JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-12-152 (2012)

Reviewer's report
Title:Analysis of the clinical relevance of antimitochondrial antibodies to the
beta- and gamma-subunits of the F1F0-ATPase in patients with primary biliary
cirrhosis
Version: 1Date:25 June 2012
Reviewer: Dimitrios Bogdanos
Reviewer's report:
This is a well-written and interesting paper. It originates from an experienced
group of investigators with long-lasting interest in the autoantibody serology of
primary biliary cirrhosis. The major finding indicating that antibodies against the
beta- and gamma-subunits of F1F0-ATPase do not have clinical significance is of
interest.
Major comments
I feel that the major weakness of the paper is the current illustration of the figures
which do not clearly convey the points made in the text.
Table 1 gives a summary of the results obtained related to the behaviour of the
autoantibodies over time, before and after liver transplantation. I think this table
could take the form of illustrated Figure showing the behaviour of the
autoantibody concentrations of the samples from the same patient and could
replace at least in part Figure 4.
Figure 1.The Authors state in their Results’ section that "IgG antibody activity
towards the beta-subunit was significantly higher in PBC patients" and refer to
Figure 1. The legend of the Figure 1 also indicates reactivity of antibodies to the
beta and gamma-subunits of F1F0-ATPase in PBC patients and healthy controls.
However, it is not clear whether this figure includes the absorbance values of the
readings obtained in the total number of 425 sera tested (before and after
transplantation) or the baseline readings.
I strongly suggest the Authors to give this figure in the form of scatter plot.
Other points:
I am wondering whether antibody concentrations against beta and gamma
subunits of F1F0-ATPase correlate or not with those against individuals
mitochondrial antigens, and in particular that against PDC-E2, the predominant
mitochondrial autoantigen. It would be great if the Authors have any data
regarding this.
The ROCs are missing and the authors need to submit them as supplementary
data.
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-12-152 (2012)

Reviewer's report
Title:Analysis of the clinical relevance of antimitochondrial antibodies to the
beta- and gamma-subunits of the F1F0-ATPase in patients with primary biliary
cirrhosis
Version: 1Date:18 July 2012
Reviewer: Patrick Leung
Reviewer's report:
The manuscript is focused on investigating whether the titers of antimitochondrial
antibodies to the beta- and gamma-subnunits of the F1F0-ATPase correlate with
any clinical and histological parameters in PBC. The study included 59 patients
with PBC, Effects of UCDA therapy on anti beta and anti-gamma subunits of
F1F0-ATPase was also reported. Base on their data, the authors conclude that
the antibodies may serve as a useful diagnostic tool in anti-M2 negative PBC, but
do not correlate with clinical activity or prognosis. In general, this paper is highly
descriptive. The observation and data substantiate their conclusion.
Minor Revisions :
1. Since the antibodies to beta- and gamma-subunits of F1F0-ATPase were
abbreviated as anti-beta and gamma antibodies and widely used in the article, it
must be clearly noted at the beginning.
2. How many non-PBC controls were studied ? The controls should also include
non-PBC, i.e. other autoimmune liver diseases ?
3. Immunofluorescence was introduced in the Methods and performed to
demonstrate distinct ANA staining patterns. However, no data was included.
4. Since IFT and ELISA were both performed to detect autoantibodies, the
authors should discuss whether results from these two analyses correspond to
each other?
5. N numbers were missing in Fig. 3 and 4. Since not all of the patients received
treatment/OLT were anti-beta/gamma positive, those anti-beta/gamma negative
patients should be excluded while comparing the difference of antibody reactivity
before and after treatment/OLT.
6. Based on their results, The authors should discuss the clinical significance and
impact on patient care moderate.
7. The authors should also discuss autoantibodies that may play important roles
in diagnosis and/or prognosis of PBC, such as anti-gp210, anti-sp100
8. The authors stated that there are CD8+ T cells to the F1F0-ATPase beta
subunit. Please include reference.
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-12-152 (2012)

Reviewer's report
Title:Analysis of the clinical relevance of antimitochondrial antibodies to the
beta- and gamma-subunits of the F1F0-ATPase in patients with primary biliary
cirrhosis
Version: 2Date:31 August 2012
Reviewer: Dimitrios Bogdanos
Reviewer's report:
The revised version of the manuscript is satisfactorily address most of my
comments. I laso noticed that the Authors attempted to address the comments
raised by the other reviewers.
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.
Review for 10.1186/1471-230X-12-152 (2012)

Reviewer's report
Title:Analysis of the clinical relevance of antimitochondrial antibodies to the
beta- and gamma-subunits of the F1F0-ATPase in patients with primary biliary
cirrhosis
Version: 2Date:13 September 2012
Reviewer: Patrick Leung
Reviewer's report:
No further changes are required.
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.
Review for 10.1186/1471-230X-12-150 (2012)

