or more of the following three criteria can determine the endpoint for AKET: (a) the examiner’s perception of firm resistance; (b) the visible onset of pelvic rotation; and (c) the participant experiencing a strong but tolerable stretch, slightly before the onset of pain. In a previous study [44], researchers proposed a clinically significant improvement of 10.2°.

The AKET has demonstrated high reliability in evaluating hamstring flexibility in healthy people, with intraclass correlation coefficients (ICC) of 0.87 for the dominant knee and 0.81 for the non-dominant knee, while the intra-rater (test-retest) reliability ICC scores varied between 0.75 and 0.97 [45].

Interventions

Intervention group: upper limb isometric training combined with standard ACLR rehabilitation program.

Participants in the intervention group will perform ULIT in addition to the standard ACLR rehabilitation program from weeks 4–12 post-surgery. A trained physiotherapist will administer the ULIT program, providing verbal instructions, demonstrations, and written guidelines (S5 Appendix).

ULIT Protocol:

The ULIT program consists of three isometric exercises performed in a standing position (S5 Appendix):

  1. Wall push-ups: Participants stand facing a solid wall, feet shoulder-width apart, approximately arm’s length from the wall. With hands positioned at shoulder height, they perform an isometric push-up by applying force against the wall while maintaining arm alignment. Each push-up is held for 5 seconds, followed by 5 seconds of rest. Participants perform 1 set of 5 repetitions, once or twice daily.

  2. Shoulder extension: Participants position themselves with their backs against the wall, arms fully extended downward at their sides. They push their arms backward against the wall while maintaining a neutral spine and full knee extension. Each repetition is held for 5 seconds, followed by 5 seconds of rest. One set of 5 repetitions is performed, once or twice daily.

  3. Shoulder external rotation: Participants position themselves sideways to the wall, with their elbow flexed at a 90-degree angle and tucked against their side. They press the back of their hand against the wall, engaging the shoulder muscles without changing arm position. Each repetition is held for 5 seconds, followed by 5 seconds of rest. One set of 5 repetitions is performed, once or twice daily.

Intensity and Neuromuscular Considerations:

To maximize neuromuscular activation while minimizing fatigue, patients will perform these exercises at 50% of their maximum voluntary contraction (MVC). Research indicates that intensities at or above 40% MVC effectively stimulate neuromuscular adaptations without causing excessive fatigue [28]. Specifically, training at 50% MVC optimally recruits Type IIA muscle fibers, which are critical for enhancing kinetic chain efficiency while limiting early fatigue and excessive muscle tension [46,47].

Lower intensities, such as 30% MVC, primarily activate slow-twitch fibers, resulting in limited force transmission and reduced neuromuscular adaptation. Conversely, higher intensities such as 70% MVC are more likely to induce early fatigue and compromise mechanical efficiency, potentially hindering sustained participation in rehabilitation exercises [48,49].

Implementing 50% MVC in the ULIT protocol achieves an optimal balance, effectively enhancing neuromuscular activation while ensuring safety and practicality in ACLR rehabilitation.

Furthermore, Xu et al. highlight the importance of optimizing muscle activation and movement strategies for both injury prevention and rehabilitation, supporting our intensity selection [50].

General instructions:

  • Effort Level: The first repetition of each exercise is performed at maximal effort (100%), whereas the subsequent five repetitions are performed at 50% effort.

  • Rest Intervals: A 1-minute interval is advised between exercises.

  • Environment: Exercises should be performed against a stable wall (e.g., concrete or brick) on a non-slip floor surface to ensure stability and safety.

Safety and Modifications:

Participants are instructed to maintain steady breathing throughout the exercises and avoid breath-holding. If maintaining the correct posture is challenging, they may reduce intensity by stepping closer to the wall. Participants are advised to stop the exercise if they experience sharp pain, excessive fatigue, or difficulty maintaining controlled breathing.

In addition to ULIT, patients in the intervention group will perform the standard care ACL rehabilitation protocol (S6 Appendix).

Control group: standard ACLR rehabilitation program.

