JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/1471-230X-10-108 (2010)

Reviewer's report
Title:Differences in gut microbial metabolism are responsible for reduced
hippurate synthesis in Crohn's disease.
Version: 1Date:22 August 2010
Reviewer: Harry Sokol
Reviewer's report:
The study by Williams et al. aimed to assess the baseline and peak urinary
hippurate excretion in Crohn’s disease patients compared to healthy subjects.
Hippuric acid is an interesting metabolite to study as its production is a result of
the combined action of the gut microbiota and the host. Bacteria of the gut
microbiota degrade dietary aromatic compounds in benzoate. Hippurate is the
product of the conjugation of benzoate with glycine by the host. If benzoate from
alimentation is excluded, urinary hippurate excretion can thus be seen as a
marker of gut microbiota function (admitting that the host conjugation step is
conserved). As the gut microbiota is known to have a major role in Crohn’s
disease pathogenesis, analysis of urinary hippurate excretion is relevant.
The paper is well written, the measuring method used is accurate and the results
are clearly presented. The authors showed that baseline urinary hippurate
excretion is decreased in Crohn’s disease patients compared to healthy subjects
(which is already known and published). This study demonstrate that patients
with CD do not have an intrinsic (host) defect in conjugation of benzoate with
glycine underlying the fact that the decrease in hippurate excretion in CD patients
is due to alteration in the gut microbiota function.
Minor Essential Revisions
- The weakness of this paper is the lack of analysis of the gut microbiota
composition in the studied patients. Correlation between dysbiosis and baseline
urinary hippurate excretion would be interesting.
- Although only descriptive, this study is useful as it points out a functional
consequence of the dysbiosis in CD. This point should be mentioned in 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:
I declare that I have no competing interests
Review for 10.1186/1471-230X-10-108 (2010)

Reviewer's report
Title:Differences in gut microbial metabolism are responsible for reduced
hippurate synthesis in Crohn's disease.
Version: 1Date:31 August 2010
Reviewer: Carolyn Slupsky
Reviewer's report:
The manuscript entitled “Differences in gut microbial metabolism are responsible
for reduced hippurate synthesis in Crohn’s disease” by Williams et al. is a
manuscript that measures hippurate excretion in control and CD patients using
1H NMR spectroscopy before and after ingestion of benzoate while subjects are
on a low benzoate diet. After ingestion, the amount of hippurate in the urine of
the control group and the Crohn’s group was similar, with a larger increase in
hippurate in the Crohn’s group as compared to the control group. This was
attributed to the enzyme kinetics of the synthesis of hippurate in the liver and
kidney cells. Based on these results, the authors suggest that lower levels of
hippurate in Crohn's disease patients are due to altered gut microbial metabolism
rather than a defect in hippurate synthesis.
This is a well-written manuscript, and the experiments seem sound. I recommend
publication of this article as is.
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-10-108 (2010)

Reviewer's report
Title:Differences in gut microbial metabolism are responsible for reduced
hippurate synthesis in Crohn's disease.
Version: 2Date:6 September 2010
Reviewer: Harry Sokol
Reviewer's report:
OK 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-10-109 (2010)

Reviewer's report
Title:Duodenal carcinoma at the ligament of Treitz. A molecular and clinical
perspective.
Version: 1Date:14 June 2010
Reviewer: Patrick G Brady
Reviewer's report:
Minor Essential Revisions:
1.In the background, it should be mentioned that familial adenomatosis polyposis
(FAP) is associated with carcinoma of the duodenum. Although this is most
common in the second portion of the duodenum, it can aslo occur in the third and
fourth portions of the dudoenum. Gardner's syndrome is mentioned in the last
sentence of page 3 as a hereditary syndrome that increases the risk of small
bowel neoplasm. Gardner's syndrome is a variant of FAP.
2. On page 14 mutations in the APC gene are discussed. Duodenal carcinoma is
the second most common carcinoma in FAP. Thus the comments regarding the
low rate of APC mutations in duodenal adenocarcinoma refer primarily to
sporadic adenocarcinomas and not those associated with FAP and its variants.
3.Patients with duodenal adenomas and carcinomas have and increased risk of
colonic neoplasms. The case presentation illustrates this since the patient had
several colonic adenomas. Current recommendations call for colonoscopy in all
patients with duodenal adenomas and carcinomas. This needs to be pointed out
in the disscussion.
4. Celiac disease is another disorder assciated with an increased risk of small
bowel, including duodenal, carcinoma. This should be noted in the background
section.
5.On page 10, double balloon enteroscopy is discussed. Single balloon
enteroscopy is not mentioned. Since single balloon enteroscopy is an alternative
to double balloon enteroscopy with comparable success rates and yields, it
should be mentioned in the discussion. The term "balloon assisted enteroscopy"
can be applied to both techniques.
Discretionary Revisions:
Either figure 1 or figure 2 can be used, but both are not necessary.
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-10-109 (2010)

