Reviewer ’s report  
 
Title: Management of Helicobacter pylori infections  
 
Version: 0 Date: 24 Jan 2016 
 
Reviewer:  Marco  Pizzi  
 
Reviewer’s report:  
 
In their paper, Talebi Bezmin Abadi and Kusters address compelling issues on the clinical 
management of H.pylori infection. After presenting a brief overview of H.pylori biology, 
virulence mechanisms and Hp -associated gastric damage, they discuss the current diagnostic and 
therapeutic approaches, also highlighting several drawbacks and inconsistencies. The subject of  
this paper is valuable and potentially interesting for a broad spectrum of readers (from clinicians 
to microbiologists, epidemiologists and pathologists), but there are major concerns which should 
be addressed:  
 
1) My major issue is about the misleading co nsiderations on the increased incidence of asthma, 
IBD and Barrett's esophagus in Hp -negative patient ("reports are indicating increasing trends of 
inflammatory diseases including pediatric asthma, inflammatory bowel diseases (IBS), and 
Barrett's Esophagus  (BE) in Helicobacter free patients"; lines 28 -38). The quoted reference [31] 
indeed demonstrates an association between chronic respiratory disorders and H.pylori infection. 
Furthermore, despite some studies actually failed to find an association between Hp-infection 
and asthma (see, for instance, Wang Y, Bi Y, Zhang L, Wang C. Is Helicobacter pylori infection 
associated with asthma risk? A meta -analysis based on 770 cases and 785 controls. Int J Med 
Sci. 2012;9:603 -10), it appears to be scientifically uns ound to say that the absence of H.pylori 
infection correlates with an "increase trend" of this respiratory disorder. Similar consideration 
may be done for Barrett's esophagus. Finally, there is no reference sustaining the negative 
association between Hp -infection and IBD (this should be added).  
 
2) At line 41 -42, the Authors affirm: "Hence the challenge would be to develop an algorithm that 
would predict people with high risk of developing gastric cancer." Actually, histologic 
algorithms to assess gastric ca ncer risk have been proposed in the literature (see, for instance, the 
OLGA or OLGIM Staging Systems). Much debate is also ongoing on possible integrations 
between such  invasive tests an less costly serological analyses. The Authors should report these 
data. 
 
3) I would advice to down -tune the sentence at line 46 -47, as not all the available tests for 
H.pylori infection can be consider very expensive and time consuming.  
 
4) English grammar and mis -splling errors should be thoroughly reviewed, as they make ve ry 
difficult to understand some very important passages. Also (but I realize this may be only a 
personal opinion), the text is somehow redundant and a more linear discussion of the several 
highlighted issues could greatly help the reader understand the sub ject. 
 
Are the methods appropriate and well described?  
If not, plea se specify what is required in your comments to the authors.  
 
Unable to assess  
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the dat a shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the c ontent of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organiz ation that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have a ny non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests to declare.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will b e posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Management of Helicobacter pylori infections  
 
Version: 0 Date: 24 Jan 2016 
 
Reviewer:  Marco  Pizzi  
 
Reviewer’s report:  
 
In their paper, Talebi Bezmin Abadi and Kusters address compelling issues on the clinical 
management of H.pylori infection. After presenting a brief overview of H.pylori biology, 
virulence mechanisms and Hp -associated gastric damage, they discuss the current diagnostic and 
therapeutic approaches, also highlighting several drawbacks and inconsistencies. The subject of  
this paper is valuable and potentially interesting for a broad spectrum of readers (from clinicians 
to microbiologists, epidemiologists and pathologists), but there are major concerns which should 
be addressed:  
 
1) My major issue is about the misleading co nsiderations on the increased incidence of asthma, 
IBD and Barrett's esophagus in Hp -negative patient ("reports are indicating increasing trends of 
inflammatory diseases including pediatric asthma, inflammatory bowel diseases (IBS), and 
Barrett's Esophagus  (BE) in Helicobacter free patients"; lines 28 -38). The quoted reference [31] 
indeed demonstrates an association between chronic respiratory disorders and H.pylori infection. 
Furthermore, despite some studies actually failed to find an association between Hp-infection 
and asthma (see, for instance, Wang Y, Bi Y, Zhang L, Wang C. Is Helicobacter pylori infection 
associated with asthma risk? A meta -analysis based on 770 cases and 785 controls. Int J Med 
Sci. 2012;9:603 -10), it appears to be scientifically uns ound to say that the absence of H.pylori 
infection correlates with an "increase trend" of this respiratory disorder. Similar consideration 
may be done for Barrett's esophagus. Finally, there is no reference sustaining the negative 
association between Hp -infection and IBD (this should be added).  
 
