Autoimmune Heart Disease: A Comprehensive Summary for Forensic Practice

Round 1

Reviewer 1 Report

Dear Authors,

I have carefully reviewed your manuscript titled "Characteristics of Cardiac Pathology in Autoimmune Diseases: A Systematic Review Based on PRISMA Standards." Overall, I find your work to be of high quality and commend you on your thorough approach in addressing this important topic in the field of forensic pathology. The utilization of the PRISMA standards in conducting the systematic review has enhanced the rigor and transparency of your study.

One of the major strengths of your paper is the detailed layout and classification, which greatly aids in organizing the information and facilitating comprehension. The wide scope of your study ensures that readers will gain a comprehensive understanding of the characteristics of cardiac pathology in autoimmune diseases, making it a valuable resource for professionals in the field.

I particularly appreciate the inclusion of a literature review from multiple databases and the examination of bibliographies to identify additional relevant studies. This approach ensures that your systematic review is comprehensive and minimizes the risk of overlooking important research in the field.

I have a couple comments listed below;

I would like to bring to your attention a minor discrepancy in the text regarding the reference to the clinical criteria for the diagnosis of classic or complete KD. In the paragraph discussing the diagnosis of KD, you state that the clinical criteria and principal clinical features are presented in "Table 1." However, it appears that this information is actually found in "Table 2."

I have a few suggestions for further improvement. Firstly, it would be beneficial to provide some clarity on the specific inclusion and exclusion criteria used during the study selection process. This would assist readers in understanding the rationale behind the selection of the included studies.

Additionally, while the methodological appraisal of each study and evaluation of bias were mentioned, it would be helpful to provide more details on the specific criteria used for assessing the quality of the selected studies. This information would enhance the transparency of your review process.

Lastly, I recommend considering a short discussion section where you can summarize the key findings and implications of the included studies. This would provide readers with a concise synthesis of the evidence and help them understand the broader implications for clinical practice or further research.

Overall, your manuscript is a valuable contribution to the field, and with some minor revisions and additions, it has the potential to become an even stronger publication. I commend your efforts and look forward to seeing the revised version.

Sincerely

Author Response

Dear Revisor,

in the first part of this letter, you will see your assessment, and in the second part marked in yellow the explanation to the text changes we made following your advice.

All changes in the manuscript were made using the "Track Changes" mode, however, because the revision was extensive, it may appear confusing.

For this region, all the changes made have been highlighted in yellow so that you can see them more quickly even if you turn off the "Track Changes" mode.

Author Response File: Author Response.docx

Reviewer 2 Report

Thank you for inviting me to review this manuscript that reviews autoimmune heart disease for forensic practice. As an expert in autopsy practice, but not in autoimmune disease, I found the paper helpful and interesting. Given its length and detail, it is more akin to a book chapter (in which case it would be helpful to include images of macroscopic and microscopic pathology) than a journal article.

Clearly a lot of work has gone into this manuscript, but the result is very lengthy. I wonder whether a less comprehensive article, focused on autopsy findings, might be more appropriate, given that the article is targeted towards forensic pathologists. At present, it contains more detail that I have ever needed at autopsy and an autopsy pathologist seeking such detail is more likely, I think, to reach for their textbook on cardiac pathology than to search for this article.

As this article is targeted to forensic pathologists, a section detailing the samples that should be collected at autopsy for the diagnosis of these conditions would be helpful.

Overall, the manuscript is well written and comprehensive but there are frequent errors in the text that should be addressed:

 

1. Page 2 line 50. '...state cases by accelerating atherosclerotic...'.  Causes what? I think there is a missing word or phrase.

2. Page 2 lines 51-53. Text not clear. Suspect 'increased' should be 'increases' and that 'lead' should be 'leads'.

3. Page 2 line 58. 'Kawasaky' should be 'Kawasaki'. 

4. Page 2 line 65. Please expand the abbreviation LES.

5. Page 2 lines 64-83 - this list could be presented as a table.

6. Page 2 line 83. 'Sars-Cov-2' should be 'SARS-CoV-2'.

7. Page 3, line 112. Sentence beginning 'Predominantly...' should be changed to 'It predominantly...' 

8. Page 3 line 117. The term 'lung district' is strange. Suggest change to either 'the lungs' or 'the respiratory system'.

9. Page 3 line 119. Please expand the abbreviation EGPA.

10. Page 4 line 156. 'al' should be 'all'.

11. Page 4 line 160. Please expand the abbreviation LVEF. (Left ventricular Ejection Fraction, I think)

12. Page 4 line 163. Change this sentence to start, 'In the living subject, MRI examination shows...'.

13. Page 4 line 170. Wrong word choice - the word 'interested' should be something else. I wonder if you mean 'affected'?