Reviewer's report
Title:Duodenal carcinoma at the ligament of Treitz. A molecular and clinical
perspective.
Version: 1Date:2 July 2010
Reviewer: Adriana Safatle-Ribeiro
Reviewer's report:
This is a case report and a review of the literature about carcinoma of the
duodenum and how important is to make the early diagnosis of such lesion.
However, this case cleared demonstrated the delayed diagnosis due to the lack
of clinical suspicion. Nowadays, obscure GI bleeding is a formerly indication for
an investigation through capsule endoscopy and balloon assisted enteroscopy
(DBE or SBE).
Despite of an extensive review of the literature into the discussion, about double
balloon endoscopy and radiologic tests, the authors did not indicate them to the
specific case. Fortunately, the lesion could be reached by push-enteroscopy.
Additionally, the genetic markers discussed were not analyzed by the authors
(except EGFR, which was negative). Maybe, the authors could study other
markers, since the patient presents adenomas in the colon. Please, comment.
The authors did not mention the type of reconstruction and if the patient received
or not adjuvant treatment. Please discuss.
The discussion is too long and should be reduced, as well as the number of
references.
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-10-107 (2010)

Reviewer's report
Title:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 1Date:23 February 2010
Reviewer: Christina Haston
Reviewer's report:
In this manuscript De Lisle et al. evaluate the effect of lubiprostone treatment on
the intestinal phenotype of cystic fibrosis mice. The data are new and largely
clearly presented but two main limitations, the lack of cell physiology data, and
the n=1 sample number for the array data which negates a significance
determination, need to be addressed.
Major compulsory revisions
1. introduction. References are needed to substantiate statements in the first
paragraph, and the assertion that "Various novel approaches that correct mutant
CFTR function, or activate alternate electrolyte secretory mechanisms are under
investigation." The references for the CF phenotype being similar in patients and
mice are all to mice. References to clinical data are needed here.
2. The effect of lubiprostone on CLC2 is hypothesized but not evaluated. The
hypothesis actually tested should be indicated or the effect on CLC2 function in
the intestines of treated mice assessed.
3. Preliminary experiments showed that a dose of 10 µg/kg-day was maximally
effective (data not shown). What effect was maximal at this dose?
4. In figure 1 the comparison tested is not clear. What is the weight of CF mice
on peptamen alone, for comparison? Why is CF mouse weight gain compared to
WT?
5. The effect of the intervention on mucous accumulation is modest, at best,
within the CF mice. What is the p value comparing the distribution of lubiprostone
treated CF mice to that of CF controls in fig 3b? The analysis presented in fig 3C
should be statistically justified or removed.
6. What statistical test was applied to show the effect of lubiprostone treatment
on bacterial counts in CF mice? Is there literature support for this change as
physiologically relevant? Would such a change alter the intestinal distress in the
CF mouse?
7. Gene regulation was not assessed in this study so references to up/down
regulation in the Tables and text should be corrected. How were functions listed
in table determined? The table notes should indicate n=1.
8. A more complete description of the RT experiment is needed. Are the data
technical replicates of the chip result? If yes, the chip result should be removed
as the more valid data are from the RT experiment.
9. That Mcpt2 is increased in CF and decreased by treatment is not enough data
to support an effect on the innate immune response. This conclusion should be
justified with more data or removed.
Minor:
1. Mouse strain…C57BL/6J is stated in abstract, not methods.
2. The effects of lubiprostone on body weight gain was assessed. Grammatical
change needed.
3. page 14, drug name misspelled.
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-10-107 (2010)

Reviewer's report
Title:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 2Date:9 July 2010
Reviewer: Christina Haston
Reviewer's report:
No further comment
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-10-107 (2010)