2) At line 41 -42, the Authors affirm: "Hence the challenge would be to develop an algorithm that 
would predict people with high risk of developing gastric cancer." Actually, histologic 
algorithms to assess gastric ca ncer risk have been proposed in the literature (see, for instance, the 
OLGA or OLGIM Staging Systems). Much debate is also ongoing on possible integrations 
between such  invasive tests an less costly serological analyses. The Authors should report these 
data. 
 
3) I would advice to down -tune the sentence at line 46 -47, as not all the available tests for 
H.pylori infection can be consider very expensive and time consuming.  
 
4) English grammar and mis -splling errors should be thoroughly reviewed, as they make ve ry 
difficult to understand some very important passages. Also (but I realize this may be only a 
personal opinion), the text is somehow redundant and a more linear discussion of the several 
highlighted issues could greatly help the reader understand the sub ject. 
 
Are the methods appropriate and well described?  
If not, plea se specify what is required in your comments to the authors.  
 
Unable to assess  
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the dat a shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the c ontent of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organiz ation that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have a ny non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests to declare.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will b e posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Management of Helicobacter pylori infections  
 
Version: 0 Date: 24 Jan 2016 
 
Reviewer:  Marco  Pizzi  
 
Reviewer’s report:  
 
In their paper, Talebi Bezmin Abadi and Kusters address compelling issues on the clinical 
management of H.pylori infection. After presenting a brief overview of H.pylori biology, 
virulence mechanisms and Hp -associated gastric damage, they discuss the current diagnostic and 
therapeutic approaches, also highlighting several drawbacks and inconsistencies. The subject of  
this paper is valuable and potentially interesting for a broad spectrum of readers (from clinicians 
to microbiologists, epidemiologists and pathologists), but there are major concerns which should 
be addressed:  
 
1) My major issue is about the misleading co nsiderations on the increased incidence of asthma, 
IBD and Barrett's esophagus in Hp -negative patient ("reports are indicating increasing trends of 
inflammatory diseases including pediatric asthma, inflammatory bowel diseases (IBS), and 
Barrett's Esophagus  (BE) in Helicobacter free patients"; lines 28 -38). The quoted reference [31] 
indeed demonstrates an association between chronic respiratory disorders and H.pylori infection. 
Furthermore, despite some studies actually failed to find an association between Hp-infection 
and asthma (see, for instance, Wang Y, Bi Y, Zhang L, Wang C. Is Helicobacter pylori infection 
associated with asthma risk? A meta -analysis based on 770 cases and 785 controls. Int J Med 
Sci. 2012;9:603 -10), it appears to be scientifically uns ound to say that the absence of H.pylori 
infection correlates with an "increase trend" of this respiratory disorder. Similar consideration 
may be done for Barrett's esophagus. Finally, there is no reference sustaining the negative 
association between Hp -infection and IBD (this should be added).  
 
2) At line 41 -42, the Authors affirm: "Hence the challenge would be to develop an algorithm that 
would predict people with high risk of developing gastric cancer." Actually, histologic 
algorithms to assess gastric ca ncer risk have been proposed in the literature (see, for instance, the 
OLGA or OLGIM Staging Systems). Much debate is also ongoing on possible integrations 
between such  invasive tests an less costly serological analyses. The Authors should report these 
data. 
 
3) I would advice to down -tune the sentence at line 46 -47, as not all the available tests for 
H.pylori infection can be consider very expensive and time consuming.  
 
4) English grammar and mis -splling errors should be thoroughly reviewed, as they make ve ry 
difficult to understand some very important passages. Also (but I realize this may be only a 
personal opinion), the text is somehow redundant and a more linear discussion of the several 
highlighted issues could greatly help the reader understand the sub ject. 
 
Are the methods appropriate and well described?  
If not, plea se specify what is required in your comments to the authors.  
 
Unable to assess  
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the dat a shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the c ontent of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organiz ation that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have a ny non -financial competing interests in relation to this paper?  
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests to declare.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named report 
including any attachments I upload will b e posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published . 
 
I agree to the open peer review policy of the journal  
assistant