Patients in the control group will receive the standard ACLR rehabilitation program from the Department of Medical Rehabilitation Services (HCTM). Five physiotherapists, each with over five years of experience in musculoskeletal rehabilitation, will oversee the sessions. The standard ACLR rehabilitation program includes knee mobilization exercises, cryotherapy, progressive resistance exercises (e.g., eccentric strengthening), proprioceptive training, and dynamic stabilization drills. Each follow-up session lasts approximately one hour, and patients will be instructed to perform these exercises at home 1–2 sessions per day for up to three months post-surgery. Additionally, all participants are encouraged to adhere diligently to their prescribed daily home exercise program.

Adherence and adverse events monitoring

All patients are required to document their home-based exercises and report any adverse events using an exercise diary provided in the form of a weekly Google Form. Participants will be classified as adhered (≥3 sessions/week) or non-adhered (≤2 sessions/week) based on their average weekly exercise frequency [51]. A physiotherapist will conduct weekly follow-ups via phone or WhatsApp to support adherence. The study will set an adherence target of a self-perceived rating ≥80% [52].

Adverse events will be documented using a non-leading questionnaire as part of participants’ training diaries throughout the intervention (S7 Appendix). Participants may contact the PI or physiotherapist at any time during the study. All adverse events, regardless of outcome, will be reported and published. A summary of this trial is outlined in Fig 2.

Fig 2. Study flowchart.

Fig 2

Data management

Access to the data will be restricted to the supervisor, Principal Investigator (PI), co-researchers, and independent statistician, with no disclosure to unauthorized parties. The supervisor and PI will advise trial investigators on monitoring withdrawals, ensuring ethical conduct, addressing missing data, and reviewing major adverse events. A case report form (CRF) will document unavailable data to ensure consistency, accuracy, and proper analysis. All data will be securely stored in a locked cabinet in the PI’s office and retained for at least five years following study completion and publication.

Statistical analysis

Data analysis will be conducted using the SPSS Windows Version 29.0 software (SPSS, Chicago, IL, USA). Baseline characteristics of the intervention and control groups will be presented to assess group equivalence and identify potential confounders. Continuous data will be expressed as mean ± standard deviation (SD), or median ± interquartile range (IQR) based on data distribution, while categorical data will be presented as frequency (n) and percentage (%). Comparisons between groups will be performed using independent t-tests for continuous variables and chi-square tests for categorical variables. Any significant differences between groups will be acknowledged and adjusted for in the final analysis to ensure accurate outcome interpretation.

For the primary outcome variable, the principle of intention-to-treat (ITT) will be applied, including data from participants with incomplete data or protocol deviations. To address missing data, 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 such as Little’s MCAR test to determine the suitability of multiple imputation (MI). If the data align with MAR or MCAR, MI will be used; however, if an MNAR pattern is detected, alternative strategies such as sensitivity analyses or pattern-mixture models will be explored to ensure the robustness of our findings.

If the missing rate exceeds 20%, additional sensitivity analyses will be performed using alternative approaches including case analysis and last observation carried forward (LOCF) to assess the robustness of the findings [53,54].

One-way repeated-measures ANOVA will be used to explore changes in hamstring and quadriceps MVIC within and between groups over time. A p-value of <0.05 would be significant.

Rigour

The study protocol has been developed in conformity with the evidence-based guidelines of the SPIRIT 2013 Statement [55] on the essential elements of a clinical trial protocol. The study design conforms to the CONSORT 2010 guidelines for conducting parallel group randomized controlled trials (RCTs). The TIDieR checklist is added as a tool to describe and replicate the intervention proposal (S8 Appendix). Upon completion of the study, the data collected here will be made available to those investigators who request it.

Status of study

Participant recruitment will commence in January 2025 and is expected to conclude by January 2026. The intervention phase and final follow-up assessments are anticipated to be completed by May 2026.

