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. 2025 Sep 5;20(9):e0331285. doi: 10.1371/journal.pone.0331285

Safety and resource utilisation efficiency of semi-skeletonised versus skeletonised left internal mammary artery harvesting techniques: The BANGABANDHU study

Redoy Ranjan 1,2,3,*, Aziz Momin 2, Riyaz A Kaba 4, Gie Ken-Dror 1, Sanjay Kumar Raha 5, Md Kamrul Hasan 5, Venkatachalam Chandrasekaran 2, Asit Baran Adhikary 3,6
Editor: Eyüp Serhat Çalık7
PMCID: PMC12412939  PMID: 40911587

Abstract

Background

The ideal harvesting techniques of the left internal mammary artery (LIMA) for coronary artery bypass graft (CABG) are elusive. We assessed the safety and resource utilisation efficiency of semi-skeletonised LIMA harvesting techniques, focusing on length, harvesting time, and the number of Ligaclips used compared to skeletonised techniques within a single surgeon’s practice.

Methods

The BANGABANDHU (Bangladeshi Atherosclerosis Biobank AND Hub) study was an ambispective observational cohort that evaluated age- and sex-matched 2209 adult Bangladeshi isolated CABG population from 1st January 2015 to 31 January 2025. Univariate analysis observed the difference pattern in the dataset, while multivariate logistic regression (LR) analysis identified the independent variables associated with the advantage of semi-skelitonised LIMA. The area under the receiver operating characteristic (AUROC) curve demonstrated the goodness-of-fit of the prediction model.

Results

We evaluated 2209 age- and sex-matched adult isolated CABG patients (skeletonised LIMA; n = 1050 and semi-skeletonised LIMA; n = 1159) with identical comorbidities (EuroSCORE II, hypertension, diabetes, renal impairment, COPD, left main and multivessel coronary artery disease) between study groups (p > 0.05). LIMA harvest time (35.9 ± 5.5 vs 16.6 ± 3.9; p < 0.001) and number of used Ligaclip (23.6 ± 4.8 vs 11.7 ± 3.6; p < 0.001) were significantly higher in the skeletonised compared to the semi-skeletonised LIMA sample. Furthermore, an age and sex-adjusted multivariate logistic regression model found LIMA harvest time (odds ratio [OR] 0.067, 95% CI 0.01–0.39; p = 0.003) and number of used Ligaclip (OR 0.561, 95% CI 0.41–0.76; p < 0.001) significantly lower among semi-skeletonised LIMA techniques.

Conclusion

The semi-skeletonised LIMA technique is advantageous as it significantly reduces harvesting time and requires fewer Ligaclips compared to the skeletonised technique.

Introduction

Coronary artery bypass graft (CABG) surgery frequently utilises the left internal mammary artery (LIMA) for revascularisation of the left anterior descending (LAD) artery in ischaemic heart disease (IHD) [1,2]. A skeletonised LIMA harvesting technique involves dissecting the mammary artery free from the surrounding fascia, veins, and surrounding adipose tissue of the chest wall, leaving only the LIMA itself, which is commonly utilised conduits in CABG surgery [3,4]. Previously published papers observed that the skeletonised LIMA conduits have a longer conduit length and better postoperative clinical and angiographic profile compared to the pedicled LIMA graft [3,5–7]. Further, several authors reported that it is associated with reduced sternal wound complications and mediastinitis, making it the preferred harvesting technique for patients undergoing CABG surgery, especially with bilateral internal mammary artery grafting [6–8]. However, skeletonised LIMA has potential risks, especially a higher conduit haematoma due to iatrogenic injury and a higher graft occlusion rate requiring repeat revascularisation. On top of that, the skeletonised LIMA harvest technique is time-consuming and requires more Ligaclip to occlude the branches, which costs more money [7–10].

Nowadays, cardiac surgeons have utilised a modified harvesting technique known as the semi-skeletonised technique, which involves harvesting the LIMA with the veins and thin rim of connective tissues that act as a protective shield from iatrogenic and inadvertent trauma, especially from electrocautery [11,12]. This semi-skeletonised harvesting technique was found to have minimal postoperative bleeding, and the total amount of bleeding was comparable to that of the skeletonised and pedicle techniques, regardless of pleural integrity [13]. Nevertheless, existing literature found less incidence of sternal wound infection in semi-skeletonised LIMA compared to the pedicled technique, which paradoxically suggests similar findings in the skeletonised LIMA procedure [12–15]. However, it is essential to note that the decision between skeletonised and semi-skeletonised mammary harvest depends on the surgeon’s comfort level and expertise, and both techniques can be used effectively [11,14,15].

To the best of our knowledge, this is the first large-scale study comparing the skeletonised and semi-skeletonised LIMA harvesting techniques to evaluate the benefits of the semi-skeletonised LIMA harvesting techniques over skeletonised LIMA, with a secondary aim to identify early complications associated with the semi-skeletonised LIMA technique.

Materials and methods

The BANGABANDHU (Bangladeshi Atherosclerosis Biobank AND Hub) is an ambispective observational study with protocols published elsewhere [16]. We evaluated 2209 age- and sex-matched adult IHD patients undergoing either primary or redo isolated coronary artery bypass graft (CABG) surgery in a single surgeon’s practice from January 1, 2015, to January 31, 2025. We recruited the study population into two groups based on the stochastically performed LIMA harvest techniques: either the skeletonised or the semi-skeletonised group. We utilised a probabilistic sampling method. Prior to the recruitment of the study population, ethical clearance was obtained from the institutional review board of Bangabandhu Sheikh Mujib Medical University (BSMMU/2024/5390; date 21 May 2024), Bangladesh, and this study complied with the Declaration of Helsinki. Due to its ambispective nature, we recruited participants retrospectively from preexisting hospital databases and prospectively from 1 June 2024 until 31 January 2025 for research purposes. For retrospectively recruited participants, all data were fully anonymised before accessing the data, and informed consent was obtained during their follow-up visits, while prospective participants provided informed consent at the recruitment. To ensure quality control and data completeness, we utilised standardised data collection tools, which have been described elsewhere [16] and provided thorough training for data collectors who were post-graduate surgical trainees. Further, two independent investigators cross-verified the data integrity and applied statistical methods to assess completeness, reducing biases and enhancing reliability. Data were fully anonymised and encrypted to maintain confidentiality. We recruited extensive sociodemographic data, such as age, gender, comorbidities and details of LIMA harvesting technique, harvesting time, LIMA length, and number of Ligaclip used. Furthermore, we recorded complications related to the harvesting techniques, such as LIMA spasm, haematoma, and any chest re-exploration required due to bleeding. LIMA haematoma is defined as a localised intramural or extramural collection of blood within or around the adjacent soft tissue, appearing as a bulging, discoloured arterial segment that may compromise graft patency. Although no standard distance threshold defines a LIMA haematoma, we discarded the conduit if the haematoma extended beyond 2 cm and was likely to impair distal run-off, opting instead for alternative conduits such as the radial artery or saphenous vein. In this study, we ensured at least 1–2 cm of healthy distal LIMA with good run-off, as assessed visually, for safe anastomosis. Furthermore, LIMA spasm was defined as arterial blanching or narrowing resulting from a transient vasoreactive response to mechanical manipulation, excessive dissection, or thermal injury from cautery, which potentially reduces distal blood flow, either temporarily or persistently, thereby compromising conduit patency. In this study, we applied warm topical vasodilators, including papaverine, nitroglycerin, and calcium channel blockers (e.g., diltiazem), and ensured continuous hydration of the LIMA during harvesting. Additionally, intraluminal vasodilators, such as papaverine and nitroglycerin, were administered if needed to improve the spasm.

LIMA harvesting technique

The LIMA harvest was conducted via a standard median sternotomy, beginning with the dissection of the parietal pleura, connective tissue, and endothoracic fascia using low-power electrocautery. The starting point of the LIMA harvest typically depends on the individual case, usually initiated at the 3rd or 4th intercostal space or the most visibly accessible part of the LIMA. For skeletonised LIMA, dissection proceeded meticulously along the adventitial layer, leading to the exposed entire artery down to its distal bifurcation and only the artery was harvested (Fig 1a,b). Side branches were carefully clipped, and the chest wall side of these branches was cauterised and clipped for optimal haemostasis, depending on the size of the branches. The semiskeletonised LIMA was excised as a veno-arterial pedicle with surrounding thin adipose tissue, keeping ~1 cm of tissue on either side of the LIMA, except for muscular support and endothoracic fascia (Fig 1c,d,e), as Horii and Suma described previously [17]. The initial incision of the pleura and endothoracic fascia was performed along the medial aspect of the accompanying vein, without an incision on the lateral side. The semi-skeletonised LIMA was then mobilised by scraping it from the endothoracic fascia with the cautery tip, while keeping it attached to the chest wall. For branches >1mm size, Ligaclips were applied on the LIMA side, while the thoracic side was electrocauterised. For intercostal branches <1 mm in size, coagulation was performed for approximately 3–4 seconds, with division occurring about 1 mm from the LIMA wall to minimise damage to the LIMA conduits. In both harvesting techniques, the LIMA was dissected proximally above the first intercostal branch and distally till bifurcation into the musculophrenic and superior epigastric arteries while avoiding coagulation of adjacent veins.