Reviewer's report
Title:Acupuncture for irritable bowel syndrome: primary care based pragmatic
randomised controlled trial
Version: 1Date:16 July 2012
Reviewer: Charlotte Paterson
Reviewer's report:
This is a very clear and comprehensive report of a pragmatic randomised trial of
traditional acupuncture for people with irritable bowel syndrome. It builds on a
pilot project and the methods are appropriate and well justified.
Minor Essential Revisions
1. The following sentence in the introduction is not clear:
In a UK survey, interest in acupuncture for IBS has been shown by 5% of
patients receiving acupuncture reporting having consulted primarily for
gastrointestinal complaints, the most common being IBS(3).
Discretionary Revisions
2. The statement (in discussion and elsewhere) that ‘This effect was largely
sustained through to 12 months’ is a bit ambiguous. In fact it was sustained
through to 9 months and then became non-significant (just!). I think it would be
clearer, and less open to challenge, to say ‘This effect was sustained for 9
months’. This may also be advisable because the IBS Non- Colonic Score
showed a statistically significant difference at 3 months and not beyond.
3. Discussion point: should, if possible, comment on the low uptake of invitation
from GP (GP practices identified and invited 1,651 potentially eligible patients to
participate and 243 patients responded.) Do you know how this compares with
other trial intervention uptakes?
4. Discussion point: Is it worth hypothesising – for future trials – that more
sessions might give more benefit? Your data shows that patients were still
attending for treatment up to the end of 10 sessions and Figure 2 shows a steep
improvement which levels off quite abruptly when treatment ceases.
5. If there is room for another Table, the secondary outcome score table is of
great interest to people working in this field.
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-12-150 (2012)

Reviewer's report
Title:Acupuncture for irritable bowel syndrome: primary care based pragmatic
randomised controlled trial
Version: 1Date:27 July 2012
Reviewer: Klaus Linde
Reviewer's report:
The manuscript reports a pragmatic randomized trial investigating short- and
long-term effects of usual case alone vs. usual care plus acupuncture in patients
with irrtable bowel syndrome. The manuscript is clearly written. The trial is well
planned, a pilot study had been done, the protocol of the definitive trial has been
published, and the study seems to be performed and analyzed adequately. The
clear strenghts of the trial are the long follow-up and study conditions close to
reality. Inevitably, the study has the usual problems of pragmatic trials of
non-pharmacological trials (no blinding, unclear contribution of specific and
non-specific effects).
Minor essential revision
- My only major comment regards the discussion of the clinical relevance of the
observed differences. These are small to moderate for the main outcome
measure and even smaller for secondary outcomes. Given the risk of reporting
bias (which is discussed) I think the authors should discuss the issue of clinical
relevance of the findings in more detail
Discretionary Revisions
- Introduction, end of first parapragh: In the first moment I was a bit surprised on
the focus of two trials on non-specific effects. In its brevity it can be confusing to
readers. Furthermore, I would not say the Schnieder trials focuses on
non-specific effects.
- Statistical analysis, first phrase on sample size calculation: to be reproducible
the assumed standard deviation should be added.
- Page 9, paragraph 1: some consider a Cohen’s d < 0.4 as small. Maybe it
would be more correct to say small to moderate.
- Page 9, first phrase paragraph 2: the phrase does not seem fully correct
- Figure 2: could confidence intervals be added? Seeing only the means is not
very informative.
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-12-149 (2012)

Reviewer's report
Title:Cost-effectiveness of acupuncture for irritable bowel syndrome: findings
from an economic evaluation conducted alongside a pragmatic randomised
controlled trial in primary care.
Version: 2Date:21 June 2012
Reviewer: Julie Ratcliffe
Reviewer's report:
This paper documents a well conducted economic evaluation of the cost
effectiveness of acupuncture for irritable bowel syndrome.
Minor essential revisions
I have one comment which needs to be addressed. This relates to
the discussion section on page 10 and the finding that acupuncture may be a
cost effective treatment option for patients with severe IBS. The paper would be
strengthened by a re-phrasing of the statement that this group 'sometimes' use a
substantial use of health care resources. Is there any evidence available in the
form of published papers which could be referenced here to back up this
statement? For what proportion of severe IBS patients are costs and resource
use generally high and if there is some variation in treattment patterns, resource
use and costs why is this the case? The authors should also highlight that an
economic model to extrapolate long term costs and effects would also be helpful
in more clearly demonstrating the cost effectiveness or otherwise of acupunctire
for this group of severe IBS patients since the utilisation of health care resources
over the long term could then be incorporated directly into the economic
modelling approach and accounted for in the economic analysis.
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-12-148 (2012)

