JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-14-145 (2014)

Reviewer's report
Title:Alpha-Fetoprotein Level as a Biomarker of Liver Fibrosis Status in 621
consecutive patients with Chronic Hepatitis B
Version: 1Date:13 September 2013
Reviewer: Vincenza Calvaruso
Reviewer's report:
In this manuscript Liu and co-workers aimed at identifying the role of
Alpha-Fetoprotein Level as a biomarker of liver fibrosis in a cohort of patients
with chronic hepatitis B. .
However, there are several limitations of the manuscript:
One of the main features of chronic hepatitis B is the occurrence of acute flares
which have an important role in the progression of the disease. However this
significant difference of the inflammation grade during the time, make extremely
difficult the evaluation of performance of fibrosis biomarkers. This is particularly
evident for a marker which is strongly influenced by inflammation like AFP.
A repeated and dynamic evaluation of the biomarker may be more useful in this
setting.
The performance of AFP in the evaluation of the different grades and stages
could be not considered satisfasfactory (AUROC always lower than 0.80).
A proof of the unreliability of the AFP in this setting is demonstrated also by the
fact that the median values of AFP at liver inflammation stages null (6.1 ng/ml)
was higher than the median value of stage G1-G3.
Moreover the analysis using with AFP cut off > 400 ng/ml should be eliminated
because a test with high specificity but so low sensitivity is not clinically relevant.
I suppose that only a very few number of subjects had AFP higher than 400
ng/ml.
As the author stated in the discussion they applied the accepted pathological
staging system used in China but there are no known comparisons between this
system and other universal systems. This is an important limitation of the study.
The discussion is too long and the session explaining the performances of the
available not invasive tests of liver fibrosis should be eliminated.
All figures showing the histological features of the differences stages of liver
fibrosis did not add any informations to the study results and should be
eliminated.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
No competing interests to declare
Review for 10.1186/1471-230X-14-145 (2014)

Reviewer's report
Title:Alpha-Fetoprotein Level as a Biomarker of Liver Fibrosis Status in 619
consecutive patients with Chronic Hepatitis B
Version:2Date:19 April 2014
Reviewer: Vincenza Calvaruso
Reviewer's report:
In this second version the authors improved the readability of the manuscript and
listed the several limitations of the manuscript in the discussion.
Even if the performance of AFP in predicting fibrosis among patients with chronic
hepatitis B remains contestable, the proposal to create a model using a
combination of different biomarkers could lead to interesting results.
In the previous version of the manuscript the median values of AFP at liver
inflammation stages null was 6.1 ng/ml which was higher than the values
reported for the severe stages of inflammation. However in the table 3 of this new
version the median value is 2.7 ng/ml. How the authors explain this difference?
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
NA
Review for 10.1186/1471-230X-14-145 (2014)

Reviewer's report
Title:Alpha-Fetoprotein Level as a Biomarker of Liver Fibrosis Status in 619
consecutive patients with Chronic Hepatitis B
Version:2Date:7 May 2014
Reviewer: Anna Pecorelli
Reviewer's report:
In this paper Liu and co-workers aimed to identifyng the association between
Alfa-Fetoprotein levels and different stages of liver fibrosis and inflammations.
The authors have adequately revised the manuscript according to the major
revisions suggested.
Statistics has been improved as well as quality of written English.
The study has still some limitations, clearly stated in the discussion:
- mild accuracy in defined both inlfammation and fibrosis by AFP (as defined by
AUROC < 0.8;);
- the use of the pathological staging system used in China, without comparison
with others staging system;
- not dynamic measurements of AFP;
To increase the quality of the work it could be usefull to compare AFP levels with
APRI score for fibrosis.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-145 (2014)

Reviewer's report
Title:Alpha-Fetoprotein Level as a Biomarker of Liver Fibrosis Status: A
cross-sectional study of 619 consecutive patients with Chronic Hepatitis B
Version:3Date:18 July 2014
Reviewer: Vincenza Calvaruso
Reviewer's report:
The authors have addressed my previous questions.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-14-146 (2014)

Reviewer's report
Title:Magnetic resonance enterography in pregnant women with Crohn's
disease: case series and literature review
Version:2Date:3 June 2014
Reviewer: Tamás Molnár
Reviewer's report:
Major Compulsory Revision
It is a good study, which prove that MRI with a special safety is a safe and
effective imaging modality also during pregnancy. The disadvantage of the study
is the retrospective study design and the low patient number,
Minor revision
There are some spelling mistake, like:
264 In conclusion, modified MRE sequencing provided accurate and clinically
meaningful resukt in
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Review for 10.1186/1471-230X-14-146 (2014)