Fig 1. LIMA harvesting techniques- skeletonised (1a, 1b) and semi-skeletonised (1c, 1d, 1e); Purple (1a) and Blue (1b) circles indicate the used Ligaclips.

Fig 1

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1c: The yellow arrow shows the distal end of LIMA just before the bifurcation; 1d: The red arrow shows the left anterior descending artery on a Dextrocardia, and the red circle shows the diameter of semi-skeletonised LIMA; 1e: The black circle indicates the diameter (1 cm) of semi-skeletonised LIMA.

After 2–3 minutes of systematic heparinisation, achieving an ACT of >350 seconds, the distal end of the LIMA was divided at or just before the level of the bifurcation. Once the conduit was divided, LIMA flow quality was assessed visually by allowing the graft to bleed for a few seconds. The distal end was then gently clamped with an atraumatic bulldog clamp or clipped to prevent unnecessary bleeding while we prepared for distal anastomosis. We applied intermittent topical warm papaverine spray throughout the LIMA harvest, maintaining systolic blood pressure around 100 mmHg. After harvesting, the LIMA was wrapped with warm papaverine-soaked gauze, avoiding direct papaverine injection into the lumen to prevent damage, until it’s needed to improve the spasm. Care was taken to prevent phrenic nerve injury during proximal dissection. Further, direct grasping of the LIMA with forceps was avoided by grasping nearby adventitial tissue. In both cases, we opened the left pleura to enhance LIMA visualisation and placed a drain tube as a precaution against cardiac tamponade – a standard practice in our procedure; though postoperative chest reopening due to bleeding was rare, occurring in less than 0.5% of our cases. Both the skeletonised and semi-skeletonised LIMA harvesting techniques were performed by two equally qualified surgeons, those who had completed postgraduate surgical training in cardiac surgery under a single-surgeon practice and performed both harvesting techniques stochastically. We used the same standard LIMA harvesting techniques for both elective and emergency CABG surgeries, as well as for redo CABG procedures when the LIMA is available for harvesting. Furthermore, we employed reusable Ligaclips applicators to apply the Ligaclips during these harvesting procedures.

Statistical analysis

We utilised version 28.0 SPSS (Statistical Package for the Social Sciences) software for statistical analysis. Initially, a univariate analysis was conducted to ascertain the difference patterns in the BANGABANDHU dataset. Study variables with a p value of ≤0.05 between LIMA harvesting techniques were included in a multivariate logistic regression model to identify the independent variables associated with the benefits of semi-skeletonised LIMA. Additionally, the goodness-of-fit of the prediction model was confirmed by the area under the receiver operating characteristic (AUROC) curve. A p-value of <0.05 was considered statistically significant.

Results

The BANGABANDHU study evaluated 2209 age- and sex-matched adult Bangladeshi isolated CABG patients, which included 1050 patients with a skeletonised LIMA and 1159 patients with a semi-skeletonised LIMA. Preoperative risk profiles and comorbidities (EuroSCORE II, hypertension, diabetes, renal impairment, COPD, left main disease and multivessel CAD) were identical between study groups (p > 0.05) (Table 1). However, LIMA length (15.7 ± 0.3 vs 15.5 ± 0.5; p = 0.05), harvest time in minutes (35.9 ± 5.5 vs 16.6 ± 3.9; p < 0.001) and number of used Ligaclip (23.6 ± 4.8 vs 11.7 ± 3.6; p < 0.001) were significantly higher in skeletonised compared to the semi-skeletonised LIMA sample. Additionally, postoperative pain and superficial or deep sternal wound infections were similar between study groups.

Table 1. Baseline characteristics of study population (n = 2209).

Variables Skeletonised LIMA (n = 1050) Semi-skeletonised LIMA (n = 1159) P value
Age (mean ±SD) 57.3 ± 6.9 57.9 ± 7.1 0.09
Male 899 (85.7%) 999 (86.2%) 0.81
Preop EuroSCORE II 3.8 ± 0.8 3.9 ± 0.9 0.07
Hypertension 921 (87.7%) 1041 (89.8%) 0.21
Diabetes mellitus 780 (74.3%) 887 (76.9%) 0.27
Reanl impairment 23 (2.2%) 12 (1.0%) 0.07
COPD 113 (10.8%) 117 (10.1%) 0.67
LM disease 43 (4.1%) 42 (3.6%) 0.64
Multivessel CAD 950 (90.5%) 1037 (89.5%) 0.53
LVEF <30% 72 (6.9%) 94 (8.1%) 0.41
Emergency CABG 18 (1.7%) 29 (2.5%) 0.34
Operative variables
LIMA length (cm) (mean ±SD) 15.7 ± 0.3 15.5 ± 0.5 0.05
LIMA harvest time (minute) 35.9 ± 5.5 16.6 ± 3.9 <0.001
Number of LigaClip (mean ±SD) 23.6 ± 4.8 11.7 ± 3.6 <0.001
LIMA spasm 16 (1.5%) 8 (0.7%) 0.11
LIMA haematoma 12 (1.1%) 0 (0.0%) <0.001
Extra-pleural LIMA 723 (68.9%) 746 (64.4%) 0.08
Re-exploration 16 (1.5%) 20 (1.7%) 0.76
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Here, COPD -chronic obstructive pulmonary disease; CAD -coronary artery disease; LVEF -left ventricular ejection fraction; and LIMA -left internal mammary artery. The P-value reached from the chi-square test and independent t-test, as appropriate; P < 0.05 confirms statistical significance.

An age and gender adjusted multivariate logistic regression model found LIMA harvest time (odds ratio [OR] 0.067, 95% CI 0.01–0.39; p = 0.003) and number of Ligaclips used (OR 0.561, 95% CI 0.41–0.76; p < 0.001) were significantly and positively associated with the semi-skeletonised LIMA techniques (Table 2). The OR demonstrated that the harvest time and the number of used Ligaclips were 93.3% and 43.9% lower, respectively, in the semi-skeletonised LIMA compared to the skeletonised LIMA. The area under the receiver operating characteristic (AUROC) curve was 0.99 for the LIMA harvest time and 0.97 for the number of Ligaclips used, representing the goodness-of-fit of the model (Fig 2). Furthermore, the LIMA harvest time showed a sensitivity of 98.5% and specificity of 88.5%, while the number of Ligaclips used had a sensitivity of 92.5% and specificity of 82.0% among semi-skeletonised LIMA technique samples. Furthermore, overall LR model quality was excellent 99.9% for LIMA harvest time and 97.5% for the number of Ligaclip used variables in predicting advantage of semi-skeletonised LIMA techniques (S1 Fig).

Table 2. Age and gender adjusted multivariate logistic regression model predicting advantages of semi-skeletonised LIMA techniques.

Odds Ratio 95% CI P value
Lower Upper
LIMA harvest time (min) 0.067 0.01 0.39 0.003
Ligaclip used (number) 0.561 0.41 0.76 <0.001
LIMA length (cm) 0.191 0.01 11.10 0.42
Age 0.949 0.84 1.07 0.40
Gender 0.067 0.01 12.57 0.31
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Dependent variable: Semi-skeletonised LIMA techniques.

Variable(s): LIMA length in cm, LIMA harvest time, Ligaclip used, Age, Gender. CI -Confidence Interval.

Fig 2. The receiver operating characteristic (ROC) curve illustrates the area under the ROC curve with the sensitivity and specificity of the risk prediction model.

Fig 2

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Discussion

We found that the LIMA harvesting time and number of Ligaclips used have significantly lower odds, approximately 93.3% and 43.9%, respectively, among the semi-skeletonised LIMA group compared to the skeletonised LIMA group. Further, identical sociodemographic variables and complications associated with LIMA harvesting techniques validate our findings on the advantage of semi-skeletonised over skeletonised LIMA techniques.

Skeletonised LIMA harvesting typically takes longer than pedicle techniques due to the meticulous dissection of the surrounding tissues to avoid trauma to the LIMA, which aims to provide better conduit quality [3–8,18]. Despite similar surgical skills, we found that semi-skeletonised LIMA harvesting is faster due to simpler dissection, which preserves some surrounding tissues, requiring less meticulous dissection and fewer clips of small LIMA branches, resulting in quicker conduit preparation compared to skeletonised LIMA techniques. Additionally, the higher skeletonised LIMA harvesting time results in an extended operative time, which is associated with increased resource utilisation, such as operating room time, anaesthesia services, and staffing, leading to increased operative costs [19,20]. Depending on the surgeon’s experience, the average skeletonised LIMA harvest time ranges from 25 to 45 minutes, similar to our findings [3–8,10,13]. Further, existing literature found that skeletonised LIMA was associated with lower wound infections, postoperative pain, short hospital stays, and better preservation of lung function but required longer operative time [4,6]. Contrarily, studies also observed that skeletonised LIMA has no early or mid-term outcomes benefits, [7] and does not appear to lower the occurrence of postoperative chest pain despite causing significantly less inner chest wall trauma [8]. Furthermore, higher operative time substantially impacts the total costs of CABG procedures, increasing hospital expenses and the risk of postoperative complications, [20] which supports less time-consuming but safe semi-skeletonised LIMA harvest techniques.

