Matrix Metalloproteinases as Markers of Acute Inflammation Process in the Pulmonary Tuberculosis
and Eugene B. Postnikov 4,†Round 1
Reviewer 1 Report
The manuscript is interesting.
Please:
1. At the beginning of the manuscript, modify the year 2016 with 2017 (reference 1 of the WHO )
2. Modify the words “false “ or “ true” with p values in the text and tables when you report the statistics
3. In the excel files, for decimal values, please modify the commas with dots
Author Response
We thank Reviewer 1 for the attention and suggestions. The year (item 1) is corrected and the table is supplied with $p$-values (item 2) as well as some related additional discussion is expanded.
What concerns the form of decimal values separator, it seems to be regulated by Excel user settings (\url{https://www.officetooltips.com/excel_2016/tips/change_the_decimal_point_to_a_comma_or_vice_versa.html}). According to our own system preferences, the original excel files contained dots as decimal separators.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The submitted manuscript, "Matrix metalloproteinases as markers of acute inflammation process in the pulmonary tuberculosis" by Lavrova etal emphasizes on utility of MMP as biomarker for MTB infection and subsequent pulmonary tuberculosis. The authors have analyzed a wide range of patient samples and presented them as comparative score of MMP1, 8 and 9. Also the internal control of TIMP concentrations supports their analysis. Authors have analyzed their data using statistical tools and presented well. Their conclusion that MMP/MMPs could serve as prognostic/biomarker for MTB/pulmonary tuberculosis is interesting and requires further investigation. However, in current report, the authors have provided reasonable justification to their hypothesis but some more inputs from previous studies published with similar approach should be added to complement their analysis. An updated discussion of previous literature would improve the overall value of this report. I recommend acceptance of this article for publication with minor modifications.Author Response
Please see the attachment
Author Response File: Author Response.pdf
Reviewer 3 Report
In this manuscript Lavrova et al analyze patients with pulmonary tuberculosis, with a particular focus on the presence of MMPs and their inhibitors. The study is based on a dataset (provided as a supplementary excel file) with patient data and data obtained by ELISA quantification of MMP-1, -8, -9 and TIMP-1. Unfortunately, I cannot recommend this paper for publication due to many major shortcommings:
Missing data. A considerable amount of the data is lacking. In fact, only approximately 10 out of the 233 patients have a complete record. Although I understand that some data can be missing is clinical studies, this case seems excessive. In addition, I do not understand why the healthy controls don’t have basic data shown such as Sex, Age, Height, Weight, BMI… since the healthy controls were local scientists and clinicians, this should be possible. Hence, the authors cannot draw any conclusions and make statements such as ‘may be significant’. Poor definition/description of the dataset. Several aspects of the dataset are not clear. In what unit are the values shown for the MMPs and TIMP-1 shown? µg/ml? OD? The diagnosis column contains values 3 and 8. What does this mean? Study design. The FCTB group was already treated with antibiotics. Hence, you can expect that these patients will have an altered MMP expression pattern since MMPs are affected by antibiotics (and also a reduction in inflammation can be expected in the non-resistant cases). These data should be excluded from comparisons such as shown in Figure 1 (since these patients are expected to bring down the values for the ‘sens’ group.I would recommend that the authors collect more data and aim for full patient profiles.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Round 2
Reviewer 3 Report
The authors have now commented on all my remarks and have done their best to adjust the manuscript. However, I still do not see al the items in the main data file (supplementary Table 1) sufficiently described. In particular, please at a description for the meaning of the numbers (3, 8, 1) shown in the column (diagnosis).
Author Response
Please, find the meaning of the numbers (3, 8 and 1) shown in the column (diagnosis) are already described (Round 1) in the supplementary table named Table2rev_vb, see the row called "Column index 2 index (highlighted blue color)
