Genicular Artery Embolization with Imipenem/Cilastatin for Pigmented Villonodular Synovitis of the Knee: A Case Report

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Thank you for your submission. First question, are PVNS and TGCT (tenosynovial giant cell tumor0 the same entity? If so, please mention this in the introduction. Next, I would suggest putting the pre and post MRI images side-by-side for easier comparison. Lastly, please add your thoughts on how this technique could be improved further. What research remains for PVNS in you opinion. Thank you.

Author Response

Dear Editor,

Thank you for your valuable feedback on our manuscript. We have carefully addressed all your suggestions and made the necessary revisions. Below, we summarize the changes made in response to your comments:

1. Correlation between PVNS and TGCT:
   In the introduction, we have clarified that pigmented villonodular synovitis (PVNS) refers to a subtype of tenosynovial giant cell tumors (TGCT) that diffusely affect the soft tissue lining of joints and tendons. This clarification helps establish the connection between the two terminologies and aligns the manuscript with current nomenclature.

2. Pre- and Post-Intervention MRI Images:
   To facilitate an easier comparison of the patient’s condition before and after the procedure, we have reorganized the images in Figure 3. The pre- and post-MRI images are now presented side-by-side to allow for a clearer visual assessment of the changes following the genicular artery embolization (GAE).

3. Improvements to the Technique and Future Research:
   We have revised the conclusion to include our thoughts on how the GAE technique using imipenem/cilastatin could be further improved. Specifically, we discussed the potential for:

   • Developing more advanced embolic agents with enhanced anti-inflammatory and anti-angiogenic properties.
   • Incorporating advanced imaging techniques, such as dynamic contrast-enhanced MRI or PET imaging, for more precise monitoring and early detection of recurrence.
   • Conducting randomized controlled trials to compare GAE with traditional surgical treatments and other non-surgical approaches.
   • Expanding the application of GAE to other joints and conditions.
   • Establishing clear patient selection criteria to optimize clinical outcomes and reduce recurrence rates.

These points aim to highlight the potential for innovation and further validation of GAE as a standard treatment option for PVNS.

We hope these revisions address your comments and improve the clarity and impact of our manuscript. Please let us know if there are any additional concerns or suggestions.

Thank you for your time and consideration.

Reviewer 2 Report

Comments and Suggestions for Authors

The authors presented an interesting case of genicular artery embolization with imipemen for pigmented villonodular synovitis which represents a novel approach. The following comments could be useful to the authors:

1. Please adhere reporting to the CARE case report guidelines.

2. Provide a filled-in checklist adhering to the checklist.

3. In the background section, provide rationale on how imipenem cilastatin could be useful in treating PNVS. Particularly, provide both preclinical and clinical evidence supporting the antiangiogenic, anti-inflammatory properties of imipenem cilastatin that could potentially be useful in PNVS.

4. Discuss the risk of antimicrobial emergence in view of using imipenem cilastatin for the purpose of embolotherapy in PNVS. Discuss the benefit-risks of all treatment options for treating PNVS compared to the risks (including antimicrobial resistance) of using imipenem for this purpose.   

Author Response

Dear Reviewer,

Thank you for your thoughtful and valuable feedback on our case report. We have made the following revisions to address your comments:

1. Adherence to the CARE Case Report Guidelines: We have carefully reviewed and aligned our report with the CARE guidelines. All necessary components have been included to ensure compliance with the standards. We have updated our manuscript to reflect these guidelines.
2. Filled-in Checklist: A filled-in checklist adhering to the CARE case report guidelines has been added to the supplementary materials, as requested.
3. Rationale on Imipenem/Cilastatin for PVNS Treatment: In the background section, we have provided a detailed rationale for the potential use of imipenem/cilastatin in treating PVNS. We have incorporated both preclinical and clinical evidence supporting its antiangiogenic and anti-inflammatory properties, which may be beneficial for managing the condition. Studies have highlighted its potential in modulating inflammatory pathways and inhibiting angiogenesis, key processes in PVNS pathogenesis, and we have elaborated on this evidence in the revised manuscript.
4. Discussion of Antimicrobial Resistance Risk: We have expanded the discussion to include a thorough analysis of the risk of antimicrobial resistance (AMR) when using imipenem/cilastatin for embolotherapy in PVNS. We compared the benefit-risk profiles of GAE with imipenem/cilastatin to traditional surgical approaches and other non-surgical therapies, such as anti-TNF monoclonal antibodies. We highlighted the concerns regarding antimicrobial resistance and how the use of imipenem outside of its primary antibiotic role could potentially contribute to the emergence of resistant strains. We also emphasized the need for long-term studies to assess the sustainability and safety of this treatment option.

We hope these revisions address your comments and improve the clarity and depth of our manuscript. Please feel free to let us know if any further modifications are required.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Thanks for the revision