Reviewer's report
Title:Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia,
phosphorylation of NMDA receptors, and cytokines expression in the thoracic
spinal dorsal horn
Version: 1Date:17 May 2012
Reviewer: Nian-Song NSQ Qian
Reviewer's report:
Minor Essential Revisions
In this study, Feng et al observed that intrathecal injection of Resolvin D1 could
dose-dependently attenuate pain of CP. They also showed that intrathecal
injection of RvD could remarkably reverse NMDA receptor phosphorylation and
cytokine expressions in the spinal dorsal horn of CP rats. The present study is a
These findings are interesting and important and may provide new insights into
mechanism and treatment of pain in patients of chronic pancreatitis. The
methods are appropriately described, the experiments are well designed, and the
data is sound and convincing. The discussion and conclusions are well balanced
and adequately supported by the data. However, there are a few errors in
grammar and spelling that need to be corrected. Figure 3 and 4 Legends: Please
provide more explanatory information in the legend.
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-12-148 (2012)

Reviewer's report
Title:Resolvin D1 reverses chronic pancreatitis-induced mechanical allodynia,
phosphorylation of NMDA receptors, and cytokines expression in the thoracic
spinal dorsal horn
Version: 2Date:1 August 2012
Reviewer: Ihsan Ekin Demir
Reviewer's report:
In the revised version of their manuscript, Feng et al. extended their study by
additional experiments related to the role of resolvin D1 in pain-associated
behavior in chronic pancreatitis (CP). Here they observed that resolvin-D1
(RvD1) did not affect the behavior of animals in open-field and the elevated plus
maze tests. Additionally, they showed that RvD1 treatment significantly
suppressed the secretion of pro-inflammatory cytokines in the spinal cord of rats.
Overall, the study benefited significantly from these revisions. I have a single
major comment related to the current version of the study.
Major Compulsory Revisions
1) Pain continues to be an enigma not only in CP but in numerous neuropathic
pain disorders, and understanding its exact mechanism of generation bears
major importance. In the presence of several studies reporting on the beneficial
impact of several therapeutic agents on CP-related pain, it remains important to
demonstrate the cells upon which these agents act. Therefore, in my view,
showing this cell type by e.g. double immunolabeling as suggested before would
confer the study a very high quality. In particular, the authors should make use 1)
of a neuronal marker, 2) of a microglial marker, and 3) of an astrocyte marker to
show the site of RvD1 action.
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.
Review for 10.1186/1471-230X-12-145 (2012)

Reviewer's report
Title:Effects of coffee, smoking, and alcohol on liver function tests : a
comprehensive cross-sectional study
Version: 1Date:18 July 2012
Reviewer: Neal D Freedman
Reviewer's report:
The authors examine associations between coffee, smoking, and alcohol use
with liver function tests in 500 Korean health check examinees. Although these
exposures have been examined before, less information is available in Asian
populations and thus the current results are of interest.
Major Compulsory Revisions:
1. Statistical analysis methods, paragraph 1—rather than performing chi-square
tests for categorical variables, the authors should perform tests for trend (for
table 1 and 2)
2. Did the authors have complete information on all exposures, was there any
missing information and if so, how was it treated.
3. Although the prevalence of hepatitis was low, were results similar if the
patients testing positive were excluded?
4. In addition, 45% of the eligible examinees refused to participate in the study
which could affect the generalizability of the results. This should be mentioned as
a limitation.
Minor Essential Revisions:
1. Discussion paragraph 2—c-reactive protein and total protein are very different
exposures such that they should not be considered on the same causal pathway.
2. The authors do not describe the proportion of instant and brewed coffee
consistently. In paragraph 1 of the results section, the authors state that 57.8% of
participants preferred instant coffee and 48.0% preferred brewed coffee.
Whereas in the last paragraph of the discussion, they state that 81% of
participants drank instant coffee. In Table 1, it looks like about 57.8% drank
purely instant and 8% drank instant and brewed coffee. The results should be
presented in a consistent way.
3. Instead of individual studies, the authors should cite one of the meta-analyses
of coffee and liver cancer (introduction paragraph 2).
4. Please specify what the p-value is testing in tables 1 and 2. For table 1, is it
the comparison between men and women?
5. Did the authors have information about decaffeinated or caffeinated coffee? If
not, this should be added as a limitation.
Discretionary Revisions:
1. Did the authors have information on tea consumption? This would be an
interesting addition as few studies of liver enzymes have been conducted in
heavy tea drinking populations.
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:
I declare that I have no competing interests.
Review for 10.1186/1471-230X-12-145 (2012)

