JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-12-46 (2012)

Reviewer's report
Title:Diabetes and insulin use are linked to Helicobacter pylori eradication
Version: 5Date:24 February 2012
Reviewer: David Whiteman
Reviewer's report:
Diabetes and insulin use are linked to Helicobacter pylori eradication
Chin-Hsiao Tseng
This is an interesting analysis of a population database in Taiwan. The author
has used routine health data (in this case, insurance data) to explore the
relationship between type 2 diabetes and treatment for Helicobacter pylori
infection. They are attempting to infer a causal association from this retrospective
analysis.
A number of issues present themselves when attempting to interpret this paper.
1. Is the question posed by the author well defined? No, the author has not
explicitly stated their research question as a clearly testable hypothesis; rather,
the question is implied in the title and in the Introduction to the study. This is a
MINOR ESSENTIAL REVISION
2. Are the methods appropriate and well described? No. I am not clear that I
understand how exposure and outcome were defined. It is not stated explicitly
whether the intent of the analysis was to constrain H pylori eradication to occur
only AFTER diabetes was diagnosed, or whether it could occur at any time within
the study interval. The former would imply that diabetes preceded H pylori
treatment, and might therefore imply some temporal order. This has major
implications for interpreting the analysis. Most readers would be expecting a
retrospective cohort design, in which the cohort has been defined by date of
assembly, and that the diagnosis of diabetes must precede the date of
eradication of H pylori. Is this what happened? It appears not, and that there is
simply an attempt to assess a cross-sectional association. This is a MAJOR
ESSENTIAL REVISION
3. Are the data sound? The data were obtained from the national health
insurance records of Taiwan. They are likely to be reasonably complete, and are
not likely to be biased with respect to diabetes status or records of H pylori
eradication. However, I suspect that there is considerable under-diagnosis and
under-treatment of H pylori in this population. Some comment from the
investigators is required. This is a MINOR ESSENTIAL REVISION
4. Does the manuscript adhere to the relevant standards for reporting and data
deposition? Yes.
5. Are the discussion and conclusions well balanced and adequately supported
by the data? Yes.
6. Are limitations of the work clearly stated? Yes
7. Do the authors clearly acknowledge any work upon which they are building,
both published and unpublished? Yes.
8. Do the title and abstract accurately convey what has been found? Yes
9. Is the writing acceptable? Yes.
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.
Review for 10.1186/1471-230X-12-45 (2012)

Reviewer's report
Title:High mobility group B1 impairs hepatocyte regeneration in acetaminophen
hepatotoxicity
Version: 2Date:12 February 2012
Reviewer: Vincent Zimmer
Reviewer's report:
This is an important preclinical study examining the efficacy of anti-HMGB1 in
attenuating liver injury in a mouse model of acetaminophen (APAP)
hepatotoxicity. The Authors show that blocking HMGB1 after APAP exposure
results in attenuation of liver injury most pronounced so after 48 h (relative to the
first time point 24 h) suggesting a role for HMGB1 as a progression factor in this
injury model.
Improvements in hepatocyte regeneration by the anti-HMGB1 strategy is
supported by up-regulation of NF-kB DNA binding capacity and the cell-cycle
regulator cyclin D1.
However, there remain some minor concerns to be addressed:
1. The exclusive use of Western blots has to be critically discussed - for HMGB1
serum measurements complementary use of e.g. reliable commercial ELISAs or
in case of e.g. cyclin D1 complementary use of immunohistochemistries might
have strengthened the validity of experimental data. These limitations, if not
eliminated in the first place, should at least be stated and discussed appropriately
in the manuscript.
2. The legend for Figure 2 is not readily comprehensible and should be
rephrased - it is motivated to first introduce the general experimental protocol and
then to individually state what the corresponding pictures show.
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:
Nothing to declare
Review for 10.1186/1471-230X-12-45 (2012)