Skeletonised LIMA harvesting required more extensive use of Ligaclips to secure the numerous small branches of the artery than the pedicled method [21]. In another study, Wendler et al. [22] indicated that the skeletonised technique, by exposing more arterial branches, indeed necessitated a greater number of Ligaclips to achieve haemostasis. Additionally, several published papers also stated that with experienced surgical techniques, the increased use of Ligaclips can be minimised even with skeletonised LIMA harvesting, which implies that the number of Ligaclips used may be more related to the surgeon’s proficiency and technique rather than the harvesting method alone [23–25]. Furthermore, a recent Randomised Control Trial found that a semi-skeletonised LIMA graft to the left anterior descending artery resulted in good distal run-off with less operative time, supporting our study findings [26]. Despite similar LIMA spasm and re-exploration events, we found the LIMA haematoma rate was significantly lower in the semi-skeletonised LIMA group, which also supports the safety profile of the semi-skeletonised technique, consistent with existing study findings [11,13,27]. This is the first South Asian study to observe that semi-skeletonised LIMA was not inferior to skeletonised LIMA in terms of number of used Ligaclips, harvest time and early postoperative bleeding during off-pump CABG surgery.

Strength and limitation

Despite the robustness of the study results, a few limitations must be acknowledged, especially the observational nature of the study. The study population is primarily of Bangladeshi ancestry, so the LIMA length might not be generalised to other Asian countries or across the globe. Despite ongoing debate regarding the optimal length of the LIMA in various harvesting techniques, our protocol specified dissection of the LIMA from proximal to the first intercostal branch, extending to the distal bifurcation into the musculophrenic and superior epigastric arteries. This approach was designed to minimize outcome bias related to conduits length and harvesting time. The harvesting time and number of Ligaclip used might vary between surgical trainees and surgeons; however, utilising a database from all equally qualified surgeons who completed postgraduate surgical training in cardiac surgery in a single surgeon practice minimises the risk of outcome bias. Nevertheless, further studies evaluating the cost-effectiveness of semi-skeletonised versus skeletonised LIMA, considering factors such as total procedural costs, length of hospital stay, and follow-up expenses, may shed more light on the current study findings. Additionally, we acknowledge the potential for recruitment bias due to the ambispective nature of the study; however, using an age- and sex-matched study sample with similar comorbidities and standardised data collection tools minimises this risk of bias. While the mean difference in LIMA length between study groups is very minimal, a p-value of 0.05 raises concerns about a type I error. However, a large sample size with low variability in LIMA length can make even minor differences more detectable, leading to potential misinterpretation [28]. The inclusion of all primary, isolated elective, and emergency CABG, as well as redo CABG cases with available LIMA, may raise concerns about bias in harvesting techniques and the number of Ligaclip uses. However, the harvesting techniques for the LIMA remained consistent, which helps mitigate the risk of bias. Finally, utilising similar clinical profiles of study participants cross-validates our short harvesting time, representing lower total operative time, and the low number of used Ligaclips, which demonstrates the resource utilisation efficiency of the semi-skeletonised LIMA harvest technique.

Conclusion

Semi-skeletonised techniques are safe and feasible, with resource utilisation efficiency on LIMA harvesting, especially significantly shorter harvesting time and fewer Ligaclips than skeletonised techniques. We recommend conducting further studies to assess the long-term graft patency and survival benefits of semi-skeletonised compared to skeletonised LIMA in CABG surgery to validate the robustness of the current study’s findings.

Suppvorting information

S1 Fig. The goodness-of-fit of the logistic regression model.

(DOCX)

pone.0331285.s001.docx (54.4KB, docx)

Data Availability

The data are not publicly available due to privacy or ethical restrictions; however, the data supporting current study findings are available on reasonable request from Dr Sanjoy Kumar Saha, Consultant of Cardiac Anaesthesia (email: sanjoydr@bsmmu.edu.bd), who holds the data and responds to external requests for data access. Further, we will ensure long-term data storage using institutional archives, reliable repositories, and cloud storage, as well as employ redundancy like multiple backups to enhance data availability.

Funding Statement

This study was funded by a research grant from the Bangladesh Medical Research Council (BMRC), reference number BMRC/Research Grant/2025/191 (1-10). The funders had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

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  • 27.Deng Y, Byth K, Paterson HS. Semi-skeletonized internal mammary artery grafts and sternal wound complications. Asian Cardiovasc Thorac Ann. 2004;12(3):227–32. doi: 10.1177/021849230401200310 [DOI] [PubMed] [Google Scholar]
  • 28.Kaplan RM, Chambers DA, Glasgow RE. Big data and large sample size: a cautionary note on the potential for bias. Clin Transl Sci. 2014;7(4):342–6. [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Usama Waqar

12 Mar 2025

Dear Dr. Ranjan,

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 26 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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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.

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We look forward to receiving your revised manuscript.

Kind regards,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: PLOS ONE

Safety and cost-effectiveness of semi-skeletonised versus skeletonised left internal mammary artery harvesting techniques: the BANGABANDHU study

PONE-D-25-07678

March 7, 2025

I want to thank the authors for their research efforts and for the opportunity to review their manuscript.

I have included some comments below followed by some line items.

First, the three techniques would be skeletonised, semi-skeletonised and pedicled. Based on your description of semi-skeletonised, you need to explain how that is different than a pedicled LIMA (a pedicle also includes the veins, adipose, endothoracic fascia and muscle). I cannot tell the difference between semi-skeletonised and pedicled other than some arbitrary distance from the LIMA that is included in the dissection.

Second, you mention the length of the LIMA as a difference but you say that the protocol requires the same distance from proximal to the first intercostal branch to the bifurcation, so how is there a difference in length? In the results, the lengths need to be included. The difference was found to be significant at p=0.05 with the difference being 0.2 (which is inside the standard deviation so I am not sure how that is statistically significant). This seems to not be a important difference.

Third, there is more than a doubling of time between skeletonised and semi-skeletonised. That seems to be excessive. This should be explored or explained a little more.

Fourth, you should make clear how many surgeons were included in this study. I believe you are saying that they all trained under the same surgeon. Is the current population from a single surgeon practice? Is it the CABG surgeon taking down the IMA or is it an assistant surgeon? This area of how many surgeons are participating is important to document.

Line 36: “that evaluated 2209 age- and sex-matched adult Bangladeshi isolated CABG patients”

Line 38: I am not sure “curtailed” is the correct word here

Line 39: should be consistent and use “-“ in semi-skeletonised or not (this is the first time it was not used)

Line 42: “we evaluated 2209 age- and sex-matched adult isolated CABG patients”

Line 44: should not capitalize anything other than EuroSCORE II and COPD

Line 45: usually, “p” is not capitalized (p> 0.05)

Line 48: Further more, AN age- and sex-adjusted multivariate….

Line 52: you mention cost-effectiveness here without any discussion of it in the Results (you should not include a result in the Conclusion that was not presented in the Results)

Line 86: “its blood supply” – do you mean the chest wall’s blood supply? It is not clear in the way this sentence is written (the blood supply presumably refers to the chest wall and minimal surrounding tissue presumably refers to the LIMA but these two items are separated by an “and” which presumes both items are related to the same thing).

Line 95: “which is expensive” – I would say costs more money, but “expensive” is relative and in comparison with the cost of the entire operation, the Ligaclip is not a major driver of cost.

Line 51: “We recruited 2209 age- and sex-matched adult CABG patients”

Line 53: “We divided the study population into 2 groups based on….”

Line 65: no need for the word “specifically”

Line 79: when skeltonising, were Ligasure clips only used on the LIMA side just like in the semi-skeletonised scenario? This would be a difference in treatment if they were not the same.

Line 86: “conduit is” – the paper has been written in the past tense, you switch to present here and then continue in the present tense in the next sentence.

Line 93: “direct grasping of the LIMA with forceps was avoided by grasping nearby adventitial tissue.”

Line 208: you switch from preterite to present here as well

Line 223: “evaluated 2209 age- and sex-matched adult Bangladeshi isolated CABG patients which included 1050 with a skeletonized LIMA and 1159 with a semi-skeletonised LIMA.”

Line 225: no words should be capitalized other than EuroSCORE II, COPD and CAD)

Line 227: you should include the lengths, times and number of clips here

Line 228: “number of Ligaclips used”

Line 228: “compared to THE semi-skeletonised”

Line 231: AN age- and gender-adjusted

Line 232: “number of Ligaclips used”

Line 233: were significantly and positively associated with the semi-skeletonised LIMA technique

Line 234-236: I do not understand this sentence

Line 236: this sentence needs to be re-worked

Line 284: this sentence needs to be re-worked

Line 288: “is not”

Line 297: if the protocol was from proximal to the first intercostal branch to the bifurcation, then why was the skeletonised longer if both were prepared the same way in terms of length?

