Diagnostic Value of ¹⁸F-FDG-PET/CT in Patients with FUO

Round 1

Reviewer 1 Report

JCM-837391-Peer Review: General comment

They have studied diagnostic value of FDG-PET/CT in the survey of causative disease of FUO. Their study population was just a mixture of patients having variety of pre-PET examination, including from basic items to even biopsy, also variety of pre-PET history of therapy, from non-therapy to antibiotics/steroids. It may be a nature of retrospective study of such type of disease status FUO. While, many of retrospective studies of FUO using FDG-PET/CT have already been published including two meta-analysis. Diagnostic value of FDG-PET/CT for FUO is partly validated through these previous achievements. Because of the high cost and the heterogeneity of causative diseases of FUO, application of FDG-PET/CT to FUO has not yet became popular in the world. What we want to know now may be in which specific situation of FUO FDG-PET/CT could be used most effectively.  Analysis and the results of this study were well described with high standard, but not focusing any specific point.

Specific comments for possible revision

1. Please provide the diagnostic contribution of pre-PET examination especially CT, MRI, echocardiography, and biopsy.
2. Several previous studies excluded patients of recent history of malignancy, because of high possibility of recurrence of known disease. Your studies included 8 pts of known or history of malignancy (Table2), and the final diagnosis included again 8 pts of malignancy (Table3). Were theses recurrence or new disease, please clarify.
3. p9 line 275. on the case of adult's onset of Still disease. Several papers have described characteristic of FDG-PET/CT findings of AOSD (Yamashita H. et al. Mod Rheumatol. 2014 Jul;24(4):645-50. Gerfaud-Valentin M.et al. Medicine (Baltimore). 2014 Mar;93(2):91-9. etc.). Of course, sometimes it may be non-specific, but I wonder if you know these and evaluate the images.
4. p14 line 483. ref. [46] Chinese multicenter study seems to be the retrospective one, not the prospective.

Author Response

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Reviewer 2 Report

Dear Authors,

This study is clinically relevant and well presented.  I would be interested in additional information on the clinical presentation of the patients in this study.  How long were patients ill/febrile prior to the PET scan?  Are their other clinical information that help decide when a PET scan is going to be useful?  Was the PET scan actually necessary or from review of the chart does it appear that the diagnosis would/could have been made in a less expensive way?  This study definitely adds to the literature and I commend you for taking on this challenging topic.

 

Author Response

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Reviewer 3 Report

OVERVIEW

In their article, Georga et al. speak to the diagnostic utility of ¹⁸F-FDG-PET/CT in patients with fever of unknown origin (FUO). For this purpose, they performed a retrospective review of 50 unique patients with various etiologies for FUO. Through their analysis, they determined that, of these 50 patients, 78% had a final diagnosis and 70% of patients had their diagnosis made with contributions from ¹⁸F-FDG-PET/CT.

COMMENTS

2: The title is incorrectly spelled. It should be “Diagnostic value of ¹⁸F-FDG-PET/CT in patients with FUO”. The original title misspells ¹⁸F-FDG-PET/CT as ¹⁸FDG-PET/CT.

155: In what proportion of the cases was the diagnosis already made known with the advanced studies prior to the ¹⁸F-FDG-PET/CT? For example, in the malignancies, had these already been picked up by the other tests? If so, the definition of contributory is misleading, because the diagnosis would have already been made or suggested by these other tests. Some clarity on this is warranted.

184: Table 1 is confusing due to the centered alignment of the “Characteristic” column. It is not immediately evident which items in the table are subitems. This should be made left aligned with indents for the subitems. Additionally, miscellaneous is spelled incorrectly in the table.

257: The quality of Figure 1 is too low to read the figure axes.

265: What prevalence rates were used to determine the PPV and NPV? This should be stated in the manuscript. These prevalence rates should be the population rates rather than the study rates given that this was retrospective and not prospectively collected.

283: The threshold for elevated ESR and CRP should be noted in the methods.

290: Painful is spelled incorrectly.

295: There are random strikethroughs in this line, and it is unclear what they mean.

325: Non-Hodgkin’s lymphoma is spelled incorrectly.

338: The distribution and statistics showing no significant differences should be reported in a table given that the authors state they performed this analysis.

343: “found” should be “find”.

348: It seems that increased CRP tracked really well with ¹⁸F-FDG-PET/CT showing positive regions. A possible area of discussion would speak to how CRP levels could be used to determine whether ¹⁸F-FDG-PET/CT is needed.

381: Should be spelled “Non-Hodgkin's lymphoma”. The text is missing the apostrophe.

388: The authors mention the “timing of ¹⁸F-FDG-PET/CT examination” in this line and in line 390, but do not describe what timely use of ¹⁸F-FDG-PET/CT means or entails.

409: Should be “change” instead of “changed”

412: It is not clear what a “’non-depictable’ core” means. This should be explained or rewritten

426: It seems out of place to mention that comparison of different studies in terms of sensitivity and specificity is difficult when the previous paragraph is entirely dedicated to that comparison. This should be rearranged.

454: Should be “adoption of” and “as a first-line”

457: Random strikethroughs in the text again.

491: Should discuss the need for prospective studies in order to validate the utility of ¹⁸F-FDG-PET/CT. Also should discuss the small sample sizes for non-malignancy FUO.

495: Should be “49/50”

Overall: Should check grammar more thoroughly.

Author Response

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Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

I fully appreciated the author's sincere response to the reviewer's comment. I think the manuscript was improved satisfactory reflecting the reviewer's comments.