Reviewer's report
Title:High mobility group B1 impairs hepatocyte regeneration in acetaminophen
hepatotoxicity
Version: 3Date:26 March 2012
Reviewer: Leo A van Grunsven
Reviewer's report:
Yang et al.
High mobility group B1 impairs hepatocyte regeneration in acetaminophen
Hepatotoxicity
Authors have addressed all comments and modified the manuscript accordingly
and is suitable for publication in BMG.
Minor comments on their changes and letter:
The authors make a strong point that NF-kB bandshift withouth supershift or cold
competition are informative in this study. Their comment on my request was
“Nowadays, most of the papers and journals no longer require NF-kB cold
competition and supershift tests”
This is probably true because the standard nowadays is ChIP, nobody bothers
with EMSA anymore due to its low predictability of the real binding situation of
the protein of interest. It gives the potential of the protein to bind and in this
manuscript it indicates the amount of activated NF-kB present in the
ant-HMGB-1-2 injected animals. Since this is the only claim that the authors
make “activation of NF-kB by blockade of HMGB1” the experiment is valid and
rightly used.
Figure 6 has been added, but the legend is not very clear, i.e. it is not clear what
is A, B or C in the figure.
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-12-45 (2012)

Reviewer's report
Title:High mobility group B1 impairs hepatocyte regeneration in acetaminophen
hepatotoxicity
Version: 3Date:8 April 2012
Reviewer: Vincent Zimmer
Reviewer's report:
This is acceptable in its current form.
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:
Nothing to declare.
Review for 10.1186/1471-230X-12-44 (2012)

Reviewer's report
Title:Fibroblast growth factor 23 contributes to diminished bone mineral density
in childhood inflammatory bowel disease
Version: 1Date:13 March 2012
Reviewer: Franco Scaldaferri
Reviewer's report:
Well written, interesting paper, clear and simple descriptive aim. Methods are
well detailed, and data consistent with previous reports.
The introduction session is probably to brief, at least few more information about
the exact role of FGF23 and PHEX should be better clarified, so that the
hypothesis would sound more interesting and intriguing.
Few points need to be better addressed:
1 - which therapy enrolled patients were following before and after the flare;
2 - time for the second evaluation after reaching the remission (weeks,
months??)
3 - into the discussion session it should be stated issues related to bone density
and time related to normalization/reduction
4 - clarify, in case of vit D deficiency whether a therapeutical intervention was
provided and if not (as it appears reading this article), why and how this can be
justified
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.
Review for 10.1186/1471-230X-12-44 (2012)

Reviewer's report
Title:Fibroblast growth factor 23 contributes to diminished bone mineral density
in childhood inflammatory bowel disease
Version: 1Date:15 March 2012
Reviewer: Federica Nuti
Reviewer's report:
Major Compulsory Revisions
In the DISCUSSION:
could you please explain more exstensively the importance of unraveling the
defects in bone metabolism in IBD patients, especially children,
and are you then able to hypothize a clinical implication deriving from your
findings?
Another important variable when assessing improvements in bone metabolism is
evaluation of physical activity, do you have the chance to evaluate this variable
when assessing the BMD improvements in your children?
In the discussion there is a sentence that, to me, appears not to clear as its
reference number 39 doesn't appear correlated to the sentence, could you
please check and explain?
Did you note any difference in the flare values of BMD, FGF 23 and the other
biochemical markers, in patients with a new diagnosis compared to patients with
a previous diagnosis (and so with a past history of therapy!)?
Minor essential revisions
In the PTH paragraph, in the first sentence "high" should be changed in "higher".
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-12-42 (2012)

Reviewer's report
Title:Efficacy of omeprazole, famotidine, mosapride and teprenone in patients
with upper gastrointestinal symptoms: an omeprazole-controlled randomized
study (J-FOCUS)
Version: 2Date:12 June 2011
Reviewer: Arne Kandulski
Reviewer's report:
Accept with discretionary revisions.
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-12-42 (2012)

Reviewer's report
Title:Efficacy of omeprazole, famotidine, mosapride and teprenone in patients
with upper gastrointestinal symptoms: an omeprazole-controlled randomized
study (J-FOCUS)
Version: 2Date:9 September 2011
Reviewer: Tiberiu Hershcovici
Reviewer's report:
This is an interesting study performed in Japan.Although the study's metodology
is correct, the question adrressed by the study is irrelevant to the daily
gastroenterologist. No one will treat today a patient aged more than 45 years with
upper GI symptoms (non-reflux )without a previous investigation. Although PPI
treatment is well known to be efficacious for the treatment of these dyspeptic
symptoms (and more eficacious than H2RA), its use can be even dangerous in
some population groups (such as Japanese people) with high incidence of
gastric cancer.Accordingly, the conclusions of this study can give a sense of
false security to some physicians to use PPI as first line treatment of patients
with uninvestigated upper GI symptoms.Although PPI is well known as first line
treatment for reflux symptoms, its use for uninvestigated dyspepsia is
unacceptable.
Level of interest: An article of limited interest
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-12-42 (2012)

