Is Urine Egress into the Female Urethra a Risk Factor for UTI?

Round 1

Reviewer 1 Report

I read this paper with a great interest. The paper seems interesting bu some aspects should be improved.

Please include some anatomic pictures in order to give to the readers the opportunity to follow your theory.

Morevoer, please consider a table including all relevant risk factors for UTI in women according the international guidelines and according your new theory. It could be helpfull for convince the readers about your theory.

Author Response

We appreciate the reviewers concerns comments and suggestions. The paper has been extensively revised with the addition of two figures. There were so many changes that it was not possible to annotate, and the entire final revision is presented.

Reviewer 1. I read this paper with a great interest. The paper seems interesting but some aspects should be improved. Response: We appreciate this thought and have extensively revised the submission.

Concern 1. Please include some anatomic pictures in order to give to the readers the opportunity to follow your theory. Response: Two figures have been added.

Concern 1. Moreover, please consider a table including all relevant risk factors for UTI in women according the international guidelines and according your new theory. It could be helpful for convince the readers about your theory. Response: The table has been added. We agree, it should help convince the readers.

Author Response File: Author Response.docx

Reviewer 2 Report

Dear Authors,

 

thank you very much for submitting your opinion statement on this journal. The paper needs some minor changes in order to be ready for pubblication.

Abstract

The authors should mention the correlation between overactive bladder and urine egress.

●      Manuscript

1.         At lines 30-31 authors affirm  “Fifty percent of women will experience at least one symptomatic urinary tract infection (UTI), also called cystitis”. If the authors intend to refer exclusively to cystitis, I recommend replacing the word “UTI” with “cystitis” in the entire article.

2.         Reference 9 is not consistent with what is written at lines 48-50. I recommend authors to add some references to motivate that “urine egress would seem to be an obvious risk for UTI”.

3.         I invite the authors to better explain the role of incontinence as a risk factor for UTI.

4.         At line 95 I suggest authors to specify the type of drugs (anticholinergics  and Beta3-adrenergic agonist drugs)

5.         At line 98 I suggest authors to mention non-pharmacological therapies for urge incontinence (pelvic floor muscle training, behavioral training such as bladder training, neuromodulation including electrical and magnetic stimulation)

6.         At line 104 I recommend to explain better  the relationship between coitus and urine egress.

7.         At line 112 I suggest the authors to add other kind of treatment for stress incontinence (pelvic floor muscle exercises, vaginal cones, urethral bulking and surgical treatment)

Author Response

We appreciate the reviewers concerns comments and suggestions. The paper has been extensively revised with the addition of two figures. There were so many changes that it was not possible to annotate, and the entire final revision is presented.

Reviewer 2. thank you very much for submitting your opinion statement on this journal. The paper needs some minor changes in order to be ready for publication. Response: We appreciate and have revised.

Concern 1. Abstract. The authors should mention the correlation between overactive bladder and urine egress. Response: The effects of OAB for urine egress have been added too.

Concern 2. Manuscript. At lines 30-31 authors affirm  “Fifty percent of women will experience at least one symptomatic urinary tract infection (UTI), also called cystitis”. If the authors intend to refer exclusively to cystitis, I recommend replacing the word “UTI” with “cystitis” in the entire article. Response: Thank you, we removed the word cystitis and now refer to UTI.

Concern 3. Reference 9 is not consistent with what is written at lines 48-50. I recommend authors to add some references to motivate that “urine egress would seem to be an obvious risk for UTI”. Response: This is clarified: “The physiology of urethral closure suggests a possible mechanisms of urine egress. During bladder filling, the urethra primarily remains closed by passive mechanism of mucosal coaptation, smooth muscle, connective tissue, and vasculature [8,9,11]. Associated with elevated bladder pressures, as occurs with OAB, these passive mechanisms of urethral closure can be compromised, which will increase the likelihood of urine egress. In addition, due to the skeletal urethral sphincter, there is also a urethral closure tone. The skeletal sphincter tone can be reduced from prior parturition, menopause and prolapse, increasing the likelihood of urine egress [12,13]. “

 

Concern 4. I invite the authors to better explain the role of incontinence as a risk factor for UTI. Response: Thank you, it no states: “Female lower urinary tract conditions such as urge and stress incontinence may provide insight into urine egress as a possible risk factor for UTI. Urinary incontinence, the unplanned loss of urine, has characteristics similar to urine egress, in that urine is in the urethra at inappropriate times. Urge incontinence due to OAB has increased bladder pressure during bladder filling, which is a pressure that can open the bladder neck and urethra, a condition for urine egress [5,10].”