Reviewer's report
Title:Magnetic resonance enterography in pregnant women with Crohn's
disease: case series and literature review
Version:2Date:24 June 2014
Reviewer: KONSTANTINOS KATSANOS
Reviewer's report:
It is a well-written manuscript from experienced authors and on a very importnat
topic.
Minor comment
1. Please discuss more extensively the imcat of concommitant therapy during
pregnancy on the MRI finding during follow up.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-14-144 (2014)

Reviewer's report
Title:Dietary Guideline Adherence for Gastroesophageal Reflux Disease
Version:2Date:22 June 2014
Reviewer: davide festi
Reviewer's report:
The study by Kubo et al is clinically important; the manuriteria: the manuscript is
well written and the results well explained. There is a question regarding the
inclusion criteria: the Authors enrolled patients with a physician-assigned GERD
diagnosis and the considered symptoms were heartburn and acid regurgitation. It
is well known that the clinical picture of GERD may be characterized by typical
symptoms (such as heartburn) but also by atypical symptoms (such as
non-cardiac toracic pain, etc). Did the Authors enrolled also patients with atypical
symptoms?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
None
Review for 10.1186/1471-230X-14-143 (2014)

Reviewer's report
Title:Advanced Biliary Tract Carcinomas: A Retrospective Multicenter Analysis of
First and Second-line Chemotherapy
Version:1Date:6 June 2014
Reviewer: Minsig Choi
Reviewer's report:
Fiteni et. al reviewed 64 patients with advanced biliary tract carcinomas as a
retrospective multicenter analysis in first and second-line setting. The aim of the
study was to assess the efficacy and safety of different platinum-based
chemotherapies administered as first line in patients with aBTC. Although this is
not a randomized clinical trial, the clinical results in a rare disease like aBTC has
a merit to be published. However in a retrospective like this, it can not make any
conclusion about the hypothesis rather the clinical results are generally
hypothesis generating.
1. statistics section should be simplified to show primary and secondary
end-points. I would remove the univariate and multivariate analysis of the other
factors in this setting (N=64) with two different chemotherapy and 5 different
variables. Such analysis does not have any merit in this setting.
2. results section
Showing survival data in the two groups and safety data are presented nicely but
i would remove the univariate and multivariate analysis section.
3. safety
since this is a retrospective study; would elucidate how the safety information is
collected; medical chart review or electronic data capture.
4. discussion
as authors eluded in the introduction, the standard of care for fit patients in this
setting is gem+cis; so discussion should focus on why gem+ox was used in the
institution and what are comparable difference in the two regimen.
Evidence based approach should recommend Gem+cis and the arguments of the
authors insisting GEMOX based on a retropsective study is not very compelling.
Authors mention 16 patients with poor PS; the clinical outcome on these patients
would be helpful to argue in favor or GEMOX or safety profile of GEMOX can be
compared to the ABC study.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I have no competing interests'
Review for 10.1186/1471-230X-14-143 (2014)

Reviewer's report
Title:Advanced Biliary Tract Carcinomas: A Retrospective Multicenter Analysis of
First and Second-line Chemotherapy
Version:1Date:11 June 2014
Reviewer: Chigusa Morizane
Reviewer's report:
Major comment
1. Because current standard regimen is Gem/CDDP, You should describe the
reason why you use Gem/Carb in clinical practice settings in introduction. Is
there no patients treated with GEM/CDDP regimen in your institutions and
hospitals?
This study is retrospective study. Therefore you have treated patients as a
clinical practice settings without informed consent of clinical trial using new
treatment regimen. It is unethically to treat patients with non-standard regimens
in clinical practice settings.
2. Patients number was too small to perform multivariate analysis. I think it is
under-powered analysis and it makes results unreliable .
Minor comments
1. Page5, Line 2 ###former standard, Gem/Carb regimen.
"Gem/CDDP " is standard regimen.
2. Page 7, last line
Ethics committee approved the analysis protocol.
Ethics committees of "All "participated institutions and hospitals?
3. Page8, last line
Their PFS was ###
PFS? recurrent free survival? these two patients received resection.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-143 (2014)

Reviewer's report
Title:Advanced Biliary Tract Carcinomas: A Retrospective Multicenter Analysis of
First and Second-line Chemotherapy
Version:2Date:10 July 2014
Reviewer: Chigusa Morizane
Reviewer's report:
Author replied to my comments well.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-143 (2014)