Reviewer's report
Title:Efficacy of omeprazole, famotidine, mosapride and teprenone in patients
with upper gastrointestinal symptoms: an omeprazole-controlled randomized
study (J-FOCUS)
Version: 3Date:16 October 2011
Reviewer: Tiberiu Hershcovici
Reviewer's report:
Thank you for sending me the revised version of the manuscript.
I think the manuscript was improved by the changes performed in response to
Dr. Leontiadis.However, some of the points raised by the reveiwer and also by
myself can not be resolved. They are inherent problems due to the design of the
study and its methodology.
Although, in my opinion, the quality of this article is still debatable, I agree that it
can be published in BMC Gastroenterology.
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.
Review for 10.1186/1471-230X-12-42 (2012)

Reviewer's report
Title:Efficacy of omeprazole, famotidine, mosapride and teprenone in patients
with upper gastrointestinal symptoms: an omeprazole-controlled randomized
study (J-FOCUS)
Version: 3Date:28 October 2011
Reviewer: Grigorios Leontiadis
Reviewer's report:
The authors have adequately responded to the points, with the exception of
points #5, 6 and 8. Please see my comments below:
Point # 5. (Urine antibody testing is not a valid method to test for H. pylori
infection. Were all patients tested for H. pylori or only a proportion of them?)
Response to authors’ response: Urine antibody testing is FDA approved, but if
the authors cannot identify national or international guidelines that recommend
this test as a diagnostic test in clinical practice, they should add the choice of test
in the list of study limitations.
Point #6. (One of the exclusion criteria was when a patient was “judged to be
ineligible for study entry by the investigator”. This is vague and subjective and
does not allow comparison of the results of the current study with previous or
future studies. It also undermines the generaliseablity of the results in clinical
practice. How can the clinicians be sure that their patients are similar to the study
population if one exclusion criterion is not defined?)
Response to authors’ response: I do not agree that this is a common criterion in
clinical trials, at least not in high quality trials. The purpose of having pre-defined
and well-defined inclusion criteria is to minimize subjectivity during eligibility
assessment; this purpose is defeated when an additional exclusion criterion
named “judged to be ineligible for study entry by the investigator” is used. The
authors should elaborate on this in the discussion of study limitations.
Point # 8. (What measures were taken to maintain concealment of allocation
prior to study entry?)
Response to authors’ response: The authors’ response is not relevant to the
question. The authors are advised to read the article: Schulz, K.F., Grimes, D.A.
(2002). Allocation concealment in randomised trials: Defending against
deciphering. The Lancet, 359(9306), 614-618. This explains what allocation
concealment is and what is meant by measures taken to maintain it. The revised
response to point #8 should be included in the article.
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 have acted as a consultant for AstraZeneca and Axcan Pharma and have
received speaking honoraria from AstraZeneca, Sanofi-Aventis, Janssen-Cilag,
and GlaxoSmithKline
Review for 10.1186/1471-230X-12-42 (2012)

Reviewer's report
Title:Efficacy of omeprazole, famotidine, mosapride and teprenone in patients
with upper gastrointestinal symptoms: an omeprazole-controlled randomized
study (J-FOCUS)
Version: 4Date:18 December 2011
Reviewer: Grigorios Leontiadis
Reviewer's report:
The authors have addressed adequately point #6 and point #8 adequately.
With regards to point #5, I still believe that the use of urine antibody test was
inappropriate, but it is not worth engaging in further exchange of arguments. My
understanding is that my thoughts will be published alongside the article. The
final decision rests with the Editors. I am confident that future readers will be able
to see that future guidelines will not propose this test for clinical use, let alone for
selection of participants in clinical trials. For the time being, a reasonable
compromise that will protect the reputation of BMC Gastroenterology, would be
to re-phrase the wording as follows:
“First, we used a urine antibody test to screen patients for evidence of H. pylori
infection. Although this test shows high sensitivity and accuracy specificity, it is
has not been recommended by guidelines as a screening test as yet. It is
possible that some patients without H. pylori infection were included in this
study.”
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-12-43 (2012)