Concern 5. At line 95 I suggest authors to specify the type of drugs (anticholinergics  and Beta3-adrenergic agonist drugs). Response: Thank you, this has been done.

Concern 6. At line 98 I suggest authors to mention non-pharmacological therapies for urge incontinence (pelvic floor muscle training, behavioral training such as bladder training, neuromodulation including electrical and magnetic stimulation). Response: Thank you, this has been done.

Concern 7. At line 104 I recommend to explain better  the relationship between coitus and urine egress. Response: Thank you, this has been clarified.

Concern 8. At line 112 I suggest the authors to add other kind of treatment for stress incontinence (pelvic floor muscle exercises, vaginal cones, urethral bulking and surgical treatment). Response: Thank you, this has been done.

 

Reviewer 3 Report

Thank you for let me review this work.

The authors aim to share their opinion about the UTI risk related to urine egress. Actually, this is an unexplored field so this work is futuristic. They also propose the video urodynamics application to characterize it. 

The work is structured as "opinion" and the methodology fits the work type. 

The cited references are relevant, updated and do not include abused self-citations.

Dear Authors,

I think that your work is interesting, well written and structured.

Nevertheless, I believe that the current layout penalizes the scientific soundness and does not simplify its reading and comprehension. 

A more structured layout may give to the reader a better sense of analysis, emphasizing the impact, the perspectives and the expectations of urine egress concept on the different spheres treated. 

I would offer my suggestions to improve the readability of your manuscript. I hope you will follow them and consider useful. If you choose to not accept any suggestion, please show me the reason. 

Point 1: In the abstract section, "fifty" (line 1) should be written "50%" according to MDPI Guidelines. 

Point 2: "Nonneurogenic" (abstract line 1) is a correct word that can appear without brackets. 

Point 3: (abstract line 2) "cystitis". I would remove brackets and write it as "among which cystistis is most frequent", or something like this. In alternative you may remove completely the word.

Point 4: Authors are encouraged to a correct use of the template. The lack of lines numeration makes the review process difficult. In this text I will cite the line. 

Point 5: I would appreciate a subdivision in paragraphs. For example, the first part of the main text, up to "Even with the many factors included in UTI risk models, there remains limited accuracy in predicting when a new infection will occur" (included) may became the paragraph "introduction". 

A second paragraph may be identified up to "The skeletal sphincter tone can be reduced from prior parturition and menopause, increasing the risk of urine egress [10]." and called "Whats urine egress?" or something captivating like this.

The successive paraghraph may be "Diagnostic assessment", "study design and validation", "limits", "urine egress and comorbidities", and so on. 

Point 6: I think that the first two lines "Micturition is coordinated in the pontine micturition center. Urination is under conscious control, and there is skeletal urethral sphincter relaxation during voiding [1]." should be replaced at the end of "Even with the many factors included in UTI risk models, there remains limited accuracy in predicting when a new infection will occur [2,4]."

Anyway, it appears detached from the context. I will improve the cohesion explaining better the importance of micturition and urination mechanism in the field of UTI. 

Point 7: the phrase "During micturition, pathogens are washed out of the urethra, which reduces UTI risk [2,3]." lacks cohesion with the rest of the text. Please, harmonize.

Point 8: the part "Our hope is that urine egress assessment and management could be incorporated into UTI risk prevention. Current UTI prevention includes alkalizing the urine, vaginal hygiene, antibiotics, and incontinence management [2-4]. We believe that urine egress, detailed above, could be add to consideration for reducing UTI risk." may be improved and better developed and reorganized, to briefly treat the topic "Urine egress and UTIs prevention strategies"(or similiar). 

Point 9: I would remove "In summary" (in the last part of the main text). The rest of the text may became an appropriate "conclusion" section.

Point 10: I suggest to offer a graphical content (table, illustration, pictures) of the proposed composite score.

Best Regards

Author Response

We appreciate the reviewers concerns comments and suggestions. The paper has been extensively revised with the addition of two figures. There were so many changes that it was not possible to annotate, and the entire final revision is presented.

