Pathophysiology, Treatment, and Prognosis of Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome: A Review
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsAn interesting manuscript, which gives new perspectives for one of the newly discovered diseases. I am giving some objections in order for authors to improve manuscript.
1. Authors need to change the title. Suggestion: Pathophysiology, Treatment and Prognosis of TAFRO Syndrome: A Review.
2. Line 31-42, missing reference.
3. Figure 1 is unclear. Please describe it in text and give more sense.
4. I suggest adding a table or figure for Differences between TAFRO Syndrome and iMCD.
5. I suggest to rename chapter 4. Causes of TAFRO Syndrome to 4. Pathophysiology of TAFRO Syndrome. In this chapter You are discussing pathogenesis not etiology.
6. Authors should discuss TAFRO syndrome etiology also, if there are any previous papers considering this scientific doubt.
7. Considering the acronym for TAFRO syndrome, other authors use: thrombocytopenia, anasarca, fever, reticulin fibrosis of bone marrow/renal dysfunction, organomegaly OR thrombocytopenia (T), anasarca (A), fever (F), reticulin myelofibrosis (R), and organomegaly (O). Is there any possibility of it being uniform? For example, cite a textbook where the above topic is covered.
8. Please add a figure/scheme and try to explain the pathophysiology of TAFRO Syndrome in more detail.
Author Response
Reviewer 1
Comments and Suggestions for Authors
An interesting manuscript, which gives new perspectives for one of the newly discovered diseases. I am giving some objections in order for authors to improve manuscript.
1. Authors need to change the title. Suggestion: Pathophysiology, Treatment and Prognosis of TAFRO Syndrome: A Review.
Thank you very much for pointing that out. I have revised it to Pathophysiology, Treatment and Prognosis of Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal Failure, and Organomegaly (TAFRO) Syndrome: A Review.
2. Line 31-42, missing reference.
Thank you very much for pointing this out. I have added the references [11] and made the corrections. Thank you very much.
3. Figure 1 is unclear. Please describe it in text and give more sense.
I have added the following explanation: iMCD-TAFRO syndrome is classified as a combination of cases that present with symptoms similar to TAFRO syndrome, have histological evaluations that reveal MCD-like findings, and cases that do not undergo histological evaluations and exclude other diseases similar to TAFRO syndrome. Thank you very much for pointing this out.
4. I suggest adding a table or figure for Differences between TAFRO Syndrome and iMCD.
Thank you. I have added a comment to Figure 1 to address the issue. Thank you very much for pointing that out.
5. I suggest to rename chapter 4. Causes of TAFRO Syndrome to 4. Pathophysiology of TAFRO Syndrome. In this chapter You are discussing pathogenesis not etiology.
Thank you very much for pointing that out. I have corrected it to Pathophysiology of TAFRO syndrome.
6. Authors should discuss TAFRO syndrome etiology also, if there are any previous papers considering this scientific doubt.
Thank you very much for pointing that out. I think that is a very important point. I understand that the cause of TFRO syndrome is still unknown, and the pathways involved in its pathology are gradually being elucidated. I have described and explained the details as pathophysiology in chapter 4. Thank you for pointing out this important point.
7. Considering the acronym for TAFRO syndrome, other authors use: thrombocytopenia, anasarca, fever, reticulin fibrosis of bone marrow/renal dysfunction, organomegaly OR thrombocytopenia (T), anasarca (A), fever (F), reticulin myelofibrosis (R), and organomegaly (O). Is there any possibility of it being uniform? For example, cite a textbook where the above topic is covered.
Thank you very much for your accurate comment. As far as I can tell from a PubMed search, there are no reports that mention a clear distinction between the two, and both are considered to be important symptoms, including renal dysfunction.
8. Please add a figure/scheme and try to explain the pathophysiology of TAFRO Syndrome in more detail.
Thank you very much for pointing that out. I have noted it on page 11 line 410-412 and Figures 4 and 5. Thank you very much.
Reviewer 2 Report
Comments and Suggestions for AuthorsThe manuscript attempts to review the pathophysiology and Treatment prognosis of TAFRO syndrome. Although the manuscript briefly presents the status quo of the research in this area, some improvements are suggested.
- The “A review” part in the title could require more in-depth review of the pathophysiology and prognosis.
- A systematic review with proper design would provide better overview.
- Based on the title the prognosis part is expected to get equal importance in the text. However, in the manuscript it is not sufficiently discussed.
- It’s not clear what question this study aims to answer. Although, the problem statement has been discussed. It is not clear how this study would overcome the problem mentioned in the abstract section. “due to the lack of appropriate treatment, it often presents with multiple organ fatality.”
Overall, the contribution of this study does is not sufficiently conveyed in the manuscript. It is suggested that the objectives and the conclusion be clearly stated.
Author Response
Reviewer 2
Comments and Suggestions for Authors
The manuscript attempts to review the pathophysiology and Treatment prognosis of TAFRO syndrome. Although the manuscript briefly presents the status quo of the research in this area, some improvements are suggested.
- The “A review” part in the title could require more in-depth review of the pathophysiology and prognosis.
Thank you very much for your comment. I added pathophysiology to chapter 4 and prognosis to chapter 6. Thank you for your very important comment.
- A systematic review with proper design would provide better overview.
Thank you very much for your comment. I have described histopathology in chapter 4, pathophysiology in chapter 5, treatment in chapter 6, and prognosis in chapter 7, and have systematically discussed pathology, treatment, and prognosis. Thank you very much for your valuable opinion.
- Based on the title the prognosis part is expected to get equal importance in the text. However, in the manuscript it is not sufficiently discussed.
Thank you very much for pointing that out. I am very sorry for not mentioning the prognosis. I have included it in the chapter 6. I apologize for the insufficient description.