Discussion

This study will focus on evaluating the effects of ULIT on hamstring strength deficits in individuals after undergoing ACLR. The primary outcome, MVIC of hamstring and quadriceps peak force, will be measured pre-operatively and at 4-, 8-, and 12-weeks post-operatively. Secondary outcomes will assess hamstring flexibility, knee symptoms, physical activity levels, and knee-related quality of life. Previous research has demonstrated significant correlations between patient-reported and objective outcomes, providing insight into muscle function deficits associated with ACLR [9,12]. ULIT is believed to have potential as an early post-operative ACLR rehabilitation, complementing standard ACLR rehabilitation programs by enhancing knee strength, flexibility, and functional outcomes.

This study’s strength lies in its focused design, which targets individuals within a specific age range who have undergone ACLR with a hamstring graft. This approach ensures greater uniformity in participant characteristics, thus enhancing internal validity. The study effectively captures essential early recovery milestones by focusing on the critical early rehabilitation phase, spanning from pre-operation to three months post-surgery. The standardized eight-week ULIT intervention further strengthens consistency across participants, while the inclusion of a control group receiving standard ACLR care allows for a robust comparison and clearer evaluation of the intervention’s effectiveness.

However, this study has some limitations. One notable limitation is the absence of a cost-effectiveness analysis, which was not feasible given the modest sample size, despite its recognized importance. Additionally, while our study is designed to assess the short-term impact of ULIT, we acknowledge the need to explore potential compensatory loads and imbalances that may arise from prolonged ULIT use beyond 12 weeks.

To address this, future research should incorporate biomechanical assessments to monitor long-term neuromuscular adaptations. Recommended approaches include surface electromyography (sEMG) to evaluate muscle activation patterns and firing rates, along with video kinematic analysis to assess movement quality and detect compensatory strategies. These assessments will provide valuable insights into the potential risks of upper limb overuse and core stability imbalances, ultimately guiding the refinement of ULIT protocols to ensure both effectiveness and long-term safety in ACLR rehabilitation.

Future studies with extended follow-up periods exceeding 6–9 months are also warranted to assess the sustained benefits of ULIT in achieving positive clinical outcomes and minimizing injury risk during the return-to-sport phase.

Conclusion and clinical relevance

This randomized clinical trial will evaluate the effect of upper limb isometric training on hamstring strength in ACLR patients with hamstring autografts. No previous trials have examined upper limb resistance training combined with standardized early-stage ACLR rehabilitation. If effective, this approach could enhance current treatment strategies and introduce a novel rehabilitation method.

Supporting information

S1 Appendix. Study Protocol for Ethics Application.

(PDF)

pone.0319724.s001.pdf (1.4MB, pdf)
S2 Appendix. Participant Information Sheets.

(PDF)

pone.0319724.s002.pdf (1,003.8KB, pdf)
S3 Appendix. Participant Consent Form.

(PDF)

pone.0319724.s003.pdf (642.1KB, pdf)
S4 Appendix. International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) Questionnaire.

(PDF)

pone.0319724.s004.pdf (911.4KB, pdf)
S5 Appendix. Upper Limb Isometric Training (ULIT) Protocol.

(PDF)

pone.0319724.s005.pdf (156.4KB, pdf)
S6 Appendix. Anterior Cruciate Ligament Reconstruction (ACLR) Exercise Protocol.

(PDF)

pone.0319724.s006.pdf (2.1MB, pdf)
S7 Appendix. Adverse Events Form.

(PDF)

pone.0319724.s007.pdf (321.4KB, pdf)
S8 Appendix. TIDieR Checklist.

(PDF)

pone.0319724.s008.pdf (772.1KB, pdf)
S9 Appendix. Study Ethics Approval.

(PDF)

pone.0319724.s009.pdf (607.9KB, pdf)
S10 Appendix. SPIRIT Checklist.

(PDF)

pone.0319724.s010.pdf (934KB, pdf)

Acknowledgments

The authors would like to express their gratitude to all the patients who will participate in the study, as well as to Hospital Canselor Tuanku Muhriz and Universiti Malaya for their invaluable support.

