Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder

Round 1

Reviewer 1 Report

This study investigated the relationship between atherosclerosis and endometriosis. The rational behind the experiment was clear and straight forward. The manuscript is almost well written.

The authors should mentioned in the method section of the abstract more details about the women selected.

While many different sources are used to set up the study in the introduction, little previous evidence is stated. The introduction is thus short and poorly sets up the rationale for the study. More attention to how this study fits into previous work in endometriosis and inflammation should be added to improve this section.

Please refer to doi: 10.3390/antiox10050720. 

There are some minor grammar issues that should be fixed in order to aid the accessibility of the results to

the reader.

The discussion does a good job at explaining the importance of the results in the context of the inflammatory

pathways involved. However, incorporation of previous results from other related studies is lacking.

Incorporating comparisons with other studies would increase the strength of the paper.

 

Author Response

Thank for your attention and care in reading and reviewing our paper.

This study investigated the relationship between atherosclerosis and endometriosis. The rational behind the experiment was clear and straight forward. The manuscript is almost well written.

 

The authors should mentioned in the method section of the abstract more details about the women selected.

 

While many different sources are used to set up the study in the introduction, little previous evidence is stated. The introduction is thus short and poorly sets up the rationale for the study. More attention to how this study fits into previous work in endometriosis and inflammation should be added to improve this section. Please refer to doi: 10.3390/antiox10050720.

According to your suggestion, we improved introduction in order to ameliorate the rationale of the study (page 2 lines 68-72). We added the reference suggested.

 

There are some minor grammar issues that should be fixed in order to aid the accessibility of the results to

the reader.

According to your suggestion we improved the results.

 

The discussion does a good job at explaining the importance of the results in the context of the inflammatory pathways involved. However, incorporation of previous results from other related studies is lacking. Incorporating comparisons with other studies would increase the strength of the paper.

We added data from other studies in order to increase the relevance of the results concerning the relationship between inflammation and diet (page 15 lines 541-555).

Reviewer 2 Report

Cirillo et al made a good effort to support the effectiveness of Mediterranean diet.

ln 36:the sentence ha sto be stopped at "endothelial activation".  Remove "which".

ln 36-37: A new sentence should be: "ED promotes all stages of atherogenesis as a pro-inflammatory, proliferative, and procoagulant."

Statistics: Repeated measures analysis or survival analysis should be performed given that there are repeated measurements to each subject.

ln 197: α is not the error but the odds of committing error I. they should write "α was set at 0.05".

More importantly, my concern is that no ECG or vascular clinical index is provided (i.e. intima media thickness). Authors have to soften their conclusions. they do not provide evidence but indications that should be proved in the future.

Author Response

Thank for your attention and care in reading and reviewing our paper.

Cirillo et al made a good effort to support the effectiveness of Mediterranean diet.

ln 36: the sentence ha sto be stopped at "endothelial activation".  Remove "which".

We removed “which” according to your suggestion.

ln 36-37: A new sentence should be: "ED promotes all stages of atherogenesis as a pro-inflammatory, proliferative, and procoagulant."

We modified the sentence according to your suggestion.

Statistics: Repeated measures analysis or survival analysis should be performed given that there are repeated measurements to each subject.

We used McNemar test to analyse dichotomous variables and Wilcoxon rank-sum test for continuous variables for paired data, instead of repeated-measures ANOVA because some data about third evaluation were missing (at T2 16 women completed the evaluation). Therefore, we evaluated each woman at T0 vs. T1 (35 vs.35, paired data) and after, T0 vs. T2 (16 vs.16, paired data).

ln 197: α is not the error but the odds of committing error I. they should write "α was set at 0.05".

We modified the sentence according to your suggestion.

More importantly, my concern is that no ECG or vascular clinical index is provided (i.e. intima media thickness). Authors have to soften their conclusions. they do not provide evidence but indications that should be proved in the future.

We added this issue as limitation of the study according to your request (page 16 lines 564-567).

Reviewer 3 Report

It is an interesting topic, and nothing much published extensively, so good effort overall.

The exclusion and inclusion criteria are unambiguous.

1: Not sure why coagulative profile, including VIII Factor (FVIII), and von Willebrand Factor (vWF) were tested. How come is the diet going to affect these parameters? 

2: The criticism could be a very short interval + the low number of patients for real intervention effect. but the Authors have mentioned this in a discussion so happy with that.

3: Line 415:  endometriosis is casual to loss of body weight and body fat.

4: Medeterain diet was specified, or its a general term authors used?

If as a researcher I want to study then what '' Researchers should be telling the women''. I expect that there should be some kind of diet plan or some  ''Structured Dietary plan to follow'' otherwise to me it sounds very vague. Because diet can be specific with calculated proportions to see the impact.

This is my main criticism and if authors can reply. 

Not casual probably authors mean ''causal'' ...check 

Overall It is a good attempt and baseline source for future researchers who can consider big numbers including other variables like ethnicity etc.

Author Response

Thank for your attention and care in reading and reviewing our paper.

It is an interesting topic, and nothing much published extensively, so good effort overall.

The exclusion and inclusion criteria are unambiguous.

1: Not sure why coagulative profile, including VIII Factor (FVIII), and von Willebrand Factor (vWF) were tested. How come is the diet going to affect these parameters? 

We investigated factor VIII and factor von Willebrand because they are endothelial related markers, in order to better frame cardiovascular profile and mechanisms related to atherosclerotic process.

2: The criticism could be a very short interval + the low number of patients for real intervention effect. but the Authors have mentioned this in a discussion so happy with that.

3: Line 415:  endometriosis is casual to loss of body weight and body fat. Not casual probably authors mean ''causal'' ...check 

We corrected this error.

4: Medeterain diet was specified, or its a general term authors used?

If as a researcher I want to study then what '' Researchers should be telling the women''. I expect that there should be some kind of diet plan or some  ''Structured Dietary plan to follow'' otherwise to me it sounds very vague. Because diet can be specific with calculated proportions to see the impact.

We added a sentence in order to clarify the composition of dietary plan (percentage of carbohydrates, percentage of protein and percentage of lipids, according to Mediterranean diet) (page 3 lines 125-126).

This is my main criticism and if authors can reply. 

Overall It is a good attempt and baseline source for future researchers who can consider big numbers including other variables like ethnicity etc.

Round 2

Reviewer 2 Report

Repeated measures should be applied

Cardiovascular function indices measurements should be calculated. The value of the results reported is limited.

Author Response

Repeated measures should be applied

We performed repeated measures analysis. We added Table 4 and Figure 6.

Cardiovascular function indices measurements should be calculated. The value of the results reported is limited.

We evaluated biomarkers indicative of atherosclerosis, as reported from the scientific literature, such as lipid profile, hs-CRP, and parameters expression of endothelial function (i.e. homocysteine). We did not perform cIMT, ECG or ankle-brachial index, also in relation to the young age of patients. We evaluated cIMT only in women with more than 40 years (n=4), therefore we did not add this datum in the study. Moreover, we already added this limitation in our paper. In particular, previous study (Santoro L, D'Onofrio F, Campo S, et al. Endothelial dysfunction but not increased carotid intima-media thickness in young European women with endometriosis. Hum Reprod. 2012 May;27(5):1320-6.) underlined that structural alteration were often absent in a population of young women with endometriosis, and that an increase in cIMT reflects a structural vascular damage that takes a longer time to realize.

Moreover, in order to reduce potential biases, we must consider that we enrolled only women with endometriosis without cardiovascular risk factors as hypertension or diabetes.

Finally, in our University Hospital, the use of instrumental exams in young women without risk factors is considered not fully ethical.