14. Page 4, line 193. Given Wegener's nazi links, the term 'Wegener's granulomatosis' is to be avoided. Instead, please use the now-preferred term, 'Granulomatosis with polyangiitis'.

15. Page 6 line 252. Start the paragraph 'Takayasu's arteritis (TA) is a rare...'

16. Page 6 line 287. I would spell it 'myocytolysis' rather than 'myocitolisis'.

17. Page 6 line 293. I do not know what 'intima tonaca' is. I think you mean 'tunica intima'.

18. Page 6 line 295. I do not know what 'tonaches' means, and do not know what you mean.

19. Page 7 lines 201-302. Why is some of the text in italics? It does not seem to be needed.

20. Page 7 line 330. Change the word 'use' to 'are'.

21. Page 7 lines 2330-331. Change the sentence to 'Normally, pulmonary capillaritis and purpura are not typical features.'

22. Pages 7-8 lines 348 to 349. Change 'however, not in all individuals with PAN does this gene appear mutated...' to 'however this gene is not mutated in all individuals with PAN and so it cannot be attributed to the disease with certainty.'

23. Page 8 lines 352-361. These three paragraphs should be collapsed to form a single paragraph.

24. Page 8 line 366-367. 'coronaric' is not a word. I wonder if you mean, 'coronary'.

25. Page 8 line 368. 'hipotizing' is not a word. Do you mean, 'hypothesising'?

26. Page 8 line 391. 'no collateral' should be 'non-collateral'.

27. Page 9 line 418. 'Behcet's' should be 'Behçet's'.

28. Page 10 line 446. 'Know' should be 'known'.

29. Page 10 line 450. 'Identified' does not need a capital letter.

30. Page 10 lines 464-467. Presented as bullet points that do not follow from the preceding paragraph, this seems incomplete. Either expand into prose or delete.

31. Page 11 line 484. The first sentence should read, 'It has been reported that veins and arteries of all sizes are affected.', I think.

32. Page 11 line 485-486. The four capital I's should all be lower case.

33. Page 11 line 488. 'In' should be 'in'.

34. Page 11 line 491. 'Involving' does not need a capital letter.

35. Page 11 line 512. The words 'Is Involved' do not need capital letters.

36. Page 11 line 513. The word 'It' does not need a capital letter. PLEASE NOTE - AT THIS POINT I HAVE STOPPED COMMENTING ON EXTRANEOUS CAPITAL LETTERS, BUT THEY EXIST IN THE REMAINDER OF THE ARTICLE AND THE AUTHORS SHOULD PROOF READ CAREFULLY TO CORRECT THEM. They exist on lines: 522, 531, 533, 551, 578, 580, 582, 

37. Page 12 line 538. The word 'vasculities' should be 'vasculitides'. 

38. Page 12 line 574. Replace 'then' with 'since then'.

39. Page 12 line 577. Replace 'lips' with 'lip'. The same also applies in the table on page 13.

40. Page 13 line 596-597. I think the word 'impairment' is incorrect in this context. I am not sure what the authors mean. Perhaps, 'involvement'?

41. Page 13 line 602. 'infection' should be 'infectious'.

42. Page 14, lines 650-652. The second sentence does not follow on from the first. It is stated that coronary artery lesions are studied, but then a list of other arteries is presented. This is confusing.

43. Page 15 line 670. 'finding' should be 'findings'.

44. Page 19 line 861. Change to "12. Polymyositis and Dermatomyositis"

45. Page 21 line 941. Change 'Multisystem inflammatory síndrome in children' to 'Multisystem Inflammatory Syndrome in Children'.

46. Page 21 line 942. Change 'healt' to 'health'.

47. Page 21 line 942. Suggest change 'COVID-19' to 'SARS-CoV-2' as COVID-19 is the disease that results from SARS-CoV-2 infection.

48. Page 21 line 943. Change 'was first described as early as of sping 2020' to 'was first described in spring 2020'.

49. Page 21 line 943. Change 'COVID-19 pandemics' to 'the COVID-19 pandemic'.

50. Page 21 line 947 and Page 22 line 964 and Page 22 line 969 and Page 22 line 971. Change 'SARS-COV2' to 'SARS-CoV-2'.

51. Page 21 line 948. Change 'conjuntivitisanosmia' to 'conjunctivitis and anosmia'.

52. Page 21 line 949 and Page 23 line 1060. Change 'sever' to 'severe'.

53. Page 21 line 951. Change 'hypotention' to 'hypotension'.

54. Page 21 line 953. Change "patients'" to "patient's".

55. Page 21 line 955. I think '2 3' can be deleted.

56. Page 21 line 964. Change 'arthery' to 'artery'.

57. Page 22 line 985-986. Change 'fever, al lof them associated with elevated inflammatory markers. Grimaud at el.' to 'fever, all of them associated with elevated inflammatory markers. Grimaud et al.'.