Reviewer's report
Title:Advanced Biliary Tract Carcinomas: A Retrospective Multicenter Analysis of
First and Second-line Chemotherapy
Version:2Date:19 July 2014
Reviewer: Minsig Choi
Reviewer's report:
the manuscript addressed the major issues raised by both reviewers and
modified the manuscript and responded to the key points.
I would accept the paper with spelling checks and some minor grammatical
issues review.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
None
Review for 10.1186/1471-230X-14-142 (2014)

Reviewer's report
Title:Diagnostic accuracy for the extent and activity of newly diagnosed and
relapsed Crohn's disease: a multicentre prospective comparison of magnetic
resonance enterography and small bowel ultrasound compared to a reference
standard in those aged 16 and over
Version:1Date:2 May 2014
Reviewer: Zhaoxiang Bian
Reviewer's report:
Minor essential revision:
1. Follow the format of SPIRIT
2. Title is too long, please cut it short.
3. Dropout rate is 10%, probably it is too optimistic.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-14-141 (2014)

Reviewer's report
Title:Endoscopic optical diagnosis provides high diagnostic accuracy of
esophageal squamous cell carcinoma
Version:1Date:3 June 2014
Reviewer: Rajvinder Singh
Reviewer's report:
I have reviewed the manuscript and have the following specific comment:
The authors have very clearly shown the benefit of endoscopic diagnosis
compared to histology obtained by biopsies in this very elegant study. Can the
authors please clarify further how the diagnosis of these lesions were made
using NBI; particularly if any classification was used and if optical magnification
played a role.
Review for 10.1186/1471-230X-14-141 (2014)

Reviewer's report
Title:Endoscopic optical diagnosis provides high diagnostic accuracy of
esophageal squamous cell carcinoma
Version:1Date:9 June 2014
Reviewer: Yasuhiro Shirakawa
Reviewer's report:
Minor Essential Revisions
1) Endoscopic examination and biopsy in METHODS- I understood that only
single biopsy specimen was taken from each lesion for histological diagnosis in
this study. If it is true, the author should describe it in METHODS.
2) Figures- The order of figure legends doesn’t match the order of figures. The
author should correct it.
Discretionary Revisions
1) Endoscopic examination and biopsy in METHODS- The author had better use
“Magnified Endoscopic Classification for Superficial Esophageal Squamous Cell
Carcinoma–Classification of Japan Esophageal Society” for the diagnosis using
NBI, if possible.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-141 (2014)

Reviewer's report
Title:Endoscopic optical diagnosis provides high diagnostic accuracy of
esophageal squamous cell carcinoma
Version:1Date:10 June 2014
Reviewer: kenro kawada
Reviewer's report:
Endoscopic optical diagnosis provides high diagnostic accuracy of esophageal
squamous cell carcinoma#
Thank you for allowing me the opportunity to review this manuscript. In this
study, the authors compared the accuracy of endoscopic and biopsy diagnosis. It
is believed that the gold standard of diagnosis is biopsy, but sometimes, there is
sampling error. The authors mentioned the usefulness of magnifying endoscopy
with NBI system. It is very interesting and useful, although it has some problems
to be solved before acceptance in its present form.
Minor revise
Major point
# The illustration [Figure 3,4,5,6,] does not match Figure Legend (Figure 3, 4a
4b, 4c,4d). please correct the mistake.
# Figure2 + Figure 3= Figure2??
The difference the accuracy between NBI with biopsy ?? please correct it.
# It is divided into three categories( Cancer, Undetermined, No cancer) of the
NBI diagnosis, please show the typical images each.
Minor point
Line 3 on page 6: The author mentioned optical coherence tomography, confocal
endocroscopy. Please add the endocytoscopy (Dr.Kumagai et al.)
Line 20 on page 9
[The lesions diagnosed as cancer on NBI and the lesions diagnosed as HGIN or
cancer on biopsy were resected endoscopically or surgically]
= How many lesions were diagnosed as cancer on NBI?
How many lesions were diagnosed as undetermined on NBI, but cancer on
biopsy?
How many lesions were diagnosed cancer using iodine staining?
Please describe in detail.
Line 8 on page 13
The median size of tumor was 55mm?? Is it really? I think it too big. Please make
sure again.
# Line 7 on page 15 [Retrospective analysis of ten lesions misdiagnosed as no
cancer by endoscopic diagnosis was performed]
= Which categories does it belong to ‘undetermined’ or ‘no cancer’ on NBI.
# Line 4~6 on page 20
[Promising results~ multicenter study] : This is not a conclusion.
Please move the article to the discussion (limitation)
Review for 10.1186/1471-230X-14-140 (2014)