Line 302: I am not sure that this “mitigates the risk of outcome bias”

Reviewer #2: This manuscript addresses a clinically relevant topic comparing semi-skeletonised and skeletonised LIMA harvesting techniques. However, several key issues limit its current suitability for publication.

First, the authors emphasize cost-effectiveness but provide inadequate economic analysis. Simply counting Ligaclips is insufficient; a detailed cost breakdown including operative time, resource utilization, and hospital stay should be presented.

Second, the multivariate logistic regression model raises concerns. The odds ratios reported (e.g., OR 10.8 for LIMA harvest time) appear unusually large, suggesting potential errors in statistical modeling or interpretation. Clarification and re-analysis are needed.

Third, the authors mention early complications but do not adequately define or systematically evaluate them. Clear definitions, standardized follow-up periods, and explicit complication rates should be provided.

Lastly, the manuscript lacks clarity regarding surgeon experience standardization. Although a single surgeon's practice is mentioned, variability among trainees and junior surgeons may significantly confound results.

Reviewer #3: Dear Authors,

Thank you for submitting your manuscript for review. I was pleased to receive it.

Your study addresses a clinically relevant question and provides useful insights into the practical and cost-effective aspects of IMA harvesting techniques. However, I have some comments for your consideration:

1. In the abstract conclusion, you could briefly include clinical relevance or outcomes (e.g., complication rates, recovery, postoperative morbidity) alongside procedural efficiency.

2. You mention the “ambispective” nature of the study. Could you clarify how the prospective and retrospective data were integrated and managed to avoid biases regarding quality and completeness across the two collection approaches?

3. Why were certain covariates (e.g., hypertension, diabetes, COPD) matched but not directly included in the multivariate regression model? Could you explain this choice in the Methods?

4. Regarding the harvesting techniques, descriptions are clear. However, could you include additional intraoperative images (if available) to show differences between the techniques?

5. The use of Ligaclips as a cost indicator is well-justified. Still, could you provide an economic analysis or at least a brief comparative analysis of the overall economic impact (e.g., average procedural cost differences or estimated financial savings per case)?

6. Your confidence intervals in the logistic regression (e.g., OR 10.8 with CI 0.01-0.39) seem incorrect in terms of directionality. Typically, OR >1 indicates increased odds. Please clarify.

7. Can you compare semi-skeletonised and skeletonised techniques regarding long-term patency or graft survival, if this data is available?

8. Given that all surgeries were performed by qualified surgeons within a single surgeon's practice, how generalizable do you believe these results are? Could you briefly discuss how the familiarity of surgeons with each technique may influence results?

9. You have mentioned the identical comorbidities between study groups, demonstrating good baseline comparability. However, given the single-center, single-surgeon practice setting, could there be any institutional protocols or perioperative management peculiarities that may have influenced outcomes differently from broader multi-institutional contexts?

Thank you again for the opportunity to review your work.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: Yes:  Robert J. Chen, MD, MPH

Reviewer #3: Yes:  Savvas Lampridis

**********

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PLoS One. 2025 Sep 5;20(9):e0331285. doi: 10.1371/journal.pone.0331285.r002

Author response to Decision Letter 1

28 Mar 2025

Reviewer #1: I want to thank the authors for their research efforts and for the opportunity to review their manuscript. I have included some comments below followed by some line items.

Q: First, the three techniques would be skeletonised, semi-skeletonised and pedicled. Based on your description of semi-skeletonised, you need to explain how that is different than a pedicled LIMA (a pedicle also includes the veins, adipose, endothoracic fascia and muscle). I cannot tell the difference between semi-skeletonised and pedicled other than some arbitrary distance from the LIMA that is included in the dissection.

Response: I appreciate your concerns, which are not untrue. However, as a cardiac surgeon, you must recognise that minimising tissue damage during LIMA harvesting is crucial, especially since pedicled LIMA grafts are prone to sternal wound infections, particularly in patients with comorbidities. Therefore, we hypothesised that harvesting in a semi-skeletonised fashion, as you said, "some arbitrary distance from the LIMA that is included in the dissection", could be safe. Despite the lack of a standard definition, we defined the semiskelitonised technique in our study on page 7, lines 181-183 (yellow highlighted), which might be helpful in future studies to define semi-skeletonised LIMA.

Q: Second, you mention the length of the LIMA as a difference but you say that the protocol requires the same distance from proximal to the first intercostal branch to the bifurcation, so how is there a difference in length? In the results, the lengths need to be included. The difference was found to be significant at p=0.05 with the difference being 0.2 (which is inside the standard deviation so I am not sure how that is statistically significant). This seems to not be a important difference.

Response: Yes, we agreed, and in this study, we set a p-value of <0.05 as statistically significant, which we mentioned on page 8, lines 216,217 (yellow highlighted).

Q: Third, there is more than a doubling of time between skeletonised and semi-skeletonised. That seems to be excessive. This should be explored or explained a little more.

Response: While we mentioned it on page 10, lines 257-259 (highlighted in yellow), we have also added a brief explanation in lines 260-262 (highlighted in yellow).

Q: Fourth, you should make clear how many surgeons were included in this study. I believe you are saying that they all trained under the same surgeon. Is the current population from a single surgeon practice? Is it the CABG surgeon taking down the IMA or is it an assistant surgeon? This area of how many surgeons are participating is important to document.

Response: All study patients are from a single surgeon's practice, which we mentioned on page 6, lines 152,153. Further, the LIMA was harvested by two equally trained cardiac surgeons, which we mentioned in methodology sections lines 204-207.

Q: Line 36: "that evaluated 2209 age- and sex-matched adult Bangladeshi isolated CABG patients"

Response: Modifications are done as you suggested

Q: Line 38: I am not sure "curtailed" is the correct word here

Response: Thanks for your suggestions, "curtailed" replaced with "observed".

Q: Line 39: should be consistent and use "-"in semi-skeletonised or not (this is the first time it was not used)

Response: Modifications are done as you suggested

Q: Line 42: "we evaluated 2209 age- and sex-matched adult isolated CABG patients"

Response: Modifications are done as you suggested

Q: Line 44: should not capitalize anything other than EuroSCORE II and COPD

Response: Modifications are done as you suggested

Q: Line 45: usually, "p" is not capitalized (p> 0.05)

Response: Modifications are done as you suggested throughout the manuscript.

Q: Line 48: Furthermore, AN age- and sex-adjusted multivariate….

Response: Modifications are done as you suggested

Q: Line 52: you mention cost-effectiveness here without any discussion of it in the Results (you should not include a result in the Conclusion that was not presented in the Results)

Response: Conclusion modified as you suggested

Q: Line 86: "its blood supply" – do you mean the chest wall's blood supply? It is not clear in the way this sentence is written (the blood supply presumably refers to the chest wall and minimal surrounding tissue presumably refers to the LIMA but these two items are separated by an "and" which presumes both items are related to the same thing).

Response: The statement was modified as you suggested, with lines 84-86 (yellow highlighted).

Q: Line 95: "which is expensive" – I would say costs more money, but "expensive" is relative and in comparison with the cost of the entire operation, the Ligaclip is not a major driver of cost.

Response: Statement modified as you suggested, line 95 (yellow highlighted).

Q: Line 151: "We recruited 2209 age- and sex-matched adult CABG patients"

Response: Statement modified as you suggested, yellow highlighted

Q: Line 153: "We divided the study population into 2 groups based on…."

Response: Statement modified as you suggested, yellow highlighted

Q: Line 165: no need for the word "specifically"

Response: Statement modified as you suggested, yellow highlighted

Q: Line 179: when skeltonising, were Ligasure clips only used on the LIMA side just like in the semi-skeletonised scenario? This would be a difference in treatment if they were not the same.

Response: Yes. Ligaclips were usually used on the LIMA side in both the semi-skeletonised & skeletonised techniques which we mentioned in lines 179-181 (yellow highlighted).

Q: Line 186: "conduit is" – the paper has been written in the past tense, you switch to present here and then continue in the present tense in the next sentence.

Response: I appreciate your concern; line 193 (yellow highlighted) has been addressed and corrected.

Q: Line 193: "direct grasping of the LIMA with forceps was avoided by grasping nearby adventitial tissue."

Response: Modifications are done as you suggested, line 200 (yellow highlighted).

Q: Line 208: you switch from preterite to present here as well

Response: Modifications are done as you suggested, line 217, (yellow highlighted).

Q: Line 223: "evaluated 2209 age- and sex-matched adult Bangladeshi isolated CABG patients which included 1050 with a skeletonized LIMA and 1159 with a semi-skeletonised LIMA."

Response: Modifications are done as you suggested, lines 224-226 (yellow highlighted).

Q: Line 225: no words should be capitalized other than EuroSCORE II, COPD and CAD)

Response: Modifications are done as you suggested

Q: Line 227: you should include the lengths, times and number of clips here

Response: Modifications are done as you suggested, lines 228-230 (yellow highlighted).

Q: Line 228: "number of Ligaclips used"

Response: Modifications are done as you suggested

Q: Line 228: "compared to THE semi-skeletonised"

Response: Modifications are done as you suggested, line 231 (yellow highlighted).