Reviewer's report
Title:Effects of coffee, smoking, and alcohol on liver function tests : a
comprehensive cross-sectional study
Version: 1Date:5 August 2012
Reviewer: Valentina Medici
Reviewer's report:
Jang et al. conducted a cross-sectional study on 500 subjects who responded to
a self-administered questionnaire about their alcohol and coffee drinking and
smoking habits. In addition, BMI was calculated and subjects underwent
abdominal ultrasound for determination of presence of fatty liver and blood tests
for measurement of serum total cholesterol, total protein, serum albumin, alkaline
phosphatase, total bilirubin, AST, ALT, and GGT.
Coffee drinking was associated with lower total serum protein, albumin, and AST.
Smoking was associated with higher GGT and lower serum protein, whereas
alcohol drinking was associated with higher GGT.
Major critiques:
1) the study provides some useful information but overall it lacks of originality. In
addition, the finding of inverse correlation between coffee drinking and serum
protein and albumin levels is unexpected and the authors do not have a
convining explanation for their findings. This result in particular is concerning for
selection bias where potentially coffee drinkers were also drinking more alcohol
and may had lower serum protein levels.
2) The definition used for heavy and non-heavy drinking is very questionable.
The authors included among non-heavy drinkers men all subjects with alcohol
consumption of < 60 grams/daily. Given that one alcoholic drink is 14 grams of
alcohol, the non-heavy drinkers men included subjects who were drinking 3-4
drinks/day which is already classified as heavy drinking. This most likely
represents a major confounder. The authors should perform a new analysis with
a new classification of drinkers.
Minor essential revisions:
The authors definition of “liver function tests” is questionable. In the background,
they say that LFTs consist of total cholesterol, total protein, albumin, ALP, total
bilirubin, AST, ALT, and GGT. It would be more appropriate to consider protein
and albumin, liver function tests. AST, ALT, and ALP are liver enzymes. There
are no data on INR which would have been a useful information among other
liver function tests.
Level of interest: An article of limited interest
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-12-147 (2012)

Reviewer's report
Title:Keratin 8 variants and prognosis of patients with alcoholic cirrhosis
Version: 1Date:14 August 2012
Reviewer: Johannes Haybaeck
Reviewer's report:
Review for BMC Gastroenterology
Manuscript entitled: "Keratin 8 variants and prognosis of patients with alcoholic
cirrhosis"
Dear colleague,
it was interesting to review the article entitled "Keratin 8 variants and prognosis of
patients with alcoholic cirrhosis" by Valentyn Usachov et al. There the authors
aimed at analyzing the prognostic impact of K8 variants. They basically found
negative results. As the work was conducted in an accurate and logical manner
these data are important, and are another puzzle stone for the understanding of
intermediate filament biology, liver integrity and hepatic physiology.
Overall the study was thoroughly designed and conducted. The questions raised
by the authors are relevant and therefore this nice piece of work is appropriate
for publication in BMC Gastroenterology. Only maybe the title could be a bit more
informative providing information about the results.
Level of interest: An exceptional article
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-12-147 (2012)

Reviewer's report
Title:Keratin 8 variants and prognosis of patients with alcoholic cirrhosis
Version: 1Date:3 September 2012
Reviewer: TREPO Eric
Reviewer's report:
In this manuscript the authors study the association between various K8 variants
and the presence of HCC as well as mortality. They report that none of these
variants have significant impact regarding these outcomes. The topic is
interesting and relevant, considering the role of keratins in various liver diseases.
The manuscript is also well written. My comments are as follows:
I) Major comment:
Although this work is interesting and the analyses clearly performed, the authors
do not distinctly state its limits which should be stated in the Discussion section.
Thus, in genetic association studies a replication cohort is strongly recommended
to exclude false negative/positive results. Moreover, since the results reported
are negative and the frequency of the mutated variants low, the authors should
calculate the power of the analyses with respect to the mains outcomes (HCC
and mortality).
Furthermore, a SUGESTION to overcome this limitation could be to genotype the
cohort for a “positive control” that already showed a reproducible association with
HCC in various cohorts (e.g. PNPLA3 rs738409 C>G).
II) Minor comments:
a) Please correct the sentence which claims that “14 patients harbored
amino-acid-altering K8 variants” when the sum of variants (in brackets) is 13.
b) The objectives of the study at the end of the introduction section are
confusing. I suggest that the authors clearly outline the primary (presence of
HCC) and secondary (mortality) aims.
c) In Table 2, please replace the word mRNA by DNA or cDNA.
d) I suggest the authors suppress from the Abstract, the sentence claiming that
K8 R341H variant may predispose to non-HCC-related liver mortality. Indeed,
this does not take into account multiple testing corrections and is invalidated by
log-rank analysis.
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-12-146 (2012)