Data Availability

No datasets were generated or analyzed during the current study. All relevant data from this study will be made available upon study completion.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Matar HE, Platt SR, Bloch BV, James PJ, Cameron HU. A Systematic Review of Randomized Controlled Trials in Anterior Cruciate Ligament Reconstruction: Standard Techniques Are Comparable (299 Trials With 25,816 Patients). Arthrosc Sports Med Rehabil. 2021;3(4):e1211–26. doi: 10.1016/j.asmr.2021.03.017 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Hiemstra LA, Webber S, MacDonald PB, Kriellaars DJ. Knee strength deficits after hamstring tendon and patellar tendon anterior cruciate ligament reconstruction. Med Sci Sports Exerc. 2000;32(8):1472–9. doi: 10.1097/00005768-200008000-00016 [DOI] [PubMed] [Google Scholar]
  • 3.Zbrojkiewicz D, Vertullo C, Grayson JE. Increasing rates of anterior cruciate ligament reconstruction in young Australians, 2000-2015. Med J Aust. 2018;208(8):354–8. [DOI] [PubMed] [Google Scholar]
  • 4.Kuenze C, Weaver A, Grindstaff TL, Ulman S, Norte GE, Roman DP, et al. Age-, Sex-, and Graft-Specific Reference Values From 783 Adolescent Patients at 5 to 7 Months After ACL Reconstruction: IKDC, Pedi-IKDC, KOOS, ACL-RSI, Single-Leg Hop, and Thigh Strength. J Orthop Sports Phys Ther. 2023;53(4):194–201. doi: 10.2519/jospt.2023.11389 [DOI] [PubMed] [Google Scholar]
  • 5.Fairus FZ, Ibrahim SA, Md Nadzalan A, Md Yusoff BAH, Mohamad N, Hendri EN. Pattern of anterior cruciate ligament reconstruction (ACLR) among athletes in Malaysia between 2015 and 2020. Teor Metod Fiz Vihov. 2022;22(3s):S51–8. [Google Scholar]
  • 6.Herbawi F, Lozano-Lozano M, Lopez-Garzon M, Postigo-Martin P, Ortiz-Comino L, Martin-Alguacil JL, et al. A Systematic Review and Meta-Analysis of Strength Recovery Measured by Isokinetic Dynamometer Technology after Anterior Cruciate Ligament Reconstruction Using Quadriceps Tendon Autografts vs. Hamstring Tendon Autografts or Patellar Tendon Autografts. Int J Environ Res Public Health. 2022;19(11):6764. doi: 10.3390/ijerph19116764 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Kotsifaki R, Korakakis V, King E, Barbosa O, Maree D, Pantouveris M, et al. Aspetar clinical practice guideline on rehabilitation after anterior cruciate ligament reconstruction. Br J Sports Med. 2023;57(9):500–14. doi: 10.1136/bjsports-2022-106158 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Buckthorpe M, Gokeler A, Herrington L, Hughes M, Grassi A, Wadey R, et al. Optimising the Early-Stage Rehabilitation Process Post-ACL Reconstruction. Sports Med. 2024;54(1):49–72. doi: 10.1007/s40279-023-01934-w [DOI] [PubMed] [Google Scholar]
  • 9.Svantesson E, Hamrin Senorski E, Webster KE, Karlsson J, Diermeier T, Rothrauff BB, et al. Clinical Outcomes After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Clinical Outcomes Consensus Group. Orthop J Sports Med. 2020;8(7). doi: 10.1177/2325967120934751 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Pietrosimone B, Lepley AS, Kuenze C, Harkey MS, Hart JM, Blackburn JT, et al. Arthrogenic Muscle Inhibition Following Anterior Cruciate Ligament Injury. J Sport Rehabil. 2022;31(6):694–706. doi: 10.1123/jsr.2021-0128 [DOI] [PubMed] [Google Scholar]