Reviewer's report
Title:Changes of Treg andTh17 balance in the development of acute and
chronic HBV infection
Version: 2Date:23 January 2012
Reviewer: Michael Robek
Reviewer's report:
This manuscript by Liang Xue-Song and colleagues reports differences in the
Th17 and Treg cell proportions in HBV-infected patients with different disease
states (acute, chronic, carrier, liver failure). The immunological correlates of HBV
persistence and disease pathogenesis are not well understood, and relatively
little is known about the role of Th17 and Treg cells in these processes. Although
this manuscript is somewhat descriptive, this is not unusual for clinical studies of
this kind. Also, although the data reported here in some cases only confirm
results published by other groups, this study nevertheless contributes to our
understanding of HBV immunopathogenesis.
Minor Essential Revisions:
1. Figure 1: The symbols for statistical significance do not appear to display or
print properly. Although this may only be a PDF conversion issue, it should be
corrected.
2. Figure 1: The data shown in Fig 1C do not appear to be referenced in the
results along with the other panels of this figure. What is the purpose of showing
these results? This figure panel should either be discussed, or removed from the
figure.
3. Figure 3: Although r and P values are appropriately shown here, it would also
be useful to show the trend line that corresponds to these values.
4. The abbreviations for the disease states should be defined the first time they
are used.
5. Although the paper is thoroughly referenced, that authors missed one relevant
study (Zhang et al. Gastroenterology. 2011 Nov; 141(5):1897-906. Epub 2011
Jun 25). This paper also shows an association between Th17 cells and acute
hepatitis B, as well as an association between Th17 cell proportion and
ALT/AST.
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: 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-12-43 (2012)

Reviewer's report
Title:Changes of Treg andTh17 balance in the development of acute and
chronic HBV infection
Version: 4Date:9 April 2012
Reviewer: Christoph Neumann-Haefelin
Reviewer's report:
The authors have now revised their manuscript, adressing the reviewers'
comments. It is now acceptale for publication in BMC Gastroenterology.
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-12-40 (2012)

Reviewer's report
Title:Luminal lactate in acute pancreatitis - Validation and relation to disease
severity.
Version: 1Date:30 November 2011
Reviewer: Hans-Ulrich Schulz
Reviewer's report:
In this research article, the authors tested the hypothesis that intestinal lactate
release occurs in acute pancreatitis and that a single measurement of rectal
luminal lactate at admission predicts the severity of acute pancreatitis including
length of hospital stay, need of intensive care and mortality.
Rectal luminal equilibration dialysis for the measurement of gut luminal lactate
was performed in 30 consecutive patients with acute pancreatitis. Three patients
had to be excluded from analysis because of technical failure (n=1) or missing
data (n=2). Of the remaining 27 patients, eight developed local complications.
One patients required admission to intensive care department. Mean hospital
stay was seven days. No mortality was observed.
High rectal luminal lactate was associated with low mucosal partial tension of
oxygen, indicating the physiological validity of the method. Rectal luminal lactate
at hospital admission was not associated with SOFA score, CRP level, length of
hospital or ICU stay, development of local complications or mortality. Low
precision and high bias was observed between two different lactate analyzers.
As adequately discussed by the authors themselves, the major limitation of the
investigation is the limited number of patients who suffered from severe acute
pancreatitis. Only one patient required intensive care and no deaths occurred.
Highest SOFA score was 3. For those reasons, the clinical value of a single
rectal luminal lactate measurement at admission to predict pancreatitis severity
remains obscure. In addition, two different methods of lactate analysis yielded
different results. However, since high rectal luminal lactate concentration was
associated with low mucosal partial tension of oxygen, the physiological validity
of the method could be established in acute pancreatitis for the first time by this
study.
The reviewer recommends major compulsory revisions to weaken the aims of the
investigation by the authors. Length of hospital stay, need for intensive care and
mortality aren’t appropriate study parameters in this small group of patients
suffering from mild acute pancreatitis in the majority of cases in whom no single
organ failure or death occurred.
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, 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-12-40 (2012)

Reviewer's report
Title:Luminal lactate in acute pancreatitis - Validation and relation to disease
severity.
Version: 1Date:5 December 2011
Reviewer: Basil Ammori
Reviewer's report:
Major Compulsory Revisions
- The authors' hypothesis was that luminal lactate on admission predicts severity
of acute pancreatitis, yet their conclusion does not refer to this at all. That luminal
lactate did not predict severity needs to be stated. Moreover, the patients were
not classified into mild and severe attacks and no method of classification was
adopted. This shortcoming needs to be addressed.
- The authors overstate their conclusion "The association between rectal luminal
lactate and oxygen tension indicates that luminal lactate is a marker mucosal
anaerobiosis." In fact, that association was weak with an r2=0.3. This gives little
support to the conclusion statement. This needs to be discussed.
- The 'Primary and secondary end point parameters" should be replaced with
"Primary and secondary endpoints".
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-12-40 (2012)

