The Composition of the L5-S1 Neural Foramen on MRI—A Retrospective Cohort Study Examining the Anatomy Relevant to Transforaminal Epidural Steroid Injections

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The objective of this study is to exhibit notable differences that are crucial in determining the approach for transforaminal epidural steroid injections for the treatment of radicular pain. The study observations suggest that there is a difference in the way foraminal epidural fat is distributed across the two types of foramina, with a greater quantity of fat often observed in the posteroinferior foramina. If those problems can be resolved (mentioned in the attached file), this study has the potential to be published in MDPI Anesthesia Research.

Comments for author File: Comments.docx

Author Response

Dear Reviewer,

Thank you for taking the time to review our manuscript. We appreciated you suggestions and have made every effort to address your concerns. Please see below for our line-by-line responses and the actions that we have taken to remedy the issues.

1. Please place the methods section before the result section.
   1. This format was used based upon the guidelines provided by the journal. I have modified the paper to a standard format of Into, Methods, Results, Discussion, Conclusion.
2. Please correct the formatting in Table 1, specifically remove the unnecessary numerical value located on the left side of the table.
   1.  I am uncertain why the line numbering overlays the table in the version that is uploaded to the portal. It does not appear that way in my word processor. My hope is that I have remedied this issue.
3. To ensure proper alignment, position the table at the center of the page.
   1. The table should now be centered. I am uncertain why it does not appear that way in the version you uploaded.
4. Is the selected analytical methodology proven adequately dependable for assessing the data? Please provide some details regarding the methodology that was used.
   1. The analytical methodology is a retrospective imaging analysis performed by experts (sub-specialty trained radiologists). There is always a degree of subjectivity with image interpretation. That is why we included inter-rater reliability as well as other commonly assessed features on MRI as references for internal control. We recognize this as a limitation and mention this in the discussion.
5. Does the data generated from 26 patients provide enough evidence to support these findings? Please give a citation regarding the minimal sample size required for research.
   1. A post-hoc power calculation based on the achieved sample size of 29 foramina—with 19 foramina with “None to mild” stenosis, and 10 foramina with “Moderate to severe” stenosis—provided 80% power for detecting clinically meaningful differences between these two groups (0.5 absolute difference in proportions), based on Fisher’s exact test and assuming a two-tailed 5% alpha. Power calculations were performed using G*Power software (University of Dusseldorf, Germany). Achieving 80% power is generally appropriate for research (Cohen J. A power primer. Psychol Bull. 1992;112(1):155-159. doi:10.1037//0033-2909.112.1.155)
6. Please add a conclusion section to facilitate the reader's comprehension of this paperwork.
   1. Thank you for this suggestion. This has now been added.
7. Considering the subjective nature of MRI evaluation resulting from individual interpretation, would it be acceptable to include a competent musculoskeletal radiologist with over a decade of experience to serve as an arbitrator? Give more references to guarantee the validity of the following statement.
   1. There is inherent subjectivity to MRI interpretation. The use of experienced subspecialty trained radiologists for is common in observational imaging studies. Use of a 3rd expert allowed for consensus--this arbiter, or “tie-breaker”, is a commonly employed method to find consensus. Importantly, the subjectivity of the interpretation is made clear in the paper by providing the inter-rater reliability for each variable. There are not references available that specifically support this, but there is ample precedent in the imaging literature.
8. Please give more explanation about the application of this paperwork because this study suggests that there is a difference in the distribution of foraminal epidural fat between the posteroinferior and anterosuperior foramen at L5-S1. How it's used will influence future applications.
   1. Thank you for this suggestion. This is expanded upon in the conclusion.

1.  

Reviewer 2 Report

Comments and Suggestions for Authors

low sample size

less clinical significance.

risk of vessel embolus not significant as projected

Comments for author File: Comments.pdf

Comments on the Quality of English Language

Average

Author Response

Dear reviewer,

Thank you for reviewing this manuscript. We the authors, recognize the limitations of this manuscript, including the small sample size and challenges related to the characterization of foraminal anatomic features by MRI.  With this in mind, we confirmed by post-hoc analysis that we were able to achieve an 80% power with our sample of 29 foramina. We are transparent with the challenge of characterizing foraminal characteristics. The implication of this is now expounded upon in the inclusion. We have also been sure to included inter-rater reliability in our results and, for statistical analysis, used results as determined by a consensus of 3 or 4 imaging experts (fellowship trained academic musculoskeletal radiologists with years of experience). 

We have added a conclusion section to the manuscript with the hope that the clinical relevance of the findings in this study may resonate better with the reader. The risk of injury related to intra-vascular injection of particulate steroid is low, but can be catastrophic if it does occur. As referenced in the discussion of the paper, this has prompted collaboration between multiple stakeholders in the US to establish guidelines to help mitigate the risk of this complication.

We have also taken your style and language suggestions. We have replaced the word "neuroforamen" with "neural foramen" throughout the manuscript. We have also hyphenated words like "postero-inferior", and "antero-superior", etc.

Thank you for taking the time to review our manuscript. We sincerely hope that you will find these changes satisfactory.

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors 

The article needs extensive editing and revision to be considered furhter. The manuscript is very difficult to follow. I think you need to re-order the text and submit it again. 

In this study, the aim is to retrospectively assess the relevant anatomy of the affected neuroforamina at L5-S1 in 42 patients presenting for transforaminal epidural steroid injection at L5-S1. Specifically, they used magnetic resonance 43 imaging (MRI) to characterize the pattern of foraminal fat and the presence/location and/or absence of MR-visible 44 foraminal vessels.