  • 11.Pinto FG, Thaunat M, Daggett M, Kajetanek C, Marques T, Guimares T, et al. Hamstring Contracture After ACL Reconstruction Is Associated With an Increased Risk of Cyclops Syndrome. Orthop J Sports Med. 2017;5(1). doi: 10.1177/2325967116684121 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Cristiani R, Mikkelsen C, Wange P, Olsson D, Stålman A, Engström B. Autograft type affects muscle strength and hop performance after ACL reconstruction. A randomised controlled trial comparing patellar tendon and hamstring tendon autografts with standard or accelerated rehabilitation. Knee Surg Sports Traumatol Arthrosc. 2021;29(9):3025–36. doi: 10.1007/s00167-020-06334-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.San Jose AT, Maniar N, Timmins RG, Beerworth K, Hampel C, Tyson N. Explosive hamstrings strength asymmetry persists despite maximal hamstring strength recovery following anterior cruciate ligament reconstruction using hamstring tendon autografts. Knee Surg Sports Traumatol Arthrosc. 2023;31(1):299–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Harput G, Kılınç H, Özer H, Baltaci G, Mattacola C. Quadriceps and hamstring strength recovery during early period of neuromuscular rehabilitation following ACL hamstring tendon autograft reconstruction. J Sport Rehabil. 2015;24. [DOI] [PubMed] [Google Scholar]
  • 15.Ko MS, Yang SJ, Ha JK, Choi JY, Kim JG. Correlation between hamstring flexor power restoration and functional performance test: 2-year follow-up after ACL reconstruction using hamstring autograft. Knee Surg Relat Res. 2012;24(2):113–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Ohji S, Aizawa J, Hirohata K, Ohmi T, Mitomo S, Koga H, et al. Changes in subjective knee function and psychological status from preoperation to 6 months post anterior cruciate ligament reconstruction. J Exp Orthop. 2022;9(1):114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Sengoku T, Nakase J, Mizuno Y, Ishida Y, Yanatori Y, Takemoto N, et al. Knee flexor strength at 6 months after anterior cruciate ligament reconstruction using hamstring tendon can be predicted from that at 3 months. Knee Surg Sports Traumatol Arthrosc. 2024;32(9):2474–83. doi: 10.1002/ksa.12370 [DOI] [PubMed] [Google Scholar]
  • 18.Myers TWLMT. Anatomy trains: myofascial meridians for manual and movement therapists. 3rd ed. Elsevier; 2014. [Google Scholar]
  • 19.Stecco A, Giordani F, Fede C, Pirri C, De Caro R, Stecco C. From muscle to the myofascial unit: current evidence and future perspectives. Int J Mol Sci. 2023;24(5). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Carvalhais VO do C, Ocarino J de M, Araújo VL, Souza TR, Silva PLP, Fonseca ST. Myofascial force transmission between the latissimus dorsi and gluteus maximus muscles: an in vivo experiment. J Biomech. 2013;46(5):1003–7. doi: 10.1016/j.jbiomech.2012.11.044 [DOI] [PubMed] [Google Scholar]
  • 21.Marpalli S, Rao MKG, Venkatesan P, George BM. Role of posterior layer of thoracolumbar fascia in epimuscular myofascial force transmission from gluteus maximus to latissimus dorsi and lower trapezius. Muscles, Ligaments and Tendons J. 2022;12(2):173–80. [Google Scholar]
  • 22.Vleeming A, Pool-Goudzwaard AL, Stoeckart R, van Wingerden JP, Snijders CJ. The posterior layer of the thoracolumbar fascia. Its function in load transfer from spine to legs. Spine (Phila Pa 1976). 1995;20(7):753–8. [PubMed] [Google Scholar]
  • 23.Wilke J, Krause F, Vogt L, Banzer W. What Is Evidence-Based About Myofascial Chains: A Systematic Review. Arch Phys Med Rehabil. 2016;97(3):454–61. doi: 10.1016/j.apmr.2015.07.023 [DOI] [PubMed] [Google Scholar]
  • 24.Jungseo P, Daehee L, Sangyong L. Isometric contraction of an upper extremity and its effects on the contralateral lower extremity. J Phys Ther Sci. 2014;13(26):1707–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Kaur N, Bhanot K, Ferreira G. Effects of lower extremity and trunk kinetic chain recruitment on serratus anterior muscle activation during forward punch plus exercise on stable and unstable surfaces. Int J Sports Phys Ther. 2020;15(1):126–38. [PMC free article] [PubMed] [Google Scholar]