Q: Line 231: AN age- and gender-adjusted

Response: Modifications are done as you suggested, line 233 (yellow highlighted).

Q: Line 232: "number of Ligaclips used"

Response: Modifications are done as you suggested

Q: Line 233: were significantly and positively associated with the semi-skeletonised LIMA technique

Response: Modifications are done as you suggested

Q: Line 234-236: I do not understand this sentence

Response: Sorry for the inconvenience. We have updated the statement as you suggested, and the changes are highlighted in yellow, lines 238-243.

Q: Line 236: this sentence needs to be re-worked'

Response: Statement modified as you suggested, yellow highlighted

Q: Line 284: this sentence needs to be re-worked

Response: Statement modified, lines 283-285 (yellow highlighted).

Q: Line 288: "is not"

Response: Modifications are done as you suggested, line 286 (yellow highlighted).

Q: Line 297: if the protocol was from proximal to the first intercostal branch to the bifurcation, then why was the skeletonised longer if both were prepared the same way in terms of length?

Response: We understand your concerns; however, the LIMA length was not significantly different between the study groups. This study was conducted because our senior consultants believe that a skeletonised LIMA provides more length, which was not the scenario in our study. However, the minimum length difference may be due to the adjacent fascia and veins associated with a semi-skeletonised LIMA rather than a skeletonised one.

Q: Line 302: I am not sure that this "mitigates the risk of outcome bias"

Response: We understand your concerns; however, every study has the potential for risk of bias, and we did our best to minimise the risk of bias by utilising two equally qualified surgeons to harvest the LIMA. Additionally, we changed "mitigates" to "minimises" in line 301 (highlighted in yellow).

Reviewer #2: This manuscript addresses a clinically relevant topic comparing semi-skeletonised and skeletonised LIMA harvesting techniques. However, several key issues limit its current suitability for publication.

Q: First, the authors emphasize cost-effectiveness but provide inadequate economic analysis. Simply counting Ligaclips is insufficient; a detailed cost breakdown including operative time, resource utilization, and hospital stay should be presented.

Response: We appreciate your concerns. The current study aimed to evaluate specific research questions regarding the safety and effectiveness of the LIMA harvesting technique rather than the whole CABG procedure, including hospital stay. Nevertheless, the overall operation cost was similar as all cases were performed by the same surgeon using off-pump techniques. However, we have revised our study objective statement for better clarity for our readers on page 2, and lines 31-33 (yellow highlighted).

Q: Second, the multivariate logistic regression model raises concerns. The odds ratios reported (e.g., OR 10.8 for LIMA harvest time) appear unusually large, suggesting potential errors in statistical modeling or interpretation. Clarification and re-analysis are needed.

Response: We agreed, and thank you very much for your suggestions. We revised the LR model by considering semi-skeletonised LIMA as a dependent variable. The modified OR values replaced the previous one on page 9, including an interpretation of our findings, lines 234-238 (yellow highlighted).

Q: Third, the authors mention early complications but do not adequately define or systematically evaluate them. Clear definitions, standardized follow-up periods, and explicit complication rates should be provided.

Response: This study evaluated specific research questions related to the intra-operative LIMA harvesting technique rather than the whole CABG procedure and follow-up outcomes. However, we modified the definition of study variables, including complications on page 6 and lines 168-172 (yellow highlighted).

Q: Lastly, the manuscript lacks clarity regarding surgeon experience standardization. Although a single surgeon's practice is mentioned, variability among trainees and junior surgeons may significantly confound results.

Response: Two equally qualified surgeons harvested LIMA who had completed postgraduate surgical training in cardiac surgery under a single-surgeon practice, which is mentioned on page 8 and lines 204-207 (yellow highlighted). However, we agreed that there might be a bias between surgeons, which we acknowledged as study limitations on page 11/12, lines 299-302 (yellow highlighted).

Reviewer #3: Dear Authors, Thank you for submitting your manuscript for review. I was pleased to receive it. Your study addresses a clinically relevant question and provides useful insights into the practical and cost-effective aspects of IMA harvesting techniques. However, I have some comments for your consideration:

1. In the abstract conclusion, you could briefly include clinical relevance or outcomes (e.g., complication rates, recovery, postoperative morbidity) alongside procedural efficiency.

Response: Thanks for your suggestion; however, an abstract conclusion should ideally be based on the most significant findings, which are short and precise. As you suggested, we modified our conclusive statement on page 2 (yellow highlighted).

2. You mention the "ambispective" nature of the study. Could you clarify how the prospective and retrospective data were integrated and managed to avoid biases regarding quality and completeness across the two collection approaches?

Response: We detailed the "ambispective" nature of the study on page 6, lines 158-167 (highlighted in yellow). Further, we have added a statement on how we integrated and managed quality and completeness across the two data collection approaches on page 6 and acknowledged a limitations statement on the risk of potential bias on page 12, lines 302-304 (yellow highlighted).

3. Why were certain covariates (e.g., hypertension, diabetes, COPD) matched but not directly included in the multivariate regression model? Could you explain this choice in the Methods?

Response: We detailed the selection of study variables for the regression model on page 8, lines 212-215 (highlighted in yellow).

4. Regarding the harvesting techniques, descriptions are clear. However, could you include additional intraoperative images (if available) to show differences between the techniques?

Response: Thanks, I appreciate your comments. We have added more pictures of skeletonised & semi-skeletonised LIMA, and Figure 1 has been modified as you suggested.

5. The use of Ligaclips as a cost indicator is well-justified. Still, could you provide an economic analysis or at least a brief comparative analysis of the overall economic impact (e.g., average procedural cost differences or estimated financial savings per case)?

Response: We appreciate your concerns. The current study aimed to evaluate specific research questions regarding the safety and effectiveness of the LIMA harvesting technique rather than the whole CABG procedure, including hospital stay. Nevertheless, the overall operation cost was similar as all cases were performed by the same surgeon using off-pump techniques. However, we have revised our study objective statement for better clarity for our readers on page 2, and lines 31-33 (yellow highlighted).

6. Your confidence intervals in the logistic regression (e.g., OR 10.8 with CI 0.01-0.39) seem incorrect in terms of directionality. Typically, OR >1 indicates increased odds. Please clarify.

Response: We agreed, and thank you very much for your suggestions. We revised the LR model by considering semi-skeletonised LIMA as a dependent variable. The modified OR values replaced the previous one on page 9, including an interpretation of our findings, lines 234-238 (yellow highlighted).

7. Can you compare semi-skeletonised and skeletonised techniques regarding long-term patency or graft survival, if this data is available?

Response: We apologise, but this study focuses specifically on evaluating the LIMA harvesting technique; unfortunately, we do not have long-term follow-up data on patency or graft survival. However, in response to your suggestions, we have included a recommendation for future studies to validate the robustness of our findings on page 12, lines 314-316 (yellow highlighted).

8. Given that all surgeries were performed by qualified surgeons within a single surgeon's practice, how generalizable do you believe these results are? Could you briefly discuss how the familiarity of surgeons with each technique may influence results?

Response: We understand your concerns; however, Professor Adhikary is one of the most senior CTh surgeons, with over 30 years of experience in CABG surgery. He has trained surgeons at the only medical university hospital in Bangladesh, which is why we believe the outcome results are generalisable despite the inherent risk of bias that is standard in any observational study. Additionally, in this study, the LIMA was harvested by two equally trained cardiac surgeons, as noted on page 8, lines 204-207 (highlighted in yellow). However, we agreed that there might be a bias between surgeons, which we acknowledged as study limitations on page 11/12, lines 299-3

Attachment

Submitted filename: Response to Reviewers.docx

pone.0331285.s002.docx (24.3KB, docx)

Decision Letter 1

Usama Waqar

7 May 2025

Dear Dr. Ranjan,

Please submit your revised manuscript by Jun 21 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.

  • 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,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: PLOS ONE

Safety and cost-effectiveness of semi-skeletonised versus skeletonised left internal mammary artery harvesting techniques: the BANGABANDHU study

PONE-D-25-07678R1

April 17, 2025

I want to thank the authors for their thorough responses to prior comments.

I have one comment below followed by some line items.

1. I am still concerned that the central item around which the entire paper revolves is the “semi-skeletonized” LIMA and you are unable to provide a definition that distinguishes it from the only other most commonly used harvest technique which is the pedicled technique. The two most common techniques are skeletonized and pedicled and so it is glaring that this paper does not mention the pedicled technique in any substantial or comparative way. In order to do that, you would have to distinguish the semi-skeletonized and the pedicled and I do not know how you would distinguish those. As you mention, as a cardiac surgeon, they all recognize that minimizing tissue damage during LIMA harvesting is crucial so pedicled LIMAs are usually small (surgeons shy away from taking a large swath of chest wall when taking the pedicle) so how small is small to qualify as semi-skeletonized as opposed to a small pedicle? I think you need to try an attempt at distinguishing the semi-skeletonized vs a pedicled LIMA since even though you do not bring up pedicled LIMAs (other than a few sentences in the Discussion), every surgeon reading this will be wondering what makes your technique different than theirs (if they take small pedicles).