Reviewer's report
Title:Clinicopathological characteristics of high expression of Bmi-1 in
esophageal adenocarcinoma and squamous cell carcinoma
Version: 3Date:31 July 2012
Reviewer: Reuben Kim
Reviewer's report:
Minor essential revisions
In this manuscript entitled, “Clinicopathological characteristics of high expression
of Bmi-1 in esophageal adenocarcinoma and squamous cell carcinoma,” Choy et
al. examined the correlation between the expression of Bmi-1 in esophageal
cancers and clinicopathological parameters. From this study, they conclude that
Bmi-1 expression positively correlates with different histological grades of
esophageal tissues from normal to cancers. The authors ruled out Bmi-1
amplification as a reason form the high expression of Bmi-1 in tissues. From the
study, the authors concluded that Bmi-1 may play an important role in early
carcinogenesis in esophageal adenocarcinoma. The current study is interesting,
and the results were supported by the findings. However, prior to publication
consideration in GMC Gasteroenterology, the manuscript needs grammatical
corrections.
Major Issues
1) There are typos in the Abstract; “Bmi-1” is either spelled as “Bmil-1” or
“BMI-1.”
2) All the references should come before the period. For example, not “.[1,2]” but
“[1,2].”
3) In method section, “5-µ” should be “5 µm.”
4) Please include the reference for “Dulak et al.”
5) When scoring IHC, the authors did not count the cytoplasmic staining patterns
for Bmi-1. Cytoplasmic staining of Bmi-1 on tissue sections was frequently noted.
Therefore, authors should include rationale as to why cytoplasmic staining was
not counted. Authors should consider citing Cohen et al., MCB, 1996.
6) It is recommended to put the results of multivariate survival analysis of clinical
covariates including p values in the table form.
Minor issues
1) Any reasons to leave blank columns in the Table 1 and Table 2?
Level of interest: An article of importance in its field
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-12-146 (2012)

Reviewer's report
Title:Clinicopathological characteristics of high expression of Bmi-1 in
esophageal adenocarcinoma and squamous cell carcinoma
Version: 3Date:14 August 2012
Reviewer: Huamin Wang
Reviewer's report:
Minor Essential 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-12-144 (2012)

Reviewer's report
Title:The Optimal Screening Interval for Gastric Cancer using
Esophago-gastro-duodenoscopy in Japan
Version: 1Date:19 April 2012
Reviewer: Kenneth E.L. McColl
Reviewer's report:
More information is required concerning the exact protocol for the endoscopies.
Major Compulsory Revisions:
1. Did each patient have an annual endoscopy over the five year period? Were
any lost to follow-up? If so details of that are required. If a patient was found to
have gastric cancer were they then removed from further annual follow-up?
2. Further details are also required regarding the stage of each cancer
diagnosed.
3. Had any of the patients had an endoscopy before they were entered into this
endoscopy screening protocol?
4. Surely the stage and curability of the cancer detected is more important than
the actual incidence? This should be discussed.
5. The most important risk factor for the development of gastric cancer is atrophic
gastritis. Information is required concerning the presence and severity of
histological atrophy of both the antral and body mucosa and relationship between
that and the subsequent risk of gastric cancer.
6. When determining the frequency of screening for gastric cancer it is surely
important to take into account the influence of atrophic gastritis.
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-12-144 (2012)

Reviewer's report
Title:The Optimal Screening Interval for Gastric Cancer using
Esophago-gastro-duodenoscopy in Japan
Version: 2Date:27 September 2012
Reviewer: Kenneth E.L. McColl
Reviewer's report:
nil
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.
Review for 10.1186/1471-230X-12-143 (2012)

Reviewer's report
Title:Nrf2-mediated heme oxygenase-1 induction of PPI confers adaptive
survival response to NSAID-induced gastric damages
Version: 1Date:22 June 2012
Reviewer: Tomohisa Takagi
Reviewer's report:
In this manuscript by Lee HJ and his/her co-workers, it has been demonstrated
that pantoprazole prevented NSAID-induced gastric injuries through the
expression of HO-1, independent of its acid suppression. This basic research has
abundant persuasive data, and was very interesting for most of
gastroenterologists. I hope that the authors revise this manuscript as following
comments, and plan the clinical investigation in near future.
Major
1, In your paper, the mechanism that ZnPPIX inhibited the expression of HO-1
induced by pantoprazole (Figure 3.) remains unclear. The authors should discuss
this issue.
2, In Figure 4B, IL-1 expression was faint in the group treated with indomethacin
(500µM) plus pantoprazole (100µM) plus ZnPPIX (50µM). The author should
discuss the reason why.
3, In Figure 4B, NOX-1 expression was inhibited by treatment with pantoprazole.
Why?
4, Figure 4D is absent (p. 10).
Minor
1, This paper has many wrong spells. The authors should revise more carefully.
p1, 300 M >>>> 300 µM
p2, 500 M >>>> 500 µM
TNF- >>>> TNF-# ……..
2, p8 Figure 2B >>>>> Figure 2E?
Figure 2A >>>>>>> Figure 3A?
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-12-143 (2012)