Reviewer's report
Title:Luminal lactate in acute pancreatitis - Validation and relation to disease
severity.
Version: 4Date:27 January 2012
Reviewer: Hans-Ulrich Schulz
Reviewer's report:
The authors responded in an adaequate manner to the points I raised in my initial
review. The revisions made by the authors lead to significant improvement of the
paper.
Level of interest: An article whose findings are important to those with closely
related research interests
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-12-40 (2012)

Reviewer's report
Title:Luminal lactate in acute pancreatitis - Validation and relation to disease
severity.
Version: 4Date:29 January 2012
Reviewer: Basil Ammori
Reviewer's report:
The revised manuscript is satisfactory and suitable for publication. The raised
issues have been adequately addressed.
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-12-41 (2012)

Reviewer's report
Title:Dietary L-Arginine Supplementation Reduces Methotrexate-Induced
Intestinal Mucosal Injury in Rat
Version: 2Date:8 December 2011
Reviewer: Daniel H. Teitelbaum
Reviewer's report:
I think this is a well-written article which nicely demonstrates a unique role for
Arginine.
A few comments.
1. would the authors comment if the protein or energy delivered in the ARG
group might influence the effects, or was this relatively small?
2. Fig 1 should have a scale (e.g. 50 um with bar showing this length) on one of
the panels
3. Fig 4 should show standard deviation or SEM
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 declare that I have no competing interests'
Review for 10.1186/1471-230X-12-41 (2012)

Reviewer's report
Title:Dietary L-Arginine Supplementation Reduces Methotrexate-Induced
Intestinal Mucosal Injury in Rat
Version: 2Date:15 December 2011
Reviewer: Moïse Coëffier
Reviewer's report:
Major Compulsory Revisions
1/ The authors choose to provide 2% Arginine in drinking water. What was the
water intake in the different groups? The provision of arg in different models is
associated with beneficial or deleterious effects according to the dose of supplied
Arginine. It is thus important to know the dose of Arg really received by rats.
2/ In the present study, Arg was provided in drinking water in MTX-ARG group. In
MTX group, animals received only water. Thus there was no isonitrogenous MTX
group. Thus, the authors should be not able to conclude that Arg supply limits
intestinal damage. Will other amino acids have similar effects? An additional
group MTX-isonitrogenous AA should be done.
3/ How were expressed the mRNA levels? Bax to erk2? What was the
housekeeping gene used to quantify bax and bcl-2 mRNA? For my opinion, Erk-2
mRNA cannot be used as housekeeping mRNA.
Minor Essential Revisions
1/ How the authors explain the difference between mRNA expression of BCl-2 in
Jejunum and ileum in the MTX-ARG group?
2/ Did westernblot analysis of proliferation and apoptosis markers perform both in
jejunum and ileum or only in jejunum. This point should be clarified.
3/ In figure 4, the standard error and statistical analysis should be provided in the
densitometric analysis.
Discretionary Revisions
1/ In the introduction, the part on immunonutrition using impact solution is not
necessary because in the present study, authors did not use n-3 fatty acids and
data on this immunoenhancing diet are obtained in other pathophysiological
conditions.
2/ Figure 4 legend should be more detailed
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-12-41 (2012)

Reviewer's report
Title:Dietary L-Arginine Supplementation Reduces Methotrexate-Induced
Intestinal Mucosal Injury in Rat
Version: 3Date:25 January 2012
Reviewer: Daniel H. Teitelbaum
Reviewer's report:
The authors have addressed all of the reviewer's comments and requests
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:
none
Review for 10.1186/1471-230X-12-41 (2012)