  • 26.Krause DA, Dueffert LG, Postma JL, Vogler ET, Walsh AJ, Hollman JH. Influence of Body Position on Shoulder and Trunk Muscle Activation During Resisted Isometric Shoulder External Rotation. Sports Health. 2018;10(4):355–60. doi: 10.1177/1941738118769845 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Sato H, Maruyama H. Influence of the difference of PNF upper limb position on both lower limb extension muscle strength. Rigakuryoho Kagaku. 2007;22(2):249–53. [Google Scholar]
  • 28.Manca A, Hortobágyi T, Carroll TJ, Enoka RM, Farthing JP, Gandevia SC, et al. Contralateral Effects of Unilateral Strength and Skill Training: Modified Delphi Consensus to Establish Key Aspects of Cross-Education. Sports Med. 2021;51(1):11–20. doi: 10.1007/s40279-020-01377-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Smyth C, Broderick P, Lynch P, Clark H, Monaghan K. To assess the effects of cross-education on strength and motor function in post stroke rehabilitation: a systematic literature review and meta-analysis. Physiotherapy. 2023;119:80–8. doi: 10.1016/j.physio.2023.02.001 [DOI] [PubMed] [Google Scholar]
  • 30.Manca A, Dragone D, Dvir Z, Deriu F. Cross-education of muscular strength following unilateral resistance training: a meta-analysis. Eur J Appl Physiol. 2017;117(11):2335–54. doi: 10.1007/s00421-017-3720-z [DOI] [PubMed] [Google Scholar]
  • 31.Choi Y, Lee S. Effects of isometric contraction of the affected-side upper limb in the supine position on the opposite side muscle activity of the body trunk muscles of normal adults. J Phys Ther Sci. 2018;30(11):1346–8. doi: 10.1589/jpts.30.1346 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Deng N, Soh KG, Zaremohzzabieh Z, Abdullah B, Salleh KM, Huang D. Effects of Combined Upper and Lower Limb Plyometric Training Interventions on Physical Fitness in Athletes: A Systematic Review with Meta-Analysis. Int J Environ Res Public Health. 2022;20(1):482. doi: 10.3390/ijerph20010482 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Behm DG, Alizadeh S, Hadjizedah Anvar S, Hanlon C, Ramsay E, Mahmoud MMI, et al. Non-local Muscle Fatigue Effects on Muscle Strength, Power, and Endurance in Healthy Individuals: A Systematic Review with Meta-analysis. Sports Med. 2021;51(9):1893–907. doi: 10.1007/s40279-021-01456-3 [DOI] [PubMed] [Google Scholar]
  • 34.Hansford HJ, Parmenter BJ, McLeod KA, Wewege MA, Smart NA, Schutte AE, et al. The effectiveness and safety of isometric resistance training for adults with high blood pressure: a systematic review and meta-analysis. Hypertens Res. 2021;44(11):1373–84. doi: 10.1038/s41440-021-00720-3 [DOI] [PubMed] [Google Scholar]
  • 35.Marterer N, Mugele H, Schäfer SK, Faulhaber M. Effects of Upper Body Exercise Training on Aerobic Fitness and Performance in Healthy People: A Systematic Review. Biology (Basel). 2023;12(3):355. doi: 10.3390/biology12030355 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.James KE, Bloch DA, K L S in. An index for assessing blindness in a multi‐centre clinical trial: disulfiram for alcohol cessation—a VA cooperative study. Wiley Online Library. 1996. [DOI] [PubMed] [Google Scholar]
  • 37.Giampetruzzi N, Weaver AP, Roman DP, Cleland JA, Ness BM. Which Tests Predict 6-Month Isokinetic Quadriceps Strength After ACL Reconstruction? An Examination of Isometric Quadriceps Strength and Functional Tests at 3 Months. Int J Sports Phys Ther. 2023;18(6):1261–70. doi: 10.26603/001c.89263 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Mellemkjær F, Madeleine P, Nørgaard J, Jorgensen M, Kristiansen M. Assessing isometric quadriceps and hamstring strength in young men and women: between-session reliability and concurrent validity. Appl Sci. 2024;14:958. [Google Scholar]