- It’s not clear what question this study aims to answer. Although, the problem statement has been discussed. It is not clear how this study would overcome the problem mentioned in the abstract section. “due to the lack of appropriate treatment, it often presents with multiple organ fatality.”
Overall, the contribution of this study does is not sufficiently conveyed in the manuscript. It is suggested that the objectives and the conclusion be clearly stated.
Thank you very much for pointing this out. I have added figures, mentioned treatment and pathology, and made corrections regarding prognosis. Thank you very much.
Reviewer 3 Report
Comments and Suggestions for AuthorsReview of the manuscript cimb-3137272
Pathophysiology and Treatment Prognosis of 2 Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal 3 Failure, and Organomegaly (TAFRO) Syndrome: A Review
By Yotaro Tamai et al.
The evaluated manuscript is a narrative review. The authors focus on the description of the classification, diagnostic criteria of TAFRO syndrome, its pathogenesis, current treatment possibilities, and the differences between the described syndrome and idiopathic multicentric Castleman disease.
It should be emphasized that the issue of pathophysiology and treatment of TAFRO syndrome is not a unique topic. In the PubMed database, in the last 5 years alone, 40 review papers dedicated to this topic have been registered (including 9 published in 2024). Additionally, 19 papers on TAFRO have already been published in MDPI journals, including a comprehensive review by Caballero et al. in Biomedicines 2024, 12(5), 1076, and diagnostic and therapeutic guidelines by Miura et al. in Biomedicines 2024, 12(6), 1277. The manuscript under review is therefore another article addressing the issues of TAFRO syndrome, and it is challenging to assume that the authors address issues rarely discussed in the literature. Nevertheless, the work by Yotaro Tamai et al. is another attempt to summarize and present TAFRO syndrome, and therefore may have educational value.
Before publishing the manuscript, the authors should consider the following comments and suggestions:
1. TAFRO syndrome is classified as one of the rare diseases (ICD-10: M35.8, https://www.orpha.net/en/disease/detail/457077). It would be beneficial to mention the prevalence of this disease globally and in specific regions in the Introduction.
2. Chapter 2 presents the diagnostic criteria for TAFRO. Is there a detailed diagnostic pathway for TAFRO syndrome specifying the order of tests performed?
3. It is worth presenting the common and distinguishing features of TAFRO and iMCD in a tabular or graphical format.
4. Chapter 4 - it would be better to title it "Pathophysiology of TAFRO syndrome". The histological aspects of diagnosing TAFRO should also be described.
5. In Chapter 5, regarding treatment, it is worth mentioning the potential role of thalidomide and tacrolimus.
6. The paper would gain significant value by including a comprehensive figure illustrating the key pathogenic elements of TAFRO syndrome, along with potential points of pharmacological action.
Author Response
Reviewer 3
Comments and Suggestions for Authors
Review of the manuscript cimb-3137272
Pathophysiology and Treatment Prognosis of 2 Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/Renal 3 Failure, and Organomegaly (TAFRO) Syndrome: A Review
By Yotaro Tamai et al.
The evaluated manuscript is a narrative review. The authors focus on the description of the classification, diagnostic criteria of TAFRO syndrome, its pathogenesis, current treatment possibilities, and the differences between the described syndrome and idiopathic multicentric Castleman disease.
It should be emphasized that the issue of pathophysiology and treatment of TAFRO syndrome is not a unique topic. In the PubMed database, in the last 5 years alone, 40 review papers dedicated to this topic have been registered (including 9 published in 2024). Additionally, 19 papers on TAFRO have already been published in MDPI journals, including a comprehensive review by Caballero et al. in Biomedicines 2024, 12(5), 1076, and diagnostic and therapeutic guidelines by Miura et al. in Biomedicines 2024, 12(6), 1277. The manuscript under review is therefore another article addressing the issues of TAFRO syndrome, and it is challenging to assume that the authors address issues rarely discussed in the literature. Nevertheless, the work by Yotaro Tamai et al. is another attempt to summarize and present TAFRO syndrome, and therefore may have educational value.
Before publishing the manuscript, the authors should consider the following comments and suggestions:
- TAFRO syndrome is classified as one of the rare diseases (ICD-10: M35.8, https://www.orpha.net/en/disease/detail/457077). It would be beneficial to mention the prevalence of this disease globally and in specific regions in the Introduction.
Thank you very much for pointing that out. I have added a quote from the report on the promising rate in Japan. Thank you very much.
- Chapter 2 presents the diagnostic criteria for TAFRO. Is there a detailed diagnostic pathway for TAFRO syndrome specifying the order of tests performed?
Thank you very much for pointing that out. I have added it as Figure 4. Thank you very much for your clear indication.
- It is worth presenting the common and distinguishing features of TAFRO and iMCD in a tabular or graphical format.
Thank you for pointing that out. I have added a comment to Figure 2 to explain it. Thank you.
- Chapter 4 - it would be better to title it "Pathophysiology of TAFRO syndrome". The histological aspects of diagnosing TAFRO should also be described.
Thank you very much for pointing that out. I am very sorry that the content was immature. I have added the item "Histopathological finding of TAFRO syndrome" to 3.1 and have described it in detail. Thank you very much for your accurate comment.
- In Chapter 5, regarding treatment, it is worth mentioning the potential role of thalidomide and tacrolimus.
Thank you very much for pointing that out. I apologize for not giving sufficient consideration to the treatment. I have added each item to the p line. I am very grateful for your guidance.
- The paper would gain significant value by including a comprehensive figure illustrating the key pathogenic elements of TAFRO syndrome, along with potential points of pharmacological action.
Thank you very much for pointing this out. I have corrected it by adding a figure. Thank you very much for your precise comment.
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors have successfully responded all the all objections raised.