Reviewer's report
Title:Nrf2-mediated heme oxygenase-1 induction of PPI confers adaptive
survival response to NSAID-induced gastric damages
Version: 1Date:30 June 2012
Reviewer: Kazuhide Higuchi
Reviewer's report:
The author reported that pantoprazole can protect stomach against
NSAIDs-induced damages by not only acid suppression but also Nrf2-driven
HO-1 induction which occurs the improvement of NSAIDs-induced ischemia,
attenuation of adhesion molecule, and decreasing inflammatory mediators. This
study is interest. In vitro angiogenesis assay, the author reported that
pantoprazole increase expression of angiogenic factors and activate
NSAIDs-induced angiogenesis. However, there are some problems.
Comments to the author
Major
(1) The author reported that pantoprazole improve NSAIDs-induced ischemia.
However, in this study, although pantoprazole increase expression of angiogenic
factors and activate NSAIDs-induced angiogenesis, it is not enough persuasive
to conclude that pantoprazole improve the ischemia. The authors should discuss
about this point.
(2) In Figure2A, the author demonstrated that Western blots for either cytosolic
keap1 or nuclear Nfr2 in a different time in the presence of 300 M pantoprazole.
However, the author did not describe whether the lower concentration of
pantoprazole could increase cytosolic keap1 and nuclear Nfr2 or not.
(3) Figure4 and Figure5 showed that indomethacin alone did not increase the
expression of HO-1. However, indomethacin induced inflammation. Some reports
found that indomethacin increased the expression of HO-1. The authors should
discuss about this point.
(4) Figure4 and Figure5 showed that ZnPP# decreased the expression of HO-1. I
think that ZnPP# inhibit only activity of HO-1. Can ZnPP# decrease the
expression of HO-1?
(5) Figure3C showed that pantoprazole increased the expression of HIF-1.
However, Figure5 showed that pantoprazole decreased HIF-1-#-DNA binding. It
seems contradictory.
(6) The authors think all PPIs may induce HO-1 from the discussion. However,
Yoda et al. (J Physiol Pharmacol. 2010 Jun;61(3):287-94) reported that
lansoprazole, but not omeprazole, induced HO-1. The authors should refer this
paper and discuss about this point.
Minor
(1) There is Figure2E which show the change of DCF-DA fluorescence after
different dosing of pantoprazole. However, in Figure legend, there is no
description of Figure2E. Is Figure2E the part of Figure2D?
(2) In p.8 l.23, the author described “PPI also increased expression of VEGF,
mRNA and protein levels(Figure2A) in RGM-1 gastric mucosal cells.” However,
not Figuer2A but Figure3A showed the expression of VEGF.
(3) In p.9 l.16-18, the author described “Additionally indomethacin challenge
significantly increased the expressions of NADPH oxidase-1(NOX-1) as seen in
Fig.4B”. However, Weston blotting of NOX-1 is shown in Figure4A.
(4) In p.10 l.16, the author described “ICAL-1”. Is it mistake?
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.
Review for 10.1186/1471-230X-12-143 (2012)

Reviewer's report
Title:A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation
in protective effect of the proton pump inhibitor pantoprazole against
indomethacin-induced gastric damage in rats
Version: 2Date:5 August 2012
Reviewer: Tomohisa Takagi
Reviewer's report:
I re-reviewed your revised manuscript. This paper was well revised along with
our comments. In future, I hope that the authors would elucidate the importance
of HO-1 signal by pantoprazole in human gastric mucosa in human clinical trials.
Level of interest: An exceptional article
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-12-143 (2012)

Reviewer's report
Title:A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation
in protective effect of the proton pump inhibitor pantoprazole against
indomethacin-induced gastric damage in rats
Version: 2Date:20 August 2012
Reviewer: Kazuhide Higuchi
Reviewer's report:
none
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-12-143 (2012)