  • 39.Grgic J, Lazinica B, Schoenfeld BJ, Pedisic Z. Test–retest reliability of the one-repetition maximum (1RM) strength assessment: A systematic review. Sports Med Open. 2020;6(1):31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Jeon Y-S, Lee J-W, Kim S-H, Kim S-G, Kim Y-H, Bae JH. Determining the Substantial Clinical Benefit Values for Patient-Reported Outcome Scores After Primary ACL Reconstruction. Orthop J Sports Med. 2022;10(5):23259671221091795. doi: 10.1177/23259671221091795 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Zebis MK, Warming S, Pedersen MB, Kraft MH, Magnusson SP, Rathcke M, et al. Outcome Measures After ACL Injury in Pediatric Patients: A Scoping Review. Orthop J Sports Med. 2019;7(7):2325967119861803. doi: 10.1177/2325967119861803 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Richardson RD, Casanova MP, Reeves AJ, Ryu S, Cady AC, Baker RT. Evaluating Psychometric Properties of the International Knee Documentation Committee Subjective Knee Form in a Heterogeneous Sample of Post-Operative Patients. Int J Sports Phys Ther. 2023;18(4):923–39. doi: 10.26603/001c.83940 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Cameron DM, Bohannon RW. Relationship between active knee extension and active straight leg raise test measurements. J Orthop Sports Phys Ther. 1993;17(5):257–60. doi: 10.2519/jospt.1993.17.5.257 [DOI] [PubMed] [Google Scholar]
  • 44.Niewiadomy P, Szuścik-Niewiadomy K, Kochan M, Kuszewski MT. The relationship between active and passive flexibility of the knee flexors. Muscles, Ligaments and Tendons J. 2021;11(02):360. [Google Scholar]
  • 45.Olivencia O, Godinez GM, Dages J, Duda C, Kaplan K, Kolber MJ, et al. The reliability and minimal detectable change of the ely and active knee extension tests. Int J Sports Phys Ther. 2020;15(5):776–82. doi: 10.26603/ijspt20200776 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Petajan JH. AAEM minimonograph #3: motor unit recruitment. Muscle Nerve. 1991;14(6):489–502. doi: 10.1002/mus.880140602 [DOI] [PubMed] [Google Scholar]
  • 47.Valenčič T, Ansdell P, Brownstein CG, Spillane PM, Holobar A, Škarabot J. Motor unit discharge rate modulation during isometric contractions to failure is intensity- and modality-dependent. J Physiol. 2024;602(10):2287–314. doi: 10.1113/JP286143 [DOI] [PubMed] [Google Scholar]
  • 48.Avrillon S, Hug F, Enoka RM, Caillet AHD, Farina D. The identification of extensive samples of motor units in human muscles reveals diverse effects of neuromodulatory inputs on the rate coding. Elife. 2024;13:RP97085. doi: 10.7554/eLife.97085 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Miller W, Kang M, Jeon S, Ye X. A meta-analysis of non-local heterologous muscle fatigue. J Trainol. 2019;8(1):9–18. [Google Scholar]
  • 50.Xu D, Zhou H, Quan W, Ma X, Chon TE, Fernandez J, et al. New insights optimize landing strategies to reduce lower limb injury risk. Cyborg Bionic Syst. 2025;6:0126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Welling W. Return to sports after an ACL reconstruction in 2024 - A glass half full? A narrative review. Phys Ther Sport. 2024;67:141–8. doi: 10.1016/j.ptsp.2024.05.001 [DOI] [PubMed] [Google Scholar]
  • 52.Cimino J, Braun C. Design a Clinical Research Protocol: Influence of Real-World Setting. Healthcare (Basel). 2023;11(16):2254. doi: 10.3390/healthcare11162254 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.White IR, Horton NJ, Carpenter J, Pocock SJ. Strategy for intention to treat analysis in randomised trials with missing outcome data. BMJ. 2011;342:d40. doi: 10.1136/bmj.d40 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Bell ML, Fiero M, Horton NJ, Hsu C-H. Handling missing data in RCTs; a review of the top medical journals. BMC Med Res Methodol. 2014;14:118. doi: 10.1186/1471-2288-14-118 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7. doi: 10.7326/0003-4819-158-3-201302050-00583 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Yaodong Gu