Reviewer's report
Title:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 2Date:20 July 2010
Reviewer: Jonathan Kaunitz
Reviewer's report:
Comment:
The authors have revised the manuscript somewhat by adding some of the
citations suggested by the reviewers. Nevertheless, many of the reviewers'
comments have not yet been answered satisfactorily.
Major Compulsory Revisions
1. As Dr. De Jonge stated in his review, the main intestinal phenotype of CFTR
-/- mice is intestinal obstruction and decreased survival. The phenotypic changes
reported by the authors, such as bacterial overgrowth and delayed intestinal
transit although present, are less well characterized.
2. Although the literature is divided about the mechanism of action of
lubiprostone with regard to intestinal anion secretion, the preponderance of the
data strongly favors lubiprostone acting as a local prostaglandin that activates
CFTR in most cases. I am aware of few in situ data obtained from intact
organisms that support the alternative explanation.
3. The authors make several statements stating that lubiprostone "may" increase
bicarbonate secretion, even this was clearly shown in rats in ref. 20.
4. The authors use rhoadmine dextran to measure intestinal transit. Although the
authors state that it is a "nondigestible, nonabsorbable tracer", dextran is
fermented by colonic flora into butyrate (Olano-Martin E, Mountzouris KC, Gibson
GR, Rastall RA. In vitro fermentability of dextran, oligodextran and maltodextrin
by human gut bacteria. Br J Nutr. 2000 83:247-55). Given the marked differences
of intestinal bacterial colonization between the groups, would the use of this
marker add artifact to the measurements?
5. The authors speculate that some of their findings may be due to changes in
the hydration status of mucus. Yet, mucus in biological systems in considered to
be 99% hydrated. If the authors area aware of intestinal mucus in healthy living
animals that is not fully hydrated, these data should be cited.
6. Since the authors did not measure immune cell function but rather reported
expression changes of immune-function related genes, I reiterate my prior
comment that the data should not be reported as the "innate immune response"
or equivalent. Lacking direct measurements of mast cell migration or actual
measures of immune function, it is exceedingly difficult to interpret expression
changes of this nature.
7. The Discussion is overly long and speculative and would thus benefit from
deletion of many of its sections, despite the authors statements to the contrary.
Minor Essential Revisions
The authors should consider combining Figs. 2 and 3
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:
Yes, reserach support from Takeda NA.
Review for 10.1186/1471-230X-10-107 (2010)

Reviewer's report
Title:Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype
Version: 3Date:8 September 2010
Reviewer: Hugo De Jonge
Reviewer's report:
The author's reply to comments 1-3 of my re-review is satisfactory. With respect
to the author's answer to comment 1, it should be noted that ex vivo studies of
lubiprostone action in native mouse and human intestine, reporting a high
potency of lubiprostone in inducing CFTR activation via EP4-cAMP-PKA
signaling (EC50 of 50 nM; ref. 23), are clinically more relevant as compared to
studies in the A6 Xenopus kidney cell line, which might lack one ore more
components of this signal transduction pathway, such as EP4 receptors.
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-10-105 (2010)

Reviewer's report
Title:A case report of mesenteric mucinous cystoadenoma with review of the
literature.
Version: 2Date:4 June 2010
Reviewer: adriana handra-luca
Reviewer's report:
This is a report of a cystic lesion unusual by its location in the mesentery.
Major compulsory revisions are required in order to be included as one of the
categories (Instructions for Authors guidelines items 1-7) of case reports
accepted for publication in BMC Gastroenterology.
The authors should highlight the peculiarities of this case with regard to those
already reported in the literature.
Major Compulsory Revisions
The entire manuscript has to be modified in order to focus on the present case, in
order to outline its peculiarities.
The Reference format has to be according to the Instructions for Authors
guidelines.
The writing of the entire manuscript should be checked for medical English.
Minor Essential Revision
The preoperative clinical diagnosis should be added and the morphological
diagnosis should be detailed (presence /absence of ovarian-like stroma ;
immunohistochemistry)
Discretionary Revisions
Please see the comments.
Abstract Section
The Abstract can be unstructured, and can be written on the page following the
Title page.
Cystoadenoma » should be written correctly within the entire manuscript («
cystadenoma »). Paragraph/sentence 3: « Dimensional growth » can be replaced
by « size », and this sentence should be reformulated.
Paragraph/sentence: « Were » should be replaced by « was ».
Paragraph/sentence 6 « Conclusion »:
The peculiarities of this case should be mentioned. The words « story », « sense
» « confirm » are used inadequately.
Key Words Section
« Retropenitoneal » should be written correctly.
Background Section
Paragraph/sentence 5: This paragraph/sentence fits better in a discussion
subsection. The use of a Table already published, should be avoided; the
authors could add 1-2 sentences with the main findings noted in this table.
Case Presentation Section
Paragraph/sentence 2: « didn’t » could be written as « did not ».
The authors should add the preoperative, clinical diagnosis.
In the morphological description part, the authors should add data on the
presence/absence of the ovarian-like mesenchymal stroma, and if special stains
(Alcian blue) or immunohistochemical analysis was performed.
This section should include a discussion focused on the peculiarities of this case
(clinical, pathogenesis) as well as the new and original findings.
Conclusions Section
The authors should highlight the importance and relevance of this case.
The discussion of the pathogenesis should be noted in the Case presentation
section (eventually with a Discussion subheading).
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
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.
AHL
Review for 10.1186/1471-230X-10-105 (2010)