Line 57-60: I am not sure what section this belongs to, but there needs to be a reference noted for all these claims

Line 102: to what drainage are you referring?

Line 154-155: this should be mentioned in limitations that you divided (did not randomize) the group into how the LIMA was harvested. It is possible that a significant sorting mechanism was already operating when the patient was chosen for skeletonized vs semi-skeletonized.

Line 180: the word “should” should not be here – you are describing what happened, you are not explaining how to do it

Line 280: you are now comparing semi-skeletonized to pedicled – I am not sure of the relevance to this paper as you have not discussed pedicled LIMAs. What is the drainage compared to the skeletonized (the comparison in this paper)?

Reviewer #2: The authors' revisions significantly improve manuscript clarity, but critical issues persist. Firstly, the semi-skeletonised technique remains inadequately defined, described ambiguously as "some arbitrary distance" from LIMA, raising reproducibility concerns. The authors' reply partially addresses this but needs explicit anatomical landmarks for precision. Secondly, statistical interpretation remains problematic. Despite revision, the statistical significance of minimal length differences (0.2 cm) within the standard deviation requires clearer clinical justification, potentially representing type I error. Thirdly, the doubled operative time in the skeletonised group requires deeper analysis beyond superficial acknowledgment; underlying procedural variations or surgeon-specific factors should be clarified further. Lastly, economic analysis remains superficial, relying solely on Ligaclip counts without comprehensive cost breakdown. Recommend: revise thoroughly to address definition precision, statistical robustness, detailed procedural explanations, and comprehensive economic analysis.

Reviewer #3: Dear Authors,

Thank you for your thorough responses and revisions. The manuscript has been significantly improved, and many prior concerns have been addressed. I have only two further suggestions:

1. The term “cost-effectiveness” may overstate the economic implications of your study given the absence of broader economic analyses (e.g., total procedural costs, hospital stay, follow-up costs). Consider revising this term to “procedural efficiency” or “resource utilization efficiency” throughout the manuscript, including the title and abstract.

2. The clinical relevance of early complications (e.g., LIMA spasm, hematoma, re-exploration) is not sufficiently discussed. For instance, you could note the low incidence of these events and the absence of significant between-group differences to support the safety profile of the semi-skeletonized technique.

Thank you again for your efforts.

**********

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Reviewer #1: No

Reviewer #2: Yes:  Robert J. Chen, MD, MPH

Reviewer #3: Yes:  Savvas Lampridis

**********

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PLoS One. 2025 Sep 5;20(9):e0331285. doi: 10.1371/journal.pone.0331285.r004

Author response to Decision Letter 2

18 May 2025

Response to reviewer's comments

Reviewer #1: I want to thank the authors for their thorough responses to prior comments. I have one comment below followed by some line items.

1. I am still concerned that the central item around which the entire paper revolves is the “semi-skeletonized” LIMA and you are unable to provide a definition that distinguishes it from the only other most commonly used harvest technique which is the pedicled technique. The two most common techniques are skeletonized and pedicled and so it is glaring that this paper does not mention the pedicled technique in any substantial or comparative way. In order to do that, you would have to distinguish the semi-skeletonized and the pedicled and I do not know how you would distinguish those. As you mention, as a cardiac surgeon, they all recognize that minimizing tissue damage during LIMA harvesting is crucial so pedicled LIMAs are usually small (surgeons shy away from taking a large swath of chest wall when taking the pedicle) so how small is small to qualify as semi-skeletonized as opposed to a small pedicle? I think you need to try an attempt at distinguishing the semi-skeletonized vs a pedicled LIMA since even though you do not bring up pedicled LIMAs (other than a few sentences in the Discussion), every surgeon reading this will be wondering what makes your technique different than theirs (if they take small pedicles).

Response: Thanks for your critical appraisal. We have briefly described the semi-skelitonised LIMA technique with appropriate in-text citations (lines 206-212; New Ref number 17). In brief, Horii and Suma have described the semiskeletonised LIMA as a venoarterial pedicle with surrounding thin tissue without muscular support, and keeping the endothoracic fascia attached to the chest wall.

Line 57-60: I am not sure what section this belongs to, but there needs to be a reference noted for all these claims

Response: We understand your concerns. However, as the PLOS One manuscript guidelines don't include those sections, we have deleted the "What is already known on this topic? What this study adds? & How might this study affect research, practice or policy?" sections.

Line 102: to what drainage are you referring?

Response: Apologies for the inconvenience. The sentence has been modified, as highlighted in yellow on line 124.

Line 154-155: this should be mentioned in limitations that you divided (did not randomize) the group into how the LIMA was harvested. It is possible that a significant sorting mechanism was already operating when the patient was chosen for skeletonized vs semi-skeletonized.

Response: Appreciate your comments. There was no sorting mechanism; the LIMA harvesting was conducted randomly. We have modified statements as you suggested, lines 176 & 177, highlighted in yellow.

Line 180: the word “should” should not be here – you are describing what happened, you are not explaining how to do it

Response: Thank you for your attention to detail. We modified the statement as you suggested in line 202 (highlighted in yellow).

Line 280: you are now comparing semi-skeletonized to pedicled – I am not sure of the relevance to this paper as you have not discussed pedicled LIMAs. What is the drainage compared to the skeletonized (the comparison in this paper)?

Response: We understand and appreciate your concerns, so we have removed line 280, as pedicle LIMA is irrelevant to this paper.

Reviewer #2: The authors' revisions significantly improve manuscript clarity, but critical issues persist.

Firstly, the semi-skeletonised technique remains inadequately defined, described ambiguously as "some arbitrary distance" from LIMA, raising reproducibility concerns. The authors' reply partially addresses this but needs explicit anatomical landmarks for precision.

Response: Thanks for your critical appraisal. We have added a brief description of the semi-skelitonised LIMA technique as previously described elsewhere with appropriate in-text citations (lines 206-212; New Ref number 17).

Secondly, statistical interpretation remains problematic. Despite revision, the statistical significance of minimal length differences (0.2 cm) within the standard deviation requires clearer clinical justification, potentially representing type I error.

Response: We defined P <0.05 as significant (not P =0.05), but acknowledge your concerns about P =0.05 being borderline significant, which can occur with a small mean ±SD difference due to the large sample size, and low variability in LIMA length as mean (SD) decreases with increasing sample size and low variability in data, making even minor differences more detectable. However, we acknowledged and discussed these issues in the limitations section with appropriate in-text citations (lines 332-335).

Thirdly, the doubled operative time in the skeletonised group requires deeper analysis beyond superficial acknowledgment; underlying procedural variations or surgeon-specific factors should be clarified further.

Response: We understand your concerns. However, there were no procedural variations as all cases were performed using off-pump CABG techniques and no surgeon-specific factors influenced LIMA harvesting time as all surgeons or trainees harvested both skeletonised and semi-skeletonised LIMA, which we mentioned on page 8, line 233-236.

Lastly, economic analysis remains superficial, relying solely on Ligaclip counts without comprehensive cost breakdown. Recommend: revise thoroughly to address definition precision, statistical robustness, detailed procedural explanations, and comprehensive economic analysis.

Response: Thanks for your suggestions; however, as I said earlier, comprehensive economic analysis was beyond the study objectives, as the current study aimed to compare the 2 LIMA harvest techniques in OPCABG surgery. Further, we modified the “cost-effectiveness” term and replaced it with “resource utilisation efficiency” throughout the manuscript as per the suggestions of Reviewer 3 (yellow highlighted). Nonetheless, we have added a recommendation to conduct further research on the cost-effectiveness of two harvesting techniques, considering factors such as total procedural costs, length of hospital stay, and follow-up expenses (lines 326-329; highlighted in yellow).

Reviewer #3: Dear Authors, Thank you for your thorough responses and revisions. The manuscript has been significantly improved, and many prior concerns have been addressed. I have only two further suggestions:

1. The term “cost-effectiveness” may overstate the economic implications of your study given the absence of broader economic analyses (e.g., total procedural costs, hospital stay, follow-up costs). Consider revising this term to “procedural efficiency” or “resource utilization efficiency” throughout the manuscript, including the title and abstract.

Response: Thanks for your suggestions; we modified the “cost-effectiveness” term and replaced it with “resource utilisation efficiency” throughout the manuscript as per your suggestions (yellow highlighted). Nonetheless, we recommend conducting a further study to evaluate the cost-effectiveness of two harvesting techniques, taking into account the details of total procedural costs, length of hospital stay, and follow-up expenses, etc., as you suggested (lines 326-329; yellow highlighted).

2. The clinical relevance of early complications (e.g., LIMA spasm, hematoma, re-exploration) is not sufficiently discussed. For instance, you could note the low incidence of these events and the absence of significant between-group differences to support the safety profile of the semi-skeletonized technique. Thank you again for your efforts.

Response: Thanks for your suggestions, we have added a brief discussion on these issues on page 11, lines 306-309 (yellow highlighted).

Attachment

Submitted filename: R2_Response Letter.docx

pone.0331285.s003.docx (17.7KB, docx)

Decision Letter 2

Usama Waqar

2 Jun 2025

Dear Dr. Ranjan,

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 Jul 17 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.

  • 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'.