Reviewer's report
Title:Decreasing Incidence of Inflammatory Bowel Disease in Eastern Canada: A
Population database study
Version:2Date:23 May 2014
Reviewer: Govind Makharia
Reviewer's report:
Based on the population database over 2 decades, the authors have shown a
decrease in the incidence of inflammatory bowel disease, both UC and CD, in
Eastern Canada. Such information is very useful and relevant
1. If we look at the evolution of IBD over a period of time; CD followed UC. As the
diagnostic methods improved and were made easily available, the incidence of
CD started rising and equaled that of UC. That would have lead to increase in
incidence of CD. Now the authors describe a decline in the incidence of CD. Is it
a true decline in the incidence (because of change in the risk factors) or a decline
secondary to most undiagnosed patients were diagnosed during the past two
decades. That also explains no decrease in the incidence of IBD in those less
than 20 years of age.
2. The basis of classification of UC, CD and IBD-U based on the administrative
database (i.e. Discharge Abstract and Physician Billings claims databases) and
ICD diagnostic code is not very clear. Did use of these criteria have affected the
number of IBD-U.
Minor:
Discussion may be shortened
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare, No competing interest
Review for 10.1186/1471-230X-14-138 (2014)

Reviewer's report
Title:Alkaline sphingomyelinase (NPP7) activity and isoforms in bile from
patients undergoing endoscopic retrograde cholangiopancreatography (ERCP)
Version:1Date:26 June 2014
Reviewer: James Tabibian
Reviewer's report:
In this study, the investigators sought to examine NPP7 activity and the presence
of two NPP7 isoforms in bile from 59 patients undergoing diagnostic and/or
therapeutic ERCP for a variety of benign and malignant disease-related
indications. This is largely an exploratory descriptive study with perhaps some a
priori hypotheses regarding how NPP7 activity might vary (e.g. be decreased) in
malignant versus benign disease. The findings are intriguing and, albeit based on
a limited dataset, provide direction for future studies, including mechanistic
investigation. While there are no major limitations, a number of issues merit
consideration, as listed below:
ABSTRACT
-The background section of the abstract is fairly long and should be tightened.
-The aim of the study should be provided in the background section.
-Bilirubin is misspelled as “bilirubine”
INTRODUCTION
-The overview of NPP7 in general/in the intestine should be more abridged; this
would allow more opportunity to provide some additional background about
NPP7 in the liver/biliary tree, if desired.
METHODS
-There should be a paragraph dedicated for what specifically the
outcomes/endpoints were of the study (primary, secondary). Were there a priori
hypotheses being tested? Were all the statistical tests univariate, or was their
multivariate analysis as well? The reader can make some assumptions regarding
these points based on the last sentence of the introduction section, but it would
be preferable to delineate these points more clearly (for example in the data
analysis subsection).
RESULTS
-If “benignant” is being used to mean “benign”, please use “benign”, as used in
other parts of the manuscripts.
-What does the “O” in “(G + O)” represent? If this is “Other”, please define this
abbreviation prior to initial use.
-PSC should be defined in the body of the manuscript.
-Figure 5: it’s not clear that there is a strong association or that the relationship is
linear. Statistical consultation may be advisable, e.g. for X or Y transformation.
DISCUSSION
-The first paragraph of the discussion section is too long and should focus more
on the study findings/NPP7 in liver rather than including sentences dealing with
other studies/NPP7 in the intestines. The major findings of the study should
stand out more clearly.
-“Week” should be changed to “weak”
-There should be a paragraph added for limitations.
GENERAL:
-English language proofreading may be helpful to increase readability, e.g. in the
sentence “In order to see whether the 1.2 kb form earlier demonstrated in tumour
cell lines occurred in bile and could be linked to occurrence of tumours, all the
biles available were also analyzed by Western blotting.”
Review for 10.1186/1471-230X-14-139 (2014)

Reviewer's report
Title:Complicated coeliac disease: two different patterns of natural history, two
different prognoses. A multicentre case control study
Version:2Date:25 April 2014
Reviewer: Christophe Cellier
Reviewer's report:
This study describes, in a multicentre retrospective study, the various forms of
complicated celiac disease, as well their prognosis and show that complicated
celiac disease may be a serious condition..
The major weakness of the study is that data regarding the diagnosis of these
complicated CCD in term of endoscopic, radiological, histological (and
phenotypic) features are missing. Furthermore neither the adherence to the
gluten free diet, nor the treatment used for these patients are described. Thus it
remains difficult to draw any clear conclusions from such study.
If available such data should be provided in the manuscript.
For example, ulcerative jejunitis may be frequently associated with RCD type 2 or
EATL, but its is not clearly assessed in this paper, regarding the initial diagnostic
work-up.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interest
Review for 10.1186/1471-230X-14-139 (2014)