Reviewer's report
Title:A case report of mesenteric mucinous cystoadenoma with review of the
literature.
Version: 2Date:21 June 2010
Reviewer: Yu-Meng Tan
Reviewer's report:
This is a case report a rare type of tumour. The report is concise and includes
histological slides together with a review of the literature. It is informative on this
rare subject but the language needs minor revisions. A CT scan of the original
tumor may also be of interest.
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 I have no competing interest.
Review for 10.1186/1471-230X-10-105 (2010)

Reviewer's report
Title:A case report of mesenteric mucinous cystoadenoma with review of the
literature
Version: 4Date:17 August 2010
Reviewer: adriana handra-luca
Reviewer's report:
This is a report of a cystic lesion with unusual presentation: its mesenteric
location and the associated clinical features.
Major compulsory revisions are required although several changes according to
the previous review have been made.
Major Compulsory Revisions
The Conclusion section has to be brief; differential diagnosis and other
discussion detail should be noted in the Case Report/Discussion section.
The manuscript should be checked for medical English (terms and phrases).
The characteristics of this case should be compared to those of the already
reported case of mesenteric location (age, gender, etc). The authors have to be
more precise in what concerns the reference of the paper reporting this previous
case, since one of the peculiarities is the site of the cyst.
Minor Revisions
Page 2: the point at the end of the sentences has to be added (4th and last
sentence).
Page 3:
2nd sentence: the point at the end of the sentence should be added
Last paragraph: The authors can reformulate and indicate that the ultrasound
and colonoscopy features of the mass were concordant and, suggestive of “an
oval mass ///”. This sentence contains too many informations, it can be split into
several.
Page 4: The abbreviation “TC” has to be written uniformly within the entire
manuscript, and rather as “CT” (see page 6).
The precise pathology diagnosis, and the arguments which favor this diagnosis
(although lack of ovarian-like stroma) should be clearly stated at the end of the
pathology/immunohistochemistry description.
Page 5: After sentence 2, the authors can add that the patient was well after 2
years (information that is noted page 6, end of the Conclusion).
The pathogenesis paragraph should be simplified and shortened. The lack of
ovarian-like stroma should be discussed.
The discussion of differential diagnoses (last sentence on the page) is more
appropriate in the Case presentation/Discussion section.
Page 6: The Conclusion should be brief and avoid mixture with too many already
reported data.
References: the references should be written according to the Instructions for
Authors (no point at the end of the reference), the reference 5 should be checked
for the word “retroperitoneal”.
Page 8: The figure legends would be more comprehensible if organized as
complete sentences (subject, verb).
Level of interest: An article of limited interest
Quality of written English: Not suitable for publication unless extensively edited
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-10-106 (2010)

Reviewer's report
Title:Psychological stress and coeliac disease in childhood: a cohort study
Version: 3Date:17 September 2009
Reviewer: Per Farup
Reviewer's report:
The paper describes surveys in children aged 1 and 2.5 years with focus on
stress after birth. These children have been followed up and 73 children have
developed biopsy-verified CD. The hypothesis is that stress is associated with
CD because stress has been related to autoimmune diseases.
The paper is well written and easy to read.
Major compulsory revisions that should be clarified.
1. Why is the research question of interest? Has it any importance? Is it of
theoretical interest only, or has it any practical consequences? Previous studies
have shown that stress during pregnancy is unrelated to CD (published by the
same group in Scand J Gastroenterol in 2003), why should stress after birth have
other effects? Is the paper written only because data are available from the ABIS
project and information about CD could easily be retrieved based on the previous
publication?
2. Stress might be related to autoimmune disorders, but is CD an autoimmune
disorder? Immune mechanisms are for sure involved in CD, but I don’t think it is
an autoimmune disorder like rheumatic diseases. The immune disturbances
normalize when gluten is withdrawn from the diet.
3. The analyses have been performed with asymptotic methods using SPSS. I
doubt that the method is correct. In table II the number of subjects with CD was 1
in the group with “A serious life event”. Such a low number (1) makes the method
unreliable, and exact methods are preferable. I have remade the calculation in
table II, row 1 and the results with exact statistics are OR 0.45 (as reported in the
paper), but the 95% CI is 0.011-2.6, and p=0.71 (a marked difference). Please
ask for statistical expertise, I am not a statistician.
4. The study concludes that psychological stress is unlikely to be a risk factor for
CD in childhood. This is probably correct, but in a negative trial like this one, a
discussion of a type II error is mandatory. In table II – row one, the prevalence of
CD in children with and without a serious life event are 0.224% and 0.495%
respectively, which means that CD is 2.21 times more common in children
without a serious life event. The 95% CI for the ratio is 0.39-12.72 (calculated
with asymptotic methods since the authors use this method). These findings
mean that CD might be 12.7 times more prevalent in children without stress. Is
really a 12.7 times reduction or a 2.56 (1/0.39) times increase in children with a
serious life event without importance?
Minor compulsory revisions.
Page 8 and 12. Why is breastfeeding excluded from the analyses when
breastfeeding has been shown to influence the risk of CD; it seems to be based
only on some unpublished data? Could stress reduce breastfeeding?
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-10-106 (2010)