Reviewer's report
Title:Dietary L-Arginine Supplementation Reduces Methotrexate-Induced
Intestinal Mucosal Injury in Rat
Version: 3Date:8 February 2012
Reviewer: Moïse Coëffier
Reviewer's report:
'Dietary L-Arginine Supplementation Reduces Methotrexate-Induced Intestinal
Mucosal Injury in Rat'
Tal Koppelmann, Yulia Pollak, Jorge Mogilner, Jacob Bejar, Arnold G. Coran and
Igor Sukhotnik
BMC Gastroenterology
Research article
General comments:
I thank the authors for their responses and revision of the manuscript.
Minor Essential Revisions
1/ As arginine was provide arginine in drinking water, I think that water intake
should be provide in the text (even if water intake was similar in all groups).
2/ I understand that an additional group with an isonitrogenous supply would
complicate the experimental design. However, I think that this type of group is
necessary to conclude. It was previously reported that other amino acids like
glutamine, glycine or histidine have protective effects on intestinal mucosa during
chemotherapy or inflammatory conditions. Thus, in the present study, is it a
specific effect of arginine? The authors should thus discuss the limits of their
study.
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-12-39 (2012)

Reviewer's report
Title:Postoperative Complications Following Colectomy for Ulcerative Colitis: A
Validation Study
Version: 2Date:24 November 2011
Reviewer: Ashwin N Ananthakrishnan
Reviewer's report:
I appreciate the several changes made by the authors and find their manuscript
in its present version acceptable for publication.
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-12-38 (2012)

Reviewer's report
Title:Elevated circulating soluble interleukin-2 receptor in patients with chronic
liver diseases is associated with non-classical monocytes
Version: 1Date:19 March 2012
Reviewer: Jaap Kwekkeboom
Reviewer's report:
Major Compulsory Revisions:
1. The authors should include a statistical comparison of the numbers of
monocytes, classical monocytes, pro-inflammatory monocytes between patients
and healthy controls, preferably in an additional figure. In the current version the
numbers are mentioned in Table 1, but no statistics is provided.
2. The authors should explain why they focused on sIL2R, while a large
number of cytokines and chemokines seem also to be elevated in CLD-patients
according to Table 2. Are differences in these parameters smaller between
CLD-patients and healthy subjects, or between cirrhotic and non-cirrhotic
patients?
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-12-38 (2012)

Reviewer's report
Title:Elevated circulating soluble interleukin-2 receptor in patients with chronic
liver diseases is associated with non-classical monocytes
Version: 1Date:20 March 2012
Reviewer: kang xiaonan
Reviewer's report:
Minor essentioal revision
It was long known that sIL-2R levels offer a rapid, reliable, and noninvasive
measure of disease activity, response to therapy, and, in some cases, prognosis
in a broad spectrum of conditions associated with T- or B-cell immune activation.
Elevated sIL-2R has been reported for distinct hepatic disorders but the clinical
significance of this finding remained vague. This work measured serum sIL-2R
levels in 71 patients with chronic liver diseases and analyzed the correlation
between sIL-2R serum concentration and various routine and experimental
laboratory parameters including liver function, heptatic fibrosis, inflammation and
renal function.sIL2-R levels correlated closely with circulating monocytes,
especially non-classical CD14+CD16+ monocytes. sIL-2R could be possibly a
useful marker in chronic liver diseases (CLD).
Here is a question that in Fig 1 ABCF, what does the symbol “ # ” represent ?
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-12-36 (2012)

Reviewer's report
Title:Statin use is associated with a reduced incidence of colorectal cancer: a
colonoscopy-controlled case-control study
Version: 2Date:6 March 2012
Reviewer: Trine Lembrecht Lembrecht Jorgensen
Reviewer's report:
This is still a nicely conducted, though small, case-control study. The question
asked by the authors is well defined, the methods seem appropriate and are well
described. I think the new table 2 has improved the manuscript, and the
explaining of post-colonoscopy including of cases is also beneficial.
I still don’t think the study results reflect the true association of statin use and crc,
but as the authors point out: those are their results, perhaps due to low sample
size.
Overall, I think the manuscript has improved markedly.
Discretionary revisions:
Abstract, results & tables. No need for p values where confidence intervals are
provided as these are much more informative.
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 have no competing interests
Review for 10.1186/1471-230X-12-36 (2012)

Reviewer's report
Title:Statin use is associated with a reduced incidence of colorectal cancer: a
colonoscopy-controlled case-control study
Version: 2Date:14 March 2012
Reviewer: Yana Vinogradova
Reviewer's report:
I have no further questions or suggestions to the authors.
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-12-34 (2012)