Reviewer's report
Title:Complicated coeliac disease: two different patterns of natural history, two
different prognoses. A multicentre case control study
Version:2Date:19 May 2014
Reviewer: Benjamin Lebwohl
Reviewer's report:
In this study, Biagi and colleagues analyze outcomes of 87 patients with
complicated celiac disease (a composite classification including refractory celiac
disease types 1 and 2, ulcerative jejunitis, enteropathy associated T cell
lymphoma, small bowel adenocarcinoma, and collagenous sprue) and 136
patients with uncomplicated celiac disease. They found that those with
complicated celiac disease had lower hemoglobin, albumin, and total cholesterol
at diagnosis than those with uncomplicated celiac disease, and higher
inflammatory markers (ESR and CRP). Moreover, they found that those patients
whose complications developed after an initial improvement had an lower
mortality compared to those who did not have an initial improvement.
Limitations of this study include 1) its relatively short median follow-up (2.9 years
after the onset of complications), though this was driven in part by the mortality
associated with complicated celiac disease; and 2) insufficient power to account
for the relative contributions of each component of the umbrella term of
complicated celiac disease.
Minor essential revisions:
- Abstract: "37 cases died." Specify how many were in group A and how many
were in group B.
- Introduction: "However, due to its retrospective nature, this study cannot
provide
epidemiological data." I am uncertain as to the intent of the authors here. This
paper provides epidemiological data regarding outcomes in complicated celiac
disease. Perhaps the authors are referring to population-based data.
- Methods: Up to how many control patients were matched to each case?
- Do the authors have information on how many patients with complicated CD
had persistently elevated serum TTG levels? On a related note: the authors
report that adherence to the gluten-free diet was inferior among those with
complicated CD. Diagnosing refractory celiac disease requires strict adherence
to the gluten-free diet, and many providers consider those with persistently
elevated TTG levels as having persistent villous atrophy due to gluten exposure
and not true refractory celiac disease.
- Tables 1 and 2: It would be helpful to report percentages.
- Figure 1: the Y axis should be labeled "Complication-Free Survival."
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-139 (2014)

Reviewer's report
Title:Complicated coeliac disease: two different patterns of natural history, two
different prognoses. A multicentre case control study
Version:3Date:17 July 2014
Reviewer: Christophe Cellier
Reviewer's report:
Substantial modifications and improvement have been made.
Limitations due to restrospective study persist.
This paper can be publish in its present form
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
No conflict of interest
Review for 10.1186/1471-230X-14-137 (2014)

Reviewer's report
Title:Modelling the impact of improving screening and treatment of chronic
hepatitis C virus infection on future hepatocellular carcinoma rates and
liver-related mortality
Version:2Date:7 May 2014
Reviewer: John Dillon
Reviewer's report:
This is a well written report of a model adjusted to England's specific HCV
epidemiology and demonstrates the benefits of treatment. I suggest no revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing interests
Review for 10.1186/1471-230X-14-136 (2014)

Reviewer's report
Title:Zinc treatment ameliorated diarrhea and intestinal inflammation in
undernourished rats
Version:2Date:9 May 2014
Reviewer: Simon Keely
Reviewer's report:
The current study by de Queiroz et al. examined zinc supplementation as a
therapeutic strategy in a rat model of diarrheal disease.
While this study is interesting a number of issues need to be addressed
Major Compulsory Revisions
1. There are no legends provided for the figures. This makes review of the
manuscript extremely difficult. Please provide legends for all figures.
2. A clear statement of the study hypothesis and aims would help the flow of the
manuscript greatly.
3. Rationale behind the experimental approach is not justified. For instance, why
look at bacteria in the spleen rather than the mesenteric lymph nodes? Why were
the cytokines chosen? Why were the specific animal models of disease used?
4. Figure 5. The western blot for villin, rows 3 and 4 appear heavily pixelated.
Were these rows pasted in? If so, these should be run on one blot. A higher
resolution image of this western should be rpovided.
5. Bednorz et al (2013 Int. J . Med Microbiol) have shown that Zinc
supplementation increases bacterial plasmid transfer and multi drug resistance in
E. coli. This should be discussed with respect to the current study.
6. With this in mind, how do the authors know that stool consistency was due to
diarrhea (water transport) as opposed to metabolic changes in the microbiome?
This could be easily addressed by assessing stool water content (wet/dry weight
ratios).
7. Why are there such varying experimental numbers between groups? n=11 vs
n=18?
8. zinc supplementation promotes growth via secretion of IGF-1 (Alves et al,
2012, J Pediatr Endocrinol Metab), which itself is protective against
enteropathies. This could be addressed in discussion.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Review for 10.1186/1471-230X-14-135 (2014)