Reviewer's report
Title:Psychological stress and coeliac disease in childhood: a cohort study
Version: 3Date:25 November 2009
Reviewer: Daniel Leffler
Reviewer's report:
Thank you for allowing me to review the present study entitled: "psychological
stress and coeliac disease in childhood: a cohort study'. The concept that via
some affect on the immune system, early stress may precipitate the development
of autoimmune disease has been around for quite some time, though with limited
evidence. this study makes use of a large, well designed, prospectively collected
database on family stressors in the years after a child's birth.
This paper is well written, addresses a relevant topic and I really have no major
comments or suggestions.
One point that the authors may consider, although it may be beyond the scope of
this work, is the reverse of their hypothesis. E.g. Not just what is the effect of
family stress on the development of celiac disease, but what is the effect of the
development of celiac disease on subsequent family stress. I think this would be
a fruitful area to explore.
Minor comments: Second paragraph on page 7: 'tree' should be 'three'
first paragraph on page 8: CD at age... would be clearer if stated CD after age...
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-10-106 (2010)

Reviewer's report
Title:Psychological stress and coeliac disease in childhood: a cohort study
Version: 4Date:27 January 2010
Reviewer: Per Farup
Reviewer's report:
The response given by the authors is well written and to the point, but the
revision of the paper is not so extensive as I had expected.
1. The comments on a type 2 error are short and insignificant without any clear
estimation of differences that might have been missed (except for 95%CI) or
clinical significance of a type 2 error.
2. I still find it incorrect that data from another trial are used to exclude variables
from the analyses in this study, although it is a study based on the ABIS children
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-10-106 (2010)

Reviewer's report
Title:Psychological stress and coeliac disease in childhood: a cohort study
Version: 5Date:5 April 2010
Reviewer: Per Farup
Reviewer's report:
I do not have the previous version of the paper ahead of me, and do not find the
results I commented upon (95% CI for the ratio is 0.39 – 12.72) in the new
manuscript. The authors have probably performed new analyses.
I comment now only upon the OR and CI, Table 3 refers to a 95% CI 0.00-2.34.
An OR of 0 is nonsense. If you turn it around, the increased risk of CD in
non-exposed compared exposed, the OR is indefinite and the upper limit of the
95%CI is indefinite. This shows that the difference between non-exposed and
exposed might be enormous despite the fact that this study does not show a
significant difference.
Table 2 . Serious life event at age 1: Turn the table around and you see the
problem. The increased prevalence of CD in no serious life event compared with
a serious life event, OR = 2.22 with 95% CI 0.37 – 89.62. Your results show that
there might be a huge (enormous) difference in the prevalence between no
serious life event and a serious life event despite the fact that this study does not
show a significant difference.
It is correct that this study does not show a significant association between
psychological stress and CD, but does not exclude an enormous (indefinite)
association because of the small numbers of patients with CD. This has to be
discussed and mentioned also in the abstract.
This negative study is nearly valueless because it does not exclude an immense
effect of psychological stress on CD, and should not be published unless this is
made clear. Do the authors know what a type II error is? They mention that
“inappropriate reassurance to parents” is a type II error.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-10-106 (2010)

Reviewer's report
Title:Psychological stress and coeliac disease in childhood: a cohort study
Version: 6Date:10 August 2010
Reviewer: Ryan Lennon
Reviewer's report:
I believe the authors have responded appropriately to the reviewer. An odds ratio
confidence limit of zero is possible using exact methods when one group has
observed no events (as was the case here). Furthermore, the reviewer was quite
right to insist that the authors discuss and highlight the limited statistical power of
the study, as evidenced by the very wide confidence intervals. The authors have
appropriately added such statements in multiple places, including the abstract.
The study seems to be scientifically sound. The major issue with it is that the
confidence intervals are so wide, that we really have learned almost nothing
about the association between psychological stress and coeliac disease. It is one
thing to publish a negative study with narrow confidence intervals, such that
readers can be confident that whatever association exists, it must not be too
large. This negative study has not ruled out much. Still, as a negative study I
suppose it merits publication if only to show that the hypothesis was investigated.
I have no competing interests with regards to this article.
Sincerely,
Ryan Lennon
Declaration of competing interests:
I have no competing interests with regards to this article
Review for 10.1186/1471-230X-10-103 (2010)