58. Page 22 line 992. Change 'pase' to 'phase'.

59. Page 22 line 998. Change 'arryhmic' to 'arrhythmic'.

60. Page 22 line 1005-106. Change 'There are no autoptic data referring to MIS-C patients, nor hematoxylin-eosin stain-ing pools analyses could be found in literature.' to 'There are no autopsy data referring to MIS-C patients, and no hematoxylin-eosin stain-ing pools analyses could be found in literature.'.

61. Page 22 line 1011. Change 'feature' to 'features'.

62. Page 23 line 1026. Change 'Erithrocyte' to 'Erythrocyte'.

63. Page 23 lines 1033-1035. This paragraph does not make sense. Specifically what does, 'For what concerns patients' mean?

64. Page 23 line 1036. Change 'interest' to 'involvement'.

65. Page 23 line 1056. Change 'Coxsackievirus' to 'Coxsackieviruses'.

66. Page 24 line 1089. 'tissutal' is not an English word. Do you mean 'tissue'?

67. Page 24 line 1097. 'consist of' should be 'comprises a'.

68. Page 25 line 1130. 'salivar glands epitelium' should be 'salivary gland epithelium'.

I have stopped adding typographic errors at this point (less than half way through the manuscript. It should be clear that the authors will need to conduct a careful proof-reading of the remainder of the manuscript. Frequent typographic errors remain.

 

 

 

 

Overall, the written English is of high quality, but as set out in the comments and suggestions for authors, there are frequent errors that must be addressed. At present, they impair readability.

Author Response

Dear Revisor,

in the first part of this letter, you will see your assessment, and in the second part marked in yellow the explanation to the text changes we made following your advice.

All changes in the manuscript were made using the "Track Changes" mode, however, because the revision was extensive, it may appear confusing.

For this region, all the changes made have been highlighted in yellow so that you can see them more quickly even if you turn off the "Track Changes" mode.

Author Response File: Author Response.docx

Reviewer 3 Report

In the manuscript entitled ‘Autoimmune heart disease: a comprehensive summary for forensic practice’, Mezzetti et al. reviewed different types of heart diseases. In the abstract, it was mentioned that the review will focus on autoimmune cardiomyopathies, however, in the main text other types of heart diseases than cardiomyopathies were also discussed in details. The introduction section gives an insight into the main pathological background of the field and focus on the cardiac manifestation of autoimmune diseases. The systematic review seems to be incomplete. I could suggest to follow the PRISMA guidelines and include the PRISMA Flow Diagram as a Figure containing the relevant information regarding the identification, screening, eligibility and including processes. Chapters 3-19 are a very long part of the manuscript (it is like a clinical pathology textbook) containing lot of unnecessary information. The authors should focus on the main forensic and/or pathological diagnostic points and pitfalls. The name of the genes should be italicized. There is no discussion section! The conclusion is relative short and seems to be incomplete. Table 4 is very useful, however some changes are needed: ‘Cardiomyopathy’ is inappropriate term in case of the discussed diseases. The ‘target’ column in unnecessary. ‘Blood findings’ is also inappropriate term. 

Based on my opinion this manuscript is out of scope of the topic of the Special Issue (Recent Scientific Developments in Autoimmune Hematological Disorders). This Special Issue focus on autoimmune hematological disorders (and the recent scientific developments!). Autoimmune hematological disorders include all conditions in which blood components are attacked by the immune system (ie. autoimmune cytopenias [including autoimmune thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and autoimmune neutropenia], acquired thrombotic thrombocytopenic purpura and acquired hemophilia). This manuscript lacks these diseases. The scientific novelty of a paper is very limited as we can find similar papers in the field of cardiac manifestation of autoimmune diseases.  

Moderate editing of English scientific terminology and English language required.

Author Response

Dear Revisor,

in the first part of this letter, you will see your assessment, and in the second part marked in yellow the explanation to the text changes we made following your advice.

All changes in the manuscript were made using the "Track Changes" mode, however, because the revision was extensive, it may appear confusing.

For this reason, all the changes made have been highlighted in yellow so that you can see them more quickly even if you turn off the "Track Changes" mode.

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

Thank you for inviting me to review this resubmission. The authors have taken on board many of the comments that I made on the previous submission, but I continue to have concerns.  The manuscript remains very long. At 62 pages, this is more a textbook chapter than a journal article. I accept why the authors are unable to include images of the pathology, but without these, the paper is hard to follow.