Reviewer 3. Thank you for let me review this work. The authors aim to share their opinion about the UTI risk related to urine egress. Actually, this is an unexplored field so this work is futuristic. They also propose the video urodynamics application to characterize it. The work is structured as "opinion" and the methodology fits the work type. The cited references are relevant, updated and do not include abused self-citations. Response: Thank you for these comments.

Concern 3. Dear Authors. I think that your work is interesting, well written and structured. Nevertheless, I believe that the current layout penalizes the scientific soundness and does not simplify its reading and comprehension.  A more structured layout may give to the reader a better sense of analysis, emphasizing the impact, the perspectives and the expectations of urine egress concept on the different spheres treated. I would offer my suggestions to improve the readability of your manuscript. I hope you will follow them and consider useful. If you choose to not accept any suggestion, please show me the reason. Response: Thank you, this has been done; we have revised extensively as requested.

Point 1: In the abstract section, "fifty" (line 1) should be written "50%" according to MDPI Guidelines. Response: This has been done

Point 2: "Nonneurogenic" (abstract line 1) is a correct word that can appear without brackets. Response: Thank you, this has been done.

Point 3: (abstract line 2) "cystitis". I would remove brackets and write it as "among which cystistis is most frequent", or something like this. In alternative you may remove completely the word. Response: Thank you, we removed the word cystitis and now use UTI.

Point 4: Authors are encouraged to a correct use of the template. The lack of lines numeration makes the review process difficult. In this text I will cite the line. Response:  We have done this.

Point 5: I would appreciate a subdivision in paragraphs. For example, the first part of the main text, up to "Even with the many factors included in UTI risk models, there remains limited accuracy in predicting when a new infection will occur" (included) may became the paragraph "introduction". Response: Thank you, this has been done.

A second paragraph may be identified up to "The skeletal sphincter tone can be reduced from prior parturition and menopause, increasing the risk of urine egress [10]." and called "Whats urine egress?" or something captivating like this. Response: Thank you, a heading has been added to allow readers to acknowledge a detailed section on urine egress.

The successive paraghraph may be "Diagnostic assessment", "study design and validation", "limits", "urine egress and comorbidities", and so on. Response: Thank you, we have taken this in consideration and modifications has been made to address such suggestive method. 

Point 6: I think that the first two lines "Micturition is coordinated in the pontine micturition center. Urination is under conscious control, and there is skeletal urethral sphincter relaxation during voiding [1]." should be replaced at the end of "Even with the many factors included in UTI risk models, there remains limited accuracy in predicting when a new infection will occur [2,4]." Response:  We hope we have clarified this concern.

Anyway, it appears detached from the context. I will improve the cohesion explaining better the importance of micturition and urination mechanism in the field of UTI. Response: This has been clarified and is more cohesive. “. It is important to distinguish urine in the urethra during micturition and unwanted urine egress into the urethra during bladder filling. During micturition, pathogens are washed out of the urethra, which reduces UTI risk [2,3].  Urine egress during bladder filling, on the other hand, is expected to contribute to UTI risk. Thus, the diagnostic procedure should be conducted at 50 to 70% of bladder capacity to avoid effects of micturition.”

Point 7: the phrase "During micturition, pathogens are washed out of the urethra, which reduces UTI risk [2,3]." lacks cohesion with the rest of the text. Please, harmonize. Response: Thank you,  covered in response 6.

Point 8: the part "Our hope is that urine egress assessment and management could be incorporated into UTI risk prevention. Current UTI prevention includes alkalizing the urine, vaginal hygiene, antibiotics, and incontinence management [2-4]. We believe that urine egress, detailed above, could be add to consideration for reducing UTI risk." may be improved and better developed and reorganized, to briefly treat the topic "Urine egress and UTIs prevention strategies"(or similar). Response: Thank you, there have been improvements made to this paragraph to ensure that the full meaning is conveyed.

Point 9: I would remove "In summary" (in the last part of the main text). The rest of the text may become an appropriate "conclusion" section. Response: Thank you, this entire section has been improved to serve a better understanding of proposed topic – conclusion has been added.

Point 10: I suggest to offer a graphical content (table, illustration, pictures) of the proposed composite score. Best Regards. Response: this has been done