Reviewer's report
Title:Comparison of ELF, FibroTest and FibroScan for the non-invasive
assessment of liver fibrosis
Version: 2Date:21 April 2010
Reviewer: Jing-Houng Wang
Reviewer's report:
General comments
The study by Friedrich-Rust et al. evaluated the diagnostic performances of
serum markers (FibroTest and ELF) and FibroScan in the diagnosis of significant
hepatic fibrosis or cirrhosis in a cohort of 74 patients with chronic viral hepatitis or
PBC. The study made a direct comparison among fibrosis markers and
FibroScan and concluded that there are comparable diagnostic accuracies
among indirect, direct fibrosis markers and FibroScan. The main limitation of this
study was small patient population with different etiologies of hepatic fibrosis,
which weakens the result and its conclusion.
Major comments
1. For clinical practice, it is favorable to have the diagnostic validity and yield for
each test. These data are available for chronic hepatitis C and PBC in previous
studies. The authors should give the information of cut-offs and their diagnostic
validities and yields in patients as a whole, patients with chronic hepatitis C and
PBC.
2. Combined use of various non-invasive tests might increase the diagnostic
accuracy. The authors could try to combine direct serum marker with indirect
serum marker or with FibroScan to increase the diagnosis of minor to moderate
hepatic fibrosis.
3. In the conclusion, the author stated that serum markers are informative in
higher proportions of patients than FibroScan. The conclusion was made due to
8 patients in the study population had unreliable results of FibroScan. To make
this conclusion, it should be cautious considering small study population without
prospectively consecutive enrollment.
Minor comment
1. The references should be arranged in the same format.
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Declaration of competing interests:
I declare that I have no competing interests
Review for 10.1186/1471-230X-10-103 (2010)

Reviewer's report
Title:Comparison of ELF, FibroTest and FibroScan for the non-invasive
assessment of liver fibrosis
Version: 4Date:30 August 2010
Reviewer: Mona Munteanu
Reviewer's report:
Accepted as it is without further 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 a competing interest as a BioPredictive employee.
Review for 10.1186/1471-230X-10-102 (2010)

Reviewer's report
Title:Lack of association between peroxisome proliferator-activated receptors
alpha and gamma2 polymorphisms and progressive liver damage in patients with
non-alcoholic fatty liver disease: a case control study
Version: 1Date:30 May 2010
Reviewer: Katsutoshi Tokushige
Reviewer's report:
This paper is interesting, suggesting that the PPAR alpha 162 Val allele was
associated with insulin resistance, but not with liver damage in NAFLD. However,
there are several problems.
Major
1.Some of NAFLD patients had diabetes mellitus (DM). If these patients receive
drug therapy against DM, HOMA-R value is influenced by drug. Please show the
therapy in these patients.
2.In control subjects, fasting insulin and glucose were measured. How is the
relationship between HOMA-R and PPAR alpha SNP in controls?
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-10-102 (2010)

Reviewer's report
Title:Lack of association between peroxisome proliferator-activated receptors
alpha and gamma2 polymorphisms and progressive liver damage in patients with
non-alcoholic fatty liver disease: a case control study
Version: 1Date:10 June 2010
Reviewer: Véronique Barbu
Reviewer's report:
The manuscript entitled « Lack of association between peroxisome
proliferator-activated receptors alpha and gamma2 polymorphisms and
progressive liver damage in patients with nonalcoholicfatty liver disease: a case
control study » by Paola Dongiovanni et al. presents data concerning the
association of 2 SNPs of peroxisome proliferator-activated receptors alpha
(PPAR# and PPAR#2 respectively with non alcoholic fatty liver disease (NAFLD).
For that purpose, the authors chose 2 well known SNPs: PPAR# (L162V) and
PPAR#2 (P12A). The study is a case- control search in an Italian population of
202 patients with biopsy proven NAFLD and 346 healthy controls. The negative
results obtained suggest that in such study, the limitation of the statistical power
is of importance. Therefore it is disappointed because of the relevance to run
such studies especially if the statistics failed because of the number of patients
included. It is often the case.
Major revisions:
The aim of the study is of poorly interest namely because this is a negative case
control association study. Moreover, if the question defined by the authors is
relevant (association with disease severity), the genetics methods used by the
authors are a little old, nowadays.
In 2007, real time PCR allowed to perform SNP genotyping with better sensitivity
than RFLP.
The statistics on demographic features of NAFLD versus controls showed
significative differences between the two populations except sex and age.
However limit significance was obtained from PPAR# (L162V) allele and HDL or
Homa-R.
Biopsies should be illustrated: interest in the quality of histological assessment.
Haplotypes studies may help to look at relevant associations in a case – control
study using these 2 genes PPAR# and PPAR#2. Moreover multivariate analysis
could be of interest.
Authors may have a better look of their NASH cohort if they test the whole genes
PPAR# and PPAR#2 and check all the SNPs that could be relevant in addition of
the 2 they had already tested.
Minor revisions:
Some Typographical errors:
…is considered as the hepatic manifestation…. 1st§ of Background
PPAR# downregulation is involved in NASH pathogenesis. 3rd§ of Background
Abbreviation of PNPLA3 should be explained
The writing of the manuscript is acceptable.
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-10-102 (2010)