Reviewer's report
Title:The added value of using mutational profiling in addition to cytology in
diagnosing pancreaticobiliary malignancy: review of clinical cases at a single
center
Version:1Date:25 April 2014
Reviewer: Hanno Matthaei
Reviewer's report:
In their Article "The added value of using mutational profiling in addition to
cytology in diagnosing pancreaticobiliary malignancy: review of clinical cases at a
single center" Mahotra et al analyzed the value of mutational analyses
(MP=mutational profiling) of DNA from micordissected cytology slides and
supernatant specimens from biliary brushings in order to predict
histology/malignancy. The authors used an established panel of DNA alterations
in their analyses and found that these assays are capable of providing additional
information regarding the presence of cancer. The authors concluded that MP is
particularly useful in patients that were hard to diagnose by cytology alone.
In the past years large scale DNA profiling (such as next generation sequencing)
has revealed many cancer specific genetic alterations. Mahotra et al demonstrate
an important and elegant translational application of this genetic knowledge and
show a very promising approach. Cytology with its known limited sensitivity and
specificity can obviously be supported by genetic testing. Even if the authors
show only a small series the translational approach is intriguing. The manuscript
is well written and altogether I thinks very suitable for publication in BMC
Gastroenterology.
Major:
- The paper is missing some important studies in the field. For example, when
investigating the use of pancreatobiliary cancer specific DNA alterations
comprehensive DNA profiling publications such as Jiao et al. Nat Gen 2013
(intrahepatic CCC) and Jones et al. Science 2008 (PDAC) should be cited.
Minor:
- Line 41: It should be "than" instead of "that"
- Line 65: The long sentence "Patient outcomes..." should be rewritten.
Outcomes should not be categorized as malignant etc. (rather histologies). Also:
Please refer to the classification of tumors in the methods. Which lesions are
being investigated (e.g. pancreatic ductal adenocarcinoma, ampullary
adenocarcinomas, cholangiocarcinome) and according to which reference (WHO
blue book)?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-14-135 (2014)

Reviewer's report
Title:The added value of using mutational profiling in addition to cytology in
diagnosing pancreaticobiliary malignancy: review of clinical cases at a single
center
Version:1Date:6 May 2014
Reviewer: Prabodh Gupta
Reviewer's report:
In this study, Drs Malhotra and her colleagues present data supporting the
increased diagnostic value of mutational profiling in the study of pancreatobiliary
malignancies by cytology.They analysed about two dozes cytologic specimens
and used laser dissection and supernant samples for mutational studies.
The question posed is well defined and merit investiagtions. However, in my
opinion, the sample size, locations and size of the lesions, whether solid or
cystic, number of cases studied by dissection and supernant analysis, final
pathologic diagnoses and reporting terminology leave much to be desired; these
are either poorly or not documented in the present manuscript.
What were the cases that had positive mutational profile and were negative by
cytology; their location, size, nature of morphologic changes and final diagnoses
should be spelled out.
Similary, with is inderminate diagnosis, it appears similar to unsatisfactory, and
should be clarifed.These concerns lead me to question the validity of results
Minor critique:
Ten months is not one year (L57,58).
How was aggressive disease determined? (L58,59).
What is independent cytology? ((L64).
Benign or stable, please define the criteria used (L66).
Why was surgery performed on the benign cases? (L66).
Which case had false positive cytology? (L226).
.
How would you handle the Mutational data (242-244) in the patient
management?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-134 (2014)

Reviewer's report
Title:Hydroxyurea and colonic ulcers: a case report
Version:2Date:25 May 2014
Reviewer: KONSTANTINOS KATSANOS
Reviewer's report:
It is a case report on hydroxyurea-induced colonic ulcers in a patient who finally
underwent hemicolectomy.
Minor comments
1. Please use standard journa abbreviations i. e Ref 12
2. Please discuss more extensively endoscopic differential diagnosis
3. Please discuss if any preventive measure could be taken in order to avoid
colon otr GI tract ulceration in your patient.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
No conflict of interest
Review for 10.1186/1471-230X-14-134 (2014)