5 Mar 2025

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.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Yaodong Gu

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF.

3. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information .

4. We note that “Appendix 6- Standard Care ACLR HCTM Protocol.pdf” includes an image of a participant  in the study.

As per the PLOS ONE policy (http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research) on papers that include identifying, or potentially identifying, information, the individual(s) or parent(s)/guardian(s) must be informed of the terms of the PLOS open-access (CC-BY) license and provide specific permission for publication of these details under the terms of this license. Please download the Consent Form for Publication in a PLOS Journal (http://journals.plos.org/plosone/s/file?id=8ce6/plos-consent-form-english.pdf). The signed consent form should not be submitted with the manuscript, but should be securely filed in the individual's case notes. Please amend the methods section and ethics statement of the manuscript to explicitly state that the patient/participant has provided consent for publication: “The individual in this manuscript has given written informed consent (as outlined in PLOS consent form) to publish these case details”.

If you are unable to obtain consent from the subject of the photograph, you will need to remove the figure and any other textual identifying information or case descriptions for this individual.

5. Please upload a copy of your study protocol that was approved by your ethics committee/IRB as a Supporting Information file. By the study protocol, we mean the complete and detailed plan for the conduct and analysis of the trial approved by the ethics committee/IRB. Please send this in the original language. If this is in a language other than English, please also provide a translation. [https://journals.plos.org/plosone/s/submission-guidelines#loc-guidelines-for-specific-study-types

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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: 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.

PLoS One. 2025 Aug 21;20(8):e0319724. doi: 10.1371/journal.pone.0319724.r002

Author response to Decision Letter 1


6 Apr 2025

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)

Attachment

Submitted filename: Response to Reviewers 5 April 2025.docx

pone.0319724.s012.docx (23KB, docx)

Decision Letter 1

Yaodong Gu

21 Apr 2025

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. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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.

Kind regards,

Yaodong Gu

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. 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

**********

Acceptance letter

Yaodong Gu

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

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Appendix. Study Protocol for Ethics Application.

    (PDF)

    pone.0319724.s001.pdf (1.4MB, pdf)
    S2 Appendix. Participant Information Sheets.

    (PDF)

    pone.0319724.s002.pdf (1,003.8KB, pdf)
    S3 Appendix. Participant Consent Form.

    (PDF)

    pone.0319724.s003.pdf (642.1KB, pdf)
    S4 Appendix. International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) Questionnaire.

    (PDF)

    pone.0319724.s004.pdf (911.4KB, pdf)
    S5 Appendix. Upper Limb Isometric Training (ULIT) Protocol.

    (PDF)

    pone.0319724.s005.pdf (156.4KB, pdf)
    S6 Appendix. Anterior Cruciate Ligament Reconstruction (ACLR) Exercise Protocol.

    (PDF)

    pone.0319724.s006.pdf (2.1MB, pdf)
    S7 Appendix. Adverse Events Form.

    (PDF)

    pone.0319724.s007.pdf (321.4KB, pdf)
    S8 Appendix. TIDieR Checklist.

    (PDF)

    pone.0319724.s008.pdf (772.1KB, pdf)
    S9 Appendix. Study Ethics Approval.

    (PDF)

    pone.0319724.s009.pdf (607.9KB, pdf)
    S10 Appendix. SPIRIT Checklist.

    (PDF)

    pone.0319724.s010.pdf (934KB, pdf)
    Attachment

    Submitted filename: Response to Reviewers 5 April 2025.docx

    pone.0319724.s012.docx (23KB, docx)

    Data Availability Statement

    No datasets were generated or analyzed during the current study. All relevant data from this study will be made available upon study completion.


    Articles from PLOS One are provided here courtesy of PLOS

    RESOURCES