Reviewer's report
Title:Lack of association between peroxisome proliferator-activated receptors
alpha and gamma2 polymorphisms and progressive liver damage in patients with
non-alcoholic fatty liver disease: a case control study
Version: 1Date:13 June 2010
Reviewer: Masato Yoneda
Reviewer's report:
Major comment 1
As indicated
in discussion, the authors have not yet demonstrated the therapeutic capacity of PPAR gamma agonists,
thus I suggest to remove the last sentence of the abstract.
Major comment 2
In the statistical analysis section, the author mentioned about the sample size.
The authors should mention about the result of the sample size in detail in the
Result section.
Major comment 3
In this study, alcohol intake (>30/20g/day for M/F) were excluded. The references
should be needed.Generraly, the criteria for non-alcoholic is as follows.
AGA technical review (Gastroenterology 2002;123:1705-25) (20g/day?)
AASLD single topic conference (Hepatology 2003;37:1202-1219) (>20g/day for
M and F)
APASL (J Gastroenterol Hepatol 2007:705-7) (>20/10g/day for M/F)
NIH clinical research network on NAFLD/NASH (Hepatology 2006;43:S899-)
(>20/10g/day for M/F)
Major comment 4
The analysis is insufficient for the author’s conclusion. In addition to allele
frequency model, other analysis should be needed. Such as recessive model,
and dominant model.
Minor comment 1
NAS is “NAFLD activity score”. Please correct it.
Minor comment 2
What did the authors evaluate by using PAS stain, Perls stain?
Minor comment 3
The authors said that the minimum biopsy size was 1.7cm and the number of
portal areas 10. Did All samples meet this criteria? This criteria was considerably
severe for achievement for all samples.
Minor comment 4
Although none of the control subjects had abnormal liver function or was obese,
the authors cannot completely rule out the possibility that the control group
included patients with mild steatosis. The author should mention as a limitation.
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 financial relationships to disclose.
There is no conflict of interest.
Review for 10.1186/1471-230X-10-102 (2010)

Reviewer's report
Title:Lack of association between peroxisome proliferator-activated receptors
alpha and gamma2 polymorphisms and progressive liver damage in patients with
non-alcoholic fatty liver disease: a case control study
Version: 2Date:12 July 2010
Reviewer: Véronique Barbu
Reviewer's report:
Minor essential revision:
To answer to your comment 1: I do not agree with the fact that genotyping 2
SNPs by assays with Taqman probes is slower and hard working... Once the
technique is correctly done, it is faster for a lot of patients. I would appreciate if
you could introduce in the genetic part of "the materials and methods" a sentence
precising that you confirmed by sequencing the mutated patients.
I agree with all the other comments.
The manuscript has been greatly improved by the authors.
The paper is now suitable for publication.
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-10-102 (2010)

Reviewer's report
Title:Lack of association between peroxisome proliferator-activated receptors
alpha and gamma2 polymorphisms and progressive liver damage in patients with
non-alcoholic fatty liver disease: a case control study
Version: 2Date:13 July 2010
Reviewer: Masato Yoneda
Reviewer's report:
The manuscript entitled "Lack of association between peroxisome
proliferator-activated receptors alpha and gamma2 polymorphisms and
progressive liver damage in patients with nonalcoholic liver disease" by Dr. Paola
Dongiovanni and Dr. Luca Valenti et al is carefully revised and worth publication.
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-10-100 (2010)