Reviewer's report
Title:Hydroxyurea and colonic ulcers: a case report
Version:2Date:15 June 2014
Reviewer: Lajos Kiss
Reviewer's report:
The clinical case of this case report is interesting. It shows a possible association
between hydroxyurea therapy and appear of colon ulceration. The article is
well-proportioned the idioms of article are meet the requirements. This report
have four main section: background, case presentation, discussion, conclusion.
My comments are the following:
- One month after initiation of hydroxyurea therapy in line with naporxen usage
massive hemathochezia begun and periodic epigastric pain with mucous
diarrhea persisted. The author advice was avoidance of naproxen, but really
discarding of this therapy are unofficially on the text.
- After first colonoscopy findings the area of ulcers are thriven based on the
second and third colonoscopy. These concerned parts of the bowel ancillary
superior mesenteric artery and vein system, but CT angiograhy was not made for
separation of thromboembolic disorders.
- According to authors after discontinuation of hydroxyurea therapy all GI
symptoms disappeared in 2 months. The text not contains what was the gastric
or bowel complain of the patient after surgery. The hydroxyurea induced stomach
erosions or ulcers well known, so it may regrediated after discontinuation of
hydroxyurea therapy. However, the association between colon symptoms and
therapy discontinuation is not affirmable.
- Histo-pathologic findings of oro-pharyngeal ulcers shows similarity with colon
ulcers, but oro-pharyngeal deviation appeared one month later when colon ulcers
was eliminated by surgery. In spite of similarity the common procession is not
verifiable.
- Discontiunation of hydroxyurea therapy was after colon surgery procedure, so it
may not known colon ulcers would have disapperaed or not.
In summary, in this case report published appear of colon ulceration after
initiation of hydroxyurea and naproxen therapy may assumable, but association
between discontinuation of hydroxyurea therapy and disappear of colon
ulceration are not verifiable. Because of strict correlation between medical
therapy and side effect is not speakable, the case report is not proposable for
acceptance.
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-131 (2014)

Reviewer's report
Title:Treatment with Pirfenidone for two years decreases fibrosis, cytokine levels
and enhances CB2 expression in patients with chronic hepatitis C: open-label
clinical trial
Version:2Date:23 December 2013
Reviewer: Chao-Hung Hung
Reviewer's report:
Major Compulsory Revisions
In this manuscript, the authors aimed to assess whether two-year treatment with
pirfenidone influence necro-inflammation, fibrosis and steatosis, as well as serum
markers in patients with chronic hepatitis C (CHC). They found that pirfenidone
for two years benefits CHC patients and improves inflammation, fibrosis and
steatosis. Although their data seem logical, there are several issues that should
be further reconsidered or corrected.
1. The major criticism raised is the high rate (18%) of early termination from this
study. What happened in these subjects with early discontinuation? Was there
any severe adverse effect associated with study medication? What were the
causes for the mortality?
2. Intention-to-treat analyses should be performed, including liver biochemistry,
clinical status, and serum biomarkers.
3. The authors should provide the statistical analyses on the Child-pugh status
and quality of life between before and after treatment (table 2).
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-131 (2014)

Reviewer's report
Title:Treatment with Pirfenidone for two years decreases fibrosis, cytokine levels
and enhances CB2 expression in patients with chronic hepatitis C: open-label
clinical trial
Version:2Date:6 January 2014
Reviewer: lawrence serfaty
Reviewer's report:
Contreras et al have investigated the efficacy of Pirfenidone in the treatment of
chronic hepatitis C. This molecule used in the treatment of pulmonary fibrosis
was given for 2 years in 34 HCV patients with different stage of disease severity.
Control liver biopsy showed a significant improvement of steatosis, fibrosis and
inflammation. Some cirrhotic patients improved their Child score. Molecular
analysis showed modulation of CB receptors expression.
Authors published similar results in a previous small pilot study (Gut 2006).
Accordingly, I don't understand why they did not perform a randomized controlled
study rather than a second pilot study.
Moreover, in the era of DAAs, the relevance of this antifibrotic treatment is likely
out of relevance. I have also major concerns with the safety of this molecule.
Results should be presented in intend to treat (6 patients excluded of the efficacy
analysis)
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I have no competing interest with this paper.
Review for 10.1186/1471-230X-14-131 (2014)

Reviewer's report
Title:Treatment with Pirfenidone for two years decreases fibrosis, cytokine levels
and enhances CB2 expression in patients with chronic hepatitis C: open-label
clinical trial
Version:5Date:22 June 2014
Reviewer: lawrence serfaty
Reviewer's report:
This paper has been improved.
In the last part of discussion, cost of DAAs in developing countries should be
highlighted rather than their supposed low efficacy in G1/G2 infected patients
(SVR rate >90% with sofosbuvir).
Pirfenidone could also be evaluated in other chronic liver disease.
Level of interest: An article of importance in its field
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
No
Review for 10.1186/1471-230X-14-131 (2014)