Reviewer's report
Title:Gastric cancer cell supernatant causes apoptosis and fibrosis in the
peritoneal tissues and results in an environment favorable to peritoneal
metastases, in vitro and in vivo
Version: 3Date:17 September 2011
Reviewer: Yoshiharu Motoo
Reviewer's report:
This report describes a novel mechanism of peritoneal dissemination of gastric
cancer cells.
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.
Review for 10.1186/1471-230X-12-34 (2012)

Reviewer's report
Title:Gastric cancer cell supernatant causes apoptosis and fibrosis in the
peritoneal tissues and results in an environment favorable to peritoneal
metastases, in vitro and in vivo
Version: 4Date:28 February 2012
Reviewer: Masakazu Yashiro
Reviewer's report:
The revised manuscript is generally well modified. However, I regrettably should
say that it is still immature for publication.
1.They showed the additional TEM data of treated SGC-7901 cells in Figure 2C,
but it looks hard to evaluate these phenomena are common in gastric
carcinomas. To show these data as satisfactory, it would be necessary to show
both control and treated cells at least three cells. It is similarly recommended to
show data of several gastric carcinoma cells in Figure 1. And there is no
description about these additional data in the text.
2.Discussion is still too long. Excessive descriptions make the point unclear.
Minor points:
Page 9 line 29: Please change “Masakazu” to “Yashiro”.
Page 11 line 12: Please change “VI” to “IV”.
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-12-33 (2012)

Reviewer's report
Title:Genetic deletion of dectin-1 does not affect the course of murine
experimental colitis.
Version: 2Date:28 January 2012
Reviewer: Satish Keshav
Reviewer's report:
Revisions answer the points made.
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' below
Review for 10.1186/1471-230X-12-33 (2012)

Reviewer's report
Title:Genetic deletion of dectin-1 does not affect the course of murine
experimental colitis.
Version: 2Date:2 February 2012
Reviewer: Colin de Haar
Reviewer's report:
The authors have answered all major points to my satisfaction and changed the
manuscript accordingly.
Although I do not fully agree with their comment with regard to point 7, I agree
with them that this will not be contribute to the conclusion they draw with regard
to dectin-1 in mouse colitis models, but instead will give broader information
about the role of fungi in colitis models.
Discretionary revision:
Point 8:
With regard to their response:
Blocking the IL-10R does affect the levels of IL-10 by blocking its consumption,
but more importantly it inhibit its function. Since IL-10 has recently been shown to
be the key cytokine that enables rescue from Hh-colits, it could still be interesting
to see if dectin-1 deficient mice will develop Hh-colits whereas the WT will not.
However, the limited difference in IL-10 levels between the WT and dectin-1
deficient macrophages would be a sensible reason not to perform this
experiment.
Minor essential revision:
Point 8: The involvement of the adaptive immune response is mentioned here as
rationale for the Hh-colitis model, but no data are presented with regard to the
adaptive immune response. Since IFN-gamma levels were measured in the
colon homogenates (M&M), these data could be included to show that at least
this “adaptive parameter” was not affected.
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-12-32 (2012)

Reviewer's report
Title:Spirulina platensis versus silymarin in the treatment of chronic hepatitis C
virus infection. A pilot randomized, comparative clinical trial.
Version: 2Date:10 September 2011
Reviewer: Cristian Baicus
Reviewer's report:
- the study appears to be a methodologically correct randomized controlled trial,
with concealed allocation and double blind.
- the statistical analysis is adequate; however, the sample size calculation is
wrong (see bellow), so I wonder if the rest of statistical analysis is correct.
- the assumption of 20% virological response was overoptimistic;
- as a comparator was chosen silymarine, supposing, probably, that it has effect
in chronic hepatitis; however, there are not valid studies to demonstrate this (at
least concerning the standard endpoint used in viral hepatitis – viral response)!
- I dont’t think ASEX is a valid endpoint for the treatment of chronic hepatitis C.
- Major Compulsory Revisions
1. Liver related mortality/morbidity (stated as primary endpoints), the real hard
endpoints, could not have been assessed in a study on 60 patients, for 6 months
because of the lack of statistical power. Even the large studies with interferon
and ribavirin did not assess these very important endpoints and limited
themselves to virologic response.
2. I think the sample size calculation was not correct and, given the assumptions
of the authors, the sample size should have been much larger. The study had
not, in reality, enough power to detect the differences concerning the virologic
responses. The proof is that, although the authors claimed that the study was
powered for a difference of 2%, they could not find statistical significance for a
larger difference of 9.9% (13.3% vs. 3.4%, c-ETR).
3. The two scores (ASEX and CLDQ) are ordinal variables, so one should
compare them by nonparametric tests, and resume them as median and Q1-Q3
or min-max, than mean and SD. (I know that in many journals are published
articles where this kind of scales are treated as quantitative variables, with mean
and SD, and compared by parametric tests; it’s up to the editors to decide this).
4. In Table 1, there are not the baseline ASEX and CLDQ scores.
6. Child-Pugh score is used for cirrhosis, and not for chronic hepatitis, for which it
was not validated.
- Minor Essential Revisions
1. All tables were directly taken from the output of the statistical software, and not
edited (too many raws and columns, abbreviations without footnotes etc).
2. The p should be written in table 4, on the corresponding rows, rather than in
text; on the contrary, it’s not necessary to give both SD and SE in Table 4,5,6
(see also comment 3, above). In fact, results of Tables 5 and 6 could be written
in one phrase of text.
3. In Table 7 there is no need of raws with intercept, error, total, corrected total
and columns 3,4,5,6,8.
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-12-32 (2012)