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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,

Usama Waqar, M.B.B.S

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: PLOS ONE

Safety and cost-effectiveness of semi-skeletonised versus skeletonised left internal mammary artery harvesting techniques: the BANGABANDHU study

PONE-D-25-07678R2

May 30, 2025

I want to thank the authors for their responses.

Overall, I have a couple of items left.

1. The last sentence of the discussion says “cost-effectiveness” and this word should be changed as this study is not a cost-effectiveness analysis

2. Unless skeletonized vs semi-skeletonized were chosen by a randomizing mechanism, the claim that the use of either technique was randomized is not accurate and should be removed. Without a randomizing mechanism, the choice is up to the surgeon and they choose which intervention to give and that is not accepted as being randomized.

Reviewer #2: Despite these improvements in the revision, several critical issues remain unresolved:

The “semi-skeletonised” LIMA technique is still vaguely defined. The revision cites Horii’s description of a thin venoarterial pedicle but omits precise anatomical boundaries. Without clear landmarks, the method is clearly indistinguishable from a minimal pedicled harvest, undermining reproducibility.

A 0.2 cm LIMA length difference (p≈0.05) is statistically marginal and clinically negligible. Treating this borderline result as significant overstates its importance and likely reflects sample-size effects.

The skeletonised harvest time was double the semi-skeletonised time, yet this is unexplained. Claiming uniform technique and staff ignores potential learning-curve or procedural complexity factors behind such a large efficiency gap.

No substantive economic analysis is presented. Merely counting Ligaclips and renaming outcomes as “resource utilization” falls short of a genuine cost comparison, contrary to the manuscript’s framing.

Reviewer #3: Dear Authors,

Thank you for considering my suggested revisions. Overall, you have put a lot of effort into revising your work by integrating the feedback provided. I believe the resulting changes have significantly improved the rigor and overall quality of your manuscript.

Congratulations on your work.

**********

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: Yes:  Robert J. Chen, MD, MPH

Reviewer #3: Yes:  Savvas Lampridis

**********

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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

PLoS One. 2025 Sep 5;20(9):e0331285. doi: 10.1371/journal.pone.0331285.r006

Author response to Decision Letter 3

19 Jun 2025

Dear Editor-in-Chief

PLOS ONE

Thank you for considering our manuscript for publication in PLOS ONE. I am attaching our response to the reviewer comments and point-by-point clarifications for your review.

Re: Response to Review Comments on PONE-D-25-07678R2

Reviewer #1: I want to thank the authors for their responses. Overall, I have a couple of items left.

1. The last sentence of the discussion says “cost-effectiveness” and this word should be changed as this study is not a cost-effectiveness analysis.

Response: Thank you very much for your attention to detail. The statement has been modified as you suggested, with the changes highlighted in yellow (line 337).

2. Unless skeletonized vs semi-skeletonized were chosen by a randomizing mechanism, the claim that the use of either technique was randomized is not accurate and should be removed. Without a randomizing mechanism, the choice is up to the surgeon and they choose which intervention to give and that is not accepted as being randomized.

Response: We appreciate your constructive comments. Although we randomly performed either skeletonised or semi-skeletonised techniques, we agreed that the sampling procedures didn't comply with the full structure of a randomised trial, which is why we modified the sentences as you suggested (highlighted in yellow, line 177).

Reviewer #2: Despite these improvements in the revision, several critical issues remain unresolved:

1. The “semi-skeletonised” LIMA technique is still vaguely defined. The revision cites Horii’s description of a thin venoarterial pedicle but omits precise anatomical boundaries. Without clear landmarks, the method is clearly indistinguishable from a minimal pedicled harvest, undermining reproducibility.

Response: Dear Reviewer, to the best of our knowledge, Horii's description of semi-skeletonised LIMA is precise and clear, and we have precisely defined the anatomical boundaries in lines 204-212 & 215-218 (yellow highlighted). Unfortunately, neither do we have an idea nor have we found literature defining "minimal pedicled harvest" techniques.

2. A 0.2 cm LIMA length difference (p≈0.05) is statistically marginal and clinically negligible. Treating this borderline result as significant overstates its importance and likely reflects sample-size effects.

Response: We agree that a p-value of 0.05 is not statistically significant, as noted in the methodology section. A p-value of <0.05 was considered statistically significant (highlighted in the yellow, lines 244 & 245). However, we utilise independent variables with a p-value of ≤0.05 in the multivariate LR model to avoid missing potentially important effects, e.g. false negative. Nevertheless, we have already acknowledged your concerns as a study limitation in lines 332-335, highlighted in yellow with appropriate citations.

3. The skeletonised harvest time was double the semi-skeletonised time, yet this is unexplained. Claiming uniform technique and staff ignores potential learning-curve or procedural complexity factors behind such a large efficiency gap.

Response: We understand your concerns, which we have already explained in the discussion section (Yellow highlighted, lines 282-285). Furthermore, the difference in harvesting time may be associated with the learning curve or procedural complexity; however, we confirmed that all surgeons were equally qualified and performed both harvesting techniques (Yellow highlighted, lines 233-236). Despite the risk of bias, a large sample like ours minimises the risk of bias and confirms the generalisability of the findings.

4. No substantive economic analysis is presented. Merely counting Ligaclips and renaming outcomes as “resource utilization” falls short of a genuine cost comparison, contrary to the manuscript’s framing.

Response: We appreciate your concerns; however, in LMICs like Bangladesh, saving ~25 ligaclip per case indicates significant savings at the end of the year. For example, 25 Ligaclips per case saves approximately $100, which means that, annually in Bangladesh, we perform around 8,000 CABG surgeries, resulting in a potential annual savings of approximately $800,000.00. This is a significant amount for both the Bangladeshi people and the government. I understand your work in the NHS, which is well-organised and fully supported by the UK government; however, a simple modification of the skeletonised technique might help people in LMICs significantly.

However, as you raised concerns and as 3rd reviewer suggested, "cost-effectiveness" terms were replaced with "resource utilisation", and in the absence of a comprehensive economic analysis, we recommended further research on the cost-effectiveness of two harvesting techniques, considering factors such as total procedural costs, length of hospital stay, and follow-up expenses (lines 326-329; highlighted in yellow).

Reviewer #3: Dear Authors,

Thank you for considering my suggested revisions. Overall, you have put a lot of effort into revising your work by integrating the feedback provided. I believe the resulting changes have significantly improved the rigor and overall quality of your manuscript.

Congratulations on your work.

Response: Thank you very much for your constructive comments and valuable suggestions, which greatly enhance the manuscript's quality.

We hope this revised version meets your standards for publication approval.

With thanks and regards

Dr Redoy Ranjan

Associate Editor, PLOS ONE

Attachment

Submitted filename: R3_Response letter.docx

pone.0331285.s004.docx (18.5KB, docx)

Decision Letter 3

Eyüp Serhat Çalık

14 Jul 2025

Dear Dr. Ranjan,

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 Aug 28 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.

  • 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 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,

Eyüp Serhat Çalık

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

I am grateful to the distinguished authors for their revisions done and appropriate responses. Below are some additional suggestions for the manuscript. Please resubmit your manuscript with your point-by-point answers and corrections as soon as possible.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

Reviewer #1: PLOS ONE

Safety and cost-effectiveness of semi-skeletonised versus skeletonised left internal mammary artery harvesting techniques: the BANGABANDHU study

PONE-D-25-07678R3

July 2, 2025

I want to thank the authors for answering my questions. I believe that the paper is much better and helps correctly place the findings as the outcomes of a single institutional experience. I have a couple general comments below followed by some line items.

First, it should be acknowledged that your institutional preference is use Ligaclips, but many other surgeons use clips on reusable clip appliers and when using this latter method, the cost difference is likely negligible.

Second, were these all primary operations or were some redo’s? This would provide a major source of bias and so it should be addressed.

Line 205-209: it is a little unclear here with the first sentence stating “semi-skeletonised LIMA technique preserved……” followed by the subsequent sentence stating “semi-skeletonized LIMA was excised as…..” which included structures that it said were preserved in the prior sentence. These two sentences can be written more clearly to let the reader know what was the exact technique.

Line 219: “we tried to avoid opening the pleural space”

Line 231: “in both cases, we opened the left pleura to enhance LIMA visualization”

These are contradictory statements.

Line 237: you have to remove the word “randomly” here – it was not randomized. You changed it in Line 177 and it needs to be changed here too.

Line 286: “However” seems to refer to the prior sentence (semi-skeletonized) and the “However” sentence seems to refer to the skeletonized technique so the two sentences are combined together with “however” incorrectly.

Line 308: What was your definition of hematoma? Leaking of vasovasorum over a certain distance? Impeding blood flow? And what was your definition of spasm?

Line 330: I would leave out “favoring semi-skeletonized techniques” – you recommend doing future studies and you do not know the outcomes (hence the need for the studies) so you should not say that they are going to favor one technique or the other.

Reviewer #2: The authors have diligently addressed the previous reviewers' concerns.