Reviewer's report
Title:Treatment with Pirfenidone for two years decreases fibrosis, cytokine levels
and enhances CB2 expression in patients with chronic hepatitis C: open-label
clinical trial
Version:5Date:26 June 2014
Reviewer: luigi adinolfi
Reviewer's report:
The paper is substantial improved, however there are some points that must be
modified/commented.
1. the reference, Zampino et al must be numbered in progression, thus the
reference is not [42] but [15]. All the others reference must be changed
accordingly.
2.Since the variations on CB1 and CB2 are not significant or slight significant, I
strongly suggest to cite the paper of Coppola et al. suggesting that the diversity
could be due to different polymorphisms to be evaluated in future studies.
Level of interest: An article of insufficient interest to warrant publication in a
scientific/medical journal
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
'I declare that I have no competing interests'
Review for 10.1186/1471-230X-14-130 (2014)

Reviewer's report
Title:Risk Score to Predict Gastrointestinal Bleeding after Acute Ischemic Stroke
Version:2Date:6 June 2014
Reviewer: Colin Crooks
Reviewer's report:
Major compulsory revisions are listed below:
The authors do not describe in the methods how long patients were followed up
for an occurrence of GIB. Were post discharge bleeds captured? What happens
if patients present to a different hospital with GIB after discharge? Table 1 and
the discussion suggest only in patient bleeds were included. If so this is
problematic as patients with longer periods in hospital have more time to have a
GIB event observed. Therefore predictors of longer inpatient stay will be
predictors of GIB in this study, even if not associated with GIB. This could explain
or least seriously confound the findings of this study.
For the same reasons Including length of hospital stay as a predictor of bleeding
is unhelpful as clearly the longer of hospital stay the longer the period in which to
capture a GIB and therefore it will itself become a 'risk factor'. Additionally the
length of hospital stay is not known at the start of the an admission which
contradicts the authors own statement that only risk factors known at the time of
the stroke were included.
There is a comment in the discussion that seems to suggest that the time of GIB
was not recorded? If this is the case how can the researchers know for certain
whether the GIB was before or after the stroke? Or whether the recording of risk
factors was definitely before the stroke and GIB (this is not fully described in the
methods but the discussion mentions information collected in the period after
admission was included in the study)?
Aren't the responses of the GCS score covered in the NIHSS, which also
includes an assessment of consciousness? So why include the GCS in addition
to the NIHSS?
Age was included as a linear variable in the model, yet the final score uses
categories. How were these categories selected? Was there any test done for a
departure from linear trend for age?
How reliable is the recording of the risk factors and outcomes within the
datasets? Has there been any validation of the variables used in the dataset?
What is the distribution of the score in the study population? Do most people
have a score of zero or is it evenly distributed?
What is the cross over between the CNSR and the CICAS? If these datasets
come from the same hospitals then the CICAs would not be an external
validation.
The detail for the comments above was lacking in the methods. I had to deduce it
from the discussion and tables but this should have been in the methods.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-130 (2014)

Reviewer's report
Title:Risk Score to Predict Gastrointestinal Bleeding after Acute Ischemic Stroke
Version:2Date:10 June 2014
Reviewer: Siddharth Singh
Reviewer's report:
In this large cohort study, Ji and colleagues have derived and validated a risk
prediction tool for predicting in-hospital risk of gastrointestinal bleeding after
acute stroke. Their model, based on 18 variables, has a modest discriminatory
ability with an AUC of 0.76-0.79.
Overall, this is a well-designed and reported manuscript on a clinically important
topic. The investigators have used commonly available information to derive a
prediction model and subsequently validated it both internal and externally. While
the model has modest discriminatory ability, its ease of applicability would better
risk stratification for use in clinical practice.
Minor Revisions:
- It may be helpful to emphasize the modest discriminatory capability of this tool
for readers who may not be able to interpret an AUC of 0.76-0.79, and based on
this conclusions may be tempered down a little. However, the ease of
applicability in clinical practice can be highlighted.
- Was data on most comorbidities and pre-existing conditions derived from chart
review or patient self-report? The reliability of using either should be discussed
as a limitation. It is possible that patients, especially those with stroke may not
recall a history of previous GI bleed, and this may not be well-captured in the
medical chart.
Discretionary revisions:
- What proportion of patients were on PPI or H2RA at time of presentation?
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-14-129 (2014)

Reviewer's report
Title:The Epidemiology and Treatment of Anal Fissure in a Population-based
Cohort
Version:1Date:7 May 2014
Reviewer: Andrea Cariati
Reviewer's report:
interesting article to be published
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
no compending interests