Round 1

Reviewer 1 Report

See the attached file below.

Comments for author File: Comments.docx

Author Response

I sincerely thank Reviewer #1 for the obvious time taken to review Part II.  This is  much appreciated. I will send an annotated Word document along with this narrative response.  

I find two major critiques in your review; please correct me if I am in error. 

1. Relating to mention of exclusion of patients based on BPH classifications of Stage III or IV.

A critique of Parts I-III not uncommonly relates to methodology used by authors whose references were reviewed to obtain data in order to possibly come to conclusions about efficacy and safety.  A significant part of the reviewed peer-reviewed literature goes as far back as 38 years. Those early publications often excluded patients from study who were classified according to BPH staging using Alken and Vahlensieck publications.  Of course, I have no access to raw data of patients studied so typically any patient deemed Alken Stage III or Vahlensieck stage III-IV by those early authors were excluded in the original publications, and hence in the submitted manuscript.  I have added text to clarify this and also added citations to the References.  I will say that as an aside, it is very difficult for me to find the full text of Alken or Vahlensieck relating to their staging. If you have such pdfs I would be very grateful if you could send them to me. I will take the time to translate them to English and share with you.  My email is [email protected]. 

2. Table 3 and bringing the data to a single standard.  I agree and did try to get this data since it was not included in the original publication.  In fact I have written to Bob Djavan for such information and also to ask him to be a reviewer but had no reply.  I would say that this item is similar to the foundational issue of #1 above-- it is a limitation of the original publication, over which I have no power to change.  I have asked some colleagues if they know any way to solve this, but so far the response has been "no."  See attached file for comments in context with your Word doc.  Thanks again. 

Stephen 

 

Author Response File: Author Response.docx

Reviewer 2 Report

The paper is very interesting. Congratulations.

So, I have only one suggestion:

- please consider a picture expalining the pharmacological effects of Serenoa Repens, as showed in the following paper: https://www.nature.com/articles/aps20091?free=2

Author Response

To Reviewer 2. Your suggestion for a graphic such as those used by Suzuki et al., or others in publications by Ficarra, Gravas, Giulianelli, Gacci, Vela-Navarrete,  is noted and appreciated.  As a hematologist/oncologist, the issue of mechanisms of action is important to me.  In my opinion, and after an extensive read of the literature plus a clinical practice of 40 years, a super complex issue such as the pharmacology of Serenoa repens warrants more than a picture.  To support this contention, I am uploading for you a screenshot of the folders I have on my computer, with many papers in each folder, on various the pharmacology of Serenoa repens. In the future, I am hoping to write about just this topic in a comprehensive manner, and bring in laboratory testing that is currently available and would shed light on mechanisms of action relating to LSESr vs LUTS/BPH.  But I sincerely believe that bringing this into this 3-part series, already full of new findings, will digress from the main findings of this publication. I have spent the last two days looking for an appropriate graphic and found many, but they would require significant modifications that would involve many days of labor plus copyright permission.  

Unless you feel adamant about this critique of Part II, I would hope you would see my reason for not delving deeply into this topic and instead having the main input relating to narrative information on inflammation. 

Reviewer 3 Report

Dear editor in chief 

I'm glad to review this original article titled: SERENOA REPENS (SAW PALMETTO) FOR LOWER URINARY TRACT SYMP-2 TOMS (LUTS): THE EVIDENCE FOR EFFICACY AND SAFETY OF LIPIDOSTE-3 ROLIC EXTRACTS. PART II

I consider this manuscript suitable for the purpose of the journal. Anyway, some changes are needed.

 

• I strongly recommend the authors to use references in order to support the arbitrary inclusion criteria 

 

• The subset analysis of papers out of some inclusion criteria (minimum of 20 patients and the duration of at least two months) should be better pointed out.

 

• Please put references at the end of the sentences. (as on line 259)

 

• Remember to use the trademarks (as on line 153 “Permixon”) 

 

• At line 210 please add details about the therapy scheme

 

• Please do not repeat the explanations of abbreviations every time you use it (as on line 290)

Author Response

Thank you reviewer #3.  Let me reply to each constructive criticism. 

1. I strongly recommend the authors to use references in order to support the arbitrary inclusion criteria.                                                                                        ⇢ 

   The inclusion and exclusion criteria were indeed called "arbitrary" because those criteria were felt to be reasonable insofar as study duration (2 months or more), and patient number at the end of study (20 or higher).  Because they were arbitrary, these were not based on references from any peer-reviewed papers.  But, those cases excluded per the above criteria were analyzed later and found to confirm/support the findings; they did not negate or weaken them. This was specifically mentioned. And in the section on "time to onset of action of LSESr" we learned from the studies cited that LSESr can show positive effects in as little as 1 month.  This too is mentioned. 

2. The subset analysis of papers out of some inclusion criteria (minimum of 20 patients and the duration of at least two months) should be better pointed out.                                                                                                            ⇢ it is pointed out, as stated above, that of those studies excluded, the overwhelming majority were consistent with the findings in studies of ≥ 20 patients and ≥ 2 months. This was stated.  The entire manuscript was so long that the chief editors and I decided to turn this into a 3-part series. There were already so many tables and graphics that a major issue early on was length of the manuscript.  The addition of more tables to point out that studies excluded actually enhanced the findings of those deemed "evaluable" will be an important topic in a future paper.  

   3. Please put references at the end of the sentences.                                          ⇢ I have made those changes. 

   But please note that in some cases putting the references at the end of the sentence will not allow the reader to discern which reference belongs to what author (e.g., lines 133-7, 161-162 and multiple other locations). 

   4. Remember to use trademarks as on line 153.                                                ⇢ this has been done. Thank you.                                                                      5. Please do not repeat the explanations of abbreviations.                             ⇢ I have gone over the entire document to be assured that this did not recur.  Thank you.                                                                                                 6. At line 210, please add details about the therapy scheme.                             ⇢ I cannot find mention of therapy at or near line 210. Can you clarify this?  Perhaps indicate the page number and some text that applies to this recommendation.  Perhaps the manuscript line numbers that I downloaded from the Uro website are somehow different from yours.  Thanks.                                                                                                                   

   Stephen