The manuscript has been revised to replace "cost-effectiveness" with the more accurate "resource utilisation efficiency," and the inaccurate claim of randomization was corrected to "stochastically performed." The authors clarified the surgical technique by providing more precise anatomical descriptions and procedural details. They also appropriately acknowledged the marginal statistical significance of the LIMA length difference as a study limitation.

The statistical analysis is sound, and the English is suitable for publication. The authors provided compelling arguments for their findings, particularly regarding the significant differences in harvesting time and clip usage between the two methods.

Reviewer #3: Dear Authors,

Although I did not provide specific suggestions in the previous round, I appreciate the revisions you made in response to the comments from the other reviewers. These changes have further strengthened the manuscript and clearly positioned it as a resource utilization analysis.

I wish you every success with the publication of your work.

**********

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: Yes:  Robert J. Chen, MD, MPH

Reviewer #3: Yes:  Savvas Lampridis

**********

[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

PLoS One. 2025 Sep 5;20(9):e0331285. doi: 10.1371/journal.pone.0331285.r008

Author response to Decision Letter 4

17 Jul 2025

Dear Editor-in-Chief

PLOS ONE

Thank you for considering our manuscript for publication in PLOS ONE. I am attaching our response to the reviewer comments and point-by-point clarifications for your review.

Re: Response to Review Comments on PONE-D-25-07678R3

Reviewer #1: I want to thank the authors for answering my questions. I believe that the paper is much better and helps correctly place the findings as the outcomes of a single institutional experience. I have a couple general comments below followed by some line items.

1. First, it should be acknowledged that your institutional preference is use Ligaclips, but many other surgeons use clips on reusable clip appliers and when using this latter method, the cost difference is likely negligible.

Response: We appreciate your concerns; however, in Bangladesh, all surgeons and institutes utilise Ligaclips with reusable clip applicators, which I mentioned in line 252. Further, I believe you overlooked my explanation in the previous version, as the same concerns were raised by Reviewer 2.

Although "the cost difference is likely negligible", per case, like you said, saving ~25 ligaclip per case indicates significant savings at the end of the year. For example, 25 Ligaclips per case saves approximately $100, which means that, annually in Bangladesh, we perform around 8,000 CABG surgeries, resulting in a potential annual savings of roughly $800,000.00. This is a significant amount for both the Bangladeshi people and the government. I appreciate your work at a well-organised institute supported by the government; however, a simple modification of the skeletonised LIMA technique might significantly help people in LMICs.

2. Second, were these all primary operations or were some redo’s? This would provide a major source of bias and so it should be addressed.

Response: This study included isolated primary (elective and emergency) CABG procedures, including redo CABG cases if the LIMA is available for harvesting. I have revised the methodology section as you recommended for better clarity on pages 6 and 8, specifically lines 175-176 and lines 249-251. For both primary and redo CABG, the harvesting techniques for the LIMA remain consistent, as outlined in the LIMA harvesting technique section on pages 7-9. This consistency helps mitigate the risk of bias. Additionally, we have added a limitations statement regarding this concern on page 13, lines 361-364.

3. Line 205-209: it is a little unclear here with the first sentence stating “semi-skeletonised LIMA technique preserved……” followed by the subsequent sentence stating “semi-skeletonized LIMA was excised as…..” which included structures that it said were preserved in the prior sentence. These two sentences can be written more clearly to let the reader know what the exact technique was.

Response: We apologise for the inconvenience; we have revised the statement for improved clarity and presentation in lines 219-222.

4. Line 219: “we tried to avoid opening the pleural space”. Line 231: “in both cases, we opened the left pleura to enhance LIMA visualization”. These are contradictory statements.

Response: Thank you for your careful attention to detail. To improve clarity, we have removed line 219, which stated, "we tried to avoid opening the pleural space." We have retained line 231 (now line 243): "In both cases, we opened the left pleura to enhance LIMA visualisation."

5. Line 237: you have to remove the word “randomly” here – it was not randomized. You changed it in Line 177 and it needs to be changed here too.

Response: We have now replaced "randomly" with "stochastically" on line 249; the change is highlighted in yellow.

6. Line 286: “However” seems to refer to the prior sentence (semi-skeletonized) and the “However” sentence seems to refer to the skeletonized technique so the two sentences are combined together with “however” incorrectly.

Response: Thank you for your attention to detail. The statement has been modified for improved clarity and presentation, as indicated in line 310 (highlighted in yellow).

7. Line 308: What was your definition of hematoma? Leaking of vasovasorum over a certain distance? Impeding blood flow? And what was your definition of spasm?

Response: There is currently no standard distance threshold that defines a LIMA hematoma or spasm. I have briefly described the LIMA hematoma and spasm in lines 196-209. Additionally, I included the current study strategies for managing cases of LIMA hematoma or spasm and outlined our approach to dealing with these issues.

8. Line 330: I would leave out “favoring semi-skeletonized techniques” – you recommend doing future studies and you do not know the outcomes (hence the need for the studies) so you should not say that they are going to favor one technique or the other.

Response: I appreciate your attention to detail. As you suggested, I have removed "favouring semi-skeletonised techniques" from lines 355.

Reviewer #2: The authors have diligently addressed the previous reviewers' concerns.

The manuscript has been revised to replace "cost-effectiveness" with the more accurate "resource utilisation efficiency," and the inaccurate claim of randomization was corrected to "stochastically performed." The authors clarified the surgical technique by providing more precise anatomical descriptions and procedural details. They also appropriately acknowledged the marginal statistical significance of the LIMA length difference as a study limitation. The statistical analysis is sound, and the English is suitable for publication. The authors provided compelling arguments for their findings, particularly regarding the significant differences in harvesting time and clip usage between the two methods.

Response: We sincerely thank the reviewer for their kind words and thoughtful evaluation. We appreciate the recognition of the attention to detail in our work, and we are grateful for the positive feedback and encouragement. It reinforces our commitment to maintaining high standards in both methodology and presentation.

Reviewer #3: Dear Authors,

Although I did not provide specific suggestions in the previous round, I appreciate the revisions you made in response to the comments from the other reviewers. These changes have further strengthened the manuscript and clearly positioned it as a resource utilization analysis.

I wish you every success with the publication of your work.

Response: We sincerely thank the reviewer for their thoughtful and encouraging comments. We greatly appreciate your recognition of the strengths of our work and your emphasis on the importance of attention to detail. Your positive feedback reinforces our commitment to scientific rigour, and we have carefully reviewed the manuscript to ensure consistency, clarity, and precision throughout.

We hope this revised version meets your standards for publication approval.

With thanks and regards

Dr Redoy Ranjan

Associate Editor, PLOS ONE

Institute of Cardiovascular Research, Royal Holloway University of London, London, UK

Department of Cardiac Surgery, St George’s University Hospitals NHS Foundation Trust, UK

Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University, Bangladesh Email: redoy_ranjan@bsmmu.edu.bd

Attachment

Submitted filename: Response letter_PONE-D-25-07678R3.docx

pone.0331285.s005.docx (17.3KB, docx)

Decision Letter 4

Eyüp Serhat Çalık

14 Aug 2025

Safety and resource utilisation efficiency of semi-skeletonised versus skeletonised left internal mammary artery harvesting techniques: the BANGABANDHU study

PONE-D-25-07678R4

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Additional Editor Comments (optional):

Dear Authors, I am pleased to inform you that your manuscripts are now ready for acceptance. Your paper has been re-evaluated by reviewer 1, and I kindly request that you make a few minor grammatical corrections as suggested by the reviewer after acceptance. Best wishes for your success.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: I Don't Know

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4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

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Reviewer #1: Line 110: grammar needs to be corrected (“which is commonly utilized” referring to IMA)

Line 119: need to qualify Ligaclip that it is in your institution when using Ligaclip (many/maybe majority of programs do not use a Ligaclip when taking down the IMA) – you state this as if it is a general rule that skeletonized IMA harvest uses more Ligaclip and that is not true since likely most places do not use the Ligaclip for this harvest. You also say your Ligacliip is reusable. You should put in parentheses which device you are using and who makes it.

Line 128: why is this “paradoxical?”

Line 252: the paper is in the past tense and you use the present tense here

Line 331: RCT is not a proper name and does not need to be capitalized

**********

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Reviewer #1: No

**********

Acceptance letter

Eyüp Serhat Çalık

PONE-D-25-07678R4

PLOS ONE

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PLOS ONE

Associated Data

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

    Supplementary Materials

    S1 Fig. The goodness-of-fit of the logistic regression model.

    (DOCX)

    pone.0331285.s001.docx (54.4KB, docx)
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    pone.0331285.s002.docx (24.3KB, docx)
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    pone.0331285.s003.docx (17.7KB, docx)
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    pone.0331285.s005.docx (17.3KB, docx)

    Data Availability Statement

    The data are not publicly available due to privacy or ethical restrictions; however, the data supporting current study findings are available on reasonable request from Dr Sanjoy Kumar Saha, Consultant of Cardiac Anaesthesia (email: sanjoydr@bsmmu.edu.bd), who holds the data and responds to external requests for data access. Further, we will ensure long-term data storage using institutional archives, reliable repositories, and cloud storage, as well as employ redundancy like multiple backups to enhance data availability.

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