Reviewer's report
Title:A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation
in protective effect of the proton pump inhibitor pantoprazole against
indomethacin-induced gastric damage in rats
Version: 2Date:25 August 2012
Reviewer: Young-Joon Surh
Reviewer's report:
The revision has been done mostly well. The suggested tile is OK except:
A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in
protective effect of the proton pump inhibitor pantoprazole against
indomethacin-induced gastric damage in rats
-->
A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in the
protective effect of the proton pump inhibitor pantoprazole against
indomethacin-induced gastric damage in rats
(Add the word <the> before effect)
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.
Review for 10.1186/1471-230X-12-141 (2012)

Reviewer's report
Title:Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency: Prevalence
and SLC25A13 mutations among Thai Infants
Version: 1Date:14 September 2012
Reviewer: Osamu Sakamoto
Reviewer's report:
This article reported that the mutation spectrum of SLC25A13 in Thai NICCD,
comparison of clinical manifestations and blood chemistry between NICCD and
non-NICCD infants, and the prevalence of NICCD in Thai infants with idiopathic
cholestasis.
Mutation analysis was performed appropriately. The 851del4 mutation is most
common among patients of NICCD in Thai like as other Asian countries. And the
comparison of clinical manifestations and blood chemistry between NICCD and
non-NICCD infants was sensible.
Major Compulsory Revisions
1. As the authors said, there were limitations of the present study, especially,
using the panethnic incidence of infantile cholestasis for the estimation of the
prevalence of NICCD among Thai infants. Furthermore, because not all infants
with pathogenic SLC25A13 mutations on both alleles manifest NICCD
symptoms, the carrier frequency calculated based on the symptomatic patients
may be underestimated. So the carrier frequency should be obtained by the
mutation analysis of control subjects.
2. The authors showed p.M1T was found 3 among 100. That means the carrier
frequency is 3/100 (if p.M1T is pathogenic). The authors should comment the
discrepancy between the carrier frequency (1/110) by reverse calculation based
on Hardy-Weinberg equation and the other one (3/100) by population analysis.
Minor Essential Revisions
3. (Page 9, lines 14-16) Coagulopathy, galactosuria and hypoglycemia were
remarkable observed among NICCD patients but not in the suspected NICCD
infants.
Is the sentence `suspected NICCD’right? (non-NICCD ?)
4. (Table1) `p.R605Q5?’is wrong. (p.R605Q).
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-12-142 (2012)

Reviewer's report
Title:Sleep problems and functional disability in children with functional
gastrointestinal disorders: An examination of the potential mediating effects of
physical and emotional symptoms
Version: 1Date:10 August 2012
Reviewer: Christine Chambers
Reviewer's report:
This paper describes the results of a study examining sleep disturbances among
a large sample of children aged 8-17 years with functional gastrointestinal
disorders (FGIDs). Questionnaire measures of sleep, emotional functioning,
physical symptoms and functional disability were completed by children and/or
caregivers. The children were diagnosed with an FGID by a gastroenterologist.
Given the reliance of the current study on self-report of sleep (in the absence of
any objective sleep measure, such as actigraphy), and the fact that other studies
examining sleep in children (using questionnaires) and chronic pain, including
recurrent abdominal pain have already been published, I was initially expecting
not to be overly excited about this paper and its contribution. However, the paper
is so well written and presented, and the data analysis (structural equation
modeling) so sophisticated and well described that I felt very positively about the
work after reading the paper.
I have only a few minor comments about the paper, all of which I would classify
(as requested by the journal) as Minor Essential or Discretionary Revisions
It appears the authors examined sex (rather than gender) differences yet they
use the term gender. The authors should be careful regarding their language use
in the presentation of sex vs. gender differences.
Is there any evidence for the reliability of the specific FGID diagnosis?
The authors provide good evidence in support of their selection of the Sleep
Disturbance Scale for Children but they might wish to justify why they did not
select the other popular measure of sleep disturbances in children (the Children’s
Sleep Habits Questionnaire by Owens; presumably because of the age range of
their sample?).
When discussing their finding of approximately half of their sample having sleep
disturbances, the authors should note how common sleep disturbances are in
healthy children with no other clinical issues.
The additional limitation of the lack of a control group of healthy children without
FGID should also be noted in the limitations section of the Discussion.
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 conflicts.
Review for 10.1186/1471-230X-12-142 (2012)

Reviewer's report
Title:Sleep problems and functional disability in children with functional
gastrointestinal disorders: An examination of the potential mediating effects of
physical and emotional symptoms
Version: 1Date:10 August 2012
Reviewer: Rona Levy
Reviewer's report:
1. This is a very interesting study and the main message in the study, the
potential impact of sleep to the FGIDs, is one that pediatric gastroenterologists
should receive.
2. The paper would be enhanced by some information on normative data for this
population - ie what is the level of sleep disturbance in groups of children without
chronic disease in this age range.
3. The last paragraph is a little unclear: "results from this study seem to suggest
that intervening with emotional symptoms may not be the most direct pathway to
improving daily function in children with FGIDs. Instead, both sleep problems and
physical symptoms could be appropriate". How would a practitioner address
sleep problems without dealing with emotional problems such as anxiety?
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-12-139 (2012)

