Asymptomatic Bacteriuria or Urinary Tract Infection? New and Old Biomarkers

Round 1

Reviewer 1 Report

This is a very good review on several biomarkers in the diagnosis of UTI. The authors included a total of 42 publications for review. Although some biomarkers may be suitable to differentiate between lower and upper UTI, so far none of the studies showed reliable differentiation between lower UTI and ABU or between lower UTI and OAB, which would be very important.

Therefore the authors concluded, that a single biomarker could not be enough, whereas a combination of biomarkers could have more chances to help in the diagnosis, which means further systematic studies would be necessary.

The review is well performed, presented and discussed. Only two very minor commentd:

Introduction, line 42: diabetes mellitus, because there is also a diabetes insipidus

Page 8, line 165: There is a Typo: not Prince, but Price

Author Response

Dear reviewer, thanks for your kind comment. 
We followed your suggestions about diabetes mellitus and the spelling of the author name "Price". 
Best regards

Reviewer 2 Report

Dear Authors,

The work is interesting and seems to be useful in the diagnosis of UTI and the differentiation of UTI and asymptomatic bacteriuria. However, it requires many corrections. All suggestions were noted in the manuscript attached to the review and also listed below:

• Long phrases with new information without any reference. Please add appropriate citations to lines 37-50;
• Lines 53-54: Are these data still up-to-date - I mean the death rate due to urosepsis - the quoted literature is very old, 16 years ago.
• Lines 59 -60: It would be better to write 2. Search strategy instead of Materials and Methods
• Line 70: 3. It would be better to write 3. Results and discussion
• Lines 70, 108… - use the numbering 3.1, 3.2, 3.3, etc., instead of a, b, c, ...
• TABLES:
  What was the criterion for the order of studies in the table? because it is neither chronological nor alphabetical? it seems quite random - please sort it out

2. the reference number should also be provided
3. there is a lot of confusion in the third column of most tables (Type of patient) - can it be presented more uniformly
4. the order in which items appear in the table is inconsistent with their order on the reference list, e.g. Rodhe et al (2009) on No. 24 and Sundvall et al. number 27 (Table 2); Price JR has No. 36 and Gadalla AAH – 32 (Table 3) - the same is also in other tables - please change it
5. Why some of the wording in the tables are in bold – details highlighted in Tables
6. Table 4 – what does it mean – “seems good” – such statement is used 2 times

• Latin names of the bacterial species should be written in italics – Table 2; line 253
• Line 198: citation required
• Lines 209, 228: is written: “ABU=symptomatic bacteriuria” - symptomatic or asymptomatic - look Table 1 and decide
• Lines 244-248: citation required
• Lines 263-265: citation required
• Line 272: Position 53 is not Arao et al (1999)
• Line 288: remove
• REFERENCES:

1. The way the list of references is presented does not comply with the guidelines for authors
2. [11] – There are no authors - correct, please
3. citations 16 and 21 and 17 and 22 are duplicated – correct, please
4. [26] – what do these numbers mean – delete
5. [33] and Table 2 – Hernandez JG or Grönberg-Hernández J ??? - correct
6. Position 54 is not present in the manuscript

• What about the positions below? Can they be useful? if so - please add it to the list of references, if not - ignore it

1. Meister, MR; Wang, CH; (...); Mysorekar, IU. Vaginal Estrogen Therapy Is Associated With Decreased Inflammatory Response in Postmenopausal Women With Recurrent Urinary Tract Infections. FEMALE PELVIC MEDICINE AND RECONSTRUCTIVE SURGERY 2021, 27, E39-E44
2. Fang, C; Wang, ZR; (...); Ma, XL. Serum human neutrophil lipocalin: An effective biomarker for diagnosing bacterial infections CLINICAL BIOCHEMISTRY 2020, 75, 23-29

More details, not listed above, are present in the manuscript – check carefully and correct, please

Comments for author File: Comments.pdf

Author Response

Dear reviewer, 
thanks for your suggestions and for your detailed revision. 
Your recommendations were extremely clear and helped us to improve our manuscript. 
We did our best to follow your suggestions, specifically: 
1.    We added the citations as required to lines 37-50, line 198, lines 244-248, lines 263-265
2.    We added the references in all tables
3.    We meticulously reconsidered the order and the congruence of the citations, as suggested 
4.    We presented the list of references according to the guideline for the authors for "International Journal of Translational Medicine"
5.    We uniformed the description of patients in the column “type of patients”
6.    We sorted the studies in the tables by chronological criterion from the newest to oldest
7.    We followed your suggestions for the presentation of the tables 
8.    We checked the result 3.7 (±15.3) in table 1, which was correctly reported. PCT is no parametric variable and this could explain the gap between the mean and the standard deviation.
9.    We changed the statement “seems good” in table 4.
  
Finally, we want to thank the reviewer for the two studies suggested, but we cannot add those studies in the revision. Specifically, Meister MR et al. analysed some biomarkers such as IL6 in women with a history of UTI, who were receiving Vaginal Estrogen Therapy (VAT), unfortunately, there was not an adequate control group (women without VAT without UTI). Fang C et al. evaluated CRP, PCT and NHL performance in bacterial and viral infection, but no details about UTI were presented.

We hope you find the current version is adequate for publication. 
Best regards

Round 2

Reviewer 2 Report

Comments to corrected version v2:

Thank you for taking into account the suggestions, the manuscript looks much better, but there are still some mistakes. The most important is related to the literature list:

1. References - position 11 and 26 are identical – correct it, reorganize the list of references and correct citation numbers across the whole text as well as in Tables, please
2. Line 261, Table 2, and Table 6: should be “coli” instead of “Coli”

Author Response

Dear Reviewer,

thanks again for your supervision and your suggestions. We revised the manuscript according to your accommodations. 

Best regards.