The main research question is actually original however the structure is difficult to follow. It should be restructured again. I think that the clinical significance of this study should be enhanced with more information for clinical practitioners. Difficult to tell since the discussion is misplaced. References are appropriate.

 

Comments on the Quality of English Language

Moderate editing

Author Response

Dear Reviewer,

Thank you for taking the time to review our manuscript. We agree, that the order of the text seems unconventional and may render the paper difficult to follow. This was done to adhere to the guidelines that were provided by the journal, but we have now taken action to re-organize the manuscript so that it is more conventional and will read more naturally. This updated organization is as follows: Abstract, Introduction, Materials/Methods, Results, Discussion.

We have expanded the discussion in hopes of providing more useful information for clinical practitioners. Following the discussion, we have also added a short Conclusion section. This short section sufficiently summarizes our findings and their potential applications for clinical practitioners.

Thank you again for your suggestions and taking the time to review our manuscript.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The objective of this study is to exhibit notable differences that are crucial in determining the approach for transforaminal epidural steroid injections for the treatment of radicular pain. The study observations suggest that there is a difference in the way foraminal epidural fat is distributed across the two types of foramina, with a greater quantity of fat often observed in the posteroinferior foramina. If these problems can be solved (in the attached file), this research has the potential to be published in the journal MDPI Anesthesia Research

Comments for author File: Comments.docx

Author Response

Dear reviewer,

Thank you for taking the time to re-read our revised manuscript. We recognize your concerns with the manuscript and our hope is that you will find our responses, detailed below, sufficient.

Can the reliability of the 80% power achieved using a post-hoc power calculation be considered adequate for this study?

Does the data obtained from a sample of 26 patients offer sufficient evidence to substantiate these findings? Could you provide a citation on the minimum sample size necessary for research?

There is not a clear-cut answer to the question of what the minimum number of subjects in clinical research is. Opinions vary based on the type of study and clinical question. For an observational, retrospective cohort study (like this one), a text from experts in clinical research (Hulley, S., Cummings, S., Browner, W., Grady, D., & Newman, T. (2007). Designing Clinical Research (S. Seigafuse & N. Winter, Eds.; 3rd ed.). Lippincott Williams & Wilkins) states the following:

“A good general rule is that a study should have a power of 80% or greater to detect a reasonable effect size. It is often tempting to pursue research hypotheses that have less power if the cost of doing so is small, such as when doing an analysis of data that have already been collected. The investigator should keep in mind however, that she might face the difficulty of interpreting (and publishing) a study that may have found no effect because of insufficient power…”

Since we did indeed find an effect (difference in epidural fat distribution) between groups, we believe that this sample size was sufficient for reporting these findings.

We believe that the 80% power achieved using a post-hoc power calculation is adequate for this study. We recognize the small sample size (pg 9, line 244): “This study was limited by the retrospective design and small sample size.” This is considered a limitation because our confidence in the reliability of the 80% power achieved would be greater with a larger sample. Nonetheless, we still believe the findings in this study may be impactful.

Could you perhaps provide further clarification on the concept of a non-inferiority clinical trial and its relevance to this particular study?

It is made clear throughout the manuscript that there are known risks with a supra-neural approach. The authors' observation of increased foraminal fat in the postero-inferior portion of the foramen suggests that an infra-neural approach may be safer approach. This may not be clinically applicable if it the infra-neural approach is not similarly effective. The observations in this study alone are enough to make an inference, but not to say with certainty that that an infra-neural approach is safer. The non-inferiority trial referenced will address these information gaps needed for “confident clinical implementation” (or rebuke) of the infra-neural approach. We believe that the current version of the text does make this clear in this paragraph within the discussion (pg. 9, line 253):

“For confident clinical implementation, future studies should directly compare the safety and clinical efficacy of the two different approaches to TFESI. The safety concerns associated with the supra-neural approach have been discussed at length, though there are also risks that may be increased with an infra-neural approach. The primary concern unique to the infra-neural approach is inadvertent disc puncture, which generally cannot occur with a supra-neural approach [20]. Fortunately, at the time of this manuscript preparation, there is reportedly a single-blinded, non-inferiority clincial trial underway in the United Kingdom, funded by the British Journal of Anaesthesia/Royal College of Anaesthetists, aiming to prospectively compare the clinical efficacy and safety between the supra-neural and infra-neural approaches to lumbar TFESI [21].”

In conclusion, it is advisable to provide further details regarding the benefits of this research.

The conclusion is intentionally succinct. Our intention is to summarize the main results and their implication without re-writing the discussion section of the manuscript. This conclusion, it its current form, accomplishes this. It details the primary benefit/implication of the research, recognizes its limitations, and also highlights the avenues for further investigation.

 

Reviewer 2 Report

Comments and Suggestions for Authors

none

Author Response

Dear Reviewer,

Thank you for revisiting our revised manuscript. We appreciate your assistance in getting it to its current version.

Reviewer 3 Report

Comments and Suggestions for Authors

Accept as it is

Author Response

Dear Reviewer,

Thank you for revisiting our revised manuscript. We appreciate your assistance in getting it to its current version.

Round 3

Reviewer 1 Report

Comments and Suggestions for Authors

I thank the authors for their replies, and the replies satisfy me. I would like to recommend the publication of the current manuscript in the journal.