The authors have noted in the abstract that 'there still needs to be a protocol that the forensic pathologist can use to direct his or her research'. I agree with this statement, but the article does not contain such a protocol. It does not explain how to sample the heart, or what other samples are needed. What should the pathologist request when submitting blood samples to the immunology laboratory at the time of autopsy (i.e. before histology is available)? Several weeks may pass between the sample collection and the availability of the histology. It should also be remembered that in some countries (England being a good example), whether such a battery of further investigations can be undertaken will depend on the coroner (a medicolegal authority) rather than the pathologist - as such testing is at the coroner's discretion. 

Ultimately, I do not think this article reflects how autopsy pathologists work. I would not find it helpful at autopsy, particularly in the autopsy of a patient who had died suddenly and unexpectedly from a previously un-diagnosed autoimmune cardiopathy. Often there is little or no clinical history available (and where there were such history, one might expect that much of the laboratory workup would have been done in life). Were I to wish to try to differentiate between these types of cardiopathy myself, I still likely would pull a textbook from the shelf rather than look for this article. However, it is more likely that I would refer the heart to a cardiac pathologist.

Frequent typographic errors remain throughout the text.

Author Response

Dear Revisor,

in the first part of this letter, you will see your assessment, and in the second part marked in yellow the explanation to the text changes we made following your advice.

All changes in the manuscript were made using the "Track Changes" mode, however, because the revision was extensive, it may appear confusing.

For this region, all the changes made have been highlighted in yellow.

Author Response File: Author Response.docx

Reviewer 3 Report

In the revised manuscript entitled ‘Autoimmune heart disease: a comprehensive summary for forensic practice’, Mezzetti et al. reviewed different types of heart diseases.

The reviewer thinks that this article was improved only a minor degree in quality. The additional tables are useful, and improve the readability of the manuscripts. However, I believe that the manuscript still contains a lot of unnecessary information. The manuscript is extremely long, and the detailed descriptions of the clinical picture and pathomechanism make it difficult to keep the flow and find the relevant forensic pathological information.

In spite of the changes made during the revision, moderate editing of English language (both general and scientific terminology) is required. There are dozens of grammar, spelling, punctuation and phrasing errors in the manuscript. F.e.:

Table 1: Systematic Lupus Erythematosus and Familiar Mediterranean Fever. à only the first letter should be capitalized. Similar errors can be found in various part of the manuscript.

Line 106: Chaurg- Strauss Syndrome à Churg-Strauss syndrome

Line 346: 100.000 people à 100,000

Table 11: mg/dl à mg/dL

Line 1373: 47,4-129,8 days à 47.4-129.8 days

Abbreviations should be defined the first time they appear. When defined for the first time, the acronym/abbreviation/initialism should be added in parentheses after the written-out form. Please correct each (ie. line 133). The name of the genes should be italicized.

I still have the opinion that this manuscript is out of scope of the topic of the Special Issue (Recent Scientific Developments in Autoimmune Hematological Disorders). This Special Issue focus on autoimmune hematological disorders (and the recent scientific developments!). Autoimmune hematological disorders include all conditions in which blood components are attacked by the immune system (ie. autoimmune cytopenias [including autoimmune thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and autoimmune neutropenia], acquired thrombotic thrombocytopenic purpura and acquired hemophilia). This manuscript lacks these diseases.

Moderate editing of English language (both general and scientific terminology) is required. 

Author Response

Dear Revisor,

in the first part of this letter, you will see your assessment, and in the second part marked in yellow the explanation to the text changes we made following your advice.

All changes in the manuscript were made using the "Track Changes" mode, however, because the revision was extensive, it may appear confusing.

For this region, all the changes made have been highlighted in yellow.

Author Response File: Author Response.docx

Round 3

Reviewer 3 Report

Dear authours,

I express my appreciation for the revisions made to the manuscript. I have carefully reviewed the revised version and I must say that the improvements made are commendable. The technical writing and English proficiency have notably improved, resulting in a manuscript that is more concise, coherent, and accessible. While the professional aspect of the research is commendable, I have further concerns regarding the level of technical writing and English proficiency.

I appreciate the effort and improvements made to address the concerns raised during the review process. The revisions have undoubtedly strengthened the manuscript, particularly in terms of content and clarity. However, there are still a few remaining issues (out of topic manuscript, technical writing, grammar errors) that need to be addressed to ensure the manuscript meets the high standards expected by the journal.

After carefully considering the revisions made in response to the initial review, I have decided to leave the final decision to the editor.

Once again, the professional aspect of the manuscript is commendable, only further technical and grammar improvement is necessary.

 

 

Moderate editing of English language required.

Author Response

Dear Revisor,

in the first part of this letter, you will see your assessment, and in the second part marked in yellow the explanation to the text changes we made following your advice.

All changes in the manuscript made have been highlighted in yellow so that you can see them more quickly.

Author Response File: Author Response.docx