Reviewer's report
Title:Prevalence of primary biliary cirrhosis in adults referring hospital for annual
health check-up in Southern China
Version: 1Date:13 July 2010
Reviewer: Gideon Hirschfield
Reviewer's report:
This is a simple but useful large study of a Chinese population of healthy
individuals seen as part of a routine health check. It provides useful information
demonstrating that likely PBC is as common in China as it is elsewhere.
My concerns should be easy to address.
Major:
What were the rates of Hep B/Hep C in the population as a comparator.
Please draw a figure that shows in a pictorial way the results of screening
sequentially. I think this will make it much clearer to the reader. As it stands it is
quite hard at times to follow all the different permutations.
Please have a section in the Discussion more clearly on the limitations of this
cross-sectional observational study where only a small absolute number of cases
is identified, and little true clinical individual is available.
Minor:
ANA specificity in PBC is not new
Assay properties need better description
Clarify cholestatic biochemistry for diagnosis: as it stands an isolated bilirubin
from Gilberts could meet the criteria for PBC if AMA is present.
Highlight the difference between AMA by immunofluorescence and AMA by
ELISA in terms of disease specificity; interesting that by IF, nearly equal
male:female ratio.
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:
Have an ongoing academic collaboration with Inova, a company specialising in
autoimmune serological testing.
Review for 10.1186/1471-230X-10-100 (2010)

Reviewer's report
Title:Prevalence of primary biliary cirrhosis in adults referring hospital for annual
health check-up in Southern China
Version: 1Date:22 July 2010
Reviewer: Piotr Milkiewicz
Reviewer's report:
In their study Liu et al. analyzed prevalence of PBC in 8.126 adult subjects,
without apparent symptoms of liver disease, referred for annual health check-up
in Southern China. Initial screen for both AMA and ANA was done with indirect
immunofluorescence (IF) and sera which tested positive were further verified with
ELISA/immunoblot for AMA-M2 and PBC specific ANA such as sp-100 and
gp210. In total, 22 subjects tested positive for PBC specific antibodies in ELISA
and additional 17 tested for AMA on IF only.
Considering the scarcity of the literature data on the prevalence of PBC specific
antibodies in general population this study deserves publication. It contributes to
our limited knowledge in this area, particularly with regards to Asia region.
Minor Essential Revisions
I think the authors could apply recently proposed by EASL (EASL Clinical
Practice Guidelines: management of cholestatic liver diseases. J Hepatol 2009,
51, 237-267.) criteria for the diagnosis of PBC, that would simplify the message
of the paper. According to these criteria liver biopsy is not essential for the
diagnosis of PBC in subjects with cholestatic enzymes and positive AMA.
Relevant papers which I think should also be quoted are two Estonian studies
(Turchany JM, Uibo R, Kivik T, Van de WJ, Prindiville T, Coppel RL, & Gershwin
ME (1997) A study of antimitochondrial antibodies in a random population in
Estonia. Am J Gastroenterol, 92, 124-126 and Kisand KE, Metskula K, Kisand
KV, Kivik T, Gershwin ME, & Uibo R (2001). The follow-up of asymptomatic
persons with antibodies to pyruvate dehydrogenase in adult population samples.
J Gastroenterol 36, 248-254.).
Discretionary Revisions
In places (Results section) the manuscript is not easy to follow. Perhaps a figure
with a graphical presentation of obtained data (instead of the table) would be of
help and improve the clarity of the message.
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-10-100 (2010)

Reviewer's report
Title:Prevalence of primary biliary cirrhosis in adults referring hospital for annual
health check-up in Southern China
Version: 1Date:24 July 2010
Reviewer: Dimitrios Bogdanos
Reviewer's report:
The study by Liu et al is of interest. It adds to the increasing interest of the
scientific community for studies investigating the epidemiology and
characteristics of patients with autoimmune liver diseases in China.
Major points
Table 2 is very informative. Quantitative data of the primary biliary
cirrhosis-specific autoantibody positive cases are missing and must be given.
The authors tested pools of sera by indirect immunofluorescence but do not
justify why (presumably financial constraints). They need to discuss in brief this.
They also need to make clear that such testing does not comply with the
guidelines of the routine testing for autoantibodies and should be avoided. HEp-2
cell line as an antigenic source for autoantibody screening is not the norm. The
preferable substrate is that of combination of rodent tissues (Vergani et al J
Hepatol 2004; Bogdanos et al WJG 2008).
Minor points
It is HEp-2 .... instead of Hep-2
Table 4 reviews findings of previous studies in relation to the present one. Does
not add new information and can be omitted.
Page 10, line 4 from the top.. hepatitis ...instead of hepatic....
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.