Reviewer's report
Title:Spirulina platensis versus silymarin in the treatment of chronic hepatitis C
virus infection. A pilot randomized, comparative clinical trial.
Version: 3Date:6 February 2012
Reviewer: John H Kalbfleisch
Reviewer's report:
These comments follow a request for statistical review. The statistical procedures
are correct. The current presentation of results will awkward for some readers. I
offer some suggestions the authors can consider.
Major Compulsory Revisions – none.
Minor Essential Revisions – none.
Discretionary Revisions
(1)
For the key outcome events I suggest showing a figure that displays individual
measurements of the patients in both study groups at baseline,
3 months, and 6 months. Viral load measures could be plotted on a log-scale.
ALT,CLDQ and ASEX can be shown on a scale as they were recorded. Group
mean levels can be superimposed on the plots. Lines connecting values
(base,3m 6m) in each patient will show readers trends in addition to only the
general change of group mean levels.
(2)
Table 7 can be shown in an appendix (author choice), and the 2 measures
(CDLQ, ASEX) should be shown separately (Table 7a, 7b). Further, the results
implied by Table 7 can be better illustrated to the reader by presenting the
unadjusted group means and the covariate-adjusted group means (it looks like
will indicate a common conclusion).
(3) Was there a differential effect for M and F on the outcomes ?
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.
John H. Kalbfleisch, Ph.D.
Review for 10.1186/1471-230X-12-31 (2012)

Reviewer's report
Title:A retrospective case-control study of hepatitis C virus infection and oral
lichen planus in Japan: association with mutations in the core and NS5A region
of hepatitis C virus
Version: 2Date:5 January 2012
Reviewer: Takafumi Saito
Reviewer's report:
The authors reported the risk factors for the development of oral lichen planus in
Japanese patients with HCV infection. The findings of this paper are important to
understand one of the major complications associated with HCV.
Major revisions:
1.The association of lichen planus with HCV mutations they examined has not
been detected. The title of paper may mislead the readers, and thus replace it
with an appropriate one.
2.The p values of many factors to assess a potential association with the
development of lichen planus are significant in univariate analysis shown in Table
1. Which factors were included in a multiple logistic regression model to identify
factors for the development of lichen planus associated with HCV ? How about
the the thyroid disease as a factor ?
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-12-31 (2012)

Reviewer's report
Title:A retrospective case-control study of hepatitis C virus infection and oral
lichen planus in Japan: association with mutations in the core and NS5A region
of hepatitis C virus
Version: 2Date:3 February 2012
Reviewer: Shinichi Imafuku
Reviewer's report:
This paper describes the prevalence of hepatitis C in patients with oral lichen
planus and patients without oral mucosal diseases, and higher anti-HCV and
HCV- RNA are strongly related to oral lichen planus.
Authors also investigated the IFN-sensitivity–determining region (ISDR) of
nonstructural protein 5A (NS5A) of infected HCV, and found no relevance
between oral LP and a specific mutation. The conclusion drew here was the
same as previously reported with higher risk ratio, but the study revealed more
detailed risks.
A minor essential point
The selected controls are people without ANY oral disease from a different
population with obvious difference in age. Authors should clarify why this control
is selected.
If the authors are to find the prevalence of HCV in LP patients, the control should
be better in age and sex matched non-LP (including other oral diseases)
patients.
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