Reviewer's report
Title:Effects and Outcomes of Interferon Treatment in Japanese Hepatitis C
Patients
Version: 1Date:18 July 2012
Reviewer: Takafumi Saito
Reviewer's report:
Yamasaki et al. reported a long-term cohort study of HCV infection that was
carried out in small islands of Japan. In this manuscript, they have shown the
interventional effect of IFN therapy to HCV on the survival rate, irrespective of
viral response to this therapy. The findings of this paper are valuable, but several
points need to be addressed.
1. The study was carried out in the area endemic for HCV infection, where the
positivity rate of anti-HCV antibody was 7.6 %. The case of acute HCV infection
might have been included in the subjects. No information of liver histology has
been shown in 446 cases of hepatitis C in Table 1. Please put histological data in
this table to make clear whether all subjects had findings of chronic hepatitis.
2. HCV infection is involved in many extrahepatic conditions, particularly heart
disease or hematological malignancy may relate to the death. Please state “other
causes” of death in the text.
3. Fig.5 is complicated. Grouping looks a mismatch between the graph and
patients at risk . What is Group C (Fig.5B) ?
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-12-140 (2012)

Reviewer's report
Title:Esophageal peristaltic dysfunction in asthma is likely to be secondary to
increased gastro-esophageal reflux.
Version: 2Date:18 March 2012
Reviewer: Reginald V. Lord
Reviewer's report:
Review of “Esophageal peristaltic dysfunction in asthma is likely to be secondary
to increased gastro-esophageal reflux” by D Lakmali Amarasiri et al.
The study is well conducted and the manuscript is very well written. The
Discussion section is comprehensive. The study is not especially novel, as it is
well known that asthmatics have a high prevalence of GERD, esophageal
dysmotility, and hypervagal response. It may be wondered whether the
bronchospasm in some of the patients in this series did not have GERD as their
primary pathology, with the asthma secondary to reflux. This could be discussed
by the authors.
Were the control patients significantly different in terms of age, sex? Younger
individuals are less likely to have GERD and it can be tempting to enrol the
medical students etc. for these studies.
The rate of equipment failure during the esophageal manometry studies is high –
11 patients or individuals.
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.
Review for 10.1186/1471-230X-12-138 (2012)

Reviewer's report
Title:The role of aspirin in post-polypectomy bleeding a retrospective survey
Version: 2Date:26 March 2012
Reviewer: Lukejohn Day
Reviewer's report:
1. What are the characteristics of the participating hospitals? Volume of
colonoscopies performed?
2. Does the authors’ endoscopy unit follow a protocol for patients taking ASA or
NSAIDs (similar to the one described for Coumadin)? Or is is physician
dependent?
3. Could patients obtain healthcare at other hospitals outside of the ones
included in the study? For example if a patient developed symptoms of a LGIB
could they have sought care at other institutions that were not captured in the
study.
4. What predictors were examined to see if they were associated with
post-polypectomy bleeding?
5. What was the distribution of common indications for colonoscopy among the
study population?
6. Table 2 could be eliminated
7. A table looking at all of the examined factors associated with post-polypectomy
bleeding should be included.
8. Do we know the outcomes of the patients who had a post-polypectomy bleed?
For example, length of hospitalization, transfusion requirement, deaths. Also a
comparison of outcomes from post-polypectomy bleeding of ASA and non-ASA
patients would be very useful data.
9. Were comorbid medical conditions of the study population examined as a
predictor of bleeding? Some studies suggest that increased comorbidity
increases the risk for post-polypectomy bleeding.
10. Did the authors look at specific dosing of ASA to see if this was associated
with increased rates of post-polypectomy bleeding?
11. The authors focus a significant amount on primary and secondary prevention
with respect to ASA and cardiovascular disease in the discussion, this could be
shortened.
12. A number of studies have suggested that ASA does not increase the rate of
post-polypectomy bleeding (Yousfi et al; Am J Gastroenterol. 2004
Sep;99(9):1785-9 and Hui et al; Gastrointest Endosc. 2004 Jan;59(1):44-8).
These articles (and how the current study is different or improves upon them)
should be discussed.
13. Another limitation is that patients may have sought care elsewhere for their
post-polypectomy bleed thereby underestimating the effect of bleeding. This
should be discussed.
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:
None